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10,500 | 26,733,629 | Screening compared with usual care did not reduce ovarian cancer mortality .
Patient harms included overdiagnosis and false-positive results .
Although ovarian cancer screening with CA125 showed no benefit , false-positive tests , overdiagnosis and overtreatment were reported . | BACKGROUND Biomarker tests are increasingly being offered by laboratories and clinicians as self-pay health services to screen asymptomatic individuals ; however , sufficient evidence may not be available to support this practice .
We investigated the benefit-harm tradeoffs associated with 11 biomarkers currently offered in Germany as self-pay tests to screen for cancer . | CONTEXT Screening for ovarian cancer with cancer antigen 125 ( CA-125 ) and transvaginal ultrasound has an unknown effect on mortality . OBJECTIVE To evaluate the effect of screening for ovarian cancer on mortality in the Prostate , Lung , Colorectal and Ovarian ( PLCO ) Cancer Screening Trial . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of 78,216 women aged 55 to 74 years assigned to undergo either annual screening ( n = 39,105 ) or usual care ( n = 39,111 ) at 10 screening centers across the United States between November 1993 and July 2001 . Intervention The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years . Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results . The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care . Participants were followed up for a maximum of 13 years ( median [ range ] , 12.4 years [ 10.9 - 13.0 years ] ) for cancer diagnoses and death until February 28 , 2010 . MAIN OUTCOME MEASURES Mortality from ovarian cancer , including primary peritoneal and fallopian tube cancers . Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures . RESULTS Ovarian cancer was diagnosed in 212 women ( 5.7 per 10,000 person-years ) in the intervention group and 176 ( 4.7 per 10,000 person-years ) in the usual care group ( rate ratio [ RR ] , 1.21 ; 95 % confidence interval [ CI ] , 0.99 - 1.48 ) . There were 118 deaths caused by ovarian cancer ( 3.1 per 10,000 person-years ) in the intervention group and 100 deaths ( 2.6 per 10,000 person-years ) in the usual care group ( mortality RR , 1.18 ; 95 % CI , 0.82 - 1.71 ) . Of 3285 women with false-positive results , 1080 underwent surgical follow-up ; of whom , 163 women experienced at least 1 serious complication ( 15 % ) . There were 2924 deaths due to other causes ( excluding ovarian , colorectal , and lung cancer ) ( 76.6 per 10,000 person-years ) in the intervention group and 2914 deaths ( 76.2 per 10,000 person-years ) in the usual care group ( RR , 1.01 ; 95 % CI , 0.96 - 1.06 ) . CONCLUSIONS Among women in the general US population , simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality . Diagnostic evaluation following a false-positive screening test result was associated with complications . Trial Registration clinical trials.gov Identifier : NCT00002540 BACKGROUND No professional society or group recommends routine ovarian cancer screening , yet physicians ' enthusiasm for several cancer screening tests before benefit has been proven suggests that some women may be exposed to potential harms . OBJECTIVE To provide nationally representative estimates of physicians ' reported nonadherence to recommendations against ovarian cancer screening . DESIGN Cross-sectional survey of physicians offering women 's primary care . The 12-page question naire contained a woman 's annual examination vignette and questions about offers or orders for transvaginal ultrasonography ( TVU ) and cancer antigen 125 ( CA-125 ) . SETTING United States . PARTICIPANTS 3200 physicians r and omly sample d equally from the 2008 American Medical Association Physician Masterfile lists of family physicians , general internists , and obstetrician-gynecologists ; 61.7 % responded . After exclusions , 1088 respondents were included ; their responses were weighted to represent the specialty distribution of practicing U.S. physicians nationally . MEASUREMENTS Reported nonadherence to screening recommendations ( defined as sometimes or almost always ordering screening TVU or CA-125 or both ) . RESULTS Twenty-eight percent ( 95 % CI , 24.5 % to 32.9 % ) of physicians reported nonadherence to screening recommendations for women at low risk for ovarian cancer ; 65.4 % ( CI , 61.1 % to 69.4 % ) did so for women at medium risk for ovarian cancer . Six percent ( CI , 4.4 % to 8.9 % ) reported routinely ordering or offering ovarian cancer screening for low-risk women , as did 24.0 % ( CI , 20.5 % to 28.0 % ) for medium-risk women ( P ≤ 0.001 ) . Thirty-three percent believed TVU or CA-125 was an effective screening test . In adjusted analysis , actual and physician-perceived patient risk , patient request for ovarian cancer screening , and physician belief that TVU or CA-125 was an effective screening test were the strongest predictors of physician-reported nonadherence to published recommendations . LIMITATION The results are limited by their reliance on survey methods ; there may be respondent-nonrespondent bias . CONCLUSION One in 3 physicians believed that ovarian cancer screening was effective , despite evidence to the contrary . Substantial proportions of physicians reported routinely offering or ordering ovarian cancer screening , thereby exposing women to the documented risks of these tests . PRIMARY FUNDING SOURCE Centers for Disease Control and Prevention and the National Cancer Institute BACKGROUND Ovarian cancer has a high case-fatality ratio , with most women not diagnosed until the disease is in its advanced stages . The United Kingdom Collaborative Trial of Ovarian Cancer Screening ( UKCTOCS ) is a r and omised controlled trial design ed to assess the effect of screening on mortality . This report summarises the outcome of the prevalence ( initial ) screen in UKCTOCS . METHODS Between 2001 and 2005 , a total of 202 638 post-menopausal women aged 50 - 74 years were r and omly assigned to no treatment ( control ; n=101 359 ) ; annual CA125 screening ( interpreted using a risk of ovarian cancer algorithm ) with transvaginal ultrasound scan as a second-line test ( multimodal screening [ MMS ] ; n=50 640 ) ; or annual screening with transvaginal ultrasound ( USS ; n=50 639 ) alone in a 2:1:1 ratio using a computer-generated r and om number algorithm . All women provided a blood sample at recruitment . Women r and omised to the MMS group had their blood tested for CA125 and those r and omised to the USS group were sent an appointment to attend for a transvaginal scan . Women with abnormal screens had repeat tests . Women with persistent abnormality on repeat screens underwent clinical evaluation and , where appropriate , surgery . This trial is registered as IS RCT N22488978 and with Clinical Trials.gov , number NCT00058032 . FINDINGS In the prevalence screen , 50 078 ( 98.9 % ) women underwent MMS , and 48 230 ( 95.2 % ) underwent USS . The main reasons for withdrawal were death ( two MMS , 28 USS ) , non-ovarian cancer or other disease ( none MMS , 66 USS ) , removal of ovaries ( five MMS , 29 USS ) , relocation ( none MMS , 39 USS ) , failure to attend three appointments for the screen ( 72 MMS , 757 USS ) , and participant changing their mind ( 483 MMS , 1490 USS ) . Overall , 4355 of 50 078 ( 8.7 % ) women in the MMS group and 5779 of 48 230 ( 12.0 % ) women in the USS group required a repeat test , and 167 ( 0.3 % ) women in the MMS group and 1894 ( 3.9 % ) women in the USS group required clinical evaluation . 97 of 50 078 ( 0.2 % ) women from the MMS group and 845 of 48 230 ( 1.8 % ) from the USS group underwent surgery . 42 ( MMS ) and 45 ( USS ) primary ovarian and tubal cancers were detected , including 28 borderline tumours ( eight MMS , 20 USS ) . 28 ( 16 MMS , 12 USS ) of 58 ( 48.3 % ; 95 % CI 35.0 - 61.8 ) of the invasive cancers were stage I/II , with no difference ( p=0.396 ) in stage distribution between the groups . A further 13 ( five MMS , eight USS ) women developed primary ovarian cancer during the year after the screen . The sensitivity , specificity , and positive-predictive values for all primary ovarian and tubal cancers were 89.4 % , 99.8 % , and 43.3 % for MMS , and 84.9 % , 98.2 % , and 5.3 % for USS , respectively . For primary invasive epithelial ovarian and tubal cancers , the sensitivity , specificity , and positive-predictive values were 89.5 % , 99.8 % , and 35.1 % for MMS , and 75.0 % , 98.2 % , and 2.8 % for USS , respectively . There was a significant difference in specificity ( p<0.0001 ) but not sensitivity between the two screening groups for both primary ovarian and tubal cancers as well as primary epithelial invasive ovarian and tubal cancers . INTERPRETATION The sensitivity of the MMS and USS screening strategies is encouraging . Specificity was higher in the MMS than in the USS group , result ing in lower rates of repeat testing and surgery . This in part reflects the high prevalence of benign adnexal abnormalities and the more frequent detection of borderline tumours in the USS group . The prevalence screen has established that the screening strategies are feasible . The results of ongoing screening are awaited so that the effect of screening on mortality can be determined BACKGROUND The performance characteristics of serum prostate-specific antigen ( PSA ) as a diagnostic test for prostate cancer ( PCa ) are poor . The performance of the PCa antigen 3 ( PCA3 ) gene as a primary diagnostic is unknown . OBJECTIVE Assess the value of PCA3 as a first-line diagnostic test . DESIGN , SETTING AND PARTICIPANTS Participants included men aged 63 - 75 who were invited for rescreening in the period from September 2007 to February 2009 within the European R and omised Study of Screening for Prostate Cancer , Rotterdam section . INTERVENTIONS Lateral sextant biopsies were performed if the serum PSA value was > or = 3.0 ng/ml and /or the PCA3 score was > or = 10 . MEASUREMENTS Measurements included distribution and correlation of PSA value and PCA3 score and their relation to the number of cases and the characteristics of PCa detected . Additional value of PCA3 was included in men with previous negative biopsy and /or PSA < 3.0 ng/ml . RESULTS AND LIMITATIONS In 721 men , all biopsied , 122 PCa cases ( 16.9 % ) were detected . Correlation between PSA and PCA3 is poor ( Spearman rank correlation : ρ=0.14 ; p<0.0001 ) . A PSA > or = 3.0 ng/ml misses 64.7 % of the total PCa that can be detected with the sextant biopsy technique and 57.9 % of serious PCa ( T2a or higher and /or Gleason grade > or = 4 , n=19 ) , and 68.2 % of biopsies could have been avoided ; the respective data for PCA3 > or = 35 are 32 % , 26.3 % , and 51.7 % . Performance of PCA3 in men with low PSA ( area under the curve [ AUC ] : 0.63 ) and /or previous negative biopsy ( AUC : 0.68 ) is unclear but has limited reliability due to small numbers . CONCLUSIONS PCA3 as a first-line screening test shows improvement of the performance characteristics and identification of serious disease compared with PSA in this prescreened population |
10,501 | 29,673,922 | These patterns persisted up to the 5th year .
High-intensity focused ultrasound and active surveillance only have results at 1st year , showing no statistically significant worsening .
No remarkable differences in PRO appeared between modalities within each treatment . | BACKGROUND The aim of this systematic review is to assess the impact of primary treatments with curative intention in patients with localized prostate cancer , measured with Patient-Reported Outcomes ( PROs ) , and to examine differences among modalities within treatments . | PURPOSE To perform a r and omized trial comparing 70 and 80 Gy radiotherapy for prostate cancer . PATIENTS AND METHODS A total of 306 patients with localized prostate cancer were r and omized . No and rogen deprivation was allowed . The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions . Toxicity was grade d using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective , objective , management , analytic scales ( LENT-SOMA ) scales . The patients ' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Question naire 30-item cancer-specific and 25-item prostate-specific modules . RESULTS The median follow-up was 61 months . According to the 1997-American Society for Therapeutic Radiology and Oncology definition , the 5-year biochemical relapse rate was 39 % and 28 % in the 70- and 80-Gy arms , respectively ( p = .036 ) . Using the Phoenix definition , the 5-year biochemical relapse rate was 32 % and 23.5 % , respectively ( p = .09 ) . The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level > 15 ng/mL. At the last follow-up date , 26 patients had died , 10 of their disease and none of toxicity , with no differences between the two arms . According to the Radiation Therapy Oncology Group scale , the Grade 2 or greater rectal toxicity rate was 14 % and 19.5 % for the 70- and 80-Gy arms ( p = .22 ) , respectively . The Grade 2 or greater urinary toxicity was 10 % at 70 Gy and 17.5 % at 80 Gy ( p = .046 ) . Similar results were observed using the LENT-SOMA scale . Bladder toxicity was more frequent at 80 Gy than at 70 Gy ( p = .039 ) . The quality -of-life question naire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms . CONCLUSION High-dose radiotherapy provided a better 5-year biochemical outcome with slightly greater toxicity Summary Background Patient-reported outcomes ( PROs ) might detect more toxic effects of radiotherapy than do clinician-reported outcomes . We did a quality of life ( QoL ) sub study to assess PROs up to 24 months after conventionally fractionated or hypofractionated radiotherapy in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer ( CHHiP ) trial . Methods The CHHiP trial is a r and omised , non-inferiority phase 3 trial done in 71 centres , of which 57 UK hospitals took part in the QoL sub study . Men with localised prostate cancer who were undergoing radiotherapy were eligible for trial entry if they had histologically confirmed T1b – T3aN0M0 prostate cancer , an estimated risk of seminal vesicle involvement less than 30 % , prostate-specific antigen concentration less than 30 ng/mL , and a WHO performance status of 0 or 1 . Participants were r and omly assigned ( 1:1:1 ) to receive a st and ard fractionation schedule of 74 Gy in 37 fractions or one of two hypofractionated schedules : 60 Gy in 20 fractions or 57 Gy in 19 fractions . R and omisation was done with computer-generated permuted block sizes of six and nine , stratified by centre and National Comprehensive Cancer Network ( NCCN ) risk group . Treatment allocation was not masked . UCLA Prostate Cancer Index ( UCLA-PCI ) , including Short Form (SF)-36 and Functional Assessment of Cancer Therapy-Prostate ( FACT-P ) , or Exp and ed Prostate Cancer Index Composite ( EPIC ) and SF-12 quality -of-life question naires were completed at baseline , pre-radiotherapy , 10 weeks post-radiotherapy , and 6 , 12 , 18 , and 24 months post-radiotherapy . The CHHiP trial completed accrual on June 16 , 2011 , and the QoL sub study was closed to further recruitment on Nov 1 , 2009 . Analysis was on an intention-to-treat basis . The primary endpoint of the QoL sub study was overall bowel bother and comparisons between fractionation groups were done at 24 months post-radiotherapy . The CHHiP trial is registered with IS RCT N registry , number IS RCT N97182923 . Findings 2100 participants in the CHHiP trial consented to be included in the QoL sub study : 696 assigned to the 74 Gy schedule , 698 assigned to the 60 Gy schedule , and 706 assigned to the 57 Gy schedule . Of these individuals , 1659 ( 79 % ) provided data pre-radiotherapy and 1444 ( 69 % ) provided data at 24 months after radiotherapy . Median follow-up was 50·0 months ( IQR 38·4–64·2 ) on April 9 , 2014 , which was the most recent follow-up measurement of all data collected before the QoL data were analysed in September , 2014 . Comparison of 74 Gy in 37 fractions , 60 Gy in 20 fractions , and 57 Gy in 19 fractions groups at 2 years showed no overall bowel bother in 269 ( 66 % ) , 266 ( 65 % ) , and 282 ( 65 % ) men ; very small bother in 92 ( 22 % ) , 91 ( 22 % ) , and 93 ( 21 % ) men ; small bother in 26 ( 6 % ) , 28 ( 7 % ) , and 38 ( 9 % ) men ; moderate bother in 19 ( 5 % ) , 23 ( 6 % ) , and 21 ( 5 % ) men , and severe bother in four ( < 1 % ) , three ( < 1 % ) and three ( < 1 % ) men respectively ( 74 Gy vs 60 Gy , ptrend=0.64 , 74 Gy vs 57 Gy , ptrend=0·59 ) . We saw no differences between treatment groups in change of bowel bother score from baseline or pre-radiotherapy to 24 months . Interpretation The incidence of patient-reported bowel symptoms was low and similar between patients in the 74 Gy control group and the hypofractionated groups up to 24 months after radiotherapy . If efficacy outcomes from CHHiP show non-inferiority for hypofractionated treatments , these findings will add to the growing evidence for moderately hypofractionated radiotherapy schedules becoming the st and ard treatment for localised prostate cancer . Funding Cancer Research UK , Department of Health , and the National Institute for Health Research Cancer Research Network BACKGROUND Tissue preservation by means of focal therapy offers some men with clinical ly significant prostate cancer an alternative to st and ard care that appears to confer favourable genito-urinary outcomes . The precise estimates of these outcomes have so far been based on small series . OBJECTIVE This analysis pools the sexual domain related patient reported outcomes from three prospect i ve , registered studies that represent a range of inclusion criteria . DESIGN , SETTING , AND PARTICIPANTS One-hundred and eighteen men with localised prostate cancer ( prostate specific antigen ≤ 15ng/ml , Gleason ≤ 4 + 3 , stage ≤ T3aN0M0 ) treated in a tissue-preserving manner using high intensity focused ultrasound from three registered studies were included . Data on International Index of Erectile Function ( IIEF-5 ) scores and use of phosphodiesterase-5-inhibitors were collected at baseline , and 1 mo , 3 mo , 6 mo , 9 mo , and 12 mo postoperatively . The IIEF-15 total and individual domain scores were used to assess overall sexual function . Urinary function was assessed with the International Prostate Symptom Score ( IPSS ) , IPSS quality -of-life , and UCLA-Exp and ed Prostate Cancer Index Composite continence question naires . General health status was derived by means of the Charlson score . Multiple linear regression was used to assess whether age , grade , stage , qualitative scores ( IIEF , IPSS , Exp and ed Prostate Cancer Index Composite , Charlson ) , or focal therapy type duration were associated with IIEF-5 and IIEF-15 scores at 12 mo . RESULTS AND LIMITATIONS Median age was 63 yr ( interquartile range [ IQR ] 52 - 70 yr ) . Median IIEF-erectile score at baseline was 23 ( IQR 11 - 28 ) . This declined significantly to 9 ( IQR 3 - 22 , p<0.01 ) at 1 mo , but improved to 20 ( IQR 9 - 29 , p=0.30 ) at 1 yr posttreatment . Changes in total IIEF and other IIEF domains were only significantly different from preoperative values at 1 mo and 3 mo postoperatively . In the same period , the proportion of men using phosphodiesterase-5-inhibitors was 10 % preoperatively , reaching 43 % and 42 % at 6 mo and 9 months before declining to 37 % at 1 yr . The only baseline determinants of postoperative erectile function were total IIEF and IIEF-erectile function scores ( p=0.002 ) . The primary limitation of our study is the relatively short follow-up of 1 yr . CONCLUSION Men who received a range of tissue preserving therapies from the three pertinent studies experienced small decreases in total IIEF , erectile , and individual sexual domain scores that are not significantly different to those recorded at baseline . The only determinant of erectile dysfunction after tissue preserving therapy was preoperative erectile dysfunction status . Tissue preservation confers a high probability of maintaining erectile function that appears independent of all perioperative factors with the exception of baseline status . PATIENT SUMMARY In this report , the largest prospect ively collected and published set of patients with erectile dysfunction outcomes post-focal therapy for prostate cancer , we have found a return to baseline International Index of Erectile Function-erectile and total International Index of Erectile Function scores by 6 mo post-focal therapy which was maintained at 1 yr , with the majority of patients not on any form of medical treatment for their erectile dysfunction at that point . Focal therapy may represent a suitable alternative for men of any age or comorbidity wishing to maintain erectile function This study prospect ively evaluated quality of life ( QOL ) in localized prostate cancer patients undergoing radiotherapy , and it examined the relationships between QOL , depression , fatigue , and sleep disturbance . Instruments that were used are Functional Assessment of Cancer Therapy for Prostate ( FACT-P ) , Beck Depression Inventory ( BDI ) , Piper Fatigue Scale ( PFS ) , and Epworth Sleepiness Scale ( ESS ) . We evaluated patients at preradiotherapy ( PRT ) , midway radiotherapy ( MRT ) , completion of radiotherapy ( CRT ) , follow-up radiotherapy ( 4 to 8 wk ) ( FRT ) , and long-term follow-up radiotherapy ( FRT2 ) ( 12 mo or more ) . Forty participants with a mean age of 67.8 yr were studied . Duration of radiotherapy was 7 - 8 wk . Mean long-term follow-up period post-CRT was 16.2 mo ( range 12- 24 mo ) . All patients had clinical T1c to T2b prostate cancer . Prostate Cancer Specific ( PCS ) and Physical Well-Being ( PWB ) subscales of FACT-P , scores at MRT and CRT were significantly lower than at PRT . At FRT2 , PWB scores declined further , while PCS scores increased . PFS median scores were significantly higher at CRT and at FRT2 as compared with PRT . Patients scoring higher on PFS were more likely to report a poorer QOL and PWB as measured with FACT-P question naire . No significant changes were noted in the BDI and ESS scores during the study periods . The PWB declined during and at CRT and worsened at FRT2 . Decline in PCS subscale scores during and at CRT reflects worsening of urinary symptoms and appearance of bowel problems . The scores improved at long-term follow-up . A relationship was found to exist between physical well-being and fatigue BACKGROUND The proportion of younger men ( < 65 years ) diagnosed with prostate cancer ( PCa ) has increased significantly . We sought to analyze the association between race/ethnicity , biochemical recurrence risk and outcomes in younger men with PCa . METHODS In this prospect i ve cohort study , we recruited 318 younger men with newly diagnosed PCa . Participants completed generic and prostate-specific Health Related Quality of Life ( HRQoL ) , out-of-pocket cost and satisfaction with care surveys at baseline and at 3 , 6 , 12 , and 24 months of follow-up . Health re source utilization and cost data were obtained from the hospital based administrative data bases . We compared time to return to baseline ( RTB ) of HRQoL scores across groups . Survival curves were used to compare mean time to RTB across groups . Linear mixed effects ( LMEs ) and generalized linear ( GLM ) models were used to analyze the association of race/ethnicity and biochemical recurrence groups with outcomes . RESULTS African Americans reported lower generic and prostate-specific HRQoL scores at diagnosis and required more time to RTB values for generic HRQoL. The results of LME models showed that low risk of biochemical recurrence was associated with better physical function , vitality , mental health , and general health . For prostate-specific HRQoL items , low risk of biochemical recurrence was associated with impaired urinary function and better bowel function and bowel bother . GLM model showed that treatment , hospital type and comorbidity were associated with cost . CONCLUSIONS Biochemical recurrence risk and treatment groups , not ethnicity , were associated poorer post-treatment outcomes . This information is important in planning for and communicating with patients about post-treatment care Abstract Purpose The purpose of the study is to assess longitudinal changes in general and disease-specific health-related quality -of-life ( HRQOL ) indices after intensity-modulated radiotherapy ( IMRT ) monotherapy for patients with localized prostate cancer ( PCA ) . Methods Between 2006 and 2010 , 91 patients with localized PCA underwent IMRT monotherapy and were enrolled into this prospect i ve study . At baseline , and at 3 , 6 , 12 , and 24 months after IMRT , the general and prostate-specific HRQOL were estimated using physical ( PCS ) and mental component summaries ( MCS ) calculated using the Medical Outcomes Study 8-Item Short Form Health Survey and Exp and ed Prostate Cancer Index Composite ( EPIC ) . Results For 2 years , there were no significant changes in EPIC scores in all subscales of urinary domain , hormonal function , and bother . Bowel and sexual function scores decreased after IMRT and did not return to those at baseline ( p = 0.006 and < 0.001 , respectively ) . PCS began to decrease at 3 months after IMRT and then returned to the baseline score at 24 months . In contrast , the MCS score began to significantly increase after IMRT , and thereafter the score remained constant until 24 months ( p < 0.001 ) . On multivariate logistic regression analysis , urinary ( p = 0.003 ) and sexual functions ( p = 0.0005 ) at baseline were identified as significant predictors of EPIC urinary irritative/obstructive score and sexual function at 24 months after IMRT . Conclusion Urinary function , including irritative/obstruction symptoms and hormonal function , was not affected by IMRT . However , bowel and sexual function decreased after IMRT . These findings will provide important information for PCA patients considering IMRT INTRODUCTION Patients with low-risk prostate cancer ( PCa ) often have excellent oncologic outcomes . However , treatment with curative intent can lead to decrements in health-related quality of life ( HRQoL ) . Patients treated with radical prostatectomy have been shown to suffer declines in urinary and sexual HRQoL as compared to those managed with active surveillance ( AS ) . Similarly , patients treated with external-beam radiation therapy ( EBRT ) are hypothesized to experience greater declines in bowel HRQoL. As health-related quality -of-life ( HRQoL ) concerns are paramount when selecting among treatment options for low-risk PCa , this study examined HRQoL outcomes in men undergoing EBRT as compared to AS in a prospect i ve , racially diverse cohort . METHODS A prospect i ve study of HRQoL in patients with PCa enrolled in the Center for Prostate Disease Research ( CPDR ) Multicenter National Data base was initiated in 2007 . The current study included patients diagnosed through April 2014 . HRQoL was assessed with the Exp and ed Prostate Cancer Index Composite ( EPIC ) and the Medical Outcomes Study Short Form ( SF-36 ) . Temporal changes in HRQoL were compared for patients with low-risk PCa managed on AS vs. EBRT at baseline , 1- , 2- , and 3 years post-PCa diagnosis . Longitudinal patterns were modeled using linear regression models fitted with generalized estimating equations ( GEE ) , adjusting for baseline HRQoL , demographic , and clinical patient characteristics . RESULTS Of the 499 eligible patients with low-risk PCa , 103 ( 21 % ) selected AS and 60 ( 12 % ) were treated with EBRT . Demographic characteristics of the treatment groups were similar , though a greater proportion of patients in the EBRT group were African American ( P = 0.0003 ) . At baseline , both treatment groups reported comparable HRQoL. EBRT patients experienced significantly worse bowel function and bother at 1 year ( adjusted mean score : 87 vs. 95 , P = 0.001 and 89 vs. 95 , P = 0.008 , respectively ) and 2 years ( 87 vs. 93 , P = 0.007 and 87 vs. 96 , P = 0.002 , respectively ) compared to patients managed on AS . In contrast to those on AS , more than half the number of patients who received EBRT experienced a decline in bowel function ( 52 % vs. 17 % , p=0.003 ) and bother ( 52 % vs. 15 % , P = 0.002 ) from baseline to 1 year . Patients who received EBRT were significantly more likely to experience a decrease in more than one functional domain ( urinary , sexual , bowel , or hormonal ) at 1 year when compared with those on AS ( 60 % vs. 28 % , P = 0.004 ) . CONCLUSIONS Patients receiving EBRT for low-risk prostate cancer suffer declines in bowel HRQoL. These declines are not experienced by patients on AS , suggesting that management of low-risk prostate cancer with AS may offer a means for preserving HRQoL following prostate cancer diagnosis Summary Background Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment . We present a pre-planned analysis of the efficacy and side-effects of a r and omised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up . Methods CHHiP is a r and omised , phase 3 , non-inferiority trial that recruited men with localised prostate cancer ( pT1b – T3aN0M0 ) . Patients were r and omly assigned ( 1:1:1 ) to conventional ( 74 Gy delivered in 37 fractions over 7·4 weeks ) or one of two hypofractionated schedules ( 60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks ) all delivered with intensity-modulated techniques . Most patients were given radiotherapy with 3–6 months of neoadjuvant and concurrent and rogen suppression . R and omisation was by computer-generated r and om permuted blocks , stratified by National Comprehensive Cancer Network ( NCCN ) risk group and radiotherapy treatment centre , and treatment allocation was not masked . The primary endpoint was time to biochemical or clinical failure ; the critical hazard ratio ( HR ) for non-inferiority was 1·208 . Analysis was by intention to treat . Long-term follow-up continues . The CHHiP trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N97182923 . Findings Between Oct 18 , 2002 , and June 17 , 2011 , 3216 men were enrolled from 71 centres and r and omly assigned ( 74 Gy group , 1065 patients ; 60 Gy group , 1074 patients ; 57 Gy group , 1077 patients ) . Median follow-up was 62·4 months ( IQR 53·9–77·0 ) . The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3 % ( 95 % CI 86·0–90·2 ) in the 74 Gy group , 90·6 % ( 88·5–92·3 ) in the 60 Gy group , and 85·9 % ( 83·4–88·0 ) in the 57 Gy group . 60 Gy was non-inferior to 74 Gy ( HR 0·84 [ 90 % CI 0·68–1·03 ] , pNI=0·0018 ) but non-inferiority could not be cl aim ed for 57 Gy compared with 74 Gy ( HR 1·20 [ 0·99–1·46 ] , pNI=0·48 ) . Long-term side-effects were similar in the hypofractionated groups compared with the conventional group . There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures . The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group ( RTOG ) grade 2 or worse bowel and bladder adverse events was 13·7 % ( 111 events ) and 9·1 % ( 66 events ) in the 74 Gy group , 11·9 % ( 105 events ) and 11·7 % ( 88 events ) in the 60 Gy group , 11·3 % ( 95 events ) and 6·6 % ( 57 events ) in the 57 Gy group , respectively . No treatment-related deaths were reported . Interpretation Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new st and ard of care for external-beam radiotherapy of localised prostate cancer . Funding Cancer Research UK , Department of Health , and the National Institute for Health Research Cancer Research Network Background Clinical data indicates that delivery of larger daily doses of radiation may improve the therapeutic ratio for prostate cancer compared to conventional fractionation . A phase II study of stereotactic body radiotherapy with real-time motion management and daily plan re-optimization for low to intermediate risk prostate cancer was undertaken to evaluate this hypothesis . This report details the toxicity and quality of life following treatment . Methods From 2009 to 2013 , 60 patients with T1–T2c prostate cancer with a Gleason score of 6 and PSA ≤ 15 or Gleason score of 7 and PSA ≤ 10 were enrolled . Patients with nodal metastases , an American Urological Association symptom score > 18 , or gl and size > 100 g were not eligible . Patients were treated to 37 Gy in 5 fractions . Early and late genitourinary and gastrointestinal toxicity were grade d based on NCI CTCAE v4.0 and quality of life was assessed by the American Urological Association symptom score , International Index of Erectile Function , and Exp and ed Prostate cancer Index Composite Short Form up to 36 months after treatment . Results After a median follow-up of 27.6 months , no grade 3 or greater genitourinary toxicity was observed . Four patients ( 6.7 % ) reported a late grade 2 genitourinary toxicity . One patient ( 1.7 % ) reported a late grade 3 gastrointestinal toxicity . Five patients ( 8.3 % ) developed a late grade 2 gastrointestinal toxicity . The median American Urological Association symptom score increased from 4.5 prior to treatment to 11 while on treatment ( p < 0.01 ) , but was 5 at 36 months post-treatment ( p = 0.65 ) . Median International Index of Erectile Function scores decreased from 19 to 17 over the course of follow-up ( p < 0.01 ) . Only median scores within the Exp and ed Prostate Cancer Index Composite Short Form sexual domain were significantly decreased at 36 months post-treatment ( 67.9 vs 45.2 , p = 0.02 ) . There was no significant difference in median score within the urinary , bowel , or hormonal domains at 36 months of follow-up . Conclusions Stereotactic body radiotherapy for low to intermediate risk prostate cancer is well tolerated with limited toxicity or decrease in quality of life . Longer follow-up is necessary to assess the efficacy of treatment . Trial registration Clinical trials.gov NCT00941915 Registered 17 June 2009 AIMS The aim of this phase II study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy in patients with low or intermediate risk prostate cancer . MATERIAL S AND METHODS Biopsy-confirmed prostate cancer patients were enrolled , provided that they had the following characteristics : initial prostate-specific antigen ( PSA ) ≤ 20 ng/ml , Gleason Score < 7 , International Prostate Symptom Score < 7 . The treatment schedule was 35 Gy in five fractions , delivered with volumetric modulated arcs with flattening filter free beams . Toxicity was recorded according to CTCAE criteria v4.0 . Biochemical failure was calculated according to the Phoenix definition . The Exp and ed Prostate Cancer Index Composite question naire was used to record health-related quality of life . RESULTS Between December 2011 and March 2015 , 90 patients were enrolled ( 53 low risk , 37 intermediate risk ) . The median age was 71 years ( range 48 - 82 ) . In total , 58 ( 64.5 % ) of the patients had Gleason Score=6 , the remaining had Gleason Score=7.The median initial PSA was 6.9 ng/ml ( range 2.7 - 17.0 ) . Acute toxicity was mild , with 32.2 patients presenting grade 1 urinary toxicity and 32.2 % of patients presenting grade 2 urinary toxicity , mainly represented by urgency , dysuria and stranguria . Rectal grade 1 toxicity was found in 15.5 % of patients , whereas grade 2 toxicity was recorded in 6.6 % of patients . Regarding late toxicity , grade 1 proctitis was recorded in 11.1 % of patients and grade 1 urinary in 38.8 % ; only two events of grade 2 urinary toxicity were observed ( transient urethral stenosis , resolved by a 24 h catheterisation ) . At a median follow-up of 27 months ( 6 - 62 months ) only two intermediate risk patients experienced a biochemical failure . Health-related quality of life revealed a slight worsening in all the domains during treatment , with a return to baseline 3 months after treatment . CONCLUSIONS Stereotactic body radiotherapy delivered using linac-based flattening filter free volumetric modulated arc radiotherapy in low and intermediate risk prostate cancer patients is associated with mild toxicity profiles and good patient-reported quality of life PURPOSE To compare treatment impact on health-related quality of life ( HRQL ) in patients with localized prostate cancer , from before treatment to 2 years after the intervention . METHODS AND MATERIAL S This was a longitudinal , prospect i ve study of 614 patients with localized prostate cancer treated with radical prostatectomy ( 134 ) , three-dimensional external conformal radiotherapy ( 205 ) , and brachytherapy ( 275 ) . The HRQL question naires administered before and after treatment ( months 1 , 3 , 6 , 12 , and 24 ) were the Medical Outcomes Study 36-Item Short Form , the Functional Assessment of Cancer Therapy ( General and Prostate Specific ) , the Exp and ed Prostate Cancer Index Composite ( EPIC ) , and the American Urological Association Symptom Index . Differences between groups were tested by analysis of variance and within-group changes by univariate repeated- measures analysis of variance . Generalized estimating equations ( GEE ) models were constructed to assess between-group differences in HRQL at 2 years of follow-up after adjusting for clinical variables . RESULTS In each treatment group , HRQL initially deteriorated after treatment with subsequent partial recovery . However , some dimension scores were still significantly lower after 2 years of treatment . The GEE models showed that , compared with the brachytherapy group , radical prostatectomy patients had worse EPIC sexual summary and urinary incontinence scores ( -20.4 and -14.1 ; p < 0.001 ) , and external radiotherapy patients had worse EPIC bowel , sexual , and hormonal summary scores ( -3.55 , -5.24 , and -1.94 ; p < 0.05 ) . Prostatectomy patients had significantly better EPIC urinary irritation scores than brachytherapy patients ( + 4.16 ; p < 0.001 ) . CONCLUSIONS Relevant differences between treatment groups persisted after 2 years of follow-up . Radical prostatectomy had a considerable negative effect on sexual functioning and urinary continence . Three-dimensional conformal radiotherapy had a moderate negative impact on bowel functioning , and brachytherapy caused moderate urinary irritation . These results provide relevant information for clinical decision making PURPOSE Robotic assisted radical prostatectomy has largely replaced open radical prostatectomy for the surgical management of prostate cancer despite conflicting evidence of superiority with respect to disease control or functional sequelae . Using population cohort data , in this study we examined sexual and urinary function in men undergoing open radical prostatectomy vs those undergoing robotic assisted radical prostatectomy . MATERIAL S AND METHODS Subjects surgically treated for prostate cancer were selected from 2 large population based prospect i ve cohort studies , the Prostate Cancer Outcomes Study ( enrolled 1994 to 1995 ) and the Comparative Effectiveness Analysis of Surgery and Radiation ( enrolled 2011 to 2012 ) . Subjects completed baseline , 6-month and 12-month st and ardized patient reported outcome measures . Main outcomes were between-group differences in functional outcome scores at 6 and 12 months using linear regression , and adjusting for baseline function , sociodemographic and clinical characteristics . Sensitivity analyses were used to evaluate outcomes between patients undergoing open radical prostatectomy and robotic assisted radical prostatectomy within and across CEASAR and PCOS . RESULTS The combined cohort consisted of 2,438 men , 1,505 of whom underwent open radical prostatectomy and 933 of whom underwent robotic assisted radical prostatectomy . Men treated with robotic assisted radical prostatectomy reported better urinary function at 6 months ( mean difference 3.77 points , 95 % CI 1.09 - 6.44 ) but not at 12 months ( 1.19 , -1.32 - 3.71 ) . Subjects treated with robotic assisted radical prostatectomy also reported superior sexual function at 6 months ( 8.31 , 6.02 - 10.56 ) and at 12 months ( 7.64 , 5.25 - 10.03 ) . Sensitivity analyses largely supported the sexual function findings with inconsistent support for urinary function results . CONCLUSIONS This population based study reveals that men undergoing robotic assisted radical prostatectomy likely experience less decline in early urinary continence and sexual function than those undergoing open radical prostatectomy . The clinical meaning of these differences is uncertain and longer followup will be required to establish whether these benefits are durable BACKGROUND Relatively little is known about the relationship between race/ethnicity and patient-reported outcomes after contemporary treatments for localized prostate cancer . OBJECTIVE To test the hypothesis that treatment-related changes in urinary , bowel , sexual , and hormonal function vary by race/ethnicity . DESIGN , SETTING , AND PARTICIPANTS The Comparative Effectiveness Analysis of Surgery and Radiation ( CEASAR ) study is a prospect i ve , population -based , observational study that enrolled 3708 men diagnosed with localized prostate cancer in 2011 - 2012 . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Patient-reported disease-specific function was measured using the 26-item Exp and ed Prostate Index Composite ( EPIC ) at baseline and 6 and 12 mo after enrollment . Mean treatment differences in function were compared by race using risk-adjusted generalized estimating equations . RESULTS AND LIMITATIONS While all race/ethnic groups reported considerable declines in scores for urinary incontinence after radical prostatectomy ( RP ) when compared to active surveillance , African-American men reported a greater difference than white men did ( adjusted difference-in-differences 8.4 points , 95 % confidence interval 2.0 - 14.8 ; p=0.01 ) . No difference in bother scores was noted and the overall proportion of explained variation attributable to race/ethnicity was relatively small in comparison to primary treatment and baseline function . No clinical ly significant racial variation was noted for the sexual , bowel , irritative voiding , or hormone domains . Limitations include the lack of well-established thresholds for clinical significance using the EPIC instrument . CONCLUSION While these data demonstrate that incontinence at 1 yr after RP may be worse for African-American compared to white men , the difference appears to be modest overall . Treatment selection and baseline function explain a much greater proportion of the variation in function after treatment . PATIENT SUMMARY We observed that the effect of treatment for prostate cancer on patient-reported function did not vary dramatically by race/ethnicity . Compared to white men , African-American men experienced a somewhat more pronounced decline in urinary continence after radical prostatectomy , but the corresponding changes in bother scores were not significantly different between the two groups PURPOSE Perirectal spacing , whereby bio material s are placed between the prostate and rectum , shows promise in reducing rectal dose during prostate cancer radiation therapy . A prospect i ve multicenter r and omized controlled pivotal trial was performed to assess outcomes following absorbable spacer ( SpaceOAR system ) implantation . METHODS AND MATERIAL S Overall , 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography ( CT ) and magnetic resonance imaging ( MRI ) scans for treatment planning , followed with fiducial marker placement , and were r and omized to receive spacer injection or no injection ( control ) . Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapy ( 79.2 Gy in 1.8-Gy fractions ) . Spacer safety and impact on rectal irradiation , toxicity , and quality of life were assessed throughout 15 months . RESULTS Spacer application was rated as " easy " or " very easy " 98.7 % of the time , with a 99 % hydrogel placement success rate . Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups , respectively . There were no device-related adverse events , rectal perforations , serious bleeding , or infections within either group . Pre-to postspacer plans had a significant reduction in mean rectal V70 ( 12.4 % to 3.3 % , P<.0001 ) . Overall acute rectal adverse event rates were similar between groups , with fewer spacer patients experiencing rectal pain ( P=.02 ) . A significant reduction in late ( 3 - 15 months ) rectal toxicity severity in the spacer group was observed ( P=.04 ) , with a 2.0 % and 7.0 % late rectal toxicity incidence in the spacer and control groups , respectively . There was no late rectal toxicity greater than grade 1 in the spacer group . At 15 months 11.6 % and 21.4 % of spacer and control patients , respectively , experienced 10-point declines in bowel quality of life . MRI scans at 12 months verified spacer absorption . CONCLUSIONS Spacer application was well tolerated . Increased perirectal space reduced rectal irradiation , reduced rectal toxicity severity , and decreased rates of patients experiencing declines in bowel quality of life . The spacer appears to be an effective tool , potentially enabling advanced prostate RT protocol PURPOSE The purpose of this study was to prospect ively assess the variations in health-related quality of life ( HR-QoL ) in patients who underwent low-dose rate prostate brachytherapy using iodine-125 seed source during the first year after seed implantation . METHODS AND MATERIAL S Between July 2004 and December 2006 , 109 patients underwent low-dose rate brachytherapy . The Medical Outcomes study 36-Item Short Form ; the University of California , Los Angeles-Prostate Cancer Index ; and the International Index of Erectile Function-5 were evaluated before and at 1 , 3 , 6 , and 12 months after seed implantation . RESULTS In Medical Outcomes study 36-Item Short Form analyses and the HR-QoL scores were well preserved during the first year after seed implantation . In the University of California , Los Angeles-Prostate Cancer Index analyses , the urinary function and bother scores showed significant decrease during 6 months after seed implantation . The bowel function and bother scores showed significant decrease at 3 months after seed implantation . The sexual function score showed significant decrease at 3 , 6 , and 12 months after seed implantation , whereas the sexual bother score showed no change during the first year . The International Index of Erectile Function-5 score dramatically decreased at 1 , 3 , 6 , and 12 months after seed implantation . CONCLUSIONS The general HR-QoL in the patients who underwent seed implantation was well preserved during the first year after seed implantation , whereas the urinary , bowel , and sexual function and bother scores showed transient deterioration during the first year after seed implantation . Especially , sexual function showed significant deterioration in Japanese men after seed implantation OBJECTIVE To assess the effect of nerve sparing ( NS ) quality on self-reported patient urinary outcomes after radical prostatectomy . METHODS A total of 102 preoperatively potent men underwent laparoscopic or robotic radical prostatectomy ; NS was prospect ively grade d at surgery using a 0 - 4 scale/neurovascular bundle . Urinary functional outcomes were measured by vali date d Exp and ed Prostate Cancer Index Composite question naire at baseline and follow-up time points ( 1 , 3 , 6 , 9 , and 12 months ) in 99 men who underwent various degrees of NS . Mixed linear regression was used to analyze the effect of NS quality and other clinical factors on urinary outcomes . RESULTS Patients with at least 1 neurovascular bundle spared completely , along with its supportive tissues ( NS grade 4/4 ) , noted significantly improved Exp and ed Prostate Cancer Index Composite urinary functional and continence outcomes as early as 1 month postoperatively and up to 12 months . Significantly less urinary bother was also noted in these men by 9 - 12 months postoperatively . Multivariate analysis revealed that bilateral or unilateral excellent NS ( at least 1 bundle grade d 4/4 ) , increasing time from surgery , young patient age , and lower body mass index positively and significantly affected urinary functional outcomes , including pad use . Men who received excellent unilateral NS recovered urinary function about as well as men who had both neurovascular bundles spared in similar fashion . CONCLUSION The quality of NS significantly influences patient-defined urinary functional convalescence . Completely sparing at least 1 neurovascular bundle along with its supportive tissues has a dramatic effect on the recovery of urinary continence and quality of life in preoperatively potent men 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 We conducted a cross-cultural comparison of the recovery of sexual function and bother during the first 2 years after radical prostatectomy ( RP ) between American and Japanese men . A total of 275 Japanese and 283 American men who underwent RP alone were prospect ively enrolled into longitudinal cohort studies of health-related quality of life outcomes . Sexual function and bother ( distress ) were estimated with English and vali date d Japanese versions of the UCLA Prostate Cancer Index before RP and 1 , 2–3 , 4–6 , 12 , 18 and 24 months after RP . Each subject served as his own control . Japanese men reported lower sexual function scores at baseline , even after adjusted for age , prostate-specific antigen ( PSA ) and comorbidity ( 38 vs 61 , P<0.001 ) . The two groups had similar baseline sexual bother ( 70 vs 69 , P=0.84 ) . Japanese men had a smaller improvement in sexual function ( β=0.8 vs β=5.3 ) and bother ( β=0.2 vs β=2.9 ) over time than did the American men postoperatively , after adjusting for baseline score , age , baseline PSA and nerve-sparing . American men were more likely than Japanese men to regain their baseline sexual function by 24 months after surgery ( hazard ratio (HR)=1.60 ; 95 % confidence interval (CI)=1.06–2.42 ) . In contrast , American men were less likely than Japanese men to return to baseline sexual bother ( HR=0.57 ; 95 % CI=0.44–0.75 ) . This study demonstrates that Japanese and American men experience different patterns of recovery of their sexual function and bother after RP . Ethnicity may be a contributing factor Purpose : To evaluate the impact of the clinical target volume ( CTV ) and fraction dose on quality of life ( QoL ) after external-beam radiotherapy ( EBRT ) for prostate cancer . Patients and Methods : A group of 283 patients has been surveyed prospect ively before , at the last day , at a median time of 2 months and 15 months after EBRT ( 70.2–72 Gy ) using a vali date d question naire ( Exp and ed Prostate Cancer Index Composite ) . EBRT of prostate alone ( P , n = 70 ) versus prostate with seminal vesicles ( PS , n = 213 ) was compared . Differences of fraction doses ( 1.8 Gy , n = 80 , vs. 2.0 Gy , n = 69 ) have been evaluated in the patient group receiving a total dose of 72 Gy . Results : Significantly higher bladder and rectum volumes were found at all dose levels for the patients with PS versus P within the CTV ( p < 0.001 ) . Similar volumes result ed in the groups with different fraction doses . Paradoxically , bowel function scores decreased significantly less 2 and 15 months after EBRT of PS versus P. 2 months after EBRT , patients with a fraction dose of 2.0 Gy versus 1.8 Gy reported pain with urination ( ≥ once a day in 12 % vs. 3 % ; p = 0.04 ) and painful bowel movements ( ≥ rarely in 46 % vs. 29 % ; p = 0.05 ) more frequently . No long-term differences were found . Conclusion : The risk of adverse QoL changes after EBRT for prostate cancer can not be derived from the dose-volume histogram alone . Seminal vesicles can be included in the CTV up to a moderate total dose without adverse effects on QoL. Apart from a longer recovery period , higher fraction doses were not associated with higher toxicity . Ziel : Untersuchung des Einflusses von klinischem Zielvolumen ( CTV ) und Einzeldosis auf die Lebensqualitat ( QoL ) nach perkutaner Radiotherapie ( EBRT ) beim Prostatakarzinom . Patienten und Method ik : In einer Gruppe von 283 Patienten wurde die Lebensqualitat prospektiv vor , am letzten Tag , median 2 und 15 Monate nach EBRT ( 70,2–72 Gy ) mittels eines validierten Fragebogens ( Exp and ed Prostate Cancer Index Composite ) erfasst . EBRT von Prostata allein ( P , n = 70 ) versus Prostata mit Samenblasen ( PS , n = 213 ) wurde verglichen . Unterschiedliche Einzeldosen ( 1,8 Gy , n = 80 , vs. 2,0 Gy , n = 69 ) wurden bei den Patienten mit einer Gesamtdosis von 72 Gy evaluiert . Ergebnisse : Signifikant hohere Blasen- und Rektumvolumina wurden in allen Dosisbereichen bei Patienten mit PS versus P i m CTV belastet ( p < 0,001 ) . Vergleichbare Volumina result ierten in den Gruppen mit unterschiedlichen Einzeldosen . Paradoxerweise war der Abfall der Funktionswerte fur den Darm 2 und 15 Monate nach EBRT der PS versus P signifikant geringer . 2 Monate nach EBRT berichteten Patienten mit einer Einzeldosis von 2,0 Gy versus 1,8 Gy haufiger uber Schmerzen beim Wasserlassen ( ≥ einmal taglich in 12 % vs. 3 % ; p = 0,04 ) und Stuhlgang ( ≥ selten in 46 % vs. 29 % ; p = 0,05 ) . Langzeitunterschiede f and en sich nicht . Schlussfolgerung : Das Risiko nachteiliger QoL-Ver and erungen nach EBRT des Prostatakarzinoms kann nicht allein vom Dosis-Volumen- Histogramm abgeleitet werden . Samenblasen konnen i m CTV bis zu einer moderaten Dosis ohne negative Effekte auf die QoL eingeschlossen werden . Abgesehen von einer langeren Erholungszeit waren hohere Einzeldosen nicht mit hoherer Toxizitat assoziiert PURPOSE To report clinical outcomes in patients treated with image guided proton therapy ( PT ) for localized prostate cancer . METHODS AND MATERIAL S The medical records of 1327 men were review ed . Each man was enrolled on an outcomes tracking study . Dual enrollment on a prospect i ve clinical trial was allowed . Each patient was treated for localized prostate cancer with PT at our institution between 2006 and 2010 . Ninety-eight percent of patients received 78 Gy ( radiobiological equivalent [ RBE ] ) or higher ; 18 % received and rogen deprivation therapy ( ADT ) . The 5-year freedom from biochemical progression ( FFBP ) , distant metastasis-free survival , and cause-specific survival rates are reported for each risk group . Data on patient-reported quality of life and high- grade toxicities were prospect ively collected and reported . A multivariate analysis was performed to identify clinical predictors of biochemical failure and urologic toxicity . RESULTS The median follow-up time was 5.5 years . The 5-year FFBP rates were 99 % , 94 % , and 74 % in low-risk , intermediate-risk , and high-risk patients , respectively . The actuarial 5-year rates of late grade 3 + Common Terminology Criteria for Adverse Events , version 4.0 , gastrointestinal ( GI ) and genitourinary ( GU ) toxicity were 0.6 % and 2.9 % , respectively . Multivariate analysis showed a significant correlation between grade 3 + GU toxicity and pretreatment prostate reductive procedures ( P<.0001 ) , prostate volume ( P=.0085 ) , pretreatment α-blockers ( P=.0067 ) , diabetes ( P=.0195 ) , and dose-volume histogram parameters ( P=.0208 ) . The median International Prostate Symptom Scores pretreatment scores and scores at 5 years after treatment were 7 and 7 , respectively . The mean Exp and ed Prostate Cancer Index Composite ( EPIC ) scores significantly declined for sexual summary for patients not receiving ADT ( from 67 to 53 ) between baseline and 5 years . CONCLUSIONS Image guided PT provided excellent biochemical control rates for patients with localized prostate cancer . The actuarial rates of high- grade toxicity were low after PT . From pretreatment to 5 years of follow-up , a significant decline was found only in mean EPIC sexual summary scores . Prospect i ve clinical studies are needed to determine the comparative effectiveness of PT and other radiation treatment strategies PURPOSE Men with localized prostate cancer currently face a number of treatment options that treat the entire prostate . These can cause significant sexual and urinary side effects . Focal therapy offers a novel strategy that targets the cancer rather than the prostate in an attempt to preserve tissue and function . MATERIAL S AND METHODS A prospect i ve , ethics committee approved trial was conducted to determine the side effects of focal therapy using high intensity focused ultrasound . Multiparametric magnetic resonance imaging ( T2-weighted , dynamic contrast enhanced , diffusion-weighted ) and template transperineal prostate mapping biopsies were used to identify unilateral disease . Genitourinary side effects and quality of life outcomes were assessed using vali date d question naires . Posttreatment biopsies were performed at 6 months and followup was completed to 12 months . RESULTS A total of 20 men underwent high intensity focused ultrasound hemiablation . Mean age was 60.4 years ( SD 5.4 , range 50 to 70 ) with mean prostate specific antigen 7.3 ng/ml ( SD 2.8 , range 3.4 to 11.8 ) . Of the men 25 % had low risk and 75 % had intermediate risk cancer . Return of erections sufficient for penetrative sex occurred in 95 % of men ( 19 of 20 ) . In addition , 90 % of men ( 18 of 20 ) were pad-free , leak-free continent while 95 % were pad-free . Mean prostate specific antigen decreased 80 % to 1.5 ng/ml ( SD 1.3 ) at 12 months . Of the men 89 % ( 17 of 19 , 1 refused biopsy ) had no histological evidence of any cancer , and none had histological evidence of high volume or Gleason 7 or greater cancer in the treated lobe . In addition , 89 % of men achieved the trifecta status of pad-free , leak-free continence , erections sufficient for intercourse and cancer control at 12 months . CONCLUSIONS Our results appear sufficiently promising to support the further evaluation of focal therapy as a strategy to decrease some of the harms and costs associated with st and ard whole gl and treatments OBJECTIVES To compare the general and disease-specific health-related quality of life ( HRQOL ) after laparoscopic radical prostatectomy ( LRP ) with that after retropubic radical prostatectomy ( RRP ) . METHODS A total of 45 patients who underwent LRP alone and 121 who underwent RRP alone were prospect ively enrolled in an HRQOL survey . We measured the general and disease-specific HRQOL with the Medical Outcomes Study 36-Item Short Form and University of California , Los Angeles , Prostate Cancer Index , respectively . The participants were asked to complete the question naires before and 1 , 3 , 6 , and 12 months after surgery . RESULTS No significant differences were found in the preoperative characteristics of the two groups . Repeated measures of analyses of variance revealed significantly different patterns of alteration in the several general HRQOL domains between the RRP and LRP groups . The LRP group tended to have a more delayed recovery than the RRP group in the domain of urinary function and bother . The sexual function and bother of both groups showed a substantially lower score throughout the postoperative period . When the LRP group was divided into two groups according to the surgical period , an apparent improvement in HRQOL was observed in the most recent LRP series . CONCLUSIONS The two approaches showed different patterns of alteration regarding general HRQOL for 1 year after surgery . The LRP group reported delayed recovery of urinary and sexual function , which seemed to affect their general HRQOL . LRP appears to be still an evolving procedure Background To assess the relationship between dosimetric parameters and the quality of life ( QL ) outcomes of patients with low-intermediate-risk localised prostate cancer ( LPC ) treated with low-dose-rate brachytherapy ( LDR-BT ) . Material s and methods We evaluated the participants in two consecutive prospect i ve studies of the QL of patients treated with LDR-BT for LPC . QL was evaluated by means of a patient-completed question naire assessing non functional [ physical ( PHY ) and psychological ( PSY ) well-being , physical autonomy ( POW ) , social relationships ( REL ) ] and functional scales [ urinary ( URI ) , rectal ( REC ) , and sexual ( SEX ) function ] ; a scale for erectile function ( ERE ) was included in the second study . Urethra ( D10 ≤ 210 Gy ) and rectal wall constraints ( V100 ≤ 0.5 cc ) were used for pre-planning dosimetry and were assessed with post planning computerized tomography one month later for each patient . Results QL was assessed in 251 LPC patients . Dosimetry did not influence the non-functional scales . As expected , a progressive impairment in sexual and erectile function was reported one month after LDR-BT , and became statistically significant after the third year . Rectal function significantly worsened after LDR-BT , but the differences progressively decreased after the 1-year assessment . Overall urinary function significantly worsened immediately after LDR-BT and then gradually improved over the next three years . Better outcomes were reported for V100 rectal wall volumes of ≤ 0.5 cc and D10 urethra values of ≤ 210 Gy . Conclusions The findings of this study show that dosimetric parameters influence only functional QL outcomes while non-functional outcomes are only marginally influenced PURPOSE SpaceOAR , a Food and Drug Administration-approved hydrogel intended to create a rectal-prostate space , was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy . A total of 222 men were r and omized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles . The present study reports the final results with a median follow-up period of 3 years . METHODS AND MATERIAL S Cumulative ( Common Terminology Criteria for Adverse Events , version 4.0 ) toxicity was evaluated using the log-rank test . Quality of life ( QOL ) was examined using the Exp and ed Prostate Cancer Index Composite ( EPIC ) , and the mean changes from baseline in the EPIC domains were tested using repeated measures models . The proportions of men with minimally important differences ( MIDs ) in each domain were tested using repeated measures logistic models with prespecified thresholds . RESULTS The 3-year incidence of grade ≥1 ( 9.2 % vs 2.0 % ; P=.028 ) and grade ≥2 ( 5.7 % vs 0 % ; P=.012 ) rectal toxicity favored the spacer arm . Grade ≥1 urinary incontinence was also lower in the spacer arm ( 15 % vs 4 % ; P=.046 ) , with no difference in grade ≥2 urinary toxicity ( 7 % vs 7 % ; P=0.7 ) . From 6 months onward , bowel QOL consistently favored the spacer group ( P=.002 ) , with the difference at 3 years ( 5.8 points ; P<.05 ) meeting the threshold for a MID . The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years ( P<.05 ) , but the difference did not meet the MID threshold . At 3 years , more men in the control group than in the spacer group had experienced a MID decline in bowel QOL ( 41 % vs 14 % ; P=.002 ) and urinary QOL ( 30 % vs 17 % ; P=.04 ) . Furthermore , the control group were also more likely to have experienced large declines ( twice the MID ) in bowel QOL ( 21 % vs 5 % ; P=.02 ) and urinary QOL ( 23 % vs 8 % ; P=.02 ) . CONCLUSIONS The benefit of a hydrogel spacer in reducing the rectal dose , toxicity , and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period , providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy BACKGROUND AND PURPOSE The use of HDR brachytherapy ( HDR-BT ) as monotherapy for prostate cancer ( PC ) is increasing worldwide with good tumour control rates and acceptable toxicity . We report our results on toxicity and quality of life ( QoL ) after HDR-BT monotherapy for PC patients . MATERIAL S AND METHODS 166 low- and intermediate-risk localized PC patients were treated with HDR-BT to a total dose of 38Gy in four fractions . Genitourinary ( GU ) and gastrointestinal ( GI ) toxicities were prospect ively assessed using EORTC-RTOG question naires and physicians charts . QoL was evaluated using EORTC QLQ-PR25 question naires . RESULTS Three months after treatment , acute GU and GI toxicities were reported in 10.8 % and 7.2 % . Acute toxicity resolved within two months in the majority of patients ( 61 % ) . Late grade ⩾ 2 GU and GI toxicity were reported in 19.7 % and 3.3 % of patients 12 months after HDR-BT . Mean QLQ-PR25 scores showed clinical ly relevant changes from baseline for urinary symptoms and sexual functioning . With a mean follow-up of 35 months , biochemical failure was observed in 2.4 % . Overall survival at 60 months was 93.6 % and cancer-specific survival was 100 % . CONCLUSIONS HDR-BT monotherapy for localized PC showed excellent clinical outcome and acceptable acute and late toxicity . Urinary symptoms and sexual function QoL decreased after treatment 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 Summary Background Radical whole-gl and therapy can lead to significant genitourinary and rectal side-effects for men with localised prostate cancer . We report on whether selective focal ablation of unifocal and multifocal cancer lesions can reduce this treatment burden . Methods Men aged 45–80 years were eligible for this prospect i ve development study if they had low-risk to high-risk localised prostate cancer ( prostate specific antigen [ PSA ] ≤15 ng/mL , Gleason score ≤4 + 3 , stage ≤T2 ) , with no previous and rogen deprivation or treatment for prostate cancer , and who could safely undergo multiparametric MRI and have a general anaesthetic . Patients received focal therapy using high-intensity focused ultrasound , delivered to all known cancer lesions , with a margin of normal tissue , identified on multiparametric MRI , template prostate-mapping biopsies , or both . Primary endpoints were adverse events ( serious and otherwise ) and urinary symptoms and erectile function assessed using patient question naires . Analyses were done on a per- protocol basis . This study is registered with Clinical Trials.gov , number NCT00561314 . Findings 42 men were recruited between June 27 , 2007 , and June 30 , 2010 ; one man died from an unrelated cause ( pneumonia ) 3 months after treatment and was excluded from analyses . After treatment , one man was admitted to hospital for acute urinary retention , and another had stricture interventions requiring hospital admission . Nine men ( 22 % , 95 % CI 11–38 ) had self-resolving , mild to moderate , intermittent dysuria ( median duration 5·0 days [ IQR 2·5–18·5 ] ) . Urinary debris occurred in 14 men ( 34 % , 95 % CI 20–51 ) , with a median duration of 14·5 days ( IQR 6·0–16·5 ) . Urinary tract infection was noted in seven men ( 17 % , 95 % CI 7–32 ) . Median overall International Index of Erectile Function-15 ( IIEF-15 ) scores were similar at baseline and at 12 months ( p=0·060 ) , as were median IIEF-15 scores for intercourse satisfaction ( p=0·454 ) , sexual desire ( p=0·644 ) , and overall satisfaction ( p=0·257 ) . Significant deteriorations between baseline and 12 months were noted for IIEF-15 erectile ( p=0·042 ) and orgasmic function ( p=0·003 ) . Of 35 men with good baseline function , 31 ( 89 % , 95 % CI 73–97 ) had erections sufficient for penetration 12 months after focal therapy . Median UCLA Exp and ed Prostate Cancer Index Composite ( EPIC ) urinary incontinence scores were similar at baseline as and 12 months ( p=0·045 ) . There was an improvement in lower urinary tract symptoms , assessed by International Prostate Symptom Score ( IPSS ) , between baseline and 12 months ( p=0·026 ) , but the IPSS- quality of life score showed no difference between baseline and 12 months ( p=0·655 ) . All 38 men with no baseline urinary incontinence were leak-free and pad-free by 9 months . All 40 men pad-free at baseline were pad-free by 3 months and maintained pad-free continence at 12 months . No significant difference was reported in median Trial Outcomes Index scores between baseline and 12 months ( p=0·113 ) but significant improvement was shown in median Functional Assessment of Cancer Therapy (FACT)-Prostate ( p=0·045 ) and median FACT-General scores ( p=0·041 ) . No histological evidence of cancer was identified in 30 of 39 men biopsied at 6 months ( 77 % , 95 % CI 61–89 ) ; 36 ( 92 % , 79–98 ) were free of clinical ly significant cancer . After retreatment in four men , 39 of 41 ( 95 % , 95 % CI 83–99 ) had no evidence of disease on multiparametric MRI at 12 months . Interpretation Focal therapy of individual prostate cancer lesions , whether multifocal or unifocal , leads to a low rate of genitourinary side-effects and an encouraging rate of early absence of clinical ly significant prostate cancer . Funding Medical Research Council ( UK ) , Pelican Cancer Foundation , and St Peters Trust PURPOSE Permanent interstitial brachytherapy ( IB ) has become an increasingly appealing therapeutic option for localized prostate cancer ( LPC ) among physicians and patients because it involves short hospitalization and treatment and its postulated low degree of toxicity may reduce its impact on the patients ' quality of life ( QoL ) . The aim of this prospect i ve study was to assess the impact of IB on the QoL of patients with LPC . METHODS AND MATERIAL S A vali date d self-completed question naire was administered to the patients before and after IB and then at yearly intervals . The items allowed the identification of seven subscales exploring physical well-being ( PHY ) , physical autonomy ( POW ) , psychological well-being ( PSY ) , relational life ( REL ) , urinary function ( URI ) , rectal function ( REC ) , and sexual function ( SEX ) . RESULTS The assessment of the QoL of 147 patients treated between May 2000 and February 2005 revealed no relevant differences in the PHY scale scores 1 month after IB or later , and the same was true of the POW , PSY , and REL scales . Urinary function significantly worsened after IB and returned to pretreatment levels only after 3 years ; the impact of the treatment on the URI scale was greater in the patients with good baseline urinary function than in those presenting more urinary symptoms before IB . Rectal and sexual functions were significantly worse only at the post-IB evaluation . CONCLUSIONS The results of the present study confirm that the impact of IB on the patients ' QoL is low despite its transient negative effects on some function , and extend existing knowledge concerning QoL after IB Background Hypofractionated stereotactic body radiation therapy ( SBRT ) has been advanced as monotherapy for low-risk prostate cancer . We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer . Methods Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions . Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line . PSA levels , toxicities , and quality of life ( QOL ) measures were assessed at baseline and follow-up . Results All patients completed treatment with a mean coverage by the 33 Gy isodose line extending > 5 mm beyond the prostatic capsule in all directions except posteriorly . Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months . Forty patients remain free from biochemical progression . No Grade 3 or 4 toxicities were observed . Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline . No significant change in sexual QOL was observed . Conclusions In this intermediate-risk patient population , an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients . Although prospect i ve studies are needed to confirm long-term tumor control and toxicity , the short-term PSA response , biochemical relapse-free survival rate , and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy . Trial registration The Georgetown Institutional Review Board has approved this retrospective study ( IRB 2009–510 ) Background In comparison to the conventional whole-prostate dose escalation , an integrated boost to the macroscopic malignant lesion might potentially improve tumor control rates without increasing toxicity . Quality of life after radiotherapy ( RT ) with vs. without 18F-choline PET-CT detected simultaneous integrated boost ( SIB ) was prospect ively evaluated in this study . Methods Whole body image acquisition in supine patient position followed 1 h after injection of 178 - 355MBq 18F-choline . SIB was defined by a tumor-to- background uptake value ratio > 2 ( GTVPET ) . A dose of 76Gy was prescribed to the prostate ( PTVprostate ) in 2Gy fractions , with or without SIB up to 80Gy . Patients treated with ( n = 46 ) vs. without ( n = 21 ) SIB were surveyed prospect ively before ( A ) , at the last day of RT ( B ) and a median time of two ( C ) and 19 month ( D ) after RT to compare QoL changes applying a vali date d question naire ( EPIC - exp and ed prostate cancer index composite ) . Results With a median cut-off st and ard uptake value ( SUV ) of 3 , a median GTVPET of 4.0 cm3 and PTVboost ( GTVPET with margins ) of 17.3 cm3 was defined . No significant differences were found for patients treated with vs. without SIB regarding urinary and bowel QoL changes at times B , C and D ( mean differences ≤3 points for all comparisons ) . Significantly decreasing acute urinary and bowel score changes ( mean changes > 5 points in comparison to baseline level at time A ) were found for patients with and without SIB . However , long-term urinary and bowel QoL ( time D ) did not differ relative to baseline levels - with mean urinary and bowel function score changes < 3 points in both groups ( median changes = 0 points ) . Only sexual function scores decreased significantly ( > 5 points ) at time D. Conclusions Treatment planning with 18F-choline PET-CT allows a dose escalation to a macroscopic intraprostatic lesion without significantly increasing toxicity To evaluate prospect ively the associations between illness uncertainty , anxiety , fear of progression and general and disease‐specific quality of life ( QoL ) in men with favourable‐risk prostate cancer undergoing active surveillance ( AS ) Abstract Background : Many clinicians believe that preparedness before surgery for possible post-surgery side effects reduces the level of bother experienced from urinary incontinence and decreased sexual health after surgery . There are no published studies evaluating this belief . Therefore , we aim ed to study the level of preparedness before radical prostatectomy and the level of bother experienced from urinary incontinence and decreased sexual health after surgery . Material and methods : We prospect ively collected data from a non-selected group of men undergoing radical prostatectomy in 14 centers between 2008 and 2011 . Before surgery , we asked about preparedness for surgery-induced urinary problems and decreased sexual health . One year after surgery , we asked about bother caused by urinary incontinence and erectile dysfunction . As a measure of the association between preparedness and bothersomeness we modeled odds ratios ( ORs ) by means of logistic regression . Results : Altogether 1372 men had urinary incontinence one year after surgery as well as had no urinary leakage or a small urinary dribble before surgery . Among these men , low preparedness was associated with bother result ing from urinary incontinence [ OR 2.84 ; 95 % confidence interval ( CI ) 1.59–5.10 ] . In a separate analysis of 1657 men we found a strong association between preparedness for decreased sexual health and experiencing bother from erectile dysfunction ( OR 5.92 ; 95 % CI 3.32–10.55 ) . Conclusion : In this large-sized prospect i ve trial , we found that preparedness before surgery for urinary problems or sexual side effects decreases bother from urinary incontinence and erectile dysfunction one year after surgery Objective . To evaluate long-term r and omized comparisons of patient-reported outcome of symptoms and health-related quality of life ( HRQoL ) in men with localized prostate cancer 10 years after external beam radiotherapy ( RT ) or watchful waiting ( WW ) . Material and methods . Three-year HRQoL and specific symptoms in surviving patients recruited between 1986 and 1996 were previously evaluated in a r and omized trial ; definitive RT versus WW . Two question naires were used : the European Organization for Research and Treatment of Cancer ( EORTC ) QLQ-C30 and the Prostate Cancer Symptom Scale ( PCSS ) . The present study is a prolonged follow-up with the same cohorts . Results . Fifty-four of 72 eligible patients ( 75 % ) returned the question naires at the present follow-up . The median age was 77 years in the RT group and 78 years in the WW group . The median follow-up time from r and omization was 10 years . No differences in HRQoL or bowel symptoms were measured between the RT and WW . Cognitive ( RT ) and physical function ( WW ) decreased between 4 years and 10years . Weak urinary stream differed between the RT and WW groups . Fatigue and nocturia were increased in the RT group , and erections decreased in the WW patients over time . No difference in erectile function was seen between the RT and WW groups ( p=0.292 ) . Conclusion . The pattern of urinary and bowel symptoms and sexual function was rather similar , independent of RT or WW . Treatment with RT had minimal influence on HRQoL , in comparison with that of WW , at 10-year follow-up Background There is growing evidence that prostate cancer ( PC ) cells are more sensitive to high fraction dose in hypofractionation schemes . High-dose-rate ( HDR ) brachytherapy as monotherapy is established to be a good treatment option for PC using extremely hypofractionated schemes . This hypofractionation can also be achieved with stereotactic body radiotherapy ( SBRT ) . We report results on toxicity , PSA response , and quality of life ( QOL ) in patients treated with SBRT for favorable-risk PC . Methods Over the last 4 years , 50 hormone-naïve patients with low- and intermediate-risk PC were treated with SBRT to a total dose of 38 Gy delivered in four daily fractions of 9.5 Gy . An integrated boost to 11 Gy per fraction was applied to the dominant lesion if visible on MRI . Toxicity and QoL was assessed prospect ively using vali date d question naires . Results Median follow-up was 23 months . The 2-year actuarial biochemical control rate was 100 % . Median PSA nadir was 0.6 ng/ml . Median International Prostate Symptoms Score ( IPSS ) was 9/35 before treatment , with a median increase of 4 at 3 months and remaining stable at 13/35 thereafter . The EORTC/RTOG toxicity scales showed grade 2 and 3 gastrointestinal ( GI ) acute toxicity in 12 % and 2 % , respectively . The late grade 2 GI toxicity was 3 % during 24 months FU . Genitourinary ( GU ) grade 2 , 3 toxicity was seen in 15 % , 8 % , in the acute phase and 10 % , 6 % at 24 months , respectively . The urinary , bowel and sexual domains of the EORTC-PR25 scales recovered over time , showing no significant changes at 24 months post-treatment . Conclusions SBRT to 38 Gy in 4 daily fractions for low- and intermediate-risk PC patients is feasible with low acute and late genitourinary and gastrointestinal toxicity . Longer follow-up preferably within r and omized studies , is required to compare these results with st and ard fractionation schemes Objective To quantify the risk and severity of negative effects of treatment for localised prostate cancer on long term quality of life . Design Population based , prospect i ve cohort study with follow-up over three years . Setting New South Wales , Australia . Participants Men with localised prostate cancer were eligible if aged less than 70 years , diagnosed between October 2000 and October 2002 , and notified to the New South Wales central cancer registry . Controls were r and omly selected from the New South Wales electoral roll and matched to cases by age and postcode . Main outcome measures General health specific and disease specific function up to three years after diagnosis , according to the 12 item short form health survey and the University of California , Los Angeles prostate cancer index . Results 1642 ( 64 % ) cases and 495 ( 63 % ) eligible and contacted controls took part in the study . After adjustment for confounders , all active treatment groups had low odds of having better sexual function than controls , in particular men on and rogen deprivation therapy ( adjusted odds ratio ( OR ) 0.02 , 95 % CI 0.01 to 0.07 ) . Men treated surgically reported the worst urinary function ( adjusted OR 0.17 , 95 % CI 0.13 to 0.22 ) . Bowel function was poorest in cases who had external beam radiotherapy ( adjusted OR 0.44 , 95 % CI 0.30 to 0.64 ) . General physical and mental health scores were similar across treatment groups , but poorest in men who had and rogen deprivation therapy . Conclusions The various treatments for localised prostate cancer each have persistent effects on quality of life . Sexual dysfunction three years after diagnosis was common in all treatment groups , whereas poor urinary function was less common . Bowel function was most compromised in those who had external beam radiotherapy . Men with prostate cancer and the clinicians who treat them should be aware of the effects of treatment on quality of life , and weigh them up against the patient ’s age and the risk of progression of prostate cancer if untreated to make informed decisions about treatment Background Low-dose-rate permanent prostate brachytherapy ( PPB ) is an attractive treatment option for patients with localised prostate cancer with excellent outcomes . As st and ard CT-based post-implant dosimetry often correlates poorly with late treatment-related toxicity , this exploratory ( proof of concept ) study was conducted to investigate correlations between radiation − induced DNA damage biomarker levels , and acute and late bowel , urinary , and sexual toxicity . Methods Twelve patients treated with 125I PPB monotherapy ( 145Gy ) for prostate cancer were included in this prospect i ve study . Post-implant CT based dosimetry assessed the minimum dose encompassing 90 % ( D90 % ) of the whole prostate volume ( global ) , sub-regions of the prostate ( 12 sectors ) and the near maximum doses ( D0.1cc , D2cc ) for the rectum and bladder . Six blood sample s were collected from each patient ; pre-treatment , 1 h ( h ) , 4 h , 24 h post-implant , at 4 weeks ( w ) and at 3 months ( m ) . DNA double str and breaks were investigated by staining the blood sample s with immunofluorescence antibodies to γH2AX and 53BP1 proteins ( γH2AX/53BP1 ) . Patient self-scored quality of life from the Exp and ed Prostate Cancer Index Composite ( EPIC ) were obtained at baseline , 1 m , 3 m , 6 m , 9 m , 1 year ( y ) , 2y and 3y post-treatment . Spearman ’s correlation coefficients were used to evaluate correlations between temporal changes in γH2AX/53BP1 , dose and toxicity . Results The minimum follow up was 2 years . Population mean prostate D90 % was 144.6 ± 12.1 Gy and rectal near maximum dose D0.1cc = 153.0 ± 30.8 Gy and D2cc = 62.7 ± 12.1 Gy and for the bladder D0.1cc = 123.1 ± 27.0 Gy and D2cc = 70.9 ± 11.9 Gy . Changes in EPIC scores from baseline showed high positive correlation between acute toxicity and late toxicity for both urinary and bowel symptoms . Increased production of γH2AX/53BP1 at 24 h relative to baseline positively correlated with late bowel symptoms . Overall , no correlations were observed between dose metrics ( prostate global or sector doses ) and γH2AX/53BP1 foci counts . Conclusions Our results show that a prompt increase in γH2AX/53BP1foci at 24 h post-implant relative to baseline may be a useful measure to assess elevated risk of late RT − related toxicities for PPB patients . A subsequent investigation recruiting a larger cohort of patients is warranted to verify our findings 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 Background Low-risk prostate cancer ( PCa ) patients have excellent outcomes , with treatment modality often selected by perceived effects on quality of life . Acute urinary symptoms are common during external beam radiotherapy ( EBRT ) , while chronic symptoms have been linked to urethral dose . Since most low-risk PCa occurs in the peripheral zone ( PZ ) , we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy ( US-IMRT ) could improve urinary health-related quality of life ( HRQOL ) while maintaining high rates of PCa control . Methods Patients with National Comprehensive Cancer Network ( NCCN ) defined low-risk PCa with no visible lesion within 5 mm of the prostatic urethra on MRI were r and omized to US-IMRT or st and ard ( S- ) IMRT . Prescription dose was 75.6 Gy in 41 fractions to the PZ + 3–5 mm for US-IMRT and to the prostate + 3 mm for S-IMRT . For US-IMRT , mean proximal and distal urethral doses were limited to 65 Gy and 74 Gy , respectively . HRQOL was assessed using the Exp and ed Prostate Cancer Index ( EPIC ) Quality of Life question naire . The primary endpoint was change in urinary HRQOL at 3 months . Results From June 2004 to November 2006 , 16 patients were r and omized , after which a futility analysis concluded that continued accrual was unlikely to demonstrate a difference in the primary endpoint . Mean change in EPIC urinary HRQOL at 3 months was −0.5 ± 11.2 in the US-IMRT arm and + 3.9 ± 15.3 in the S-IMRT arm ( p = 0.52 ) . Median PSA nadir was higher in the US-IMRT arm ( 1.46 vs. 0.78 , p = 0.05 ) . At 4.7 years median follow-up , three US-IMRT and no S-IMRT patients experienced PSA failure ( p = 0.06 ; HR 8.8 , 95 % CI 0.9–86 ) . Two out of 3 patients with PSA failure had biopsy-proven local failure , both located contralateral to the original site of disease . Conclusions Compared with S-IMRT , US-IMRT failed to improve urinary HRQOL and result ed in higher PSA nadir and inferior biochemical control . The high rate of PSA failure and contralateral local failures in US-IMRT patients , despite careful selection of MRI-screened low-risk patients , serve as a caution ary tale for focal PCa treatments Introduction The optimal prostate stereotactic body radiation therapy ( SBRT ) dose-fractionation scheme is controversial . This study compares long-term quality of life ( QOL ) from two prospect i ve trials of prostate SBRT to investigate the effect of increasing dose ( NCT01578902 and NCT01146340 ) . Material and methods Patients with localized prostate cancer received SBRT 35 or 40 Gy delivered in five fractions , once per week . QOL was measured using the Exp and ed Prostate Cancer Index Composite at baseline and every 6 months . Fisher ’s exact test and generalized estimating equations were used to analyze proportions of patients with clinical ly significant change and longitudinal changes in QOL . Results One hundred fourteen patients were included , 84 treated with 35 Gy and 30 treated with 40 Gy . Median QOL follow-up was 56 months [ interquartile range ( IQR ) 46–60 ] and 38 months ( IQR 32–42 ) , respectively . The proportion of patients reporting clinical ly significant declines in average urinary , bowel , and sexual scores were not significantly different between dose levels , and were 20.5 vs. 24.1 % ( p = 0.60 ) , 26.8 vs. 41.4 % ( p = 0.16 ) , and 42.9 vs. 38.5 % ( p = 0.82 ) , respectively . Similarly , longitudinal analysis did not identify significant differences in QOL between treatment groups . Conclusion Dose-escalated prostate SBRT from 35 to 40 Gy in five fractions was not associated with significant decline in long-term QOL We sought to evaluate post-operative return of urinary and sexual function in men undergoing robotic-assisted laparoscopic radical prostatectomy ( RLRP ) . Prospect i ve assessment of urinary continence and sexual function was performed in patients undergoing RLRP . Subjective assessment involved the use of the vali date d R AND -36 Item Health Survey/UCLA Prostate Cancer Index question naire . Question naires were completed pre-operatively and at 1 , 3 , 6 and 12 months post-operatively . Subset analyses were performed to assess the effect of age on functional outcomes . A total of 338 consecutive patients underwent RLRP between February 2003 and August 2005 . Included patients for evaluation comprised of 21 , 129 , and 150 patients , aged < 50 , 50–59 , and ≥60 years old , respectively . Kaplan – Meier curve analysis demonstrated that younger men ( < 60 years ) achieved subjective continence significantly earlier than older age group ( ≥60 years ) ( P = 0.02 ) . Continence rates , however , equalized among all age groups at 1 year follow-up . Younger men ( < 50 years ) also demonstrated a quicker and greater return of sexual function ( P = 0.01 ) , which persisted through assessment at 1 year post-operatively . Our results suggest that younger men may have an earlier return of continence and potency when compared to men > 60 years . Despite this finding , continence outcomes appear to be equal among age groups after 1 year of follow-up . Moreover , men < 60 years continue to report superior potency outcomes compared to men > 60 years at 1 year post-operatively . Such findings are valuable in counseling patients undergoing RLRP PURPOSE The new short Exp and ed Prostate Cancer Index Composite for Clinical Practice ( EPIC-CP ) patient-reported health-related quality of life ( HRQOL ) tool has removed the rectal bleeding question from the previous much longer version , EPIC-26 . Herein , we assess the impact of losing the dedicated rectal bleeding question in 2 independent prospect i ve multicenter cohorts . METHODS AND MATERIAL S In a prospect i ve multicenter test cohort ( n=865 ) , EPIC-26 patient-reported HRQOL data were collected for 2 years after treatment from patients treated with prostate radiation therapy from 2003 to 2011 . A second prospect i ve multicenter cohort ( n=442 ) was used for independent validation . A repeated-effects model was used to predict the change from baseline in bowel summary scores from longer EPIC instruments using the change in EPIC-CP bowel summary scores with and without rectal bleeding scores . RESULTS Two years after radiation therapy , 91 % of patients were free of bleeding , and only 2.6 % reported bothersome bleeding problems . Correlations between EPIC-26 and EPIC-CP bowel scores were very high ( r2=0.90 - 0.96 ) and were statistically improved with the addition of rectal bleeding information ( r2=0.94 - 0.98 ) . Considering all patients , only 0.2 % of patients in the test cohort and 0.7 % in the validation cohort reported bothersome bleeding and had clinical ly relevant HRQOL changes missed with EPIC-CP . However , of the 2.6 % ( n=17 ) of men with bothersome rectal bleeding in the test cohort , EPIC-CP failed to capture 1 patient ( 6 % ) as experiencing meaningful declines in bowel HRQOL . CONCLUSIONS Modern prostate radiation therapy results in exceptionally low rates of bothersome rectal bleeding , and < 1 % of patients experience bothersome bleeding and are not captured by EPIC-CP as having meaningful HRQOL declines after radiation therapy . However , in the small subset of patients with bothersome rectal bleeding , the longer EPIC-26 should strongly be considered , given its superior performance in this patient subset A recent r and omized trial to compare external beam radiation therapy ( EBRT ) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease‐specific survival . We report on the quality of life ( QOL ) outcomes for this trial OBJECTIVE To undertake a prospect ive/retrospective comparison of longer-term oncologic and quality of life outcomes in open radical prostatectomy ( ORP ) or robotic-assisted laparoscopic radical prostatectomy ( RALP ) patients . MATERIAL S AND METHODS The clinical progression of ORP and RALP patients who underwent surgery during 2004 was followed over an extended ( 10 year ) period . Pre- and perioperative parameters , oncologic outcomes , recurrence , mortality , and quality of life were compared between surgical modalities . Follow-up time was calculated from the time of surgery to the latest contact . Postoperative quality of life data were obtained from Exp and ed Prostate Cancer Index Composite survey question naires . Recurrence rates , times to recurrence , surgical time , length of stay , hematocrit , follow-up time , and sexual and urinary bother scores were compared between surgical groups . Multivariate analyses were used to predict positive surgical margins and biochemical recurrence . RESULTS 63 ORP and 116 RALP patients were included ( mean age of 60.4 ± 6.4 and 58.6 ± 5.8 years ; P = .067 ) , with follow-up times of 10.3 and 10.1 years ( P = .191 ) . RALP patients had longer operative times ( P < .001 ) , shorter hospital stays ( P < .001 ) , and higher discharge hematocrits ( P < .001 ) . With prostate-specific antigen , Gleason score , and T-stage as covariates , time to recurrence ( P = .365 ) and positive margin rate ( P = .230 ) were not statistically different between groups . Ninety-five percent of RALP patients were continent and 48.0 % were potent vs 92.6 % and 41.5 % of ORP patients ( P = .720 ; .497 ) . Urinary and sexual bother were not significantly different between groups ( P = .392 ; .985 ) . CONCLUSION Our longer-term follow-up data suggest that ORP and RALP patients have comparable oncologic and quality of life outcomes BACKGROUND We report the outcome of a phase I/II clinical trial of stereotactic body radiation therapy ( SBRT ) for low ( LR ) and select intermediate risk ( IR ) prostate cancer ( PCa ) patients . PATIENTS AND METHODS Eligible patients included men with prostate adenocarcinoma with Gleason score 6 with PSA ≤ 20 or Gleason 7 with PSA ≤ 15 and clinical stage ≤ T2b . For the phase I portion of the study patients in cohorts of 15 received 45 , 47.5 , or 50 Gray ( Gy ) in five fractions . Since the maximally tolerated dose was not met in the phase I study , an additional 47 patients received 50 Gy in five fractions in the phase II study . Toxicity using Common Toxicity Criteria for Adverse Events v. 3.0 , quality of life , and outcome data was collected . RESULTS A total of 91 patients are included for analysis ; 63.7 % had NCCN IR and 36.3 % had LR PCa . At a median follow up of 54 months the actuarial freedom from biochemical failure was 100 % at 3 years and 98.6 % at 5 years . Actuarial distant metastasis free survival was 100 % at 3 and 5 years . Overall survival was 94 % at 3 years and 89.7 % at 5 years with no deaths attributed to PCa . Acute and late urinary grade ≥ III toxicity occurred in 0 % and 5.5 % of patients , respectively . Gastrointestinal ( GI ) acute and late toxicity of grade ≥ III occurred in 2 % and 7 % of patients , respectively . A total of four men experienced grade IV toxicity ( three GI , one genitourinary ) . CONCLUSION SBRT treatment results in excellent biochemical control rates at 5 years for LR and IR PCa patients although doses greater than 47.5 Gy in five fractions led to increased severe late toxicity PURPOSE To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy ( PSPT ) and spot-scanning proton therapy ( SSPT ) . METHODS AND MATERIAL S Men with localized prostate cancer enrolled on a prospect i ve QOL protocol with a minimum of 2 years ' follow-up were review ed . Comparative groups were defined by technique ( PSPT vs SSPT ) . Patients completed Exp and ed Prostate Cancer Index Composite question naires at baseline and every 3 - 6 months after proton beam therapy . Clinical ly meaningful differences in QOL were defined as ≥0.5 × baseline st and ard deviation . The cumulative incidence of modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal ( GI ) or genitourinary ( GU ) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method . RESULTS A total of 226 men received PSPT , and 65 received SSPT . Both PSPT and SSPT result ed in statistically significant changes in sexual , urinary , and bowel Exp and ed Prostate Cancer Index Composite summary scores . Only bowel summary , function , and bother result ed in clinical ly meaningful decrements beyond treatment completion . The decrement in bowel QOL persisted through 24-month follow-up . Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4 % and 9.6 % , respectively . There was 1 grade 3 GI toxicity ( PSPT group ) and no other grade ≥3 GI or GU toxicity . Argon plasma coagulation application was infrequent ( PSPT 4.4 % vs SSPT 1.5 % ; P=.21 ) . No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL . CONCLUSION Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity , with preservation of meaningful sexual and urinary QOL at 24 months . A modest , yet clinical ly meaningful , decrement in bowel QOL was seen throughout follow-up . No toxicity or QOL differences between PSPT and SSPT were identified . Long-term comparative results in a larger patient cohort are warranted PURPOSE To evaluate the early and late health-related quality of life ( QOL ) outcomes among prostate cancer patients following stereotactic body radiation therapy ( SBRT ) . METHODS AND MATERIAL S Patient self-reported QOL was prospect ively measured among 864 patients from phase 2 clinical trials of SBRT for localized prostate cancer . Data from the Exp and ed Prostate Cancer Index Composite ( EPIC ) instrument were obtained at baseline and at regular intervals up to 6 years . SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions . A short course of and rogen deprivation therapy was given to 14 % of patients . RESULTS Median follow-up was 3 years and 194 patients remained evaluable at 5 years . A transient decline in the urinary and bowel domains was observed within the first 3 months after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years . The same pattern was observed among patients with good versus poor baseline function and was independent of the degree of early toxicities . Sexual QOL decline was predominantly observed within the first 9 months , a pattern not altered by the use of and rogen deprivation therapy or patient age . CONCLUSION Long-term outcome demonstrates that prostate SBRT is well tolerated and has little lasting impact on health-related QOL . A transient and modest decline in urinary and bowel QOL during the first few months after SBRT quickly recovers to baseline levels . With a large number of patients evaluable up to 5 years following SBRT , it is unlikely that unexpected late adverse effects will manifest themselves PURPOSE To investigate the change in health-related quality of life for men after high-dose-rate brachytherapy and external beam radiotherapy for prostate cancer and the factors associated with this change . METHODS AND MATERIAL S Eligible patients had clinical ly localized intermediate-risk prostate cancer . The patients received high-dose-rate brachytherapy as a single 15-Gy implant , followed by external beam radiotherapy to 37.5 Gy in 15 fractions . The patients were monitored prospect ively for toxicity ( Common Terminology Criteria for Adverse Events , version 3.0 ) and health-related quality of life ( Exp and ed Prostate Cancer Index Composite [ EPIC ] ) . The proportion of patients developing a clinical ly significant difference in the EPIC domain score ( minimally important difference of > 0.5 st and ard deviation ) was determined and correlated with the baseline clinical and dosimetric factors . The study accrued 125 patients , with a median follow-up of 24 months . RESULTS By 24 months , 23 % had Grade 2 urinary toxicity and only 5 % had Grade 2 bowel toxicity , with no Grade 3 toxicity . The proportion of patients reporting a significant decrease in EPIC urinary , bowel , sexual , and hormonal domain scores was 53 % , 51 % , 45 % , and 40 % at 12 months and 57 % , 65 % , 51 % , and 30 % at 24 months , respectively . The proportion with a > 1 st and ard deviation decrease in the EPIC urinary , bowel , sexual , and hormonal domain scores was 38 % , 36 % , 24 % , and 20 % at 12 months and 46 % , 48 % , 19 % , and 8 % at 24 months , respectively . On multivariate analysis , the dose to 10 % of the urethra was associated with a decreasing EPIC urinary domain score ( p = .0089 ) and , less strongly ( p = .0312 ) with a decreasing hormonal domain score . No association was found between the prostate volume , bladder dose , or high-dose volume and urinary health-related quality of life . A high baseline International Index of Erectile Function score was associated ( p = .0019 ) with a decreasing sexual domain score . The optimal maximal dose to 10 % of the urethra cutpoint for urinary health-related quality of life was 120 % of the prescription dose . CONCLUSION EPIC was a more sensitive tool for detecting the effects on function and bother than were the generic toxicity scales . The urethral dose had the strongest association with a deteriorating urinary quality of life OBJECTIVES To report our health-related quality of life ( QOL ) and functional outcomes following high-intensity focused ultrasound ( HIFU ) for localized prostate cancer . METHODS Data from prostate cancer patients undergoing HIFU at our institution between January 1999 and April 2007 were collected in our prospect i ve data base . St and ard preoperative and surgical parameters , as well as baseline urinary function , QOL and sexual assessment were included . The Japanese version of the Functional Assessment of Cancer Therapy-general ( FACT-G ) , the FACT-prostate ( P ) and the International Index of Erectile Function-5 ( IIEF-5 ) were used for the functional assessment . These self-administered question naires were collected preoperatively and again at 6 , 12 and 24 months postoperatively . RESULTS A total of 326 patients were included in the analysis . Maximum flow rate and residual urine volume were significantly impaired at 6 months ( P = 0.010 ) after HIFU , even if they returned to baseline values at 12 or 24 months after HIFU . The total FACT-G score significantly improved at 24 months ( P = 0.027 ) after HIFU . At 6 , 12 and 24 months after HIFU , 52 % , 63 % and 78 % , respectively , of the patients , not receiving neoadjuvant hormonal therapy , were potent . CONCLUSIONS In our experience , functional and QOL outcomes after HIFU therapy for localized prostate cancer are better than those after other treatment modalities PURPOSE We prospect ively analyzed quality of life in a cohort of patients with prostate cancer undergoing a course of hypofractionated image guided radiotherapy . MATERIAL S AND METHODS Between August 2006 and January 2011 , 337 patients with a median age of 73 years who had cT1-T2N0M0 prostate cancer were eligible for this prospect i ve , longitudinal study of hypofractionated image guided radiotherapy ( 70.2 Gy/26 fractions ) using 1 of 3 image guided radiotherapy modalities ( transabdominal ultrasound , x-ray or cone beam computerized tomography ) available in our radiation oncology department . Patients completed 4 question naires before treatment , and 6 , 12 and 24 months later , including the International Index of Erectile Function-5 , International Prostate Symptom Score , and EORTC ( European Organization for Research and Treatment of Cancer ) prostate cancer specific QLQ-PR25 and QLQ-C30 . RESULTS Patient followup was up date d to at least the last question naire time point . Median followup was 19 months . Significant deterioration in erectile function on the International Index of Erectile Function-5 was documented with time only in patients without and rogen deprivation ( p = 0.0002 ) . No change with time was observed in urinary symptom related quality of life on the QLQ-PR25 or International Prostate Symptom Score . Slight deterioration in QLQ-PR25 bowel symptom related quality of life was observed ( p = 0.02 ) . Overall QLQ-C30 Global Health Status improved with time ( p = 0.03 ) . On univariate analysis it significantly correlated with the maximum RTOG ( Radiation Therapy Oncology Group)/EORTC urinary and bowel late toxicity scores after radiotherapy . CONCLUSIONS The regimen of hypofractionated image guided radiotherapy with multiple imaging modalities adopted in our radiation oncology department for localized prostate cancer might be a successful strategy for dose escalation with a limited impact on different aspects of quality of life with time AIMS To report health-related quality of life ( HRQOL ) and toxicity in prostate cancer patients treated with single-fraction high dose rate ( HDR ) brachytherapy boost and external beam radiotherapy ( EBRT ) . MATERIAL S AND METHODS Patients with intermediate-risk prostate cancer were accrued to a phase II clinical trial of 15 Gy HDR boost and EBRT to a dose of 37.5 Gy in 15 fractions . HRQOL ( Exp and ed Prostate Cancer Index Composite [ EPIC ] ) , urinary symptoms ( International Prostate Symptom Score [ IPSS ] ) , erectile function ( International Index of Erectile Function [ IIEF ] ) and toxicity ( Common Terminology Criteria for Adverse Events [ CTCAE ] , version 3.0 ) were monitored prospect ively . Univariate and multivariate logistic regression analysis was used to investigate associations between HRQOL/toxicity and baseline covariates . RESULTS The median follow-up time was 5.2 years . The change in the median EPIC scores from baseline to year 5 in the urinary domain was from 91 to 85 ( P = 0.0028 ) , in the bowel domain was from 98 to 96 ( P = 0.03 ) , in the sexual domain was from 63 to 35 ( P < 0.0001 ) and the hormonal domain remained unchanged at 95 ( P = 0.93 ) . Fifty-nine per cent and 46 % of the patients with normal erectile function at baseline remained potent at year 1 and year 5 , respectively . Late genitourinary toxicity grade 1 , 2 and ≥3 occurred in 29 , 59 and 4 % of patients , respectively . The rates of late gastrointestinal toxicity grade 1 , 2 and ≥3 were documented as 45 , 19 and 0 % , respectively . On multivariate logistic regression analysis , patients with larger prostates were more likely to develop a urinary late toxicity grade ≥2 ( P = 0.01 ) . The dose to 10 % of the urethra was the only factor associated with a decline in the EPIC urinary domain score ( P = 0.012 ) . Prostate volume > 43 ml was associated with higher late genitourinary toxicity grade ≥2 . CONCLUSIONS Single 15 Gy HDR brachytherapy with EBRT has a low rate of late genitourinary and gastrointestinal toxicities . Late urinary morbidity may be minimised by limiting the dose to the urethra , particularly for patients with larger prostates 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 Objective The objective was to compare the short- and long-term impact of 3 different treatment modalities on health-related quality of life ( HRQOL ) in patients treated for localised prostate cancer at a single centre in Catalonia , Spain . Material and methods This was a longitudinal , prospect i ve study of 304 patients from a single centre in Catalonia , Spain . Patients underwent 1 of 3 treatment procedures : radical prostatectomy ( 114 patients ) , external beam radiation ( 134 ) or interstitial brachytherapy ( 56 ) . HRQOL was assessed by both general and specific question naires , including the SF-36 health survey and the Exp and ed Prostate Cancer Index Composite ( EPIC ) . Interviews were administered prior to treatment and at months 1 , 3 , 6 , 12 and 24 . One-way analysis of variance and generalised estimating equations models were constructed to assess between-group differences in HRQOL . Results After initial deterioration , HRQOL scores partially recovered , although significant differences between treatment groups persisted at two years . Worsening of urinary incontinence was especially marked for the radical prostatectomy group ( 11.45 , p=0.005 ) , while deterioration in the urinary irritative/obstructive domain was worse following brachytherapy treatment ( 4.76 , p=0.025 ) . Decline in sexual function was significantly greater for the radical prostatectomy group than for the brachytherapy group ( 18.74 , p<0.001 ) . No significant between-group differences were observed in bowel domain scores . Conclusions Quality of life 2 years after treatment for prostate cancer shows wide variability . Radical prostatectomy had the largest negative impact on the sexual and urinary incontinence domains . Differences between external radiation and brachytherapy were relatively small . Brachytherapy led to a moderate increase in urinary irritation compared to the other 2 groups PURPOSE To evaluate the impact of acute urinary retention ( AUR ) in patients treated with (125)I prostate brachytherapy on short- and long-term health-related quality of life ( HRQOL ) ; and to assess whether pretreatment HRQOL has additional value in the prediction of AUR . METHODS AND MATERIAL S For 127 patients treated with (125)I brachytherapy for localized prostate cancer between December 2000 and June 2003 , toxicity and HRQOL data were prospect ively collected . Patients received a HRQOL question naire at five time points : before and 1 month , 6 months , 1 year , and 6 years after treatment . The question naire included the R AND -36 generic health survey , the cancer-specific European Organization for Research and Treatment of Cancer core question naire ( EORTC QLQ-C30 ) , the tumor-specific EORTC prostate cancer module ( EORTC QLQ-PR25 ) , and the American Urological Association ( AUA ) symptom index . RESULTS Of 127 patients , 13 ( 10.2 % ) developed AUR . Patients with AUR had a significantly worse urinary QOL at all time points compared with patients without AUR . The mean difference over time ( 6 years ) between both groups for the EORTC QLQ-PR25 urinary symptom score was 13.0 points ( p < 0.001 ) and for the AUA urinary symptom score was 15.7 points ( p = 0.001 ) . Global QOL scores ( EORTC QLQ-C30 ) over time for patients who developed AUR were significantly worse compared with patients without AUR ( mean difference 6.7 points ; p = 0.043 ) . In multivariate logistic regression analysis , pretreatment International Prostate Symptom Score ( p = 0.004 ) and neoadjuvant hormonal treatment ( p = 0.034 ) were predictors of AUR . Quality of life did not have added predictive value . CONCLUSION Acute urinary retention after prostate brachytherapy has a significant negative impact on patient 's HRQOL up to 6 years after treatment , in terms of both global QOL measures and urinary symptom scores . Furthermore , our results suggest limited value of pretreatment HRQOL measures for the prediction of AUR 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 Objectives : Hypofractionated prostate radiotherapy may increase biologically effective dose delivered while shortening treatment duration , but information on patient-reported urinary , bowel , and sexual function after dose-escalated hypofractionated radiotherapy is limited . We report patient-reported outcomes ( PROs ) from a r and omized trial comparing hypofractionated and conventional prostate radiotherapy . Methods : Men with localized prostate cancer were enrolled in a trial that r and omized men to either conventionally fractionated intensity-modulated radiation therapy ( CIMRT , 75.6 Gy in 1.8 Gy fractions ) or to dose-escalated hypofractionated IMRT ( HIMRT , 72 Gy in 2.4 Gy fractions ) . Question naires assessing urinary , bowel , and sexual function were completed pretreatment and at 2 , 3 , 4 , and 5 years after treatment . Results : Of 203 eligible patients , 185 were evaluable for PROs . A total of 173 completed the pretreatment question naire ( 82 CIMRT , 91 HIMRT ) and 102 completed the 2-year question naire ( 46 CIMRT , 56 HIMRT ) . Patients who completed PROs were similar to those who did not complete PROs ( all P>0.05 ) . Patient characteristics , clinical characteristics , and baseline symptoms were well balanced between the treatment arms ( all P>0.05 ) . There was no difference in patient-reported bowel ( urgency , control , frequency , or blood per rectum ) , urinary ( dysuria , hematuria , nocturia , leakage ) , or sexual symptoms ( erections firm enough for intercourse ) between treatment arms at 2 , 3 , 4 , and 5 years after treatment ( all P>0.01 ) . Concordance between physician-assessed toxicity and PROs varied across urinary and bowel domains . Discussion : We did not detect an increase in patient-reported urinary , bowel , and sexual symptom burden after dose-escalated intensity-modulated prostate radiation therapy using a moderate hypofractionation regimen ( 72 Gy in 2.4 Gy fractions ) compared with conventionally fractionated radiation PURPOSE Sexual function is an important concern in men receiving intensity modulated radiation therapy ( IMRT ) for prostate cancer . Our aim was to study the impact of IMRT and and rogen deprivation therapy ( ADT ) on sexual function over time and to report the effectiveness of sexual medications or aids . METHODS AND MATERIAL S A total of 179 men , median age 69 , received definitive IMRT for prostate cancer and completed 2 surveys ( Exp and ed Prostate Cancer Index Composite-26 and a sexual medicines/devices survey ) for at least 2 time points . Surveys were prospect ively collected at baseline ( before all therapy ) , and 2 , 6 , 12 , 18 , and 24 months after IMRT . Median dose was 76 Gy to the prostate . ADT was administered to 59 % of patients ( median duration 5 months , initiated 2 months before IMRT ) . Global scores were generated for the Exp and ed Prostate Cancer Index Composite-26 questions . Longitudinal analysis was performed by constructing a generalized estimation equations model , and clinical variables were tested for association with global scores . RESULTS Overall , there was a significant decline in global sexual score through 2 years . Men receiving ADT had a lower sexual score at 2 and 6 months , but this difference disappeared at 24 months . Analysis of individual sexual symptoms showed no significant difference at 24 months except that men on ADT were less likely to be sexually active ( P = .02 ) ; this difference was not observed for men receiving short-term ADT only . Longitudinal analysis revealed that duration of ADT was the only factor associated with global sexual score . Phosphodiesterase inhibitors were attempted by roughly half of all men , with 66 % experiencing benefit , whereas other aids were attempted by roughly 5 % of men . CONCLUSIONS Although ADT adversely affected short-term sexual function , there was no significant difference in global score and most sexual symptoms by 24 months . These data are useful for anticipatory guidance regarding expectations after IMRT OBJECTIVES To prospect ively assess the health-related quality -of-life outcomes of patients undergoing robot-assisted laparoscopic prostatectomy using a vali date d patient self- assessment question naire . METHODS Patients undergoing robot-assisted laparoscopic prostatectomy between September 2003 and May 2005 were given the Exp and ed Prostate Cancer Index Composite question naire preoperatively and 1 , 3 , 6 , 9 , 12 , and 18 months postoperatively . Patients with a minimum follow-up of 3 months were included in the analysis . The mean domain-specific health-related quality -of-life scores + /- SD and the proportion of patients achieving their baseline scores were calculated . Multivariate proportional hazards regression analysis was used to determine the potential prognostic factors for a return to baseline of the domain scores and continence . RESULTS The median follow-up was 9.5 months . The median time to recovery of the baseline summary scores was 6.6 months ( 95 % confidence interval [ CI ] 5.9 to 7.2 ) in the urinary domain , 2.8 months ( 95 % CI 2.0 to 3.7 ) in the bowel domain , and 3.0 months ( 95 % CI 2.2 to 3.9 ) in the hormonal domain . The baseline sexual summary score was recovered by 19.2 % of patients at 12 months . The median time to return of continence ( 0 to 1 pads/day ) was 4.0 months ( 95 % CI 3.0 to 4.9 ) . The median time to the return of erections firm enough for intercourse was 13.5 months ( 95 % CI 9.9 to 17.1 ) . On multivariate proportional hazards regression analysis , age , body mass index , prostate size , nerve-sparing technique , and number of comorbidities were not significantly associated with the time to recovery of the baseline domain scores or continence . CONCLUSIONS Patients undergoing robot-assisted laparoscopic prostatectomy have a favorable health-related quality -of-life recovery profile that appears comparable to those of established surgical approaches 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 Comparison of health-related quality of life after whole pelvic ( WPRT ) and prostate-only ( PORT ) external beam radiotherapy for prostate cancer . METHODS AND MATERIAL S A group of 120 patients ( 60 in each group ) was surveyed prospect ively before radiation therapy ( RT ) ( time A ) , at the last day of RT ( time B ) , at a median time of 2 months ( time C ) and > 1 year after RT ( time D ) using a vali date d question naire ( Exp and ed Prostate Cancer Index Composite ) . All patients were treated with 1.8- to 2.0-Gy fractions up to 70.2 to 72.0 Gy with or without WPRT up to 45 to 46 Gy . Pairs were matched according to the following criteria : age±5 years , planning target volume±10 cc ( considering planning target volume without pelvic nodes for WPRT patients ) , urinary/bowel/sexual function score before RT±10 , and use of anti and rogens . RESULTS With the exception of prognostic risk factors , both groups were well balanced with respect to baseline characteristics . No significant differences were found with regard to urinary and sexual score changes . Mean bladder function scores reached baseline levels in both patient subgroups after RT . However , bowel function scores decreased significantly more for patients after WPRT than in those receiving PORT at all times ( p<0.01 , respectively ) . Significant differences were found for most items in the bowel domain in the acute phase . At time D , patients after WPRT reported rectal urgency ( > once a day in 15 % vs. 3 % ; p=0.03 ) , bloody stools ( ≥half the time in 7 % vs. 0 % ; p=0.04 ) and frequent bowel movements ( > two on a typical day in 32 % vs. 7 % ; p<0.01 ) more often than did patients after PORT . CONCLUSION In comparison to PORT , WPRT ( larger bladder and rectum volumes in medium dose levels , but similar volumes in high dose levels ) was associated with decreased bowel quality of life in the acute and chronic phases after treatment but remained without adverse long-term urinary effects PURPOSE To determine the short- and medium-term effects of a single high-dose-rate brachytherapy fraction of 15 Gy and hypofractionated external beam radiation therapy for prostate cancer . METHODS AND MATERIAL S Eligible patients had localized prostate cancer with a Gleason score of 7 and a prostate-specific antigen ( PSA ) concentration of < 20 ng/ml or a Gleason score of 6 with a PSA concentration of 10 to 20 ng/ml . Patients received high-dose-rate brachytherapy as a single 15-Gy dose , followed by external beam radiation therapy at 37.5 Gy in 15 fractions , and were followed prospect ively for toxicity ( using Common Terminology Criteria for Adverse Events version 3.0 ) , urinary symptoms ( using the International Prostate Symptom Score [ IPSS ] ) , erectile function ( with the International Index of Erectile Function [ IIEF ] ) , and health-related quality of life ( with the Exp and ed Prostate Cancer Index Composite [ EPIC ] ) . Clinical examinations and PSA measurements were performed at every visit , and prostate biopsies were repeated at 2 years . The trial accrued 125 patients , with a median follow-up of 1.14 years . RESULTS Acute grade 2 and 3 genitourinary toxicity occurred in 62 % and 1.6 % of patients , respectively , and acute grade 2 gastrointestinal toxicity occurred in 6.5 % of patients . No grade 3 late toxicity has occurred : 47 % of patients had grade 2 genitourinary and 10 % of patients had grade 2 gastrointestinal toxicity . Median IPSSs rose from 5 at baseline to 12 at 1 month and returned to 7 at 3 months . Of the total number of patients who were initially potent ( IIEF , > 21 ) , 8 % of patients developed mild to moderate dysfunction , and 27 % of patients developed severe erectile dysfunction . Baseline EPIC bowel , urinary , and sexual bother scores decreased by 9 , 7 , and 19 points , respectively , at 1 year . No patient has experienced biochemical failure , and 16 of the first 17 biopsy results showed no malignancy . CONCLUSIONS Treatment is well tolerated in the short and medium term , with low toxicity and encouraging early indicators of disease control Purpose : We examined postprostatectomy orgasmic function and assessed for potential predictors . Material s and Methods : Between 2005 and 2013 , 499 men underwent radical prostatectomy and completed quality of life question naires prospect ively before surgery and at regular postoperative intervals . We used mixed effects logistic regression models to evaluate average differences in followup measures and interactions with time . Results : At a median followup of 36 months orgasmic function was worse , stable or improved in 300 ( 60.1 % ) , 152 ( 30.5 % ) and 47 men ( 9.4 % ) , respectively . Orgasmic function recovery plateaued at 15 to 21 months . High postoperative orgasmic function was positively associated with younger age ( 50 years or younger vs 51 to 60 OR 3.40 , 95 % CI 1.56–7.41 ) , nerve sparing ( bilateral OR 7.11 , 95 % CI 2.55–19.77 , modified 4.34 , 95 % CI 1.38–13.58 and unilateral OR 3.93 , 95 % CI 1.17–13.16 ) , erectile function ( OR 4.67 , 95 % CI 3.32–6.57 ) and sexual desire ( OR 5.51 , 95 % CI 3.95–7.68 ) but negatively associated with lower urinary tract symptoms ( OR 0.58 , 95 % CI 0.41–0.82 ) and urinary incontinence ( OR 0.38 , 95 % CI 0.25–0.56 ) . Although robotic status did not influence orgasmic function in the overall cohort , it was associated with faster recovery on subgroup analysis of 356 patients with long followup . On another subgroup analysis of 235 men with long followup and poor erectile function the association of high preoperative orgasmic function and bilateral nerve sparing with high orgasmic function persisted , suggesting an independent effect on orgasmic function apart from that on erectile function . Conclusions : Orgasmic function recovery after radical prostatectomy is a lengthy process . Predictors of orgasmic function include preoperative orgasmic function , age , nerve sparing status , erectile function , sexual desire and urinary control and function OBJECTIVE The health-related quality of life ( HRQOL ) after treatment of prostate cancer is examined using a new HRQOL tool . HRQOL , based on the exp and ed prostate cancer index composite ( EPIC ) and SF-8 question naires , was prospect ively compared after either a radical retropubic prostatectomy ( RRP ) or a permanent prostate brachytherapy ( PPB ) at a single institute . METHODS Between October 2005 and June 2007 , 96 patients were treated by an RRP and 88 patients were treated by a PPB . A HRQOL survey was completed at baseline , and at 1 , 3 , 6 and 12 months after treatment , prospect ively . RESULTS The general HRQOL in the RRP and PPB groups was not different after 3 months . However , at baseline and 1 month after treatment , the mental component summary was significantly better in the PPB group than in the RRP group . Moreover , the disease-specific HRQOL was worse regarding urinary and sexual functions in the RRP group . Urinary irritative/obstructive was worse in the PPB group , but urinary incontinence was worse in the RRP group and had not recovered to baseline after 12 months . The bowel function and bother were worse in the PPB group than in the RRP group after 3 months . In the RRP group , the patients with nerve sparing demonstrated the same scores in sexual function as the PPB group . CONCLUSIONS This prospect i ve study revealed the differences in the HRQOL after an RRP and PPB . Disease-specific HRQOL is clarified by using EPIC survey . These results will be helpful for making treatment decisions PURPOSE The viability of laparoscopic radical prostatectomy ( LRP ) as a surgical treatment for prostate cancer depends on oncological and health related quality of life ( HRQOL ) outcomes . We present a prospect i ve assessment of HRQOL in 122 patients before and after LRP using the vali date d Exp and ed Prostate Cancer Index Composite ( EPIC ) question naire . MATERIAL S AND METHODS EPIC data were collected preoperatively , and at 3 , 6 and 12 months after LRP , and all were normalized to patient preoperative baseline responses . RESULTS Using traditional single question responses , 93.4 % of patients were continent ( 0 to 1 pads ) at postoperative month 12 . Of previously potent men who underwent bilateral nerve sparing 78.9 % reported engaging in sexual intercourse within postoperative year 1 . However , EPIC domain scores provided a more comprehensive assessment of functional outcomes . For the urinary incontinence subdomain , the majority of functional recovery was achieved by postoperative month 6 , reaching a 74 % return to baseline on average . In contrast , recovery of the sexual function subdomain continued throughout postoperative year 1 ( to a mean of 64 % ) . Recovery of sexual function was not significantly affected by age or preoperative potency status , although the extent of nerve sparing was a significant predictor of outcome ( mean recovery to 75 % of baseline for bilateral vs 36 % for no nerve sparing at 12 months , p = 0.005 ) . CONCLUSIONS Nerve sparing LRP provides satisfactory first year HRQOL outcomes when assessed with a vali date d instrument . The time course and extent of functional recovery documented in this prospect i ve study may prove useful for patient counseling before LRP PURPOSE To investigate the quality of life ( QoL ) after different treatment modalities for low-risk prostate cancer , including brachytherapy , robot-assisted laparoscopic prostatectomy ( RALP ) , and active surveillance ( AS ) with vali date d question naires . MATERIAL S AND METHODS From a prospect i ve data base , we selected a total of 144 men with low- grade localized prostate cancer including 65 ( 45.1 % ) patients with RALP , 29 ( 20.2 % ) with brachytherapy , and 50 ( 34.7 % ) whose cancer was managed with AS . QoL was routinely evaluated with vali date d question naires : The European Organization for Research and Treatment of Cancer Quality of Life Question naire Core 30 ( EORTC-QLQ-C30 ) , EORTC-QLQ-Prostate Module (PR)25 , International Index of Erectile Function (IIEF)-15 , International Consultation on Incontinence Question naire Short Form ( ICIQ-SF ) with a minimum follow-up of 1 year . RESULTS In comparison with baseline scores , the brachytherapy group showed a significant decrease of QoL domain scores of voiding complaints ( P=0.010 ) , use of incontinence aids ( P=0.011 ) , sexual functioning domain ( P=0.011 ) , and erectile function ( P≤0.001 ) . In the RALP group , sexual function ( P≤0.001 ) , incontinence ( P≤0.001 ) , and erectile function were significantly affected . A decrease in sexual function was observed in 71 % of men after RALP and 59 % after brachytherapy . In 30 % of men under AS , a decrease of erectile function score during follow-up was reported . Overall , no significant decrease in general QoL was observed neither for men under AS nor for men treated by brachytherapy or RALP . Clinical factors such as age , prostate size , prostate-specific antigen level , and nerve preservation during RALP were nonpredictive of overall QoL after treatment for the individual patient ( P=0.676 ) . CONCLUSION Patients with low-risk prostate cancer who are treated with brachytherapy or RALP report deterioration of QoL of specific domains such as voiding , continence , and sexual functioning in comparison with AS patients . A decrease of erectile function was also observed during AS . Overall QoL was similar for all three treatments options Abstract Purpose Stereotactic body radiotherapy ( SBRT ) is an emerging treatment approach reported as safe and effective strategy for low- and intermediate-risk prostate cancer patients . End point of the current study is to appraise the patient-reported quality of life according to the exp and ed prostate cancer index composite ( EPIC ) question naire . Methods In the framework of a prospect i ve mono-institutional phase II trial , EPIC question naire was dispensed ( up to 1 year after treatment ) to a cohort of 46 patients of 72 treated with 5 fractions of 7 Gy each to the prostate . SBRT was delivered with RapidArc VMAT with 10 MV flattening filter-free photon beams . Results Median follow-up of patients was 14.5 months ( range : 6–23 ) . Acute rectal toxicity was mild ( only 23/72 cases with G1–2 and no G3–4 ) as well as urinary ( 50/72 G1–2 and no G3–4 ) . At the moment , four cases of G1 late rectal toxicity and 22 cases of G1 urinary ( 1 of G2 ) were reported . Urinary , rectal , sexual , and hormonal scores result ed stable over time : 1 year scores result ed , respectively , in −0.3 , + 2.8 , −1.7 , and −2.8 % variations with respect to baseline . No significant differences were observed also when data were stratified according to functional and bother sub-scales . Conclusions Stereotactic body radiotherapy ( SBRT ) treatment of prostate with RapidArc and high-intensity photon beams result ed to be well tolerated by patients with mild toxicity profiles and good patient-reported quality of life perception for the first year after treatment . Longer follow-up in the trial cohort is in progress The aim of this study was to compare health related quality of life ( QoL ) of patients with prostate cancer , who had undergone radical prostatectomy ( RP ) , with patients who were carefully monitored . This prospect i ve study included 56 patients who had undergone the radical prostatectomy ( RP ) and 48 non-operated patients ( watchful waiting , WW ) . All patients filled EPIC question naire at baseline , 1th , 3rd , 6th and 12th month . At baseline , mean scores were similar in both groups , but one month after the surgery in RP group , patients had statistically significant lower score of urinary incontinency , urinary function and sexual function compared with WW patients . These scores were significantly higher in the 3rd , 6th and 12th month in operated patients , but there was no improvement in the WW group . Radical prostatectomy does not significantly improve quality of life . Prostatectomized patients had worse scores on the QoL scale , with exception of the urinary disturbance dimension BACKGROUND AND PURPOSE Health-related quality of life ( QoL ) concerns are important for patients selecting treatment options for clinical ly localized prostate cancer and are critical in evaluating outcomes . We report pretreatment and post-treatment general and disease-specific QoL for the following invasive interventions : open radical prostatectomy ( ORP ) , laparoscopic radical prostatectomy ( LRP ) , and palladium-103 ( (103)Pd ) brachytherapy . PATIENTS AND METHODS We performed a prospect i ve longitudinal survey of 452 patients with newly diagnosed prostate cancer treated at a single medical center between 2001 and 2003 . An Institutional Review Board-approved question naire comprised of vali date d QoL instruments was sent to patients scheduled to undergo ORP ( N = 186 ) , LRP ( N = 116 ) , or brachytherapy ( N = 150 ) . The same question naire was sent out 1 , 3 , 6 , 9 , and 12 months after therapy . Comparisons were made between the groups to determine if the choice of therapy result ed in differences in QoL. RESULTS General QoL scores were minimally affected by the choices ; however , the disease-specific domains of bowel , urinary , and sexual function were adversely affected by all modalities . The ORP and LRP groups were similar among disease-specific domains and received lower post-treatment urinary and sexual scores than the (103)Pd patients . At 12 months , 38 % of ORP and 46 % of LRP patients had returned to baseline urinary function compared with 75 % of (103)Pd patients . At 12 months , 63 % of (103)Pd patients had returned to baseline sexual function compared with 19 % of both the LRP and ORP patients . CONCLUSIONS Invasive treatments for localized prostate cancer have little impact on general QoL but significantly affect disease-specific domains . Both ORP and LRP have a greater initial negative impact on urinary and sexual function than (103)Pd . The differences among the treatments with regard to QoL provide information to patients faced with choosing a treatment Objective : To identify differences in terms of quality of life , the American Urological Association Symptom Index ( AUA ) , or adverse events ( AEs ) among patients with prostate cancer treated with either st and ard fractionation or hypofractionation proton-beam therapy . Material s and Methods : Patients were prospect ively r and omized to receive 38 Gy relative biological effectiveness ( RBE ) in 5 treatments ( n=49 ) or 79.2 Gy RBE in 44 treatments ( n=33 ) . All patients had low-risk prostate cancer and were treated with proton therapy using fiducial markers and daily image guidance . Results : Median follow-up for both groups was 18 months ; 33 patients had follow-up of 2 years or longer . Baseline median ( range ) AUA was 4.7 ( 0 to 13 ) for the 38 Gy RBE arm and 4.8 ( 0 to 17 ) for the 79.2 Gy RBE arm . We observed no difference between the groups regarding the Exp and ed Prostate Index Composite urinary , bowel , or sexual function scores at 3 , 6 , 12 , 18 , or 24 months after treatment . The only significant difference was the AUA score at 12 months ( 8 for the 38 Gy RBE arm vs. 5 for the 79.2 Gy RBE arm ; P=0.04 ) ; AUA scores otherwise were similar between groups . No grade 3 or higher AEs occurred in either arm . Conclusions : Patients treated with proton therapy in this r and omized trial tolerated treatment well , with excellent quality -of-life scores , persistent low AUA , and no grade 3 or higher AEs on either arm . We showed no apparent clinical difference in outcomes with hypofractionated proton-beam therapy compared with st and ard fractionation on the basis of this interim analysis PURPOSE To prospect ively compare health-related quality of life ( HRQOL ) , patient-reported treatment-related symptoms , and costs of iodine-125 permanent implant interstitial brachytherapy ( IB ) with those of radical prostatectomy ( RP ) during the first 2 years after these treatments for localized prostate cancer . METHODS AND MATERIAL S A total of 435 men with localized low-risk prostate cancer , from 11 French hospitals , treated with IB ( 308 ) or RP ( 127 ) , were offered to complete the European Organization for Research and Treatment of Cancer core Quality of Life Question naire QLQ-C30 version 3 ( EORTC QLQ-C30 ) and the prostate cancer specific EORTC QLQ-PR25 module before and at the end of treatment , 2 , 6 , 12 , 18 , and 24 months after treatment . Repeated measures analysis of variance and analysis of covariance were conducted on HRQOL changes . Comparative cost analysis covered initial treatment , hospital follow-up , outpatient and production loss costs . RESULTS Just after treatment , the decrease of global HRQOL was less pronounced in the IB than in the RP group , with a 13.5 points difference ( p < 0.0001 ) . A difference slightly in favor of RP was observed 6 months after treatment ( -7.5 points , p = 0.0164 ) and was maintained at 24 months ( -8.2 points , p = 0.0379 ) . Impotence and urinary incontinence were more pronounced after RP , whereas urinary frequency , urgency , and urination pain were more frequent after IB . Mean societal costs did not differ between IB ( 8,019 euros at T24 ) and RP ( 8,715 euros at T24 , p = 0.0843 ) regardless of the period . CONCLUSIONS This study suggests a similar cost profile in France for IB and RP but with different HRQOL and side effect profiles . Those findings may be used to tailor localized prostate cancer treatments to suit individual patients ' needs OBJECTIVES To determine the impact of body mass index ( BMI ) on perioperative functional and oncological outcomes in patients undergoing robotic laparoscopic radical prostatectomy ( RLRP ) when stratified by BMI . METHODS Data were collected prospect ively for 945 consecutive patients undergoing RLRP . Patients were evaluated with the UCLA-PCI-SF36v2 vali date d- quality -of-life question naire preoperatively and postoperatively to 24 months . Patients were stratified by BMI as normal weight ( BMI < 25 kg/m(2 ) ) , overweight ( BMI = 25 to < 30 kg/m(2 ) ) and obese ( BMI > or = 30 kg/m(2 ) ) for outcomes analysis . RESULTS Preoperatively , obese men had a significantly greater percentage of medical comorbidities ( P < .01 ) as well as a baseline erectile dysfunction ( lower mean baseline Sexual Health Inventory for Men score [ P = .01 ] and UCLA-PCI-SF36v2 sexual function domain scores [ P = .01 ] ) . Mean operative time was significantly longer in obese patients when compared with normal and overweight men ( 234 minutes vs 217 minutes vs 214 minutes ; P = .0003 ) . Although overall complication rates were comparable between groups , a greater incidence of case abortion caused by pneumoperitoneal pressure with excessive airway pressures was noted in obese men . Urinary continence and potency outcomes were significantly lower for obese men at both 12 and 24 months ( all P < .05 ) . CONCLUSIONS In this series , obese men experienced a longer operative time , particularly during the initial robotic experience . As such , surgeons early in their RLRP learning curve should proceed cautiously with surgery in these technically more difficult patients or reserve such cases until the learning curve has been surmounted . These details , including inferior urinary and sexual outcomes , should be discussed with obese patients during preoperative counseling PURPOSE We conducted a 3-year longitudinal study assessing the impact of unilateral sural nerve graft on recovery of potency and continence following radical prostatectomy . MATERIAL S AND METHODS A total of 113 patients undergoing radical retropubic prostatectomy were classified into 3 groups according to the degree of nerve sparing , that is unilateral nerve preservation with contralateral sural nerve graft interposition , bilateral nerve sparing and unilateral nerve sparing . Urinary continence and potency were estimated by the UCLA Prostate Cancer Index question naire . RESULTS Patients in the nerve sparing plus sural nerve graft group were younger than those in the bilateral nerve sparing or unilateral nerve sparing groups . At baseline the unilateral nerve sparing plus sural nerve graft group and the bilateral nerve sparing group reported better sexual function than the unilateral nerve sparing group ( 62.1 and 61.5 vs 49.9 , p<0.05 ) . The bilateral nerve sparing group showed more rapid recovery than the unilateral nerve sparing plus sural nerve graft group after radical retropubic prostatectomy ( p<0.01 ) . After 24 months there were no significant differences observed between the bilateral nerve sparing and the unilateral nerve sparing plus sural nerve graft group ( 28.7 vs 32.9 ) . The bilateral nerve sparing group reported a better sexual function score than the unilateral nerve sparing group throughout the postoperative period ( p<0.05 ) . The bilateral nerve sparing group maintained significantly better urinary function at 1 month after radical retropubic prostatectomy than the unilateral nerve sparing plus sural nerve graft group ( p < 0.05 ) . After 3 months these groups were almost continent . The unilateral nerve sparing group reported lower urinary function scores during the first year compared to the other groups . CONCLUSIONS The nerve graft procedure may contribute to the recovery of urinary function as well as sexual function after radical retropubic prostatectomy . This finding needs to be vali date d in a r and omized trial PURPOSE Although it is the most powerful predictor of early prostate cancer treatment-related complications and quality -of-life ( QOL ) outcomes , most studies do not stratify results by baseline function . Further , reporting functional outcomes as averaged numerical results may obscure informatively disparate courses . Using levels of treatment-related dysfunction , we address these problems and present the final QOL outcomes of our prospect i ve cohort study of patients with early prostate cancer . METHODS We created categories for sexual , bowel , and urinary function , measured using numerical scores of the vali date d Prostate Cancer Symptom Indices and stratified into " normal , " " intermediate " and " poor " levels of function by incorporating patient-reported symptom and distress information . We present QOL outcomes for 409 patients 36 months after radical prostatectomy , external-beam radiation therapy , and brachytherapy . RESULTS Different levels of baseline sexual , bowel , and urinary function produced distinctive treatment-related changes from baseline to 36 months . In general , the average scale increases in dysfunction were greatest among patients with normal baseline function , although patients with normal and intermediate baseline function had similar increases in sexual dysfunction . For patients whose baseline urinary obstruction/irritation was poor , both average scale scores and most patients ' level of function improved after treatment , particularly after surgery . CONCLUSION The use of functional levels to stratify treatment-related outcomes by pretreatment functional status and to display the proportions of patients with improved , stable , or worsened function after treatment provides information that more specifically conveys the expected impact of treatment to patients choosing among localized prostate cancer treatments OBJECTIVES To assess the impact of lifestyle on health-related quality of life ( HR-QOL ) , perceived stress , and self-reported sexual function in men with early-stage prostate cancer electing active surveillance . METHODS A total of 44 intervention and 49 usual-care control participants were enrolled in a r and omized clinical trial examining the effects of lifestyle changes on prostate cancer progression . The intervention consisted of a low-fat , vegan diet , exercise , and stress management . Participants completed the Medical Outcomes Study Short Form-36 Health Status Survey ( a measure of mental and physical HR-QOL ) , the Perceived Stress Scale , the Sexual Function subscale of the University of California , Los Angeles , Prostate Cancer Index , and measures of lifestyle behaviors ( to yield an overall lifestyle index ) at baseline and 12 months . The data were analyzed using analysis of variance for repeated measures . The relationship between lifestyle and QOL was also analyzed using multiple linear regression analyses . RESULTS Intervention participants had significantly improved their lifestyle compared with controls at 12 months . The quality -of-life scores were high across groups and time points . However , a healthier lifestyle was related to better QOL at baseline . Participants in both groups who reported a healthier lifestyle also reported better mental and physical HR-QOL and sexual function . Furthermore , participants whose lifestyle improved over time showed enhanced physical HR-QOL and decreased perceived stress . CONCLUSIONS Men who choose active surveillance for early-stage prostate cancer are able to make comprehensive lifestyle changes . Although the average QOL was already high in this sample , individuals who improved their lifestyle enhanced their QOL further BACKGROUND We evaluated the efficacy and feasibility of high-intensity-focused ultrasound ( HIFU ) for localized prostate cancer . METHODS Seventy patients received HIFU using Sonablate((R ) ) 500 ( Focus Surgery , IN , USA ) . In patients whose cancer was confined to only one lobe by multi-regional biopsies , total peripheral zone and a half portion of transitional zone were ablated ( focal therapy ) . Otherwise , patients received whole organ ablation ( whole therapy ) . Scheduled biopsies were performed at 6 and 12 months after treatment . Pre- and post-HIFU serum testosterone levels were measured . Result The 2-year biochemical disease-free survival ( DFS ) rates in patients at low , intermediate and high risk were 85.9 , 50.9 and 0 % , respectively , ( P = 0.0028 ) . After 12 months , 81.6 % ( 40/49 ) of patients were biopsy negative ; 84.4 % in patients who received whole therapy , whereas 76.5 % in those with focal therapy . The 2-year biochemical DFS rates for the patients at low and intermediate risk was 90.9 and 49.9 % , respectively , in patients with whole therapy , whereas 83.3 and 53.6 % in patients with focal therapy . In patients without neoadjuvant and rogen deprivation , serum testosterone levels continuously decreased after whole therapy , whereas no changes were seen in those with focal therapy . The patients whose follow-up biopsies were positive tended to have significantly higher changes in prostate-specific antigen levels than biopsy-negative patients . CONCLUSIONS In patients with low-risk prostate cancer , HIFU monotherapy result ed in comparable immediate cancer control with other modalities . Particularly , focal therapy might offer a feasible minimally invasive therapeutic option , which maintained serum testosterone level . To our knowledge , this is the first report that whole , but not focal , therapy affects the serum testosterone level 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 Quality -of-life outcomes are important in the choice of treatment strategy for men with localized prostate cancer . OBJECTIVE To evaluate how follow-up time , number of physical symptoms , and presence of and rogen deprivation affected quality of life among men r and omized to radical prostatectomy or watchful waiting . DESIGN , SETTING , AND PARTICIPANTS The study group was composed of all 376 living men included in the Swedish part of the Sc and inavian Prostate Cancer Group Study Number 4 ( SPCG-4 ) between January 1 , 1989 , and February 29 , 1996 . Quality -of-life data were collected after a mean follow-up time of 4.1 yr . INTERVENTION All patients were r and omly assigned to radical prostatectomy or watchful waiting . Forty-five men were and rogen deprived . MEASUREMENTS Data of specific symptoms , symptom-induced stress , sense of well-being , and self-assessed quality of life were obtained by means of a question naire . Psychological symptoms were assessed using seven-point visual digital scales . RESULTS AND LIMITATIONS In analyses stratified on the basis of the numbers of physical symptoms , anxiety and depressed mood were less common , and sense of well-being and self-assessed quality of life were better throughout in the radical prostatectomy group than in the watchful waiting group . As the number of physical symptoms increased , all psychological variables became worse and more prominent in the watchful waiting group . After a follow-up time of 6 - 8 yr , a significant decrease in quality of life ( p=0.03 ) was seen in the watchful waiting group . Twenty-four percent of and rogen-deprived patients assigned to watchful waiting reported high self-assessed quality of life compared with 60 % in the radical prostatectomy group . Eighty-eight percent of patients had clinical ly detected tumors . CONCLUSIONS And rogen deprivation negatively affected self-assessed quality of life in men assigned to watchful waiting . The number of physical symptoms was associated with the level of quality of life . Quality of life was lower with longer follow-up time in both groups and was statistically significant in the watchful waiting group ( p=0.03 ) BACKGROUND AND PURPOSE To prospect ively evaluate long-term urinary , bowel and sexual function after I-125 brachytherapy for localised prostate cancer using patient administered vali date d Quality of Life ( QoL ) instruments . MATERIAL S AND METHODS Between March 1995 and March 2004 , 673 men underwent brachytherapy and recorded urinary symptoms prospect ively using the International Prostate Symptom Score ( IPSS ) . In addition , in a subgroup of 116 patients , the Exp and ed Prostate Cancer Index Composite ( EPIC ) was used to record QoL information on urinary , bowel and sexual function before treatment and at regular time intervals for at least two years . RESULTS Initially , there was a sharp rise in urinary symptoms which was most marked within the first three months . Scores then resolved slowly and returned to within one or two units of pre-treatment level at one year . Subsequently , there was no significant deterioration in urinary symptoms up to nine years following brachytherapy . Few had significant bowel symptoms . Sexual function deteriorated initially and then improved but failed to return to pre-treatment levels by two years . Patients requiring neo-adjuvant hormones experienced significantly more dysfunction . CONCLUSIONS After an initial period of mild to moderate urinary symptoms prostate brachytherapy is well tolerated with relatively little deterioration in long-term quality of life . Long-term reduction in sexual function may be seen particularly in those requiring hormones PURPOSE To assess long-term quality of life ( QoL ) impact of treatments in localized prostate cancer patients treated with radical prostatectomy , external beam radiotherapy or brachytherapy . MATERIAL AND METHODS Observational , prospect i ve cohort study with pre-treatment QoL evaluation and follow-up until five years after treatment . 704 patients with low or intermediate risk localized prostate cancer were consecutively recruited in 2003 - 2005 . QoL was measured by the EPIC question naire , with urinary irritative-obstructive , incontinence , bowel , sexual , and hormonal scores ( ranging 0 - 100 ) . RESULTS Brachytherapy 's QoL impact was restricted to the urinary domain , Generalized Estimating Equation models showed score changes at five years of -12.0 ( 95 % CI=-15.0 , -9.0 ) in incontinence and -5.3 ( 95 % CI=-7.5 , -3.1 ) in irritative-obstructive scales . Compared to brachytherapy , radical prostatectomy fared + 3.3 ( 95 % CI=+0.0 , + 6.5 ) points better in irritative-obstructive but -17.1 ( 95 % CI=-22.7 , -11.5 ) worse in incontinence . Sexual deterioration was observed in radical prostatectomy ( -19.1 ; 95 % CI=-25.1 , -13.1 ) and external radiotherapy groups ( -7.5 ; 95 % CI=-12.5 , -2.5 ) . CONCLUSIONS Brachytherapy is the treatment causing the least impact on QoL except for moderate urinary irritative-obstructive symptoms . Our study provides novel long-term valuable information for clinical decision making , supporting brachytherapy as a possible alternative to radical prostatectomy for patients seeking an attempted curative treatment , while limiting the risk for urinary incontinence and sexual impact on PURPOSE Health-related quality of life ( HRQOL ) after prostate brachytherapy has been extensively described in published reports but hardly any long-term data are available . The aim of the present study was to prospect ively assess long-term HRQOL 6 years after (125)I prostate brachytherapy . METHODS AND MATERIAL S A total of 127 patients treated with (125)I brachytherapy for early-stage prostate cancer between December 2000 and June 2003 completed a HRQOL question naire at five time-points : before treatment and 1 month , 6 months , 1 year , and 6 years after treatment . The question naire included the R AND -36 generic health survey , the cancer-specific European Organization for Research and Treatment of Cancer core question naire ( EORTCQLQ-C30 ) , and the tumor-specific EORTC prostate cancer module ( EORTC-PR25 ) . A change in a score of > /=10 points was considered clinical ly relevant . RESULTS Overall , the HRQOL at 6 years after (125)I prostate brachytherapy did not significantly differ from baseline . Although a statistically significant deterioration in HRQOL at 6 years was seen for urinary symptoms , bowel symptoms , pain , physical functioning , and sexual activity ( p < .01 ) , most changes were not clinical ly relevant . A statistically significant improvement at 6 years was seen for mental health , emotional functioning , and insomnia ( p < .01 ) . The only clinical ly relevant changes were seen for emotional functioning and sexual activity . CONCLUSION This is the first study presenting prospect i ve HRQOL data up to 6 years after (125)I prostate brachytherapy . HRQOL scores returned to approximately baseline values at 1 year and remained stable up to 6 years after treatment . (125)I prostate brachytherapy did not adversely affect patients ' long-term HRQOL PURPOSE To determine prospect ively intermediate-term toxicity and quality of life ( QoL ) of prostate cancer patients after intensity-modulated radiotherapy ( IMRT ) . PATIENTS AND METHODS Fifty-five patients with localized prostate adenocarcinoma were treated by IMRT ( 76 Gy ) . Physicians scored acute and late toxicity using the Common Terminology Criteria for Adverse Events version 3.0 . Patients assessed general and prostate-specific QoL before IMRT ( baseline ) and at 2 , 6 , and 18 months using European Organization for Research and Treatment of Cancer question naires QLQ-C30(+3 ) and QLQ-PR25 . RESULTS Median age was 73 years ( range , 54 - 80 years ) . Risk categories were 18 % low risk , 60 % intermediate risk , and 22 % high risk ; 45 % of patients received hormonal therapy ( median duration , 6 months ) . The incidence of urinary and bowel toxicity immediately after IMRT was , respectively , 38 % and 13 % ( Grade 2 ) and 2 % and none ( Grade 3 ) ; at 18 months it was 15 % and 11 % ( Grade 2 ) and none ( Grade 3 ) . Significant worsening of QoL was reported at 2 months with regard to fatigue ( + 11.31 , p = 1.10(-7 ) ) , urinary symptoms ( + 9.07 , p = 3.10(-11 ) ) , dyspnea ( + 7.27 , p = 0.008 ) , and emotional ( -7.02 , p = 0.002 ) , social ( -6.36 , p = 0.003 ) , cognitive ( -4.85 , p = 0.004 ) , and physical ( -3.39 , p = 0.007 ) functioning . Only fatigue ( + 5.86 , p = 0.003 ) and urinary symptoms ( + 5.86 , p = 0.0004 ) had not improved by 6 months . By 18 months all QoL scores except those for dyspnea ( + 8.02 , p = 0.01 ) and treatment-related symptoms ( + 4.24 , p = 0.01 ) had returned to baseline . These adverse effects were exacerbated by hormonal therapy . CONCLUSION High-dose IMRT with accurate positioning induces only a temporary worsening of Recent reports using extreme hypofractionated regimens in the treatment of low‐risk prostate adenocarcinoma have been encouraging . Here , the authors report on their own multi‐institutional experience with extreme hypofractionated stereotactic radiotherapy for early stage disease To improve and individualise estimates of treatment outcomes for men diagnosed with prostate cancer , we examined the impact of baseline comorbidity on health‐related quality of life ( HRQL ) outcomes in an analysis of two pooled , prospect i ve cohort studies OBJECTIVE As more patients are diagnosed with prostate cancer at an early stage , it is becoming increasingly important to refine the technique of surgical excision . For this purpose we have generated objective data comparing three different surgical approaches used by three experienced surgeons . METHODS We prospect ively compared three contemporary personal series of 50 consecutive radical prostatectomy ( RP ) patients . The health-related quality of life was evaluated preoperatively and in months 1 , 3 , 6 , 12 and 24 . RESULTS Considering in turn the patients undergoing retropubic , perineal and laparoscopic RP , the median procedure time was 2 h and 27 min , 1 h and 50 min and 4 h , with a transfusion rate of 2 , 0 and 8 % , respectively . In the perineal group there were more wound infections . Median catheter drainage was 7 , 10 and 7 days and zero , 13 and one patients needed reinsertion of a catheter . Early continence varied considerably , with 57.4 , 11.4 and 6.3 % of patients pad-free after 1 month , but there were no differences in social continence ( zero or one pad ) with 97.8 , 97.8 and 91.9 % after 2 years . The Litwin score for incontinence ( preoperative minus postoperative ) was -24 , -41 and -63 % after 1 month and -13 , + 3 and -29 % after 2 years . Twenty-nine , five and 15 patients had a preoperative five-item version of International Index of Erectile Function ( IIEF-5 ) score of > or = 17 points and a nerve-sparing procedure . After 2 years , 48.1 , 0 and 0 % had an IIEF-5 score of > or = 17 points without the use of phosphodiesterase type 5 ( PDE-5 ) inhibitors , but when including patients using inhibitors there were no significant differences . CONCLUSIONS A comparison of morbidity , short-term convalescence and long-term side-effects of different surgical techniques is strongly biased by both the preoperative status of patients and the skill of the surgeons . Overall , we found some differences in the short-term results ( e.g. early continence ) and comparable long-term results PURPOSE Active surveillance is an important alternative to definitive therapy for men with low risk prostate cancer . However , the impact of active surveillance on health related quality of life compared to that in men without cancer remains unknown . In this study we evaluated health related quality of life outcomes in men on active surveillance compared to men followed after negative prostate needle biopsy . MATERIAL S AND METHODS A prospect i ve study was conducted on men who were enrolled into the Center for Prostate Disease Research Multicenter National Data base and underwent prostate needle biopsy for suspicion of prostate cancer between 2007 and 2014 . Health related quality of life was assessed at biopsy ( baseline ) and annually for up to 3 years using SF-36 and EPIC question naires . Health related quality of life scores were modeled using generalized estimating equations , adjusting for baseline health related quality of life , and demographic and clinical characteristics . RESULTS Of the 1,204 men who met the initial eligibility criteria 420 had a negative prostate needle biopsy ( noncancer comparison group ) . Among the 411 men diagnosed with low risk prostate cancer 89 were on active surveillance . Longitudinal analysis revealed that for most health related quality of life subscales there were no significant differences between the groups in adjusted health related quality of life score trends over time . CONCLUSIONS In this study most health related quality of life outcomes in patients with low risk prostate cancer on active surveillance did not differ significantly from those of men without prostate cancer . A comparison group of men with a similar risk of prostate cancer detection is critical to clarify the psychological and physical impact of active surveillance PURPOSE There are multiple treatment options for favorable-risk prostate cancer . High-dose-rate ( HDR ) brachytherapy as a monotherapy is appealing , but its use is still investigational . A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer . METHODS AND MATERIAL S This was a single-institution , prospect i ve study . Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 ( 51 % of patients ) and stage T2b to T2c cancer . Treatment with HDR brachytherapy with a single implant was administered over 2 days . One of four fractionation schedules was used in a dose escalation study design : 3 fractions of 10 , 10.5 , 11 , or 11.5 Gy . Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity , the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity , and the Exp and ed Prostate Cancer Index Composite ( EPIC ) question naire to measure patient-reported health-related quality of life . Biochemical failure was defined as a prostate-specific antigen ( PSA ) nadir plus 2 ng/ml . RESULTS Between 2003 and 2008 , 79 patients were enrolled . With a median follow-up of 39.5 months , biochemical relapse occurred in 7 patients . Three- and 5-year actuarial biochemical control rates were 88.4 % ( 95 % confidence interval [ CI ] , 78.0 - 96.2 % ) and 85.1 % ( 95 % CI , 72.5 - 94.5 % ) , respectively . Acute grade 3 urinary toxicity was seen in only 1 patient . There was no instance of acute grade 3 rectal toxicity . Rates of late grade 3 rectal toxicity , dysuria , hematuria , urinary retention , and urinary incontinence were 0 % , 10.3 % , 1.3 % , 9.0 % , and 0 % , respectively . No grade 4 or greater toxicity was recorded . Among the four ( urinary , bowel , sexual , and hormonal ) domains assessed with the EPIC question naire , only the sexual domain did not recover with time . CONCLUSIONS HDR brachytherapy as a monotherapy for favorable-risk prostate cancer , administered using a single implant over 2 days , is feasible and has acceptable acute and late toxicities . Further follow-up is still required to better evaluate the efficacy of such treatment INTRODUCTION There is no conclusive evidence that the robotic-assisted laparoscopic radical prostatectomy ( RARP ) is superior to conventional open radical prostatectomy ( ORP ) when it comes to recovery of urinary and sexual function , and that the former surgical option results in less decision regret . METHODS Patients scheduled for both surgical procedures were surveyed prior to surgery , and then again at 6 and 12 months following treatment using the sexual and urinary modules of the Exp and ed Prostate Cancer Index Composite ( EPIC ) measure . Decision regret was measured at 12 months . Propensity score regression adjustment was used to account for differences between treatment groups by summarizing all covariate information into a single probability and to simulate r and omization . RESULTS At 12 months , urinary summary scores approached baseline levels , while urinary bother scores had returned to baseline . Sexual summary and bother mean scores decreased by about half of what they were at baseline for both treatment groups at 6 and 12 months . No significant differences in the groups ' sexual summary and bother domains were identified at either 6 or 12 months . Both groups ' scores for decision regret were low . Moderate correlations ( r(2 ) range -0.333 to -0.368 ) were between current levels of urinary and sexual function and decision regret at 12 months . CONCLUSION The results of our study found no significant difference in health-related quality of life outcomes based on surgical procedure at 12 months . Moreover , patients in both groups reported low levels of decision regret at 12 months . Further multi-site prospect i ve studies are required to address this study 's limitations INTRODUCTION Although radical prostatectomy ( RP ) is an effective treatment for prostate cancer , it has potentially deleterious effects on health-related quality of life ( HRQoL ) . Utility is an important global measure of HRQoL. This utility is also used in decision-making models and economic evaluations . There are no published prospect i ve data characterizing men 's utilities for health outcomes post-RP . METHODS From July 2003 to June 2006 , patients undergoing RP at the University Health Network in Toronto , Ontario , Canada , completed the Patient-Oriented Prostate Utility Scale ( PORPUS ) , a disease-specific HRQoL and utility instrument . Men were included if they had clinical ly localized prostate cancer and had completed HRQoL measures prior to surgery and at least once within 9 to 18 months after the RP . Health-related quality of life was measured prior to surgery and at 4 stages after surgery : 0 to 3 months , 3 to 9 months , 9 to 18 months , and 18 to 30 months . Statistical analyses included pairwise t-tests and multivariable linear regression comparing changes in scores between baseline and the 9- to 18-month range . RESULTS Two hundred and thirteen men ( mean age 60.9 , median Gleason score 7 ) met the inclusion criteria . At baseline , HRQoL was high ( mean PORPUS-P [ psychometric ] = 83.8 ) . Scores declined sharply by 3 months ( 65.5 , p < 0.001 ) and improved but did not reach baseline by 9 - 18 months ( 75.1 , p < 0.001 ) . Utility scores ( PORPUS-U[utility ] ) showed the same pattern : 0.94 at baseline ; 0.81 at 3 months ( p < 0.001 ) ; and 0.88 at 9 to 18 months ( p < 0.001 ) . Predictors of HRQoL , including baseline PORPUS score , nerve-sparing surgery and smoking status , decline after RP . CONCLUSION Symptom scores are known to be affected up to 12 months after RP . Our study demonstrates that global health status also declines and remains affected 1 year after surgery PURPOSE Obesity adversely affects surgical procedures and outcomes . We used a vali date d health related quality of life measure to examine the effects of obesity on disease specific health related quality of life before and following radical retropubic prostatectomy . MATERIAL S AND METHODS From June 2000 to April 2003 , 575 consecutive patients with prostate cancer were approached to participate in a prospect i ve , health related quality of life study . Health related quality of life was assessed before surgery , and 1 , 4 , 12 , 24 and 36 months postoperatively . Repeated measures mixed models were constructed to determine the independent effects of body mass index on health related quality of life . RESULTS Of 472 consenting subjects 376 ( 80 % ) completed a baseline and at least 1 followup survey . Higher body mass index was associated with worse preoperative hormonal/vitality function ( p = 0.0009 ) and bother ( p = 0.02 ) , and delayed recovery of bowel function ( p = 0.01 ) and bother ( p = 0.01 ) health related quality of life . There were no measurable differences postoperatively in hormonal/vitality , urinary or sexual health related quality of life associated with higher body mass index . Increased body mass index was associated with prostate specific antigen recurrence ( p = 0.05 ) and adjuvant treatment ( p = 0.02 ) . Adjuvant treatment was independently associated with worse bowel function ( p = 0.01 ) and bother ( p = 0.01 ) health related quality of life in obese patients . At 24 months bowel health related quality of life in obese patients no longer significantly differed from that in nonobese patients . CONCLUSIONS Obesity is associated with worse preoperative hormonal/vitality health related quality of life , slower recovery of bowel function and bother health related quality of life after radical retropubic prostatectomy , and prostate specific antigen recurrence . Impaired health related quality of life recovery in obese patients is influenced by disease recurrence and result ant adjuvant therapies . Despite these findings obese patients should not be dissuaded from considering prostatectomy as definitive treatment for localized prostate cancer AIM We prospect ively investigated health-related quality of life ( HR-QOL ) , including sexual function and sexual bother , in patients who underwent nerve grafting during a radical prostatectomy in comparison with those who underwent a non-nerve-sparing radical prostatectomy . METHODS Between August 2001 and May 2004 , radical prostatectomies were performed on 69 patients with clinical T1-T2N0/M0 prostate cancer . Of these , 66 patients ( 22 : nerve-grafting patients , 44 : non-nerve-sparing and non-nerve-grafting patients ) were enroled into this study . The observation periods ranged from 12 - 46 months ( median : 29 months ) . The general HR-QOL was measured with the SF-36 General Health Survey and disease-specific HR-QOL was measured with the University of California Los Angeles-Prostate Cancer Index . RESULTS Penile tumescence was observed in 11 out of 15 ( 73.3 % ) prostate-specific antigen failure-free patients who underwent unilateral nerve grafting with contra-lateral nerve-sparing or bilateral nerve grafting . Vaginal penetration was observed in six out of 15 ( 40.0 % ) patients . The time for partial erection and for intercourse , respectively , ranged from 3 - 21 months ( median = 6 months ) and 6 - 36 months ( median = 13.5 months ) . There were no significant differences in general HR-QOL changes over time between the nerve-grafting patients and the patients without any nerve-preserving procedures . The sexual function score was significantly better in the nerve-grafting ( bilateral nerve graft or unilateral nerve graft with contra-lateral nerve-sparing ) patients than in the non-nerve-sparing/non-nerve-grafting patients . The sexual bother score , however , was more serious for the patients who underwent nerve-grafting surgery than for the non-nerve-sparing/non-nerve-grafting patients . CONCLUSION Sexual bother is serious for patients who attempt to maintain sexual function after special surgical procedures , such as nerve-grafting surgery . We should be aware that careful counseling is needed to avoid impatient and excessive hope for the recovery of sexual function BACKGROUND AND PURPOSE High dose-rate ( HDR ) brachytherapy is most commonly administered as a boost in two or more fractions combined with external beam radiotherapy ( EBRT ) . Our purpose is to compare outcomes with a single fraction HDR boost to that with a st and ard fractionated boost in intermediate risk prostate cancer . MATERIAL S AND METHODS Results of two sequential phase II clinical trials are compared . The Single Fraction protocol consists of 15 Gy HDR in one fraction followed by 37.5 Gy EBRT in 15 fractions over 3 weeks ; the St and ard Fractionation protocol consisted of two HDR fractions each of 10 Gy , 1 week apart , followed by 45 Gy EBRT in 25 fractions . Patients had intermediate risk disease , and were well balanced for prognostic factors . Patients were followed prospect ively for efficacy , toxicity and health-related quality of life ( Exp and ed Prostate Index Composite ) . Efficacy was assessed biochemically using the Phoenix definition , and by biopsy at 2 years . RESULTS The Single Fraction protocol accrued 123 patients and the St and ard Fractionation protocol , 60 . With a median follow-up of 45 and 72 months , respectively , the biochemical disease-free survival was 95.1 % and 97.9 % in the Single and St and ard Fractionation trials ( p=0.3528 ) . Two-year prostate biopsy was positive in only 4 % and 8 % , respectively . There was no difference in late urinary or rectal toxicity rates , or in health-related quality of life between the two protocol s. CONCLUSIONS The Single Fraction HDR protocol results in high disease control rate and low toxicity similar to our previous protocol using two HDR insertions , with significant savings in re sources . While mature results with longer follow-up are awaited , a single 15 Gy may be considered as a st and ard fractionation regimen in combination with EBRT for men with intermediate risk disease OBJECTIVES To examine the contributions of fear of recurrence and the more commonly examined treatment-related symptoms to the health-related quality of life ( HRQOL ) of men treated for localized prostate cancer . METHODS A total of 730 men with localized disease were identified from the Cancer of the Prostate Strategic Urologic Research Endeavor , a national , prospect i ve study of men with prostate cancer . Pre- to post-treatment changes in fear of recurrence , treatment-specific symptoms and burden , comorbidities at diagnosis , number of new symptoms , and post-treatment HRQOL data were analyzed . RESULTS Linear regression , adjusted for clinical and demographic characteristics , showed that improved fear of recurrence ( P < 0.01 ) , higher number of post-treatment symptoms ( P < 0.01 ) , and improved bowel function ( P < 0.01 ) significantly predicted better mental health scores . For physical health , improved urinary bother ( P < 0.01 ) and lower number of post-treatment symptoms ( P < 0.01 ) were associated with better physical health . CONCLUSION Underst and ing men 's fears about cancer recurrence and how these fears influence physical and mental health are important components of providing care to this growing population BACKGROUND Most previous studies of prostate cancer ( CaP ) patients have focused on functional side effects . In the decision about treatment , the patients ' subjective experience of function ( bother ) should also be considered . In this prospect i ve study of CaP patients , we used both categorical and dimensional methods to examine changes of sexual , urinary , and bowel bother after robot-assisted prostatectomy ( RALP ) , after high dose radiotherapy alone ( RAD ) , or with adjuvant and rogen deprivation therapy ( RAD + ADT ) . We also studied the associations between psychosocial factors and post-treatment bother and the correlations between bother and function at the follow-up time points . METHODS A total of 462 patients ( n = 150 RALP , n = 104 RAD , and n = 208 RAD + ADT ) completed question naires at all time points ( baseline , 3 , 6 , 12 , and 24 months post-treatment ) . Our outcome measures were the proportion of patients who regained their baseline bother core ( PBS-100 ) and the mean group scores on sexual , urinary , and bowel bother based on the UCLA-PCI question naire . Generalized estimating equation ( GEE ) identified the time points at which various variables were significantly associated with bother at 2 years . The time points at which the proportions of bothered patients became stable were defined . RESULTS The different treatment modalities provided distinctive patterns over time regarding urinary , sexual , and bowel bothers . RALP gave sexual and urinary bother , RAD + ADT patients reported bowel and sexual bother , while RAD patient suffered mainly from bowel bother . According to GEE , the bother scores at 3 or 6 months were significantly associated with the bother scores at 24 months for all groups . PBS-100 and stability of the recovered bother domains was reached at 3 to 6 months . Strong correlations were observed between function and bother for the urinary and bowel domains but not for the sexual domain . The associations between psychosocial factors and bother were weak . CONCLUSIONS Two years after treatment , RALP patients mainly reported sexual and urinary bother , while irradiated patients were bothered by bowel dysfunction . Sexual , urinary , and bowel bother reached stable proportions at 3 to 6 months post-treatment . Based on GEE , bother at 6 months was in general significantly associated with bother at 24 months PURPOSE We determined factors associated with bother , the distress patients experience as a result of functional detriments after treatment for localized prostate cancer . MATERIAL S AND METHODS A prospect i ve cohort of men treated for clinical ly localized prostate cancer completed a question naire comprising the UCLA-PCI , Medical Outcomes Study Short Form-36 , American Urological Association Symptom Index and Memorial Anxiety Scale for Prostate Cancer fear of recurrence subscale . We used nonlinear mixed models to identify factors associated with severe urinary , sexual and bowel bother . RESULTS Worse function scores were associated with severe urinary , sexual and bowel bother following treatment ( OR 0.88 - 0.94 , p < 0.001 ) . Worse American Urological Association Symptom Index score was associated with severe urinary bother ( OR 1.22 , 95 % CI 1.16 - 1.28 ) . Time since treatment was inversely associated with urinary ( OR 0.68 , 95 % CI 0.54 - 0.83 ) and bowel bother ( OR 0.63 , 95 % CI 0.47 - 0.80 ) early after treatment but not for the entire 48-month study period . Receipt of concomitant and rogen deprivation therapy was not associated with bother 48 months after radiation . CONCLUSIONS Addressing functional detriment may confer improvement in urinary , sexual and bowel bother . Patient distress related to dysfunction improves with time . Measuring health related quality of life after prostate cancer treatment should incorporate functional and bother assessment PURPOSE We evaluated urinary and sexual quality of life 1 year following robotic laparoscopic radical prostatectomy and identified preoperative variables predictive of a severe decrease from baseline . MATERIAL S AND METHODS Using a prospect i ve robotic laparoscopic radical prostatectomy data base we identified patients with greater than 1 year of postoperative followup . The UCLA-PCI SF-36v2 question naire was used to evaluate urinary and sexual quality of life before and 1 year after surgery . Severe worsening of the postoperative score was defined as a greater than 1 SD decrease . Demographic and preoperative clinical variables were evaluated along with baseline scores on univariate and multivariate analysis . RESULTS Between February 2003 and September 2007 a total of 1,225 robotic laparoscopic radical prostatectomies were performed at our center and 361 patients ( 52 % ) met inclusion criteria . On multivariate analysis baseline urinary function was the only predictor of significant worsening of urinary function ( OR 1.04 , p = 0.003 ) . Baseline urinary bother was the only predictor of significant worsening of urinary bother ( OR 1.05 , p < 0.0001 ) . A significant decrease in sexual function was predicted by baseline sexual function ( OR 1.03 , p = 0.0001 ) , baseline sexual bother ( OR 1.03 , p = 0.005 ) and nerve sparing technique ( OR 0.31 , p = 0.05 ) . Predictors of a significant decrease in sexual bother were also baseline sexual function ( OR 1.02 , p = 0.0001 ) , baseline sexual bother ( OR 1.04 , p = 0.0007 ) and nerve sparing technique ( OR 0.38 , p = 0.02 ) . ORs indicated that higher baseline scores corresponded to a higher risk of postoperative score worsening . CONCLUSIONS We found that overall better baseline sexual and urinary scores are associated with better postoperative outcomes . However , the risk of a significant decrease in urinary function , urinary bother , sexual function and sexual bother is higher in patients with better baseline scores . Nerve sparing positively affects sexual function and sexual bother PURPOSE To prospect ively assess health-related quality of life ( HRQOL ) during the first year after treatment with prostate brachytherapy ( PB ) alone for T1c-2a prostate cancer . MATERIAL S AND METHODS Ninety-eight patients from 24 institutions were eligible and properly entered on this study . All patients were treated with PB alone using I-125 ( Oncura Model 6711 ) . The prescription dose was 145 Gy . Three separate health-related quality of life question naires ( HRQOL ) ( Functional Assessment of Cancer Therapy-Prostate [ FACT-P ] , Sexual Adjustment Question naire [ SAQ ] , and International Prostate Symptom Score [ IPSS ] ) were self-administered before and after PB ( baseline ; 3 , 6 , 9 , and 12 months after PB ) . The st and ard error of the mean ( SEM ) was used to analyze changes in HRQOL scores over time . Patients who improved greater than the SEM were categorized as improved ; patients that declined greater than the SEM were categorized as declined ; patients were otherwise categorized as stable . All changes are measured using the pretreatment HRQOL score as baseline . RESULTS The percentage of men who reported the ability to have an erection decreased from 73 % at baseline ( 65 % unassisted , 8 % assisted ) to 57 % at 1 year ( 36 % unassisted , 21 % assisted ) . The rate of urinary incontinence increased to 14 % at 6 months but had decreased to 1 % at the 12-month follow-up . At 1 year after PB , 80 % of men reported decreased sexual functioning according to SAQ scores . More than 60 % of men reported decreased urinary function at 12 months compared with baseline . CONCLUSIONS This article represents the first prospect i ve , multi-institutional study of HRQOL in men treated with PB and demonstrates that patients undergoing PB have a very high overall HRQOL . The rate of incontinence by 1 year after PB is low , but many patients continue to have obstructive symptoms at 1 year . Although 78 % of 1-year respondents state that they can achieve an erection with or without assistance , almost 50 % report a decrease in sexual function PURPOSE Stereotactic body radiation therapy ( SBRT ) is a treatment option for patients with localized prostate cancer , with reported clinical and health-related quality -of-life ( QOL ) outcomes comparable to st and ard fractionation radiation therapy . The goal of this study was to evaluate correlations between short-term QOL outcomes and dosimetric parameters to guide future prostate SBRT planning . METHODS AND MATERIAL S From 2010 to 2013 , QOL data were prospect ively collected from 75 patients enrolled in a prostate SBRT clinical trial . A comparison was made between Exp and ed Prostate Cancer Index Composite scores for patients with the top 25th percentile versus the bottom 75th percentile of the following dose-volume histogram parameters : planning target volume V100 ; bladder V50 and V100 ; and rectum V50 , V80 , V90 , and V100 . A linear mixed-effect model was used to estimate the difference between the 2 strata for each parameter . RESULTS Median follow-up was 12 months . Patients with planning target volume V100 volumes > 120 cm(3 ) had the worst reduction in urinary QOL . Urinary QOL was also decreased significantly in patients with bladder V100 volumes > 5.5 cm(3 ) . Bowel QOL was decreased significantly in patients with rectal V90 and V100 volumes > 4.2 and > 1.5 cm(3 ) , respectively . CONCLUSIONS Patients with large prostate size or large volumes of rectum and bladder that receive ≥90 % of the prescribed radiation dose are more susceptible to short-term QOL decrements after prostate SBRT . These volumes should be minimized to maximize recovery to baseline QOL after prostate SBRT BACKGROUND AND PURPOSE Multi-fraction high dose-rate ( HDR ) brachytherapy as monotherapy is safe and effective for low and intermediate risk prostate cancer . Two or single fraction regimens have some radiobiological rationale . The purpose is to determine toxicity and effect on health related quality of life ( HRQOL ) of single fraction 19Gy or 13.5Gy × 2 . MATERIAL S AND METHODS Eligible patients had low or intermediate risk prostate cancer , prostate volume < 60cc , and no and rogen deprivation use . 170 patients were r and omized to receive either a single 19Gy or two fractions of 13.5Gy 1week apart . HRQOL was measured using the Exp and ed Prostate Index Composite ( EPIC ) , toxicity with Common Terminology for Adverse Events ( CTCAE ) v4.0 and urinary symptoms with the International Prostate Symptom Score ( IPSS ) . RESULTS Median follow-up is 20months . Grade 2 urinary toxicity occurred in 51 % within the first 3months and in 31 % thereafter with no significant difference between treatment arms . Ten patients ( 6 % ) developed urinary retention in the acute phase , although only 4 ( 2.4 % ) required a catheter for more than 48h . One Grade 3 acute ( ⩽3months ) and late ( > 3months ) urinary toxicity occurred . No more than 1 % had any Grade 2 GI toxicity . The 2-fraction arm had a higher occurrence of grade 2 erectile dysfunction ( 29 % vs. 11.5 % , p=0.0249 ) and higher IPSS scores for the first year . Mean EPIC urinary scores at 12months decreased by 4.0 and 4.6 , and sexual scores decreased by 8 and 15.9 ( p=0.035 ) in the single and 2-fraction arms , respectively . No change occurred in the bowel or hormonal domains . CONCLUSIONS Single 19Gy and 13.5Gy × 2 are both well tolerated . During the first 12months , urinary symptoms and erectile dysfunction are more common in the 2-fraction arm PURPOSE To report 5-year clinical outcomes of 3 prospect i ve trials of image-guided proton therapy for prostate cancer . METHODS AND MATERIAL S A total of 211 prostate cancer patients ( 89 low-risk , 82 intermediate-risk , and 40 high-risk ) were treated in institutional review board-approved trials of 78 cobalt gray equivalent ( CGE ) in 39 fractions for low-risk disease , 78 to 82 CGE for intermediate-risk disease , and 78 CGE with concomitant docetaxel therapy followed by and rogen deprivation therapy for high-risk disease . Toxicities were grade d according to Common Terminology Criteria for Adverse Events ( CTCAE ) , version 3.0 . Median follow-up was 5.2 years . RESULTS Five-year rates of biochemical and clinical freedom from disease progression were 99 % , 99 % , and 76 % in low- , intermediate- , and high-risk patients , respectively . Actuarial 5-year rates of late CTCAE , version 3.0 ( or version 4.0 ) grade 3 gastrointestinal and urologic toxicity were 1.0 % ( 0.5 % ) and 5.4 % ( 1.0 % ) , respectively . Median pretreatment scores and International Prostate Symptom Scores at > 4 years posttreatment were 8 and 7 , 6 and 6 , and 9 and 8 , respectively , among the low- , intermediate- , and high-risk patients . There were no significant changes between median pretreatment summary scores and Exp and ed Prostate Cancer Index Composite scores at > 4 years for bowel , urinary irritative and /or obstructive , and urinary continence . CONCLUSIONS Five-year clinical outcomes with image-guided proton therapy included extremely high efficacy , minimal physician-assessed toxicity , and excellent patient-reported outcomes . Further follow-up and a larger patient experience are necessary to confirm these favorable outcomes OBJECTIVES To prospect ively investigate the influence of 3-month neoadjuvant hormonal therapy ( NHT ) before brachytherapy ( BT ) for low-risk prostate cancer ( PCa ) on urinary function and health-related quality of life ( HRQL ) . METHODS Between 2003 and 2008 , 300 patients with PCa were treated with BT using (125)I str and ed seeds , of whom 86 received 3-month NHT to downsize the prostate before treatment . Urinary complaints were measured on all occasions with the International Prostate Symptom Score ( n = 134 ) and European Organization for Research and Treatment of Cancer- Quality of Life Question naire PR25 ( EORTC-QLQ-PR25 question naire ; n = 118 ) and HRQL with the EORTC-QLQ-C30 ( n = 120 ) question naire . RESULTS Post-BT , urinary function became worse over the first 6 weeks and then improved steadily , but did not return to baseline levels at 1 year . At baseline , the NHT group reported worse urinary function compared with the non-NHT group ( P < .01 ) . However , the post-BT improvement of urinary function was better in the NHT group at 3 months ( P < .05 ) . Global HRQL , physical , role and social functioning decreased over the first 3 months ( P < .05 ) post-BT but returned to baseline levels within 1 year . Emotional function steadily improved over the 1-year follow-up period ( P < .001 ) . The NHT group reported better global HRQL , social and emotional functioning 1 year post-BT compared with baseline ( P < 05 ) . All results were adjusted for comorbidity . This is a single-center study with a follow-up of 1 year , thereby potentially limiting the general applicability of the results . CONCLUSIONS Three months of NHT before BT might positively influence urinary function and HRQL up to 1 year post-BT . Therefore , PCa patients should not be dissuaded from considering NHT followed by BT because of prostate size 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 Importance Patients diagnosed with localized prostate cancer have to decide among treatment strategies that may differ in their likelihood of adverse effects . Objective To compare quality of life ( QOL ) after radical prostatectomy , external beam radiotherapy , and brachytherapy vs active surveillance . Design , Setting , and Participants Population -based prospect i ve cohort of 1141 men ( 57 % participation among eligible men ) with newly diagnosed prostate cancer were enrolled from January 2011 through June 2013 in collaboration with the North Carolina Central Cancer Registry . Median time from diagnosis to enrollment was 5 weeks , and all men were enrolled with written informed consent prior to treatment . Final follow-up date for current analysis was September 9 , 2015 . Exposures Treatment with radical prostatectomy , external beam radiotherapy , brachytherapy , or active surveillance . Main Outcomes and Measures Quality of life using the vali date d instrument Prostate Cancer Symptom Indices was assessed at baseline ( pretreatment ) and 3 , 12 , and 24 months after treatment . The instrument contains 4 domains — sexual dysfunction , urinary obstruction and irritation , urinary incontinence , and bowel problems — each scored from 0 ( no dysfunction ) to 100 ( maximum dysfunction ) . Propensity-weighted mean domain scores were compared between each treatment group vs active surveillance at each time point . Results Of 1141 enrolled men , 314 pursued active surveillance ( 27.5 % ) , 469 radical prostatectomy ( 41.1 % ) , 249 external beam radiotherapy ( 21.8 % ) , and 109 brachytherapy ( 9.6 % ) . After propensity weighting , median age was 66 to 67 years across groups , and 77 % to 80 % of participants were white . Across groups , propensity-weighted mean baseline scores were 41.8 to 46.4 for sexual dysfunction , 20.8 to 22.8 for urinary obstruction and irritation , 9.7 to 10.5 for urinary incontinence , and 5.7 to 6.1 for bowel problems . Compared with active surveillance , mean sexual dysfunction scores worsened by 3 months for patients who received radical prostatectomy ( 36.2 [ 95 % CI , 30.4 - 42.0 ] ) , external beam radiotherapy ( 13.9 [ 95 % CI , 6.7 - 21.2 ] ) , and brachytherapy ( 17.1 [ 95 % CI , 7.8 - 26.6 ] ) . Compared with active surveillance at 3 months , worsened urinary incontinence was associated with radical prostatectomy ( 33.6 [ 95 % CI , 27.8 - 39.2 ] ) ; acute worsening of urinary obstruction and irritation with external beam radiotherapy ( 11.7 [ 95 % CI , 8.7 - 14.8 ] ) and brachytherapy ( 20.5 [ 95 % CI , 15.1 - 25.9 ] ) ; and worsened bowel symptoms with external beam radiotherapy ( 4.9 [ 95 % CI , 2.4 - 7.4 ] ) . By 24 months , mean scores between treatment groups vs active surveillance were not significantly different in most domains . Conclusions and Relevance In this cohort of men with localized prostate cancer , each treatment strategy was associated with distinct patterns of adverse effects over 2 years . These findings can be used to promote treatment decisions that incorporate individual preferences OBJECTIVE The health-related quality of life ( HRQOL ) after a radical retropubic prostatectomy ( RRP ) or a permanent prostate brachytherapy ( PPB ) was prospect ively compared at a single institute . METHODS Between 2003 and 2005 , 122 patients were treated by RRP and 82 patients were treated by PPB . A QOL survey was completed at baseline , and 1 , 3 , 6 and 12 months after treatment , prospect ively . RESULTS The general HRQOL was not different between the RRP and PPB groups after 3 months . However , at 1 month after treatment , the general HRQOL scores , except for general health , were significantly better in the PPB group than that in the RRP group . Moreover , the disease-specific QOL was worse in urinary and sexual functions in the RRP group . Urinary function in the RRP group had not recovered to baseline after 12 months . Although the urinary function in the PPB group was better than that of the RRP group , urinary bother continued to worsen until 6 months and thereafter it recovered gradually . The bowel function was not worse in the PPB group but bowel bother was worse at 6 months in the PPB group . In the RRP group , the patients with nerve sparing demonstrated better in sexual function than those without nerve sparing , but the recovery did not reach the level of the PPB group . CONCLUSIONS This prospect i ve study revealed the differences in the QOL after RRP and PPB . These results will be helpful for making treatment decisions In this prospect i ve , longitudinal study the authors examined changes in cognitive , emotional , and interpersonal components of prostate cancer-related quality of life in 71 men who underwent robotic-assisted prostatectomy for prostate cancer . They identified significant changes across several quality -of-life domains from presurgery to 3-months and 1-year postsurgery . Although some components of quality of life returned to baseline by one year postsurgery , decrements in sexual intimacy , sexual confidence , and masculine self-esteem were enduring . These data can be used to guide patients in their expectations for quality of life following robotic prostatectomy and highlight the need for multidisciplinary approaches aim ed at improving men 's sexual adjustment after this procedure Purpose : Harms of prostate cancer treatment on urinary health related quality of life have been thoroughly studied . In this study we evaluated not only the harms but also the potential benefits of prostate cancer treatment in relieving the pretreatment urinary symptom burden . Material s and Methods : In American ( 1,021 ) and Spanish ( 539 ) multicenter prospect i ve cohorts of men with localized prostate cancer we evaluated the effects of radical prostatectomy , external radiotherapy or brachytherapy in relieving pretreatment urinary symptoms and in inducing urinary symptoms de novo , measured by changes in urinary medication use and patient reported urinary bother . Results : Urinary symptom burden improved in 23 % and worsened in 28 % of subjects after prostate cancer treatment in the American cohort . Urinary medication use rates before treatment and 2 years after treatment were 15 % and 6 % with radical prostatectomy , 22 % and 26 % with external radiotherapy , and 19 % and 46 % with brachytherapy , respectively . Pretreatment urinary medication use ( OR 1.4 , 95 % CI 1.0–2.0 , p = 0.04 ) and pretreatment moderate lower urinary tract symptoms ( OR 2.8 , 95 % CI 2.2–3.6 ) predicted prostate cancer treatment associated relief of baseline urinary symptom burden . Subjects with pretreatment lower urinary tract symptoms who underwent radical prostatectomy experienced the greatest relief of pretreatment symptoms ( OR 4.3 , 95 % CI 3.0–6.1 ) , despite the development of deleterious de novo urinary incontinence in some men . The magnitude of pretreatment urinary symptom burden and beneficial effect of cancer treatment on those symptoms were verified in the Spanish cohort . Conclusions : Men with pretreatment lower urinary tract symptoms may experience benefit rather than harm in overall urinary outcome from primary prostate cancer treatment . Practitioners should consider the full spectrum of urinary symptom burden evident before prostate cancer treatment in treatment decisions |
10,502 | 17,388,668 | The trial in Thail and , which r and omised individuals to ITNs or untreated nets , showed reductions in anaemia and fetal loss in all gravidae , but not reductions in clinical malaria or low birth weight .
CONCLUSIONS ITNs used throughout pregnancy or from mid-pregnancy onwards have a beneficial impact on pregnancy outcome in malaria-endemic Africa in the first few pregnancies . | BACKGROUND Protection from malaria with insecticide-treated bednets ( ITNs ) during pregnancy is widely advocated , but evidence of benefit has been inconsistent . | Spatial analyses of the effect of insecticide (permethrin)-treated bed nets ( ITNs ) on nearby households both with and without ITNs was performed in the context of a large-scale , group-r and omized , controlled mortality trial in Asembo , western Kenya . Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality , moderate anemia , high-density parasitemia , and hemoglobin levels . This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs . This implies that in areas with intense malaria transmission with high ITN coverage , the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not , as commonly supposed , by simple imposition of a physical barrier protecting individuals from biting . The strength of the community effect depended upon the proportion of nearby compounds with treated nets . To maximize their public health impact , high coverage with treated nets is essential The effectiveness of insecticide-treated bednets ( ITBN ) in preventing malaria and anaemia among primigravidae living in Kilifi District , Kenya , was assessed by a r and omized controlled trial between September 1994 and November 1995 . All residents within 28 community clusters received ITBN in July 1993 , whilst residents of another 28 clusters served as contemporaneous controls . All resident primigravid women with singleton pregnancies attending antenatal care at Kilifi District Hospital were eligible for recruitment . 503 primigravidae were recruited . 91.4 % were anaemic antenatally ( Hb < 11 g/dl ) : 91.0 % from the intervention arm and 92.0 % from the control arm . Severe anaemia ( Hb < 7 g/dl ) was found among 15.1 % of intervention women and 20.1 % of control women ( P = 0.28 ) . No significant differences were observed in reports of febrile illness or the presence of chloroquine in the serum or peripheral parasitaemia during the third trimester between the two groups . In the women delivering in hospital ( n = 130 ) , there was no association between placental malaria infection and the intervention : 77.4 % of placentas from control women had evidence of past or active infection , compared with 72.0 % of placentas from intervention women ( P = 0.76 ) . Similarly , in the women delivering in hospital , ITBN did not improve birth weight , and there were no differences in perinatal mortality between the two study groups . Despite ITBN having a great impact on paediatric severe malaria and mortality in this transmission setting , there was very little impact of ITBN on the morbidity associated with malaria infection in primigravidae . Alternative strategies are required to tackle this continued public health problem for pregnant women living in endemic areas similar to the Kenyan Coast The impact of insecticide (permethrin)-treated bed nets ( ITNs ) on malaria in pregnancy was studied in a rural area in western Kenya with intense perennial malaria transmission . All households in 40 of 79 villages were r and omized to receive ITNs by January 1997 . The ITNs were distributed in control villages two years later . Complete data on birth outcome were available on 2,754 ( 89.6 % ) of 3,072 deliveries . Women ( n = 780 ) were followed monthly throughout pregnancy in 19 of 79 villages . Among gravidae 1 - 4 , ITNs were associated with reductions of 38 % ( 95 % confidence interval [ CI ] = 17 - 54 % ) in the incidence of malaria parasitemia and 47 % ( 95 % CI = 6 - 71 % ) in the incidence of severe malarial anemia ( hemoglobin level < 8 g/dL with parasitemia ) during pregnancy . At the time of delivery , mean hemoglobin levels were 0.6 g/dL ( 95 % CI = 0.01 - 1.2 g/dL ) higher , the prevalence of placental or maternal malaria was reduced by 35 % ( 95 % CI = 20 - 47 % ) , and the prevalence of low birth weight was reduced by 28 % ( 95 % CI = 2 - 47 % ) in gravidae 1 - 4 from ITN villages . No beneficial impact was observed in gravidae five or higher . In areas of intense perennial malaria transmission , permethrin-treated bed nets reduce the adverse effect of malaria during the first four pregnancies As part of a community-based , group-r and omized , controlled trial of insecticide-treated bed nets ( ITNs ) in an area with intense malaria transmission in western Kenya , a birth cohort ( n = 833 ) was followed monthly until the age of 24 months to determine the potential beneficial and adverse effects of reduced malaria exposure during pregnancy and infancy . Malaria transmission and morbidity were comparable pre-intervention . The ITNs reduced malaria attack rates ( force of infection ) in infancy by 74 % , and delayed the median time-to-first parasitemia ( 4.5 to 10.7 months ; P < 0.0001 ) . The incidence of both clinical malaria and moderate-severe anemia ( hemoglobin level < 7 g/dL ) were reduced by 60 % ( P < 0.001 for both ) . Protective efficacy was greatest in infants less than three months old and similar in older infants and one-year-old children . Efficacy was lowest in the dry season . Infants from ITN villages experienced better height and weight gain . In areas of intense perennial malaria transmission , ITNs substantially reduce exposure to malaria and subsequent malaria-associated morbidity in children less than 24 months old . Reduced malaria exposure during infancy did not result , with continued ITN use , in increased malaria morbidity in one-year-old children A prospect i ve comparison of the antimalarial efficacy of bed nets was conducted with 341 pregnant women living in a mesoendemic malarious area of the Thai-Burmese border . Women in 3 adjacent study sites were allocated at r and om to receive either a single size permethrin-impregnated bed net ( PIB ) , a non-impregnated bed net ( NIB ) , or to a control group who used either their own family size non-impregnated bed net ( FNIB ) or no net . In one study site , but not the other 2 , PIB significantly reduced parasite densities and , together with FNIB , reduced the incidence of malaria in pregnancy from 56 % to 33 % ( relative risk = 1.67 , confidence interval = 1.07 - 2.61 , P = 0.03 , allowing for parity ) . Anaemia proved a more sensitive marker of bed net antimalarial efficacy than parasite rates . The incidence of anaemia ( haematocrit < 30 % ) at all study sites was significantly lower at delivery in the PIB ( 27 % ) and FNIB groups ( 21 % ) than in the NIB group ( 41 % ) or those using no net ( 56 % ) . This suggests that a significant proportion of the malaria in pregnancy in this mesoendemic area was sub-patent . Both patent Plasmodium falciparum parasitaemia and anaemia were associated with a reduction in birth weight . Infant mortality was high ( 16 % ) and strongly associated with prematurity , low birth weight and maternal anaemia . PIB were well tolerated and had no apparent adverse effect on the pregnancy or infant development . Although the overall effect of bed nets on patent parasitaemia was marginal , they were associated with a significant reduction in maternal malaria-associated anaemia . ( ABSTRACT TRUNCATED AT 250 WORDS To compare the effects of intermittent treatment with sulfadoxine-pyrimethamine ( SP ) given during the second and third trimester of pregnancy , the use of insecticide-treated nets ( ITN ) , or the combination of both on haemoglobin ( Hb ) levels during pregnancy , a r and omized , placebo-controlled intervention trial was conducted in a malaria-endemic area of western Kenya from July 1997 to September 1999 . Primigravidae and secundigravidae were enrolled into the study and r and omized into 4 intervention groups : ( i ) ITNs and SP , ( ii ) ITNs and placebo SP , ( iii ) SP alone , and ( iv ) placebo SP . All groups were offered case management and iron and folic acid supplementation . Seven hundred and fifty-two women were followed until delivery ( 53.2 % were primigravidae and 46.8 % secundigravidae ) . Among primigravidae in all the groups there was a significant improvement in Hb levels at delivery ( 107.6 g/L ) compared with recruitment ( 101.9 g/L ) ( P < 0.006 ) with the greatest improvement in the combination ITNs + SP group . The protective efficacy of ITNs + SP on anaemia was 55.8 % ( 95 % CI 30.6 - 71.8 ) , of SP alone 50.9 % ( 95 % CI 22.2 - 69.0 ) , and of ITNs 41.6 % ( 95 % CI 9.8 - 62.3 ) . Among secundigravidae , Hb levels were slightly lower at delivery compared with recruitment ( P = 0.03 ) . It was concluded that malaria is a major cause of anaemia in primigravidae but that other causes play a more significant role in secundigravidae , and that intermittent treatment with SP or use of ITNs benefits primigravidae more than secundigravidae Effects of the distribution in space of permethrin (insecticide)-impregnated bed nets ( IIBNS ) on child mortality were studied in a r and omized controlled trial of IIBNs in a an area highly endemic for Plasmodium falciparum malaria in rural northern Ghana . Eight hundred sixty-two deaths occurred among children 6 - 59 months of age during 16,841 child-years-at-risk . Mortality increased with the distance from health facilities but not with proximity to identifiable anopheline breeding sites ( reservoirs ) . The efficacy of IIBNs was independent of these distances . Mortality in users of IIBNs was independent of the proximity of nonusers , and mortality rates of nonusers and users living close to each other were similar . Poisson regression estimated a 6.7 % increase in mortality among nonusers with each 100-m shift away from the nearest compound with IIBNS , indicating that the insecticide protects nearby nonusers . High coverage of IIBNs achieves maximum impact , but users of IIBNs offer some protection to less fortunate neighbors if coverage is incomplete The impact of insecticide-treated bednet use on malaria and anaemia in pregnancy was assessed , as a supplementary study , in a major WHO/TDR-supported bednet trial in northern Ghana between July 1994 and April 1995 . The study area was divided into 96 clusters of compounds , with 48 clusters being r and omly allocated to intervention . All pregnant women were included in the study but the focus was on primigravidae and secundigravidae . 1961 pregnant women were recruited into the study --1033 ( 52.7 % ) in the treated bednet group and 928 ( 47.3 % ) in the no net group . 1806 ( 92.1 % ) had blood taken for malaria microscopy and haemoglobin determination in the third trimester . Pregnancy outcomes were reported for 847 women . The characteristics of women in intervention and control groups were comparable . The odds ratios , with 95 % confidence interval ( CI ) , for different study endpoints were , for Plasmodium falciparum parasitaemia--0.89 ( 0.73 , 1.08 ) , for anaemia--0.88 ( 0.70 , 1.09 ) , for low birthweight (LBW)--0.87 ( 0.63 , 1.19 ) , indicating no benefit for treated bednet use . Effective net use by parity varied from 42 % in primigravidae to 63 % in multigravidae , in spite of free nets and insecticide impregnation . The main reasons for not using a net were warm weather and perceived absence of mosquito biting . Chloroquine use in pregnancy was low and comparable in both groups . Implication s of findings for malaria control in pregnancy and further research are discussed |
10,503 | 23,434,074 | Significant advances have been made in HER2 targeting , result ing in a marked increase in the number of breast cancer patients experiencing tumour pCR . | Targeting human epidermal growth factor receptor 2 ( HER2 ) during or in sequence with chemotherapy improves overall survival in metastatic and early HER2-overexpressing breast cancer .
In this paper we systematic ally review neoadjuvant clinical trial data in HER2-positive breast cancer and discuss key unanswered clinical questions . | BACKGROUND Trastuzumab plus chemotherapy has become the st and ard of care for women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer . Trastuzumab-based pre-operative systemic ( neo-adjuvant ) therapy ( PST ) also appears promising , warranting further investigation . PATIENTS AND METHODS Patients with HER2-positive , stage II/III non-inflammatory , operable breast cancer requiring a mastectomy ( but who wished to conserve the breast ) received weekly trastuzumab and 3-weekly docetaxel for six cycles before surgery . The primary end point was pathological complete response ( pCR ) rate , determined from surgical specimens . RESULTS Thirty-three patients were enrolled . The majority ( 79 % ) had T2 tumors , with 42 % being N1/2 . Twenty-nine patients completed six cycles of therapy and one patient withdrew prematurely due to progressive disease . A complete or partial objective clinical response was seen in 96 % ( 73 % and 23 % , respectively ) of patients . Surgery was performed in 30 patients , breast conserving in 23 ( 77 % ) . In an intention-to-treat analysis , tumor and nodal pCR was seen in 14 ( 47 % ) patients . Treatment was generally well tolerated . Grade 3/4 neutropenia occurred in 85 % of patients while febrile neutropenia was encountered in 18 % . Only three patients withdrew prematurely due to toxicity . No symptomatic cardiac dysfunction was reported . CONCLUSIONS PST with trastuzumab plus docetaxel achieved promising efficacy , with a high pCR rate and good tolerability , in women with stage II or III HER2-positive breast cancer BACKGROUND Studies with pertuzumab , a novel anti-HER2 antibody , show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy . We investigated the combination of pertuzumab or trastuzumab , or both , with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting . METHODS In this multicentre , open-label , phase 2 study , treatment-naive women with HER2-positive breast cancer were r and omly assigned ( 1:1:1:1 ) central ly and stratified by operable , locally advanced , and inflammatory breast cancer , and by hormone receptor expression to receive four neoadjuvant cycles of : trastuzumab ( 8 mg/kg loading dose , followed by 6 mg/kg every 3 weeks ) plus docetaxel ( 75 mg/m(2 ) , escalating , if tolerated , to 100 mg/m(2 ) every 3 weeks ; group A ) or pertuzumab ( loading dose 840 mg , followed by 420 mg every 3 weeks ) and trastuzumab plus docetaxel ( group B ) or pertuzumab and trastuzumab ( group C ) or pertuzumab plus docetaxel ( group D ) . The primary endpoint , examined in the intention-to-treat population , was pathological complete response in the breast . Neither patients nor investigators were masked to treatment . This study is registered with Clinical Trials.gov , number NCT00545688 . FINDINGS Of 417 eligible patients , 107 were r and omly assigned to group A , 107 to group B , 107 to group C , and 96 to group D. Patients given pertuzumab and trastuzumab plus docetaxel ( group B ) had a significantly improved pathological complete response rate ( 49 of 107 patients ; 45·8 % [ 95 % CI 36·1 - 55·7 ] ) compared with those given trastuzumab plus docetaxel ( group A ; 31 of 107 ; 29·0 % [ 20·6 - 38·5 ] ; p=0·0141 ) . 23 of 96 ( 24·0 % [ 15·8 - 33·7 ] ) women given pertuzumab plus docetaxel ( group D ) had a pathological complete response , as did 18 of 107 ( 16·8 % [ 10·3 - 25·3 ] ) given pertuzumab and trastuzumab ( group C ) . The most common adverse events of grade 3 or higher were neutropenia ( 61 of 107 women in group A , 48 of 107 in group B , one of 108 in group C , and 52 of 94 in group D ) , febrile neutropenia ( eight , nine , none , and seven , respectively ) , and leucopenia ( 13 , five , none , and seven , respectively ) . The number of serious adverse events was similar in groups A , B , and D ( 15 - 20 serious adverse events per group in 10 - 17 % of patients ) but lower in group C ( four serious adverse events in 4 % of patients ) . INTERPRETATION Patients given pertuzumab and trastuzumab plus docetaxel ( group B ) had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel , without substantial differences in tolerability . Pertuzumab and trastuzumab without chemotherapy eradicated tumours in a proportion of women and showed a favourable safety profile . These findings justify further exploration in adjuvant trials and support the neoadjuvant approach for accelerating drug assessment in early breast cancer . FUNDING F Hoffmann-La Roche BACKGROUND We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy . METHODS In the GeparQuinto r and omised phase 3 trial , patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7 , 2007 , and July 9 , 2010 . Patients were eligible if their tumours were classified as cT3/4a-d , or hormone receptor (HR)-negative , HR-positive with clinical ly node-positive and cT2 disease ( cT2 cN+ ) , or HR-positive and pathologically node-positive in the sentinel lymph node for those with cT1 disease ( cT1 pN(SLN+ ) ) . Patients were r and omly assigned in a 1:1 ratio to receive neoadjuvant treatment with four cycles of EC ( epirubicin [ 90 mg/m(2 ) intravenously ] plus cyclophosphamide [ 600 mg/m(2 ) intravenously ] , every 3 weeks ) , and four cycles of docetaxel ( 100 mg/m(2 ) intravenously every 3 weeks ) with either trastuzumab ( 6 mg/kg intravenously , with a starting loading dose of 8 mg/kg , for eight cycles , every 3 weeks ) or lapatinib ( 1000 - 1250 mg per day orally ) throughout all cycles before surgery . R and omisation was done by dynamic allocation with the minimisation method of Pocock and patients were stratified by participating site , HR status , and extent of disease ( cT1 - 3 cN0 - 2 vs T4 or N3 ) . The primary endpoint was pathological complete response ( defined as ypT0 and ypN0 ) and was analysed in all patients who received at least one cycle of EC . Participants and investigators were not masked to treatment assignment . Pathologists in centres assessing surgery outcomes were masked to group assignment . This trial is registered with Clinical Trials.gov , number NCT00567554 . FINDINGS Of 620 eligible patients , 309 were r and omly assigned to chemotherapy with trastuzumab ( ECH-TH group ) and 311 to chemotherapy with lapatinib ( ECL-TL group ) . Two patients in the ECH-TH group and three patients in the ECL-TL group did not start treatment because of withdrawal of consent or immediate surgery . 93 ( 30·3 % ) of 307 patients in the ECH-TH group and 70 ( 22·7 % ) of 308 patients in the ECL-TL group had a pathological complete response ( odds ratio [ OR ] 0·68 [ 95%CI 0·47 - 0·97 ] ; p=0·04 ) . Chemotherapy with trastuzumab was associated with more oedema ( 119 [ 39·1 % ] vs 88 [ 28·7 % ] ) and dyspnoea ( 90 [ 29·6 % ] vs 66 [ 21·4 % ] ) , and ECL-TL with more diarrhoea ( 231 [ 75·0 % ] vs 144 [ 47·4 % ] ) and skin rash ( 169 [ 54·9 % ] vs 97 [ 31·9 % ] ) . 43 ( 14·0 % ) patients discontinued in the ECH-TH group and 102 ( 33·1 % ) in the ECL-TL group . 70 serious adverse events were reported in the ECH-TH group and 87 in the ECL-TL group . INTERPRETATION This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab . Unless long-term outcome data show different results , lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy . FUNDING GlaxoSmithKline , Roche , and Sanofi-Aventis The objective of this study is to evaluate the efficacy and safety profile of the doxorubicin followed by cisplatin/docetaxel as primary chemotherapy for patients with locally advanced breast cancer ( LABC ) . For this evaluation , 59 patients with LABC ( T2–T4 , N0–N2 , M0 ) received three cycles of doxorubicin , followed by three cycles of cisplatin/docetaxel and followed by definitive surgery and locoregional radiotherapy with or without tamoxifen . The primary end point was pathologic complete response ( pCR ) in breast and axilla . Fifty-nine patients were evaluable for analysis : median age : 41 years , premenopausal : 68 % , median tumor size : 6.0 cm ( 4–10 ) , Stage IIB : 32 % and IIIA/IIIB : 68 % , both ER/PR positive : 53 % , Her2/neu ( 3 + ) by IHC staining : 29 % . Clinical complete response was seen in 44 % , and clinical partial response was seen in 56 % . Breast conserving surgery was performed in 44 % , and MRM in 56 % . pCR in the breast was 30.5 % , in axilla was 37 % , and pCR in both breast and axilla was 24 % . Overall at follow-up of 60 months , the disease-free ( DFS ) and overall survival ( OS ) were 70 and 82 % , respectively . The DFS and OS of patients who achieved complete pathologic response in breast and axilla were 78 and 100 % , respectively , while 14 patients relapsed of which 46 % were Her2 positive . Sequential combination of doxorubicin followed by docetaxel/cisplatin is a safe , feasible , and active combination , which offers the possibility of conservative surgery and is associated with high clinical and pathologic response rates , with promising and encouraging survival outcomes BACKGROUND To evaluate capecitabine-docetaxel ( XT ) , with trastuzumab ( H ) in human epidermal growth factor receptor 2 (HER2)-positive disease , in inoperable locally advanced breast cancer ( LABC ) . PATIENTS AND METHODS Patients received up to six neoadjuvant 21-day cycles of capecitabine 900 mg/m(2 ) twice daily , days 1 - 14 , plus docetaxel 36 mg/m(2 ) , days 1 and 8 . Patients with HER2-positive disease also received trastuzumab 6 mg/kg every 3 weeks . The primary end point was pathologic complete response ( pCR ) rate , evaluated separately in HER2-negative and HER2-positive cohorts . Secondary end points included clinical response rates and tolerability . RESULTS The pCR rate was 15 % [ 95 % confidence interval ( CI ) 7 - 28 ] in 53 patients receiving XT and 40 % ( 95 % CI 26 - 55 ) in 50 patients receiving HXT . After neoadjuvant therapy , 50 patients receiving XT and 45 receiving HXT underwent surgery . No unexpected toxicity was observed : the most common grade ≥3 adverse events were diarrhea/mucositis ( 30 % and 20 % , respectively ) and grade 3 h and -foot syndrome ( 11 % and 6 % , respectively ) . Disease-free survival and overall survival were similar with XT and HXT after median follow-up of 22 months in the XT cohort and 21 months in the HXT cohort . CONCLUSION Neoadjuvant XT ( HXT in HER2-positive disease ) is highly effective in inoperable LABC , demonstrating pCR rates of 15 % and 40 % , respectively . This non-anthracycline-containing regimen offers obvious benefits in early disease , where avoidance of long-term cardiotoxicity is particularly important Background : We were able to demonstrate a predictive value of serum HER2 ( sHER2 ) in patients receiving trastuzumab in the neoadjuvant GeparQuattro trial . However , the role of sHER2 in patients receiving neoadjuvant therapy ( NT ) with lapatinib is still unclear . Methods : The neoadjuvant GeparQuinto trial compared trastuzumab vs lapatinib in addition to chemotherapy in HER2-positive primary breast cancer patients . The sHER2 levels were measured by enzyme-linked immunosorbant assay in 210 patients , of whom 109 ( 52 % ) patients received trastuzumab and 101 ( 48 % ) lapatinib at three different time points . Results : Twenty-two percent of patients had elevated baseline sHER2 levels ( > 15 ng ml−1 ) . A decrease of sHER2 levels ( > 20 % ) in the trastuzumab and lapatinib-treated group during NT was seen in 44 % and 24 % of the patients , an increase of sHER2 levels ( > 20 % ) was seen in 6 % and 41 % of patients , respectively . Higher pre-chemotherapy sHER2 levels were associated with higher pathological complete remission ( pCR ) rates in the entire study cohort ( OR 1.8 , 95 % CI 1.02–3.2 , P=0.043 ) . A decline of sHER2 levels ( > 20 % ) during NT was a predictor for pCR in the lapatinib-treated patient group ( OR : 11.7 , 95 % CI 1.3–110 , P=0.031 ) . Conclusion : Results of this study demonstrate that sHER2 levels change differently during NT depending on the anti-HER2 treatment strategy . Elevated baseline sHER2 levels ( > 15 ng ml−1 ) and a decrease of sHER2 levels ( > 20 % ) early after therapy initiation are both relevant criteria to predict response to lapatinib-based treatment Purpose : This study was aim ed at detecting and characterizing circulating tumor cells ( CTC ) before and after neoadjuvant therapy ( NT ) in the peripheral blood of patients with breast cancer . Experimental Design : The clinical trial GeparQuattro incorporated NT approaches ( epirubicin/cyclophosphamide prior to r and omization to docetaxel alone , docetaxel in combination with capecitabine , or docetaxel followed by capecitabine ) and additional trastuzumab treatment for patients with HER2-positive tumors . We used the Food and Drug Administration – approved Cell Search system for CTC detection and evaluation of HER2 expression and developed HER2 immunoscoring for CTC . Results : We detected ≥1 CTC/7.5 mL in 46 of 213 patients ( 21.6 % ) before NT and in 22 of 207 patients ( 10.6 % ) after NT ( P = 0.002 ) . Twenty ( 15.0 % ) initially CTC-positive cases were CTC-negative after NT , whereas 11 ( 8.3 % ) cases were CTC-positive after NT , although no CTC could be found before NT . CTC detection did not correlate with primary tumor characteristics . Furthermore , there was no association between tumor response to NT and CTC detection . HER2-overexpressing CTC were observed in 14 of 58 CTC-positive patients ( 24.1 % ) , including 8 patients with HER2-negative primary tumors and 3 patients after trastuzumab treatment . CTC scored HER2-negative or weakly HER2-positive before or after NT were present in 11 of 21 patients with HER2-positive primary tumors . HER2 overexpression on CTC was restricted to ductal carcinomas and associated with high tumor stage ( P = 0.002 ) . Conclusion : CTC number was low in patients with primary breast cancer . The decrease in CTC incidence during treatment was not correlated with st and ard clinical characteristics and primary tumor response . Information on the HER2 status of CTC might be helpful for stratification and monitoring of HER2-directed therapies . Clin Cancer Res ; 16(9 ) ; 2634–45 . © 2010 AACR To assess anti-tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the r and omized addition of celecoxib in HER2 negative patients or trastuzumab in HER2 positive patients . From May 2004 till October 2007 , 340 patients with stage II and III breast adenocarcinoma , ineligible for breast conserving surgery , received eight sequential three weekly cycles of EC-D [ epirubicin ( 75 mg/m2)–cyclophosphamide ( 750 mg/m2 ) for four cycles followed by docetaxel ( 100 mg/m2 ) for four cycles ] . HER2-negative patients ( N = 220 ) were r and omized to receive concomitantly with docetaxel celecoxib 800 mg/day during cycles 5–8 or no additional treatment , while HER2-positive patients confirmed by FISH ( N = 120 ) were r and omized to trastuzumab concomitant to docetaxel ( 8 mg/kg then 6 mg/kg IV every 3 weeks ) or no additional preoperative treatment . In the HER2 negative group , pCR ( grade 1 and 2 of Chevallier ’s classification ) was observed in 11.5 and 13 % of patients treated without and with neoadjuvant Celecoxib , respectively . In the HER2 positive group , pCR rate reached 26 % in those who received neoadjuvant trastuzumab versus 19 % in the others . There was no unexpected toxicity , no cardiac toxicity , and no toxic death . Triple negative breast cancers experience the highest pCR rate of 30 % . Celecoxib is not likely to improve pCR rates in addition to EC-D in patients with HER2-negative tumor . In HER2-positive tumor patients , trastuzumab added to ECD leads to increased pCR rates . It was the only combination to deserve further study according to the two-stage Fleming ’s design used in this trial PURPOSE To evaluate the efficacy and safety of docetaxel , cisplatin , and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2 ( HER2 ) -positive , locally advanced breast cancer ( LABC ) . PATIENTS AND METHODS Forty-eight patients with immunohistochemistry-confirmed HER2-positive LABC or inflammatory breast cancer received 12 weeks of docetaxel , cisplatin , and trastuzumab with filgrastim , followed by surgery , adjuvant doxorubicin and cyclophosphamide , and locoregional radiotherapy with or without tamoxifen . The primary end point was pathologic complete response ( pCR ) in breast . RESULTS Baseline mean tumor size was 9.2 cm ( range , 4 to 32 cm ) . pCR occurred in breast in 11 patients ( 23 % ; 95 % CI , 12 % to 37 % ) and breast and axilla in eight patients ( 17 % ; 95 % CI , 8 % to 30 % ) . pCR rates in breast ( HER2 positive , seven of 30 patients , 23 % v HER2 negative , four of 18 patients , 22 % ; P > .05 ) and breast and axilla ( four of 30 patients , 13 % v four of 18 patients , 22 % , respectively ; P > .05 ) were similar regardless of HER2 status by fluorescence in situ hybridization ( FISH ) . At a median follow-up time of 43 months , 4-year progression-free survival ( PFS ) rate was 81 % ( 95 % CI , 64 % to 90 % ) ; overall survival ( OS ) rate was 86 % ( 95 % CI , 71 % to 94 % ) . In patients with pCR in breast and axilla , PFS and OS rates were 100 % ( 95 % CI , inestimable ) . In patients without pCR , PFS rate was 76 % ( 95 % CI , 57 % to 88 % ; P = .15 , log-rank test ) , and OS rate was 83 % ( 95 % CI , 66 % to 92 % ; P = .21 ) . Survival rates were similar regardless of FISH status . There were only two grade 4 adverse events . CONCLUSION Twelve weeks of docetaxel , cisplatin , and trastuzumab is clinical ly active and leads to excellent survival in patients with large , HER2-positive tumors BACKGROUND we previously reported a phase I trial of liposome-encapsulated doxorubicin citrate ( LD ) , docetaxel and trastuzumab as neoadjuvant in stages II and IIIA human epidermal growth factor receptor 2-overexpressing breast cancer patients . This study evaluates the efficacy of this regimen in a phase II trial . PATIENTS AND METHODS patients were treated with LD 50 mg/m(2 ) and docetaxel 60 mg/m(2 ) every 21days associated with st and ard trastuzumab dose and pegfilgrastim support . RESULTS fifty-nine patients were enrolled ; median age : 48 years ( range 24 - 71 years ) ; premenopausal patients : 36 ( 61 % ) ; 19 patients ( 32 % ) presented stage IIIA disease and 40 patients ( 67 % ) stage II ; histological grade s 2 - 3 tumors : 50 patients ( 84 % ) and estrogen receptor-progesterone receptor negative : 28 patients ( 47 % ) . In all , 27 % achieved a pathological complete response in breast and axilla ( grade 5-Miller and Payne classification ) ; 15 % of patients achieved grade 4 . Clinical and radiological response rates were 86 % and 81 % , respectively . Forty-two patients ( 71 % ) underwent breast-conserving surgery . The main grade s 3 - 4 toxic effects were non-febrile neutropenia ( 29 % ) and fatigue ( 8 % ) . Grade 2 left ventricular ejection fraction decline was observed in nine patients . No congestive heart failure was observed . CONCLUSIONS LD plus docetaxel combination associated with trastuzumab as neoadjuvant is active in breast cancer and entails a favorable cardiotoxicity profile . This regimen is a new treatment option in these patients PURPOSE To determine , in women with primary operable breast cancer , if preoperative doxorubicin ( Adriamycin ) and cyclophosphamide ( Cytoxan ; AC ) therapy yields a better outcome than postoperative AC therapy , if a relationship exists between outcome and tumor response to preoperative chemotherapy , and if such therapy results in the performance of more lumpectomies . PATIENTS AND METHODS Women ( 1,523 ) enrolled onto National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B-18 were r and omly assigned to preoperative or postoperative AC therapy . Clinical tumor response to preoperative therapy was grade d as complete ( cCR ) , partial ( cPR ) , or no response ( cNR ) . Tumors with a cCR were further categorized as either pathologic complete response ( pCR ) or invasive cells ( pINV ) . Disease-free survival ( DFS ) , distant disease-free survival ( DDFS ) , and survival were estimated through 5 years and compared between treatment groups . In the preoperative arm , proportional-hazards models were used to investigate the relationship between outcome and tumor response . RESULTS There was no significant difference in DFS , DDFS , or survival ( P = .99 , .70 , and .83 , respectively ) among patients in either group . More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy ( 67.8 % v 59.8 % , respectively ) . Rates of ipsilateral breast tumor recurrence ( IBTR ) after lumpectomy were similar in both groups ( 7.9 % and 5.8 % , respectively ; P = .23 ) . Outcome was better in women whose tumors showed a pCR than in those with a pINV , cPR , or cNR ( relapse-free survival [ RFS ] rates , 85.7 % , 76.9 % , 68.1 % , and 63.9 % , respectively ; P < .0001 ) , even when baseline prognostic variables were controlled . When prognostic models were compared for each treatment group , the preoperative model , which included breast tumor response as a variable , discriminated outcome among patients to about the same degree as the postoperative model . CONCLUSION Preoperative chemotherapy is as effective as postoperative chemotherapy , permits more lumpectomies , is appropriate for the treatment of certain patients with stages I and II disease , and can be used to study breast cancer biology . Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases ; however , knowledge of such a response provided little prognostic information beyond that which result ed from postoperative therapy We conducted a phase II study using docetaxel and trastuzumab as preoperative systemic treatment for locally advanced HER-2-overexpressing breast cancer ( stage IIIB or IIIC ) to evaluate the efficacy and safety , and to perform a subset analysis based on tumor biomarkers . Patients received 4 mg/kg trastuzumab on day 1 , followed by weekly treatments of 2mg/kg , in addition to 75 mg/m(2 ) docetaxel every 3 weeks for 4 cycles before surgery . The primary end point was clinical response rate measured by MRI or CT . Twenty-five patients were enrolled . The median age was 54 years and median tumor size was 63 mm . The overall clinical response rate was 68 % [ 95 % CI : 47 - 85 % ] and the pCR rate was 22 % [ 95 % CI : 8 - 44 % ] . The clinical response and the pCR rates of patients with ER- and PgR- tumors were 79 % and 31 % , respectively , while they were 55 % and 10 % , respectively , in the patients with ER+ and /or PgR+ tumors ( p=0.34 , p=0.34 , respectively ) . Cardiac toxicity was well tolerated ; there was no evidence of clinical cardiac events in any patient . The combination of docetaxel and trastuzumab produced highly favorable clinical and pathological responses for locally advanced HER-2-overexpressing breast cancer . Subgroup analysis suggests that ER/PgR negative tumors might be associated with pathological response in locally advanced breast cancer BACKGROUND The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer . We argue that the two anti-HER2 agents given together would be better than single-agent therapy . METHODS In this parallel groups , r and omised , open-label , phase 3 study undertaken between Jan 5 , 2008 , and May 27 , 2010 , women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were r and omly assigned to oral lapatinib ( 1500 mg ) , intravenous trastuzumab ( loading dose 4 mg/kg [ DOSAGE ERROR CORRECTED ] , subsequent doses 2 mg/kg ) , or lapatinib ( 1000 mg ) plus trastuzumab . Treatment allocation was by stratified , permuted blocks r and omisation , with four stratification factors . Anti-HER2 therapy alone was given for the first 6 weeks ; weekly paclitaxel ( 80 mg/m(2 ) ) was then added to the regimen for a further 12 weeks , before definitive surgery was undertaken . After surgery , patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks . The primary endpoint was the rate of pathological complete response ( pCR ) , analysed by intention to treat . This trial is registered with Clinical Trials.gov , NCT00553358 . FINDINGS 154 patients received lapatinib , 149 trastuzumab , and 152 the combination . pCR rate was significantly higher in the group given lapatinib and trastuzumab ( 78 of 152 patients [ 51·3 % ; 95 % CI 43·1 - 59·5 ] ) than in the group given trastuzumab alone ( 44 of 149 patients [ 29·5 % ; 22·4 - 37·5 ] ; difference 21·1 % , 9·1 - 34·2 , p=0·0001 ) . We recorded no significant difference in pCR between the lapatinib ( 38 of 154 patients [ 24·7 % , 18·1 - 32·3 ] ) and the trastuzumab ( difference -4·8 % , -17·6 to 8·2 , p=0·34 ) groups . No major cardiac dysfunctions occurred . Frequency of grade 3 diarrhoea was higher with lapatinib ( 36 patients [ 23·4 % ] ) and lapatinib plus trastuzumab ( 32 [ 21·1 % ] ) than with trastuzumab ( three [ 2·0 % ] ) . Similarly , grade 3 liver-enzyme alterations were more frequent with lapatinib ( 27 [ 17·5 % ] ) and lapatinib plus trastuzumab ( 15 [ 9·9 % ] ) than with trastuzumab ( 11 [ 7·4 % ] ) . INTERPRETATION Dual inhibition of HER2 might be a valid approach to treatment of HER2-positive breast cancer in the neoadjuvant setting . FUNDING GlaxoSmithKline Lapatinib , a dual kinase inhibitor against epidermal growth factor receptor ( EGFR ) and human epidermal receptor two ( HER2 ) has shown efficacy in treating HER2 positive breast cancer . Nanoparticle albumin bound ( nab ) paclitaxel was developed to reduce toxicities from paclitaxel and improve its efficacy . Thirty patients with stage I – III HER2 positive breast cancer were treated in the neoadjuvant setting with lapatinib 1,000 mg/day and nab-paclitaxel 260 mg/m2 every 3 weeks for four cycles . The primary end point of the trial was clinical response rate ( cRR ) with secondary end points including pathologic complete response rate ( pCR ) , tolerability of the combination , and marker response . The cRR was 82.8 % ( 24 patients ) with six ( 20.7 % ) patients having complete clinical response , 18 ( 62.1 % ) having partial clinical response , and five ( 17.2 % ) stable disease . A pCR was observed in five of the 28 patients ( 17.9 % ) . The most frequent grade 2 toxicities were neuropathy in nine patients ( 30 % ) , fatigue in seven patients ( 23.3 % ) , rash in 11 patients ( 36.7 % ) , and bone pain in 10 patients ( 33.3 % ) . There was no significant drop in the left ventricular ejection fraction ( LVEF ) . Of the tissue markers examined , we were not able to find a predictor of response . The combination of lapatinib and nab-paclitaxel was well tolerated and provided good efficacy in women with HER2 positive breast cancer . This combination offers an alternative non-anthracycline-containing regimen for women with HER2 positive breast cancer An addition of trastuzumab preoperatively to chemotherapy for human epidermal growth factor receptor 2 ( HER2 ) positive breast cancer improved relapse-free survival ( RFS ) . This study was design ed to evaluate the efficacy and safety of preoperative paclitaxel , gemcitabine , and trastuzumab ( PGH ) combination for HER2-positive breast caner . Pathologically , proven node positive stage II/III breast cancer patients with adequate organ function and no history of anti-cancer therapy were eligible . Patients received weekly trastuzumab with paclitaxel 80 mg/m2 and gemcitabine 1,200 mg/m2 on days 1 and 8 , every 3 weeks for 6 cycles . Postoperatively , patients completed trastuzumab for 1 year and hormone therapy for 5 years if indicated . All patients received postoperative radiation therapy . Of 53 enrolled patients with a median tumor of 5.3 ( range , 2.0 to > 12 ) cm ; 43.4 % , T3/T4 ; 75.4 % , N2/N3 ; and 45.3 % , positive hormone receptors . The pathologic complete response ( pCR ) rate was 58.5 % in both tumor and lymph nodes . Grade 3/4 adverse events were neutropenia ( 32 % ) , febrile neutropenia ( 0.6 % ) , and transient elevation of AST/ALT ( 1.6 % ) during a total of 318 cycles . All patients maintained normal cardiac function . With a median follow-up of 40 months , 3-year RFS rate was 84 % with 91.7 % distant metastasis-free survival rates . Remarkable pCR rate was obtained with non-anthracycline-based PGH therapy for HER2-positive stage II/III breast cancer . Adverse events were mild with few incidences of febrile neutropenia PURPOSE Neoadjuvant treatment with chemotherapy plus trastuzumab is st and ard care for women with locally advanced , HER2-positive ( HER2(+ ) ) breast cancer . HER2 has been shown to stimulate angiogenesis through vascular endothelial growth factor upregulation . We investigated the feasibility and efficacy of bevacizumab in combination with trastuzumab , nab-paclitaxel , and carboplatin as neoadjuvant therapy for women with locally advanced HER2(+ ) breast cancer . PATIENTS AND METHODS Twenty-eight women with locally advanced HER2(+ ) breast cancer received nab-paclitaxel ( 100 mg/m(2 ) intravenously [ I.V. ] days 1,8 , and 15 ) and carboplatin ( AUC = 6 I.V. day 1 ) every 28 days × 6 cycles . Concurrent with chemotherapy , trastuzumab ( 4 mg/kg loading dose , then 2 mg/kg ) and bevacizumab ( 5 mg/kg I.V. ) were administered weekly × 23 weeks . Patients then underwent mastectomy or breast-conserving surgery ; pathologic responses were assessed . After surgery , trastuzumab 6 mg/kg and bevacizumab 15 mg/kg were administered every 3 weeks ( 54 weeks total ) ; locoregional radiotherapy and /or antiestrogen therapy was administered per st and ard guidelines . RESULTS Twenty-six patients ( 90 % ) completed neoadjuvant therapy , with objective responses in 86 % . Pathologic complete response ( pCR ) was confirmed in 14 of the 26 patients ( 54 % ) who had surgery . However , bevacizumab-related complications were common postoperatively and during adjuvant trastuzumab/bevacizumab therapy . Ten patients had wound-healing delays or infections ( 6 patients discontinued therapy ) ; 4 patients had left ventricular ejection fraction ( LVEF ) decreases ( 1 patient discontinued therapy ) . Other severe treatment-related toxicity was uncommon . Only 9 patients ( 31 % ) completed all protocol therapy . CONCLUSIONS Neoadjuvant therapy with nab-paclitaxel , carboplatin , trastuzumab , and bevacizumab was feasible in most patients , producing a pCR rate comparable to that in chemotherapy/trastuzumab combinations . In contrast , prolonged bevacizumab/trastuzumab therapy after surgical treatment was not well tolerated , primarily due to bevacizumab-related toxicity . The role of bevacizumab in neoadjuvant therapy remains undefined PURPOSE Trastuzumab combined with chemotherapy improves outcomes for women with human epidermal growth factor receptor 2 ( HER2 ) overexpressing advanced breast cancer . We conducted a pilot study of preoperative trastuzumab and paclitaxel , followed by surgery and adjuvant doxorubicin and cyclophosphamide chemotherapy in earlier stage breast cancer . PATIENTS AND METHODS Patients with HER2-positive ( 2 + or 3 + by immunohistochemistry ) stage II or III breast cancer received preoperative trastuzumab ( 4 mg/kg x 1 , then 2 mg/kg/wk x 11 ) in combination with paclitaxel ( 175 mg/m(2 ) every 3 weeks x 4 ) . Patients received adjuvant doxorubicin and cyclophosphamide chemotherapy following definitive breast surgery . Clinical and pathologic response rates were determined after preoperative therapy . Left ventricular ejection fraction and circulating levels of HER2 extracellular domain were measured serially . RESULTS Preoperative trastuzumab and paclitaxel achieved clinical response in 75 % and complete pathologic response in 18 % of the 40 women on study . HER2 3 + tumors were more likely to respond than 2 + tumors ( 84 % v 38 % ) . No unexpected treatment-related noncardiac toxicity was encountered . Four patients developed grade 2 cardiotoxicity ( asymptomatic declines in left ventricular ejection fraction ) . Baseline HER2 extracellular domain was elevated in 24 % of patients and declined with preoperative therapy . Immunohistochemical analyses of posttherapy tumor specimens indicated varying patterns of HER2 expression following trastuzumab-based treatment . CONCLUSION Preoperative trastuzumab and paclitaxel is active against HER2 overexpressing early-stage breast cancer and may be feasible as part of a sequential treatment program including anthracyclines . The observed changes in cardiac function merit further investigation . Correlative analyses of HER2 status may facilitate underst and ing of tumor response and resistance to targeted therapy BACKGROUND The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early , operable , and metastatic breast cancer that has HER2 ( also known as ERBB2 ) overexpression or amplification . We aim ed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab . METHODS We compared 1 year of treatment with trastuzumab ( given as neoadjuvant and adjuvant treatment ; n=117 ) with no trastuzumab ( 118 ) , in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin , paclitaxel , cyclophosphamide , methotrexate , and fluorouracil . R and omisation was done with a computer program and minimisation technique , taking account of geographical area , disease stage , and hormone receptor status . Investigators were informed of treatment allocation . A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen . Primary endpoint was event-free survival . Analysis was by intention to treat . This study is registered , number IS RCT N86043495 . FINDINGS Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer ( 3-year event-free survival , 71 % [ 95 % CI 61 - 78 ; n=36 events ] with trastuzumab , vs 56 % [ 46 - 65 ; n=51 events ] without ; hazard ratio 0.59 [ 95 % CI 0.38 - 0.90 ] ; p=0.013 ) . Trastuzumab was well tolerated and , despite concurrent administration with doxorubicin , only two patients ( 2 % ) developed symptomatic cardiac failure . Both responded to cardiac drugs . INTERPRETATION The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival , survival , and clinical and pathological tumour responses . FUNDING F Hoffmann-La Roche A previously published prospect i ve r and omized phase 3 trial showed that administration of 24 weeks of primary systemic chemotherapy ( PST ) with paclitaxel and FEC75 ( fluorouracil , epirubicin , cyclophosphamide ) concurrently with trastuzumab in patients with HER2‐positive primary breast cancer result ed in a 60 % pathologic complete response rate ( PCR ) with no associated severe cardiac toxicity . The purpose of this study was to review the efficacy and safety of a similar regimen outside the setting of a clinical trial PURPOSE The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response ( pCR ) rate in patients with human epidermal growth factor receptor 2 ( HER2 ) -positive disease . PATIENTS AND METHODS Forty-two patients with HER2-positive disease with operable breast cancer were r and omly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil , epirubicin , and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks . The primary objective was to demonstrate a 20 % improvement in pCR ( assumed 21 % to 41 % ) with the addition of trastuzumab to chemotherapy . The planned sample size was 164 patients . RESULTS Prognostic factors were similar in the two groups . After 34 patients had completed therapy , the trial 's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy . pCR rates were 25 % and 66.7 % for chemotherapy ( n = 16 ) and trastuzumab plus chemotherapy ( n = 18 ) , respectively ( P = .02 ) . The decision was based on the calculation that , if study continued to 164 patients , there was a 95 % probability that trastuzumab plus chemotherapy would be superior . Of the 42 r and omized patients , 26 % in the chemotherapy arm achieved pCR compared with 65.2 % in the trastuzumab plus chemotherapy arm ( P = .016 ) . The safety of this approach is not established , although no clinical congestive heart failure was observed . A more than 10 % decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms , respectively . CONCLUSION Despite the small sample size , these data indicate that adding trastuzumab to chemotherapy , as used in this trial , significantly increased pCR without clinical congestive heart failure 565 Background : Achievement of pathological complete response ( pCR ) by primary systemic therapy ( PST ) correlates with improved survival in operable breast cancer patients . Based on data of the higher pCR rate with concomitant chemotherapy and trastuzumab ( H ) reported by some clinical trials , we performed a multi-center , prospect i ve r and omized phase II study to evaluate the efficacy of adding H to st and ard chemotherapy and to determine more effective agent which will show higher pCR by the comparison between weekly paclitaxel ( P ) and tri-weekly docetaxel ( D ) in neo-adjuvant setting for HER-2 + pts . METHODS Generally , the concomitant combination with anthracycline and H is not recommended because of the increasing cardiac toxicity . PST regimen was scheduled as the sequential chemotherapy with 4 cycles of CEF ( cyclophosphamide , epirubicin 100 mg/m2 , 5FU ) followed by 4 cycles of q3w H with qw P 80 mg/m2 ( HP ) or q3w D 75 mg/m2 ( HD ) . The primary objective was design ed to evaluate the pCR , defined as no evidence of residual invasive cancer in axilla and breast . The inclusion criteria was pts with Stage II or IIIA , HER-2 overexpression , under 65-yo , adequate cardiac function ( EF>=60 % ) and a written informed consent . The sample size was estimated to detect the difference of pCR rate > = 10 % from 30 % baseline , as at least 100 pts . The pathological response was evaluated by central review . RESULTS From March 2007 to June 2008 , 102 pts were enrolled and r and omized as well balance in the same number , median age ( 51yo ) , and the same distribution of clinical stage . 88 pts ( 86 % ) was successful on complete treatment course . Pre-matured data was available for 60 pts whom central review had been completed : there was no significantly difference in pCR rate between two groups , 53 % ( 95%CI : 35.4 - 71.1 % ) on HP and 47 % ( 28.8 - 64.5 % ) on HD . Out of 30 pts with pCR , 13 pts had component of DCIS . Serious adverse events were reported on 13 cases ; mainly febrile neutropenia was experienced on 6 pts . One after the HP course had experienced the cardiac failure to fall in LVEF to 39 % . CONCLUSIONS In HER-2 + pts , PST with CEF followed by HP or HD might be equally active and achieving high pCR without significant toxicity . The final review ed results will be established until May 2009 , and presented at the ASCO meeting . No significant financial relationships to disclose e11557 Background : Neoadjuvant chemotherapy for locally advanced breast cancer was shown to improve the complete pathologic ( pCR ) and clinical response ( cCR ) as well as the disease free survival ( DFS ) . Docetaxel , cisplatin , and trastuzumab given every 21 days in her2-positive breast cancer demonstrated a pCR rate of 23 % . The concept of dose dense chemotherapy regimens has attracted much attention and we hypothesized that dose-dense regimen would further improve pCR , cCR and would maintain the safety profile while being a suitable regimen for outpatient administration . METHODS 48 patients with stage II/III HER2-positive breast cancer were prospect ively enrolled on a clinical trial of a neoadjuvant regimen consisting of docetaxel 70 mg/m2 on days 1 , 15 , 29 , and 43 ; carboplatinum at an AUC of 6 on days 1 , 15 , 29 , and 43 ; trastuzumab 4 mg/kg on day 1 and 2 mg/kg weekly x 10 starting on day 8 ; peg-filgastrim 6 mg on days 2 , 16 , 30 , and 44 . RESULTS The median age was 50 years ( range 30 - 78 ) . 52 % of patients were premenopausal , 63 % and 22 % were of Hispanic and African descent , respectively . Estrogen receptor was positive in 52 % patients and median tumor size was 5 cm at the time of diagnosis . TNM stage distribution at presentation : T1 2 % , T2 25 % , T3 57 % , T4 16 % ; N0 29 % , N1 46 % , N2 16 % , N3 7 % ; M0 100 % . pCR in breast ; axilla ; and both breast and axilla was observed in 19 of 44 patients ( 43.2 % ; 95 % CI 28.3 % - 59.0 % ) ; in 29 of 44 patients ( 65.9 % ; 95 % CI 50.1 % - 79.5 % ) ; and in 16 of 44 patients ( 36.4 % ; 95 % CI 22.4 % - 52.2 % ) , respectively . No grade 4 or 5 toxicity occurred . The most frequent grade 3 toxicities were h and -foot syndrome ( 7 % ) , neutropenia ( 4 % ) , nausea/vomiting ( 2 % ) , and bone pain ( 2 % ) . Grade 2 cardiotoxicity was seen in 8 % of patients and no grade 3 cardiotoxicity was observed . CONCLUSIONS This neoadjuvant regimen was well tolerated and yielded a good pCR rate for this high risk group of patients . No significant financial relationships to disclose Between July 1988 and May 1990 , we treated 45 women with newly diagnosed , unilateral , nonmetastatic , inflammatory breast cancer with an intensive neoadjuvant chemotherapy regimen ( FEC-HD ) repeated every 21 days , followed by surgery or radiation therapy . Evaluation of efficacy performed 3 to 4 weeks after at least 2 cycles showed disappearance of inflammatory signs in 91 % of the patients and improvement in the remaining 9 % . With regard to primary tumor and lymph nodes , there were 13 ( 28.9 % ) clinical complete responses , 30 ( 66.6 % ) partial responses , and 2 ( 4.5 % ) without change . No progressive disease was observed . Hematologic toxicity from this regimen was high with grade 4 neutropenia observed at day 14 in 100 % of the patients . Re-treatment at day 21 was possible in 83 % of the cycles . Grade 1 or 2 infections occurred in 102 cycles out of 176 ( 57.9 % ) . Grade 3 infections were seen in 9 cycles ( 5 % ) . No septicemia or septic shock occurred . No toxic death occurred . After induction chemotherapy , locoregional treatment consisted of modified radical mastectomy in 39 patients and radiotherapy alone in 6 . The mastectomy specimen showed no residual invasive tumor ( primary tumor and lymph nodes ) in 10 cases ( 25.6 % ) . Two patients judged as partial responders were in fact histologic complete responders . The clinical and histological response rates observed appeared very promising . For this reason we are currently testing FEC-HD with or without GCSF in a r and omized multicenter trial with correction of neutropenia , disease-free survival , and overall survival as main end points Purpose : To evaluate the pathologic complete response ( pCR ) rate of a combination of epirubicin ( E ) and cyclophosphamide ( C ) followed by paclitaxel ( P ) and gemcitabine ( G ) ( + trastuzumab[T ] ) in Her2 + patients ) in a sequential and dose-dense schedule as neoadjuvant chemotherapy for stages II and III patients with breast cancer . Secondary endpoints : clinical response rate , disease free survival , safety and correlation between pCR and biologic markers . Patients and Methods : Eligible patients were treated with E ( 90 mg/m2 ) and C ( 600 mg/m2 ) for 3 cycles ( first sequence ) followed by P ( 150 mg/m2 ) and G ( 2500 mg/m2 ) ( second sequence ) for 6 cycles . All drugs were administered on day 1 , every 2 weeks , with prophylactic growth factor support . Weekly T ( 2 mg/kg [ 4 mg/kg first infusion ] ) was administered concomitantly with P and G in Her2 + patients . A core biopsy was performed before treatment for biologic markers assessment . Patients underwent surgery , radiotherapy , and adjuvant hormonal therapy according to institutional practice . Results : Seventy-three patients were treated . A pCR was achieved in 27 ( 37 % ) patients ( 32.1 % , Her2− and 50 % , Her2 + ) . pCR was significantly higher in tumors that were hormonal receptor negative , poorly differentiated and positive for Ki67 and p53 . Breast-conserving surgery was performed in 47 patients ( 64.4 % ) . Most frequent grade 3/4 hematologic and nonhematological toxicities included neutropenia ( 12 % ) , nausea/vomiting ( 17 % ) , and transient liver enzymes elevation ( 7 % ) . One patient suffered an asymptomatic and reversible decrease in left ventricular ejection fraction . Conclusions : These results show a highly effective regimen in terms of pCR with a good toxicity profile in the neoadjuvant treatment of patients with breast cancer . The addition of trastuzumab increased pCR rate in Her2 + tumors PURPOSE To evaluate the efficacy and safety of neoadjuvant carboplatin and weekly paclitaxel + /- weekly trastuzumab in resectable and locally advanced breast cancer . PATIENTS AND METHODS Women with stages IIA to IIIB disease received carboplatin dosed by six times the area under the curve every 4 weeks and paclitaxel 80 mg/m(2 ) weekly for 16 weeks , and weekly trastuzumab was added for human epidermal growth factor receptor 2 ( HER2 ) -positive status . The primary end point was the pathologic complete response ( pCR ) rate , defined as the absence of invasive disease in the breast and axillary nodes . Postoperative therapies were at the discretion of the treating physicians . RESULTS Fifty-five patients were enrolled , and of these 43 had resectable disease . The median age was 54 years ( range , 31 to 74 years ) . Treatment was well tolerated ; there were no episodes of febrile neutropenia or grade 4 thrombocytopenia , and there were only two instances of grade 3 peripheral neuropathy . Overall , the pCR rate was 45 % . The pCR rate was 43 % ( 95 % CI , 28 % to 58 % ) in patients with resectable disease . Higher pCR rates occurred in patients with HER2-positive tumors ( 76 % v 31 % for HER2-negative tumors ; P = .003 ) , with estrogen receptor ( ER ) -negative tumors ( 75 % v 27 % for ER-positive tumors ; P = .001 ) , or with triple-negative tumors ( 67 % v 12 % ER-positive and HER2-negative tumors ; P = .002 ) . At a median of 28 months postoperation , recurrence-free survival ( RFS ) was 88.7 % . If patients with ER-positive and HER2-negative tumors are excluded from analysis , patients who achieved a pCR were less likely to experience disease recurrence ( RFS , 86 % ) than those who did not achieve a pCR ( RFS , 75 % ) . CONCLUSION Neoadjuvant carboplatin and weekly paclitaxel + /- trastuzumab achieve high pCR rates in patients with HER2-positive and triple-negative disease without exposure to an anthracycline . Preliminary RFS results are encouraging but are likely influenced by adjuvant therapy received . Additional study of this regimen in high-risk patients is warranted PURPOSE We conducted a phase II , open-label , multicenter study to evaluate the efficacy , safety , and tolerability of daily lapatinib plus weekly paclitaxel in treatment-naïve patients with inflammatory breast cancer ( IBC ) . PATIENTS AND METHODS The primary end point was pathologic complete response ( pCR ) . Secondary end points included combined clinical response rate ( based on Response Evaluation Criteria in Solid Tumors ( RECIST ) criteria and clinical ly evaluable skin disease criteria ) . Patients were assigned to either cohort A ( human epidermal growth factor receptor 2 [ HER2 ] 2 + or 3 + by immunohistochemistry [ IHC ] or fluorescent in situ hybridization [ FISH ] -amplified + /- epidermal growth factor receptor [ EGFR ] expression ) or cohort B ( HER2-negative/EGFR-positive ) . A sub population of cohort A considered HER2-positive by the current definition of overexpression ( 3 + by IHC or FISH-amplified ) was also analyzed . Patients received lapatinib at 1,500 mg/d for 14 days , then lapatinib at 1,500 mg/d plus weekly paclitaxel ( 80 mg/m(2 ) ) for 12 weeks , followed by surgical resection or additional chemotherapy . RESULTS Forty-nine women were enrolled ( cohort A , n = 42 ; cohort B , n = 7 ) . Cohort B was terminated because of slow accrual and lack of efficacy observed in IBC patients with HER2-negative/EGFR-positive tumors enrolled onto the parallel study , EGF103009 . pCR occurred in 18.2 % ( 95 % CI , 5.2 % to 40.3 % ) of cohort A patients . Combined clinical response rate was 78.6 % ( 95 % CI , 63.2 % to 89.7 % ) in all cohort A patients and 78.1 % ( 95 % CI , 60.0 % to 90.7 % ) in the HER2-positive subset . Common adverse events included diarrhea , rash , alopecia , and nausea ( > 50 % of patients in both cohorts ) . The incidence of grade 3 diarrhea was 55 % . CONCLUSION Lapatinib monotherapy for 14 days followed by lapatinib plus paclitaxel for 12 weeks provided clinical benefit in IBC patients with HER2-overexpressing tumors without unexpected toxicity 506 Background : Extinction of HER2 signaling in HER2 driven BC may be curative . Alternative activation pathways ( HER1 , HER3 ) & mutated downstream signal transducers allow resistance to therapy . STUDY AIM molecularly characterize HER2 + BC before & after 2 wks anti-HER2 therapy ( AHT ) with T , L , or T+L & to correlate these with pCR to continuation of same AHT with neoadjuvant chemo ( FEC75 x 4 Q3W->Paclitaxel x 12W ) . pCR is absence of all invasive cancer in breast & lymph nodes . pCR-Breast used for molecular analysis . METHODS 100 consenting patients ( pts ) with stage II/III , HER2 + BC , normal cardiac function were r and omized to T , L or T+L. Before & after AHT , all pts had core needle biopsies for tissue microarray , stem cell analysis & reverse phase protein microarrays , measuring 60 different phosphoprotein/post-translationally modified protein signaling & gene expression analysis endpoints . RESULTS pCR in the ITT-E ( ITT-E : Pts who had surgery , ≥75 % compliant to chemo and took no prohibited meds . ) pts : 54 % , 45 % , 74 % for T , L , T+L arms . Analysis by response : 1 ) Responders ( R ) have altered HER2 downstream interconnections with PI3 K ( Spearman rho correlation [ rho ] 0.5 , p=0.12 ) vs the non-responders [ NR ] ( rho 0.9 , p=0.037 ) & HER3Y1289 correlated ( p<0.001 for all endpoints ) with EGFRy1173 , mTOR 2448 , & Beta Catenin 33 . 2 ) NR have a ) intact signaling with PI3 K ( rho 0.9 , p=0.037 ) ; b ) intact interactions with autophagy ( PI3 K - LC3B rho 0.83 , p=0.04 ) ; c ) intact stem cell - proliferation signaling ( Musashi - p70S6 Kinase T389 ( p=0.007 , rho 0.89 ) , CD44 - PTEN S380 ( p<0.001 , rho 0.92 ) were not significant in R. Analysis by AHT , prior to AHT R vs. NR : 1 ) TRZ MMP-14 , 2 ) LAP EGFRtyr1068 & Fox01/03T24/32 were statistically different . CONCLUSIONS Our study provides a unique in vivo snapshot of molecular changes in signaling pathways of microdissected tumor cells before & after anti-HER2 therapy . Molecular profiles suggest NR use autophagy & stem cell related pathways to evade therapy , while R have disruption of HER2-HER3 linkages & known downstream regulators of growth & transcription . These results provide insights into novel c and i date " drugable " targets PURPOSE Neratinib is an oral , irreversible pan-ErbB receptor tyrosine kinase inhibitor . The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer-those with and those without prior trastuzumab treatment-in an open-label , multicenter , phase II trial . PATIENTS AND METHODS Patients in the two cohorts ( prior trastuzumab , n = 66 ; no prior trastuzumab , n = 70 ) received oral neratinib 240 mg once daily . The primary end point was the 16-week progression-free survival ( PFS ) rate for the evaluable population ( prior trastuzumab , n = 63 ; no prior trastuzumab , n = 64 ) , as assessed by independent review . RESULTS The 16-week PFS rates were 59 % for patients with prior trastuzumab treatment and 78 % for patients with no prior trastuzumab treatment . Median PFS was 22.3 and 39.6 weeks , respectively . Objective response rates were 24 % among patients with prior trastuzumab treatment and 56 % in the trastuzumab-naïve cohort . The most common adverse events were diarrhea , nausea , vomiting , and fatigue . Diarrhea was the most frequent grade s 3 to 4 adverse event , occurring in 30 % of patients with prior trastuzumab treatment and in 13 % of patients with no prior trastuzumab treatment , which prompted dose reductions in 29 % and 4 % of patients , respectively , but treatment discontinuation in only one patient . No neratinib-related , grade s 3 or 4 cardiotoxicity was reported . CONCLUSION Oral neratinib showed substantial clinical activity and was reasonably well tolerated among both heavily pretreated and trastuzumab-naïve patients who had advanced , ErbB2-positive breast cancer . Diarrhea was the most common adverse effect but was manageable with antidiarrheal agents and dose modification BACKGROUND Pegylated liposomal doxorubicin ( PLD ) was shown as active but less toxic compared to doxorubicin in advanced breast cancer . Given its low cardiotoxicity , the combination of PLD and trastuzumab appears most attractive in the treatment of human epidermal factor receptor 2 (HER2)-positive breast cancer . PATIENTS AND METHODS We investigated the activity of 8 courses of PLD in combination with cisplatin and infusional 5-fluorouracil ( CCF ) plus 3-week trastuzumab in patients with primary or recurrent cT2-T4 a-d , N0 - 3 , M0 any estrogen receptor ( ER ) , HER2-positive breast cancer . Patients with ER and /or progesterone receptor ( PgR ) ≥ 10 % tumors received also letrozole ( plus triptorelin if premenopausal ) . The principal endpoint was clinical response rate ; secondary endpoints were the pathologic complete response rate ( pCR ) and the cardiac safety of the combination . RESULTS Thirty-two patients were enrolled in the study and all are evaluable for response and toxicity . Fifteen patients ( 47 % ) had ER-positive tumors , 15 patients and 2 patients had ER absent and ER poor tumors , respectively . Thirteen patients ( 41 % ) had inflammatory breast cancer ( IBC ) and 84 % of patients had clinical ly positive nodes . A clinical response rate of 94 % ( 95 % CI , 79%-99 % ) and a pCR rate of 41 % ( 95 % CI , 24%-59 % ) were observed . Fifty-four percent of patients with IBC obtained a pCR . Eleven patients discontinued treatment before completing 8 courses as planned . No patient developed relevant cardiac toxicity . CONCLUSION In this series of very locally advanced breast cancer , the combination of CCF and trastuzumab was very active obtaining an impressive rate of pCR , particularly in IBC , which merits further investigation in larger series BACKGROUND Neoadjuvant chemotherapy has become st and ard treatment for women with locally advanced breast cancer ( LABC ) . Various regimens have explored the addition of newer agents to determine safety and efficacy . The aim of this phase II study was to incorporate albumin-bound paclitaxel with sequential anthracycline-based therapy . PATIENTS AND METHODS Sixty-six women with LABC but without prior treatment and regardless of hormone receptor or HER2 status were enrolled . All patients were to receive albumin-bound paclitaxel weekly for 12 weeks followed by 5-fluorouracil/ epirubicin/cyclophosphamide ( FEC ) every 3 weeks for 4 cycles . Trastuzumab was allowed in HER2-positive ( HER2 + ) patients . Primary endpoint was pathologic complete response ( pCR ; CR ) in breast . Secondary endpoints included pCR in breast and nodes , clinical CR , 2-year progression-free survival , and overall survival . RESULTS Sixty-five patients received at least 1 dose of chemotherapy and were included in this analysis . Sixty-three patients completed 4 cycles of albumin-bound paclitaxel . Sixty-two patients received at least 1 dose of FEC , and 58 completed 4 cycles . Seventeen of 19 HER2 + women received trastuzumab . The pCR in breast was 29 % ( 19 of 65 ) . For the HER2 + subset , the pCR was 58 % ( 11 of 19 ) . Both albumin-bound paclitaxel and FEC were well tolerated . The most significant toxicities were grade 2/3 neuropathy ( 16 % ) with albumin-bound paclitaxel and grade 3/4 febrile neutropenia ( 7 % ) with FEC . CONCLUSION Albumin-bound paclitaxel given over 12 weeks is well tolerated . Albumin-bound paclitaxel should be further evaluated in a r and omized setting in both adjuvant and neoadjuvant trials PURPOSE Trastuzumab plus chemotherapy has become the st and ard of care for human epidermal growth factor receptor-2 ( HER-2 ) -positive breast cancer . Trastuzumab-based preoperative systemic therapy ( PST ; neoadjuvant therapy ) also appears promising , warranting further investigation . PATIENTS AND METHODS Patients with HER-2-positive , stage II/III , noninflammatory , operable breast cancer requiring a mastectomy ( but who wanted to conserve the breast ) received trastuzumab 4 mg/kg ( day 1 ) , followed by 2 mg/kg weekly , plus docetaxel 75 mg/m2 every 3 weeks , and carboplatin ( area under curve , 6 ) for six cycles before surgery . The primary end point was pathologic complete response ( pCR ) rate , determined from surgical specimens . RESULTS Seventy patients were enrolled . Most patients had clinical T2/T3 tumors ( 100 % ) or clinical N1/2 nodes ( 53 % ) . Sixty-seven patients ( 96 % ) completed six cycles of therapy , one patient withdrew due to progressive disease , and two patients withdrew for toxicity . A complete or partial objective clinical response occurred in 95 % of patients ( 85 % and 10 % , respectively ) . Surgery was breast conservative in 45 ( 64 % ) of 70 patients . In an intent-to-treat analysis , tumor and nodal pCR were seen in 27 ( 39 % ) of 70 patients . Central ized retrospective analysis of HER-2 status demonstrated a 43 % pCR rate in the 24 of 56 confirmed HER-2-overexpressing ( 3 + ) and /or fluorescence in situ hybridization-positive tumors . Treatment was generally well tolerated . Grade 3/4 neutropenia and febrile neutropenia were uncommon ( 2 % ) . Two patients withdrew prematurely due to a transient , asymptomatic decrease in left ventricular ejection fraction . No symptomatic cardiac dysfunction occurred . CONCLUSION PST with trastuzumab plus docetaxel and carboplatin achieved promising efficacy , with a good pCR rate and favorable tolerability in stage II or III HER-2-positive breast cancer PURPOSE Trastuzumab , a humanized antibody against the human epidermal growth factor receptor type 2 ( HER2 ) , has shown high efficacy in breast cancer . We prospect ively investigated its efficacy given simultaneously with anthracycline-taxane-based neoadjuvant chemotherapy . PATIENTS AND METHODS Patients with operable or locally advanced , HER2-positive tumors were treated preoperatively with four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel with or without capecitabine ( EC-T[X ] ) and trastuzumab 6 mg/kg ( with a loading dose of 8 mg/kg ) every 3 weeks during all chemotherapy cycles . Patients with HER2-negative tumors treated in the same study with the same chemotherapy but without trastuzumab were used as a reference group . Results Of 1,509 participants , 445 had HER2-positive tumors treated with trastuzumab and chemotherapy . Pathologic complete response ( pCR ; defined as no invasive or in situ residual tumors in the breast ) rate was 31.7 % , which was 16 % higher than that in the reference group ( 15.7 % ) . HER2-positive patients without response to the first four cycles of EC showed an unexpectedly high pCR rate of 16.6 % ( 3.3 % in the reference group ) . Breast conservation rate was 63.1 % and comparable to that of the reference group ( 64.7 % ) . EC-T(X ) plus trastuzumab was associated with more febrile neutropenia and conjunctivitis , but with a comparable short-term cardiac toxicity profile as the reference group . CONCLUSION This trial confirms that combining trastuzumab with anthracycline-taxane-based neoadjuvant chemotherapy results in a high pCR rate without clinical ly relevant early toxicity . Combination of chemotherapy with trastuzumab should be considered when neoadjuvant treatment is given to patients with HER2-positive breast cancer PURPOSE To evaluate efficacy and safety of epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab as neoadjuvant treatment in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer . PATIENTS AND METHODS Patients with central ly confirmed HER2-overexpressing breast cancer ( ≥ 2 cm or inflammatory ) received four 3-week cycles epirubicin and cyclophosphamide ( 90/600 mg/m(2 ) ) followed by four 3-week cycles paclitaxel ( 175 mg/m(2 ) ) and trastuzumab ( 6 mg/kg ) before surgery . Trastuzumab was continued after surgery to complete 1 year of treatment . Primary end point was pathologic complete response ( pCR ) defined as no residual invasive tumor in breast and lymphatic tissue . RESULTS Thirty-nine percent of 217 enrolled patients achieved a pCR . Breast conservation was possible in 64 % of patients . Three-year disease-free survival ( DFS ) was 88 % in patients with pCR compared to 73 % in patients without pCR ( P = .01 ) . Three-year overall survival ( OS ) was 96 % in patients with pCR compared to 86 % in patients without pCR ( P = .025 ) . pCR was the only significant prognostic factor for DFS ( hazard ratio [ HR ] 2.5 ; 95 % CI , 1.2 to 5.1 ; P = .013 ) and OS ( HR , 4.9 ; 95 % CI , 1.4 to 17.4 ; P = .012 ) in multivariable analysis . Cardiac toxicity was reported in eight patients ( 3.7 % ) of whom six presented with an asymptomatic left ventricular ejection fraction decrease and two with symptomatic chronic heart failure . CONCLUSION Neoadjuvant combination of trastuzumab and chemotherapy result ed in a high pCR rate in HER2-overexpressing primary breast cancer . Patients with a pCR after neoadjuvant anti-HER2 therapy in combination with chemotherapy followed by maintenance trastuzumab have an improved long-term outcome . Patients without a pCR had an increased risk for relapse and death |
10,504 | 12,138,060 | A 2 - 4 day course of oral antibiotics is as effective as 7 - 14 days in eradicating lower tract UTI in children | AIMS To compare the effectiveness of short course ( 2 - 4 days ) with st and ard duration oral antibiotic treatment ( 7 - 14 days ) for urinary tract infection ( UTI ) . | OBJECTIVES To compare the efficacy of 3-day vs 10-day treatment with a combination of amoxicillin and clavulanate potassium for children with uncomplicated urinary tract infections and to determine the role of host factors , including vesicoureteral reflux , and of bacterial virulence factors , including adhesins , in treatment outcome . DESIGN R and omized , double-blind , controlled trial . SETTING A pediatric infectious diseases clinic at an urban medical center . PATIENTS Thirty-seven children with uncomplicated urinary tract infections . INTERVENTIONS Treatment with 3 days or 10 days of antibiotics at a dosage of 20 mg/kg per day of amoxicillin and 5 mg/kg per day of clavulanate potassium in three divided doses . MEASUREMENTS AND MAIN RESULTS The success rate for 10-day treatment was 82 % ( 14/17 ) compared with 55 % ( 11/20 ) for 3-day treatment ( P = .09 ) . Among the 35 patients infected with Escherichia coli , all 10 patients infected with adhesin-negative isolates were treated successfully regardless of the duration of treatment , whereas only 14 ( 56 % ) of the 25 infections involving adhesin-positive isolates were clinical ly cured ( P = .015 ) . Two of the three failures in the 10-day treatment group were in patients with reflux . CONCLUSIONS We conclude that 3-day treatment with amoxicillin and clavulanate is insufficient for afebrile childhood urinary tract infections and that both bacterial and host factors affect treatment outcome This study was design ed to determine whether serum C-reactive protein ( CRP ) concentrations could be used to identify children with uncomplicated lower urinary tract infection who would respond favorably to short-term antibiotic therapy . A one-day or ten-day regimen of cefadroxil ( 30 mg/kg/day in two divided doses ) was assigned r and omly to 80 children who had acute urinary tract infection and CRP concentrations less than 28 microgram/ml ( CRP-negative group ) . Ten days of cefadroxil therapy was used to treat 44 children with urinary tract infection and CRP values greater than or equal to 28 microgram/ml ( CRP-positive group ) . The clinical and laboratory characteristics of the children in the two CRP-negative therapy groups were similar to , but different from those of children with CRP-positive infections . Recurrent infections occurred significantly more often at four to five days after completion of therapy in CRP-negative children who received one day ( 44.4 % ) compared to ten days ( 20 % ) of cefadroxil therapy ( P less than .05 ) . When data from this study were combined with those from our previously published investigation of short-term antibiotic therapy in CRP-negative children , a significantly larger percentage of recurrences was documented immediately after one or four days of antibiotics ( 79 % ) compared to recurrences after the st and ard ten-day regimen ( 41 % ) . Additionally , the total rate of recurrent infections for all children in both studies was significantly larger in those who received short-term therapy ( 48 % ) as opposed to conventional therapy ( 34 % ) . These data indicate that short-term antibiotic therapy is less effective than the conventional ten-day regimen in children with CRP-negative urinary tract infection The efficacy of 3-day therapy with nalidixic acid in 16 children , and trimethoprim/sulphamethoxazole in 19 children , was studied prospect ively in children with an acute infection of the lower urinary tract and compared with that of a conventional 10-day course with the same drugs . The immediate cure rate was 97 % in the 3-day group and 90 % in the 10-day group . During 3 months of follow-up there were altogether six re-infections in children given short-term treatment and six in the conventionally treated group . The results give further support for the suggestion that 3-day therapy is equivalent to 10-day treatment in uncomplicated urinary infections in children and that both nalidixic acid and trimethoprim/sulphamethoxazole are good alternatives in such an approach The patients were 117 children ( aged 4 months to 14 years ) with uncomplicated urinary tract infections caused by co-trimoxazole-sensitive Escherichia coli . The patients were r and omly assigned to receive treatment with co-trimoxazole for 3 days ( n = 58 ) or 7 days ( n = 59 ) . Urine was analyzed for bacteria before and immediately after treatment and again at 1 and 2 months . After 3 days ' treatment , infection persisted in 14 of 31 patients with P-fimbriated strains of E coli and in 1 of 27 patients with non-P-fimbriated strains . After 7 days ' treatment , infection persisted in 2 of 40 patients with fimbriated strains and in none of the 19 patients with nonfimbriated strains . One or 2 months after treatment , 3 days ' treatment was rated successful in 26 of 27 patients with nonfimbriated strains and in none of the patients with fimbriated strains . Seven days ' treatment was rated successful in all patients with nonfimbriated strains and in 32 of 40 patients with fimbriated strains . The results indicate that the length of treatment of urinary tract infections in children should be adjusted according to the presence of bacterial P-fimbriae in addition to the patients ' clinical condition We conducted a prospect i ve r and omized study to evaluate the efficacy of a single daily dose of 4 mg/kg of trimethoprim coupled with 17.5 mg/kg of sulphadiazine for three ( group 1 ) or 10 days ( group 2 ) in the treatment of uncomplicated urinary tract infections in children . Forty patients ( nine boys and 31 girls ) aged 2.5‐18 years , presenting with a urinary tract infection were allocated to one of the two groups . Patients were seen three , 10 , and 38 days after the initiation of treatment . Control urine cultures were negative in all patients at days 3 and 10 . Two patients in group 1 and one patient in group 2 suffered a relapse within a month . Single doses of trimethoprim/sulphadiazine for three or 10 days are effective in the treatment of uncomplicated urinary tract infections in children One hundred thirty-two children with acute urinary tract infection were r and omly assigned to receive trimethoprim-sulfamethoxazole in one dose , two doses daily for 3 days or two doses daily for 7 days . The patient characteristics , etiologic agents and frequency of roentgenologic abnormalities were similar for the three treatment groups . There was no significant difference in bacteriologic cure rates for the single dose regimen ( 93 % ) and multidose regimens ( 96 % ) . The difference in rates of recurrent urinary tract infection between the single dose ( 20.5 % ) and 3-day ( 5.6 % ) and 7-day ( 8 % ) regimens was statistically significant ( P = 0.033 ) . A single dose of trimethoprim-sulfamethoxazole is inadequate treatment for infants and children with acute urinary tract infection Short-course therapy for pediatric urinary tract infection ( UTI ) remains controversial . The present study was undertaken to compare the effectiveness of cefuroxime axetil ( Ceftin ) as short-course ( 2-day ) versus conventional ( 10-day ) therapy for uncomplicated pediatric UTIs . In a r and omized , controlled , prospect i ve study , we enrolled 50 children , 2 - 11 years of age , to receive oral cefuroxime axetil , 125 mg twice a day , for either 2 or 10 days . UTI was defined as at least 10(5 ) colonies/ml of a single pathogen isolated on clean catch , or at least 10(4 ) colonies/ml on a catheterized specimen . A 10-fold or greater reduction in colony count of the initially isolated organism ( 3 - 5 ) days after stopping therapy was considered a bacteriologic success , as long as the absolute colony count was below the threshold for UTI described above . Patients were followed for 15 months with multiple repeat urine cultures and radiologic studies . Twenty-five of the 50 patients enrolled were withdrawn , including 12 for initially inadequate colony counts . Eight of 12 patients in the short-course group ( 67 % ) , versus 12 of 14 in the conventional-therapy group ( 86 % ) , were initial bacteriological successes , a nonsignificant difference . All 37 initially isolated uropathogens were sensitive to cefuroxime axetil in vitro . Cefuroxime axetil is an effective antimicrobial for uncomplicated pediatric UTIs . Two-day therapy with cefuroxime axetil appears to be as effective as 10-day therapy , although sample size was limited in this study |
10,505 | 22,895,974 | HRQoL and its domains were assessed using a wide range of measures .The results suggest that exercise interventions compared with control interventions have a positive impact on overall HRQoL and certain HRQoL domains .
Since there is consistency of findings on both types of measures ( change scores and difference in follow-up scores ) there is greater confidence in the robustness of these findings .When examining exercise effects by subgroups , exercise interventions had significantly greater reduction in anxiety for survivors with breast cancer than those with other types of cancer .
Further , there was greater reduction in depression , fatigue , and sleep disturbances , and improvement in HRQoL , emotional wellbeing ( EWB ) , physical functioning , and role function for cancer survivors diagnosed with cancers other than breast cancer but not for breast cancer .
There were also greater improvements in HRQoL and physical functioning , and reduction in anxiety , fatigue , and sleep disturbances when prescribed a moderate or vigorous versus a mild exercise program .
This systematic review indicates that exercise may have beneficial effects at varying follow-up periods on HRQoL and certain HRQoL domains including physical functioning , role function , social functioning , and fatigue .
Positive effects of exercise interventions are more pronounced with moderate- or vigorous-intensity versus mild-intensity exercise programs . | BACKGROUND People with cancer undergoing active treatment experience numerous disease- and treatment-related adverse outcomes and poorer health-related quality of life ( HRQoL ) .
Exercise interventions are hypothesized to alleviate these adverse outcomes .
HRQoL and its domains are important measures of cancer survivorship , both during and after the end of active treatment for cancer .
OBJECTIVES To evaluate the effectiveness of exercise on overall HRQoL outcomes and specific HRQoL domains among adults with cancer during active treatment . | Background Preliminary studies suggest that physical exercise interventions can improve physical fitness , fatigue and quality of life in cancer patients after completion of chemotherapy . Additional research is needed to rigorously test the effects of exercise programmes among cancer patients and to determine optimal training intensity accordingly . The present paper presents the design of a r and omized controlled trial evaluating the effectiveness and cost-effectiveness of a high intensity exercise programme compared to a low-to-moderate intensity exercise programme and a waiting list control group on physical fitness and fatigue as primary outcomes . Methods After baseline measurements , cancer patients who completed chemotherapy are r and omly assigned to either a 12-week high intensity exercise programme or a low-to-moderate intensity exercise programme . Next , patients from both groups are r and omly assigned to immediate training or a waiting list ( i.e. waiting list control group ) . After 12 weeks , patients of the waiting list control group start with the exercise programme they have been allocated to . Both interventions consist of equal bouts of resistance and endurance interval exercises with the same frequency and duration , but differ in training intensity . Additionally , patients of both exercise programmes are counselled to improve compliance and achieve and maintain an active lifestyle , tailored to their individual preferences and capabilities . Measurements will be performed at baseline ( t = 0 ) , 12 weeks after r and omization ( t = 1 ) , and 64 weeks after r and omization ( t = 2 ) . The primary outcome measures are cardiorespiratory fitness and muscle strength assessed by means of objective performance indicators , and self-reported fatigue . Secondary outcome measures include health-related quality of life , self-reported physical activity , daily functioning , body composition , mood and sleep disturbances , and return to work . In addition , compliance and satisfaction with the interventions will be evaluated . Potential moderation by pre- and post-illness lifestyle , health and exercise-related attitudes , beliefs and motivation will also be assessed . Finally , the cost-effectiveness of both exercise interventions will be evaluated . Discussion This r and omized controlled trial will be a rigorous test of effects of exercise programmes for cancer patients after chemotherapy , aim ing to contribute to evidence -based practice in cancer rehabilitation programmes . Trial registration This study is registered at the Netherl and s Trial Register ( NTR2153 Background : Substantial numbers of cancer patients use complementary medicine therapies , even without a supportive evidence base . This study aim ed to evaluate in a r and omized controlled trial , the use of Medical Qigong ( MQ ) compared with usual care to improve the quality of life ( QOL ) of cancer patients . Patients and methods : One hundred and sixty-two patients with a range of cancers were recruited . QOL and fatigue were measured by Functional Assessment of Cancer Therapy — General and Functional Assessment of Cancer Therapy — Fatigue , respectively , and mood status by Profile of Mood State . The inflammatory marker serum C-reactive protein ( CRP ) was monitored serially . Results : Regression analysis indicated that the MQ group significantly improved overall QOL ( t144 = −5.761 , P < 0.001 ) , fatigue ( t153 = −5.621 , P < 0.001 ) , mood disturbance ( t122 = 2.346 , P = 0.021 ) and inflammation ( CRP ) ( t99 = 2.042 , P < 0.044 ) compared with usual care after controlling for baseline variables . Conclusions : This study indicates that MQ can improve cancer patients ’ overall QOL and mood status and reduce specific side-effects of treatment . It may also produce physical benefits in the long term through reduced inflammation PURPOSE The aims of this pilot study were the following : 1 ) to examine patterns of adherence to a brisk walking program in women receiving adjuvant chemotherapy or radiation therapy for newly diagnosed breast cancer using a prospect i ve , r and omized , controlled experimental design ; 2 ) to examine the influence of disease symptoms and treatment side effects on exercise levels ; and 3 ) to suggest methods that may improve future clinical trials of moderate-intensity exercise in similar population s. DESCRIPTION OF STUDY Fifty-two patients with newly diagnosed breast cancer were r and omly assigned to one of two treatment arms : usual care or usual care plus exercise . Those assigned to the exercise group received a st and ardized , self-administered , home-based brisk walking intervention in addition to usual care . Each day subjects completed self-report diary forms that elicited information about activity levels , and the occurrence of symptoms and side effects during cancer treatment . RESULTS Analyses of self-reported daily activity levels revealed a diffusion of treatment effect . Fifty percent of the usual-care group reported maintaining or increasing their physical activity to a moderate-intensity level , while 33 % of the exercise group did not exercise at the prescribed levels . Analyses of self-reported disease symptoms and treatment side effects did not reveal clinical ly meaningful differences between the two groups . CLINICAL IMPLICATION S The results of this study suggest that women who exercised regularly before receiving a breast cancer diagnosis attempted to maintain their exercise programs . Women who lead sedentary lifestyles may benefit from a structured exercise program that includes information and support related to exercise adherence strategies BACKGROUND Anemia in patients with solid tumors is a common problem that is associated with impaired exercise capacity , increased fatigue , and lower quality of life ( QoL ) . Erythropoiesis-stimulating agents ( ESAs ) have been shown to improve these outcomes ; however , it is unknown if additional benefits can be achieved with aerobic exercise training . METHODS We conducted a single-center , prospect i ve , r and omized , controlled trial in 55 mild-to-moderately anemic patients with solid tumors . Patients were r and omized to either darbepoetin alfa alone ( DAL , n = 29 ) or darbepoetin alfa plus aerobic exercise training ( DEX ; n = 26 ) . The DEX group performed aerobic exercise training three times per week at 60%-100 % of baseline exercise capacity for 12 weeks . The primary endpoint was QoL assessed by the Functional Assessment of Cancer Therapy-Anemia scale . Secondary endpoints were fatigue , cardiorespiratory fitness ( VO(2peak ) ) , hemoglobin ( Hb ) response , and darbepoetin alfa dosing . RESULTS Intention-to-treat analyses indicated significant improvements in QoL and fatigue in both groups over time but there were no between-group differences . The DEX group had a significantly greater VO(2peak ) than the DAL group ( mean group difference , + 3.0 ml/kg per minute ; 95 % confidence interval , 1.2 - 4.7 ; p = .001 ) and there were borderline significant differences in favor of the DEX group for Hb response and darbepoetin alfa dosing . CONCLUSIONS Aerobic exercise training did not improve QoL or fatigue beyond the established benefits of DAL but it did result in favorable improvements in exercise capacity and a more rapid Hb response with lower dosing requirements . Our results may be useful to clinicians despite the more recent restrictions on the indications for ESAs Background Exercise interventions during adjuvant cancer therapy have been shown to increase functional capacity , relieve fatigue and distress and may assist rates of chemotherapy completion . These studies have been limited to breast , gastric and mixed cancer groups and it is not yet known if a similar intervention is even feasible among women with ovarian cancer . We aim ed to assess safety , feasibility and potential effect of a walking intervention in women undergoing chemotherapy for ovarian cancer . Methods Women newly diagnosed with ovarian cancer were recruited to participate in an individualised walking intervention throughout chemotherapy and were assessed pre- and post-intervention . Feasibility measures included session adherence , compliance with exercise physiologist prescribed walking targets and self-reported program acceptability . Changes in objective physical functioning ( 6-minute walk test ) , self-reported distress ( Hospital Anxiety and Depression Scale ) , symptoms ( Memorial Symptom Assessment Scale - Physical ) and quality of life ( Functional Assessment of Cancer Therapy - Ovarian ) were calculated , and chemotherapy completion and adverse intervention effects recorded . Results Seventeen women were enrolled ( 63 % recruitment rate ) . Mean age was 60 years ( SD = 8 years ) , 88 % were diagnosed with FIGO stage III or IV disease , 14 women underwent adjuvant and three neo-adjuvant chemotherapy . On average , women adhered to > 80 % of their intervention sessions and complied with 76 % of their walking targets , with the majority walking four days a week at moderate intensity for 30 minutes per session . Meaningful improvements were found in physical functioning , physical symptoms , physical well-being and ovarian cancer-specific quality of life . Most women ( 76 % ) completed ≥85 % of their planned chemotherapy dose . There were no withdrawals or serious adverse events and all women reported the program as being helpful . Conclusions These positive preliminary results suggest that this walking intervention for women receiving chemotherapy for ovarian cancer is safe , feasible and acceptable and could be used in development of future work . Trial registration Research suggests that stress‐reduction programs tailored to the cancer setting help patients cope with the effects of treatment and improve their quality of life . Yoga , an ancient Eastern science , incorporates stress‐reduction techniques that include regulated breathing , visual imagery , and meditation as well as various postures . The authors examined the effects of the Tibetan yoga ( TY ) practice s of Tsa lung and Trul khor , which incorporate controlled breathing and visualization , mindfulness techniques , and low‐impact postures in patients with lymphoma BACKGROUND AND OBJECTIVES This pilot project assessed the acceptability of a mixed-type , moderate-intensity exercise programme following breast cancer treatment , and the impact on presence of lymphoedema , fitness , body composition , fatigue , mood and quality of life . METHODS Ten women completed the programme and measures of fitness ( sub-maximal ergometer test ) , body composition ( bio-electrical impedance ) , lympoedema ( bio-electrical impedance and arm circumferences ) , fatigue ( revised Piper Fatigue Scale ) , mood ( Hospital Anxiety and Depression Scale ) , quality of life ( FACT-B ) and general well-being , at baseline , completion of the programme , and 6-week and 3-month follow-up . RESULTS Participation in the programme caused no adverse effect on the presence of lymphoedema . There was a trend towards reduction in fatigue and improved quality of life across the testing phases . Women rated the programme extremely favourably , citing benefits of the support of other women , trained guidance , and the opportunity to experience different types of exercise . CONCLUSIONS A mixed-type , moderate-intensity exercise program in a group format is acceptable to women following breast cancer treatment , with the potential to reduce fatigue and improve quality of life , without exacerbating or precipitating lymphoedema . This pilot work needs to be confirmed in larger r and omised studies Background To examine the effects of a 6 month lifestyle intervention on quality of life , depression , self-efficacy and eating behavior changes in overweight and obese endometrial cancer survivors . Methods Early stage endometrial cancer survivors were r and omized to intervention ( n = 23 ) or usual care ( n = 22 ) groups . Chi-square , Student 's t-test and repeated measures analysis of variance were used in intent-to-treat analyses . Outcomes were also examined according to weight loss . Results Morbidly obese patients had significantly lower self-efficacy , specifically when feeling physical discomfort . There was a significant improvement for self-efficacy related to social pressure ( p = .03 ) and restraint ( p = .02 ) in the LI group . There was a significant difference for emotional well-being quality of life ( p = .02 ) , self-efficacy related to negative emotions ( p < .01 ) , food availability ( p = .03 ) , and physical discomfort ( p = .01 ) in women who lost weight as compared to women who gained weight . Improvement in restraint was also reported in women who lost weight ( p < .01 ) . Conclusion This pilot lifestyle intervention had no effect on quality of life or depression but did improve self-efficacy and some eating behaviors . Trial Registration http://www . clinical trials.gov ; Goals of workProstate cancer patients receiving and rogen deprivation therapy ( ADT ) are vulnerable to a number of potentially debilitating side effects , which can significantly impact quality of life . The role of alternate therapies , such as physical activity ( PA ) , in attenuating these side effects is largely understudied for such a large population . Thus , the purpose of this study was to investigate the effects of PA intervention for men receiving ADT on PA behavior , quality of life , and fitness measures . Patients and methods One hundred participants were r and omized into an intervention ( n = 53 ) or a wait-list control group ( n = 47 ) , with 11 dropping out of the intervention group and 23 dropping out of the wait-list control group prior to post-testing . The intervention consisted of both an individually tailored home-based aerobic and light resistant training program and weekly group sessions . PA , quality of life , fitness , and physiological outcomes were assessed pre and post the 16-week intervention . Results Significant increases in PA , supported by changes in girth measures and blood pressure , support the beneficial impact of the intervention . Positive trends were also evident for depression and fatigue . However , due to the high dropout rate , these results must be interpreted with caution . Conclusions PA effectively attenuates many of the side effects of ADT and should be recommended to prostate survivors as an alternate therapy . Determining the maintenance of this behavior change will be important for underst and ing how the long-term benefits of increased activity levels may alleviate the late effects of ADT Recovering from cancer treatment can be a difficult experience , both physically and psychologically . This paper describes a r and omized controlled trial that evaluates the effects of exercise therapy upon quality of life in 120 women who have had breast cancer . To facilitate behaviour change , exercise counselling is also included as an integral component in the exercise therapy intervention . Participants are r and omized to one of three groups : exercise therapy , body conditioning ( placebo control ) or a normal care control group . The supervised exercise therapy and body conditioning sessions take place 3 times per week for 8 weeks . Outcome measures include quality of life , physical self-perceptions , depression , satisfaction with life , exercise behaviour , aerobic capacity and percentage body fat . All outcomes are assessed at baseline , 4 weeks during the intervention and at the end of the 8-week intervention . Follow-up assessment s of outcomes take place at 3 and 6 months post-intervention . As the number of women surviving breast cancer is increasing and cancer treatment is linked to reduced quality of life , it is critical to evaluate treatments that improve the quality of life of this population or hasten recovery following treatment This study examined the effect of an integrated yoga programme on chemotherapy-related nausea and emesis in early operable breast cancer out patients . Sixty-two subjects were r and omly allocated to receive yoga ( n = 28 ) or supportive therapy intervention ( n = 34 ) during the course of their chemotherapy . Both groups had similar socio-demographic and medical characteristics . Intervention consisted of both supervised and home practice of yoga sessions lasting for 60 min daily , while the control group received supportive therapy and coping preparation during their hospital visits over a complete course of chemotherapy . The primary outcome measure was the Morrow Assessment of Nausea and Emesis ( MANE ) assessed after the fourth cycle of chemotherapy . Secondary outcomes included measures for anxiety , depression , quality of life , distressful symptoms and treatment-related toxicity assessed before and during the course of chemotherapy . Following yoga , there was a significant decrease in post-chemotherapy-induced nausea frequency ( P = 0.01 ) and nausea intensity ( P = 0.01 ) , and intensity of anticipatory nausea ( P = 0.01 ) and anticipatory vomiting ( P = 0.05 ) as compared with the control group . There was a significant positive correlation between MANE scores and anxiety , depression and distressful symptoms . In conclusion , the results suggest a possible use for stress reduction interventions such as yoga in complementing conventional antiemetics to manage chemotherapy-related nausea and emesis PURPOSE Self-directed and supervised exercise were compared with usual care in a clinical trial design ed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer . PATIENTS AND METHODS One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life , aerobic capacity , and body weight . Participants were r and omly allocated to one of three intervention groups : usual care ( control group ) , self-directed exercise , or supervised exercise . Quality of life , aerobic capacity , and body weight measures were repeated at 26 weeks . The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks . RESULTS Physical functioning in the control group decreased by 4.1 points , whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups , respectively ( P = .04 ) . Post hoc analysis showed a moderately large ( and clinical ly important ) difference between the self-directed and control groups ( 9.8 points ; P = .01 ) and a more modest difference between the supervised and control groups ( 6.3 points ; P = .09 ) . No significant differences between groups were observed for changes in quality of life scores . In a secondary analysis of participants stratified by type of adjuvant therapy , supervised exercise improved aerobic capacity ( + 3.5 mL/kg/min ; P = .01 ) and reduced body weight ( -4.8 kg ; P < .05 ) compared with usual care only in participants not receiving chemotherapy . CONCLUSION Physical exercise can blunt some of the negative side effects of breast cancer treatment , including reduced physical functioning . Self-directed exercise is an effective way to improve physical functioning compared with usual care . In participants not receiving chemotherapy , supervised exercise may increase aerobic capacity and reduce body weight compared with usual care To evaluate the efficacy and economic efficiency of a multimedia , multimodal physical activity program for women undergoing adjuvant therapy following surgery for breast cancer . We conducted a r and omized trial with concurrent incremental cost-effectiveness analysis and blinded baseline , 3 , 6 and 12-month follow-up assessment s amongst women undergoing adjuvant therapy following surgery for breast cancer ( n = 89 ) . The intervention was a multimedia , multimodal exercise program comprising strength , balance and endurance training elements . The control was sham flexibility and relaxation program delivered using similar material s. The primary outcome was health-related quality of life ( EQ-5D & VAS , EORTC C30 , BR23 ) . Economic outcomes included direct health care costs and productivity gains and losses . Participants in the intervention group demonstrated greater improvement in health-related quality of life between baseline and the 3-month assessment [ mean ( sd ) EQ-5D VAS ( 0–100 ) baseline : 72.6 ( 15.6 ) , 3 month : 80.6 ( 11.6 ) ] when compared to control group participants [ baseline : 77.5 ( 13.5 ) , 3 month : 74.1 ( 20.6 ) , P = 0.006 ] and also improved more in terms of physical function [ mean ( sd ) EORTC C30 physical function scale intervention ( 0–100 ) baseline : 84.9 ( 14.8 ) , 3 month : 86.9 ( 10.7 ) , control baseline : 91.3 ( 9.6 ) , 3 month : 86.7 ( 14.9 ) , P = 0.02 ] . These improvements were not sustained beyond this point . Upper limb volumes were also lower amongst intervention group participants . However , there was low probability that the intervention would be both less costly and more effective than the control condition ( range probability = 0.05–50.02 % depending on approach ) . Provision of multimodal exercise programs will improve the short-term health of women undergoing adjuvant therapy for breast cancer but are of question able economic efficiency Patients who undergo hematopoietic SCT ( HSCT ) often experience physical and psychological problems , even long after treatment has been completed . This study was performed to evaluate the effects of a 12-week outpatient physical exercise ( PE ) program , incorporating aerobic and strength exercises , as compared with a usual care control condition on patients ’ physical performance and psychosocial well-being . Patients who had completed HSCT up to 6 months earlier were r and omly assigned to a supervised PE program ( n=64 ) or a usual care control group ( n=67 ) . Primary outcomes were quantified physical performance and self-reported physical functioning . Secondary outcomes were body composition measurement , quantified walking activity and patient-reported outcomes ( physical activity , fatigue and health-related quality of life ) . Assessment s were at baseline , immediately after program completion and at 3-month follow-up . Significant intervention effects were observed at both posttreatment and follow-up on physical performance measures . No other outcomes yielded statistically significant group differences . PE should be considered in the management of HSCT recipients to improve physical performance after discharge from the hospital . Further research is needed to determine how the program can be enhanced so that improved physical performance also translates into improved physical and psychosocial functioning in daily life BACKGROUND During the last decade , survival rates for breast cancer have increased as a result of earlier detection and increased use of adjuvant therapy . Limited data exist on the psychosocial aspects of the transitional period between the end of primary treatment and survivorship . We investigated the baseline psychosocial status of women enrolled in a r and omized trial testing two psychosocial interventions for women at the end of primary treatment . METHODS Participants , identified within 1 month after surgery ( registration ) , provided demographic information and limited measures of quality of life . They were followed until they finished primary treatment ( enrollment ) , at which time they completed a mailed baseline survey that included st and ardized measures of quality of life ( including st and ardized scales of physical and emotional functioning ) , mood , symptoms , and sexual functioning . A total of 558 patients ( mean age = 56.9 years ) were enrolled in the study between July 1 , 1999 , and June 30 , 2002 . Health outcomes were examined according to treatment received : mastectomy with and without chemotherapy , and lumpectomy with and without chemotherapy . All statistical tests were two-sided . RESULTS Among all treatment groups , patients who had a mastectomy had the poorest physical functioning at registration ( P<.001 ) and at enrollment ( P=.05 ) . At enrollment , mood and emotional functioning were similar among all patients , with no differences by type of treatment received . At enrollment , symptoms , including muscle stiffness , breast sensitivity , aches and pains , tendency to take naps , and difficulty concentrating , were common among patients in all groups and were statistically significantly associated with poor physical functioning and emotional well-being . Sexual functioning was worse for women who received chemotherapy than for those who did not , regardless of type of surgery ( P<.001 ) . CONCLUSIONS At the end of primary treatment for breast cancer , women in all treatment groups report good emotional functioning but report decreased physical functioning , particularly among women who have a mastectomy or receive chemotherapy . Clinical interventions to address common symptoms associated with treatment should be considered to improve physical and emotional functioning at the end of primary treatment for breast cancer Background Premature menopause is a major concern of younger women undergoing adjuvant therapy for breast cancer . Hormone replacement therapy is contraindicated in women with a history of breast cancer . Non-hormonal medications show a range of bothersome side-effects . There is growing evidence that cognitive behavioral therapy ( CBT ) and physical exercise can have a positive impact on symptoms in naturally occurring menopause . The objective of this study is to investigate the efficacy of these interventions among women with breast cancer experiencing treatment-induced menopause . Methods / design In a r and omized , controlled , multicenter trial , we are evaluating the effectiveness of CBT/relaxation , of physical exercise and of these two program elements combined , in reducing menopausal symptoms , improving sexual functioning , reducing emotional distress , and in improving the health-related quality of life of younger breast cancer patients who experience treatment-induced menopause . 325 breast cancer patients ( aged < 50 ) are being recruited from hospitals in the Amsterdam region , and r and omly allocated to one of the three treatment groups or a ' waiting list ' control group . Self-administered question naires are completed by the patients at baseline , and at 12 weeks ( T1 ) and 6 months ( T2 ) post- study entry . Upon completion of the study , women assigned to the control group will be given the choice of undergoing either the CBT or physical exercise program . Discussion Cognitive behavioral therapy and physical exercise are potentially useful treatments among women with breast cancer undergoing treatment-induced , premature menopause . For these patients , hormonal and non-hormonal therapies are contraindicated or have a range of bothersome side-effects . Hence , research into these interventions is needed , before dissemination and implementation in the current health care system can take place . Trial registration The study is registered at the Netherl and s Trial Register ( NTR1165 ) and Clinical Trials.gov ( NCT00582244 ) Exercise improves health in lymphoma patients but the determinants of adherence in this population are unknown . The purpose of this study is to examine predictors of exercise adherence in lymphoma patients . In a r and omized trial , 60 lymphoma patients were assigned to the exercise group and asked to attend three supervised exercise sessions per week for 12 weeks . Baseline data were collected on demographic , medical , fitness , psychosocial , and motivational variables . Adherence was assessed by objective attendance . Adherence was 77.8 % and was significantly predicted by age ( β = 0.29 ; p = 0.016 ) and past exercise ( β = 0.27 ; p = 0.024 ) ; and borderline significantly predicted by previous treatments ( β = 0.22 ; p = 0.053 ) , body mass index ( β = −0.21 ; p = 0.076 ) , and smoking ( β = −0.19 ; p = 0.092 ) . Poorer exercise adherence was experienced by lymphoma patients under age 40 , insufficiently active at baseline , previously treated with radiation therapy , overweight or obese , and smokers . Findings may facilitate the development of targeted interventions to improve exercise adherence in this understudied patient population Background Exercise adherence is a challenge for breast cancer patients receiving chemotherapy but few studies have identified the key barriers . Purpose In this paper , we report the barriers to supervised exercise in breast cancer patients participating in a r and omized controlled trial . Methods Breast cancer patients initiating adjuvant chemotherapy ( N = 242 ) were r and omly assigned to usual care ( n = 82 ) or supervised resistance ( n = 82 ) or aerobic ( n = 78 ) exercise . Participants r and omized to the two exercise groups ( n = 160 ) were asked to provide a reason for each missed exercise session . Results The two exercise groups attended 70.2 % ( 5,495/7,829 ) of their supervised exercise sessions and provided a reason for missing 89.5 % ( 2,090/2,334 ) of their unattended sessions . The 2,090 reasons represented 36 different barriers . Feeling sick ( 12 % ) , fatigue ( 11 % ) , loss of interest ( 9 % ) , vacation ( 7 % ) , and nausea/vomiting ( 5 % ) accounted for the most missed exercise sessions . Disease/treatment-related barriers ( 19 of the 36 barriers ) accounted for 53 % ( 1,102/2,090 ) of all missed exercise sessions . Demographic and medical variables did not predict the types of exercise barriers reported . Conclusions Barriers to supervised exercise in breast cancer patients receiving chemotherapy are varied but over half can be directly attributed to the disease and its treatments . Behavioral support programs need to focus on strategies to maintain exercise in the face of difficult treatment side effects In this study , we examined correlates of adherence and contamination in a r and omized controlled trial ( RCT ) of exercise in cancer survivors using the theory of planned behavior and the Five Factor Model of personality ( FFM ) . We r and omly assigned cancer survivors in group psychotherapy classes to either a waiting-list control group ( n = 45 ) or a home-based , moderate intensity exercise program ( n = 51 ) . At baseline , participants completed measures of the theory of planned behavior , the FFM , past exercise , physical fitness , medical variables , and demographics . We then monitored exercise over a 10-week period by weekly self-reports . Hierarchical multiple regression analyses indicated that the independent predictors of overall RCT exercise across both conditions were past exercise ( β = .36 , p > .001 ) , assignment to experimental condition ( β = .34 , p > .001 ) , sex ( β = .30 , p > .001 ) , and intention ( β = .14 , p > .10 ) . For exercise adherence in the exercise condition , the independent predictors were sex ( β = .38 , p > .01 ) , extraversion ( β = .30 , p > .05 ) , normative beliefs ( β = -.27 , p > .05 ) , and perceived behavioral control ( β = .23 , p > .10 ) . Finally , the independent predictors of exercise contamination in the control condition were past exercise ( β = .70 , p > .001 ) , sex ( β = .20 , p > .05 ) , and intention ( β = .17 , p > .10 ) . We conclude that the correlates of exercise adherence and contamination differ in kind as well as in degree . Explanations for these findings and practical implication s for conducting exercise RCTs in this population are offered OBJECTIVES This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer out patients undergoing adjuvant radiotherapy at a cancer centre . METHODS Eighty-eight stage II and III breast cancer out patients were r and omly assigned to receive yoga ( n = 44 ) or brief supportive therapy ( n = 44 ) prior to their radiotherapy treatment . Intervention consisted of yoga sessions lasting 60 min daily while the control group was imparted supportive therapy once in 10 days . Assessment s included European Organization for Research in the Treatment of Cancer- Quality of Life ( EORTCQoL C30 ) functional scales and Positive and Negative Affect Schedule ( PANAS ) . Assessment s were done at baseline and after 6 weeks of radiotherapy treatment . RESULTS An intention to treat GLM repeated measures ANOVA showed significant difference across groups over time for positive affect , negative affect and emotional function and social function . There was significant improvement in positive affect ( ES = 0.59 , p = 0.007 , 95%CI 1.25 to 7.8 ) , emotional function ( ES = 0.71 , p = 0.001 , 95%CI 6.45 to 25.33 ) and cognitive function ( ES = 0.48 , p = 0.03 , 95%CI 1.2 to 18.5 ) , and decrease in negative affect ( ES = 0.84 , p<0.001 , 95%CI -13.4 to -4.4 ) in the yoga group as compared to controls . There was a significant positive correlation between positive affect with role function , social function and global quality of life . There was a significant negative correlation between negative affect with physical function , role function , emotional function and social function . CONCLUSION The results suggest a possible role for yoga to improve quality of life and affect in breast cancer out patients The purpose of this r and omized , controlled clinical trial was to preliminarily examine the effects of a three-week walking exercise program ( WEP ) on fatigue-related experiences of acute myelogenous leukemia ( AML ) patients receiving chemotherapy . Eligible AML patients were r and omly assigned to either an experimental group ( n=11 ) , which received 12 minutes of WEP per day , five days per week for three consecutive weeks , or to a control group ( n=11 ) , which received st and ard ward care . Effects of the WEP were assessed by seven indicators : worst and average fatigue intensities , fatigue interference with patients ' daily life , 12-minute walking distance , overall symptom distress , anxiety , and depressive status . All patients were evaluated four times : before chemotherapy ( baseline or Day 1 ) , Day 7 , Day 14 , and Day 21 of chemotherapy . Data were analyzed by Generalized Estimating Equation and revealed that AML patients in the three-week WEP group had a significantly greater increase in 12-minute walking distance than the control group . Patients in the WEP also had lower levels of fatigue intensity and interference , symptom distress , anxiety , and depressive status than the control group . Although preliminary , our results strongly suggest that three weeks of systematic walking exercise is clinical ly feasible for AML patients undergoing chemotherapy and can effectively improve their fatigue-related experiences OBJECTIVES Supervised exercise is beneficial for lymphoma patients , but it needs to be maintained to optimize long-term benefits . Here , we report the predictors of follow-up exercise behavior 6 months after a r and omized controlled trial in lymphoma patients . METHODS Lymphoma patients were r and omly assigned to 12 weeks of supervised aerobic exercise ( n = 60 ) or usual care ( n = 62 ) . At baseline and post-intervention , data were collected on demographic , medical , health-related fitness , quality of life , and motivational variables . At 6-month follow-up , participants were mailed a question naire that assessed exercise behavior and were categorized as meeting or not meeting public health exercise guidelines . RESULTS At 6-month follow-up , 110 participants ( 90.2 % ) responded , of which 61 ( 55.5 % ) were meeting public health exercise guidelines . In univariate analyses , 16 variables predicted 6-month follow-up exercise behavior . In a stepwise regression analysis , five variables entered the model and explained 38 % ( p < 0.001 ) of the variance including the following : accepting a post-intervention exercise prescription ( β = 0.33 ; p < 0.001 ) , achieving a higher peak power output at post-intervention ( β = 0.28 ; p = 0.001 ) , experiencing a larger positive change in perceived behavioral control ( β = 0.18 ; p = 0.028 ) , having Hodgkin lymphoma ( β = 0.19 ; p = 0.025 ) , and having a stronger post-intervention intention ( β = 0.18 ; p = 0.034 ) . CONCLUSION Exercise behavior in lymphoma patients 6 months after a r and omized trial was predicted by a wide range of demographic , medical , health-related fitness , quality of life , and motivational variables . These findings may help facilitate the uptake of self-directed exercise after short-term supervised exercise in lymphoma patients Goals of the workThe goal of this study was to examine the association between exercise and quality of life ( QOL ) in multiple myeloma cancer survivors . Patients and methods Using a retrospective design , 156 multiple myeloma cancer survivors were mailed a question naire that assessed self-reported exercise behavior over three periods ( prediagnosis , active treatment , and off-treatment ) and QOL.Main results The response rate was 56 % ( 88/156 ) . Descriptive analyses indicated that 6.8 % and 20.4 % of survivors met national exercise guidelines during active and off-treatment periods , respectively . Exercise during active treatment and off-treatment were positively associated with overall QOL and all subdomains of QOL ( all P<0.05 ) except physical wellbeing . Conclusions A low percentage of multiple myeloma cancer survivors are exercising regularly either during active or off-treatment periods . Survivors who report more exercise during these periods also report higher QOL . These findings suggest that a r and omized controlled trial is warranted Question : Does restriction of full shoulder mobilisation for one week reduce the incidence and severity of lymphoedema in women after axillary lymph node dissection ( ALND ) for breast cancer ? Design : R and omised , controlled trial with concealed allocation and blinded assessment of some outcomes . Setting : Two hospitals in the United Kingdom . Participants : Adult women with early breast cancer admitted for surgery that included axillary lymph node dissection . Previous breast cancer , axillary surgery and local radiotherapy were exclusion criteria . R and omisation of 116 participants allotted 58 to a st and ard exercise regimen and 58 to the same regimen with restricted arm and shoulder movement for the first week . Interventions : All participants were prescribed four 10-minute exercise sessions per day , in which individual exercises were repeated slowly and rhythmically 3 to 4 times . The exercises included unresisted shoulder and elbow range-of-motion exercises while upright . The early mobilisation group commenced full shoulder mobilisation within two days after surgery . The exercises were modified for the delayed mobilisation group so that the arm was not elevated above horizontal for the first 7 days after surgery . Exercises encouraging full range of shoulder movement were introduced in the second week . The exercises were supervised during the hospital admission and were prescribed to continue for one year at home . Outcome measures : The primary outcome was the incidence of lymphoedema , defined as a 200 ml or greater difference in arm volume compared to the unoperated arm . Secondary outcome measures were the severity of lymphoedema again determined by volume , wound drainage volumes , range of shoulder motion , grip strength , and quality of life scores related to shoulder disability and breast cancer therapy . Results : 109 participants completed the study . After one year , 16 women in the early mobilisation group but only 6 women in the delayed mobilisation group had developed lymphoedema . Thus one case of lymphoedema was prevented for every 6 women managed with the exercise regimen that delayed shoulder mobilisation ( 95 % CI 3 to 35 ) . Lymphoedema severity and wound drainage were both significantly greater in the early mobilisation group . The groups did not differ significantly on the remaining secondary outcomes . Conclusion : The incidence of lymphoedema can be reduced by restricting exercises so that the arm is not elevated above horizontal for one week after ALND Background And rogen deprivation therapy ( ADT ) is accompanied by a number of adverse side effects including reduced bone mass and increased risk for fracture , reduced lean mass and muscle strength , mood disturbance and increased fat mass compromising physical functioning , independence , and quality of life . The purpose of this investigation is to examine the effects of long term exercise on reversing musculoskeletal-related side effects , and cardiovascular and diabetes risk factors in men receiving and rogen deprivation for their prostate cancer . Specifically , we aim to investigate the effects of a 12-month exercise program design ed to load the musculoskeletal system and reduce cardiovascular and diabetes disease progression on the following primary endpoints : 1 ) bone mineral density ; 2 ) cardiorespiratory function and maximal oxygen capacity ; 3 ) body composition ( lean mass and fat mass ) ; 4 ) blood pressure and cardiovascular function ; 5 ) lipids and glycemic control ; and 6 ) quality of life and psychological distress . Methods / Design Multi-site r and omized controlled trial of 195 men ( 65 subjects per arm ) undergoing treatment for prostate cancer involving ADT in the cities of Perth and Brisbane in Australia . Participants will be r and omized to ( 1 ) resistance/impact loading exercise , ( 2 ) resistance/cardiovascular exercise groups and ( 3 ) usual care/delayed exercise . Participants will then undergo progressive training for 12 months . Measurements for primary and secondary endpoints will take place at baseline , 6 and 12 months ( end of the intervention ) . Discussion The principal outcome of this project will be the determination of the strength of effect of exercise on the well established musculoskeletal , cardiovascular and insulin metabolism side effects of and rogen deprivation in prostate cancer patients . As this project is much longer term than previous investigations in the area of exercise and cancer , we will gain knowledge as to the continuing effects of exercise in this patient population specifically targeting bone density , cardiovascular function , lean and fat mass , physical function and falls risk as primary study endpoints . In terms of advancement of prostate cancer care , we expect dissemination of the knowledge gained from this project to reduce fracture risk , improve physical and functional ability , quality of life and ultimately survival rate in this population . Clinical Trial RegistryA Phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer ; We describe adherence to a three group r and omised controlled trial that involved aerobic exercise therapy ( N=34 ) and exercise-placebo intervention ( N=36 ) or usual care ( N=38 ) in women treated for breast cancer . We also investigated relationships between routes of trial recruitment , socio-economic characteristics , health behaviours , cancer treatment regimen(s ) and subsequent adherence to the interventions . Women who had completed breast cancer treatment 12 - 36 months previously were r and omised to one of the groups . The intervention groups attended an exercise facility three times per week for eight weeks . A total of 77 % of the aerobic exercise therapy and 88.9 % of the exercise-placebo groups attended at least 70 % of prescribed sessions . The percentage of women achieving 30min of aerobic exercise per session steadily increased during the intervention but many women were not able to achieve this goal . Routes of trial recruitment , socio-economic characteristics , health behaviours and cancer treatment regimen(s ) were not related to intervention . Exercise therapy participants were able to comply with the progressive nature of the aerobic exercise intervention , although some women were not able to achieve 30min of aerobic exercise per session by intervention completion . Research is still required to tease out all the potential determinants of exercise in this population Surgery and radiotherapy commonly cause adverse musculoskeletal problems , particularly loss of strength and range of motion , in the upper quadrant of breast cancer patients . Few well- design ed studies have investigated whether these impairments can be prevented . Stretching is an effective technique for increasing range of motion , hence the aim of this study was to investigate whether a stretching program reduced acute musculoskeletal impairments in patients undergoing radiotherapy for breast cancer . Sixty-four women were recruited prior to commencement of radiotherapy following breast cancer surgery . Participants were r and omised to either a control or stretch group . Participants in both groups were review ed by the physical therapist on a weekly basis for approximately 6 weeks , and were given general information about skin care and lymphedema . The control group received no advice about exercise . The stretch group received instruction on low-load , prolonged pectoral stretches , which were to be performed daily and were checked at weekly visits . Shoulder range of motion , strength , arm circumference , and quality of life measurements were taken prior to , and at completion of radiotherapy , and at 7 months after radiotherapy . There was no difference in any outcome between groups . Breast symptoms increased for both groups during radiotherapy , without loss of strength or range of movement . The incidence of lymphedema during the study was low for both groups and did not differ between groups . The pectoral stretching program did not influence the outcomes measured because the symptoms reported by patients were not a consequence of contracture PURPOSE To conduct a clinical trial to determine if an educational intervention and a nutritional intervention could enhance physical and psychological functioning among younger women completing treatment for early-stage breast cancer . PATIENTS AND METHODS Younger women ( 50 years of age or younger , N = 252 ) , within 2 months of having completed active nonhormonal adjuvant therapy , diagnosed with stage 0 , I , or II breast cancer with 10 or fewer positive lymph nodes were r and omly assigned to a three-arm clinical trial . Women in the control arm of the trial received st and ard medical care . Women in the two active arms received either an educational intervention , design ed to provide information about their illness and enhance adjustment , or a nutritional intervention , design ed to promote a more healthy diet . Primary end points included mental functioning , physical functioning , and depressive symptoms . Women were assessed before r and om assignment , 4 months later ( immediately post-intervention ) , and 13 months later ( 9 months post-intervention ) . RESULTS Participants assigned to the two active treatment arms had significantly less depressive symptomatology and better physical functioning by 13-month follow-up ( differences between the two active arms were nonsignificant ) . These effects were primarily accounted for by changes in intrusive thoughts , concerns regarding cancer recurrence and mortality , self-concept perceptions , and self-efficacy expectations . CONCLUSION Tailored psychosocial interventions can be effectively design ed to enhance adjustment among younger women who are completing nonhormonal adjuvant therapy Purpose Postoperative radiotherapy for breast cancer has a number of associated complications . This study examined whether supervised moderate-intensity exercise could mitigate the complications that occur during radiotherapy . Patients and Methods Forty women were r and omized before radiotherapy after various operations for breast cancer . Seventeen patients who were assigned to the exercise group performed supervised moderate-intensity exercise therapy for 50 min 3 times per week for 5 weeks . Twenty-three patients in the control group were asked to perform self-shoulder stretching exercise . The World Health Organization Quality of Life-BREF ( WHOQOL-BREF ) , brief fatigue inventory ( BFI ) , range of motion ( ROM ) of the shoulder , and pain score were assessed before and after radiotherapy . Results There were no significant differences noted at baseline between groups . In the exercise group , there was an increase in the WHOQOL-BREF and shoulder ROM and decrease in BFI and pain score after radiotherapy . On the other h and , patients in the control group showed decrease in the WHOQOL-BREF and shoulder ROM and increase in BFI and pain score after radiotherapy . There were statistically significant differences in the changes in the WHOQOL , BFI , shoulder ROM , and pain score between the groups . Conclusion Patients receiving radiotherapy for breast cancer may benefit in physical and psychological aspects from supervised moderate-intensity exercise therapy Purpose 1 ) To determine the effect of a home-based walking exercise program on the sleep quality and quality of life of cancer patients , as well as 2 ) to determine if enhanced sleep quality was associated with improvement in quality of life over time . Methods This is a prospect i ve , longitudinal , two-armed , r and omized clinical trial . Participants were recruited from oncology outpatient clinics in two university-based medical centers and were allocated to either usual care ( n = 35 ) or a home-based walking exercise intervention for 8 weeks ( n = 36 ) . Measurements included the Taiwanese version of the Pittsburgh Sleep Quality Index , the Medical Outcomes Study Short Form-36 , the Taiwanese Version Ratings of the Perceived Exertion Scale , and a walking exercise log . This study was analyzed on an intention-to-treat basis . Effects of the walking exercise program on sleep quality and quality of life were analyzed by the generalized estimating equation method . Results Patients in the exercise group reported significant improvements in sleep quality ( β = −3.54 , p < 0.01 ) and the mental health dimension of quality of life ( β = 10.48 , p < 0.01 ) . Among patients who exercised , enhanced sleep quality also corresponded with reduced bodily pain ( β = 0.98 , p = 0.04 ) and improvements over time in the mental health dimension of quality of life ( β = −3.87 , p < 0.01 ) . Conclusions A home-based walking exercise program can be easily incorporated into care for cancer patients who are suffering from sleep disturbances Advice to rest and take things easy if patients become fatigued during radiotherapy may be detrimental . Aerobic walking improves physical functioning and has been an intervention for chemotherapy‐related fatigue . A prospect i ve , r and omized , controlled trial was performed to determine whether aerobic exercise would reduce the incidence of fatigue and prevent deterioration in physical functioning during radiotherapy for localized prostate carcinoma BACKGROUND The BREX study is one of the largest r and omised prospect i ve exercise interventions of breast cancer survivors which aims at investigate whether regular exercise could reduce the long-term side effects of the adjuvant treatments and improve quality of life . MATERIAL AND METHODS The study was limited to consider patients aged 35 - 68 years , who had recently completed adjuvant chemotherapy or started endocrine therapy . In this paper , we describe the recruitment process of the 413 r and omised patients from the Helsinki University Hospital between September 2005 and September 2007 . RESULTS 768 potentially eligible patients out of the 1321 screened ( via medical records ) were contacted by phone . After the phone call 240 patients were excluded due to health problems that contraindicated exercise training . The most common health problems were musculoskeletal disorders . A total of 528 patients were considered as eligible for the intervention . Ultimately 413 of them agreed to participate result ing in a 53.8 % recruitment rate of the potentially eligible patients . The most important reasons for declining were social , not health related . Eligible patients who did not want to participate did not differ significantly from those who participated according to age , health status , breast cancer treatment and tumour type . DISCUSSION The high recruitment rate demonstrates breast cancer patient 's willingness to participate even in long-lasting supervised exercise programs shortly after adjuvant treatments . After taking into account the selection of the population by age and musculoskeletal health , the results of the present intervention can be generalized to represent urban breast cancer patient population in Finl and Background St and ard treatment for patients with disseminated germ cell tumors is combination chemotherapy with bleomycin , etoposide and cisplatin ( BEP ) . This treatment is highly effective , but the majority of patients experience severe adverse effects during treatment and are at risk of developing considerable long-term morbidity , including second malignant neoplasms , cardiovascular disease , and pulmonary toxicity . One neglected side effect is the significant muscular fatigue mentioned by many patients with testicular cancer both during and after treatment . Very limited information exists concerning the patho-physiological effects of antineoplastic agents on skeletal muscle . The primary aim of this study is to investigate the effects of BEP-treatment on the skeletal musculature in testicular cancer patients , and to examine whether the expected treatment-induced muscular deterioration can be attenuated or even reversed by high intensity progressive resistance training ( HIPRT ) . Design / Methods The PROTRACT study is a r and omized controlled trial in 30 testicular cancer patients undergoing three cycles of BEP chemotherapy . Participants will be r and omized to either a 9-week HIPRT program ( STR ) initiated at the onset of treatment , or to st and ard care ( UNT ) . 15 healthy matched control subjects ( CON ) will complete the same HIPRT program . All participants will take part in 3 assessment rounds ( baseline , 9 wks , 21 wks ) including muscle biopsies , maximum muscle strength tests , whole body DXA scan and blood sample s. Primary outcome : mean fiber area and fiber type composition measured by histochemical analyses , satellite cells and levels of protein and mRNA expression of intracellular mediators of protein turnover . Secondary outcomes : maximum muscle strength and muscle power measured by maximum voluntary contraction and leg-extensor-power tests , body composition assessed by DXA scan , and systemic inflammation analyzed by circulating inflammatory markers , lipid and glucose metabolism in blood sample s. Health related Quality of Life ( QoL ) will be assessed by vali date d question naires ( EORTC QLQ-C30 , SF-36 ) . Discussion This study investigates the muscular effects of antineoplastic agents in testicular cancer patients , and furthermore evaluates whether HIPRT has a positive influence on side effects related to chemotherapy . A more extensive knowledge of the interaction between cytotoxic-induced physiological impairment and exercise-induced improvement is imperative for the future development of optimal rehabilitation programs for cancer patients .Trial Registration Current Controlled Trials IS RCT N32132990 Background Fatigue is a major problem of cancer patients . Thirty percent of cancer survivors report serious fatigue three years after finishing treatment . There is evidence that physical exercise during cancer treatment reduces fatigue . This may also lead to an improvement of quality of life . Such findings may result in a decrease of healthcare related expenditures and societal costs due to sick leave . However , no studies are known that investigated these hypotheses . Therefore , the primary aim of our study is to assess the effect of exercise during cancer treatment on reducing complaints of fatigue and on reducing health service utilisation and sick leave . Methods / Design The Physical Activity during Cancer Treatment study is a multicentre r and omised controlled trial in 150 breast and 150 colon cancer patients undergoing cancer treatment . Participants will be r and omised to an exercise or a control group . In addition to the usual care , the exercise group will participate in an 18-week supervised group exercise programme . The control group will be asked to maintain their habitual physical activity pattern . Study endpoints will be assessed after 18 weeks ( short term ) and after 9 months ( long term ) . Vali date d question naires will be used . Primary outcome : fatigue ( Multidimensional Fatigue Inventory and Fatigue Quality List ) and cost-effectiveness , health service utilisation and sick leave . Secondary outcome : health related quality of life ( European Organisation Research and Treatment of Cancer- Quality of Life question naire-C30 , Short Form 36 healthy survey ) , impact on functioning and autonomy ( Impact on functioning and autonomy question naire ) , anxiety and depression ( Hospital Anxiety and Depression Scale ) , physical fitness ( aerobic peak capacity , muscle strength ) , body composition and cognitive-behavioural aspects . To register health service utilisation and sick leave , participants will keep diaries including the EuroQuol-5D . Physical activity level will be measured using the Short Question naire to Assess Health-Enhancing Physical Activity and will be monitored with an exercise log and a pedometer . Discussion This study investigates the (cost)-effectiveness of exercise during adjuvant treatment of patients with breast or colon cancer . If early physical exercise proves to be ( cost ) effective , establishing st and ardised physical exercise programmes during cancer treatment will be planned . Trial registration Current Controlled trials IS RCT N43801571 , Dutch Trial Register Background : Healthy lifestyle behaviors could have a role in ameliorating some of the adverse effects of and rogen suppression therapy ( AST ) in men with prostate cancer . The primary aim of this study was to assess the feasibility of a tapered supervised exercise program in combination with dietary advice in men with advanced prostate cancer receiving AST . Methods : Advanced prostate cancer patients receiving AST for a minimum of 6 months were r and omized to a 12-week lifestyle program comprising aerobic and resistance exercise , plus dietary advice ( n = 25 ) , or st and ard care ( n = 25 ) . Exercise behavior , dietary macronutrient intake , quality of life , fatigue , functional fitness , and biomarkers associated with disease progression were assessed at baseline , after the intervention , and at 6 months . Results : The lifestyle group showed improvements in exercise behavior ( P < 0.001 ) , dietary fat intake ( P = 0.001 ) , total energy intake ( P = 0.005 ) , fatigue ( P = 0.002 ) , aerobic exercise tolerance ( P < 0.001 ) , and muscle strength ( P = 0.033 ) compared with st and ard care controls . Although a high rate of attrition ( 44 % ) was observed at 6 months , the improvements in key health outcomes were sustained . No effects on clinical prostate cancer disease markers were observed . Conclusions : This preliminary evidence suggests that pragmatic lifestyle interventions have potential to evoke improvements in exercise and dietary behavior , in addition to other important health outcomes in men with advanced prostate cancer receiving AST . Impact : This study shows for the first time that pragmatic lifestyle interventions are feasible and could have a positive impact on health behaviors and other key outcomes in men with advanced prostate cancer receiving AST . Cancer Epidemiol Biomarkers Prev ; 20(4 ) ; 647–57 . © 2011 AACR PURPOSE Exercise adherence is difficult during cancer treatments , but few studies have examined the predictors of such exercise . Here , we report the predictors of adherence to supervised exercise training during breast cancer chemotherapy . METHODS Breast cancer patients ( N = 242 ) initiating adjuvant chemotherapy in Edmonton , Ottawa , and Vancouver were r and omly assigned to usual care ( n = 82 ) , supervised resistance exercise ( n = 82 ) , or supervised aerobic exercise ( n = 78 ) for the duration of their chemotherapy . Baseline data on st and ard demographic , medical , behavioral , fitness , and psychosocial variables as well as motivational variables from the Theory of Planned Behavior were collected . Adherence was assessed by objective attendance records . RESULTS Adherence to supervised exercise was 70.2 % . Univariate analyses indicated significant or borderline significant associations between exercise adherence and location/center ( r = 0.30 ; P < 0.001 ) , V[spacing dot above]O2peak ( r = 0.21 ; P = 0.008 ) , muscular strength ( r = 0.21 ; P = 0.008 ) , percent body fat ( r = -0.21 ; P = 0.012 ) , disease stage ( r = 0.17 ; P = 0.031 ) , education ( r = 0.15 ; P = 0.053 ) , depression ( r = -0.14 ; P = 0.073 ) , and smoking ( r = -0.14 ; P = 0.081 ) . In multivariate analysis , location/center ( beta = 0.28 ; P = 0.001 ) , V[spacing dot above]O2peak ( [ beta ] = 0.19 ; P = 0.016 ) , disease stage ( beta = 0.18 ; P = 0.015 ) , and depression ( beta = -0.16 ; P = 0.033 ) remained significant and explained 21 % of the variance in exercise adherence . Participants in Vancouver , with higher aerobic fitness , more advanced disease stage , and lower depression , achieved better adherence . CONCLUSION Adherence to supervised exercise training was predicted by unique aspects of the location/center , disease stage , aerobic fitness , and depression but not motivational variables . Location/center in our trial may have been a proxy for the amount of one-on-one attention received during supervised exercise . These findings may have implication s for improving adherence during breast cancer chemotherapy Quality of life ( QOL ) of cancer patients is often diminished due to the side effects of treatment and symptoms of the disease itself . Medical Qigong ( coordination of gentle exercise and relaxation through meditation and breathing exercise based on Chinese medicine theory of energy channels ) may be an effective therapy for improving QOL , symptoms and side effects , and longevity of cancer patients . In this pilot study , the feasibility , acceptability , and impact of Medical Qigong ( MQ ) were evaluated on outcomes in cancer patients . Thirty patients diagnosed with heterogeneous cancers , were r and omly assigned to two groups : a control group that received usual medical care and an intervention group who participated in a MQ program for 8 weeks in addition to receiving usual medical care . R and omization was stratified by completion of cancer treatment ( n = 14 ) or under chemotherapy ( n = 16 ) . Patients completed measures before and after the program . Quality of life and symptoms were measured by the EORTC QLQ-C 30 and progress of disease by the inflammation biomarker ( CRP : c-reactive protein ) via a blood test was assessed . The MQ intervention group reported clinical ly significant improved global QOL scores pre- and post-intervention . The MQ intervention also reduced the symptoms of side effects of cancer treatment and inflammation biomarker ( CRP ) compare to the control group . Due to the small sample size , however , the results were not statistically significant between treatment and the control groups . Data from the pilot study suggest that MQ with usual medical treatment can enhance the QOL of cancer patients and reduce inflammation . This study needs a further investigation with a larger sample size The purpose of this study was to examine the effects of an exercise intervention on the total caloric intake ( TCI ) of breast cancer patients undergoing treatment . A secondary purpose was to determine whether or not a relationship existed between changes in TCI , body fat composition ( % BF ) , and fatigue during the study , which lasted 6 months . Twenty females recently diagnosed with breast cancer , scheduled to undergo chemotherapy or radiation , were assigned r and omly to an experimental ( N = 10 ) or control group ( N = 10 ) . Outcome measures included TCI ( 3-day food diary ) , % BF ( skinfolds ) , and fatigue ( revised Piper Fatigue Scale ) . Each exercise session was conducted as follows : initial cardiovascular activity ( 6 - 12 min ) , followed by stretching ( 5 - 10 min ) , resistance training ( 15 - 30 min ) , and a cool-down ( approximately 8 min ) . Significant changes in TCI were observed among groups ( F1,18 = 8.582 ; P = 0.009 ) , at treatments 2 and 3 , and at the end of the study [ experimental ( 1973 + /- 419 ) , control ( 1488 + /- 418 ) ; experimental ( 1946 + /- 437 ) , control ( 1436 + /- 429 ) ; experimental ( 2315 + /- 455 ) , control ( 1474 + /- 294 ) , respectively ] . A significant negative correlation was found ( Spearman rho(18 ) = -0.759 ; P < 0.001 ) between TCI and % BF and between TCI and fatigue levels ( Spearman rho(18 ) = -0.541 ; P = 0.014 ) at the end of the study . In conclusion , the results of this study suggest that an exercise intervention administered to breast cancer patients undergoing medical treatment may assist in the mitigation of some treatment side effects , including decreased TCI , increased fatigue , and negative changes in body composition Cancer-related fatigue is the most disabling symptom experienced by breast cancer patients following the cancer treatment . The positive effects of physical activity in the rehabilitation of breast cancer patients are documented in several studies . In a r and omized controlled study the effects of a structured physical training program on fatigue and health-related quality of life were evaluated . Patients and Methods : 63 breast cancer patients with cancer-related chronic fatigue were r and omized at the beginning of the inpatient rehabilitation . The control group received the st and ard complex rehabilitation program , the intervention group a structured physical training program and additional muscle strength and aerobic exercises . The effects of the treatment were evaluated by question naires at the start of rehabilitation ( t1 ) , end of rehabilitation ( t2 ) , and 3 months after t2 ( t3 ) . Isometric muscle strength and aerobic capacity were evaluated at t1 and t2 . Results : There was an improvement of muscle strength at the end of rehabilitation for both groups . The increase from t1 to t2 was significantly higher for the training group . The scores for global quality of life , physical well-being , and functionality increased from t1 to t2 , but further improvement in the follow-up ( t3 ) was only observed in the training group . The cancer-related fatigue was significantly reduced in the training group from t1 to t3 , however , not in the control group . Conclusions : Structured physical training programs initiated during inpatient rehabilitation and continuously practice d in the time thereafter can improve symptoms of chronic fatigue and quality of life in breast cancer patients 9035 Background : Cancer patients often experience diminished cognitive function and quality of life ( QOL ) due to side effects of treatment and the disease symptoms . This study evaluates the effects of Medical Qigong ( combination of gentle exercise and meditation ) on cognitive function , quality of life and inflammation in cancer patients . METHODS Eighty one cancer patients were r and omly assigned to two groups : a control group ( n=44 ) who received usual healthcare , and an intervention group ( n=37 ) who participated in a 10-week Medical Qigong ( MQ ) program . Self-reported cognitive function was measured by the European Organization for Research and Treatment of Cancer ( EORTC-CF ) and the Functional Assessment of Cancer Therapy-Cognitive ( FACT-Cog ) . The Functional Assessment of Cancer Therapy- General ( FACT-G ) was used to measure QOL . C-reactive protein ( CRP ) was assessed as a biomarker of inflammation . RESULTS The MQ group self-reported significantly improved cognitive function ( t51= -2.532 , p=0.014 , mean difference = 7.78 ) in the EORTC-CF and all the FACT-Cog subscales : perceived cognitive impairment ( t43= -2.254 , p=0.029 , mean difference = 4.70 ) , impact of perceived cognitive impairment on QOL ( t45= -2.377 , p=0.024 , mean difference=1.64 ) , and perceived cognitive abilities ( t45= -2.229 , p=0.031 , mean difference = 3.61 ) compared to controls . The MQ group reported significantly improved QOL ( t45= -5.715 , p<0.001 , mean difference=12.66 ) and had reduced CRP levels ( t45= 2.092 , p=0.042 , mean difference= -0.72 ) compared to controls . CONCLUSIONS Results suggest that the MQ intervention may have positive effects on self-reported cognitive function , QOL and inflammation . Further research with an objective measure of cognitive function is needed PURPOSE To examine the effect of progressive resistance training on muscle function , functional performance , balance , body composition , and muscle thickness in men receiving and rogen deprivation for prostate cancer . METHODS Ten men aged 59 - 82 yr on and rogen deprivation for localized prostate cancer undertook progressive resistance training for 20 wk at 6- to 12-repetition maximum ( RM ) for 12 upper- and lower-body exercises in a university exercise rehabilitation clinic . Outcome measures included muscle strength and muscle endurance for the upper and lower body , functional performance ( repeated chair rise , usual and fast 6-m walk , 6-m backwards walk , stair climb , and 400-m walk time ) , and balance by sensory organization test . Body composition was measured by dual-energy x-ray absorptiometry and muscle thickness at four anatomical sites by B-mode ultrasound . Blood sample s were assessed for prostate specific antigen ( PSA ) , testosterone , growth hormone ( GH ) , cortisol , and hemoglobin . RESULTS Muscle strength ( chest press , 40.5 % ; seated row , 41.9 % ; leg press , 96.3 % ; P < 0.001 ) and muscle endurance ( chest press , 114.9 % ; leg press , 167.1 % ; P < 0.001 ) increased significantly after training . Significant improvement ( P < 0.05 ) occurred in the 6-m usual walk ( 14.1 % ) , 6-m backwards walk ( 22.3 % ) , chair rise ( 26.8 % ) , stair climbing ( 10.4 % ) , 400-m walk ( 7.4 % ) , and balance ( 7.8 % ) . Muscle thickness increased ( P < 0.05 ) by 15.7 % at the quadriceps site . Whole-body lean mass was preserved with no change in fat mass . There were no significant changes in PSA , testosterone , GH , cortisol , or hemoglobin . CONCLUSIONS Progressive resistance exercise has beneficial effects on muscle strength , functional performance and balance in older men receiving and rogen deprivation for prostate cancer and should be considered to preserve body composition and reduce treatment side effects Background Cancer chemotherapy is frequently associated with a decline in general physical condition , exercise tolerance , and muscle strength and with an increase in fatigue . While accumulating evidence suggests that physical activity and exercise interventions during chemotherapy treatment may contribute to maintaining cardiorespiratory fitness and strength , the results of studies conducted to date have not been consistent . Additional research is needed to determine the optimal intensity of exercise training programs in general and in particular the relative effectiveness of supervised , outpatient ( hospital- or physical therapy practice -based ) versus home-based programs . Methods This multicenter , prospect i ve , r and omized trial will evaluate the effectiveness of a low to moderate intensity , home-based , self-management physical activity program , and a high intensity , structured , supervised exercise program , in maintaining or enhancing physical fitness ( cardiorespiratory fitness and muscle strength ) , in minimizing fatigue and in enhancing the health-related quality of life ( HRQoL ) . Patients receiving adjuvant chemotherapy for breast or colon cancer ( n = 360 ) are being recruited from twelve hospitals in the Netherl and s , and r and omly allocated to one of the two treatment groups or to a ' usual care ' control group . Performance-based and self-reported outcomes are assessed at baseline , at the end of chemotherapy and at six month follow-up . Discussion This large , multicenter , r and omized clinical trial will provide additional empirical evidence regarding the effectiveness of physical exercise during adjuvant chemotherapy in enhancing physical fitness , minimizing fatigue , and maintaining or enhancing patients ' quality of life . If demonstrated to be effective , exercise intervention programs will be a welcome addition to the st and ard program of care offered to patients with cancer receiving chemotherapy . Trial registration This study is registered at the Netherl and s Trial Register ( NTR 2159 OBJECTIVE To determine the effect of exercise on quality of life in ( a ) a r and omized controlled trial of exercise among recently diagnosed breast cancer survivors undergoing adjuvant therapy and ( b ) a similar trial among post-treatment survivors . METHODS Fifty newly diagnosed breast cancer survivors were recruited through a hospital-based tumor registry and r and omized to a 6-month , home-based exercise program ( n=25 ) or a usual care group ( n=25 ) . In a separate trial , 75 post-treatment survivors were r and omized to a 6-month , supervised exercise intervention ( n=37 ) or to usual care ( n=38 ) . Participants in both studies completed measures of happiness , depressive symptoms , anxiety , stress , self-esteem , and quality of life at baseline and 6 months . RESULTS Forty-five participants completed the trial for newly diagnosed survivors and 67 completed the trial for post-treatment survivors . Good adherence was observed in both studies . Baseline quality of life was similar for both studies on most measures . Exercise was not associated with quality of life benefits in the full sample of either study ; however exercise was associated with improved social functioning among post-treatment survivors who reported low social functioning at baseline ( p<0.05 ) . CONCLUSIONS Exercise did not affect quality of life in either recently diagnosed or post-treatment breast cancer survivors ; however this may be due in part to relatively high baseline functioning among participants in both studies . Strategies for future research include limiting enrollment to survivors who report reduced quality of life on screening question naires and targeting survivor subgroups known to be at particular risk for quality of life impairment Fatigue is a frequent problem after surgical treatment of solid tumours . Aerobic exercise and psychosocial interventions have been shown to reduce the severity of this symptom in cancer patients . Therefore , we compared the effect of the two therapies on fatigue in a r and omised controlled study . Seventy-two patients who underwent surgery for lung ( n=27 ) or gastrointestinal tumours ( n=42 ) were assigned to an aerobic exercise group ( stationary biking 30 min five times weekly ) or a progressive relaxation training group ( 45 min three times per week ) . Both interventions were carried out for 3 weeks . At the beginning and the end of the study , we evaluated physical , cognitive and emotional status and somatic complaints with the European Organization for Research and Treatment of Cancer Quality of Life Question naire Core Module ( EORTC-QLQ-30 ) question naire , and maximal physical performance with an ergometric stress test . Physical performance of the training group improved significantly during the programme ( 9.4±20 watts , p=0.01 ) but remained unchanged in the relaxation group ( 1.5±14.8 watts , p=0.37 ) . Fatigue and global health scores improved in both groups during the intervention ( fatigue : training group 21 % , relaxation group 19 % ; global health of both groups 19 % , p for all ≤0.01 ) ; however , there was no significant difference between changes in the scores of both groups ( p=0.67 ) . We conclude that a structured aerobic training programme improves the physical performance of patients recovering from surgery for solid tumours . However , exercise is not better than progressive relaxation training for the treatment of fatigue in this setting Background : Few exercise trials in cancer patients have reported longer-term follow-up . Here , we report a 6-month follow-up of exercise behavior and patient-rated outcomes from an exercise trial in breast cancer patients . Methods : Breast cancer patients initiating adjuvant chemotherapy ( n = 242 ) were r and omly assigned to usual care ( n = 82 ) , resistance exercise training ( RET ; n = 82 ) , or aerobic exercise training ( AET ; n = 78 ) for the duration of their chemotherapy . At 6-month follow-up , participants were mailed a question naire that assessed quality of life , self-esteem , fatigue , anxiety , depression , and exercise behavior . Results : Two hundred one ( 83.1 % ) participants provided 6-month follow-up data . Adjusted linear mixed-model analyses showed that , at 6-month follow-up , the RET group reported higher self-esteem [ adjusted mean difference , 1.6 ; 95 % confidence interval ( 95 % CI ) , 0.1 - 3.2 ; P = 0.032 ] and the AET group reported lower anxiety ( adjusted mean difference , −4.7 ; 95 % CI , −0.0 to −9.3 ; P = 0.049 ) compared with the usual care group . Moreover , compared with participants reporting no regular exercise during the follow-up period , those reporting regular aerobic and resistance exercise also reported better patient-rated outcomes , including quality of life ( adjusted mean difference , 9.5 ; 95 % CI , 1.2 - 17.8 ; P = 0.025 ) . Conclusions : Improvements in self-esteem observed with RET during breast cancer chemotherapy were maintained at 6-month follow-up whereas reductions in anxiety not observed with AET during breast cancer chemotherapy emerged at 6-month follow-up . Moreover , adopting a combined aerobic and resistance exercise program after breast cancer chemotherapy was associated with further improvements in patient-rated outcomes . Exercise training during breast cancer chemotherapy may result in some longer-term and late effects for selected patient-rated outcomes . ( Cancer Epidemiol Biomarkers Prev 2007;16(12):2572–8 OBJECTIVES To determine if therapist supervision of an exercise program produced better functional outcomes in allogeneic stem cell transplant patients than a patient-directed exercise program . METHODS Sixty-one patients who were less than 6 months post allogeneic stem cell transplant were r and omly assigned to either a therapist supervised training group ( supervised ) or a patient-directed training group ( Self-directed ) . Training consisted of aerobic exercises ( treadmill , bicycle ergometer versus walking ) and resistance exercises ( free weights , weight machines versus resistive b and activities ) . Subjects completed physical performance tests ( 50-foot fast walk , 6-min walk , forward reach , repeated sit-to-st and , uniped stance ) and the Brief Fatigue Inventory ( BFI ) before and after 4 weeks of training . Pre- and post-training outcomes and group differences were analyzed by a Student t-test . RESULTS Patients in both groups were similarly deconditioned at baseline . Training increased the 6-min walk distance and 50-foot walk in the supervised group by 12 and 14 % , respectively , and increased the 6-min walk distance by 10 % in the Self-directed group ( p<0.05 ) . BFI score for worst level of fatigue declined in both groups but not significantly . CONCLUSIONS These results demonstrate that allogeneic transplant patients derive functional benefits from short-term exercise training regardless of how the training program is supervised . Determining ( 1 ) the reasons for the low participation rate ( 28 % ) , ( 2 ) the patient-preferred characteristics of each exercise supervision style and ( 3 ) how best to match patient preference to exercise supervision style remain significant issues in this area of patient delivery services Loss of physical performance is a universal problem of cancer patients undergoing chemotherapy . We postulated that this impairment can be partially prevented by aerobic exercise . In a r and omized study , 33 cancer patients receiving high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation ( training group , T ) performed an exercise program consisting of biking on an ergometer in the supine position after an interval-training pattern for 30 minutes daily during hospitalization . Patients in the control group ( C , n = 37 ) did not train . Maximal physical performance was assessed with a treadmill test by admission and discharge . Physical performance of the two groups was not different on admission . The decrement in performance during hospitalization was 27 % greater in the control group than in the training group ( P = .05 ) ; this result ed in a significantly higher maximal physical performance at discharge in the trained patients ( P = .04 ) . Duration of neutropenia ( P = .01 ) and thrombopenia ( P = .06 ) , severity of diarrhea ( P = .04 ) , severity of pain ( P = .01 ) , and duration of hospitalization ( P = . 03 ) were reduced in the training group . We conclude that aerobic exercise can be safely carried out immediately after high-dose chemotherapy and can partially prevent loss of physical performance . Based on the potential significance of the observed outcomes , further studies are warranted to confirm our results Objectives . This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer out patients undergoing adjuvant radiotherapy at a cancer center . Methods . Eighty-eight stage II and III breast cancer out patients are r and omly assigned to receive yoga ( n = 44 ) or brief supportive therapy ( n = 44 ) prior to radiotherapy treatment . Assessment s include diurnal salivary cortisol levels 3 days before and after radiotherapy and self-ratings of anxiety , depression , and stress collected before and after 6 weeks of radiotherapy . Results . Analysis of covariance reveals significant decreases in anxiety ( P < .001 ) , depression ( P = .002 ) , perceived stress ( P < .001 ) , 6 a.m. salivary cortisol ( P = .009 ) , and pooled mean cortisol ( P = .03 ) in the yoga group compared with controls . There is a significant positive correlation between morning salivary cortisol level and anxiety and depression . Conclusion . Yoga might have a role in managing self-reported psychological distress and modulating circadian patterns of stress hormones in early breast cancer patients undergoing adjuvant radiotherapy PURPOSE S/ OBJECTIVES To test the hypothesis that women participating in a walking exercise program during radiation therapy treatment for breast cancer would demonstrate more adaptive responses as evidence d by higher levels of physical functioning and lower levels of symptom intensity than women who did not participate . DESIGN Experimental , two-group pretest , post-test . SETTING Two university teaching hospital outpatient radiation therapy departments . SAMPLE 46 women beginning a six-week program of radiation therapy for early stage breast cancer . METHODS Following r and om assignment , subjects in the exercise group maintained an individualized , self-paced , home-based walking exercise program throughout treatment . The control group received usual care . Dependent variables were measured prior to and at the end of radiation therapy . In addition , symptoms were assessed at the end of three weeks of treatment . MAIN RESEARCH VARIABLES Participation in the walking exercise program , physical functioning fatigue , emotional distress , and difficulty sleeping . FINDINGS Hypothesis testing by multivariate analysis of covariance , with pretest scores as covariates , indicated significant differences between groups on outcome measures ( p < 0.001 ) . The exercise group scored significantly higher than the usual care group on physical functioning ( p = 0.003 ) and symptom intensity , particularly fatigue , anxiety , and difficulty sleeping . Fatigue was the most frequent and intense subjective symptom reported . CONCLUSIONS A self-paced , home-based walking exercise program can help manage symptoms and improve physical functioning during radiation therapy . IMPLICATION S FOR NURSING PRACTICE Nurse-prescribed and -monitored exercise is an effective , convenient , and low-cost self-care activity that reduces symptoms and facilitates adaptation to breast cancer diagnosis and treatment The use of exercises in the treatment of patients with vestibular deficits has become increasingly popular , and evidence exists that these exercises are beneficial in patients with chronic vestibular deficits . The question as to whether patients with acute unilateral vestibular loss would benefit from vestibular adaptation exercises is particularly compelling , however , because animal studies have demonstrated that the acute stage after unilateral vestibular loss is a critical period for recovery . Deprivation of visuomotor experience during that period can delay the onset of recovery as well as prolong the recovery period . Patients often avoid movement during the early stage because , with movement , they experience an increase in dysequilibrium and nausea . We examined the recovery of postural stability in patients during the acute stage after resection of acoustic neuroma to determine whether vestibular adaptation exercises facilitate the onset of recovery and improve the rate of recovery . The results suggest that vestibular adaptation exercises result in improved postural stability and in a diminished perception of dysequilibrium Objectives To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer , with six month follow-up . Design Pragmatic r and omised controlled prospect i ve open trial . Setting Three National Health Service oncology clinics in Scotl and and community exercise facilities . Participants 203 women entered the study ; 177 completed the six month follow-up . Interventions Supervised 12 week group exercise programme in addition to usual care , compared with usual care . Main outcome measures Functional assessment of cancer therapy ( FACT ) question naire , Beck depression inventory , positive and negative affect scale , body mass index , seven day recall of physical activity , 12 minute walk test , and assessment of shoulder mobility . Results Mixed effects models with adjustment for baseline values , study site , treatment at baseline , and age gave intervention effect estimates ( intervention minus control ) at 12 weeks of 129 ( 95 % confidence interval 83 to 176 ) for metres walked in 12 minutes , 182 ( 75 to 289 ) for minutes of moderate intensity activity reported in a week , 2.6 ( 1.6 to 3.7 ) for shoulder mobility , 2.5 ( 1.0 to 3.9 ) for breast cancer specific subscale of quality of life , and 4.0 ( 1.8 to 6.3 ) for positive mood . No significant effect was seen for general quality of life ( FACT-G ) , which was the primary outcome . At the six month follow-up , most of these effects were maintained and an intervention effect for breast cancer specific quality of life emerged . No adverse effects were noted . Conclusion Supervised group exercise provided functional and psychological benefit after a 12 week intervention and six months later . Clinicians should encourage activity for their patients . Policy makers should consider the inclusion of exercise opportunities in cancer rehabilitation services . Trial registration Current controlled trials IS RCT N12587864 PURPOSE To examine the effects of aerobic exercise therapy on quality of life ( QoL ) and associated outcomes in women treated for breast cancer . Evidence suggests that exercise may be beneficial , but no trial has included an exercise-placebo and a usual-care group to control for the attention effects that might be associated with aerobic exercise interventions in cancer patients . PATIENTS AND METHODS A total of 108 women who had been treated for breast cancer 12 to 36 months previously were r and omly assigned to supervised aerobic exercise therapy ( n = 34 ) , exercise-placebo ( body conditioning ; n = 36 ) , or usual care ( n = 38 ) . Exercise therapy and exercise-placebo sessions took place three times per week for 8 weeks . Outcomes included QoL , depression , exercise behavior , aerobic fitness ; outcomes were assessed at baseline and at the 8- and 24-week follow-up . RESULTS Analyses of covariance revealed a significant mean difference of 9.8 units in Functional Assessment of Cancer Therapy-General ( primary outcome ) favoring aerobic exercise therapy at 8 weeks , relative to usual care . Significant differences that favored aerobic exercise therapy relative to usual care were recorded for Functional Assessment of Cancer Therapy-Breast , social/family well-being , functional well-being , and breast cancer subscale scores at 8-week follow-up . Psychological health outcomes improved modestly for both intervention groups ; these improvements were sustained for several end points . CONCLUSION Exercise therapy had large , clinical ly meaningful , short-term beneficial effects on QoL in women treated for breast cancer ; this finding can not be attributable to attention , given that the exercise-placebo group did not report similar effects relative to usual care PURPOSE / OBJECTIVES To examine the effects of a comprehensive rehabilitation program on facilitating physical and psychosocial adaptation of women with breast cancer who are receiving adjuvant chemotherapy . DESIGN Experimental . SETTING Breast evaluation clinics of two New Engl and medical centers with comprehensive cancer treatment programs . SAMPLE 14 women ( mean age = 44 years ) receiving adjuvant chemotherapy for breast cancer ( 86 % stage II ) following surgical treatment . METHODS Subjects were assigned r and omly to the experimental group or the usual care group . Experimental group members began a structured exercise program of walking and attended support group meetings . All subjects were tested before beginning chemotherapy , during the course of chemotherapy , and one month following chemotherapy completion . MAIN RESEARCH VARIABLES Performance status , physical functioning , psychosocial adjustment , self-concept and body image , and 12 symptoms ( e.g. , fatigue , nausea , anxiety ) . FINDINGS Measures of physical performance , psychosocial adjustment , and symptom intensity revealed improved adaptation in subjects who completed the walking/support group program . CONCLUSIONS Physical and psychosocial benefits from a modest walking exercise program and a support group are possible for patients receiving adjuvant chemotherapy . IMPLICATION S FOR NURSING PRACTICE Although more detailed research is necessary to answer some of the questions raised by this study , implementing the walking program and forming a support group are achievable in an outpatient setting AIM This paper is a report of a study analysing the effect of a home-based walking exercise program on symptoms and mood distress among breast cancer women receiving chemotherapy postoperatively . BACKGROUND Treatment-related symptoms , mood distress and decline in physical activity have been identified as major complaints among cancer patients . Studies on the efficacy of home-based walking exercise for symptoms and mood did not fully describe the exercise prescriptions that could be safe and beneficial for women with breast cancer , especially these receiving adjuvant chemotherapy . METHOD This is a prospect i ve , r and omized clinical trial . In 2008 - 2009 , participants were recruited from the oncology outpatient clinic of a medical center in Taiwan , and were assigned to either the exercise group ( n=19 ) or the control group ( n=21 ) . Women in the exercise group participated in a moderate-intensity home-based walking program for 12 weeks during their chemotherapy treatments . Symptoms , mood status and physical activity level were measured at baseline , 6- and 12-week follow-up . Data were analysed by two-way repeated- measures analysis of variance . RESULTS Women in the exercise group reported significantly lower symptom severity scores and mood disturbance compared with those in the control group throughout the study period . CONCLUSION Regular moderate-intensity exercise can play an important role in improving treatment-related symptoms and mood in women with breast cancer . A home-based walking exercise program can be easily incorporated into care for women with breast cancer undergoing chemotherapy PURPOSE Breast cancer chemotherapy may cause unfavorable changes in physical functioning , body composition , psychosocial functioning , and quality of life ( QOL ) . We evaluated the relative merits of aerobic and resistance exercise in blunting these effects . PATIENTS AND METHODS We conducted a multicenter r and omized controlled trial in Canada between 2003 and 2005 that r and omly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care ( n = 82 ) , supervised resistance exercise ( n = 82 ) , or supervised aerobic exercise ( n = 78 ) for the duration of their chemotherapy ( median , 17 weeks ; 95 % CI , 9 to 24 weeks ) . Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy-Anemia scale . Secondary end points were fatigue , psychosocial functioning , physical fitness , body composition , chemotherapy completion rate , and lymphedema . RESULTS The follow-up assessment rate for our primary end point was 92.1 % , and adherence to the supervised exercise was 70.2 % . Unadjusted and adjusted mixed-model analyses indicated that aerobic exercise was superior to usual care for improving self-esteem ( P = .015 ) , aerobic fitness ( P = .006 ) , and percent body fat ( adjusted P = .076 ) . Resistance exercise was superior to usual care for improving self-esteem ( P = .018 ) , muscular strength ( P < .001 ) , lean body mass ( P = .015 ) , and chemotherapy completion rate ( P = .033 ) . Changes in cancer-specific QOL , fatigue , depression , and anxiety favored the exercise groups but did not reach statistical significance . Exercise did not cause lymphedema or adverse events . CONCLUSION Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy , but they did improve self-esteem , physical fitness , body composition , and chemotherapy completion rate without causing lymphedema or significant adverse events PURPOSE Despite the recognition of fatigue as a common and distressing symptom during cancer treatment , there are few evidence -based interventions available to manage such fatigue . The purpose of this multi-institutional pilot study was to explore the effects of a home-based moderate walking exercise intervention on fatigue , physical functioning , emotional distress , and quality of life ( QOL ) during breast cancer treatment . DESCRIPTION OF STUDY Fifty-two women were recruited from five university hospital outpatient departments for this pilot study with an experimental design . Subjects were r and omly assigned to the walking program or to usual care during adjuvant chemotherapy or radiation therapy for breast cancer . Symptoms , physical functioning , and QOL were measured at baseline , midtreatment , and at the end of treatment . RESULTS Women who exercised at least 90 minutes per week on 3 or more days reported significantly less fatigue and emotional distress as well as higher functional ability and QOL than women who were less active during treatment . CLINICAL IMPLICATION S A home-based walking exercise program is a potentially effective , low-cost , and safe intervention to manage fatigue and to improve QOL during adjuvant chemotherapy or radiation therapy for breast cancer . This health-promoting self-care activity needs further testing in large r and omized clinical trials Purpose : We previously reported the effectiveness of a 12-week physical activity behavior change intervention for breast cancer survivors postintervention with this report , aim ing to determine delayed and /or persistent effects 3 months after intervention completion . Methods : Forty-one sedentary women with stage I , II , or IIIA breast cancer currently receiving hormonal therapy were r and omly assigned to receive the 12-week Better Exercise Adherence after Treatment for Cancer intervention or usual care . Assessment s occurred at baseline , postintervention , and 3 months postintervention . Results : Weekly minutes of greater than or equal to moderate intensity physical activity measured by accelerometer showed a significant group by time interaction ( F = 3.51 ; P = 0.035 ; between group difference in the mean change from baseline to 3 months postintervention , 100.1 minute , P = 0.012 ) . Significant group by time interactions also showed sustained improvements from baseline to 3 months postintervention in strength ( F = 3.82 ; P = 0.027 ; between group difference , 11.2 kg ; P = 0.026 ) , waist-to-hip ratio ( F = 3.36 ; P = 0.041 ; between group difference , −0.04 ; P = 0.094 ) , and social well-being ( F = 4.22 ; P = 0.023 ; between group difference , 3.9 ; P = 0.039 ) . A delayed reduction in lower extremity dysfunction 3 months postintervention was noted ( F = 3.24 ; P = 0.045 ; between group difference in the mean change from postintervention to 3 months follow-up ; P = −7.6 ; P = 0.015 ) . No group by time effect was noted for fitness , body mass index , percent fat , bone density , total quality of life ( Functional Assessment of Cancer Therapy-General ) , fatigue , endocrine symptoms , cognitive function , or sleep . Conclusions : The intervention result ed in sustained improvements in physical activity , strength , central adiposity , and social well-being with lower extremity function benefits appearing 3 months after intervention completion . Testing translation in a multisite study is warranted . ( Cancer Epidemiol Biomarkers Prev 2009;18(5):1410–8 Objective To assess the effect of a multimodal group exercise intervention , as an adjunct to conventional care , on fatigue , physical capacity , general wellbeing , physical activity , and quality of life in patients with cancer who were undergoing adjuvant chemotherapy or treatment for advanced disease . Design R and omised controlled trial . Setting Two university hospitals in Copenhagen , Denmark . Participants 269 patients with cancer ; 73 men , 196 women , mean age 47 years ( range 20 - 65 ) representing 21 diagnoses . Main exclusion criteria were brain or bone metastases . 235 patients completed follow-up . Intervention Supervised exercise comprising high intensity cardiovascular and resistance training , relaxation and body awareness training , massage , nine hours weekly for six weeks in addition to conventional care , compared with conventional care . Main outcome measures European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) , Medical Outcomes Study Short Form ( MOS SF-36 ) , Leisure Time Physical Activity Question naire , muscular strength ( one repetition maximum ) , maximum oxygen consumption ( Vo2max ) . Statistical methods The general linear model was used for continuous outcome while analysis of associates between categorical outcomes was performed as analysis of marginal homogeneity in contingency tables . Results Adjusted for baseline score , disease , and demographic covariates , the intervention group showed an estimated improvement at six weeks for the primary outcome , fatigue , of −6.6 points ( 95 % confidence interval −12.3 to −0.9 , P=0.02 ; effect size=0.33 , 0.04 to 0.61 ) . Significant effects were seen on vitality ( effect size 0.55 , 95 % CI 0.27 to 0.82 ) , physical functioning ( 0.37 , 0.09 to 0.65 ) , role physical ( 0.37 , 0.10 to 0.64 ) , role emotional ( 0.32 , 0.05 to 0.59 ) , and mental health ( 0.28 , 0.02 to 0.56 ) scores . Improvement was noted in physical capacity : estimated mean difference between groups for maximum oxygen consumption was 0.16 l/min ( 95 % CI 0.1 to 0.2 , P<0.0001 ) and for muscular strength ( leg press ) was 29.7 kg ( 23.4 to 34.9 , P<0.0001 ) . No significant effect was seen on global health status/ quality of life . Conclusion A supervised multimodal exercise intervention including high and low intensity components was feasible and could safely be used in patients with various cancers who were receiving adjuvant chemotherapy or treatment for advanced disease . The intervention reduced fatigue and improved vitality , aerobic capacity , muscular strength , and physical and functional activity , and emotional wellbeing , but not quality of life . Trial registration Current Controlled trials IS RCT N05322922 Background The Lung Cancer Exercise Training Study ( LUNGEVITY ) is a r and omized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness ( VO2peak ) , patient-reported outcomes , and the organ components that govern VO2peak in post-operative non-small cell lung cancer ( NSCLC ) patients . Methods / Design Using a single-center , r and omized design , 160 subjects ( 40 patients / study arm ) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center ( DUMC ) will be potentially eligible for this trial . Following baseline assessment s , eligible participants will be r and omly assigned to one of four conditions : ( 1 ) aerobic training alone , ( 2 ) resistance training alone , ( 3 ) the combination of aerobic and resistance training , or ( 4 ) attention-control ( progressive stretching ) . The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70 % of the individually determined VO2peak for aerobic training and an intensity between 60 and 80 % of one-repetition maximum for resistance training , for 30 - 45 minutes/session . Progressive stretching will be matched to the exercise groups in terms of program length ( i.e. , 16 weeks ) , social interaction ( participants will receive one-on-one instruction ) , and duration ( 30 - 45 mins/session ) . The primary study endpoint is VO2peak . Secondary endpoints include : patient-reported outcomes ( PROs ) ( e.g. , quality of life , fatigue , depression , etc . ) and organ components of the oxygen cascade ( i.e. , pulmonary function , cardiac function , skeletal muscle function ) . All endpoints will be assessed at baseline and postintervention ( 16 weeks ) . Sub studies will include genetic studies regarding individual responses to an exercise stimulus , theoretical determinants of exercise adherence , examination of the psychological mediators of the exercise - PRO relationship , and exercise-induced changes in gene expression . Discussion VO2peak is becoming increasingly recognized as an outcome of major importance in NSCLC . LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect . Overall , this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum . Trial Registration Background Currently 1 in 11 women over the age of 60 in Australia are diagnosed with breast cancer . Following treatment , most breast cancer patients are left with shoulder and arm impairments which can impact significantly on quality of life and interfere substantially with activities of daily living . The primary aim of the proposed study is to determine whether upper limb impairments can be prevented by undertaking an exercise program of prolonged stretching and resistance training , commencing soon after surgery . Methods / design We will recruit 180 women who have had surgery for early stage breast cancer to a multicenter single-blind r and omized controlled trial . At 4 weeks post surgery , women will be r and omly assigned to either an exercise group or a usual care ( control ) group . Women allocated to the exercise group will perform exercises daily , and will be supervised once a week for 8 weeks . At the end of the 8 weeks , women will be given a home-based training program to continue indefinitely . Women in the usual care group will receive the same care as is now typically provided , i.e. a visit by the physiotherapist and occupational therapist while an inpatient , and receipt of pamphlets . All subjects will be assessed at baseline , 8 weeks , and 6 months later . The primary measure is arm symptoms , derived from a breast cancer specific question naire ( BR23 ) . In addition , range of motion , strength , swelling , pain and quality of life will be assessed . Discussion This study will determine whether exercise commencing soon after surgery can prevent secondary problems associated with treatment of breast cancer , and will thus provide the basis for successful rehabilitation and reduction in ongoing problems and health care use . Additionally , it will identify whether strengthening exercises reduce the incidence of arm swelling . Trial Registration The protocol for this study is registered with the Australian Clinical Trials Registry ( ACTRN012606000050550 ) Background Treatment with And rogen Deprivation Therapy ( ADT ) for prostate cancer is associated with changes in body composition including increased fat and decreased lean mass ; increased fatigue , and a reduction in quality of life . No study to date has evaluated the effect of dietary and physical activity modification on the side-effects related to ADT . The aim of this study is to evaluate the efficacy of a 6-month dietary and physical activity intervention for prostate cancer survivors receiving ADT to minimise the changes in body composition , fatigue and quality of life , typically associated with ADT . Methods Men are recruited to this study if their treatment plan is to receive ADT for at least 6 months . Men who are r and omised to the intervention arm receive a home-based tailored intervention to meet the following guidelines a ) ≥ 5 servings vegetables and fruits/day ; b ) 30%-35 % of total energy from fat , and < 10 % energy from saturated fat/day ; c ) 10 % of energy from polyunsaturated fat/day ; d ) limited consumption of processed meats ; e ) 25 - 35 gm of fibre/day ; f ) alcoholic drinks ≤ 28 units/week ; g ) limited intake of foods high in salt and /or sugar . They are also encouraged to include at least 30 minutes of brisk walking , 5 or more days per week . The primary outcomes are change in body composition , fatigue and quality of life scores . Secondary outcomes include dietary intake , physical activity and perceived stress . Baseline information collected includes : socio-economic status , treatment duration , perceived social support and health status , family history of cancer , co-morbidities , medication and supplement use , barriers to change , and readiness to change their health behaviour . Data for the primary and secondary outcomes will be collected at baseline , 3 and 6 months from 47 intervention and 47 control patients . Discussion The results of this study will provide detailed information on diet and physical activity levels in prostate cancer patients treated with ADT and will test the feasibility and efficacy of a diet and physical activity intervention which could provide essential information to develop guidelines for prostate cancer patients to minimise the side effects related to ADT.Trial registration IS RCT N trial number Background Patient preference for group assignment may affect outcomes in unblinded trials but few studies have attempted to underst and such preferences . The purpose of the present study was to examine factors associated with breast cancer patients ' preference for two types of exercise training during chemotherapy . Methods Breast cancer patients ( N = 242 ) completed a battery of tests including a question naire that assessed patient preference and the theory of planned behavior ( TPB ) prior to being r and omized to usual care , resistance exercise training ( RET ) , or aerobic exercise training ( AET ) . Results 99 ( 40.9 % ) participants preferred RET , 88 ( 36.4 % ) preferred AET , and 55 ( 22.7 % ) reported no preference . Past exercisers ( p = 0.023 ) , smokers ( p = 0.004 ) , and aerobically fitter participants ( p = 0.005 ) were more likely to prefer RET . As hypothesized , participants that preferred AET had more favorable TPB beliefs about AET whereas participants that preferred RET had more favorable TPB beliefs about RET . In multivariate modeling , patient preference for RET versus AET was explained ( R2 = .46 ; p < 0.001 ) by the difference in motivation for RET versus AET ( β = .56 ; p < 0.001 ) , smoking status ( β = .13 ; p = 0.007 ) , and aerobic fitness ( β = .12 ; p = 0.018 ) . Motivational difference between RET versus AET , in turn , was explained ( R2 = .48 ; p < 0.001 ) by differences in instrumental attitude ( β = .27 ; p < 0.001 ) , affective attitude ( β = .25 ; p < 0.001 ) , and perceived behavioral control ( β = .24 ; p < 0.001 ) . Conclusion Breast cancer patients ' preference for RET versus AET during chemotherapy was predicted largely by a difference in motivation for each type of exercise which , in turn , was based on differences in their beliefs about the anticipated benefits , enjoyment , and difficulty of performing each type of exercise during chemotherapy . These findings may help explain patient preference effects in unblinded behavioral trials . Trial Registration Clinical Trials.gov Identifier NCT00115713 BACKGROUND There are very few r and omized controlled studies on exercise in cancer patients . Consequently , there are no guidelines available with regard to the exercises that can be recommended and difficulties are encountered in the clinical practice as to which exercise is more suitable to the patients . AIM The purpose of this study was to investigate the impact of pilates exercises on physical performance , flexibility , fatigue , depression and quality of life in women who had been treated for breast cancer . DESIGN R and omized controlled trial . SETTING Out patient group , Department of Physical Medicine and Rehabilitation and Medical Oncology Department , University Hospital . POPULATION Fifty-two patients with breast cancer were divided into either pilates exercise ( group 1 ) and control group ( group 2 ) . METHODS Patients in Group 1 performed pilates and home exercises and patients in group 2 performed only home exercises . Pilates exercise sessions were performed three times a week for a period of eight weeks in the rehabilitation unit . MAIN OUTCOME MEASURES Subjects were assessed before and after rehabilitation program , with respect to , 6-min walk test ( 6MWT ) , modified sit and reach test , Brief Fatigue Inventory ( BFI ) , Beck Depression Index ( BDI ) and the European Organisation for Research and Treatment of Cancer Quality of Life C30 ( EORTC QLQ-C30 ) and EORTC QLQ BR23 . RESULTS After the exercise program , improvements were observed in Group 1 in 6-minute walk test , BDI , EORTC QLQ-C30 functional , and EORTC QLQ-C30 BR23 functional scores ( P<0.05 ) . In contrast , no significant improvement was observed in Group 2 after the exercise program in any of parameters in comparison to the pre-exercise period ( P>0.05 ) . When the two exercise groups were compared , there were significant differences in 6MWT in pilates-exercise group ( P<0.05 ) . CONCLUSION Pilates exercises are effective and safe in female breast cancer patients . There is a need for further studies so that its effect can be confirmed . CLINICAL REHABILITATION IMPACT This study addressed the effects of pilates exercise , as a new approach , on functional capacity , fatigue , depression and quality of life in breast cancer patients in whom there are doubts regarding the efficacy and usefulness of the exercise Background : The Healthy Exercise for Lymphoma Patients trial showed that aerobic exercise training improved important health outcomes in lymphoma patients . Here , we examine potential moderators of the exercise training response . Methods : Lymphoma patients were stratified by major disease type and current treatment status and r and omly assigned to usual care ( n = 62 ) or aerobic exercise training ( n = 60 ) for 12 weeks . Endpoints were quality of life , cardiovascular fitness , and body composition . Moderators were patient preference for group assignment , age , sex , marital status , disease stage , body mass index , and general health . Results : Patient preference did not statistically moderate the effects of exercise training on quality of life ( P for interaction = 0.36 ) , but the interaction effect of 7.8 points favoring patients with no preference was clinical ly meaningful . Marital status ( P for interaction = 0.083 ) , general health ( P for interaction = 0.012 ) , and body mass index ( P for interaction = 0.010 ) moderated the effects of aerobic exercise training on quality of life with better outcomes for unmarried versus married patients , patients in poor/fair health versus good-to-excellent health , and normal weight/obese versus overweight patients . Disease stage ( P for interaction = 0.056 ) and general health ( P for interaction = 0.012 ) moderated the effects of aerobic exercise training on body composition with better outcomes for patients with advanced disease versus early disease/no disease and patients in good health versus very good-to-excellent health . No variables moderated intervention effects on cardiovascular fitness . Findings were not explained by differences in adherence . Conclusions : Clinical ly available variables predicted quality of life and body composition responses to aerobic exercise training in lymphoma patients . If replicated , these results may inform future r and omized trials and clinical practice . ( Cancer Epidemiol Biomarkers Prev 2009;18(10):2600–7 The aim of the present study was to investigate the impact of a multidimensional exercise intervention focusing on physical capacity ; one-repetition maximum ( 1RM ) and maximum oxygen uptake ( VO2Max ) , activity level , general well-being and quality of life in cancer patients undergoing chemotherapy . The intervention comprised resistance and fitness training , massage , relaxation and body-awareness training . Eighty-two cancer patients , with or without evidence of residual disease , were included : 66 patients with 13 different types of solid tumours and 16 patients with 6 types of haematological malignancies . The patients trained in mixed groups for 9 h weekly for 6 weeks . Physical capacity , physical activity level and psychosocial well-being as measured by the Medical Outcomes Study 36-item Short-Form Health Survey and the European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 were assessed pre- and post-intervention . Highly significant increases were achieved in muscular strength ( p<0.001 ) , physical fitness ( p<0.001 ) and physical activity levels ( p<0.001 ) . The patients reported significant reduction in treatment-related symptoms , i.e. , fatigue ( p=0.006 ) and pain ( p=0.03 ) . Highly significant improvements were observed in physical functioning ( p<0.001 ) and role functioning ( p<0.001 ) . Even patients with advanced disease were able to improve their results after 6 weeks . It is concluded that a multidimensional exercise intervention , including resistance training , may be beneficial for cancer patients undergoing chemotherapy . This study indicates significant clinical meaningful improvements . The exact role of the intervention has to be defined in a r and omized controlled design . A clinical ly controlled trial including 250 patients is currently being carried out PURPOSE To examine the effect of a progressive upper-body exercise program on lymphedema secondary to breast cancer treatment . METHODS Fourteen breast cancer survivors with unilateral upper extremity lymphedema were r and omly assigned to an exercise ( n = 7 ) or control group ( n = 7 ) . The exercise group followed a progressive , 8-week upper-body exercise program consisting of resistance training plus aerobic exercise using a Monark Rehab Trainer arm ergometer . Lymphedema was assessed by arm circumference and measurement of arm volume by water displacement . Patients were evaluated on five occasions over the experimental period . The Medical Outcomes Trust Short-Form 36 Survey was used to measure quality of life before and after the intervention . Significance was set at alpha < or = 0.01 . RESULTS No changes were found in arm circumference or arm volume as a result of the exercise program . Three of the quality -of-life domains showed trends toward increases in the exercise group : physical functioning ( P = .050 ) , general health ( P = .048 ) , and vitality ( P = .023 ) . Mental health increased , although not significantly , for all subjects ( P = .019 ) . Arm volume measured by water displacement was correlated with calculated arm volume ( r = .973 , P < .001 ) , although the exercise and control group means were significantly different ( P < .001 ) . CONCLUSIONS Participation in an upper-body exercise program caused no changes in arm circumference or arm volume in women with lymphedema after breast cancer , and they may have experienced an increase in quality of life . Additional studies should be done in this area to determine the optimum training program Fatigue is one of the most frequent side effects of cancer treatments . According to a number of studies , the incidence of fatigue as a side effect of radiation therapy ( RT ) ranges from 65 % to 100 % depending on which instruments were used ( Greenberg et al. , 1992 ; Jacobsen-Thors , 2003 ) . For many cancer patients , cancer-related fatigue is severe and imposes limitations on normal daily activities ( JereczekFossa et al. , 2002 ) . Patients often report that cancerrelated fatigue differs from fatigue experienced before initiation of cancer . They describe it as severe , chronic and frustrating , effects that fail to be relieved by rest . In many studies in the past , patients have felt that fatigue has adversely affected their quality of life more than pain and sexual dysfunction or other treatment-related side effects ( Stone et al. , 1998 ) . Fatigue has negative impact on various aspects of quality of life , so it is imperative to find non-invasive and nonpharmacological solutions for managing it . There is little however known as to which techniques can help alleviate fatigue . Physical exercise has been shown to be effective , convenient and a low-cost self-care method for reducing anxiety and sleep difficulties , and increasing adaptation during radiotherapy . Aerobic exercises ( e.g. walking ) have been suggested for the rehabilitation of cancer patients affected by energy loss but this is not a fully accepted approach as yet . Nevertheless , exercise has been shown BACKGROUND The project conducted at the Tumour Centre in Regensburg aims to integrate quality of life ( QL ) diagnostics with the therapy of breast cancer patients and to evaluate the efficacy of QL diagnostics in the context of a r and omized clinical trial . METHODS The Regensburg Tumour Centre provides the infrastructure of the present project ( telemedicine , project groups , quality circle ) . The treatment of breast cancer patients is based on the recent national breast cancer therapy guideline , including assorted QL-enhancing therapy options such as pain therapy , physiotherapy and lymphatic drainage , psychotherapy , social counselling and rehabilitation , nutrition and sports . During an implementation phase a new method of QL diagnostics has been developed . Five experts with varying professional background use the individual patient 's QL profile and clinical and socio-demographic information in order to generate a QL report including a treatment recommendation . The study is design ed as a two- arm r and omized clinical trial with one test group ( communication of the QL findings to the co-ordinating physician ) and a control group ( no communication ) . Patients with newly diagnosed breast cancer who are treated in the study region by one of the co-ordinating doctors will be included in this r and omized study . At design ated points in time QL assessment s ( EORTC QLQ-C30 plus BR23 ) will be conducted over a 12-months period . EXPECTED RESULTS We expect that patients in the test group will experience a lower amount of QL deficits at the end of the study period ( M = 1 , SD = 2 ) than patients in the control group ( M = 2 , SD = 2 ) . The statistical confirmation of this expected effect requires a total sample size of N = 200 ( n = 100 vs. n = 100 , alpha = 5 % [ two-tailed ] , beta = 10 % ) . CONCLUSIONS This is the first study to evaluate a new form of QL diagnostics in the complexity of a real patient care environment , and it promises to make the inclusion of the quality of life concept into the current breast cancer treatment guideline more tangible Purpose : Fatigue is a common side effect of cancer treatment that impacts quality of life . Exercise is one approach suggested to improve fatigue . The purpose of this study was to explore the relationship of exercise to fatigue and quality of life . Methods : Thirty-one subjects with breast cancer were enrolled prior to beginning chemotherapy and 27 completed the study . All baseline measures were obtained before the first chemotherapy treatment . Subjects were instructed on a home-based , 8-week exercise program . Results : Women who adopted the exercise program ( 60 % ) showed significant increases in functional ability and less weight gain . Exploratory , stepwise multiple regression analyses suggested that the maximum effect of exercise on quality of life outcomes may be mediated by fatigue . Conclusions : The low-to-moderate intensity , home-based exercise program was feasible for some women with breast cancer receiving chemotherapy . The results suggest that exercise may affect quality of life and that this effect may be mediated by the effects of exercise on fatigue . Better retention of functional ability and better weight control are additional possible benefits of exposing breast cancer patients to increased exercise . A r and omized , controlled clinical trial is needed to establish confidence in these observed relationships OBJECTIVE To show fatigue prevention and quality of life ( QOL ) improvement from cardiovascular exercise during radiotherapy . DESIGN Prospect i ve enrollment ( n=21 ) , r and omized to exercise ( n=11 ) and control groups ( n=10 ) , with pre- and post-radiotherapy between- and within-group comparisons . SETTING Academic medical center . PARTICIPANTS Localized prostate cancer patients undergoing radiotherapy . INTERVENTIONS The interventional group received radiotherapy plus aerobic exercise 3 times a week for 8 weeks whereas the control group received radiotherapy without exercise . MAIN OUTCOME MEASURES Pre- and post-radiotherapy differences in cardiac fitness , fatigue , depression , functional status , physical , social , and functional well-being , leg strength , and flexibility were examined within and between 2 groups . RESULTS No significant differences existed between 2 groups at pre-radiotherapy assessment . At post-radiotherapy assessment , the exercise group showed significant within group improvements in : cardiac fitness ( P<.001 ) , fatigue ( P=.02 ) , Functional Assessment of Cancer Therapy-Prostate ( FACT-P ) ( P=.04 ) , physical well-being ( P=.002 ) , social well-being ( P=.02 ) , flexibility ( P=.006 ) , and leg strength ( P=.000 ) . Within the control group , there was a significant increase in fatigue score ( P=.004 ) and a decline in social well-being ( P<.05 ) at post-radiotherapy assessment . Between-group differences at post-radiotherapy assessment were significant in cardiac fitness ( P=.006 ) , strength ( P=.000 ) , flexibility ( P<.01 ) , fatigue ( P<.001 ) , FACT-P ( P=.006 ) , physical well-being ( P<.001 ) , social well-being ( P=.002 ) , and functional well-being ( P=.04 ) . CONCLUSIONS An 8-week cardiovascular exercise program in patients with localized prostate cancer undergoing radiotherapy improved cardiovascular fitness , flexibility , muscle strength , and overall QOL and prevented fatigue Breast screening programmes have facilitated more conservative approaches to the surgical and radiotherapy management of women diagnosed with breast cancer . This study investigated changes in shoulder movement after surgery for primary , operable breast cancer to determine the effect of elective physiotherapy intervention . Sixty-five women were r and omly assigned to either the treatment ( TG ) or control group ( CG ) and assessment s were completed preoperatively , at day 5 and at 1 month , 3 , 6 , 12 and 24 months postoperatively . The CG only received an exercise instruction booklet in comparison to the TG who received the Physiotherapy Management Care Plan ( PMCP ) . Analyses of variance revealed that abduction returned to preoperative levels more quickly in the TG than in the CG . The TG women had 14 ° more abduction at 3 months and 7 ° at 24 months . Functional recovery at 1 month was greater in those r and omised to the TG , with a dominant operated arm ( OA ) or receiving breast-conserving surgery . However , it was not possible to predict recovery over the 2 years postoperatively on the basis of an individual woman 's recovery at 1 month postoperatively . The eventual recovery of abduction or flexion range of movement was not related to the dominance of the OA nor to the surgical procedure performed . The PMCP provided in the early postoperative period is effective in facilitating and maintaining the recovery of shoulder movement over the first 2 years after breast cancer surgery Objective : To conduct a r and omized controlled trial and compare the effects on cancer survivors ’ quality of life in a 12-week group-based multidisciplinary self-management rehabilitation program , combining physical training ( twice weekly ) and cognitive-behavioral training ( once weekly ) with those of a 12-week group-based physical training ( twice weekly ) . In addition , both interventions were compared with no intervention . Methods : Participants ( all cancer types , medical treatment completed ≥3 months ago ) were r and omly assigned to multidisciplinary rehabilitation ( n = 76 ) or physical training ( n = 71 ) . The nonintervention comparison group consisted of 62 patients on a waiting list . Quality of life was measured using the R AND -36 . The rehabilitation groups were measured at baseline , after rehabilitation , and 3-month follow-up , and the nonintervention group was measured at baseline and 12 weeks later . Results : The effects of multidisciplinary rehabilitation did not outperform those of physical training in role limitations due to emotional problem ( primary outcome ) or any other domains of quality of life ( all p > .05 ) . Compared with no intervention , participants in both rehabilitation groups showed significant and clinical ly relevant improvements in role limitations due to physical problem ( primary outcome ; effect size ( ES ) = 0.66 ) , and in physical functioning ( ES = 0.48 ) , vitality ( ES = 0.54 ) , and health change ( ES = 0.76 ) ( all p < .01 ) . Conclusions : Adding a cognitive-behavioral training to group-based self-management physical training did not have additional beneficial effects on cancer survivors ’ quality of life . Compared with the nonintervention group , the group-based self-management rehabilitation improved cancer survivors ’ quality of life . PT = physical training ; CBT = cognitive-behavioral training ; PT+CBT = physical training plus cognitive-behavioral training ; WLC = waiting-list comparison ; QoL = quality of life ; ANOVA = analysis of variance ; ES = effect size This pilot study examined whether exercise as an adjunctive rehabilitation therapy could benefit women who have early stage breast cancer and are currently receiving chemotherapy/radiotherapy . The study was design ed as a r and omised controlled trial ( RCT ) . Physical functioning , fatigue and Quality of Life ( QoL ) outcomes were evaluated pre and post a 12-week intervention . The results showed that after 12 weeks the women who participated in the exercise programme ( n = 12 ) displayed significantly higher levels of physical functioning and reported higher QoL scores than the controls ( n = 10 ) . Changes in fatigue and satisfaction with life favoured the intervention group but did not reach significance . These results are encouraging and suggest that a structured group exercise programme during adjuvant treatment is a safe , well tolerated and effective way of providing physical and psychological health benefits to women during treatment for early stage breast cancer . Since this was a pilot study the numbers did not allow appropriately powered analyses of some variables of interest and favoured relatively young and socio-economically advantaged women . Future studies need to address these issues and determine if these short-term benefits can be sustained UNLABELLED An allogeneic hematopoietic stem cell transplantation ( HSCT ) can have profound and lasting adverse effects on a patient 's physical and psychological well-being . So far , only few studies have investigated the effectiveness of physical activity over the entire inpatient phase of an allogeneic HSCT . PURPOSE We performed a r and omized controlled study to examine the influence of a controlled moderate exercise program starting parallel to chemotherapeutic conditioning and total body irradiation on the patient 's physical and psychological constitution . PATIENTS AND METHODS Forty-seven patients undergoing an allogeneic HSCT were r and omly assigned to an exercise group ( EG ) or a control group ( CG ) . While the EG took part in an endurance and activity of daily living-training twice a day , the CG received the clinic 's st and ard physiotherapy program once a day . RESULTS Significant differences and /or trends in favor of the EG were observed regarding the primary endpoint endurance performance ( P=0.002 ) , muscular strength ( P=0.022 ) , fatigue ( P=0.046 ) , and emotional state ( P=0.028 ) without posing an additional risk for the individual . CONCLUSION The results show that the training program is feasible and seems to have positive influences on physical performance and quality of life in patients undergoing an allogeneic HSCT . However , further studies are necessary to confirm these results Background : Since physical exercise programs have the potential to help cancer patients regain physical fitness and may exert a range of positive consequences for recovery and psychological well-being , the impact of a physical exercise program was investigated in this prospect i ve study . Patients and Methods : Women with primary nonmetastatic breast cancer after a minimum 4-week period post chemotherapy and /or radiotherapy completion were r and omly assigned to one of 2 groups : intervention group ( IG ) ( n = 30 ) and waiting group ( WG ) ( n = 28 ) . The 10-week twice weekly exercise group program consisted of gymnastics , movement games , relaxation , walking , and jogging . Anxiety , depression , body image , and quality of life were measured using st and ardized question naires . Maximal oxygen uptake ( VO2max/kg ) was assessed as a measure of physical fitness . Results : Patients in the IG improved significantly over time with regard to anxiety ( p = 0.03 , d = 0.45 ) , depression ( p = 0.05 , d = 0.43 ) , individual body image ( p = 0.006 , d = 0.44 ) , and VO2max/kg ( p < 0.001 , d = 0.50 ) , whereas no improvements were observed in the WG . However , this r and omized controlled trial failed to demonstrate significant intervention effects in quality of life and social body image . Conclusions : This prospect i ve study provided evidence for the effectiveness of a 10-week physical exercise intervention to significantly improve psychosocial wellbeing , individual body image , and physical fitness 9617 Background : The quality of life ( QOL ) of cancer patients is often diminished due to the side effects of treatment and symptoms of the disease itself . This study examines the impact of Medical Qigong ( MQ ) , including gentle exercise and relaxation through meditation and breathing exercise based on the Chinese Medicine theory of energy channels , on quality of life ( QOL ) , fatigue , side effects , mood status and inflammation . METHODS One hundred sixty two patients diagnosed with a range of cancers recruited from three university teaching hospitals were r and omly assigned to two groups : a control group ( n=83 ) that received usual health care and an intervention group ( n=79 ) who participated in a MQ program for 10 weeks in addition to receiving usual health care at the hospital . Quality of life and symptoms were measured by the FACT-G , cancer related fatigue by FACT-F and mood status by POMS . The inflammatory marker serum C-reactive protein ( CRP ) was also monitored serially . RESULTS Regression analysis indicated that the MQ intervention group significantly improved on measures of overall QOL ( t144= -5.761 , p<0.001 ) , fatigue ( t153= -5.621 , p<0.001 ) , mood disturbance ( t122=2.346 , p=0.021 ) and inflammation ( CRP ) ( t99=2.042 , p<0.044 ) compared to the usual care control group after controlling for baseline variables . Analysis of the FACT-G subscales revealed that the MQ intervention group also significantly improved in satisfaction with sex life ( t92=-3.783 , p<0.001 ) and reduced side effects of nausea ( t152=-2.071 , p=0.040 ) and sleep disturbance ( t150=-2.603 , p=0.010 ) compared to the usual care control group . Pain was improved in both intervention and control groups . CONCLUSIONS This study suggests that MQ with usual health care can improve overall QOL , fatigue , positive mood status and reduce the side effects of nausea , sleep disturbance and inflammation of cancer patients . This study supports the use of MQ as an intervention for cancer care . No significant financial relationships to disclose Exercise participation has been shown to improve cardiovascular fitness and reduce psychological distress among women receiving chemotherapy and /or radiation . The purpose of this pilot study was to examine the changes in distress and body image , and fitness following exercise participation among 24 women who had been diagnosed with breast cancer within the previous 3 years . The women were r and omly assigned to participate in a 12-week supervised aerobic exercise program in a hospital setting or a wait-list control group . Assessment s of distress and body image were conducted at pre- and post-treatment . Data showed that the women in the exercise group improved significantly in body image ( Physical Condition and Weight Concerns subscales ) vs control group participants at post-treatment . Reductions in distress were also noted in the exercise group , but these were nonsignificant . At post-treatment , there were modest improvements in fitness in the exercise group BACKGROUND Active for Life After Cancer is a r and omized trial evaluating the efficacy of a 6-month group-based lifestyle physical activity program ( Lifestyle ) for prostate cancer patients to improve quality of life ( QOL ) including physical and emotional functioning compared to a group-based Educational Support Program and a St and ard Care Program ( no group ) . METHOD A total of 134 prostate cancer patients receiving continuous and rogen-ablation were r and omly assigned to one of the three study conditions . RESULTS Results indicated no significant improvements in QOL at 6 or 12 months . Both group-based programs were positively received and yielded good attendance and retention . Lifestyle participants demonstrated significant improvements in most theoretical mediators proposed by the Transtheoretical Model and Social Cognitive Theory to affect physical activity . Despite these improvements , no significant changes were found for most physical activity measures . CONCLUSIONS Results suggest a lifestyle program focusing on cognitive-behavioral skills training alone is insufficient for promoting routine physical activity in these patients Purpose To examine predictors of exercise adherence in breast cancer survivors . Methods Seventy-five breast cancer survivors were r and omly assigned to exercise ( n = 37 ) or usual care ( n = 38 ) . Demographic , prognostic , physiologic , and psychosocial information was collected at baseline and 6 months . The exercise goal was 30 min of exercise 5 days/week for 6 months . Results Women r and omized to exercise participated in moderate-intensity recreational exercise for 123 ± 52 min/week ( 81 % of the prescribed 150 min/week ) over 6 months . Baseline variables associated with better adherence were lower body mass index ( BMI ) , smaller waist circumference , higher amounts of physical activity 6 months prior to enrollment , being in the preparation vs. contemplation Stage of Change and higher FACT-B breast cancer subscale score . After adjusting for these variables , lower BMI and higher Stage of Change continued to be associated with better adherence ( p < 0.05 ) . Conclusions Future studies of exercise and breast cancer prognosis should target obese women for participation , as well as women just beginning to contemplate participation and its benefits after a cancer diagnosis OBJECTIVES Restorative yoga ( RY ) is a gentle type of yoga that may be beneficial for cancer patients and post-treatment survivors . Study goals were : to determine the feasibility of implementing a RY intervention for women with breast cancer ; and to examine group differences in self-reported emotional , health-related quality of life , and symptom outcomes . METHODS Women with breast cancer ( n=44 ; mean age 55.8 years ) enrolled in this study ; 34 % were actively undergoing cancer treatment . Study participants were r and omized to the intervention ( 10 weekly 75-minute RY classes ) or a waitlist control group . Participants completed question naires at Week 0 ( baseline ) and Week 10 ( immediately post-intervention for the yoga group ) . RESULTS Group differences favoring the yoga group were seen for mental health , depression , positive affect , and spirituality ( peace/meaning ) . Significant baseline*group interactions were observed for negative affect and emotional well-being . Women with higher negative affect and lower emotional well-being at baseline derived greater benefit from the yoga intervention compared to those with similar values at baseline in the control group . The yoga group demonstrated a significant within-group improvement in fatigue ; no significant difference was noted for the control group . CONCLUSIONS Although limited by sample size , these pilot data suggest potential benefit of RY on emotional outcomes and fatigue in cancer patients . This study demonstrates that a RY intervention is feasible for women with breast cancer ; implication s for study design and implementation are noted with an emphasis on program adoption and participant adherence Purpose Cancer patients often experience diminished cognitive function ( CF ) and quality of life ( QOL ) due to the side effects of treatment and the disease symptoms . This study evaluates the effects of medical Qigong ( MQ ; combination of gentle exercise and meditation ) on CF , QOL , and inflammation in cancer patients . Methods Eighty-one cancer patients recruited between October 2007 and May 2008 were r and omly assigned to two groups : a control group ( n = 44 ) who received the usual health care and an intervention group ( n = 37 ) who participated in a 10-week MQ program . Self-reported CF was measured by the European Organization for Research and Treatment of Cancer ( EORTC-CF ) and the Functional Assessment of Cancer Therapy — Cognitive ( FACT-Cog ) . The Functional Assessment of Cancer Therapy — General ( FACT-G ) was used to measure QOL . C-reactive protein ( CRP ) was assessed as a biomarker of inflammation . Results The MQ group self-reported significantly improved CF ( mean difference ( MD ) = 7.78 , t51 = −2.532 , p = 0.014 ) in the EORTC-CF and all the FACT-Cog subscales [ perceived cognitive impairment ( MD = 4.70 , t43 = −2.254 , p = 0.029 ) , impact of perceived cognitive impairment on QOL ( MD = 1.64 , t45 = −2.377 , p = 0.024 ) , and perceived cognitive abilities ( MD = 3.61 , t45 = −2.229 , p = 0.031 ) ] compared to controls . The MQ group also reported significantly improved QOL ( MD = 12.66 , t45 = −5.715 , p < 0.001 ) and had reduced CRP levels ( MD = −0.72 , t45 = 2.092 , p = 0.042 ) compared to controls . Conclusions Results suggest that MQ benefits cancer patients ’ self-reported CF , QOL , and inflammation . A larger r and omized controlled trial including an objective assessment of CF is planned Increasing numbers of women with breast cancer are seeking alternatives to st and ard group support in coping with their illness . This study examines outcomes for 181 women with breast cancer r and omized to either a 12-week st and ard group support or a 12-week complementary and alternative medicine ( CAM ) support intervention . Participants in the CAM group were taught the use of meditation , affirmation , imagery and ritual . The st and ard group combined cognitive-behavioral approaches with group sharing and support . Both interventions were found to be associated with improved quality of life ( CAM , P=0.008 ; St and ard , P=0.006 ) , decreased depression ( CAM , P=0.004 ; St and ard , P=0.02 ) , decreased anxiety ( CAM , P=0.0003 ; St and ard , P=0.02 ) and increased " spiritual well-being " ( CAM , P=002 ; St and ard , P=0.003 ) . Only the CAM group showed increases in measures of Spiritual Integration ( P=0.001 ) which were also significant between groups ( P=0.003 ) . The St and ard group was associated with decreased confusion ( P=0.01 ) and decreased helplessness/hopelessness ( P=0.01 ) , while the CAM group was associated with decreased avoidance ( P=0.01 ) . None of these latter changes were significant between groups . At baseline , very high correlations were noted between measures of quality of life , mood , and spiritual integration . At the end of the intervention , the CAM group showed higher satisfaction ( P=0.006 ) and fewer dropouts ( P=0.006 ) compared to the st and ard group . Better outcomes in quality of life in the CAM group were associated with lower initial fighting spirit ( r=-.39 , P=0.001 ) . No baseline factors predicted better outcomes in the St and ard group . In summary , the study found equivalence on most psychosocial outcomes between the two interventions Cheville AL , Girardi J , Clark MM , Rummans TA , Pittelkow T , Brown P , Hanson J , Atherton P , Johnson ME , Sloan JA , Gamble G : Therapeutic exercise during outpatient radiation therapy for advanced cancer : Feasibility and impact on physical well-being . Objective : To characterize the feasibility of delivering a structured physical therapy ( PT ) program as part of a multidisciplinary intervention to patients undergoing outpatient radiation therapy for advanced cancer . Design : A single-blinded , r and omized , controlled trial at a quaternary medical center outpatient clinic . One hundred three adults undergoing radiation therapy for advanced cancer with prognoses ≥6 mos and 5-yr survival estimates ≤50 % were r and omized to usual care or participation in eight 90-min , multidisciplinary interventional sessions with 30 mins of each session devoted to PT . PT consisted of truncal and limb isodynamic strengthening targeting major upper- and lower-limb muscle groups as well as education and provision with instructional material s. Physical well-being and fatigue were assessed with Linear Analog Scale of Assessment . The Profile of Mood States-Short form , including Fatigue-Inertia and Vigor-Activity subscales , was also administered . Results : PT session attendance was 89.3 % . Relative to baseline , mean physical well-being Linear Analog Self Assessment scores at week 4 improved in the intervention group , 0.4 ( SD , 23.6 ) , and declined significantly in the control group , −10.0 ( SD , 21.5 ) ( P = 0.02 ) . Fatigue and vigor were not significantly different between the groups . All intergroup differences had resolved at 8 and 27 wks . Baseline characteristics were not associated with the magnitude or direction of change in outcomes related to physical functioning . Conclusions : Delivery of a st and ardized resistive exercise PT intervention is feasible during outpatient radiation therapy and is associated with preserved physical well-being . However , benefits were not sustained , and fatigue was not affected PURPOSE The purpose of this study was to investigate the effect of a comprehensive rehabilitation program on physical function , immune response , fatigue and quality of life in mastectomy patients . METHOD The subjects included fifty-five patients with breast cancer ( 27 in the control group and 28 in the experimental group ) . The subjects in the experimental group participated in a comprehensive rehabilitation program for 10 weeks , which was composed of 1 session of education , 2 sessions of stress management , 2 sessions of exercise , and 1 session of peer support group activity per week . RESULT The results revealed an increase in shoulder extension , abduction , external rotation , and internal rotation of the affected upper extremity , and in shoulder extension and abduction of the healthy upper extremity . Also an increase in quality of life and a decrease in fatigue were significantly higher in the experimental group than the control group . However , the results revealed that the natural killer cell ratio of the experimental group increased but there was no significant difference from that of the control group . CONCLUSION The 10-week comprehensive rehabilitation program showed a large affirmative effect on physical function , fatigue and quality of life of breast cancer patients after a mastectomy PURPOSE To assess the influence of physiotherapy performed during radiotherapy ( RT ) on the quality of life ( QL ) of women under treatment for breast cancer . METHODS This was a r and omized clinical trial conducted on 55 women under RT treatment , 28 of whom were assigned to a group su bmi tted to physiotherapy ( PG ) and 27 to the control group receiving no PG ( CG ) . The physiotherapy technique used for PG was kinesiotherapy for the upper limbs using 19 exercises actively performed , with a series of ten rhythmic repetitions or stretching movements involving flexion , extension , abduction , adduction , internal and external shoulder rotation , separate or combined . QL was evaluated using the Functional Assessment of Cancer Therapy-Breast ( FACT-B ) , at the beginning and at the end of RT and six months after the end of RT . The physiotherapy sessions were started concomitantly with RT , 90 days after surgery , on average . RESULTS There was no difference between subgroups regarding the following subscales : physical well-being ( p=0.8 ) , social/family well-being ( p=0.3 ) , functional well-being ( p=0.2 ) and breast subscale ( p=0.2 ) at the three time points assessed . A comparison of the emotional subscale applied at the three evaluations demonstrated a better behavior of PG as compared to CG ( p=0.01 ) , with both groups presenting improvement on the breast subscale between the beginning and the end of RT ( PG p=0.0004 and CG p=0.003 ) . There was improvement in FACT-B scores at the end of RT in both groups ( PG p=0.0006 and CG p=0.003 ) . However , at the sixth month after RT , this improvement was maintained only in PG ( p=0,005 ) . QL assessed along time by the FACT B ( p=0.004 ) and the Trial Outcome Index ( TOI ) ( sums of the physical and functional well-being subscales and of the breast subscale ) was better for PG ( p=0.006 ) . There was no evidence of negative effects associated with the exercises . CONCLUSIONS The execution of exercises for the upper limbs was beneficial for QL during and six months after RT We retrospectively analysed acute radiation toxicity data for patients who had participated in a r and omised controlled study in our centre in order to assess the impact of aerobic exercise on acute rectal and bladder morbidity during treatment . Data from 65 of 66 patients were analysed : 33 allocated into a control group ( st and ard advice ) and 33 into an exercise group ( aerobic walking for 30 min at least three times per week ) during 4 weeks of external beam radiotherapy ; one patient in the exercise group withdrew after r and omisation before starting radiotherapy . There was a trend towards less severe acute rectal toxicity in the exercise group with a statistically significant difference in mean toxicity scores over the 4 weeks of radiotherapy ( P=0.004 ) , with no significant difference in bladder toxicity scores between the two groups ( P=0.123 ) . The lack of an association for severity of bladder toxicity could be attributed to the confounding effect of lower urinary tract symptoms from their prostate cancer . Keeping active and being asked to adhere to a well-defined exercise schedule appears to reduce the severity of rectal toxicity during radiotherapy to the prostate During radiation therapy , cancer patients may report cancer-related fatigue ( CRF ) , which impairs aerobic capacity , strength , muscle mass , and , ultimately , quality of life ( QOL ) . The purpose of this pilot clinical trial was to examine the feasibility and initial efficacy of a home-based aerobic and progressive resistance exercise intervention for aerobic capacity , strength , muscle mass , CRF , and QOL . Daily steps walked ( DSW ) , daily minutes of resistance exercise ( MRE ) , and number of resistance exercise days ( RED ) were assessed to evaluate intervention adherence . Breast and prostate cancer patients ( n = 38 ) beginning radiation therapy were r and omized to undergo 4 weeks of exercise or no exercise . Participants in the exercise group demonstrated good adherence to the exercise intervention , with significantly more DSW , MRE , and RED at post intervention and 3 month follow-up than controls . Participants in the exercise intervention exhibited significantly higher QOL and significantly lower CRF post intervention and at 3-month follow-up than controls . Results of this pilot study provide positive preliminary evidence that exercise during radiation may be beneficial for cancer patients OBJECTIVE To investigate the feasibility of a pragmatic lifestyle intervention in patients who had recently completed surgery and chemotherapy for colon cancer and to obtain preliminary data of its impact on important health outcomes . DESIGN A prospect i ve , r and omized , controlled pilot trial . SETTING University rehabilitation facility . PARTICIPANTS Eighteen ( N=18 ) colon cancer survivors ( mean age=69y ; range , 52 - 80y ) , Dukes stage A to C. INTERVENTIONS Participants were r and omized 6 to 24 months postoperatively to either a 12-week program of combined exercise and dietary advice or st and ard treatment . MAIN OUTCOME MEASURES Exercise and dietary behavior , fatigue , health-related quality of life ( QOL ) , aerobic exercise tolerance , functional capacity , muscle strength , and anthropometery were assessed at baseline and immediately after the intervention . RESULTS Adherences to supervised and independent exercise during the intervention were 90 % and 94 % , respectively , and there was low attrition ( 6 % ) . The lifestyle intervention elicited improvements in exercise behavior ( P=.068 ) , fatigue ( P=.005 ) , aerobic exercise tolerance ( P=.010 ) , chair sit-to-st and performance ( P=.003 ) , and waist-to-hip ratio ( P=.002 ) . A positive change in dietary fiber intake ( P=.044 ) was also observed in the intervention group . No change in QOL was observed ( P=.795 ) . CONCLUSIONS These preliminary results suggest that a pragmatic lifestyle intervention implemented 6 to 24 months after primary treatment for colon cancer was feasible . We observed a significant impact on dietary behavior , fatigue , aerobic exercise tolerance , functional capacity , and waist-to-hip ratio . These findings need to be confirmed with a larger-scale definitive r and omized controlled trial OBJECTIVE To determine the feasibility and efficacy of a physical activity behavioural change intervention in managing cancer-related fatigue among gynaecological cancer survivors during and post anti-cancer treatments . METHODS A two arm , single blind , r and omised controlled trial was conducted within the Northern Irel and regional Cancer Centre . Thirty three sedentary gynaecological cancer survivors ( stage I-III ; ≤3 years post diagnosis ) , experiencing cancer-related fatigue ( mild-severe ) took part . Participants were r and omly assigned to a behavioural change , moderate intensity physical activity intervention ( n=16 ) or a Contact Control group ( n=17 ) . The primary outcome was fatigue ( Multidimensional Fatigue Symptom Inventory-Short Form and Functional Assessment in Chronic Illness Therapy-Fatigue subscale ) . Secondary outcomes included quality of life , physical functioning , positive and negative affect , depression , body composition , sleep dysfunction and self-reported physical activity . Feasibility was assessed based on the recruitment rate , programme and physical activity adherence and participants ' programme evaluation , including optional focus groups ( n=16 ) . RESULTS Twenty five percent of eligible women took part ( 33/134 ) . Participants were 8.7 ( SD=9.1 ) months post diagnosis , with a mean age of 53 ( SD=10.3 ) years . The majority of the sample had a diagnosis of ovarian ( n=12 ) or endometrial cancer ( n=11 ) . Significant differences favouring the intervention group were observed for fatigue at 12 weeks and 6 months follow-up ( 12 week : mean difference=-11.06 ; 95 % confidence interval (CI)=-21.89 to -0.23 ; effect size (d)=0.13 ; p=0.046 ; 6 month : mean difference=-19.48 ; 95 % CI=-19.67 to -19.15 ; effect size (d)=0.20 ; p=0.01 ) . A mean of 10 calls ( SD=1.2 calls ) were delivered to the Physical Activity Group , and 10 ( SD=1.6 calls ) to the CC group . The intervention was positively perceived based on exit question naire and focus group findings . CONCLUSIONS A physical activity behavioural change intervention for gynaecological cancer survivors is feasible in terms of participants ' programme adherence and evaluation , and the intervention demonstrates improvements in fatigue . However , confirmation in the form of a larger fully powered RCT is warranted The purpose of this study was to determine if an eight-week intrahospital supervised , conditioning program improves functional capacity and quality of life ( QOL ) in children ( 4 boys , 4 girls ) ( mean [ SD ] age : 10.9 [ 2.8 ] years [ range : 8 - 16 ] ) who have undergone bone marrow transplantation ( BMT ) for leukemia treatment within the last 12 months . A group of 8 age and gender-matched healthy children served as controls . The experimental group performed 3 weekly sessions of resistance and aerobic training inside an intra-hospital gymnasium . A significant combined effect of group and time ( p < 0.05 ) was observed for muscle functional capacity ( Timed Up and Down Stairs [ TUDS ] test ) and peak oxygen uptake ( V.O(2peak ) ) , i.e. , with BMT children showing greater improvements than controls ( V.O(2peak ) at pre- and post-training of 25.9 ( 8.2 ) and 31.1 ( 7.6 ) mL/kg/min in diseased children ) . Muscle strength ( 6 RM test for bench and leg press and seated row ) also improved after training ( p < 0.05 ) in the BMT group . Concerning QOL , a significant combined effect of group and time ( p < 0.05 ) was also observed for children 's self-report of comfort and resilience and for parents ' report of their children 's satisfaction and achievement . In summary , children who have received BMT experience physical and overall health benefits after a relatively short-term ( 8 weeks ) supervised exercise training program PURPOSE / OBJECTIVES To examine the effects of a seated exercise program on fatigue and quality of life ( QOL ) in women with metastatic breast cancer . DESIGN R and omized , controlled , longitudinal trial . SETTING Outpatient clinic of a comprehensive cancer center . SAMPLE Convenience sample of 38 women who were beginning outpatient chemotherapy . METHODS Subjects were r and omized to a control or intervention group ; the intervention was performance of a seated exercise program using home videotape three times per week for four cycles of chemotherapy . All subjects completed the Functional Assessment of Chronic Illness Therapy Fatigue Version IV ( FACIT F ) at baseline and at the time of the next three cycles . Subjects were asked to document the frequency , duration , and intensity of all exercise participation on monthly calendars . MAIN RESEARCH VARIABLES Exercise , fatigue , and QOL . FINDINGS 32 subjects , 16 per group , completed the study follow-up . With a mixed modeling approach , total FACIT F scores for the entire sample declined at a significant rate ( p = 0.003 ) beginning with cycle 3 but at a slower rate for the experimental group ( p = 0.02 ) . Fatigue scores indicated less increase and physical well-being subscale scores showed less decline for the experimental group ( p = 0.008 and p = 0.02 , respectively ) . CONCLUSIONS Women with advanced breast cancer r and omized to the seated exercise intervention had a slower decline in total and physical well-being and less increase in fatigue scores starting with the third cycle of chemotherapy . IMPLICATION S FOR NURSING Seated exercise may be a feasible exercise program for women with advanced cancer for controlling fatigue and improving physical well-being Background : Patients receiving high-dose chemotherapy and hematopoietic stem cell transplantation ( HSCT ) experience considerable reductions in physical activity and deterioration of their health status . Objective : The purpose of this pilot study was to test the effects of strength training compared with usual activity on physical activity , muscle strength , fatigue , health status perceptions , and quality of life following HSCT . Methods : Nineteen subjects were r and omized to the exercise or control group . Moderate-intensity strength training began following discharge from the hospital . Dependent variables included physical activity , muscle strength , fatigue , health status perceptions , and quality of life . Variables were measured prior to admission to the hospital for HSCT , day 8 following HSCT , and 6 weeks following discharge from the hospital . Results : Significant time effects were noted for many variables with anticipated declines in physical activity , muscle strength , fatigue , and health status perceptions immediately after HSCT with subsequent improvements 6 weeks following hospital discharge . One group effect was noted with subjects in the exercise group reporting less fatigue than subjects in the control group . Although no significant interactions were detected , the trends suggest that the exercise group may be more physically active following the intervention compared with the usual-activity group . Conclusions : This study demonstrates the potential positive effects of strength training on physical activity , fatigue , and quality of life in people receiving high-dose chemotherapy and HSCT . Implication s for Practice : Preliminary evidence is provided for using strength training to enhance early recovery following HSCT . Elastic resistance b and s are easy to use and relatively inexpensive Purpose : To examine the effect of regular Iyengar yoga practice on measures of self‐perceived psychosocial function and diurnal salivary cortisol secretion in stage II – IV breast cancer survivors ( n = 18 ) . Data sources : Women were r and omly assigned to attend yoga practice for 90 min twice weekly for 8 weeks ( n = 9 ) or to a wait‐listed , noninterventional control group ( n = 9 ) . Traditional Iyengar yoga routines that progressively increased in difficulty as participants gained strength and flexibility were used . At baseline and after the 8‐week study period , women completed self‐report instruments to document various aspects of psychosocial and physical functioning , and collected salivary sample s for cortisol analysis four times during the day for two consecutive days . Conclusions : The yoga group had lower morning and 5 p.m. salivary cortisol and improved emotional well‐being and fatigue scores . Implication s for practice : Breast cancer survivors are at risk for chronic psychosocial distress that may alter activity of the hypothalamic – pituitary – adrenal axis , result ing in aberrant regulation of cortisol secretion and increased risk of immune dysfunction and cancer progression . Regular yoga practice may be a low‐risk , cost‐effective way to improve psychosocial functioning , fatigue , and regulation of cortisol secretion in breast cancer survivors . These findings require validation with a larger r and omized study We conducted a r and omized controlled trial to determine the effects of a home-based exercise intervention on change in quality of life ( QOL ) in recently resected colorectal cancer survivors , most of whom were receiving adjuvant therapy . Participants were r and omly assigned in a 2:1 ratio to either an exercise ( n = 69 ) or control ( n = 33 ) group . The exercise group was asked to perform moderate intensity exercise 3 - 5 times per week for 20 - 30 min each time . The primary outcome was change in QOL as measured by the Functional Assessment of Cancer Therapy-Colorectal ( FACT-C ) scale . Adherence in the exercise group was good ( 75.8 % ) but contamination in the control group was problematic ( 51.6 % ) . Intention-to-treat analysis revealed no significant differences between groups for change in the FACT-C ( mean difference , -1.3 ; 95 % CI , -7.8 to 5.1 ; P = 0.679 ) . In an ' on-treatment ' ancillary analysis , we compared participants who decreased versus increased their cardiovascular fitness over the course of the intervention . This analysis revealed significant differences in favour of the increased fitness group for the FACT-C ( mean difference , 6.5 ; 95 % CI , 0.4 - 12.6 ; P = 0.038 ) . These data suggest that increased cardiovascular fitness is associated with improvements in QOL in colorectal cancer survivors but better controlled trials are needed OBJECTIVES Cancer treatment-related fatigue is a common and disruptive side effect of chemotherapy . Exercise is an intervention proposed to reduce fatigue in cancer patients . The purpose of this study was to describe the patterns of daily fatigue in women with breast cancer who did and did not exercise while receiving the first three cycles of adjuvant chemotherapy . MATERIAL S AND METHODS Women received instruction to follow an 8-week home-based exercise program and to maintain daily exercise and fatigue diaries . Functional ability ( 12-minute walk ) was measured pretest and post-test . RESULTS Several distinct patterns of fatigue emerged . The most common pattern of fatigue after chemotherapy demonstrated a sharp rise in fatigue . However , several women demonstrated a chaotic pattern with erratic and wide swings in their fatigue throughout the entire study period . Women who adopted exercise experienced fewer days of high fatigue levels and more days of low levels of fatigue for both average and worst levels of fatigue . Women who did not exercise experienced more bad days ( high fatigue ) and fewer good days ( low fatigue ) . CONCLUSIONS Exercise appears to reduce the levels of average and worst fatigue and may help women recognize their pattern of fatigue . Exercise may reduce the intensity of fatigue by reorganizing women 's interpretation of fatigue . Routine clinical assessment and education about fatigue by health professionals can help patients to underst and their pattern of fatigue and may help them to manage the symptom PURPOSE And rogen deprivation therapy is a common treatment in men with prostate cancer that may cause fatigue , functional decline , increased body fatness , and loss of lean body tissue . These physical changes can negatively affect health-related quality of life . Resistance exercise may help to counter some of these side effects by reducing fatigue , elevating mood , building muscle mass , and reducing body fat . METHODS In a two-site study , 155 men with prostate cancer who were scheduled to receive and rogen deprivation therapy for at least 3 months after recruitment were r and omly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks ( 82 men ) or to a waiting list control group ( 73 men ) . The primary outcomes were fatigue and disease-specific quality of life as assessed by self-reported question naires after 12 weeks . Secondary outcomes were muscular fitness and body composition . RESULTS Men assigned to resistance exercise had less interference from fatigue on activities of daily living ( P = .002 ) and higher quality of life ( P = .001 ) than men in the control group . Men in the intervention group demonstrated higher levels of upper body ( P = .009 ) and lower body ( P < .001 ) muscular fitness than men in the control group . The 12-week resistance exercise intervention did not improve body composition as measured by changes in body weight , body mass index , waist circumference , or subcutaneous skinfolds . CONCLUSION Resistance exercise reduces fatigue and improves quality of life and muscular fitness in men with prostate cancer receiving and rogen deprivation therapy . This form of exercise can be an important component of supportive care for these patients PURPOSE The efficacy of a home-based physical activity ( PA ) intervention for early-stage breast cancer patients was evaluated in a r and omized controlled trial . PATIENTS AND METHODS Eighty-six sedentary women ( mean age , 53.14 years ; st and ard deviation , 9.70 years ) who had completed treatment for stage 0 to II breast cancer were r and omly assigned to a PA or contact control group . Participants in the PA group received 12 weeks of PA counseling ( based on the Transtheoretical Model ) delivered via telephone , as well as weekly exercise tip sheets . Assessment s were conducted at baseline , after treatment ( 12 weeks ) , and 6 and 9 month after baseline follow-ups . The post-treatment outcomes are reported here . RESULTS Analyses showed that , after treatment , the PA group reported significantly more total minutes of PA , more minutes of moderate-intensity PA , and higher energy expenditure per week than controls . The PA group also out-performed controls on a field test of fitness . Changes in PA were not reflected in objective activity monitoring . The PA group was more likely than controls to progress in motivational readiness for PA and to meet PA guidelines . No significant group differences were found in body mass index and percent body fat . Post-treatment group comparisons revealed significant improvements in vigor and a reduction in fatigue in the PA group . There was a positive trend in intervention effects on overall mood and body esteem . CONCLUSION The intervention successfully increased PA and improved fitness and specific aspects of psychological well-being among early-stage breast cancer patients . The success of a home-based PA intervention has important implication s for promoting recovery in this population The primary purpose of this study was to examine differences in quality of life ( QoL ) between non-Hodgkin 's lymphoma ( NHL ) survivors meeting and not meeting public health exercise guidelines . A secondary purpose was to examine exercise behavior changes across three distinct cancer-related time periods ( i.e. prediagnosis , on treatment and off treatment ) . Using a retrospective survey design , 438 NHL survivors residing in Alberta , Canada completed a mailed question naire that assessed self-reported exercise prediagnosis , on treatment and off treatment , and current QoL. Descriptive analyses indicated that 33.8 , 6.5 and 23.7 % of NHL survivors met public health exercise guidelines during prediagnosis , on treatment , and off treatment time periods , respectively . Multivariate analyses of variance indicated that NHL survivors meeting public health exercise guidelines during postdiagnosis time periods had higher current QoL scores than NHL survivors not meeting guidelines . QoL difference scores between the two groups met proposed st and ards for clinical ly important differences . Multivariate analyses also indicated significant differences in exercise behavior across the three cancer-related time periods ( all p's<0.01 ) . These analyses were unchanged after statistically controlling for important medical and demographic variables . The results of this study provide evidence that NHL survivors meeting public health exercise guidelines on and off treatment reported higher current QoL than those survivors not meeting guidelines . These findings corroborate research examining exercise behavior in other cancer survivor groups and provide preliminary data to support a r and omized controlled trial on exercise and QoL in this population Abstract Background . The diagnosis and treatment of cancer may cause clinical ly significant and persistent psychological morbidity . The objective of this study was to determine the short-term effect of a six week exercise intervention on anxiety and depression in cancer patients undergoing chemotherapy ( The ‘ Body & Cancer ’ trial ) . Methods . Two hundred and nine self-referred patients ( 52 males , 157 females , mean age 47 years ) were r and omised into an intervention group and a waiting-list control group . Anxiety and depression was measured by the Hospital Anxiety and Depression Scale . Results . At baseline , 23.5 % and 11.5 % of the population scored > 8 on the HADS and were classified as suspicious or definite cases of anxiety and depression , respectively . Adjusted for baseline score , disease and demographic covariates the estimated intervention effect showed improvement at six weeks for depression of −0.7 points ( 95 % confidence interval [ CI ] −1.27 to −0.14 , p = 0.0153 ) . No significant effect was seen on anxiety . Further sub analysis , including only suspicious or definite cases of depression , result ed in an estimated intervention effect of −2.53 points ( 95 % CI , −0.64 to −0.42 , p = 0.021 ) . Conclusion . Anti-depressant effects could be caused by exercise in self-referred cancer patients undergoing chemotherapy . Dedicated trials and follow-up studies are needed to clarify the optimal duration and content of exercise interventions to meet the needs of clinical ly depressive or anxious patients Background : Cancer-related fatigue ( CRF ) is a frequently occurring , burdensome side effect of radiation therapy that can result in detrimental effects to health-related quality of life ( HRQL ) . The findings from a pilot study examining the efficacy of the complementary and alternative practice of Polarity Therapy ( PT ) in reducing CRF and improving HRQL are reported . Methods : Fifteen women undergoing radiation therapy for breast cancer and experiencing fatigue were r and omized to receive 1 , 2 , or no PT treatments . Treatments were given 1 week apart to the patients receiving 2 treatments . Fatigue and HRQL were assessed at baseline prior to PT , 3 days following the first PT treatment ( week 1 ) , and 3 days following the second PT treatment ( week 2 ) . Results : There was a statistically significant improvement in both CRF and HRQL in the 10 patients who received a PT treatment compared to the 5 control patients at the week 1 assessment . In addition , there was a statistically significant difference among the 3 treatment groups in improvement in CRF at the week 2 assessment . This finding , coupled with a visual inspection of the means , supports the plausibility of a dose response concerning PT . Conclusion : Results from this pilot investigation suggest that PT may have a positive influence on CRF and HRQL in women undergoing radiation treatment for breast cancer . R and omized , controlled clinical trials with larger sample sizes are needed Substantial physical and functional deconditioning and diminished psychological wellbeing are all potential adverse effects of allogeneic stem cell transplantation ( allo-HSCT ) . The aim of this study was to evaluate the feasibility , safety and benefits ( physical and functional capacity ) of a 4–6 week supervised and structured mixed-type exercise , progressive relaxation and psychoeducation programme in patients undergoing allo-HSCT . Nineteen patients were r and omized to an intervention or a conventional care group ( CC ) and were tested for physical and functional capacity before admission and upon hospital discharge . In all , 14 patients completed all study requirements ( 74 % ) and no adverse reactions that could be attributed to the intervention were observed . At the time of discharge , the intervention group showed significant improvements in several muscle strength scores as compared to the CC group ; chest press ( P=0.023 ) , leg extension ( P=0.007 ) and isometric right knee flexor ( P=0.033 ) . The intervention proved feasible , safe and well tolerated in this small sample of patients undergoing allo-HSCT . An intervention of this type may be a useful strategy for maintaining or improving muscle strength , and minimizing loss of physical and functional capacity in patients undergoing allo-HSCT PURPOSE To evaluate the effectiveness of a supervised home-based flexible training program on cardiorespiratory fitness ( CRF ) , mental distress , and health-related quality of life ( HRQOL ) parameters in young and middle-aged cancer patients shortly after curative chemotherapy . PATIENTS AND METHODS One hundred eleven patients age 18 to 50 years who had received chemotherapy for lymphomas or breast , gynecologic , or testicular cancer completed the trial . These patients were r and omly allocated to either an intervention group ( n = 59 ) , which underwent a 14-week training program , or a control group ( n = 52 ) that received st and ard care . Primary outcome was change in CRF , as determined by Astr and -Rhyming indirect bicycle ergometer test ( maximum oxygen uptake [ VO(2max ) ] ) , between baseline ( T0 ) and follow-up ( T1 ) . Secondary outcomes were mental distress , as assessed by the Hospital Anxiety and Depression Scale , and HRQOL , as assessed by the European Organisation for Research and Treatment of Cancer Core Quality of Life Question naire . Two-way analysis of covariance was used to analyze changes from T0 to T1 . RESULTS VO(2max ) increased by 6.4 mL/kg(-1)/min(-1 ) in patients in the intervention group and by 3.1 mL/kg(-1)/min(-1 ) in patients in the control group ( P < .01 ) . The fatigue score decreased by 17.0 points in the control group compared with only 5.8 points in the intervention group ( P < .01 ) . There were no intergroup differences in mental distress or HRQOL . CONCLUSION A supervised , home-based , flexible training program has significant effect on CRF in young and middle-aged cancer patients shortly after curative chemotherapy , but it has no favorable effect on patients ' experience of fatigue , mental distress , or HRQOL AIMS In this prospect i ve controlled r and omized trial we assessed the effects of early , intensive , prolonged pelvic floor exercises ( PFE ) on urinary incontinence following bladder neck ( BN ) sparing RRP . METHODS A sample of 152 patients with localized prostate cancer underwent RRP with BN preservation . Out of this group we r and omized 107 incontinent patients into 2 groups . We considered incontinent patients with 24 hr Pad test > 2 g. The T group received instructions regarding an intensive program of PFE , from 7 days after catheter removal for as long as any degree of incontinence persisted , within a period of 1 year . The control ( C ) group did not receive instructions . The outcome was assessed using the 24 hr Pad test , a visual analogue scale ( VAS ) and a single question of QoL. Results at baseline and at 1 , 3 , 6 , and 12 months were available for 54 and 40 patients , respectively . RESULTS The overall spontaneous continence rate after catheter removal was 23.6 % . The proportion of men still incontinent was significantly higher in the C group than treatment ( T ) group at 1 ( 97.5 % vs. 83.3 % ; P = 0.04 ) , 3 ( 77.5 % vs. 53.7 % ; P = 0.03 ) , 6 ( 60 % vs. 33.3 % ; P = 0.01 ) , and 12 months ( 52.5 % vs. 16.6 % ; P < 0.01 ) . Similarly , the VAS and the response to the QoL question at 12 months significantly differed between the two groups ( P = 0.01 and 0.03 , respectively ) . CONCLUSIONS Our study suggests that early intensive prolonged PFE can further increase the number of continent patients and this improvement persists in the first 12 months . The second 6 months following surgery are still useful to recovery The aim of this study was to explore the effects of presurgical exercise training on quality of life ( QOL ) in patients with malignant lung lesions . Using a single-group prospect i ve design , patients were enrolled in supervised aerobic exercise training for the duration of surgical wait time ( mean 59.7 days ) . Participants completed assessment s of cardiorespiratory fitness ( peak oxygen consumption ) and QOL using the Functional Assessment of Cancer Therapy-Lung scales , including the trial outcome index ( TOI ) and the lung cancer subscale ( LCS ) at baseline , immediately presurgery , and postsurgery ( mean , 57 days ) . 9 participants provided complete data . Repeated- measures analysis indicated a significant effect for time on TOI ( P = .006 ) and LCS ( P = .009 ) . Paired analysis revealed that QOL was unchanged after exercise training ( ie , baseline to presurgery ) , but there were significant and clinical ly meaningful declines from presurgery to postsurgery in the LCS ( −3.6 , P = .021 ) and TOI ( −8.3 , P = .018 ) . Change in peak oxygen consumption from presurgery to postsurgery was significantly associated with change in the LCS ( r = 0.70 , P = .036 ) and TOI ( r = 0.70 , P = .035 ) . Exercise training did not improve QOL from baseline to presurgery . Significant declines in QOL after surgery seem to be related to declines in cardiorespiratory fitness . A r and omized controlled trial is needed to further investigate these relationships 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 ) OBJECTIVES To assess the impact of lifestyle on health-related quality of life ( HR-QOL ) , perceived stress , and self-reported sexual function in men with early-stage prostate cancer electing active surveillance . METHODS A total of 44 intervention and 49 usual-care control participants were enrolled in a r and omized clinical trial examining the effects of lifestyle changes on prostate cancer progression . The intervention consisted of a low-fat , vegan diet , exercise , and stress management . Participants completed the Medical Outcomes Study Short Form-36 Health Status Survey ( a measure of mental and physical HR-QOL ) , the Perceived Stress Scale , the Sexual Function subscale of the University of California , Los Angeles , Prostate Cancer Index , and measures of lifestyle behaviors ( to yield an overall lifestyle index ) at baseline and 12 months . The data were analyzed using analysis of variance for repeated measures . The relationship between lifestyle and QOL was also analyzed using multiple linear regression analyses . RESULTS Intervention participants had significantly improved their lifestyle compared with controls at 12 months . The quality -of-life scores were high across groups and time points . However , a healthier lifestyle was related to better QOL at baseline . Participants in both groups who reported a healthier lifestyle also reported better mental and physical HR-QOL and sexual function . Furthermore , participants whose lifestyle improved over time showed enhanced physical HR-QOL and decreased perceived stress . CONCLUSIONS Men who choose active surveillance for early-stage prostate cancer are able to make comprehensive lifestyle changes . Although the average QOL was already high in this sample , individuals who improved their lifestyle enhanced their QOL further PURPOSE The primary goal of this study was to evaluate the feasibility and effectiveness of a structured , multidisciplinary intervention targeted to maintain the overall quality of life ( QOL ) , which is more comprehensive than psychosocial distress , of patients undergoing radiation therapy for advanced-stage cancer . PATIENTS AND METHODS Radiation therapy patients with advanced cancer and an estimated 5-year survival rate of 0 % to 50 % were r and omly assigned to either an eight-session structured multidisciplinary intervention arm or a st and ard care arm . The eight 90-minute sessions addressed the five domains of QOL including cognitive , physical , emotional , spiritual , and social functioning . The primary end point of maintaining overall QOL was assessed by a single-item linear analog scale ( Linear Analog Scale of Assessment or modified Spitzer Uniscale ) . QOL was assessed at baseline , week 4 ( end of multidisciplinary intervention ) , week 8 , and week 27 . RESULTS Of the 103 participants , overall QOL at week 4 was maintained by the patients in the intervention ( n = 49 ) , whereas QOL at week 4 significantly decreased for patients in the control group ( n = 54 ) . This change reflected a 3-point increase from baseline in the intervention group and a 9-point decrease from baseline in the control group ( P = .009 ) . Intervention participants maintained their QOL , and controls gradually returned to baseline by the end of the 6-month follow-up period . CONCLUSION Although intervention participants maintained and actually improved their QOL during radiation therapy , control participants experienced a significant decrease in their QOL . Thus , a structured multidisciplinary intervention can help maintain or even improve QOL in patients with advanced cancer who are undergoing cancer treatment Prostate cancer patients receiving and rogen ablation therapy experience significant physical and psychological sequelae associated with their disease and treatment . Because physical activity improves physical and psychological well-being , a lifestyle physical activity intervention may help slow or reverse the associated decline in quality of life ( QOL ) . No studies have evaluated an intervention to improve multiple QOL domains in patients receiving and rogen ablation therapy . Active for Life After Cancer is a three-group r and omized controlled trial design ed to evaluate the effectiveness of a lifestyle physical activity intervention ( Lifestyle Program ) in improving QOL . The Lifestyle Program , a 6-month behavioral skills training group , is compared to an Educational Support Program and St and ard Care . The purpose of this paper is to describe the design of the r and omized trial and present baseline data that will characterize the QOL of the sample . Challenges to recruitment for the trial also will be presented and discussed PURPOSE The purpose of this study was to examine the longer-term effects of pedometers and print material s on changes in physical activity ( PA ) and health-related quality of life ( HRQoL ) in breast cancer survivors who participated in a 3-month behavior change intervention . METHODS Breast cancer survivors ( N = 377 ) were r and omly assigned to receive either ( a ) a st and ard public health recommendation for PA ( SR ) , ( b ) previously developed breast cancer-specific PA print material s ( PM ) , ( c ) a step pedometer ( PED ) , or ( d ) a combination of the two ( COM ) . The primary endpoint was self-reported moderate/vigorous PA minutes per week at 6-month follow-up after the initial 3-month intervention period . RESULTS Seventy-one percent ( 266/377 ) of participants completed the 6-month follow-up assessment . According to intention-to-treat linear mixed-model analyses , self-reported moderate to vigorous PA increased by 9 min x wk(-1 ) in the SR group compared with 39 min x wk(-1 ) in the PM group ( mean difference = 30 min x wk(-1 ) ; 95 % CI = -44 to 104 ; P = 0.425 ) , 69 min x wk(-1 ) in the PED group ( mean difference = 60 min x wk(-1 ) ; 95 % CI = -13 to 132 ; P = 0.107 ) , and 56 min x wk(-1 ) in the COM group ( mean difference = 47 min x wk(-1 ) ; 95 % CI = -26 to 119 ; P = 0.210 ) . The same pattern was observed for self-reported , brisk walking . No differences were found for HRQoL or fatigue . CONCLUSION ( S ) Breast cancer-specific PM and PED did not maintain significantly higher PA or HRQoL at 6-month follow-up in breast cancer survivors , but the magnitude of the effect on PA ( 30 - 60 min x wk(-1 ) ) was consistent with the immediate postintervention effect observed at the 3-month postintervention time point . Issues of power result ing from additional loss to follow-up may account for the failure to achieve statistical significance . Additional research with larger sample sizes and more complete follow-up is warranted OBJECTIVES This study aim ed to assess the feasibility of a lifestyle intervention for promoting physical activity ( PA ) and diet quality during adjuvant chemotherapy for ovarian cancer . METHODS Patients were enrolled post-operatively and received PA and nutrition counseling , at every chemotherapy visit for six cycles . Quality of life ( QoL ) was measured with the Functional Assessment of Cancer Therapy ( FACT-G ) , PA with the Leisure Score Index ( LSI ) , dietary intake with 3-day food records , and symptom severity/distress by the Memorial Symptom Assessment Scale ( MSAS ) . Pedometer step count was collected during chemotherapy cycles . RESULTS Recruitment was 73 % with 27 patients enrolled . Mean [ 95 % confidence interval ] change in minutes of PA from cycle # 3 to following cycle # 6 was 61 min [ -3 , 120 ] p=0.063 , and from baseline to after cycle # 6 was 73 min [ -10 , 15 ] ; p=0.082 . Mean change in total fruit and vegetable consumption between baseline and during chemotherapy was 0.56 [ -0.09 , 0.64 ] ; p=0.090 . FACT-G increased from 75.4 at baseline to 77.6 during chemotherapy and 83.9 following chemotherapy ( p=0.001 for change from baseline to post-chemotherapy ) . Mean total MSAS score was 20.6 at baseline , 26.6 at cycle # 3 and decreased to 17.0 following chemotherapy ( p=0.01 comparison of cycle # 3 and following chemotherapy ) . Increased moderate to strenuous PA was correlated with higher physical well-being during chemotherapy ( r=0.48 , p=0.037 ) . CONCLUSIONS Lifestyle counseling during adjuvant chemotherapy for ovarian cancer is feasible and may improve PA and diet quality . R and omized controlled trials examining the effects of lifestyle counseling on quality of life and treatment outcomes in ovarian cancer patients are warranted BACKGROUND Exercise for Health was a pragmatic , r and omised , controlled trial comparing the effect of an eight-month exercise intervention on function , treatment-related side effects and quality of life following breast cancer , compared with usual care . The intervention commenced six weeks post-surgery , and two modes of delivering the same intervention was compared with usual care . The purpose of this paper is to describe the study design , along with outcomes related to recruitment , retention and representativeness , and intervention participation . METHODS Women newly diagnosed with breast cancer and residing in a major metropolitan city of Queensl and , Australia , were eligible to participate . Consenting women were r and omised to a face-to-face-delivered exercise group ( FtF , n = 67 ) , telephone-delivered exercise group ( Tel , n = 67 ) or usual care group ( UC , n = 60 ) and were assessed pre-intervention ( 5-weeks post-surgery ) , mid-intervention ( 6 months post-surgery ) and 10 weeks post-intervention ( 12 months post-surgery ) . Each intervention arm entailed 16 sessions with an Exercise Physiologist . RESULTS Of 318 potentially eligible women , 63 % ( n = 200 ) agreed to participate , with a 12-month retention rate of 93 % . Participants were similar to the Queensl and breast cancer population with respect to disease characteristics , and the r and omisation procedure was mostly successful at attaining group balance , with the few minor imbalances observed unlikely to influence intervention effects given balance in other related characteristics . Median participation was 14 ( min and max : 0 and 16 ) and 13 ( min and max : 3 and 16 ) intervention sessions for the FtF and Tel , respectively , with 68 % of those in Tel and 82 % in FtF participating in at least 75 % of sessions . DISCUSSION Participation in both intervention arms during and following treatment for breast cancer was feasible and acceptable to women . Future work , design ed to inform translation into practice , will evaluate the quality of life , clinical , psychosocial and behavioural outcomes associated with each mode of delivery BACKGROUND Exercise may reduce anxiety and depression associated to the diagnosis and treatment of cancer . AIM To assess the effects of a physical training program during chemotherapy among women with breast cancer . PATIENTS AND METHODS Twenty two women aged 49 + /- 7 years with breast cancer voluntarily agreed to take part in the study , after surgical treatment . Functional capacity ( Karnofsky Performance Status ) , psychological status ( General Health Question naire , GHQ ) and quality of life ( EORTC QLQ-C30 ) were evaluated at baseline and at the end of the study . Before beginning with adjuvant chemotherapy , ten women were r and omly assigned to a program of physical exercise and seven to a control group . The program lasted 18 to 22 weeks , depending on the duration of chemotherapy . RESULTS Five women were lost from follow up . Before starting chemotherapy , 41 % of women were working and all had to kit . At baseline all had a normal Karnofski score and quality of life was compromised . At the end of the study , the intervention group had an improvement of their quality of life , compared to the control group that did not experience significant changes . CONCLUSIONS An exercise training program improves quality of life of women with breast cancer on chemotherapy Little is known about the role of exercise in improving cancer patients ' mood while undergoing chemotherapy . In this phase II study changes in self-reported anxiety and depression and fitness ( VO2max ) are reported in relation to a 6-week , 9 h weekly , multidimensional exercise program . A total of 91 patients receiving chemotherapy , between 18 and 65 years old , completed a Hospital Anxiety and Depression Scale Question naire ( HADS ; response rate 91 % , adherence rate 78 % ) . Anxiety ( p < 0.001 ) and depression ( p = 0.042 ) was significantly reduced . The mean + /- SD of the change was -1.14 + /- 2.91 for anxiety and -0.44 + /- 2.77 for depression . Improvements in fitness were correlated with improvements in depression , chi2(1 ) = 3.966 , p = 0.046 , but not with improvements in anxiety , chi2(1 ) = 0.540 , p = 0.462 . The research suggests that exercise intervention may have a beneficial impact on psychological distress for cancer patients receiving chemotherapy with low to moderate levels of baseline psychomorbidity . The study furthermore indicates that changes in distress may be associated with disease status and levels of physical activity undertaken during disease . The study is followed up by an ongoing r and omized clinical controlled trial to evaluate potential causal effects of exercise intervention on psychological distress and fitness in cancer patients undergoing chemotherapy This study examined the effects of yoga on quality of life ( QOL ) and psychosocial outcomes in women with breast cancer undergoing radiotherapy . Sixty-one women were r and omly assigned to either a yoga or a wait-list group . Yoga classes were taught biweekly during the 6 weeks of radiotherapy . Participants completed measures of QOL , fatigue , benefit finding ( finding meaning in the cancer experience ) , intrusive thoughts , sleep disturbances , depressive symptoms , and anxiety before radiotherapy and then again 1 week , 1 month , and 3 months after the end of radiotherapy . General linear model analyses revealed that compared to the control group , the yoga group reported significantly better general health perception ( p = .005 ) and physical functioning scores ( p = .04 ) 1 week postradiotherapy ; higher levels of intrusive thoughts 1 month postradiotherapy ( p = .01 ) ; and greater benefit finding 3 months postradiotherapy ( p = .01 ) . There were no other group differences in other QOL subscales for fatigue , depression , or sleep scores . Exploratory analyses indicated that intrusive thoughts 1 month after radiotherapy were significantly positively correlated with benefit finding 3 months after radiotherapy ( r = .36 , p = .011 ) . Our results indicated that the yoga program was associated with statistically and clinical ly significant improvements in aspects of QOL The aim of this r and omized controlled trial was to investigate the effect of a 4- to 6-week multimodal program of exercise , relaxation and psychoeducation on physical capacity , functional performance and quality of life ( QOL ) in allogeneic hematopoietic cell transplantation ( allo-HSCT ) adult recipients . In all , 42 patients were r and omized to a supervised multimodal intervention or to a control group receiving usual care . The primary end point was on aerobic capacity measured in VO2 max . Secondary end points were muscle strength , functional performance , physical activity level , QOL , fatigue , psychological well-being and clinical outcomes . The multimodal intervention had a significant effect on physical capacity : VO2 max ( P<0.0001 ) and muscle strength : chest press ( P<0.0001 ) , leg extension ( P=0.0003 ) , right elbow flexor ( P=0.0009 ) , right knee extensor ( P<0.0001 ) and functional performance ( stair test ) ( 0.0008 ) . Moreover , the intervention group showed significantly better results for the severity of diarrhea ( P=0.014 ) and fewer days of total parenteral nutrition ( P=0.019 ) . Longitudinal changes in QOL , fatigue and psychological well-being favored the intervention group , but did not reach statistical significance . Assignment of a multimodal intervention during allo-HSCT did not cause untoward events , sustained aerobic capacity and muscle strength and reduced loss of functional performance during hospitalization PURPOSE Lymphoma patients commonly experience declines in physical functioning and quality of life ( QoL ) that may be reversed with exercise training . PATIENTS AND METHODS We conducted a r and omized controlled trial in Edmonton , Alberta , Canada , between 2005 and 2008 that stratified 122 lymphoma patients by major disease type and current treatment status and r and omly assigned them to usual care ( UC ; n = 62 ) or 12 weeks of supervised aerobic exercise training ( AET ; n = 60 ) . Our primary end point was patient-rated physical functioning assessed by the Trial Outcome Index-Anemia . Secondary end points were overall QoL , psychosocial functioning , cardiovascular fitness , and body composition . RESULTS Follow-up assessment for our primary end point was 96 % ( 117 of 122 ) at postintervention and 90 % ( 110 of 122 ) at 6-month follow-up . Median adherence to the supervised exercise program was 92 % . At postintervention , AET was superior to UC for patient-rated physical functioning ( mean group difference , + 9.0 ; 95 % CI , 2.0 to 16.0 ; P = .012 ) , overall QoL ( P = .021 ) , fatigue ( P = .013 ) , happiness ( P = .004 ) , depression ( P = .005 ) , general health ( P < .001 ) , cardiovascular fitness ( P < .001 ) , and lean body mass ( P = .008 ) . Change in peak cardiovascular fitness mediated the change in patient-rated physical functioning . AET did not interfere with chemotherapy completion rate or treatment response . At 6-month follow-up , AET was still borderline or significantly superior to UC for overall QoL ( P = .054 ) , happiness ( P = .034 ) , and depression ( P = .009 ) without an increased risk of disease recurrence/progression . CONCLUSION AET significantly improved important patient-rated outcomes and objective physical functioning in lymphoma patients without interfering with medical treatments or response . Exercise training to improve cardiovascular fitness should be considered in the management of lymphoma patients The aim of this study was determine the effectiveness of a mindfulness-based stress-reduction ( MBSR ) program on quality of life ( QOL ) and psychosocial outcomes in women with early-stage breast cancer , using a three-arm r and omized controlled clinical trial ( RCT ) . This RCT consisting of 172 women , aged 20–65 with stage I or II breast cancer consisted of the 8-week MBSR , which was compared to a nutrition education program ( NEP ) and usual supportive care ( UC ) . Follow-up was performed at three post-intervention points : 4 months , 1 , and 2 years . St and ardized , vali date d self-administered question naires were adopted to assess psychosocial variables . Statistical analysis included descriptive and regression analyses incorporating both intention-to-treat and post hoc multivariable approaches of the 163 women with complete data at baseline , those who were r and omized to MBSR experienced a significant improvement in the primary measures of QOL and coping outcomes compared to the NEP , UC , or both , including the spirituality subscale of the FACT-B as well as dealing with illness scale increases in active behavioral coping and active cognitive coping . Secondary outcome improvements result ing in significant between-group contrasts favoring the MBSR group at 4 months included meaningfulness , depression , paranoid ideation , hostility , anxiety , unhappiness , and emotional control . Results tended to decline at 12 months and even more at 24 months , though at all times , they were as robust in women with lower expectation of effect as in those with higher expectation . The MBSR intervention appears to benefit psychosocial adjustment in cancer patients , over and above the effects of usual care or a credible control condition . The universality of effects across levels of expectation indicates a potential to utilize this stress reduction approach as complementary therapy in oncologic practice OBJECTIVE To examine the potential impact of elderly age on response to participation in a structured , multidisciplinary quality -of-life ( QOL ) intervention for patients with advanced cancer undergoing radiation therapy . METHODS Study design was a r and omized stratified , two group , controlled clinical trial in the setting of a tertiary care comprehensive cancer center . Subjects with newly diagnosed cancer and an estimated 5-year survival rate of 0%-50 % who required radiation therapy were recruited and r and omly assigned to either an intervention group or a st and ard care group . The intervention consisted of eight 90-min sessions design ed to address the five QOL domains of cognitive , physical , emotional , spiritual , and social functioning . QOL was measured using Spitzer uniscale and linear analogue self- assessment ( LASA ) at baseline and weeks 4 , 8 , and 27 . RESULTS Of the 103 study participants , 33 were geriatric ( 65 years or older ) , of which 16 ( mean age 72.4 years ) received the intervention and 17 ( mean age 71.4 years ) were assigned to the st and ard medical care . The geriatric participants who completed the intervention had higher QOL scores at baseline , at week 4 and at week 8 , compared to the control participants . SIGNIFICANCE OF RESULTS Our results demonstrate that geriatric patients with advanced cancer undergoing radiation therapy will benefit from participation in a structured multidisciplinary QOL intervention . Therefore , geriatric individuals should not be excluded from participating in a cancer QOL intervention , and , in fact , elderly age may be an indicator of strong response to a QOL intervention . Future research should further explore this finding Background and Aims : Major surgery is often followed by fatigue and reduced physical function . We wished to study if postoperative physical training reduced fatigue and improved physical function . Material and Methods : R and omised , placebo-controlled , single-blinded study . Participants were unselected patients ≥ 60 years undergoing elective colorectal surgery without disseminated cancer or inflammatory bowel disease . Group A trained muscular strength and work capacity . Group B performed relaxation exercises and received hot wrappings and massage . Main outcome measures were : fatigue ( visual analogue scale ) , muscular strength , walking speed , physical performance test , and physical function questions ( SF-36 ) . Results : Preoperatively the two groups were similar except that A was more fatigued than B. By postoperative day seven fatigue had increased compared to preoperatively , more in B than A , but by day 30 and 90 there were no significant differences between groups . All indices of physical function decreased postoperative day seven and were at the preoperative level day 90 with no significant differences between groups in change in function . Day seven the change in knee extension strength tended to be lower in B than A but by day 30 changes were similar in both groups . Conclusion : Postoperative training did not improve physical function , but reduced fatigue in hospital Objectives : This study compares the effects of an integrated yoga program with brief supportive therapy on distressful symptoms in breast cancer out patients undergoing adjuvant radiotherapy . Material s and Methods : Eighty-eight stage II and III breast cancer out patients were r and omly assigned to receive yoga ( n = 44 ) or brief supportive therapy ( n = 44 ) prior to their radiotherapy treatment . Intervention consisted of yoga sessions lasting 60 min daily while the control group was imparted supportive therapy once in 10 days during the course of their adjuvant radiotherapy . Assessment s included Rotterdam Symptom Check List and European Organization for Research in the Treatment of Cancer— Quality of Life ( EORTC QoL C30 ) symptom scale . Assessment s were done at baseline and after 6 weeks of radiotherapy treatment . Results : A GLM repeated- measures ANOVA showed a significant decrease in psychological distress ( P = 0.01 ) , fatigue ( P = 0.007 ) , insomnia ( P = 0.001 ) , and appetite loss ( P = 0.002 ) over time in the yoga group as compared to controls . There was significant improvement in the activity level ( P = 0.02 ) in the yoga group as compared to controls . There was a significant positive correlation between physical and psychological distress and fatigue , nausea and vomiting , pain , dyspnea , insomnia , appetite loss , and constipation . There was a significant negative correlation between the activity level and fatigue , nausea and vomiting , pain , dyspnea , insomnia , and appetite loss . Conclusion : The results suggest beneficial effects with yoga intervention in managing cancer- and treatment-related symptoms in breast cancer patients Abstract This study examined the effect of combined Pelvic Floor Muscle Exercises ( PFME ) and support group on quality of life of postprostatectomy patients . Twenty — nine participants learned PFME through biofeedback and were r and omized to the control group ( n = 15 ) and support group ( n = 14 ) . Assessment of quality of life was conducted at baseline and 3-month follow — up . The findings indicated a trend of increased functioning and reduced perception of illness intrusiveness in the support group , compared with the control group . Improved urinary continence was significantly associated with reduced depression and symptom distress over time . The findings suggest that an intervention focusing on urinary continence improves quality of life in these patients PURPOSE Patients with breast cancer on adjuvant chemotherapy can experience weight gain and concurrent losses in muscle mass . Exercise interventions can prevent these changes , but time and travel pose barriers to participation . The Survivor Training for Enhancing Total Health ( STRENGTH ) trial assessed the feasibility and impact of 2 home-based interventions . PATIENTS AND METHODS Ninety premenopausal patients with breast cancer on adjuvant chemotherapy were r and omized to a calcium-rich diet ( CA ) intervention ( attention control ) or to 2 experimental arms : a CA + exercise ( EX ) arm or a CA + EX and high fruit and vegetable , low-fat diet ( FVLF ) arm . Exercise arms included aerobic and strength-training exercises . Body composition , weight status , waist circumference , dietary intake , physical activity , quality of life , anxiety , depression , serum lipids , sex hormone binding globulin , insulin , proinsulin , C-reactive protein , interleukin-1B , and tumor-necrosis factor receptor-II were measured at baseline and at 6-month follow-up . RESULTS Accrual targets were achieved and modest attrition was observed ( 8.8 % ) . Self-reports suggest increased calcium intakes in all arms , and higher fruit and vegetable and lower fat intake in the CA + EX + FVLF arm ; no differences in physical activity were observed . While measures of adiposity were generally lower in the CA + EX + FVLF arm , the only significant difference was in percentage of body fat ( arms and legs ) ; change in scores ( mean + /- st and ard deviation ) were + 0.7 % + /- 2.3 % ( CA ) ; + 1.2 % + /- 2.7 % ( CA + EX ) ; and + 0.1 % + /- 2 % ( CA + EX + FVLF ; P = .047 ) . Lean body mass was largely preserved , even in the control arm ( net gain of 452 g + /- 2395 g ) . No differences were observed in other endpoints . CONCLUSION Diet and exercise interventions can prevent weight gain and adverse body composition changes , but more research is needed to determine optimally effective interventions that can be implemented during active treatment and that promote adherence PURPOSE This study examines the impact of yoga , including physical poses , breathing , and meditation exercises , on quality of life ( QOL ) , fatigue , distressed mood , and spiritual well-being among a multiethnic sample of breast cancer patients . PATIENTS AND METHODS One hundred twenty-eight patients ( 42 % African American , 31 % Hispanic ) recruited from an urban cancer center were r and omly assigned ( 2:1 ratio ) to a 12-week yoga intervention ( n = 84 ) or a 12-week waitlist control group ( n = 44 ) . Changes in QOL ( eg , Functional Assessment of Cancer Therapy ) from before r and om assignment ( T1 ) to the 3-month follow-up ( T3 ) were examined ; predictors of adherence were also assessed . Nearly half of all patients were receiving medical treatment . RESULTS Regression analyses indicated that the control group had a greater decrease in social well-being compared with the intervention group after controlling for baseline social well-being and covariates ( P < .0001 ) . Secondary analyses of 71 patients not receiving chemotherapy during the intervention period indicated favorable outcomes for the intervention group compared with the control group in overall QOL ( P < .008 ) , emotional well-being ( P < .015 ) , social well-being ( P < .004 ) , spiritual well-being ( P < .009 ) , and distressed mood ( P < .031 ) . Sixty-nine percent of intervention participants attended classes ( mean number of classes attended by active class participants = 7.00 + /- 3.80 ) , with lower adherence associated with increased fatigue ( P < .001 ) , radiotherapy ( P < .0001 ) , younger age ( P < .008 ) , and no antiestrogen therapy ( P < .02 ) . CONCLUSION Despite limited adherence , this intent-to-treat analysis suggests that yoga is associated with beneficial effects on social functioning among a medically diverse sample of breast cancer survivors . Among patients not receiving chemotherapy , yoga appears to enhance emotional well-being and mood and may serve to buffer deterioration in both overall and specific domains of QOL Background : Fatigue has a significant impact on the quality of life ( QOL ) of cancer patients . Recent research has suggested that physical activity can reduce fatigue in patients receiving active cancer treatment . In this project , we examined the impact that participation in a r and omized controlled trial of a multidisciplinary intervention design ed to impact overall QOL had on fatigue for advanced cancer patients actively receiving treatment . Methods : Patients with newly diagnosed cancer were r and omly assigned to an 8-session structured multidisciplinary intervention or a st and ard-care arm at the beginning of their course of radiotherapy ( RT ) design ed to impact QOL . Ninety-minute sessions were led by either a psychiatrist or psychologist , collaborating with a nurse , physical therapist , chaplain , or social worker , depending on the session 's theme . The fatigue assessment s used in this trial included the Linear Analogue Self Assessment ( LASA ) , the Profile of Mood States ( POMS ) , Spielberger 's State-Trait Anxiety Inventory ( STAI ) , and the Symptom Distress Scale ( SDS ) . Results : There were 115 participants enrolled and the 2 r and omization arms were well balanced in terms of baseline characteristics and treatment received except for increased commuting distance for the patients in the intervention arm ( P = 0.042 ) . Most of scores indicated less fatigue ( higher score ) in the st and ard treatment group , but there were no statistically significant differences found at baseline and weeks 4 , 8 , and 27 except for SDS at week 8 ( P = 0.018 ) with less patients reporting significant fatigue in the st and ard treatment arm . For the entire participant population , fatigue levels initially worsened with radiotherapy , stabilized at week 8 , and returned to baseline by week 27 . Disease site , chemotherapy use , and radiotherapy dose did not have a significant impact on fatigue levels . Conclusions : Radiotherapy initially caused a worsening of fatigue but with time fatigue levels returned to baseline . Clinical ly , this structured multidisciplinary intervention had no impact on fatigue , and there was the suggestion the multiple sessions may have contributed to worse fatigue during active cancer treatment PURPOSE / OBJECTIVES To test the effects of foot reflexology on anxiety and pain in patients with breast and lung cancer . DESIGN Quasi-experimental , pre/post , crossover . SETTING A medical/oncology unit in a 314-bed hospital in the southeastern United States . SAMPLE Twenty-three in patients with breast or lung cancer . The majority of the sample were female , Caucasian , and 65 years or older ; had 12 or fewer years of education and an annual income of $ 20,000 or more ; and were receiving regularly scheduled opioids and adjuvant medications on the control and intervention day . METHODS Procedures included an intervention condition ( foot reflexology to both feet for 30 minutes total by a certified reflexologist ) and a control condition for each patient ( with at least a two-day break ) . No changes were made in patients ' regular schedule or medications . MAIN RESEARCH VARIABLES Anxiety and pain . FINDINGS Following the foot reflexology intervention , patients with breast and lung cancer experienced a significant decrease in anxiety . One of three pain measures showed that patients with breast cancer experienced a significant decrease in pain . CONCLUSIONS The significant decrease in anxiety observed in this sample of patients with breast and lung cancer following foot reflexology suggests that this may be a self-care approach to decrease anxiety in this patient population . IMPLICATION S FOR NURSING PRACTICE Professionals and lay people can be taught reflexology . Foot reflexology is an avenue for human touch , can be performed anywhere , requires no special equipment , is noninvasive , and does not interfere with patients ' privacy OBJECTIVE This study sought to investigate the effects of yoga on the quality of life in patients with breast cancer . DESIGN Twenty patients between 30 and 50 years of age presently under treatment for breast cancer were included in the study . The physical characteristics of the patients were recorded and general physiotherapy assessment s performed . Eight sessions of a yoga program including warming and breathing exercises , asanas , relaxation in supine position , and meditation were applied to participants . MAIN OUTCOME MEASURES The pre- and post-yoga quality of life assessment s for the patients were conducted using the Nottingham Health Profile ( NHP ) . Patients ' stress levels were assessed using the STAI-I and STAI-II anxiety inventory . Their satisfaction levels about the yoga program was evaluated using the visual analog scale ( VAS ) . RESULTS It was found that patients ' quality of life scores after the yoga program were better than scores obtained before the yoga program ( p < 0.05 ) . After sessions , there was a statistically significant decrease in their STAI-I ( measuring the reactions of anxiety ) scores and STAI-II ( measuring the permanence of anxiety ) scores ( p < 0.05 ) . It was found out that the satisfaction score concerning the yoga program was considerably increased after the yoga program ( p < 0.05 ) . CONCLUSIONS It can be concluded that yoga is valuable in helping to achieve relaxation and diminish stress , helps cancer patients perform daily and routine activities , and increases the quality of life in cancer patients . This result was positively reflected in patients satisfaction with the yoga program OBJECTIVES Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen ( PSA ) levels , inhibition of LNCaP cell growth , and fewer prostate cancer-related clinical events at the end of 1 year compared with controls . The aim of this study was to examine the clinical events in this trial during a 2-year period . METHODS The Prostate Cancer Lifestyle Trial was a 1-year r and omized controlled clinical trial of 93 patients with early-stage prostate cancer ( Gleason score < 7 , PSA 4 - 10 ng/mL ) undergoing active surveillance . The patients in the experimental arm were encouraged to adopt a low-fat , plant-based diet , to exercise and practice stress management , and to attend group support sessions . The control patients received the usual care . RESULTS By 2 years of follow-up , 13 of 49 ( 27 % ) control patients and 2 of 43 ( 5 % ) experimental patients had undergone conventional prostate cancer treatment ( radical prostatectomy , radiotherapy , or and rogen deprivation , P < .05 ) . No differences were found between the groups in other clinical events ( eg , cardiac ) , and no deaths occurred . Three of the treated control patients but none of the treated experimental patients had a PSA level of > or=10 ng/mL , and 1 treated control patient but no treated experimental patients had a PSA velocity of > 2 ng/mL/y before treatment . No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years . CONCLUSIONS Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle BACKGROUND The purpose of this study was to examine the effects of physical therapy intervention in children with acute lymphoblastic leukemia ( ALL ) . PROCEDURE Twenty-eight children aged 4 - 15 years were r and omly assigned to an intervention or control group . The intervention group received five sessions of physical therapy and was instructed to perform an individualized home exercise program consisting of ankle dorsiflexion stretching , lower extremity strengthening , and aerobic exercise . RESULTS After 4 months children who received physical therapy intervention had significantly improved ankle dorsiflexion active range of motion and knee extension strength ( P < 0.01 ) . Differences were not found between the two groups for any of the other dependent variables . CONCLUSIONS Physical therapy intervention for children with ALL receiving maintenance chemotherapy improved two body functions important for normal gait . Physical therapy programs initiated earlier in treatment and with greater emphasis on endurance activities may also improve stamina and quality of life ( QOL ) The effect of a 10-week aerobic interval-training cycle ergometer protocol on the functional capacity ( VO2Lmax ) of 45 women receiving chemotherapy for treatment of Stage II breast cancer was studied . Subjects were stratified by baseline functional capacity ( ± 1 MET ) and r and omized to experimental ( EX ) , placebo ( PL ) , and control ( CO ) groups . EX subjects completed a 10-week , 3 times/week exercise training program ; PL subjects participated in 10 weeks of nonaerobic stretching and flexibility exercises ; the CO group maintained normal activities . The EX group showed significant , p < .05 , improvement on pre- to posttest VO2Lmax as well as workload and test time compared to the PL and CO groups . The interval-training exercise intervention was effective in improving the functional capacity of Stage II breast cancer patients on adjuvant chemotherapy Physical exercise has been shown to enhance quality of life ( QOL ) in cancer survivors using pretest-posttest design s and compared to usual care ( i.e. no intervention ) . In the present study , we conducted a r and omized controlled trial to determine if exercise could improve QOL in cancer survivors beyond the known benefits of group psychotherapy ( GP ) . We matched 22 GP classes ( N=108 ) on content and then r and omly assigned 11 ( n=48 ) to GP alone and 11 ( n=60 ) to GP plus home-based , moderate-intensity exercise ( GP+EX ) . Participants completed a physical fitness test and QOL measures ( e.g. Functional Assessment of Cancer Therapy scales ) at the beginning and end of GP classes ( about 10 weeks ) . We had excellent recruitment ( 81 % ) , retention ( 89 % ) , and adherence ( 84 % ) rates and a modest contamination ( 22 % ) rate . Using intention-to-treat repeated measures analyses of variance , we found significant Time by Condition interactions for functional well-being , fatigue , and sum of skinfolds . We also found borderline significant interactions for physical well-being , satisfaction with life , and flexibility . All interactions favored the GP+EX condition . We conclude that a home-based , moderate intensity exercise program may im-prove QOL in cancer survivors beyond the benefits of GP , particularly in relation to physical and functional well-being Evidence -based exercise and relaxation recommendations for people with breast cancer-related lymphedema ( BCRL ) are needed . We report a r and omized controlled study of one program , design ed to achieve synergistic improvements in physical and emotional BCRL symptoms . People in the treatment group received an exercise and relaxation program , The Breast Cancer Recovery Program ( N=16 ) . The control participants ( N=16 ) continued with health professionals ' recommendations . Participants were tested at entry , 2.5 weeks , 5 weeks , and 3 months . Treatment group participants , compared with control participants , demonstrated significant treatment effects for improved bioimpedance z , arm flexibility , quality of life , mood at 3 months , and weight loss . Adherence was high for this safe and effective program , which improved lymphedema physical and emotional symptoms Fatigue is a common and often severe problem in cancer patients undergoing chemotherapy . The authors postulated that physical activity training can reduce the intensity of fatigue in this group of patients Fatigue is the most prevalent and debilitating symptom experienced by breast cancer patients receiving adjuvant chemotherapy or radiation therapy and few evidence -based treatments are available to manage this distressing side-effect . The purpose of this multi-institutional r and omized controlled trial was to determine the effects of exercise on fatigue levels during treatment for breast cancer . Sedentary women ( N=119 ) with Stage 0-III breast cancer receiving outpatient adjuvant chemotherapy or radiation therapy were r and omized to a home-based moderate-intensity walking exercise program or to usual care for the duration of their cancer treatment . Of participants r and omized to exercise , 72 % adhered to the exercise prescription ; 61 % of the usual care group adhered . The intention-to-treat analysis revealed no group differences in part because of a dilution of treatment effect as 39 % of the usual care group exercised and 28 % of the exercise group did not . When exercise participation was considered using the data analysis method of instrumental variables with principal stratification , a clinical ly important and statistically significant ( p=0.03 ) effect of exercise on pretest-to-posttest change in fatigue levels was demonstrated . Adherence to a home-based moderate-intensity walking exercise program may effectively mitigate the high levels of fatigue prevalent during cancer treatment We have compared different modes of rehabilitation after breast cancer surgery on a population of 257 patients treated at the Institute Gustave-Roussy in 1990 and 1991 . The mode of rehabilitation was r and omized according to a 2 X 2 design , between physiotherapy alone , shoulder movement alone , both or neither . Treatment began the day after breast surgery and continued for 7 days . Afterwards , all patients had physiotherapy and shoulder movements until the end of hospitalisation . Treatment efficacy was evaluated at day 7 by the volume of lymph drained , and by degree of shoulder movement . The volume of lymph collected by day 7 was reduced in the physiotherapy groups , but was not modified in the groups with shoulder movement . The degree of motion was larger in the group who had had both physiotherapy and shoulder movement . The frequencies of complications at day 7 and later were similar in the four treatment groups , but locoregional pain was less frequent in the two groups with shoulder movement than in the two other groups . An early treatment including both physiotherapy and shoulder movement seems advisable The aim of this study was to compare a conventional oncological inpatient rehabilitation programme with an inpatient step-by-step rehabilitation programme with regard to quality of life in breast cancer patients . Patients and Methods : Women with the diagnosis of breast cancer were r and omly assigned to either the step-by-step programme ( group A : 3-week rehabilitation plus 4 and 8 months later a 1-week sojourn each time ) or the conventional rehabilitation programme ( group B : 4- week stay and no further interventions afterwards ) . Quality of life was assessed with the QLQ-C30 of the EORTC at t0 ( beginning of the study ) , t1 ( end of 3- or 4-week stay ) and t2 ( 12 months after t0 , end of study ) . Results : Between t0 and t1 , a tendency ( 0.1 > p = 0.05 ) could be shown in group B towards better improvement in global quality of life and emotional function . In the subgroup of patients that had impaired functions of quality of life at t0 , superiority in group B reached significance ( p < 0.05 ) for emotional and cognitive function at t1 . Between t1 and t2 , cognitive function improved further in group A , but diminished in group B. For the subgroup of patients with impaired cognitive function at t0 , this difference between both groups became significant ( p = 0.0098 ) . Conclusions : Although not generally superior to conventional inpatient rehabilitation programmes , the analysed stepby- step rehabilitation provided marked benefits for patients with cognitive impairments Given observational findings that physical activity reduces breast cancer risk , improves survival , and improves quality of life in breast cancer survivors , a need has been identified for r and omized controlled trials that testthe efficacy of exercise on biological mechanisms associated with breast cancer survival . The primary aims of the Yale Exercise and Survivorship Study were to 1 ) determine the feasibility of recruiting breast cancer survivors into a r and omized controlled trial of the effects of exercise on biological markers and /or mechanisms associated with survival , 2 ) compare the effectiveness of various recruitment strategies on accrual rates and baseline characteristics , and 3 ) report adherence to the exercise trial Before , during , and after allogeneic hematopoietic stem cell transplantation ( allo-HSCT ) , patients experience considerable physical and psychologic distress . Besides graft-versus-host disease and infections , reduced physical performance and high levels of fatigue affect patients ' quality of life . This multicenter r and omized controlled trial examined the effects of a partly self-administered exercise intervention before , during , and after allo-HSCT on these side effects . After r and omization to an exercise and a social contact control group 105 patients trained in a home-based setting before hospital admission , during inpatient treatment and a 6- to 8-week period after discharge . Fatigue , physical performance , quality of life , and physical/psychologic distress were measured by st and ardized instruments at baseline , admission to , and discharge from hospital and 6 to 8 weeks after discharge . The exercise group showed significantly improvement in fatigue scores ( up to 15 % improvement in exercise group vs up to 28 % deterioration in control ; P<.01-.03 ) , physical fitness/functioning ( P=.02-.03 ) and global distress ( P=.03 ) . All effects were at least detectable at one assessment time point after hospitalization or repeatedly . Physical fitness correlated significantly with all reported symptoms/variables . In conclusion , this partly supervised exercise intervention is beneficial for patients undergoing allo-HSCT . Because of low personnel requirements , it might be valuable to integrate such a program into st and ard medical care PURPOSE Radiotherapy for prostate cancer ( PCa ) may cause unfavorable changes in fatigue , quality of life ( QOL ) , and physical fitness . We report results from the Prostate Cancer Radiotherapy and Exercise Versus Normal Treatment study examining the effects of 24 weeks of resistance or aerobic training versus usual care on fatigue , QOL , physical fitness , body composition , prostate-specific antigen , testosterone , hemoglobin , and lipid levels in men with PCa receiving radiotherapy . PATIENTS AND METHODS Between 2003 and 2006 , we conducted a r and omized controlled trial in Ottawa , Canada , where 121 PCa patients initiating radiotherapy with or without and rogen deprivation therapy were r and omly assigned to usual care ( n = 41 ) , resistance ( n = 40 ) , or aerobic exercise ( n = 40 ) for 24 weeks . Our primary end point was fatigue assessed by the Functional Assessment of Cancer Therapy-Fatigue scale . RESULTS The follow-up assessment rate for our primary end point of fatigue was 92.6 % . Median adherence to prescribed exercise was 85.5 % . Mixed-model repeated measures analyses indicated both resistance ( P = .010 ) and aerobic exercise ( P = .004 ) mitigated fatigue over the short term . Resistance exercise also produced longer-term improvements ( P = .002 ) . Compared with usual care , resistance training improved QOL ( P = .015 ) , aerobic fitness ( P = .041 ) , upper- ( P < .001 ) and lower-body ( P < .001 ) strength , and triglycerides ( P = .036 ) , while preventing an increase in body fat ( P = .049 ) . Aerobic training also improved fitness ( P = .052 ) . One serious adverse event occurred in the group that performed aerobic exercise . CONCLUSION In the short term , both resistance and aerobic exercise mitigated fatigue in men with PCa receiving radiotherapy . Resistance exercise generated longer-term improvements and additional benefits for QOL , strength , triglycerides , and body fat Abstract Weight gain is common during and following cancer treatment and contributes to many adverse health consequences and increased risk of recurrence for cancer survivors . The purpose of this longitudinal r and omized controlled trial was to compare differences in weight change and body composition among newly diagnosed cancer survivors receiving chemotherapy who were r and omly assigned to usual care control , aerobic exercise , or resistance exercise interventions . It was hypothesized that cancer survivors become more sedentary during treatment , leading to positive energy balance that in turn worsens body composition . One hundred one subjects completed the 12-month study . Data collected included body composition ( body weight and dual energy x-ray absorptiometry scan ) , aerobic capacity ( 12-minute walk ) , and muscle strength ( 1 repetition maximum ) . Aerobic exercisers were found to have significant improvements in body composition , aerobic capacity , and muscle strength . Resistance exercisers also benefitted , but were less compliant with the intervention over time . Thus , exercise during and following cancer treatment is an important intervention to maintain and perhaps improve body composition of cancer survivors , which may improve survival , reduce comorbidities , and improve quality of life Background Many patients suffer from severe shoulder complaints after breast cancer surgery and axillary lymph node dissection . Physiotherapy has been clinical ly observed to improve treatment of these patients . However , it is not a st and ard treatment regime . The purpose of this study is to investigate the efficacy of physiotherapy treatment of shoulder function , pain and quality of life in patients who have undergone breast cancer surgery and axillary lymph node dissection . Methods Thirty patients following breast cancer surgery and axillary lymph node dissection were included in a r and omised controlled study . Assessment s were made at baseline and after three and six months . The treatment group received st and ardised physiotherapy treatment of advice and exercises for the arm and shoulder for three months ; the control group received a leaflet containing advice and exercises . If necessary soft tissue massage to the surgical scar was applied . Primary outcome variables were amount of pain in the shoulder/arm recorded on the Visual Analogue Scale , and shoulder mobility ( flexion , abduction ) measured using a digital inclinometer under st and ardized conditions . Secondary outcome measures were shoulder disabilities during daily activities , edema , grip strength of both h and s and quality of life . The research er was blinded to treatment allocation . Results All thirty patients completed the trial . After three and six months the treatment group showed a significant improvement in shoulder mobility and had significantly less pain than the control group . Quality of life improved significantly , however , h and grip strength and arm volume did not alter significantly . Conclusion Physiotherapy reduces pain and improves shoulder function and quality of life following axillary dissection after breast cancer . Trial registration IS RCT |
10,506 | 23,340,544 | This investigation showed that nucleoplasty constitutes an effective , minimally invasive treatment option for patients with symptomatic contained disc herniations . | In 2010 Gerges et al ( 1 ) published a meta- analysis on the topic of nucleoplasty .
Our study aim ed to present the current data available from RCTs on the application of nucleoplasty . | Purpose To evaluate changes in nucleus pulposus volume as a potential parameter for the effects of disc decompression . Methods Fifty-two discs ( T8 to L1 ) were extracted from 26 pigs and separated into thoracic ( T8 to T11 ) and thoracolumbar discs ( T12 to L1 ) . The discs were imaged using 7.1 Tesla ultrahigh-field magnetic resonance imaging ( MRI ) with acquisition of axial T2-weighted turbo spin-echo sequences for determination of baseline and postinterventional nucleus pulposus volumes . Volumes were calculated using OsiriX ® ( http://www.osirix-viewer.com ) . After r and omization , one group was treated with nucleoplasty , while the placebo group was treated with an identical procedure but without coblation current . The readers analyzing the MR images were blinded to the kind of procedure performed . Baseline and postinterventional volumes were compared between the nucleoplasty and placebo group . Results Average preinterventional nucleus volume was 0.799 ( SD : 0.212 ) ml . Postinterventional volume reduction in the nucleoplasty group was significant at 0.052 ( SD : 0.035 ) ml or 6.30 % ( p<0.0001 ) ( thoracic discs ) and 0.082 ( SD : 0.042 ) ml or 7.25 % ( p = 0.0078 ) ( thoracolumbar discs ) . Nucleoplasty achieved volume reductions of 0.114 ( SD : 0.054 ) ml or 14.72 % ( thoracic ) and 0.093 ( SD : 0.081 ) ml or 11.61 % ( thoracolumbar ) compared with the placebo group . Conclusions Nucleoplasty significantly reduces thoracic and thoracolumbar nucleus pulposus volumes in porcine discs In this study two strategies in the treatment of Mechanical Spinal Discogenic Pain have been compared : Disc Coablation and Epidural Injection of Steroids . In 2003 50 patients treated with one or two epidural injections have been selected " ad r and om " and 50 patients treated with disc coablation . Comparison of the data indicated an improvement of average VAS when relaxed for both groups ( p < 0.01 ) , while after slight-moderate strain , this value was significant only after coablation ( p < 0.001 ) . Finally , average VAS was clearly lower ( p < 0.01 ) after coablation as compared to epidural injections Background Cervical disc nucleoplasty is a significant and clinical ly demonstrated innovation in percutaneous disc decompression in case of non-herniated disc protrusions or prolpase . It allows a percutaneous decompression via a 19-gauge needle under utilization of the Coblation ® technique and under C-arm control . Until now the patients suffering of a cervicobrachialgia in cause of a disc prolapse had only the therapeutical solution between conservative treatment and monosegmental spondylodesis or disc prosthesis of the mentioned motion segment . Methods We wanted to demonstrate a new and practicable anatomical pathway for reaching the cervical disc prolapse comparable to the technique for discography of the cervical spine . The introducer needle is advanced into the disc under fluoroscopic guidance using a st and ard anterior – lateral approach . The controller delivers radiofrequency energy to quickly ablate tissue at temperatures between 50 ° and 60 ° C . The decompression will be done in ablation mode by rotating the device through 180 ° for 5 s in the posterior , medial and ventral third of the cervical disc . After failed conservative treatment over an average time period of 3 months we treated 26 patients with a contained herniated prolapse or protrusion with radicular arm pain by percutaneous decompression under utilization of the Coblation ® technique with a controlled energy plasma-mediated field . A r and omized control group of 30 patients was treated alone conservatively with medical and physical therapy in the same period . Results The average preoperative VAS was 8.8 . With a follow-up time of 2-years we found an average pain reduction with the visual pain score ( VAS ) of 2.3 who had a further check-up . The VAS was checked 24 h , 1 week , 3 , 6 , 12 and 24 months postoperatively . No complications with this method were seen . Comparable to the surgically treated group the conservative patients have had a VAS of 8.4 . Under using conservative treatment with physical therapy , physiotherapy , analgetics and perineural injections we have had a diminution of the VAS to 5.1 after 2 years . Conclusion The percutaneous decompression of the cervical disc protrusion with the Perc DC ® —Spine W and by using the Coblation mode is a quick and safe procedure . Furthermore , one may state a persistent pain relief in the follow-up time up to 2 years after the percutaneous decompression of the disc Prospect i ve case series studies have shown that plasma disc decompression ( PDD ) using the COBLATION SpineW and device ( ArthroCare Corporation , Austin , TX ) is effective for decompressing the disc nucleus in symptomatic contained cervical disc herniations . This prospect i ve , r and omized controlled clinical trial was conducted to evaluate the clinical outcomes of percutaneous PDD as compared to conservative care ( CC ) through 1 year . Patients ( n = 115 ) had neck/arm pain > 50 on the visual analog scale ( VAS ) pain scale and had failed at least 30 days of failed CC . Patients were r and omly assigned to receive either PDD ( n = 62 ) or CC ( n = 58 ) . Clinical outcome was determined by VAS pain score , neck disability index ( NDI ) score , and SF-36 health survey , collected at 6 weeks , 3 months , 6 months , and 1 year . The PDD group had significantly lower VAS pain scores at all follow-up time points ( PDD vs. CC : 6 weeks , −46.87 ± 2.71 vs. −15.26 ± 1.97 ; 3 months , −53.16 ± 2.74 vs. −30.45 ± 2.59 ; 6 months , −56.22 ± 2.63 vs. −40.26 ± 2.56 ; 1 year , −65.73 ± 2.24 vs. −36.45 ± 2.86 ; GEE , P < 0.0001 ) . PDD patients also had significant NDI score improvement over baseline when compared to CC patients at the 6 weeks ( PDD vs. CC : −9.15 ± 1.06 vs. −4.61 ± 0.53 , P < 0.0001 ) and 1 year ( PDD vs. CC : −16.70 ± 0.29 vs. −12.40 ± 1.26 , P = 0.005 ) follow-ups . PDD patients showed statistically significant improvement over baseline in SF-36 physical component summary scores when compared to CC patients at 6 weeks and 1 year ( PDD vs. CC : 8.86 + 8.04 vs. 4.24 ± 3.79 , P = 0.0004 ; 17.64 ± 10.37 vs. 10.50 ± 10.6 , P = 0.0003 , respectively ) . In patients who had neck/arm pain due to a contained cervical disc herniation , PDD was associated with significantly better clinical outcomes than a CC regimen . At 1 year , CC patients appeared to suffer a “ relapse , showing signs of decline in most measurements , whereas PDD patients showed continued stable improvement Conventional open cervical discectomy , with or without bony fusion , in common neurosurgical knowledge is considered the st and ard treatment for cervical disc herniation . Percutaneous procedures are minimally invasive and offer decreased morbidity , require no bone graft and promise shorter recuperation time . Nevertheless , c and i date s for a percutaneous procedure as inclusion criteria must complain of symptoms related to contained herniated disc or focal protrusion . It does not substitute conventional open procedures required for extruded discs . We used the coblation technology for nucleoplasty of the cervical intervertebral discs . Early and long-term effects and /or complications observed with this procedure have not been reported yet . Fifty consecutive patients presenting with contained herniated cervical disc or focal protrusion causing compression of the cervical roots or cervical pain underwent a nucleoplasty procedure on the pathological disc . A r and omized control group of twenty patients was treated conservatively with medical and physical therapy in the same period and completed the identical follow-up form . In the nucleoplasty group results were complete resolution of symptoms in 80 % of cases , only 10 % referred some residual cervical or radicular pain and are still under follow-up with a wait- and -see prospect i ve . Patients who did not have a clinical resolution were treated with alternative traditional methods ( 10 % ) . Despite the relative low cases number and the limited follow-up the encouraging results induce us to utilize this technique in well-selected cases OBJECT Patients with radiculopathy , with or without back pain , often do not respond to conservative care and may be considered for epidural steroid injection therapy or a disc decompression procedure . Plasma disc decompression ( PDD ) using the Coblation SpineW and device is a percutaneous , minimally invasive interventional procedure . The purpose of this study was to evaluate clinical outcomes with PDD as compared with st and ard care using fluoroscopy-guided transforaminal epidural steroid injection ( TFESI ) over the course of 2 years . METHODS This was a multicenter r and omized controlled clinical study . Ninety patients ( 18 - 66 years old ) who had sciatica ( visual analog scale score > or = 50 ) associated with a single-level lumbar contained disc herniation were enrolled . In all cases , their condition was refractory to initial conservative care and 1 epidural steroid injection had failed . Participants were r and omly assigned to receive either PDD ( 46 patients ) or TFESI ( 44 patients , up to 2 injections ) . RESULTS The patients in the PDD Group had significantly greater reduction in leg pain scores and significantly improved Oswestry Disability Index and 36-Item Short Form Health Survey ( [ SF-36 ] , physical function , bodily pain , social function , and physical components summary ) scores than those in the TFESI Group . During the 2-year follow-up , 25 ( 56 % ) of the patients in the PDD Group and 11 ( 28 % ) of those in the TFESI Group remained free from having a secondary procedure following the study procedure ( log-rank p = 0.02 ) . A significantly higher percentage of patients in the PDD Group showed minimum clinical ly important change in scores for leg and back pain and SF-36 scores that exceeded literature -based minimum clinical ly important changes . Procedure-related adverse events , including injection site pain , increased leg or back pain , weakness , and lightheadedness , were observed in 5 patients in the PDD Group ( 7 events ) and 7 in the TFESI Group ( 14 events ) . CONCLUSIONS In study patients who had radicular pain associated with a contained lumbar disc herniation , those patients treated with PDD had significantly reduced pain and better quality of life scores than those treated using repeated TFESI . In addition , significantly more PDD patients than TFESI patients avoided having to undergo a secondary procedure during the 2-year study follow-up |
10,507 | 30,671,941 | Of all TMS and tDCS modalities , rTMS is most promising with moderate evidence that it contributes to reductions in headache frequency , duration , intensity , abortive medication use , depression , and functional impairment .
However , only few studies reported changes greater than sham treatment . | BACKGROUND Headache is among the most prevalent causes of disability worldwide .
Non-pharmacologic interventions , including neuromodulation therapies , have been proposed in patients who are treatment resistant or intolerant to medications .
OBJECTIVE To perform a systematic review on the use of transcranial magnetic stimulation ( TMS ) and transcranial direct current stimulation ( tDCS ) for the treatment of specific headache disorders ( ie , migraine , tension , cluster , posttraumatic ) . | Background Preventive pharmacotherapy for migraine is not satisfactory because of the low efficacy/tolerability ratio of many available drugs . Novel and more efficient preventive strategies are therefore warranted . Abnormal excitability of cortical areas appears to play a pivotal role in migraine pathophysiology . Transcranial direct current stimulation ( tDCS ) is a non-invasive and safe technique that is able to durably modulate the activity of the underlying cerebral cortex , and is being tested in various medical indications . The results of small open studies using tDCS in migraine prophylaxis are conflicting , possibly because the optimal stimulation setting s and the brain targets were not well chosen . We have previously shown that the cerebral cortex , especially the visual cortex , is hyperresponsive in migraine patients between attacks and provided evidence from evoked potential studies that this is due to a decreased cortical preactivation level . If one accepts this concept , anodal tDCS over the visual cortex may have therapeutic potentials in migraine prevention , as it is able to increase neuronal firing . Objective To study the effects of anodal tDCS on visual cortex activity in healthy volunteers ( HV ) and episodic migraine without aura patients ( MoA ) , and its potentials for migraine prevention . Methods We recorded pattern-reversal visual evoked potentials ( VEP ) before and after a 15-min session of anodal tDCS over the visual cortex in 11 HV and 13 MoA interictally . Then 10 MoA patients reporting at least 4 attacks/month subsequently participated in a therapeutic study , and received 2 similar sessions of tDCS per week for 8 weeks as migraine preventive therapy . Results In HV as well as in MoA , anodal tDCS transiently increased habituation of the VEP N1P1 component . VEP amplitudes were not modified by tDCS . Preventive treatment with anodal tDCS turned out to be beneficial in MoA : migraine attack frequency , migraine days , attack duration and acute medication intake significantly decreased during the treatment period compared to pre-treatment baseline ( all p < 0.05 ) , and this benefit persisted on average 4.8 weeks after the end of tDCS . Conclusions Anodal tDCS over the visual cortex is thus able to increase habituation to repetitive visual stimuli in healthy volunteers and in episodic migraineurs , who on average lack habituation interictally . Moreover , 2 weekly sessions of anodal tDCS had a significant preventive anti- migraine effect , proofing the concept that the low preactivation level of the visual cortex in migraine patients can be corrected by an activating neurostimulation . The therapeutic results indicate that a larger sham-controlled trial using the same tDCS protocol is worthwhile A recent fMRI study showed that dorsolateral prefrontal cortex ( DLPFC ) exerts an inhibitory control on pain pathways in humans . We investigated whether high-frequency rTMS over left DLPFC could ameliorate chronic migraine . Treatment consisted of 12 rTMS sessions , delivered in alternate days over left DLPFC . Sham rTMS was used as placebo . Eleven patients were r and omly assigned to the rTMS ( n=6 ) or to the placebo ( n=5 ) treatment . Measures of attack frequency , headache index , number of abortive medications ( outcome measures ) were recorded in the month before , during and in the month after treatment . Subjects treated by rTMS showed a significant reduction of the outcome measures during and in the month after the treatment as compared to the month before treatment . No significant differences in the outcome measures were observed in the placebo group . High-frequency rTMS over left DLPFC was able to ameliorate chronic migraine . This is in agreement with the suggested role of DLPFC in pain control We report the efficacy of three versus single session of 10 Hz repetitive transcranial magnetic stimulation ( rTMS ) in chronic migraine ( CM ) and chronic tension-type headache ( CTTH ) . Ninety-eight patients with CM or CTTH were included and their headache frequency , severity , functional disability and number of abortive medications were noted . Fifty-two patients were r and omly assigned to group I ( three true sessions ) and 46 to group II ( one true and two sham rTMS sessions ) treatment . 10 Hz rTMS comprising 600 pulses was delivered in 412.4 s on the left frontal cortex . Outcomes were noted at 1 , 2 and 3 months . The primary outcome was 50 % reduction in headache frequency , and secondary outcomes were improvement in severity , functional disability , abortive drugs and side effects . The baseline headache characteristics were similar between the two groups . Follow up at different time points revealed significant improvement in headache frequency , severity , functional disability and number of abortive drugs compared to baseline in both group I and group II patients , although these parameters were not different between the two groups . In group I , 31 ( 79.4 % ) had reduction of headache frequency and 29 ( 74.4 % ) converted to episodic headache . In group II , these were 24 ( 64.8 % ) and 22 ( 59.2 % ) , respectively . In chronic migraine , the severity of headache at 2 months reduced in group I compared to group II ( 62.5 vs 35.3 % ; P = 0.01 ) . Both single and three sessions of 10 Hz rTMS were found to be equally effective in CM and CTTH , and result ed in conversion of chronic to episodic headache in 67.1 % patients Objective To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation ( sTMS ) for the preventive treatment of migraine . Background sTMS was originally developed for the acute treatment of migraine with aura . Open label experience has suggested a preventive benefit . The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention . Methods The e Neura S pringTMS P ost-Market O bservational U .S. S tudy of Migrain e ( ESPOUSE ) Study was a multicenter , prospect i ve , open label , observational study . From December 2014 to March 2016 , patients with migraine ( n = 263 ) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment . The treatment protocol consisted of preventive ( four pulses twice daily ) and acute ( three pulses repeated up to three times for each attack ) treatment . Patients reported daily headache status , medication use , and device use with a monthly headache diary . The primary endpoint , mean reduction of headache days compared to baseline , was measured over the 28-day period during weeks 9 to 12 . The primary endpoint was compared to a statistically-derived placebo estimate ( performance goal ) . Secondary endpoints included : 50 % responder rate , acute headache medication consumption , HIT-6 , and mean reduction in total headache days from baseline of any intensity . Results Of a total of 263 consented subjects , 229 completed a baseline diary , and 220 were found to be eligible based on the number of headache days . The device was assigned to 217 subjects ( Safety Data Set ) and 132 were included in the intention to treat Full Analysis Set . For the primary endpoint , there was a −2.75 ± 0.40 mean reduction of headache days from baseline ( 9.06 days ) compared to the performance goal ( −0.63 days ) ( p < 0.0001 ) . The 50 % responder rate of 46 % ( 95 % CI 37 % , 56 % ) was also significantly higher ( p < 0.0001 ) than the performance goal ( 20 % ) . There was a reduction of −2.93 ( 5.24 ) days of acute medication use , headache impact measured by HIT-6 , −3.1 ( 6.4 ) ( p < 0.0001 ) , and total headache days of any intensity −3.16 days ( 5.21 ) compared to the performance goal ( −0.63 days ) ( p < 0.0001 ) . The most common adverse events were lightheadedness ( 3.7 % ) , tingling ( 3.2 % ) , and tinnitus ( 3.2 % ) . There were no serious adverse events . Conclusions This open label study suggests that sTMS may be an effective , well-tolerated treatment option for migraine prevention . Trial registration number Repetitive transcranial magnetic stimulation ( rTMS ) is an emerging treatment for pain but there is no class 1 study on its role in migraine prophylaxis . In this study we report the efficacy and safety of high-rate rTMS in migraine prophylaxis . Adult migraine patients having > 4 attacks/month were r and omized to high-rate rTMS or sham stimulation . Stimulation in the form of 10 Hz rTMS , 600 pulses in 10 trains were delivered to the hot spot of the right abductor digiti minimi in 412 s. Three sessions were delivered on alternate days . The outcome was defined at 1 month . The primary outcome measures were reduction in headache frequency and severity > 50 % as assessed by the Visual Analogue Scale ( VAS ) . The secondary outcome measures were functional disability , rescue medication and adverse events . Fifty patients each were r and omized to rTMS or sham stimulation . The baseline characteristics of rTMS and sham stimulation groups were similar . At 1 month , headache frequency ( 78.7 vs. 33.3 % ; P = 0.0001 ) and VAS score ( 76.6 vs. 27.1 % ; P = 0.0001 ) improved significantly in the patients receiving rTMS compared to those in the sham stimulation group . Functional disability also improved significantly in rTMS group ( P = 0.0001 ) . Only one patient following rTMS developed transient drowsiness and was withdrawn from the study . This study provides evidence of the efficacy and safety of 10 Hz rTMS in migraine prophylaxis Background Single pulse transcranial magnetic stimulation ( sTMS ) is a novel treatment for acute migraine . Previous r and omised controlled data demonstrated that sTMS is effective and well tolerated in the treatment of migraine with aura . The aim of the programme reported here was to evaluate patient responses in the setting of routine clinical practice . Methods Migraine patients with and without aura treating with sTMS had an initial review ( n = 426 ) and training call , and then participated in telephone surveys at week six ( n = 331 ) and week 12 during a 3-month treatment period ( n = 190 ) . Results Of patients surveyed with 3 month data ( n = 190 ; episodic , n = 59 ; chronic , n = 131 ) , 62 % reported pain relief , finding the device effective at reducing or alleviating migraine pain ; in addition there was relief reported of associated features : nausea- 52 % ; photophobia- 55 % ; and phonophobia- 53 % . At 3 months there was a reduction in monthly headache days for episodic migraine , from 12 ( median , 8–13 IQ range ) to 9 ( 4–12 ) and for chronic migraine , a reduction from 24 ( median , 16–30 IQ range ) to 16 ( 10–30 ) . There were no serious or unanticipated adverse events . Conclusions TMS may be a valuable addition to options for the treatment of both episodic and chronic migraine Background Chronic migraine is a prevalent disabling disease , with major health-related burden and poor quality of life . Long-term use of preventive medications carries risk of side effects . Objectives The aim of this study was to compare repetitive transcranial magnetic stimulation ( rTMS ) to botulinum toxin-A ( BTX-A ) injection as preventive therapies for chronic migraine . Methods A pilot , r and omized study was conducted on a small-scale sample of 29 Egyptian patients with chronic migraine , recruited from Kasr Al-Aini teaching hospital outpatient clinic and diagnosed according to ICHD-III ( beta version ) . Patients were r and omly assigned into two groups ; 15 patients received BTX-A injection following the Phase III Research Evaluating Migraine Prophylaxis Therapy injection paradigm and 14 patients were subjected to 12 rTMS sessions delivered at high frequency ( 10 Hz ) over the left motor cortex ( MC , M1 ) . All the patients were requested to have their 1-month headache calendar , and they were subjected to a baseline 25-item ( beta version ) Henry Ford Hospital Headache Disability Inventory ( HDI ) , Headache Impact Test ( HIT-6 ) , and visual analogue scale assessment of headache intensity . The primary efficacy measures were headache frequency and severity ; secondary measures were 25-item HDI , HIT-6 , and number of acute medications . Follow-up visits were scheduled at weeks 4 , 6 , 8 , 10 , and 12 after baseline visit . Results A reduction in all outcome measures was achieved in both the groups . However , this improvement was more sustained in the BTX-A group , and both the therapies were well tolerated . Conclusion BTX-A injection and rTMS have favorable efficacy and safety profiles in chronic migraineurs . rTMS is of comparable efficacy to BTX-A injection in chronic migraine therapy , but with less sustained effect The objective was to assess the impact of transcranial magnetic stimulation ( TMS ) on pain and the autonomic nervous system ( ANS ) in migraine . Fortytwo people [ mean age 41.43±11.69 ( SD ) years , 36 females ] were r and omised into high vs. low TMS stimulation groups and received 2 brief pulses of TMS . Thirty-three ( 33/42 ) individuals had heart-rate variability assessed , before and after stimulation . No group effects were found . Pain decreased by 75 % ; 32 % of people after 1 treatment reported no headache after 24 h. Mean heart rate decreased from 79.05±10.27 to 72.89±11.35 beats/min . The low-frequency ( LF ) and the high-frequency ( HF ) areas derived from power spectral analyses increased [ mean 6522±1277 to 8315±1009 beats/min2 ( LF ) ( p=0.001 ) and mean 5600±1568 to 8755±3071 beats/min2 ( HF ) ( p=0.001 ) ] . The LF : HF ratio decreased from mean 1.31±0.51 to 1.13±0.48 ( NS ) . TMS produces immediate , sustained reductions in pain and modification of the ANS BACKGROUND Two small studies had evaluated the efficacy of rTMS in migraine . One tested high frequency rTMS over the dorsolateral prefrontal cortex while the other evaluated 1 Hz rTMS over the vertex . AIM To test the feasibility of 10 Hz rTMS of motor cortex as an adjunctive therapy in patients with chronic migraine Material s and Methods : We r and omized ( 2:1 ratio ) chronic migraine patients on medical preventive treatment to receive either rTMS or sham therapy for 10 sessions . rTMS ( 80 % resting motor threshold , 10Hz , 20 trains , 5 secs/train , inter-train interval 1 min , total 1000 stimuli/session ) was applied over the right motor cortex . RESULT Nine patients were r and omized . Six received rTMS and three had sham therapy . Three patients in the rTMS arm withdrew from the study due to increased headache frequency and discomfort from the treatment . The remaining six cases ( 3 rTMS , 3 sham ) completed the study . The study was prematurely stopped due to the significant worsening of headache from rTMS . No significant differences in outcome measures were found between real and sham rTMS . CONCLUSION Although the study was terminated prematurely , the high dropout rate ( 50 % ) due to worsening headaches suggested that rTMS over the motor cortex is poorly tolerated in chronic migraine The present study aim ed to investigate the efficacy of repetitive cathodal direct current stimulation ( rct DCS ) over the visual cortex as a prophylactic treatment in patients with menstrual migraine . 20 female patients were recruited in this double-blind , placebo-controlled study and were assigned to receive either cathodal or sham stimulation . Over 3 menstrual cycles , tDCS with 2mA intensity and 20 min duration was applied to the visual cortex of the patients , in 5 consecutive sessions 1 - 5 days prior to the first day of their menstruation . The primary endpoint of the study was the frequency of the migraine attacks at the end of the treatment period , however , additional parameters , such as the number of migraine related days and the intensity of pain were also recorded 3 months before , during and 3 months post-treatment . Visual cortex excitability was determined by measuring the phosphene thresholds ( PTs ) using single pulse transcranial magnetic stimulation ( TMS ) over the visual cortex . Sixteen patients completed the study . A significant decrease in the number of migraine attacks ( p=0.04 ) was found in the cathodal group compared to baseline but not compared to sham ( p=0.053 ) . In parallel the PTs increased significantly in this group , compared to the sham group ( p<0.05 ) . Our results indicate that prophylactic treatment with rct DCS over the visual cortex might be able to decrease the number of attacks in patients with menstrual migraine , probably by modifying cortical excitability High-frequency repetitive transcranial magnetic stimulation ( rTMS ) increases and low-frequency rTMS decreases neural excitability . Clinical ly , rTMS shows beneficial effects in the treatment of neurological and psychiatric disorders . Furthermore , chronic and neuropathic pain has been shown to respond to rTMS treatment . A small pilot study revealed prophylactic effects of high-frequency rTMS in migraine . As there is evidence of neuronal hyperexcitability in migraine , we conducted a placebo-controlled , blinded study to evaluate the therapeutic effects of low-frequency rTMS in migraine . The primary end-point was defined as a reduction of migraine attacks compared with placebo , secondary outcomes were a reduction in the total number of days with headache , hours with headache , pain intensity and a decrease of analgesic intake for migraine . Twenty-seven migraineurs completed the study and were treated with rTMS on five consecutive days . For the verum group , two trains of 500 pulses with a frequency of 1 Hz were applied over vertex with a round coil . For the treatment of the placebo group , a figure-of-eight sham coil was used . A significant decrease of migraine attacks could be observed in the verum group . However , when comparing these effects with placebo , no significance was evident . The same was true concerning secondary outcome measures with regard to days with migraine and total hours with migraine . No effects were evident for pain intensity and use of analgesics . The rTMS treatment was tolerated well . rTMS stimulation over vertex with 1 Hz was not effective in migraine prophylaxis when compared with placebo . The positive effects regarding migraine attacks , days and total hours with migraine in the verum group are encouraging and indicate that further research on this topic is warranted BACKGROUND Migraine is a common headache syndrome in adult population s. Prophylaxis is necessary to improve the quality of life but some patients with migraine have contraindication or suffer from side effects of medication , and therefore , establishing non-medical , neuromodulatory approaches is necessary . Past evidence had shown that consecutive motor cortex ( M1 ) stimulation with anodal transcranial direct current stimulation ( tDCS ) was effective to relieve central pain . OBJECTIVE To determine whether 20 consecutive days of the left M1 can be an effective prophylactic treatment for migraine . MATERIAL AND METHOD Forty-two episodic migraine patients who had never received any prophylactic treatment , failed prophylactic treatment , or discontinued treatment due to adverse events were recruited in the present study . Patients were r and omized to receive either active tDCS or sham tDCS 1mA , 20 m for 20 consecutive days and followed up for 12 weeks . Differences between and within groups were determined using repeated measures ANOVA . The level of significance was set at p < 0.05 . RESULTS Thirty-seven patients participated in the final analyses ( active : n = 20 , sham : n = 17 ) . Between-groups comparison of attack frequency , pain intensity , and abortive medications used were performed at 4 , 8 , and 12 weeks after treatment . The results showed statistically significant reduction in attack frequency and abortive medications at week 4 and 8 after treatment . The pain intensity was statistically significant reduced at week 4 , 8 , and 12 . All patients tolerated the tDCS well without any serious adverse events . CONCLUSION The present study suggests that anodal M1 tDCS may be a safe and useful clinical tool in migraine prophylaxis . The mechanism of action of anodal tDCS on neuromodulation in migraine patients needs further investigation BACKGROUND Depression has a significant impact on poststroke recovery and mortality . There are a proportion of patients with poststroke depression ( PSD ) who do not respond to antidepressants . Repetitive Transcranial Magnetic Stimulation ( rTMS ) might be a safe and effective alternative in these refractory cases . METHODS We conducted a r and omized , parallel , double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD . After discontinuing antidepressants , patients were r and omly assigned to receive 10 sessions of active ( 10 Hz , 110 % of the motor threshold , 20 trains of 5 seconds duration ) or sham left prefrontal rTMS . Efficacy measures included HAM-D scores , response and remission rates . Patients completed a neuropsychological battery at baseline and after completing the protocol . RESULTS When compared with sham stimulation , 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms . This reduction was not influenced by patient 's age , type or location of stroke , volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex . However , there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes . There were no significant changes in cognitive functioning between the active and the sham stimulation groups . In addition , there were few and mild adverse effects that were equally distributed among groups . CONCLUSIONS Taken together , these preliminary findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke Background Theta burst stimulation is a type of pattern‐specific repetitive transcranial magnetic stimulation that requires less stimulation time and lower intensity to induce long‐lasting effects comparable to those of other repetitive transcranial magnetic stimulation protocol s. This pilot study investigated whether continuous theta burst stimulation ( cTBS ) on the primary motor cortex reduced headache frequency in patients with migraine . Methods Nine patients with migraine were recruited into our study . All patients received 20 cTBS sessions ( bursts of 3 50‐Hz TMS pulses at 200‐ms intervals for 40 seconds ) , administered every weekday for 4 consecutive weeks . All patients kept headache diaries for 4 weeks before stimulation ( baseline ; T1 ) , during stimulation ( T2 ) , and 4 weeks after stimulation ( T3 ) . The primary outcome measures were the changes of total headache and migraine days from baseline ( Wilcoxon signed‐rank test ; T2 and T3 vs. T1 ) . Results The number of total headache days was reduced at T2 and T3 compared with T1 [ 9.4 ± 6.2 days ( p = 0.024 ) and 8.7 ± 10.1 days ( p = 0.012 ) vs. 13.4 ± 10.1 days ] . The number of migraine days was also reduced at T2 and T3 compared with T1 [ 2.9 ± 2.7 days ( p = 0.021 ) and 1.0 ± 1.6 days ( p = 0.008 ) vs. 8.6 ± 8.7 days ] . Conclusion Our results indicate that cTBS on the primary motor cortex might reduce the number of total headache and migraine days in patients with migraine . However , large‐scale r and omized controlled trials are necessary to further vali date the findings OBJECTIVE Persistent mild traumatic brain injury related headache ( MTBI-HA ) represents a neuropathic pain state . This study tested the hypothesis that repetitive transcranial magnetic stimulation ( rTMS ) at the left prefrontal cortex can alleviate MTBI-HA and associated neuropsychological dysfunctions . METHODS AND MATERIAL S Veterans with MTBI-HA were r and omized to receive four sessions of either real ( REAL group ) or sham ( SHAM group ) high frequency rTMS delivered at 10 Hz , 80 % of resting motor threshold and 2000 pulses per session at > 24 and < 72 hours apart . Pre-treatment , post-treatment 1-week and 4-week headache and neuropsychological assessment s were conducted . RESULTS Twenty nine out of forty-four consented subjects completed the study . A two-factor ( visit × treatment ) repeated measures ANOVA showed a significant ( p = 0.002 , F = 11.63 , df = 1 ) interaction for the average daily persistent headache intensity with the REAL group exhibiting a significant ( p < 0.0001 ) average reduction ( ±SD ) of 25.3 ± 16.8 % and 23.0 ± 17.7 % reduction in their numerical rating scale at the one-week and four-week post-treatment assessment s in comparison to < 1 ± 11.7 % and 2.3 ± 14.5 % reduction found in the SHAM group . In addition , a significant ( p < 0.01 ) 50 % and 57 % reduction was found in the prevalence of persistent headache in the REAL group at the one-week and four-week assessment s in comparison to 7 % and 20 % reduction found in the SHAM group . Furthermore , the REAL group demonstrated a significant ( p = 0.033 ) improvement ( from 22.3 ± 6.4 at pre-treatment to 19.0 ± 5.0 at post-treatment one-week ) in the Hamilton Rating Scale for Depression score , while the SHAM group 's score remained largely unchanged ( from 25.33 ± 8.43 to 24.64 ± 5.03 ) in the same time frame . This trend of improvement , although not statistically significant , continues to the post-treatment four-week assessment . CONCLUSION A short-course rTMS at the left DLPFC can alleviate MTBI-HA symptoms and provide a transient mood enhancing benefit . Further studies are required to establish a clinical protocol balancing both treatment efficacy and patient compliance One hundred patients were enrolled in a multicenter double-blind study to evaluate the safety and effectiveness of the Pain Suppressor Unit , a cranial electrotherapy stimulator for the symptomatic treatment of tension headaches . Treatment consisted of extremely low level , high frequency current applied transcranially . Pain scores before and after 20 minute treatments of individual headaches as well as patient and physician global evaluations were the primary efficacy variables . Following use of the active unit , patients reported an average reduction in pain intensity of approximately 35 % . Placebo patients reported a reduction of approximately 18 % . The difference was statistically significant ( p = 0.01 ) . The active unit was rated as moderately or highly effective in 40 % by physicians , and in 36 % by patients . Both physicians and patients scored the placebo unit moderately or highly effective for only 16 % . The difference in ordered outcomes was statistically significant ( p = 0.004 ) . Approximately 10 % of patients in each group reported at least one minor adverse experience . Cranial electrotherapy stimulation is distinct from TENS , and is safe and often effective in ameliorating the pain intensity of tension headaches . It should be considered as an alternative to the chronic usage of analgesics PURPOSE The aims of this paper are ( i ) to compare the excitability of visual cortex in migraine patients with healthy volunteers ; and ( ii ) if an abnormal excitability has been found , to modulate cortical excitability in migraine patients with transcranial direct current stimulation ( tDCS ) and observe their clinical and neurophysiological effects . METHODS The study was divided into two steps . A cross-sectional study ( step 1 ) was conducted to compare the cortical excitability of 23 migraineurs ( 11 with and 12 without aura ) on 11 healthy individuals . On step 2 , a r and omized , double blinded , controlled pilot trial was carried on with 19 migraineurs , r and omly divided into : experimental and control group . During 12 sessions , experimental and group received active tDCS to visual cortex and control group received sham tDCS . The headache diary was applied for a total of 90days ( before , during and after tDCS sessions ) . Phosphene threshold ( PT ) induced by transcranial magnetic stimulation was recorded to measure the excitability of the visual cortex before and after each session . RESULTS Step 1 showed higher level of cortical excitability between migraineurs when compared to healthy volunteers ; therefore , cathodal tDCS was applied over visual cortex in step 2 . After tDCS application , a significant decrease was observed in a number of migraine attacks , painkiller intake and duration of each attack just in experimental group . The analysis of PT indicated no difference in cortical excitability after tDCS . CONCLUSIONS Findings of the study suggested that inhibitory tDCS on visual cortex might be an alternative and non-pharmacological treatment for migraine prophylaxis . However the clinical improvements of patients after tDCS treatment are not correlated with changes in cortical excitability OBJECTIVE Headache is one of the most common debilitating chronic pain conditions in either active or retired military personnel with mild traumatic brain injury ( MTBI ) . This study assessed the effect of repetitive transcranial magnetic stimulation ( rTMS ) in alleviating MTBI-related headache ( MTBI-HA ) . MATERIAL S AND METHOD Veterans with MTBI-HA were r and omized to receive either real rTMS ( REAL group ) at 10 hz for a total of 2000 pulses divided into 20 trains with one-sec inter-train interval or sham rTMS ( SHAM group ) at the left motor cortex ( LMC ) with brain magnetic resonance imaging neuronavigation guidance . Pretreatment , posttreatment one-week and four-week headache and neuropsychological assessment s were conducted . RESULT Thirty veterans were screened and twenty four ( 21 men and 3 women with average year-old ± SD at 14.3 ± 12.6 ) subjects ' data were analyzed . A two-factor ( visit × treatment ) repeated measures analysis of variance ( RM-ANOVA ) indicated a close to significant ( p = 0.06 ) trend of interaction between pretreatment and posttreatment one-week assessment with the intensity of the persistent daily headache decreasing from 5.7 ± 1.9 to 2.2 ± 2.7 and 4.6 ± 1.3 to 3.5 ± 2.0 for the REAL and SHAM groups , respectively . Subsequent analyses indicated REAL group demonstrated a significantly ( p = 0.041 ) higher % of reduction in persistent headache intensity than the SHAM group ( 56.3 ± 48.2 % vs.15.4 ± 43.6 % ) at the posttreatment one-week assessment and the trend continued to the four-week assessment . Overall , a significantly ( p = 0.035 ) higher percentage of the subjects in the REAL group ( 58.3 % ) demonstrated at least a 50 % headache intensity reduction at posttreatment one-week assessment compared with the SHAM group ( 16.6 % ) . The overall composite score of functionally debilitating headache exacerbation is significantly ( p = 0.017 ) reduced in REAL group at the posttreatment four-week assessment in comparison with the SHAM group . No major sustained change in neuropsychological assessment s was noted . CONCLUSION The studied rTMS protocol appears to be a clinical ly feasible and effective treatment option in managing MTBI-HA Background Sensitization and impaired habituation of cortical neurons have been reported in migraineurs . Repetitive transcranial magnetic stimulation ( rTMS ) may change these phenomena and be the basis of therapeutic response . We report the effect of 10 Hz rTMS on sensitization and habituation of median somatosensory evoked potential ( SEP ) in migraineurs , and correlate these changes with clinical response . Methods Migraineurs having four or more episodes of headache per month were included and their clinical details were noted . Three sessions of 10 Hz rTMS , 600 pulses in 412.4 seconds were delivered on the left frontal cortex corresponding to the hot spot of right abductor digiti minimi , on alternate days . Median SEP was done before and 30 minutes after the third rTMS session . Sensitization ( block I N20 amplitude ) and impaired habituation ( if N20 amplitude of block 2 or 3 were not suppressed compared to block I ) were noted . The reduction in frequency and severity of headache in the next month were noted and correlated with SEP changes . Results Ninety-four migraineurs were included ; 56 received true rTMS and 38 sham stimulation . Following stimulation , reduction in N20 amplitude of block 1 correlated with a reduction in frequency and severity of headache at one month . The impaired habituation significantly improved in the true rTMS group compared to sham stimulation , and correlated with a reduction in the severity of headache but not with frequency . Conclusion In migraineurs , 10 Hz rTMS improves habituation and may be the biological basis of headache relief Mild traumatic brain injury ( mTBI ) is typically followed by various postconcussive symptoms ( PCS ) , including headache , depression , and cognitive deficits . In 15 - 25 % of cases , PCS persists beyond the usual 3-month recovery period , interfering with activities of daily living and responding poorly to pharmacotherapy . We tested the safety , tolerability , and efficacy of repetitive transcranial magnetic stimulation ( rTMS ) over the left dorsolateral prefrontal cortex ( DLPFC ) for alleviating PCS . Fifteen eligible patients with mTBI and PCS > 3 months postinjury consented to 20 sessions of rTMS ( 20 × 5-sec trains ; 10 Hz at 110 % threshold ) , with clinical and functional magnetic resonance imaging ( fMRI ) assessment s before and after intervention and clinical assessment at 3-month follow-up . Primary outcomes were tolerability , safety , and efficacy , as measured with the PCS Scale . Secondary outcomes included the Cognitive Symptoms Question naire , neuropsychological test performance , and working memory task-associated activity as assessed with fMRI . Twelve patients completed all sessions . Three withdrew because of worsening symptoms or for an unrelated event . Stimulation intensity was increased gradually across sessions , and all subjects tolerated the protocol by the sixth session . Commonly reported side effects among completers were increased headache ( n = 3 ) and greater sleep disturbance ( n = 3 ) . Participants also reported positive outcomes such as less sleep disturbance ( n = 3 ) , and better mental focus ( n = 3 ) . On average , PCS scores declined by 14.6 points ( p = 0.009 ) and fMRI task-related activation peaks in the DLPFC increased after rTMS . rTMS is safe , tolerated by most patients with mTBI , and associated with both a reduction in severity of PCS and an increase in task-related activations in DLPFC . Assessment of this intervention in a r and omized , control trial is warranted Background High-frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex ( rTMS-DLPFC ) is an effective treatment for depression . Preliminary studies indicated beneficial effects of rTMS-DLPFC on pain relief in patients treated for depression , and in patients with chronic migraine . Methods In this r and omized , double-blind , parallel-group , single-center , proof-of-principle clinical trial , we tested the hypothesis that 23 sessions of active rTMS-DLPFC delivered over eight weeks would be feasible , safe and superior to sham rTMS to decrease the number of headache days in 18 patients with chronic migraine without severe depression . Per- protocol analysis was performed . Results rTMS-DLPFC applied over eight weeks was feasible and safe in patients with chronic migraine . Contrary to our primary hypothesis , the number of headache days decreased significantly more in the sham group than in the group treated with active rTMS-DLPFC at eight weeks . Average decrease in headache days was > 50 % in the sham group , indicating a powerful placebo response . Pain intensity improved in both groups to a similar extent . Conclusions Positive results of M1 stimulation in other studies , and the absence of significant benefits of active high-frequency rTMS of the DLPFC in the present study , point to M1 as a more promising target than the DLPFC , for larger trials of noninvasive brain stimulation in patients with chronic migraine Abstract Objective : To evaluate the effect of high rate repetitive transcranial magnetic stimulation ( rTMS ) in migraine prophylaxis in medically refractory patients . Methods : Migraine patients above 15 years of age , having more than 7 attacks/month and refractory to at least two prophylactic drugs were included . The patients were evaluated for migraine frequency , severity , functional disability , number of rescue medications and migraine index . Three sessions of alternate day 10 Hz rTMS comprising of 600 pulses in 10 trains were delivered to left frontal cortex . The response was evaluated at the end of session and weekly for 4 weeks . Results : Fifty-one patients aged 16–61 years and 45 females were treated . Fifty ( 98 % ) patients had more than 50 % reduction of headache frequency at the end and 1 week after rTMS and the improvement persisted till the fourth week in 80·4 % patients . The headache frequency , severity , functional disability , migraine index , and rescue medications significantly reduced at all time points , but the maximum benefit was observed in the first 2 weeks . There were no serious adverse events . Conclusion : High rate rTMS in left frontal cortex is effective and well tolerated for migraine prophylaxis INTRODUCTION Deep Transcranial Magnetic Stimulation ( dTMS ) can be an alternative treatment to relieve pain in chronic migraine ( CM ) . The aim of this study was to evaluate the effect of high-frequency dTMS in add-on to st and ard treatment for CM in patients not responding to effective abortive or preventive drug treatment . METHODS We r and omized 14 patients with International Classification of Headache Disorders , 3rd Edition ( ICHD-3 ) treatment-resistant CM to add-on dTMS ( n=7 ) or st and ard abortive or preventive antimigraine treatment ( n=7 ) . Three sessions of alternate day 10Hz dTMS consisting of 600 pulses in 10 trains were delivered to the dorsolateral prefrontal cortex ( DLPFC ) , bilaterally , but with left hemisphere prevalence , for 12 sessions spread over one month . RESULTS The add-on dTMS treatment was well tolerated . Patients treated with dTMS showed significant reduction of pain intensity , frequency of attacks , analgesic overuse , and depressive symptoms during treatment and one month later , compared to the month preceding treatment and at the same time-points compared to the control group . CONCLUSIONS As compared to st and ard pharmacological treatment alone , add-on high-frequency dTMS of the bilateral DLPFC reduced the frequency and intensity of migraine attack , drug overuse , and depressive symptoms . This study supports the add-on dTMS treatment in treatment-resistant CM |
10,508 | 31,198,900 | Pentacam repeatability of different indices is not affected by CXL .
However , the change of indices showed high variance , which should be taken into consideration , especially in systematic review s because inter- study differences can be due to low repeatability of the measures of change | To determine the effect of corneal cross-linking ( CXL ) on the anterior and posterior corneal indices in terms of their repeatability and change as measured with Pentacam . | PURPOSE To present the results after simultaneous photorefractive keratectomy ( PRK ) followed by corneal collagen cross-linking ( CXL ) for progressive keratoconus . METHODS Twelve patients ( 14 eyes ) with progressive keratoconus were prospect ively treated with customized topography-guided PRK with the Pulzar Z1 ( wavelength 213 nm , CustomVis ) immediately followed by corneal collagen CXL with the use of riboflavin and ultraviolet A irradiation . RESULTS Mean follow-up was 10.69+/-5.95 months ( range : 3 to 16 months ) . Mean preoperative spherical equivalent refraction ( SE ) was -3.03+/-3.23 diopters ( D ) and defocus was 4.67+/-3.29 D ; at last follow-up SE and defocus were statistically significantly reduced to -1.29+/-2.05 D and 3.04+/-2.53 D , respectively ( P<.01 ) . Preoperative mean ( logMAR ) uncorrected visual acuity was 0.99+/-0.81 and best spectacle-corrected visual acuity was 0.21+/-0.19 , which improved postoperatively to 0.16+/-0.15 and 0.11+/-0.15 , respectively . The mean steepest keratometry was reduced from 48.20+/-3.40 D preoperatively to 45.13+/-1.80 D at last follow-up . CONCLUSIONS Simultaneous PRK followed by CXL seems to be a promising treatment capable of offering functional vision in patients with keratoconus Purpose To determine the variability in Scheimpflug image – derived posterior elevation measurements in eyes with keratoconus or corneal collagen crosslinking ( CXL ) . Setting Eye Institute of Thrace , Alex and roupolis , Greece . Design Prospect i ve observational study . Methods Two operators in 2 sessions obtained posterior elevation measurements using the Pentacam Scheimpflug system . Variability in measurements was assessed using Bl and ‐Altman analysis and intraclass correlation coefficients ( ICCs ) . Measurements were associated with a series of Scheimpflug‐derived keratoconus indices using the Pearson correlation and multivariate linear‐regression analysis . Results Mean interobserver differences for the central elevation point ( e1 ) and the highest elevation point ( HEP ) in the keratoconus group were −0.9 μm ( 95 % limits of agreement [ LoA ] , 5.7 to −7.5 μm ) and 1.7 μm ( 95 % LoA , 26 to −22.6 μm ) , respectively . In the CXL group , the mean differences were 0.2 μm ( 95 % LoA , 6.0 to −5.5 μm ) and −6.1 μm ( 95 % LoA , 16.8 to −29 μm ) , respectively . The ICC values in the keratoconus group were satisfactory for most elevation points ; the ICC values were unsatisfactory for a series of points in the lower corneal hemisphere . The ICC values for points in both hemispheres were unsatisfactory in the CXL group ; HEP had adequate reproducibility . The e1 and HEP parameters correlated significantly with most Scheimpflug‐derived indices ( P<.05 ) in the keratoconus group but not in the CXL group . Regression analysis indicated that the central keratoconus index was the primary determinant of the variability in keratoconus eyes . Conclusions Scheimpflug‐derived posterior elevation measurements had acceptable reproducibility in keratoconus eyes and post‐CXL eyes . Less consistent measurements were obtained in the lower hemisphere . Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned Purpose : To evaluate the clinical and topographic effects after accelerated corneal collagen cross-linking ( CXL ) in keratoconus . Methods : This was a prospect i ve interventional study in 25 eyes of 24 Asian patients with keratoconus , where 10 eyes in group 1 had mild to moderate keratoconus with the steepest keratometry reading ( Kmax ) < 58 diopters ( D ) , and 15 eyes in group 2 had advanced keratoconus with Kmax ≥ 58.0 D. The patients underwent accelerated CXL with 18 W/cm2 UV-A light for 5 minutes . Clinical and topographic parameters were obtained before and 1 year after treatment . Results : Overall , spectacle-corrected distance visual acuity , refraction , average keratometry readings , Kmax , anterior elevation at the apex , and corneal endothelial cell density remained stable ( P < 0.102 ) . Posterior elevation at the apex increased at 1 year ( P = 0.002 ) . The thinnest pachymetry readings also showed significant reduction ( P < 0.001 ) . Kmax in group 1 increased by 1.00 ± 1.63 D ( range , −2.2 to 5.4 D ; P = 0.012 ) , whereas Kmax in group 2 reduced by 1.69 ± 2.61 D ( range , −8.4 to 3.2 D ; P = 0.013 ) at 1 year after accelerated CXL . The change in Kmax between the 2 groups was significantly different ( P < 0.001 ) . There was no intergroup difference for the change in other parameters . A significant correlation was found between the preoperative Kmax and postoperative change in Kmax at 1 year ( r = −0.648 ; P < 0.001 ) . Conclusions : Accelerated CXL seems to be effective in preventing progression and causing topographic flattening in advanced cases of keratoconus but not as effective in the less progressed counterparts PURPOSE To compare the long-term outcomes of accelerated and st and ard corneal cross-linking protocol s in the treatment of progressive keratoconus . DESIGN Prospect i ve r and omized clinical trial . METHODS Thirty-one eyes with keratoconus were treated with an accelerated protocol ( 18 mW/cm(2 ) , 5 min ) and all contralateral eyes were treated with the st and ard method ( 3 mW/cm(2 ) , 30 min ) using the same overall fluence of 5.4 J/cm(2 ) . RESULTS At 18 months after the procedure , the st and ard group showed significant improvement in spherical equivalent ( P < .05 ) , K-readings ( P < .05 ) , Q value ( P < .05 ) , index of surface variance ( P < .05 ) , and keratoconus index ( P = .008 ) and decline in central corneal thickness ( P < .05 ) , but no significant change in visual acuity , corneal hysteresis , corneal resistance factor , P2 area , or endothelial cell density . In the accelerated group , central corneal thickness was the only parameter with statistically significant change . However , neither of these parameters showed significant differences between the st and ard and the 18 mW/cm(2 ) accelerated protocol , except K-reading ( P = .059 ) and index surface variance ( P = .034 ) . CONCLUSION An accelerated cross-linking protocol , using 18 mW/cm(2 ) for 5 minutes , shows a comparable outcome and safety profile when compared to the st and ard protocol , but better corneal flattening is achieved with the st and ard method than the accelerated method . Overall , both methods stop the disease progression similarly . This study will continue to examine more long-term results PURPOSE In animal eyes , a significant increase in corneal biomechanical stiffness has been found after collagen crosslinking by combined riboflavin/ultraviolet-A ( UVA ) treatment . The aim of the present study was to evaluate the clinical usefulness of riboflavin/UVA-induced collagen crosslinking for bringing the progression of keratoconus to a halt . DESIGN Prospect i ve , nonr and omized clinical pilot study . METHODS Twenty-three eyes of 22 patients with moderate or advanced progressive keratoconus ( maximum K value , 48 - 72 diopters ) were included . After central corneal abrasion , photosensitizing riboflavin drops were applied and the eyes exposed to UVA ( 370 nm , 3 mW/cm(2 ) ) in a 1-cm distance for 30 minutes . Postoperative examinations were performed in 6-month intervals , including visual acuity testing , corneal topography , slit-lamp examination , measurement of endothelial cell density , and photographic documentation . The follow-up time was between 3 months and 4 years . RESULTS In all treated eyes , the progression of keratoconus was at least stopped . In 16 eyes ( 70 % ) regression with a reduction of the maximal keratometry readings by 2.01 diopters and of the refractive error by 1.14 diopters was found . Corneal and lens transparency , endothelial cell density , and intraocular pressure remained unchanged . Visual acuity improved slightly in 15 eyes ( 65 % ) . CONCLUSIONS Collagen crosslinking may be a new way for stopping the progression of keratectasia in patients with keratoconus . The need for penetrating keratoplasty might then be significantly reduced in keratoconus . Given the simplicity and minimal costs of the treatment , it might also be well-suited for developing countries . Long-term results are necessary to evaluate the duration of the stiffening effect and to exclude long term side-effects PURPOSE To assess the repeatability and agreement of three rotating Scheimpflug cameras , Pentacam , Galilei , and Sirius , in measuring the mean keratometry ( Km ) , thinnest corneal thickness ( TCT ) , anterior chamber depth ( ACD ) , and mean posterior keratometry ( pKm ) in keratoconus patients in a prospect i ve study . METHODS Fifty-five eyes of 55 patients with keratoconus underwent three consecutive scans on each machine , performed by a single operator . Within-subject st and ard deviation ( Sw ) , test-retest repeatability ( TRT ) , and coefficient of variation ( COV ) for assessing repeatability and Bl and -Altman plots for the agreement between the mean measurements of each machine were examined . RESULTS The Sw of Km and pKm measurements with Pentacam ( 0.23 and 0.10 diopters [ D ] , respectively ) were significantly lower ( better ) than those of Galilei ( 0.60 and 0.17 ) and Sirius ( 0.23 and 0.36 ) . The Sw of TCT measurements with Sirius ( 8.88 μm ) was significantly lower than that of Galilei ( 11.64 μm ) . The COV ranged between 0.5 for the Km measurements of Pentacam and 2.8 for the TCT measurements of Galilei . Significant proportional bias in agreement was detected for the pKm measurements with all the three device pairs and for the ACD measurements between Pentacam and Galilei and between Galilei and Sirius . CONCLUSIONS Though Pentacam , Galilei , and Sirius showed repeatable measurements for Km , TCT , ACD , and pKm , repeatabilities with Pentacam and Sirius were better than those with Galilei . There were significant differences in the measurements between the three devices ; hence they can not be used interchangeably for anterior segment measurements in keratoconus patients PURPOSE To evaluate the long-term results of corneal collagen cross-linking ( CXL ) in patients with progressive keratoconus . DESIGN Prospect i ve case series . PARTICIPANTS This study was conducted on 40 eyes of 32 patients with progressive keratoconus between 2006 and 2012 . METHODS Patients underwent CXL no later than 1 month after baseline examinations . For CXL , ultraviolet irradiation was applied for 30 minutes , during which riboflavin instillation was repeated every 3 minutes . MAIN OUTCOME MEASURES Patients were tested for best-corrected visual acuity ( BCVA ) , uncorrected visual acuity ( UCVA ) , manifest refraction spherical equivalent ( MRSE ) , and Scheimpflug imaging from which we extracted maximum keratometry reading ( max-K ) , average of minimum and maximum keratometry readings ( mean-K ) , central corneal thickness ( CCT ) , and anterior and posterior elevation at the apex at baseline , at 1 , 3 , 6 months after CXL , and 1 , 2 , 4 , and 5 years later . We studied results at 5 years after CXL as well as the trend of changes over the 5-year period . RESULTS Mean UCVA was 0.67 ± 0.52 logarithm of the minimum angle of resolution ( logMAR ) at baseline and 0.65 ± 0.51 logMAR at 5 years after the procedure . For mean BCVA , these values were 0.31 ± 0.28 and 0.19 ± 0.20 logMAR , respectively ( P = 0.016 ) . The mean MRSE changed from -3.18±2.23 diopters ( D ) to -2.77 ± 2.18 D , and mean refractive cylinder error changed from -3.14 ± 2.22 to -2.49 ± 1.71 D ( P = 0.089 ) . Mean max-K and mean-K decreased by 0.16 ± 2.20 and 0.10 ± 1.69 D , respectively . The CCT increased from 483.87 ± 29.07 to 485.95 ± 28.43 μm . Mean anterior elevation at the apex changed from 13.9 2 ± 8.28 to 11.45 ± 8.18 μm ( P = 0.030 ) and posterior elevation at this point changed from 29.54 ± 18.39 to 26.34 ± 19.59 μm . The mean-K , max-K , UCVA , and astigmatism showed no change over time during these 5 years . After the first year , BCVA , MRSE , and CCT showed no change and stabilized , whereas elevation readings continued to decrease up to 5 years after CXL . CONCLUSIONS Based on our 5-year results , treatment of progressive keratoconus with CXL can stop disease progression , without raising any concern for safety , and can eliminate the need for keratoplasty . FINANCIAL DISCLOSURE(S ) The authors have no proprietary or commercial interest in any of the material s discussed in this article PURPOSE To study the effect of different protocol s of collagen cross-linking on visual , refractive , and tomographic parameters in patients with progressive keratoconus . DESIGN Prospect i ve r and omized interventional study . METHODS In this study , 138 eyes of 138 patients with progressive keratoconus underwent corneal collagen cross-linking ( CXL ) . Following detailed preoperative examination , Group I underwent conventional cross-linking ( 36 patients , 3 mW/cm(2 ) for 30 min ) ; Group II ( 36 patients , 9 mW/cm(2 ) for 10 min ) , Group III ( 33 patients , 18 mW/cm(2 ) for 5 min ) , and Group IV ( 33 patients , 30 mW/cm(2 ) for 3 min ) underwent accelerated cross-linking . Changes in corrected distance visual acuity ( CDVA ) , spherical equivalent ( SE ) , flat keratometry , steep keratometry , thinnest pachymetry , specular microscopy , and demarcation line were studied at 6 and 12 months . RESULTS Improvement in the mean CDVA and SE were statistically significant in all groups except Group IV ( P = .15 at 6 months , P = .17 at 12 months ) , with Group III ( P = .01 at 6 and 12 months ) showing the best results . Flattening of steep and flat keratometry was significant in Groups I ( P = .01 ) and II ( P = .01 ) as compared to the other groups . There was no significant difference in the pachymetry or specular microscopy in any of the groups . Groups I and II demonstrated a good demarcation line when compared to other groups . CONCLUSION Conventional CXL ( Group I ) and accelerated CXL with irradiations of 9 mW/cm(2 ) ( Group II ) and 18 mW/cm(2 ) ( Group III ) showed better visual , refractive , and tomographic improvements at the end of 12 months |
10,509 | 20,614,428 | There was moderate quality evidence that : i ) operant therapy was more effective than waiting list ( SMD -0.43 ; 95%CI -0.75 to -0.11 ) for short-term pain relief;ii ) little or no difference exists between operant , cognitive , or combined behavioural therapy for short- to intermediate-term pain relief;iii ) behavioural treatment was more effective than usual care for short-term pain relief ( MD -5.18 ; 95%CI -9.79 to -0.57 ) , but there were no differences in the intermediate- to long-term , or on functional status;iv ) there was little or no difference between behavioural treatment and group exercise for pain relief or depressive symptoms over the intermediate- to long-term;v ) adding behavioural therapy to inpatient rehabilitation was no more effective than inpatient rehabilitation alone .
For patients with CLBP , there is moderate quality evidence that in the short-term , operant therapy is more effective than waiting list and behavioural therapy is more effective than usual care for pain relief , but no specific type of behavioural therapy is more effective than another .
In the intermediate- to long-term , there is little or no difference between behavioural therapy and group exercises for pain or depressive symptoms . | BACKGROUND Behavioural treatment is commonly used in the management of chronic low-back pain ( CLBP ) to reduce disability through modification of maladaptive pain behaviours and cognitive processes .
Three behavioural approaches are generally distinguished : operant , cognitive , and respondent ; but are often combined as a treatment package .
OBJECTIVES To determine the effects of behavioural therapy for CLBP and the most effective behavioural approach . | Study Design . A r and omized trial . Objective . To evaluate the effectiveness of a semi-intensive multidisciplinary rehabilitation for patients with chronic low back pain in an outpatient setting . Summary and Background Data . Systematic review s have shown that there is strong evidence that intensive multidisciplinary treatment ( > 100 hours ) , which includes functional restoration , improves function among chronic patients with low back pain , and moderate evidence that it reduces pain but contradictory evidence regarding improvement of working ability . However , there is paucity of data whether semi-intensive outpatient multidisciplinary rehabilitation in groups is more effective than individual physiotherapy . Material s and Methods . A total of 120 women employed as healthcare and social care professionals with nonspecific chronic low back pain were recruited from two occupational healthcare centers . The patients were r and omized into two intervention programs . Multidisciplinary rehabilitation ( n = 59 ) was conducted in groups and comprised of physical training , workplace interventions , back school , relaxation training , and cognitive-behavioral stress management methods for 70 hours . The individual physiotherapy ( n = 61 ) included physical exercise and passive treatment methods administered for 10 hours . Main outcome measures were : back pain and sciatic pain intensity , disability , sick leaves , healthcare consumption , symptoms of depression , and beliefs of working ability after 2 years . Results . There were no statistically significant differences between the two treatment groups in main outcome measures just after rehabilitation , at 6- , at 12- , or 24-month follow-up . In both intervention arms , however , the before- and -after comparison showed favorable effects , and the effects were still maintained at 2 years follow-up . Conclusions . The results of this study indicate that semilight outpatient multidisciplinary rehabilitation program for female chronic low back pain patients does not offer incremental benefits when compared with rehabilitation carried out by a physiotherapist having a cognitive-behavioral way of administering the treatment The aim of the study was to evaluate the effect of cognitive intervention ( information and physical exercise ) , on patients with long-lasting back pain referred for surgical evaluation at an orthopaedic hospital , but evaluated as unfit for surgery . One hundred and fifty-two patients were r and omized to a five days intervention or control . The intervention had no significant effects on pain . At three-month follow-up , the patients in the intervention group used significantly more active strategies to cope with the back pain compared to the control group . This effect seemed to increase over time , being more pronounced at one-year follow-up evaluation Objectives The aim of this r and omized controlled study was to investigate whether additional psychologic interventions in the context of multidisciplinary inpatient pain treatment increases treatment efficacy compared with normal orthopedic rehabilitation . In addition , we aim ed to demonstrate the additional benefit of a subsequent maintenance program in further stabilizing treatment successes . Methods We r and omly assigned 363 chronic back pain patients to 1 of 3 treatment conditions : traditional orthopedic rehabilitation , multidisciplinary ( behavioral-medical ) rehabilitation alone , and multidisciplinary rehabilitation with subsequent booster sessions . Pain disability , depression , self-efficacy , health status , life satisfaction , and coping strategies were assessed at admission , discharge , and 12 months follow-up . The completion rate was 94 % . Results All 3 treatment conditions were effective in improving core outcome measures in chronic back pain patients in the short term . The results were almost maintained at follow-up ( small-to-medium within-group effect sizes ) . Significant advantages in favor of behavioral-medical interventions were found on almost all pain coping strategies and depression compared with traditional orthopedic rehabilitation . We found only slight advantages for the behavioral-medical treatment with subsequent booster sessions compared with the condition without a further maintenance program . Discussion The results concerning the efficacy of the multidisciplinary treatment are in accordance with former meta-analyses . Surprisingly , the findings suggest that the presented traditional orthopedic treatment was inherently very effective . The implication s of these findings are discussed with respect to the benefit of additional psychologic interventions and the benefit of aftercare approaches for chronic pain patients This study examined the supplemental value of a cognitive coping skills training when added to an operant-behavioral treatment for chronic low-back pain patients . The complete treatment package ( OPCO ) was compared with an operant program + group discussion ( OPDI ) and a waiting-list control ( WLC ) . After the WL period , the WLC patients received a less protocol ized operant program usually provided in Dutch rehabilitation centers ( OPUS ) . Regression analyses showed that , compared with WLC , both OPCO and OPDI led to less negative affect , higher activity tolerance , less pain behavior , and higher pain coping and pain control . At posttreatment , OPCO led to better pain coping and pain control than OPDI . Calculation of improvement rates revealed that OPCO and OPDI had significantly more improved patients than OPUS on all the dependent variables . The discussion includes findings regarding treatment credibility , compliance , and contamination bias Study Design . Single blind r and omized study . Objectives . To compare the effectiveness of lumbar instrumented fusion with cognitive intervention and exercises in patients with chronic low back pain and disc degeneration . Summary of Background Data . To the authors ’ best knowledge , only one r and omized study has evaluated the effectiveness of lumbar fusion . The Swedish Lumbar Spine Study reported that lumbar fusion was better than continuing physiotherapy and care by the family physician . Patients and Methods . Sixty-four patients aged 25–60 years with low back pain lasting longer than 1 year and evidence of disc degeneration at L4–L5 and /or L5–S1 at radiographic examination were r and omized to either lumbar fusion with posterior transpedicular screws and postoperative physiotherapy , or cognitive intervention and exercises . The cognitive intervention consisted of a lecture to give the patient an underst and ing that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it . This was reinforced by three daily physical exercise sessions for 3 weeks . The main outcome measure was the Oswestry Disability Index . Results . At the 1-year follow-up visit , 97 % of the patients , including 6 patients who had either not attended treatment or changed groups , were examined . The Oswestry Disability Index was significantly reduced from 41 to 26 after surgery , compared with 42 to 30 after cognitive intervention and exercises . The mean difference between groups was 2.3 ( −6.7 to 11.4 ) ( P = 0.33 ) . Improvements inback pain , use of analgesics , emotional distress , life satisfaction , and return to work were not different . Fear-avoidance beliefs and fingertip-floor distance were reduced more after nonoperative treatment , and lower limb pain was reduced more after surgery . The success rateaccording to an independent observer was 70 % after surgery and 76 % after cognitive intervention and exercises . The early complication rate in the surgical group was 18 % . Conclusion . The main outcome measure showed equal improvement in patients with chronic low back pain and disc degeneration r and omized to cognitive intervention and exercises , or lumbar fusion Study Design . A r and omized controlled design superimposed on treatment as usual was used to compare the effects of a cognitive-behavior intervention aim ed at preventing chronicity with two different forms of information . Objective . To develop a coping-oriented preventive intervention applicable in primary care , and to compare its impact with educational information . Summary of Background Data . Preventing long-term disability result ing from spinal pain has proved difficult . The information provided by health care professions and early interventions aim ed at preventing long-term disability may be important , but little scientific evidence exists concerning their use . Methods . A protocol for a six-session cognitive-behavior group intervention was developed on the basis of earlier research . The main focus was to prevent long-term disability by changing patients ’ behaviors and beliefs so they can cope better with their problems . Comparison groups received either a pamphlet shown earlier to have an effect , or a more extensive information package consisting of six installments . All the groups continued to receive treatment as usual in primary care . There were 243 patients with acute or subacute spinal pain who perceived that they were at risk for developing a chronic problem . These patients were r and omized to the cognitive-behavioral intervention or one of the two information groups . Because the aim was to prevent long-term disability , the key outcome variables at the 1-year follow-up assessment were sick absenteeism and health care use . Other variables were pain , function , fear-avoidance beliefs , and cognitions . Results . The comparison groups reported benefits . However , the risk for a long-term sick absence developing was lowered ninefold for the cognitive-behavior intervention group as compared with the risk for the information groups ( relative risk , 9.3 ) . Participants in the cognitive-behavior group also reported a significant decrease in perceived risk . In addition , the cognitive-behavior group demonstrated a significant decrease in physician and physical therapy use as compared with two groups receiving information , in which such use increased . All three groups tended to improve on the variables of pain , fear-avoidance , and cognitions . Conclusions . This study demonstrates that a cognitive-behavior group intervention can lower the risk of a long-term disability developing . These findings underscore the significance of early interventions that specifically aim to prevent chronic problems . This approach might be applied to primary care setting & NA ; Several treatment principles for the reduction of chronic low back pain associated disability have been postulated . To examine whether a combination of a physical training and an operant‐behavioral grade d activity with problem solving training is more effective than either alone in the long‐term , a cluster r and omized controlled trial was conducted . In total 172 patients , 18–65 years of age , with chronic disabling non‐specific low back pain referred for rehabilitation treatment , were r and omized in clusters of four consecutive patients to 10 weeks of aerobic training and muscle strengthening of back extensors ( active physical treatment ; APT ) , 10 weeks of gradual assumption of patient relevant activities based on operant‐behavioral principles and problem solving training ( grade d activity plus problem solving training ; GAP ) , or APT combined with GAP ( combination treatment ; CT ) . The primary outcome was the Rol and Disability Question naire adjusted for centre of treatment , cluster , and baseline scores . Secondary outcomes were patients ’ main complaints , pain intensity , self‐perceived improvement , depression and six physical performance tasks . During the one‐year follow‐up , there were no significant differences between each single treatment and the combination treatment on the primary outcome , the Rol and Disability Question naire . Among multiple other comparisons , only one significant difference emerged , with GAP and APT showing higher self‐perceived improvement than CT . We conclude that the combination treatment integrating physical , grade d activity with problem solving training is not a better treatment option for patients with chronic low back pain & NA ; Many psychological factors have been suggested to be important obstacles to recovery from low back pain , yet most studies focus on a limited number of factors . We compared a more comprehensive range of 20 factors in predicting outcome in primary care . Consecutive patients consulting 8 general practice s were eligible to take part in a prospect i ve cohort study ; 1591 provided data at baseline and 810 at 6 months . Clinical outcome was defined using the Rol and and Morris Disability Question naire ( RMDQ ) . The relative strength of the baseline psychological measures to predict outcome was investigated using adjusted multiple linear regression techniques . The sample was similar to other primary care cohorts ( mean age 44 years , 59 % women , mean baseline RMDQ 8.6 ) . The 20 factors each accounted for between 0.04 % and 33.3 % of the variance in baseline RMDQ score . A multivariate model including all 11 scales that were associated with outcome in the univariate analysis accounted for 47.7 % of the variance in 6 months RMDQ score ; rising to 55.8 % following adjustment . Four scales remained significantly associated with outcome in the multivariate model explaining 56.6 % of the variance : perceptions of personal control , acute/chronic timeline , illness identify and pain self‐efficacy . When all independent factors were included , depression , catastrophising and fear avoidance were no longer significant . Thus , a small number of psychological factors are strongly predictive of outcome in primary care low back pain patients . There is clear redundancy in the measurement of psychological factors . These findings should help to focus targeted interventions for back pain in the future & NA ; The effects of outpatient group cognitive therapy , relaxation training , and cognitive therapy in combination with relaxation training on chronic low back pain and associated physical and psychosocial disability were evaluated and compared . One‐hundred and two mildly disabled chronic low back pain patients were assigned r and omly to a waiting‐list ( WL ) control condition and the 3 treatments . Patient self‐report and observational measures were obtained pretreatment and post‐treatment for all conditions , and at 6‐ and 12‐month follow‐ups for the treatment conditions . Pain intensity decreased significantly pre‐ to post‐treatment for patients in all 3 treatment conditions , but not the WL condition . Depressive symptoms and disability improved significantly in all conditions ( including the waiting list ) from pretreatment to post‐treatment , with no statistically significant differences among treatments . At both follow‐ups , all 3 treatment groups remained significantly improved from pretreatment , with no statistically significant differences between treatments Background The treatment of non-specific chronic low back pain is often based on three different models regarding the development and maintenance of pain and especially functional limitations : the deconditioning model , the cognitive behavioral model and the biopsychosocial model . There is evidence that rehabilitation of patients with chronic low back pain is more effective than no treatment , but information is lacking about the differential effectiveness of different kinds of rehabilitation . A direct comparison of a physical , a cognitive-behavioral treatment and a combination of both has never been carried out so far . Methods The effectiveness of active physical , cognitive-behavioral and combined treatment for chronic non-specific low back pain compared with a waiting list control group was determined by performing a r and omized controlled trial in three rehabilitation centers . Two hundred and twenty three patients were r and omized , using concealed block r and omization to one of the following treatments , which they attended three times a week for 10 weeks : Active Physical Treatment ( APT ) , Cognitive-Behavioral Treatment ( CBT ) , Combined Treatment of APT and CBT ( CT ) , or Waiting List ( WL ) . The outcome variables were self-reported functional limitations , patient 's main complaints , pain , mood , self-rated treatment effectiveness , treatment satisfaction and physical performance including walking , st and ing up , reaching forward , stair climbing and lifting . Assessment s were carried out by blinded research assistants at baseline and immediately post-treatment . The data were analyzed using the intention-to-treat principle . Results For 212 patients , data were available for analysis . After treatment , significant reductions were observed in functional limitations , patient 's main complaints and pain intensity for all three active treatments compared to the WL . Also , the self-rated treatment effectiveness and satisfaction appeared to be higher in the three active treatments . Several physical performance tasks improved in APT and CT but not in CBT . No clinical ly relevant differences were found between the CT and APT , or between CT and CBT . Conclusion All three active treatments were effective in comparison to no treatment , but no clinical ly relevant differences between the combined and the single component treatments were found Background Low back pain is a common disorder in western industrialised countries and the type of treatments for low back pain vary considerably . Methods In a r and omised controlled trial the cost-effectiveness and cost-utility of an intensive group training protocol versus physiotherapy guideline care for sub-acute and chronic low back pain patients is evaluated . Patients with back pain for longer than 6 weeks who are referred to physiotherapy care by their general practitioner or medical specialist are included in the study . The intensive group training protocol combines exercise therapy with principles of behavioural therapy ( " grade d activity " ) and back school . This training protocol is compared to physiotherapy care according to the recently published Low Back Pain Guidelines of the Royal Dutch College for Physiotherapy . Primary outcome measures are general improvement , pain intensity , functional status , work absenteeism and quality of life . The direct and indirect costs will be assessed using cost diaries . Patients will complete question naires at baseline and 6 , 13 , 26 and 52 weeks after r and omisation . Discussion No trials are yet available that have evaluated the effect of an intensive group training protocol including behavioural principles and back school in a primary physiotherapy care setting and no data on cost-effectiveness and cost-utility are available Intensive group training using principles of grade d activity has been proven to be effective in occupational care for workers with chronic low back pain . Objective of the study was to compare the effects of an intensive group training protocol aim ed at returning to normal daily activities and guideline physiotherapy for primary care patients with non-specific chronic low back pain . The study was design ed as pragmatic r and omised controlled trial with a setup of 105 primary care physiotherapists in 49 practice s and 114 patients with non-specific low back pain of more than 12 weeks duration participated in the study . In the intensive group training protocol exercise therapy , back school and operant-conditioning behavioural principles are combined . Patients were treated during 10 individual sessions along 20 group sessions . Usual care consisted of physiotherapy according to the Dutch guidelines for Low Back Pain . Main outcome measures were functional disability ( Rol and Morris disability question naire ) , pain intensity , perceived recovery and sick leave because of low back pain assessed at baseline and after 6 , 13 , 26 and 52 weeks . Both an intention-to-treat analysis and a per- protocol analysis were performed . Multilevel analysis did not show significant differences between both treatment groups on any outcome measures during the complete follow-up period , with one exception . After 26 weeks the protocol group showed more reduction in pain intensity than the guideline group , but this difference was absent after 52 weeks . We finally conclude that an intensive group training protocol was not more effective than usual physiotherapy for chronic low back pain The application of single motor unit biofeedback training ( SMUBT ) techniques was compared to traditional therapies in treating chronic low back pain ( CLBP ) . Thirty-six volunteers ( who experienced daily pain for 7 years in the T8 to S1 area ) were r and omly assigned to one of three treatments ; SMUBT , relaxation training , or an educational program . The pain level and electromyographic activity of all subjects were assessed by a person blind to the treatment ; before , immediately after , and 90 days after treatment . The SMUBT group reported immediately decreased pain which was maintained at 90 days , the relaxation group showed no changes , while the education group reported decreased pain at 90 days . The EMG results showed decreased amplitude and bilateral differences for the SMUBT and education groups . A 4-year follow-up revealed the SMUBT group remained symptom free . Implication s and discussion of the results concludes the paper & NA ; Since pain‐related fear may contribute to the development and maintenance of chronic low back pain ( CLBP ) , an exposure in vivo treatment ( EXP ) was developed for CLBP patients . We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant grade d activity ( GA ) directly and 6 months post‐treatment in a multi‐centre r and omized controlled trial . In total , 85 patients suffering from disabling non‐specific CLBP reporting at least moderate pain‐related fear were r and omly allocated to EXP or GA . It was demonstrated that EXP , despite excelling in diminishing pain catastrophizing and perceived harmfulness of activities , was equally effective as GA in improving functional disability and main complaints , although the group difference almost reached statistical significance favouring EXP . Both treatment conditions did not differ in pain intensity and daily activity levels either . Nor was EXP superior to GA in the subgroup of highly fearful patients . Irrespective of treatment , approximately half the patients reported clinical ly relevant improvements in main complaints and functional disability , although for the latter outcome the group difference was almost significant favouring EXP . Furthermore , the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities . In sum , this study demonstrates that up to 6 months after treatment EXP is an effective treatment , but not more effective than GA , in moderately to highly fearful CLBP patients , although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established . Possible explanations for these findings are discussed Introduction : Behaviorally oriented grade d activity interventions have been suggested for sick-listed workers with low back pain on return to work , but have not been extensively evaluated . Methods : One hundred and thirty-four workers were r and omly assigned to either a grade d activity intervention ( n = 67 ) or usual care ( n = 67 ) and followed-up for 12 months . Results : The grade d activity group returned back to work faster with a median of 54 days compared to 67 days in the usual care group . The grade d activity intervention was more effective after approximately 50 days post-r and omization ( HRR = 1.9 , CI = 1.2–3.1 , p = 0.01 ) . Differences between the groups in number of recurrent episodes , total number of days of sick leave due to low back pain , and total number of days of sick leave due to all diagnoses , were in favor of the grade d activity group , although not statistically significant . No effects of the grade d activity intervention were found for functional status or pain . Conclusion : Grade d activity intervention is a valuable strategy to enhance short-term return to work outcomes Back pain and injury are a widespread problem for direct care providers and can lead to disability and job loss . Although most intervention studies focus on the number of reported injuries as the outcome variable , pain is a leading indicator of impending injury . More secondary prevention interventions focusing on early detection and treatment of pain are needed to reduce injuries . The primary aim of this study was to assess the feasibility and effect size of a cognitive behavioral therapy ( CBT ) intervention to reduce the measures of back pain , stress , and disability in direct care providers working with back pain . The secondary aim was to assess the association between affect and outcome variables , particularly unscheduled work absence , which is a component of disability . This r and omized clinical trial recruited 32 registered nurses and nursing assistants with a history of back pain in the past year and assigned them to either an intervention or a control group . The CBT intervention was a weekly stress and pain management session over 6 weeks led by a clinical psychologist . Data for both groups were collected at baseline and at 6 weeks , with work absence data caused by back pain self-reported for 12 weeks . Pain intensity scores declined in the intervention group , indicating a large effect . However , stress scores increased . Depression scores accounted for one-third of the variance in hours absent because of back pain . Although there was a high dropout rate in the intervention group , a cognitive-behavioral intervention shows promise as a secondary prevention intervention Abstract Objectives To assess the clinical effectiveness of surgical stabilisation ( spinal fusion ) compared with intensive rehabilitation for patients with chronic low back pain . Design Multicentre r and omised controlled trial . Setting 15 secondary care orthopaedic and rehabilitation centres across the United Kingdom . Participants 349 participants aged 18 - 55 with chronic low back pain of at least one year 's duration who were considered c and i date s for spinal fusion . Intervention Lumbar spine fusion or an intensive rehabilitation programme based on principles of cognitive behaviour therapy . Main outcome measure The primary outcomes were the Oswestry disability index and the shuttle walking test measured at baseline and two years after r and omisation . The SF-36 instrument was used as a secondary outcome measure . Results 176 participants were assigned to surgery and 173 to rehabilitation . 284 ( 81 % ) provided follow-up data at 24 months . The mean Oswestry disability index changed favourably from 46.5 ( SD 14.6 ) to 34.0 ( SD 21.1 ) in the surgery group and from 44.8 ( SD14.8 ) to 36.1 ( SD 20.6 ) in the rehabilitation group . The estimated mean difference between the groups was –4.1 ( 95 % confidence interval –8.1 to –0.1 , P = 0.045 ) in favour of surgery . No significant differences between the treatment groups were observed in the shuttle walking test or any of the other outcome measures . Conclusions Both groups reported reductions in disability during two years of follow-up , possibly unrelated to the interventions . The statistical difference between treatment groups in one of the two primary outcome measures was marginal and only just reached the predefined minimal clinical difference , and the potential risk and additional cost of surgery also need to be considered . No clear evidence emerged that primary spinal fusion surgery was any more beneficial than intensive rehabilitation Background In the industrial world , non-specific back and neck pain ( BNP ) is the largest diagnostic group underlying sick-listing . For patients with subacute and chronic (= full-time sick-listed for 43 – 84 and 85 – 730 days , respectively ) BNP , cognitive-behavioural rehabilitation was compared with primary care . The specific aim was to answer the question : within an 18-month follow-up , will the outcomes differ in respect of sick-listing and number of health-care visits ? Methods After stratification by age ( ≤ 44/≥ 45 years ) and subacute/chronic BNP , 125 Swedish primary -care patients were r and omly allocated to cognitive-behavioural rehabilitation ( rehabilitation group ) or continued primary care ( primary -care group ) . Outcome measures were Return-to-work share ( percentage ) and Return-to-work chance ( hazard ratios ) over 18 months , Net days ( crude sick-listing days × degree ) , and the number of Visits ( to physicians , physiotherapists etc . ) over 18 months and the three component six-month periods . Descriptive statistics , Cox regression and mixed-linear models were used . Results All patients : Return-to-work share and Return-to-work chance were equivalent between the groups . Net days and Visits were equivalent over 18 months but decreased significantly more rapidly for the rehabilitation group over the six-month periods ( p < .05 ) . Subacute patients : Return-to-work share was equivalent . Return-to-work chance was significantly greater for the rehabilitation group ( hazard ratio 3.5 [ 95%CI1.001 – 12.2 ] ) . Net days were equivalent over 18 months but decreased significantly more rapidly for the rehabilitation group over the six-month periods and there were 31 days fewer in the third period . Visits showed similar though non-significant differences and there were half as many in the third period . Chronic patients : Return-to-work share , Return-to-work chance and Net days were equivalent . Visits were equivalent over 18 months but tended to decrease more rapidly for the rehabilitation group and there were half as many in the third period ( non-significant ) . Conclusion The results were equivalent over 18 months . However , there were indications that cognitive-behavioural rehabilitation in the longer run might be superior to primary care . For subacute BNP , it might be superior in terms of sick-listing and health-care visits ; for chronic BNP , in terms of health-care visits only . More conclusive results concerning this possible long-term effect might require a longer follow-up . Trial registration NCT00488735 OBJECTIVE To evaluate the effect of function-centered compared with pain-centered inpatient rehabilitation in patients whose absence from work is due to chronic nonspecific low back pain ( LBP ) . DESIGN Single-blinded r and omized controlled trial with follow-up assessment s immediately after treatment and at 3 months . SETTING Center for work rehabilitation in Switzerl and . PARTICIPANTS Patients with more than 6 weeks of work absence due to chronic nonspecific LBP ( N=174 ; 137 men , 37 women ; mean age + /- st and ard deviation , 42+/-8 y ; mean sick leave before study , 6.5 mo ) . INTERVENTIONS Function-centered treatment ( FCT ) ( 4h/d , 6d/wk , for 3 wk ) consisted of work simulation , strength , endurance , and cardiovascular training . Pain-centered treatment ( PCT ) ( 2.5h/d , 6d/wk , for 3 wk ) used a mini back school , individually selected passive and active mobilization , stretching , and low-intensity strength training . MAIN OUTCOME MEASURES The number of days at work in 3 months after treatment , self-efficacy , lifting capacity , pain , mobility , strength , and global perceived effect . Effect sizes ( ESs ) ( Cohen d ) were defined as small ( ES range , 0.2 - 0.5 ) , moderate ( ES range , 0.5 - 0.8 ) , and large ( ES , > 0.8 ) . RESULTS Groups were comparable at baseline . Moderate ESs for the FCT group versus PCT group were found for days at work ( 25.9 d vs 15.8d , ES=.36 , P = .029 ) , self-efficacy ( 5.9 points vs -7.4 points , ES=.55 , P = .003 ) , and lifting capacity ( 2.3 kg vs 0.2 kg , ES=.54 , P = .004 ) . CONCLUSIONS Function-centered rehabilitation increases the number of work days , self-efficacy , and lifting capacity in patients with nonacute nonspecific LBP A prospect i ve r and omized study of 542 injured workers with continuing pain compared 271 workers who were treated at either one of two clinics that provided functional restoration with a control group of 271 subjects . Chronic pain was caused by low back injury in 78 % of patients ; 79 % of those treated were at work 12 months after completion of treatment compared with 78 % of the control subjects . When the patients were divided into subsets , based on the accident date and followed monthly , the duration of absence from work , the compensation costs , the disability award costs , and the total costs were less for those treated than the control subjects , but these were not statistically significant . Using the difference in total costs as a measure of relative success , back injuries had better results than other injuries in this study 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 Study Design . A prospect i ve clinical r and omized controlled trial . Objectives . To determine the long-term effect of a combined exercise and motivational program on the level of disability of patients with chronic and recurrent low back pain ( LBP ) . Summary of Background Data . There is agreement on the importance of exercise during the course of chronic LBP . However , it is well known that long-term adherence with exercises is particularly low . Methods . A total of 93 patients with LBP were r and omly assigned to the control group ( st and ard exercise program ) or the motivational group ( combined exercise and motivational program ) . Follow-up assessment s were performed at 3.5 weeks , 4 months , 12 months , and 5 years . Main outcome measures were disability scores , pain intensity , and working ability . In addition to classic statistics , the sophisticated linear partial credit model was used to test the effects of treatment on disability scores . Results . In both groups , significant improvements in the disability scores were found at all points of follow-up assessment , however , the cumulative effect of the treatment in the motivational group was more than twice as much as in the control group . This result is in accordance with the increasing divergence in pain intensity between groups between 12 months and 5 years after intervention . A significant , positive long-term effect at the 5-year re assessment in working ability was only seen in the motivational group . All statistically significant results were confirmed by intention-to-treat analyses . Conclusions . Regarding long-term efficacy , the combined exercise and motivation program was superior to the st and ard exercise program . Five years after the supervised combined exercise and motivational program , patients had significant improvements in disability , pain intensity , and working ability The aim of this study was to determine whether grade d activity restored occupational function in industrial blue-collar workers who were sick-listed for 8 weeks because of subacute , nonspecific , mechanical low back pain ( LBP ) . Patients with LBP , who had been examined by an orthopedic surgeon and a social worker , were r and omly assigned to either an activity group ( n = 51 ) or a control group ( n = 52 ) . Patients with defined orthopedic , medical , or psychiatric diagnoses were excluded before r and omization . The grade d activity program consisted of four parts : ( 1 ) measurements of functional capacity ; ( 2 ) a work-place visit ; ( 3 ) back school education ; and ( 4 ) an individual , submaximal , gradually increased exercise program , with an operant-conditioning behavioral approach , based on the results of the tests and the dem and s of the patient 's work . Records of the amount of sick leave taken over a 3-year period ( ie , the 1-year periods before , during , and after intervention ) were obtained from each patient 's Social Insurance Office . The patients in the activity group returned to work significantly earlier than did the patients in the control group . The median number of physical therapist appointments before return to work was 5 , and the average number of appointments was 10.7 ( SD = 12.3 ) . The average duration of sick leave attributable to LBP during the second follow-up year was 12.1 weeks ( SD = 18.4 ) in the activity group and 19.6 weeks ( SD = 20.7 ) in the control group . Four patients in the control group and 1 patient in the activity group received permanent disability pensions . The grade d activity program made the patients occupationally functional again , as measured by return to work and significantly reduced long-term sick leave Study Design . A r and omized controlled trial . Objectives . To determine 1 ) whether , among patients with persistent disabling low back pain ( LBP ) , a group program of exercise and education using a cognitive behavioral therapy ( CBT ) approach , reduces pain and disability over a subsequent 12-month period ; 2 ) the cost-effectiveness of the intervention ; and 3 ) whether a priori preference for type of treatment influences outcome . Summary of Background Data . There is evidence that both exercise and CBT delivered in specialist setting s is effective in improving LBP . There is a lack of evidence on whether such interventions , delivered by trained individuals in primary care , result in improved outcomes . Methods . The study was conducted in nine family medical practice s in East Cheshire , UK . Patients 18 to 65 years of age , consulting with LBP , were recruited ; those still reporting LBP 3 months after the initial consultation were r and omized between the two trial arms . The intervention arm received a program of eight 2-hour group exercise session over 6 weeks comprising active exercise and education delivered by physiotherapists using a CBT approach . Both arms received an educational booklet and audio-cassette . The primary outcome measures were pain ( 0–100 Visual Analogue Scale ) and disability ( Rol and and Morris Disability Scale ; score 0–24 ) . Results . A total of 196 subjects ( 84 % ) completed follow-up 12 months after the completion of the intervention program . The intervention showed only a small and nonsignificant effect at reducing pain ( −3.6 mm ; 95 % confidence interval , −8.5 , 1.2 mm ) and disability ( −0.6 score ; 95 % confidence interval , −1.6 , 0.4 ) . The cost of the intervention was low with an incremental cost-effectiveness ratio of £ 5000 ( U.S. $ 8650 ) per quality adjusted life year . In addition , patients allocated to the intervention that had expressed a preference for it had clinical ly important reductions in pain and disability . Conclusions . This intervention program produces only modest effects in reducing LBP and disability over a 1-year period . The observation that patient preference for treatment influences outcome warrants further investigation OBJECTIVE To investigate return to work and cost-effectiveness of the addition of cognitive-behavioral treatment to st and ard therapy compared to st and ard 3-week inpatient rehabilitation for patients with chronic low back pain . METHODS A prospect i ve economic evaluation alongside a r and omized controlled trial was performed . Outcomes included days off work due to spinal complaints , health-related quality of life , and direct and indirect disease-related costs . RESULTS A total of 409 patients with chronic low back pain , who were admitted to a 3-week inpatient rehabilitation , were r and omly assigned to usual care or usual care plus cognitive behavioral treatment . Average incremental costs for psychological treatment during rehabilitation were Euros 127 ( 95 % CI 125.6 , 130.9 ; p < 0.001 ) . Six months after rehabilitation , patients in the intervention group were absent from work an average of 5.4 ( 95 % CI -1.4 , 12.1 ; p = 0.12 ) days less than patients receiving usual treatment . Between groups , there were no significant differences in quality -adjusted life-years gained or in direct medical or nonmedical costs . The cognitive behavioral treatment showed lower indirect costs : Euros 751 ( 95 % CI -145 , 1641 ; p = 0.097 ) . CONCLUSION Adding a cognitive behavioral component to st and ard therapy may reduce work days lost and thus decrease indirect costs . From a societal perspective , the cost of the psychological treatment was compensated by lower indirect costs Study Design . A critical appraisal of the literature . Objectives . To increase awareness of the importance of applicability and clinical relevance of the results of r and omized controlled trials ( RCTs ) in the field of spinal disorders by formulating a list of items for assessment of applicability and clinical relevance of results of RCTs . Summary of Background Data . In systematic review s of r and omized controlled trials ( RCTs ) , critical appraisal of method ologic quality is considered important . Less attention has been paid to the assessment of the applicability and the clinical relevance of the results . Methods . RCTs in an up date of the Cochrane review on exercise therapy for low back pain were used . Most of the trials did not score positively on the five Cochrane Back Review Group basic items describing patients : intervention and setting , outcome , effect size , and benefits related to adverse effects . Item 1 was met by 88 % of the trials , but item 2 only by 51 % , item 3 by 67 % , item 4 by 35 % , and item 5 by 0 % . Subsequently , a more comprehensive list of items for the assessment of applicability and clinical relevance of results of RCTs was developed . These criteria were pilot tested on the RCTs . After pilot testing and a subsequent consensus meeting , the list of items was drafted and circulated among the members of the Editorial Board of the Cochrane Back Review Group . Changes were made in response to comments . Results . The final list consists of 40 items . The items are ordered on two headings : Does the report enable the assessment of applicability ? Are the study results clinical ly relevant ? We present examples of informative and noninformative reporting of RCTs in order to illustrate how information on applicability and clinical relevance of results can be assessed . Conclusions . Authors of RCTs should adequately report on items that are essential to assess the applicability and clinical relevance of results . The presented list of items may help clinicians reading RCTs and authors of systematic review s to draw more balanced conclusions on applicability and clinical relevance of results UNLABELLED The aim of this study was to examine whether treatments based on different theories change pain catastrophizing and internal control of pain , and whether changes in these factors mediate treatment outcome . Participants were 211 patients with nonspecific chronic low back pain ( CLBP ) participating in a r and omized controlled trial , attending active physical treatment ( APT , n = 52 ) , cognitive-behavioral treatment ( CBT , n = 55 ) , treatment combining the APT and CBT ( CT , n = 55 ) , or waiting list ( WL , n = 49 ) . Pain catastrophizing decreased in all 3 active treatment groups and not in the WL . There was no difference in the change in internal control across all 4 groups . In all the active treatment groups , patients improved regarding perceived disability , main complaints , and current pain at post-treatment , and no changes were observed in the WL group . Depression only changed significantly in the APT group . Change in pain catastrophizing mediated the reduction of disability , main complaints , and pain intensity . In the APT condition , pain catastrophizing also mediated the reduction of depression . Not only cognitive-behavioral treatments but also a physical treatment produced changes in pain catastrophizing that seemed to mediate the outcome of the treatment significantly . The implication s and limitations of these results are discussed . PERSPECTIVE This article shows that treatment elements that do not deliberately target cognitive factors can reduce pain catastrophizing . Reduction in pain catastrophizing seemed to mediate the improvement of functioning in patients with chronic low back pain . The results might contribute to the development of more effective interventions The aim of this cost-effectiveness study was to compare a combined operant programme plus cognitive/relaxation programme with an operant programme plus attention-control and to compare both programmes with a waiting-list control group and with operant rehabilitation provided , as usual , by the same rehabilitation centre . One hundred and forty eight patients with chronic low back pain were r and omly assigned to the different conditions . The economic endpoints were the costs of the programme and other health care utilisation , costs for the patient , and indirect costs associated with production losses due to low back pain . The effects were measured in terms of global assessment of change and utilities , using rating scale and st and ard gamble methods . The 3-year study determined that adding a cognitive component to an operant treatment did not lead to significant differences in costs and improvement in quality of life when compared with the operant treatment alone . Compared with the common individual rehabilitation therapy it can be concluded that the same effects can be reached at the same or lower costs with a shorter , more intense st and ardised group programme . The operant treatment alone is more effective than providing no treatment in the waiting-list control group Purpose : Loving-kindness meditation has been used for centuries in the Buddhist tradition to develop love and transform anger into compassion . This pilot study tested an 8-week loving-kindness program for chronic low back pain patients . Method : Patients ( N = 43 ) were r and omly assigned to the intervention or st and ard care . St and ardized measures assessed patients ’ pain , anger , and psychological distress . Findings : Post and follow-up analyses showed significant improvements in pain and psychological distress in the loving-kindness group , but no changes in the usual care group . Multilevel analyses of daily data showed that more loving-kindness practice on a given day was related to lower pain that day and lower anger the next day . Conclusions : Preliminary results suggest that the loving-kindness program can be beneficial in reducing pain , anger , and psychological distress in patients with persistent low back pain . Implication s : Clinicians may find loving-kindness meditation helpful in the treatment of patients with persistent pain Abstract The effectiveness of lumbar fusion for chronic low back pain after surgery for disc herniation has not been evaluated in a r and omized controlled trial . The aim of the present study was to compare the effectiveness of lumbar fusion with posterior transpedicular screws and cognitive intervention and exercises . Sixty patients aged 25–60 years with low back pain lasting longer than 1 year after previous surgery for disc herniation were r and omly allocated to the two treatment groups . Experienced back surgeons performed transpedicular fusion . Cognitive intervention consisted of a lecture intended to give the patient an underst and ing that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it . This was reinforced by three daily physical exercise sessions for 3 weeks . The primary outcome measure was the Oswestry Disability Index ( ODI ) . Outcome data were analyzed on an intention‐to‐treat basis . Ninety‐seven percent of the patients , including seven of eight patients who had either not attended treatment ( n = 5 ) or changed groups ( n = 2 ) , completed 1‐year follow‐up . ODI was significantly improved from 47 to 38 after fusion and from 45 to 32 after cognitive intervention and exercises . The mean difference between treatments after adjustment for gender was −7.3 ( 95 % CI −17.3 to 2.7 , p = 0.15 ) . The success rate was 50 % in the fusion group and 48 % in the cognitive intervention/exercise group . For patients with chronic low back pain after previous surgery for disc herniation , lumbar fusion failed to show any benefit over cognitive intervention and exercises CONTEXT Patients suffering from chronic low back pain ( cLBP ) are often unsatisfied with conventional medical care and seek alternative therapies . Many mind-body techniques are said to help patients with low back pain by enhancing body awareness , which includes proprioception deficit in cLBP , but have not been rigorously studied in cLBP . Breath therapy is a western mind-body therapy integrating body awareness , breathing , meditation , and movement . Preliminary data suggest benefits from breath therapy for proprioception and low back pain . OBJECTIVE To assess the effect of breath therapy on cLBP . DESIGN R and omized , controlled trial . SETTING Academic medical center . PARTICIPANTS Thirty-six patients with cLBP . INTERVENTIONS Six to eight weeks ( 12 sessions ) of breath therapy versus physical therapy . MAIN OUTCOME MEASURES Pain by visual analog scale ( VAS ) , function by Rol and Scale , overall health by Short Form 36 ( SF-36 ) at baseline , six to eight weeks , and six months . Balance as a potential surrogate for proprioception and body-awareness measured at the beginning and end of treatment . RESULTS Pre- to post-intervention , patients in both groups improved in pain ( VAS : -2.7 with breath therapy , -2.4 with physical therapy ; SF-36 : + 14.9 with breath therapy and + 21.0 with physical therapy ) . Breath therapy recipients improved in function ( Rol and : -4.8 ) and in the physical and emotional role ( SF-36 : + 15.5 and 14.3 ) . Physical therapy recipients improved in vitality ( SF-36 : + 15.0 ) . Average improvements were not different between groups . At six to eight weeks , results showed a trend favoring breath therapy ; at six-months , a trend favoring physical therapy . Balance measures showed no improvements and no correlations with other outcomes . CONCLUSIONS Patients suffering from cLBP improved significantly with breath therapy . Changes in st and ard low back pain measures of pain and disability were comparable to those result ing from high- quality , extended physical therapy . Breath therapy was safe . Qualitative data suggested improved coping skills and new insight into the effect of stress on the body as a result of breath therapy . Balance measures did not seem to be valid measures of clinical change in patients ' cLBP BACKGROUND Pain-related fear is related to disability in persistent pain conditions . Exposure treatment has been reported to be of great benefit in replicated single case experiments . AIM To evaluate the effects of exposure in vivo on fear and function in patients with persistent pain and work disability . METHOD We recruited 46 patients suffering from long-term back pain and reduced function , who also were deemed fearful according to st and ardized measures . Participants were r and omized into either an exposure plus usual treatment or waiting list control plus usual treatment group . After the waiting period the control group crossed over and received the exposure treatment . RESULTS Between group comparisons showed a significantly better result for the exposure group on function , but not for fear or pain and effect sizes were modest ( function=.6 ; fear=.4 ; pain=.1 ) . When the control group crossed over to treatment significant treatment effects were noted for fear and function . For all patients treated , the pre to post-treatment effect sizes were large ( function=.7 ; fear=1.1 ; pain=.9 ) . There were 12 dropouts ( 8 in exposure and 4 in the control ) during the first treatment phase and an additional 4 when the control group crossed over to exposure . CONCLUSIONS Compared to a group receiving usual treatment and waiting for exposure , the exposure in vivo group demonstrated a significantly larger improvement on function . Overall exposure had moderate effects on function , fear and pain intensity . We conclude that exposure may be important in treatment , but is not recommended as a " st and alone " adjunct to usual treatment & NA ; Psychological treatments for chronic pain , particularly those based upon cognitive behavioural principles , have generally been shown to be efficacious . Recently , a treatment has been developed based upon the fear‐avoidance model of chronic musculoskeletal pain , which suggests chronic pain can be relieved by exposing the individual to movements and tasks that have been avoided due to fear of (re)injury . This grade d in vivo exposure treatment has been found to be beneficial in case studies . The present investigation utilized a r and omized controlled trial method to assess the effectiveness of grade d in vivo exposure relative to other conditions . Forty‐four chronic low back pain patients were r and omly assigned to grade d in vivo exposure , grade d activity , or a wait‐list condition . While only trend differences were observed for pain‐related disability , patients in the grade d in vivo exposure condition demonstrated ( a ) significantly greater improvements on measures of fear of pain/movement , fear avoidance beliefs , pain‐related anxiety , and pain self‐efficacy when compared to those in the grade d activity condition , and ( b ) significantly greater improvements on measures of fear‐avoidance beliefs , fear of pain/movement , pain‐related anxiety , pain catastrophising , pain experience , and anxiety and depression when compared to those in the wait‐list control condition . Additionally , patients in the grade d in vivo exposure condition maintained improvements in these areas at one month follow‐up . Implication s of these findings for the treatment of individuals with chronic low back and other pain conditions are discussed Fifty-eight out patients with chronic low back pain were r and omly allocated to one of six experimental conditions . Four conditions were design ated as treatment conditions and two as control conditions . The four treatment groups consisted of : cognitive treatment ( either with or without relaxation training ) and behavioural treatment ( either with or without relaxation training ) . The cognitive and behavioural groups also received physiotherapy . The two control conditions consisted of : attention ( physiotherapy plus discussion sessions ) and no-attention ( physiotherapy-only ) conditions . All conditions , including the two controls , received the same physiotherapy back-education and exercise program . For the sample as a whole , improvements were obtained on measures of affective distress , functional impairment , medication use , pain-related dysfunctional cognitions and use of active coping strategies . These improvements were generally maintained at 6- and 12-month follow-ups . The combined psychological/physiotherapy treatment conditions improved significantly more than the physiotherapy-only conditions from pre to posttreatment on measures of pain intensity , self-rated functional impairment and pain-related dysfunctional cognitions . However , these differences were only weakly maintained at 6- and 12-month follow-ups . The behavioural conditions improved significantly more than the cognitive conditions from pre to posttreatment on the self-rated measure of functional impairment , but this difference was not maintained at 6- and 12-month follow-ups . Progressive relaxation training was found to make little contribution to either cognitive or behavioural treatments The use of complementary and alternative medicine ( CAM ) for the management of chronic low back pain ( CLBP ) continues to rise . However , questions regarding the efficacy of many CAM therapies for CLBP remain unresolved . The present study investigated the effectiveness of reflexology for CLBP . A pragmatic r and omised controlled trial was conducted . N=243 patients were r and omised to one of three groups : reflexology , relaxation , or non-intervention ( usual care ) . All completed a question naire booklet before and after the treatment phase , and at six months follow up . This measured their general health status , pain , functioning , coping strategies and mood . After adjusting for pre-treatment scores repeated measures ANCOVA found no significant differences between the groups pre and post treatment on the primary outcome measures of pain and functioning . There was a main effect of pain reduction , irrespective of group . Trends in the data illustrated the pain reduction was greatest in the reflexology group . Thus , the current study does not indicate that adding reflexology to usual GP care for the management of CLBP is any more effective than usual GP care alone Forty-four chronic , but relatively well functioning , low back pain patients were assigned to either Cognitive Behaviour Therapy ( CBT ) . Electromyographic Biofeedback ( EMGBF ) or Wait List Control ( WLC ) . Both treatments were conducted over eight sessions in groups of four subjects . Results at post-treatment indicated significant improvements in functioning on measures of pain intensity , perceived level of disability , adaptive beliefs about pain and the level of depression in both the CBT and EMGBF conditions . These improvements were not evident for the WLC condition . At 6 months follow-up , treatment gains were maintained in the areas of pain intensity , pain beliefs , and depression , for both treatment groups , with further improvements occurring in anxiety and use of active coping skills . No significant differences were found between CBT and EMGBF on any of the outcome measures at either post-treatment or at 6 months follow-up . Further research is required to determine the degree to which these results reflect the mild level of psychological impairment and disability status of patients in the present study & NA ; The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem . A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods . The treatment group received an intervention design ed to reduce current problems , but above all to prevent reinjury and minor pains from becoming chronic medical problems , and it included a physical and behavioral therapy package . The control group was placed on a waiting‐list . Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity , anxiety , sleep quality and fatigue ratings , observed pain behavior , activities , mood , and helplessness . These differences were generally maintained at the 6 month follow‐up . In addition , the treatment group broke a trend for increasing amounts of pain‐related absenteeism , while the control group did not . Taken as a whole , the results suggest that a secondary prevention program aim ed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems 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 & NA ; Given the dem and for interventions that may prevent the development of persistent musculoskeletal pain problems , we investigated the effects of a cognitive‐behavioral program in a group of non‐ patients with neck or back pain symptoms . Two hundred and fifty‐three people selected from a population study were invited to participate . These people had experienced four or more episodes of relatively intense spinal pain during the past year but had not been out of work more than 30 days . Participants were r and omly assigned to either a cognitive‐behavioral group intervention or a treatment as usual comparison group . The experimental group received a st and ardized six‐session program , provided by a trained therapist according to a manual . A significant overall analysis at the 1‐year follow‐up showed that the cognitive‐behavioral group produced better results on 26 of the 33 outcome variables . Group comparisons indicated that the cognitive‐behavioral group , relative to the comparison group , had significantly better results with regard to fear‐avoidance beliefs , number of pain‐free days , as well as the key variable of sick leave . Participation in the cognitive behavioral group reduced the risk for long‐term sick leave during the follow‐up by threefold . Thus , despite the strong natural recovery rate for back pain , the cognitive‐behavioral intervention produced a significant preventive effect with regard to disability Objective To test the predictive utility of the Örebro Musculoskeletal Pain Screening Question naire in identifying patients at risk for developing persistent back pain problems . Design Prospect i ve , where participants completed the question naire and their cases were followed for 6 months to assess outcome with regard to pain , function , and absenteeism due to sickness . Participants One hundred seven patients , recruited from seven primary care units . Results Discriminant analyses showed that the items on the question naire were significantly related to future problems . For absenteeism due to sickness , 68 % of the patients were correctly classified into one of three groups , whereas an even distribution would have produced 33 % . The analyses for function correctly classified 81 % , and for pain 71 % , into one of two groups , compared with a chance level of 50 % . A total score analysis demonstrated that a cutoff score of 90 points had a sensitivity of 89 % and a specificity of 65 % for absenteeism due to sickness , and a sensitivity of 74 % and a specificity of 79 % for functional ability . Conclusions The results underscore that psychological variables are related to outcome 6 months later , and they replicate and extend earlier findings indicating that the Örebro Screening Question naire is a clinical ly reliable and valid instrument . The total score was a relatively good predictor of future absenteeism due to sickness as well as function , but not of pain . The results suggest that the instrument could be of value in isolating patients in need of early interventions and may promote the use of appropriate interventions for patients with psychological risk factors In primary care and physical therapy setting s , we evaluated an intervention for chronic back pain patients which incorporated fear reducing and activating techniques . Primary care patients seen for back pain in primary care were screened to identify persons with significant activity limitations 8–10 weeks after their visit . Eligible and willing patients were r and omized ( N=240 ) . A brief , individualized program to reduce fear and increase activity levels was delivered by a psychologist and physical therapists . Over a 2 year follow‐up period , intervention patients reported greater reductions in pain‐related fear ( P<0.01 ) , average pain ( P<0.01 ) and activity limitations due to back pain ( P<0.01 ) relative to control patients . The percent with greater than a one‐third reduction in Rol and Disability Question naire scores at 6 months was 42 % among Intervention patients and 24 % among control patients ( P<0.01 ) . Over the 2 year follow‐up , fewer intervention patients reported 30 or more days unable to carry out usual activities in the prior 3 months ( P<0.01 ) . The adjusted mean difference in activity limitation days was 4.5 days at 6 months , 2.8 days at 12 months , and 6.9 days at 24 months . No differences were observed in the percent unemployed or the percent receiving worker 's compensation or disability benefits , but these outcomes were relatively uncommon . We conclude that an intervention integrating fear reducing and activating interventions into care for chronic back pain patients produced sustained reductions in patient fears , common activity limitations related to back pain , and days missed from usual activities due to back pain Background : Low back pain is a common medical and social problem associated with disability and absence from work . Knowledge on effective return to work ( RTW ) interventions is scarce . Objective : To determine the effectiveness of grade d activity as part of a multistage RTW programme . Design : R and omised controlled trial . Setting : Occupational healthcare . Subjects : 112 workers absent from work for more than eight weeks due to low back pain were r and omised to either grade d activity ( n = 55 ) or usual care ( n = 57 ) . Intervention : Grade d activity , a physical exercise programme aim ed at RTW based on operant-conditioning behavioural principles . Main outcome measures : The number of days off work until first RTW for more then 28 days , total number of days on sick leave during follow up , functional status , and severity of pain . Follow up was 26 weeks . Results : Grade d activity prolonged RTW . Median time until RTW was equal to the total number of days on sick leave and was 139 ( IQR = 69 ) days in the grade d activity group and 111 ( IQR = 76 ) days in the usual care group ( hazard ratio = 0.52 , 95 % CI 0.32 to 0.86 ) . An interaction between a prior workplace intervention and grade d activity , together with a delay in the start of the grade d activity intervention , explained most of the delay in RTW ( hazard ratio = 0.86 , 95 % CI 0.40 to 1.84 without prior intervention and 0.39 , 95 % CI 0.19 to 0.81 with prior intervention ) . Grade d activity did not improve pain or functional status clinical ly significantly . Conclusions : Grade d activity was not effective for any of the outcome measures . Different interventions combined can lead to a delay in RTW . Delay in referral to grade d activity delays RTW . In implementing grade d activity special attention should be paid to the structure and process of care Study Design . R and omized , controlled trial . Objective . To evaluate a four‐session self‐management group intervention for patients with pain in primary care , led by trained lay persons with back pain . The intervention was design ed to reduce patient worries , encourage self‐care , and reduce activity limitations . Background Data . R and omized trials of educational interventions suggest that activating interventions may improve back pain outcomes . Expert opinion increasingly regards effective self‐management of back pain as important in achieving good outcomes . In this study , an educational intervention design ed to activate patients and support effective self‐management was evaluated . Methods . Six to 8 weeks after a primary care visit for back pain , patients were invited to participate in an educational program to improve back pain self‐management . Those showing interest by returning a brief question naire became eligible for the study . Participants ( n = −255 ) r and omly were assigned to either a self‐management group intervention or to a usual care control group . The effect of the intervention , relative to usual care , was assessed 3 , 6 , and 12 months after r and omization , controlling for baseline values . The intervention consisted of a four‐session group applying problem‐solving techniques to back pain self‐management , supplemented by educational material s ( book and videos ) supporting active management of back pain . The groups were led by lay persons trained to implement a fully structured group protocol . The control group received usual care , supplemented by a book on back pain care . Results . Participants r and omly assigned to the self‐management groups reported significantly less worry about back pain and expressed more confidence in self‐care . Rol and Disability Question naire Scores were significantly lower among participants in the self‐management groups relative to the usual care controls at 6 months ( P = 0.007 ) , and this difference was sustained at 12 months at borderline significance levels ( P = 0.09 ) . Among self‐management group participants , 48 % showed a 50 % or greater reduction in Rol and Disability Question naire Score at 6 months , compared with 33 % among the usual care controls . Conclusions . Self‐management groups led by trained lay persons following a structured protocol were more effective than usual care in reducing worries , producing positive attitudes toward self‐care , and reducing activity limitations among patients with back pain in primary care Study Design : A r and omized between-groups design evaluated massage therapy versus relaxation for chronic low back pain . Objectives : Treatment effects were evaluated for reducing pain , depression , anxiety and stress hormones , and sleeplessness and for improving trunk range of motion associated with chronic low back pain . Summary of Background Data : Twenty-four adults ( M age = 39.6 years ) with low back pain of nociceptive origin with a duration of at least 6 months participated in the study . The groups did not differ on age , socioeconomic status , ethnicity or gender . Methods : Twenty-four adults ( 12 women ) with lower back pain were r and omly assigned to a massage therapy or a progressive muscle relaxation group . Sessions were 30 minutes long twice a week for five weeks . on the first and last day of the 5-week study participants completed question naires , provided a urine sample and were assessed for range of motion . Results : By the end of the study , the massage therapy group , as compared to the relaxation group , reported experiencing less pain , depression , anxiety and improved sleep . They also showed improved trunk and pain flexion performance , and their serotonin and dopamine levels were higher . Conclusions : Massage therapy is effective in reducing pain , stress hormones and symptoms associated with chronic low back pain . Precis : Adults ( M age = 39.6 years ) with low back pain with a duration of at least 6 months received two 30-min massage or relaxation therapy sessions per week for 5 weeks . Participants receiving massage therapy reported experiencing less pain , depression , anxiety and their sleep had improved . They also showed improved trunk and pain flexion performance , and their serotonin and dopamine levels were higher OBJECTIVES Because musculoskeletal pain is the second most frequent reason for seeking health care , the aims of this study were to determine the value of psychosocial variables in evaluating risk for developing chronic back pain problems and to develop a screening methodology to identify patients likely to have a poor prognosis . STUDY DESIGN A prospect i ve study was conducted on consecutive patients with acute or subacute back pain , in which patients completed a screening question naire and were then followed up for 6 months to determine outcome . The primary outcome variable was accumulated sick leave . METHODS One hundred forty-two consecutive patients were asked to complete a question naire design ed for this study . This question naire contained 24 items concerning psychosocial aspects of the problem . Six months later , patients were contacted to complete outcome questions about accumulated sick leave . RESULTS A total of 97 % of the patients completed both question naires . Although patients , on average , improved greatly , 18 % had 1 - 30 days and 20 % had fewer than 30 days of sick leave during the follow-up period . Five variables were found to be the strongest predictors of sick leave outcome ( fear-avoidance work beliefs , perceived improvement , problems with work function , stress , and previous sick leave ) , correctly classifying 73 % of the patients as opposed to a chance rate of 33 % . A total score was evaluated as a means of judging risk and found to be strongly related to outcome . CONCLUSION Potent psychosocial risk factors associated with future sick absenteeism were identified . Because the total score was related to outcome , the instrument may have use in screening patients with acute or subacute spinal pain in clinical situations Patients with nonspecific mechanical low back pain ( n = 103 ) , examined by an orthopaedic surgeon and a social worker , were r and omized to an activity group ( n = 51 ) and a control group ( n = 52 ) . Patients with defined orthopaedic , medical , or psychiatirc diagnoses were excluded before r and omization . No patients were excluded due to place of birth or difficulties in speaking or underst and ing the Swedish language . The purpose of the study was to compare mobility , strength and fitness after traditional care and after traditional care plus a grade d activity program with a behavioral therapy approach . A grade d activity program , with a behavioral therapy approach was given under the guidance of a physical therapist . The endpoint of the grade d activity program was return to work . This program significantly increased mobility , strength , and fitness more than could be explained by only a time recovery effect , especially in males . The patients in the activity group returned to work earlier than did the patients in the control group . Spinal rotation , abdominal muscle endurance time and lifting capacity were significantly correlated to rate of return to work . Traditional care plus a grade d activity program were superior to only traditional care , evaluated in terms of mobility , strength and fitness . The grade d activity program proved to be a successful method of restoring occupational function and facilitating return to work in subacute low back pain patients . The patients in the grade d activity program learned that it is safe to move , while regaining function Abstract Twenty chronic low back pain ( LBP ) patients with relatively high st and ing paraspinal EMG levels ( > 5 gmV ) were r and omly assigned to 2 groups . One group ( N = 10 ) received EMG biofeedback training to reduce st and ing paraspinal EMG levels , the other group ( N = 10 ) served as a waiting list control group . Changes in perceived pain ( duration × intensity ) and paraspinal EMG in st and ing position were measured at a 3 week pretreatment baseline , during the 3 week treatment period , and at a 3 week post‐treatment baseline . Compared to patients in the waiting list control group , those who received EMG biofeedback showed a significant decrease in st and ing paraspinal EMG from pretreatment to post‐treatment baseline . However , no significant differences in reported pain were found during these periods . It is concluded that reduction of st and ing paraspinal EMG does not lead to reduction in pain Cognitive behavioral treatment has been incorporated into st and ard medical treatment procedures in German pain centers . Acceptance of the treatment by patients and outcome in terms of pain , coping , and disability was investigated . Components of the psychological treatment are education , relaxation and imagery , modifying thoughts and feelings , enhancement of pleasant activities , and training of good postural habits . The program was conducted in a group setting in accordance with a treatment manual and consists of 12 weekly 2.5-h sessions . A two-factor experiment with repeated measures on one factor was applied . Ninety-four consecutive patients with low-back pain were r and omly assigned to an experimental group having a combined medical and cognitive-behavioral treatment , or to a control group with medical treatment only . Assessment s were taken pre-treatment , post-treatment , and --in the treated group only -- at a 6-months follow-up . At each assessment , patients kept a pain diary over a period of 4 weeks , and filled in self-report question naires . The sample consisted of 36 experimental and 40 control subjects at post-treatment . Experimental subjects reported less pain , better control over pain , more pleasurable activities and feelings , less avoidance and less catastrophizing . In addition , disability was reduced in terms of social roles , physical functions and mental performance . The results were maintained at follow-up . Patients who only received medical treatment showed little improvement . Data indicate that the program meets the needs of the patients and should be continued Seventy-one chronic low back pain patients were assigned to one of three behavioural rehabilitation treatments or a waiting-list condition . The first intervention consisted of an operant treatment , aim ed at increasing health behaviours and activity levels and at reducing pain and illness behaviours . In the second intervention , a cognitive treatment , aim ed at the reinterpretation of catastrophizing pain cognitions and at enhancing self-control , was combined with an operant treatment . The third intervention consisted of the combination of the operant approach and a respondent treatment . During the respondent treatment , patients were taught to decrease muscle tension levels , using the ' applied relaxation ' technique supported by EMG-biofeedback and grade d exposure to tension-eliciting situations . A repeated measurements design included observer rating of pain behaviours , observer ratings of mood , self-reported depression , residual health behaviours , pain cognitions and experienced pain intensity . Follow-up assessment occurred at six months and one year after termination of treatment . Results suggest that , for the sample as a whole , improvements are found on measures of pain behaviours , health behaviours , pain cognitions and affective distress and that these improvements are maintained at six months and one year follow-up . During the treatment the three treatment groups improved significantly more than the waiting-list control group on most of the measures . Further , the results of this study provide evidence that the operant-cognitive and operant-respondent conditions are more efficacious in decreasing pain behaviours and in increasing health behaviours and efficacy expectations than operant treatment alone . This differential effect among the conditions is maintained at follow-up . Patients who received the OC and OR treatments catastrophize less than OP patients , and OC patients showed better scores on outcome -efficacy than OR patients . In general , the results suggest that behavioural rehabilitation programmes for chronic low back pain are effective and that the effects of an operant treatment are magnified when self-control techniques are added 24 patients with chronic low back pain were r and omly assigned to three treatment conditions : ( a ) EMG biofeedback , ( b ) relaxation training , and ( c ) a placebo condition . Patients were seen for eight sessions and were evaluated before Session 1 and after Session 8 . Eight analyses of covariance which were adjusted for age and pretest scores were computed on the final scores to find which variables could detect significant difference between treatments . Age was included as a covariate because the differences in age between conditions were significant . Four variables with significant and nearly significant differences were chosen for analysis . The second set of analyses identified the nature of the differences among the three conditions . These included a priori planned comparisons among conditions , and paired t tests . Relaxation-trained subjects were significantly superior to subjects in the placebo condition , in decreasing pain during the function test , increasing relaxation , and decreasing Upper Trapezius EMG . They were superior to EMG Biofeedback training in increasing reported activity . Both Relaxation and EMG trained subjects were able to reduce Upper Trapezius EMG by Session 8 Relaxation-trained subjects showed significant change on eight of the 14 possible comparisons for each treatment condition . EMG biofeedback training showed significant favorable results in only one condition ; the placebo condition showed no significant results . Relaxation training gave better results in reducing EMG and pain , and in increasing relaxation and activity than either EMG biofeedback alone or a placebo condition & NA ; Back pain is a significant health care problem that has been managed unsatisfactorily in primary care setting s. Providers typically address medical issues but do not adequately address patient concerns or functional limitations related to back pain . We evaluated a brief intervention for primary care back pain patients design ed to provide accurate information about back pain , instill attitudes favorable towards self care , reduce fears and worries , assist patients in developing personalized action plans to manage their back pain , and improve functional outcomes . Patients enrolled in a large health maintenance organization were invited to participate in an educational program to improve back pain self care skills 6–8 weeks after a primary care back pain visit . Patients ( n=226 ) were r and omly assigned to a Self Care intervention or to Usual Care , and were assessed at baseline , 3‐ , 6‐ , and 12‐months . The intervention involved a two‐session Self Care group and an individual meeting and telephone conversation with the group leader , a psychologist experienced in chronic pain management . The intervention was supplemented by educational material s ( book and videos ) supporting active management of back pain . The control group received usual care supplemented by a book on back pain care . Participants assigned to the Self Care intervention showed significantly greater reductions in back‐related worry and fear‐avoidance beliefs than the control group . Modest , but statistically significant , effects on pain ratings and interference with activities were also observed & NA ; Forty‐five low back pain patients were r and omly assigned to either a st and ard inpatient rehabilitation program or the st and ard program with additional psychological components . The st and ard program emphasized education , support , and physical reconditioning through exercise . Patients receiving the psychological program were given additional training in relaxation and other coping skills and received contingent reinforcement for exercise . Both programs included reduction of medication intake and an emphasis on family involvement after discharge . Measures of functional status were taken prior to the program , at discharge from the 3‐week inpatient program , and at a 6‐month follow‐up appointment . These data revealed that patients improved their overall functioning at discharge and maintained these gains at the follow‐up assessment . A similar pattern of findings was obtained for self‐reported pain and interference . Furthermore , 81 % of the patients had returned to work or were engaged in active job retraining by the follow‐up . Using a conservative measure of full‐time return to the same or an equivalent job , 57 % were employed by the follow‐up . Patient improvement , however , was not differentially affected by treatment group assignment , suggesting that the psychological treatment failed to add to the effectiveness obtained by the st and ard rehabilitation program . Results are discussed in the context of improving patient outcomes from rehabilitation for low back pain BACKGROUND Low-back pain is a common and costly problem . We estimated the effectiveness of a group cognitive behavioural intervention in addition to best practice advice in people with low-back pain in primary care . METHODS In this pragmatic , multicentre , r and omised controlled trial with parallel cost-effectiveness analysis undertaken in Engl and , 701 adults with troublesome subacute or chronic low-back pain were recruited from 56 general practice s and received an active management advisory consultation . Participants were r and omly assigned by computer-generated block r and omisation to receive an additional assessment and up to six sessions of a group cognitive behavioural intervention ( n=468 ) or no further intervention ( control ; n=233 ) . Primary outcomes were the change from baseline in Rol and Morris disability question naire and modified Von Korff scores at 12 months . Assessment of outcomes was blinded and followed the intention-to-treat principle , including all r and omised participants who provided follow-up data . This study is registered , number IS RCT N54717854 . FINDINGS 399 ( 85 % ) participants in the cognitive behavioural intervention group and 199 ( 85 % ) participants in the control group were included in the primary analysis at 12 months . The most frequent reason for participant withdrawal was unwillingness to complete question naires . At 12 months , mean change from baseline in the Rol and Morris question naire score was 1.1 points ( 95 % CI 0.39 - 1.72 ) in the control group and 2.4 points ( 1.89 - 2.84 ) in the cognitive behavioural intervention group ( difference between groups 1.3 points , 0.56 - 2.06 ; p=0.0008 ) . The modified Von Korff disability score changed by 5.4 % ( 1.99 - 8.90 ) and 13.8 % ( 11.39 - 16.28 ) , respectively ( difference between groups 8.4 % , 4.47 - 12.32 ; p<0.0001 ) . The modified Von Korff pain score changed by 6.4 % ( 3.14 - 9.66 ) and 13.4 % ( 10.77 - 15.96 ) , respectively ( difference between groups 7.0 % , 3.12 - 10.81 ; p<0.0001 ) . The additional quality -adjusted life-year ( QALY ) gained from cognitive behavioural intervention was 0.099 ; the incremental cost per QALY was 1786 pound sterling , and the probability of cost-effectiveness was greater than 90 % at a threshold of 3000 pound sterling per QALY . There were no serious adverse events attributable to either treatment . INTERPRETATION Over 1 year , the cognitive behavioural intervention had a sustained effect on troublesome subacute and chronic low-back pain at a low cost to the health-care provider . FUNDING National Institute for Health Research Health Technology Assessment Programme Sixty-six chronic low back pain sufferers were r and omly divided into three groups . Following individual assessment s consisting of psychological question naires , pain monitoring , and measurement of paraspinal electromyogram ( EMG ) , one group received paraspinal EMG biofeedback and another a placebo treatment . The third group received no intervention . Two further assessment s were carried out on all groups immediately after treatment and at a 3-month follow-up . All groups showed significant reduction in pain , anxiety , depression , and paraspinal EMG following treatment and at follow-up , but there were no differences between groups . A regression analysis failed to identify subjects ' characteristics that predicted positive outcome in the biofeedback group . However , high scores on the Evaluative scale of the McGill Pain Question naire and high hypnotizability were significant predictors of positive outcome for the placebo group . It is concluded that paraspinal EMG biofeedback is not a specific treatment for chronic low back pain in a nonhospitalized population Study design . Eighty‐four patients with chronic low back pain were treated using cognitive behavioral principles on a pain management program . Outcome data were collected at four points : 10 weeks before treatment , immediately before and immediately after treatment , and 6 months after treatment . In part 1 of the study , patients were assigned r and omly to group or individual treatment context s. In part 2 of the study , patients were assigned r and omly to programs of 15 , 30 , or 60 hours duration . Objectives . To identify the differences in outcome between programs that treated patients as part of a group and those that treated patients individually and the effects of duration of treatment on outcome . Summary of Background Data . Cognitive behavioral programs have been shown to be an effective means of managing chronic low back pain . The literature is concerned with group programs , however , the duration of which vary widely . Method . Psychological and functional variables were measured before and after treatment and at the 6‐month follow‐up visit . Changes in these variables were measured , and comparisons were made between group and individual programs and between 15‐ , 30‐ , and 60‐hour programs . Results . Data analysis showed a significant , beneficial effect of intervention in terms of the majority of variables ; however , these changes were generally independent of whether patients were treated as part of a group or individually and whether patients completed a 15‐ , 30‐ , or 60‐hour program . Conclusions . Cognitive behavioral rehabilitation programs have been demonstrated to be an effective means of reducing psychological distress , of changing cognition , and of improving the function of patients with chronic low back pain ; however , the length of program and whether patients were treated individually or as part of a group did not affect outcome . This finding has clinical and economic implication Objective : Recent recommendations suggest that reassuring patients with an acute bout of low back pain and encouraging a return to normal activities may be helpful in preventing the development of chronic disability . There is also a question as to whether psychologic or physical therapy interventions actually add anything to such reassurance and advice in terms of preventing chronicity . This study aim ed to ascertain the preventive effects on future sick leave and health-care utilization of adding on a cognitive-behavioral group intervention or a cognitive-behavioral group intervention and preventive physical therapy ( focused on activity and exercise ) relative to a minimal treatment group ( examination , reassurance , and activity advice ) . Subjects : A total of 185 patients seeking care for nonspecific back or neck pain who were employed and at risk for developing long-term disability volunteered to participate in the study . Of these 185 , 158 ( 85 % ) completed the pre- and 1-year follow-up assessment s. Results : Significant differences were observed on the key outcome variables of future health-care utilization and work absenteeism . For health-care utilization , the cognitive-behavioral intervention group and preventive physical therapy group had significantly fewer healthcare visits than did the Minimal Treatment Group . For work absenteeism , the cognitive-behavioral intervention group and cognitive-behavioral intervention and preventive physical therapy group had fewer days during the 12-month follow-up than did the Minimal Treatment Group . The risk for developing long-term sick disability leave was more than five-fold higher in the Minimal Group as compared with the other 2 groups . However , there was no difference between the cognitive-behavioral intervention group and cognitive-behavioral intervention and preventive physical therapy group on sick leave . Conclusion : Taken as a whole , this study shows that adding cognitive-behavioral intervention and cognitive-behavioral intervention and preventive physical therapy can enhance the prevention of long-term disability . There was no substantial difference in the results between the cognitive-behavioral intervention group and cognitive-behavioral intervention and preventive physical therapy group & NA ; The aim of the present study was to evaluate the outcome of a behavioral medicine ( BM ) rehabilitation program and the outcome of its two main components , compared to a ‘ treatment‐as‐usual ’ control group ( CG ) . The study employed a 4 × 4 repeated‐ measures design with four groups and four assessment periods ( pre‐treatment , post‐treatment , 6‐month follow‐up , and 18‐month follow‐up ) . The group studied consisted of subjects on sick leave identified in a nationwide health insurance scheme in Sweden . After inclusion , the subjects were r and omized to one of four conditions , which were : ( 1 ) behavior‐oriented physical therapy ( PT ) ; ( 2 ) cognitive behavioral therapy ( CBT ) ; ( 3 ) BM rehabilitation consisting of PT+CBT ( BM ) ; ( 4 ) a ‘ treatment‐as‐usual ’ CG . The treatments were given over a period of 4 weeks , PT and CBT on a part‐time basis and BM on a full‐time basis . Outcome variables were sick leave , early retirement , and health‐related quality of life ( measured using the Short Form Health Survey , SF‐36 ) . The results showed that the risk of being granted full‐time early retirement was significantly lower for females in PT and CBT compared to the CG during the 18‐month follow‐up period . However , the total absence from work ( sick listing plus early retirement ) in days over the 18‐month follow‐up period was not significantly different in the CG compared to the treatments . On the SF‐36 , women in CBT and BM reported a significantly better health‐related quality of life than women in the CG at the 18‐month follow‐up . No significant differences for men were found on the SF‐36 scales . In conclusion , the results revealed gender differences in the outcome of the treatments and that the components of this BM program yielded as good results as the whole program OBJECTIVE To assess the effect of a combined exercise and motivation program on the compliance and level of disability of patients with chronic and recurrent low back pain . DESIGN A double-blind prospect i ve r and omized controlled trial . SETTING Physical therapy outpatient department , tertiary care . PATIENTS Ninety-three low back pain patients were r and omly assigned to either a st and ard exercise program ( n = 49 ) or a combined exercise and motivation program ( n = 44 ) . INTERVENTIONS Patients were prescribed 10 physical therapy sessions and were advised to continue exercising after treatment termination . The motivation program consisted of five compliance-enhancing interventions . Follow-up assessment s were performed at 3 1/2 weeks , 4 months , and 12 months . MAIN OUTCOME MEASURES Disability ( low back outcome score ) , pain intensity , physical impairment ( modified Waddell score , fingertip-to-floor distance , abdominal muscle strength ) , working ability , motivation , and compliance . RESULTS The patients in the motivation group were significantly more likely to attend their exercise therapy appointments ( p = .0005 ) . Four and 12 months after study entry there was a significant difference in favor of the motivation group with regard to the disability score ( p = .004 ) and pain intensity ( p < or = .026 ) . At 4 months , there was a significant advantage for the motivation group in the fingertip-to-floor distance ( p = .01 ) and in abdominal muscle strength ( p = .018 ) . No significant differences were found in motivation scores , self-reported compliance with long-term exercise , and modified Waddell score . In terms of working ability , there was a trend favoring the combined exercise and motivation program . CONCLUSION The combined exercise and motivation program increased the rate of attendance at scheduled physical therapy sessions , ie , short-term compliance , and reduced disability and pain levels by the 12-month follow-up . However , there was no difference between the motivation and control groups with regard to long-term exercise compliance Several treatment principles for the reduction of chronic low back pain associated disability have been postulated . To examine whether a combination of a physical training and operant‐behavioral grade d activity with problem solving training is cost‐effective compared to either alone one year post‐treatment , a full economic analysis alongside a r and omized controlled trial was conducted . In total 172 patients with chronic disabling non‐specific low back pain referred for rehabilitation treatment , were r and omized to 10 weeks of aerobic training and muscle strengthening of back extensors ( active physical treatment ; APT ) , 10 weeks of gradual assumption of patient relevant activities based on operant‐behavioral principles and problem solving training ( grade d activity plus problem solving training ; GAP ) , or APT combined with GAP ( combination treatment ; CT ) . Total costs , existing of direct health and non‐health costs and indirect costs due to absence of paid work were calculated by using cost diaries and treatment attendance lists . The Rol and Disability Question naire was used to calculate the cost‐effectiveness to reduce disability and the gain in quality adjusted life year ( QALY ) by using the EuroQol‐5D . APT , followed by CT showed , although not significant , higher total costs than GAP . Reduction of disability and gain in QALY did not differ significantly between CT and the single treatment modalities . Based on the incremental cost effectiveness ratios ( ICERs ) and cost‐effectiveness acceptability curves CT is not cost‐effective at all . However , GAP is cost‐effective regarding the reduction of disability and gain in QALY , and to a lesser degree APT is more cost‐effective than CT in reducing disability One hundred and eleven females volunteered to take part in this intervention study of musculoskeletal pain . They all completed a survey of pain among five hundred and eighty-six female hospital staff and presented mild to severe pain in the neck , shoulder and /or low back . They were r and omly assigned to one of the following groups ; Focus on job-stress and psychosocial coping ( Cognitive ) , relaxation training ( Relaxation ) , the combination of the two ( Combined ) or to a control group ( Control ) . Musculoskeletal pain ( intensity and duration ) was assessed by self-report prior to interventions , immediately after interventions , and at a four months follow-up . Results from multivariate analyses of variance as well as covariance ( pre-intervention levels of pain as covariate ) showed that magnitude of pain reduction was dependent upon the interaction between area of the back and type of intervention . These trends were more significant for intensity than for duration scores . They were due to reductions of pain in ( 1 ) neck and shoulders for the Cognitive and Combined groups and ( 2 ) in the low back and shoulders for the Relaxation group . The four month follow-up assessment revealed a significant risk of relapse only for duration of low back pain among subjects in the Combined group . Results from the Cognitive approach to intervention may reflect a causal role for ability to cope with psychosocial job stress in the development of neck and shoulder pain in female hospital staff |
10,510 | 23,828,487 | There is no evidence for any short-term or long-term advantage in peritoneal closure for non-obstetric operations . | BACKGROUND There is no consensus regarding whether the peritoneum should be closed or left open during non-obstetric operations involving laparotomy .
Neither is there consensus about the method of closure of the peritoneum ( continuous suture versus interrupted suture ) .
If closing the peritoneum could be omitted without complications , or even with benefit for patients , this could result in reductions in the cost of abdominal operations by reducing both the number of sutures used and the operating time .
OBJECTIVES To compare the benefits and harms of parietal peritoneal closure compared with no parietal peritoneal closure in patients undergoing non-obstetric abdominal operations . | This study describes a prospect i ve r and omized controlled trial to evaluate whether suture of the peritoneal layer is necessary as a separate step in the closure of midline abdominal surgical wounds . Consecutive patients undergoing abdominal operation — elective and emergency surgery — through a midline abdominal wound were r and omized to have the peritoneal layer closed with continuous catgut , or to have this step omitted . The linea alba was closed with interrupted stainless steel sutures , and the skin approximated with staples . Patients were evaluated for wound sepsis , wound dehiscence , and subsequent incisional hernia development . Postoperative pain was assessed by a self-administered visual analogue score , and by measuring narcotic requirements . There was no significant difference in narcotic requirements , pain scores , or wound complications between the 2 groups . Single-layer closure of the abdominal wall is quicker , less costly , and theoretically safer than layered closure , and it is recommended that separate suture of the peritoneum be ab and oned . ResuméDans cette étude prospect i ve , r and omisée , et contrôlée , nous avons cherché à savoir si la fermeture individualisée du péritoine était nécessaire dans la fermeture d'une laparotomie médiane . Deux cents patients consécutifs — opérés à froid ou en urgence — par laparotomie médiane , ont été r and omisés : dans un groupe , le péritoine a été fermé en un plan individualisé par un surjet au catgut , dans l'autre , le péritoine n'a pas été suturé . La ligne blanche a été fermée en un plan par des points séparés de fils d'acier ; la peau a été fermée par des agrafes . On a étudié le nombre des abcès de paroi , des éviscérations , et , à distance , des éventrations . La douleur postopératoire a été évaluée par un score analogue visuel , établi par le patient lui-même , ainsi que par la nécessité d'utiliser des antalgiques . Il n'y avait pas de différence significative entre les 2 groupes en ce qui concerne le taux de complications pariétales ou l'existence de douleur . Comme la fermeture pariétale en un seul plan est plus rapide , coûte moins cher , et , est théoriquement plus sûre ( on peut surveiller le contenu intrapéritonéal pendant la fermeture ) que la fermeture plan par plan , nous recomm and ons d'ab and oner la fermeture individualisée du péritoine . ResumenEl presente articulo describe un ensayo clínico prospect ivo destinado a investigar si es necesaria la sutura de la capa peritoneal como un paso independiente en el cierre de incisiones abdominales de línea media . Una serie de pacientes consecutivos sometidos a operaciones abdominales fueron r and omizados a cierre peritoneal con sutura continua de catgut o a omisión de este paso . La línea alba fue cerrada con suturas interrumpidas de acero inoxidable y la piel con agrafes . Se estudió la incidencia de infección de herida , de dehiscencia , y de desarrollo de hernia incisional subsiguientes . La valoración del dolor postoperatorio fue realizada mediante autoevaluación con una escala linear análoga y la determinación de los requerimientos de narcóticos . No se encontraron diferencias significativas en el requerimiento de narcóticos para analgesia , en el nivel de la escala de dolor , o en la tasa de complicaciones entre los 2 grupos . El cierre de la pared abdominal en una capa única es más rápido , menos costoso , y teóricamente más seguro ; por lo tanto , se recomienda ab and onar la sutura del peritoneo Purpose Different suture techniques and various suture material s are in use to close midline incisions after primary laparotomy . The ISSAAC study aim ed to assess the safety and efficacy of the new ultra-long-term absorbable , elastic monofilament suture material MonoMax ® for abdominal wall closure . Methods This is a single-arm , multicentre prospect i ve study that included 150 patients undergoing a primary elective midline incision . The control group consists of 141 patients from the INSECT study who received MonoPlus ® or PDS ® for abdominal wall closure . The incidences of burst abdomen and wound infection until the day of discharge were defined as the primary composite endpoints . The rate of incisional hernias 1 year after surgery , the length of postoperative hospital stay and safety parameters served as secondary endpoints . The study has been registered under www . clinical trials.gov [ NCT005725079 ] . Results Eleven patients in the ISSAAC study [ 7.3 % ; 95 % CI = ( 3.9 ; 13.1 % ) ] experienced wound infection or burst abdomen until the day of discharge as compared to 16 [ 11.3 % ; 95 % CI = ( 6.6 ; 17.8 % ) ] patients in the INSECT control group ( p = 0.31 ) . The length of postoperative hospital stay was comparable in both study groups . One year after surgery , incisional hernias were observed in 21 ISSAAC patients ( 14.0 % ) in contrast to 30 hernias ( 21.3 % ) in the INSECT control group . Conclusions The ultra-long-term absorbable , elastic monofilament suture material MonoMax ® is safe and efficient for abdominal wall closure The lateral paramedian incision has been advocated as the strongest incision for abdominal surgery . We have evaluated this incision and tested the necessity for closing the deep peritoneal layer by a prospect i ve r and omized trial . All 206 patients undergoing laparotomy in the Surgical Unit in 1984 , both elective and emergency cases , were included . In patients undergoing laparotomy through unscarred tissue , a lateral paramedian incision was performed and they were r and omized to have either the peritoneum closed ( n = 77 ) or left open ( n = 75 ) . Patients in whom the laparotomy was performed through a previous incision ( n = 51 ) and those in whom the abdomen had to be opened urgently ( n =3 ) were excluded from the trial but studied separately ( n = 54 ) . The rectus sheath was closed with monofilament nylon in all cases . Patients were assessed for wound integrity during the immediate postoperative period and at 1 , 3 , 6 and 12 months after operation . So far the patients have been followed up for between 1 and 2 years and follow‐up is continuing as in some cases incisional hernia may not be detected until several years after operation . There have been no cases of burst abdomen . No incisional hernias have developed in patients in whom a lateral paramedian incision was performed and the peritoneum was closed , and one incisional hernia has occurred in the patients in whom the peritoneum was left open . Seven incisional hernias have occurred in patients excluded from the trial of the lateral paramedian incision ( 13 per cent ) . We conclude that the lateral paramedian incision successfully abolishes the burst abdomen and that incisional hernia is rare . It is not necessary to close the peritoneum with this incision Objective : To determine the volume of pelvic fluid and febrile morbidity after hysterectomy in which the peritoneum was or was not closed . Design : Prospect i ve single-center study . Participants : Fifty-four women undergoing abdominal hysterectomy were enrolled in the study . Patients were r and omized into two groups according to peritoneal closure : group I ( n = 28 ) in which the peritoneum was closed , and group II ( n = 26 ) in which the peritoneum was left open . All participants had early postoperative transvaginal ultrasound . Outcome Measures : Volume of pelvic fluid accumulated after hysterectomy , total leukocytic count before and after hysterectomy , body temperature over the first 24 h , and wound healing . Results : There was a statistically significant difference between both groups regarding the volume of pelvic fluid collection , the duration of the operation and number of ampoules needed ( p < 0.05 ) . There was no statistically significant difference regarding body temperature , TLC , and wound complications . Conclusion : Peritoneal non-closure does not increase short-term morbidity , however it does cause an increase in peritoneal pelvic fluid . The impact of this on long-term sequelae as adhesions should be investigated Abstract . Background : A transverse skin crease incision for right hemicolectomy may result in more rapid recovery than traditional vertical midline incision . This hypothesis was tested with a prospect i ve r and omised trial . Methods : Patients from 2 centres undergoing right hemicolectomy were r and omised to received a midline or transverse incision . Incision lengths were sufficient to enable unrestricted resection of the right colon . Patients and carers were blinded to the incisions using strategically placed dressings . Analgesia and oral intake were controlled by the patient . Operative details and recovery parameters were compared . Results : A total of 28 patients were r and omised . Demographic data and tumour characteristics of the two treatment groups were similar . The transverse incision group had a slightly shorter median wound ( 10 cm vs. 11 cm , p<0.05 ) . Operative time , analgesia requirements , recovery parameters ( time to discharge , 6.5 vs. 6.5 days ) and frequency of complications were otherwise comparable . Conclusions : A transverse skin crease incision for right hemicolectomy results in a slightly smaller wound but no other advantages were demonstrated compared with a traditional vertical midline incision The effects of pelvic and periaortic peritoneal closure or ( non-closure ) on morbidity and adhesion formation were prospect ively compared in 102 patients with ovarian cancer who had undergone a pelvic and periaortic lymphadenectomy . Hysterectomy with bilateral salpingoophorectomy , bilateral pelvic and periaortic lymphadenectomy , omentectomy , appendectomy and lysis of pelvic adhesions for the st and ardization of initial adhesion scores was performed on all patients . The pelvic and periaortic peritoneum were re-approximated in group I ( n = 50 ) patients , and left open in group II ( n = 52 ) patients . The groups were similar for mean age , previous surgery , tumour histology and disease stage . Morbidity characteristics such as blood loss , transfusion rate , post-operative infectious and non-infectious complications , and total hospital stay were also similar . After six courses of PAC ( cisplatin 50 mg/m(2 ) , Adriamycin 50 mg/m(2 ) , cyclophosphamide 500 Mg/M(2 ) ) chemotherapy , all patients underwent a second-look laparotomy . Persistent cancer was detected in 49 of 102 ( 48.03 % ) patients . Adhesion scores were detected at the time of second-look laparotomy . Adhesion scores for group I ( 8.9 + /- 2.9 ) were significantly higher than the group II ( peritoneum non-closure ) ( 5.8 + /- 2.3 ) ( P<0.01 ) . Closing the pelvic and periaortic peritoneum did not effect morbidity , but leaving the pelvic and periaortic peritoneum open significantly decreased the adhesion formation Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Objective To compare closure and nonclosure of the peritoneum at radical abdominal hysterectonmy and pelvic node dissection with respect to postoperative morbidity . Methods Women with uterine cancer who underwent radical abdominal hysterectomy and node dissection type II or III of Piver-Rutledge were assigned r and omly to have a st and ard closure of pelvic and parietal peritoneum and placement of a T-shaped suction drain or to have the peritoneum left open but the vagina closed and two abdominal drains placed . Adjuvant radiotherapy was given to patients with risk factors . The postoperative incidence of lymphocysts ( within 8 weeks from the operation and after 1 year ) and infection-related and non-infection-related complications were analyzed . Results One hundred twenty subjects were enrolled , of whom 59 had peritoneal closure and 61 did not . Both groups were similar with regard to age , weight , nodes removed , nodal metastases , operative time , type of surgery , need for transfusion , and incidence of postoperative radiotherapy . The median follow-up was 36 months ( range 11–72 ) . Eleven patients died , four because of treatment-related complication . The amount of drainage was significantly higher in the closed group than in the unclosed group ( median 740 mL , range 50–5980 versus median 340 mL , range 40–4000 ; P < .005 ) . The incidence of asymptomatic lymphocysts was similar in the closed and open groups at 2 weeks ( 17 of 59 versus 15 of 6 , respectively ) , at 8 weeks ( eight of 56 versus ten of 61 , respectively ) , and after 1 year ( one of 21 versus four of 22 , respectively ) . No difference was found between closed and open groups in terms of symptomatic lymphocysts ( one of 59 versus two of 61 , respectively ) , wound and pelvic infection ( seven of 59 versus 11 of 61 , respectively ) , febrile morbidity ( two of 59 versus one of 61 , respectively ) , and obstruction ( zero of 59 versus one of 61 , respectively ) . Conclusion Nonclosure of the peritoneum at radical abdominal hysterectomy and node dissection is not hazardous and is not associated with an increased incidence of infection- or adhesion-related complications OBJECTIVE To compare the analgesic requirement and pain scores in the postoperative period between closure and nonclosure of the peritoneum in women undergoing gynecological abdominal surgery . METHODS We conducted this study as a 2 parallel grouped , double blind , r and omized , controlled trial between February 2002 and March 2003 . The current study consists of 79 eligible women who were enrolled and completed baseline assessment s. We carried out this study at the Cumhuriyet University Hospital , Sivas , Turkey . RESULTS When the age , gravidity , parity , body mass index , type of surgery , operative time and length of hospital stay were compared , between the 2 groups , no statistically significant difference was found ( p>0.05 ) . The postoperative pain was found higher in the closure group than the nonclosure group ( p<0.05 ) when the pain with visual analogue scale ( VAS ) scores compared . CONCLUSION There was no significant difference in analgesic requirements between the 2 groups in the postoperative period . However , less pain and low VAS scores were evident especially after postoperative 2nd and 48th hours in the nonclosure group . We recommend non-closure of peritoneum at abdominal gynecologic procedure as the method of choice This investigation was carried out to evaluate the surgical wound outcome of patients who underwent cholecystectomy via Kocher incision , without peritoneal closure . Consecutive patients ( n = 129 ) were r and omized either to have the peritoneal closure ( n = 66 ) or to have this step omitted ( n = 63 ) . Demographic data of the patients were similar in both groups . There were no significant differences in overall wound complication ( p = 0.44 ) , wound infection ( p = 0.71 ) , wound dehiscense ( p = 0.96 ) and incisional hernia ( p = 0.95 ) . This study provides strong evidence that the avoidance of the peritoneal closure represents no adverse effect to the postoperative course of the patients Closure of vertical laparotomy wounds was r and omized between a two‐layer technique of continuous catgut to peritoneum and continuous nylon to sheath and a one‐layer technique in which the peritoneal suture line was omitted . In 162 two‐layer closures there were 4 burst abdomens and 7 wound hernias ( 6·8 per cent wound failures ) ; in 164 one‐layer closures there were 5 burst abdomens and 7 hernias ( 7·3 per cent failures ) . Of 21 patients in this series with jaundice , the abdominal wounds dehisced in 3 , and 4 patients developed incisional hernias ( 33·3 per cent failures ) compared with a 5·2 per cent failure rate in the 305 non‐jaundiced patients ( P < 0·01 ) A total of 349 patients were r and omized to undergo laparotomy through a lateral paramedian incision with layered closure ( n = 137 ) , a midline incision with mass closure ( n = 104 ) or a midline incision using layered closure ( n = 108 ) , endeavouring to close the latter two incisions with a measured suture length to wound length ratio of greater than 4:1 . After 18 months follow‐up , no patient in the lateral paramedian group had developed an incisional hernia whereas 7 of 104 patients undergoing a midline incision with mass closure and 7 of 108 patients undergoing a midline incision with layered closure had incisional hernias ( P<0·01 ) . The mean suture length to wound length ratios for the three groups were 2·6 ( range 1·3‐6·2 ) , 5·0 ( range 3·0‐8·7 ) and 3·7 ( range 2·0‐6·3 ) respectively ( P<0·0001 ) . The lateral paramedian incision remains superior to the midline incision closed with the mass technique and its integrity is independent of the suture length to wound length ratio |
10,511 | 32,300,295 | VR sickness profiles were also influenced by visual stimulation , locomotion and exposure times . | The use of head-mounted displays ( HMD ) for virtual reality ( VR ) application-based purpose s including therapy , rehabilitation , and training is increasing .
Despite advancements in VR technologies , many users still experience sickness symptoms .
VR sickness may be influenced by technological differences within HMDs such as resolution and refresh rate , however , VR content also plays a significant role .
The primary objective of this systematic review and meta- analysis was to examine the literature on HMDs that report Simulator Sickness Question naire ( SSQ ) scores to determine the impact of content . | This paper describes an investigation of the types of problems that may be experienced by Virtual Reality ( VR ) users . Initial concerns have been voiced about various issues concerning the design of VR equipment , particularly the physical ergonomics of head-mounted displays ( HMDs ) and h and -held input devices , and the problems associated with display resolution and lags . This study investigated a number of VR users ' perceptions of the types of physical ergonomics issues that they were aware of when participating in a number of different virtual environments ( VEs ) , using different VR systems . Several different methods were employed , including question naires , body mapping , user observation and interviews . Issues highlighted as either causing participants discomfort or interfering with their experience of the VE were : discomfort from static posture requirements , general discomfort from wearing the HMD , difficulty becoming accustomed to 3D h and held input devices , dissatisfaction with deficits in the visual display and fear of getting ' tangled ' in connecting cables . The implication s of these findings for developers , implementers and users of VR are discussed Although head-mounted displays ( HMDs ) are ideal devices for personal viewing of immersive stereoscopic content , exposure to VR applications on them results in significant discomfort for the majority of people , with symptoms including eye fatigue , headaches , nausea , and sweating . A conflict between accommodation and vergence depth cues on stereoscopic displays is a significant cause of visual discomfort . This article describes the results of an evaluation used to judge the effectiveness of dynamic depth-of-field ( DoF ) blur in an effort to reduce discomfort caused by exposure to stereoscopic content on HMDs . Using a commercial game engine implementation , study participants report a reduction of visual discomfort on a simulator sickness question naire when DoF blurring is enabled . The study participants reported a decrease in symptom severity caused by HMD exposure , indicating that dynamic DoF can effectively reduce visual discomfort Background Virtual reality ( VR ) has recently been explored as a tool for neurorehabilitation to enable individuals with Parkinson ’s disease ( PD ) to practice challenging skills in a safe environment . Current technological advances have enabled the use of affordable , fully immersive head-mounted displays ( HMDs ) for potential therapeutic applications . However , while previous studies have used HMDs in individuals with PD , these were only used for short bouts of walking . Clinical applications of VR for gait training would likely involve an extended exposure to the virtual environment , which has the potential to cause individuals with PD to experience simulator-related adverse effects due to their age or pathology . Thus , our objective was to evaluate the safety of using an HMD for longer bouts of walking in fully immersive VR for older adults and individuals with PD . Methods Thirty-three participants ( 11 healthy young , 11 healthy older adults , and 11 individuals with PD ) were recruited for this study . Participants walked for 20 min while viewing a virtual city scene through an HMD ( Oculus Rift DK2 ) . Safety was evaluated using the mini-BESTest , measures of center of pressure ( CoP ) excursion , and question naires addressing symptoms of simulator sickness ( SSQ ) and measures of stress and arousal . Results Most participants successfully completed all trials without any discomfort . There were no significant changes for any of our groups in symptoms of simulator sickness or measures of static and dynamic balance after exposure to the virtual environment . Surprisingly , measures of stress decreased in all groups while the PD group also increased the level of arousal after exposure . Conclusions Older adults and individuals with PD were able to successfully use immersive VR during walking without adverse effects . This provides systematic evidence supporting the safety of immersive VR for gait training in these population It has been reported that females are more susceptible to motion sickness than males . Supporting evidence is primarily based on retrospective survey question naires and self-reporting . We investigated if there is a gender difference in motion sickness susceptibility using objective and subjective measurements under controlled laboratory conditions . Thirty healthy subjects ( 14 males and 16 females ) between the ages of 18 - 46 years were exposed to Coriolis cross-coupling stimulation , induced by 120 degrees /s yaw rotation and a simultaneous 45 degrees pitch forward head movement in the sagittal plane every 12 seconds . Cutaneous forearm and calf blood flow , blood pressure , and heart rate were monitored . Graybiel 's diagnostic criteria were used to assess sickness susceptibility before and after motion exposure . Golding and Kerguelen 's scale was used to assess the severity of symptoms during motion exposure . A significant ( p<0.01 ) increase of forearm and calf blood flow during cross-coupling stimulation was observed in both sexes . However , the subjective symptoms rating and blood flow measurements indicate that there was no significant difference between male and female subjects . Our data also suggests that females may be more inclined to admit discomfort as indicated by their responses to a survey of motion sickness history prior to the experiment Stroke and traumatic brain injury affect an increasing number of people , many of whom retain permanent damage in cognitive functions . Conventionally , cognitive function has been assessed by a paper-based neuropsychological evaluation . However these test environments differ substantially from everyday life . This problem can be overcome by using virtual reality ( VR ) to objective ly evaluate behaviors and cognitive function in simulated daily activities . With our virtual shopping simulation , we compared people who had undergone a stroke with control participants in an immersive VR program that used a head-mounted display ( HMD ) . We evaluated user satisfaction with the tests , complications , and the user interface . Significant differences were consistently found between the stroke group and the control group for the following tasks : stage 1 performance index , interaction error ; stage 2 delayed recognition memory score , attention index ; and stage 3 executive index ( p < 0.001 ) . Perceptive dysfunction , visuospatial dysfunction , level of computer experience , and level of education affected the performance of the stroke group . The frequency of complications in the stroke group , calculated using the cut-off score for the Simulator Sickness Question naire , was 9.6 % for nausea , 41.9 % for oculomotor complications , and 25.8 % for disorientation . The frequency of complications between the stroke and control groups was not significantly different . Thirty-five percent of participants in the stroke group and 13 % in the control group reported difficulties with using the joystick . This computer-generated VR-based cognitive test shows promise in assessing cognitive function in patients with stroke . More refinements are needed in the user interface and the projection methods BACKGROUND Interactions between frequency and amplitude of latency in head-mounted displays ( HMDs ) are thought to affect simulator sickness . Many studies have linked system latency to subjective sickness , but recent research has found that at least with the case of inertia-based head tracking technology , latency is not a constant ; rather it varies systematic ally over time due to sensor errors and clock asynchronization . The purpose of this experiment was to further explore the relationship between frequency and amplitude of latency as they relate to subjective sickness experienced in an HMD . METHODS In a 2 ( frequency ) × 2 ( amplitude ) design , 120 subjects were r and omly assigned to 4 latency conditions . Frequency of latency was either 0.2 Hz or 1.0 Hz . Amplitude of latency was either 100 ms fixed or 20 - 100 ms varying . RESULTS A main effect of frequency of latency was found . Subjects reported greater sickness in the 0.2-Hz frequency conditions ( 39.0 ± 27.8 ) compared to the 1-Hz conditions ( 30.3 ± 17.0 ) . Additionally , 18 subjects withdrew their participation early in the 0.2-Hz conditions compared to 7 in the 1.0-Hz conditions . DISCUSSION In conclusion , frequency of latency appears to play a role in the experience of sickness in HMDs in both subjective reporting of symptoms and subject performance . The current study confirms results of earlier studies , finding that real motion around a frequency of 0.2 Hz is more sickening than other frequencies . Future work should continue to parse the effects of frequency and amplitude of latency in head-tracked HMDs . Kinsella A , Mattfeld R , Muth E , Hoover A. Frequency , not amplitude , of latency affects subjective sickness in a head-mounted display . Aerosp Med Hum Perform . 2016 ; 87(7):604 - 609 Virtual simulation sickness ( VSS ) is a form of visually induced motion sickness that can result fromimmersion in a virtual environment ( VE ) . As in their susceptibility to the sickness induced by real motion , womenhave been reported to be more susceptible than men to VSS , yet the reason for this difference is not known . The aim of the current study was to investigate the influence of themenstrual cycle on susceptibility to VSS in 16 naturally cycling women and to compare the responses of this group with control groups consisting of 1 ) 16 premenopausal women taking a combined monophasic oral contraceptive and 2 ) 16 men . All female participants were immersed in a nauseogenic VE on days 5 , 12 , 19 , and 26 of their menstrual/pill cycle . These days were chosen because they fall in line with peaks and troughs of ovarian hormone levels . Menstrual cycle phase was confirmed by salivary estradiol and progesterone levels . A 4-week “ pseudo-cycle ” was assigned to the male participants . Hormone analysis revealed that 9 participants in the experimental group had been tested at the desired phases of their cycle . These participants exhibited a significant increase in susceptibility to VSS on day 12 of their cycle . The hormone analysis also showed that the cycles of the 7 remaining members of the experimental group had not precisely followed the expected pattern , and so these people had been tested on days that did not coincide with peaks and troughs of ovarian hormone levels . No consistent variation in susceptibility was observed over the cycle in these volunteers . In addition , no change in susceptibility was observed over the pill cycle of the oral contraceptive group nor over the pseudo-cycle applied to the male control group . The authors conclude that susceptibility to VSS varies over the menstrual cycle as a consequence of hormonal variation For those interested in using head-coupled PC-based immersive virtual environment ( VE ) technology to train , entertain , or inform , it is essential to underst and the effects this technology has on its users . This study investigated potential adverse effects , including the sickness associated with exposure and extreme responses ( emesis , flashbacks ) . Participants were exposed to a VE for 15 to 60 min , with either complete or streamlined navigational control and simple or complex scenes , after which time measures of sickness were obtained . More than 80 % of participants experienced nausea , oculomotor disturbances , and /or disorientation , with disorientation potentially lasting > 24 hr . Of the participants , 12.9 % prematurely ended their exposure because of adverse effects ; of these , 9.2 % experienced an emetic response , whereas only 1.2 % of all participants experienced emesis . The results indicate that design ers may be able to reduce these rates by limiting exposure duration and reducing the degrees of freedom of the user 's navigational control . Results from gender , body mass , and past experience comparisons indicated it may be possible to identify those who will experience adverse effects attributable to exposure and warn such individuals . Applications for this research include military , entertainment , and any other interactive systems for which design ers seek to avoid adverse effects associated with exposure Background . Memory decline is a prevalent aspect of aging but may also be the first sign of cognitive pathology . Virtual reality ( VR ) using immersion and interaction may provide new approaches to the treatment of memory deficits in elderly individuals . Objective . The authors implemented a VR training intervention to try to lessen cognitive decline and improve memory functions . Methods . The authors r and omly assigned 36 elderly residents of a rest care facility ( median age 80 years ) who were impaired on the Verbal Story Recall Test either to the experimental group ( EG ) or the control group ( CG ) . The EG underwent 6 months of VR memory training ( VRMT ) that involved auditory stimulation and VR experiences in path finding . The initial training phase lasted 3 months ( 3 auditory and 3 VR sessions every 2 weeks ) , and there was a booster training phase during the following 3 months ( 1 auditory and 1 VR session per week ) . The CG underwent equivalent face-to-face training sessions using music therapy . Both groups participated in social and creative and assisted-mobility activities . Neuropsychological and functional evaluations were performed at baseline , after the initial training phase , and after the booster training phase . Results .The EG showed significant improvements in memory tests , especially in long-term recall with an effect size of 0.7 and in several other aspects of cognition . In contrast , the CG showed progressive decline . Conclusions . The authors suggest that VRMT may improve memory function in elderly adults by enhancing focused attention |
10,512 | 27,785,116 | There is a scarcity of psychometrically sound , comprehensive , and generic measures of experiences of using prescription medicines among adult patients living with chronic illnesses . | BACKGROUND There is an increasing drive to measure and so improve patients ' experiences and outcomes of health care .
This also applies to medicines , given their ubiquity as health care interventions .
Patients ' experiences of using medicines vary , and instruments which measure these are seen as an essential component to improve care .
We aim ed to identify generic measures of patients ' experiences of using prescription medicines and to examine their properties and suitability for use in research or practice . | Background The objective of this study was to develop and psychometrically evaluate a general measure of patients ' satisfaction with medication , the Treatment Satisfaction Question naire for Medication ( TSQM ) . Methods The content and format of 55 initial questions were based on a formal conceptual framework , an extensive literature review , and the input from three patient focus groups . Patient interviews were used to select the most relevant questions for further evaluation ( n = 31 ) . The psychometric performance of items and result ing TSQM scales were examined using eight diverse patient groups ( arthritis , asthma , major depression , type I diabetes , high cholesterol , hypertension , migraine , and psoriasis ) recruited from a national longitudinal panel study of chronic illness ( n = 567 ) . Participants were then r and omized to complete the test items using one of two alternate scaling methods ( Visual Analogue vs. Likert-type ) . Results A factor analysis ( principal component extraction with varimax rotation ) of specific items revealed three factors ( Eigenvalues > 1.7 ) explaining 75.6 % of the total variance ; namely Side effects ( 4 items , 28.4 % , Cronbach 's Alpha = .87 ) , Effectiveness ( 3 items , 24.1 % , Cronbach 's Alpha = .85 ) , and Convenience ( 3 items , 23.1 % , Cronbach 's Alpha = .87 ) . A second factor analysis of more generally worded items yielded a Global Satisfaction scale ( 3 items , Eigenvalue = 2.3 , 79.1 % , Cronbach 's Alpha = .85 ) . The final four scales possessed good psychometric properties , with the Likert-type scaling method performing better than the VAS approach . Significant differences were found on the TSQM by the route of medication administration ( oral , injectable , topical , inhalable ) , level of illness severity , and length of time on medication . Regression analyses using the TSQM scales accounted for 40–60 % of variation in patients ' ratings of their likelihood to persist with their current medication . Conclusion The TSQM is a psychometrically sound and valid measure of the major dimensions of patients ' satisfaction with medication . Preliminary evidence suggests that the TSQM may also be a good predictor of patients ' medication adherence across different types of medication and patient population BACKGROUND Medication therapy management ( MTM ) services position pharmacists to prevent , detect , and resolve medication-related problems ( MRPs . ) However , selecting patients for MTM who are most at risk for MRPs is a challenge . Using self-administered scales that are practical for use in clinical practice are one approach . OBJECTIVE The objective of this study was to estimate the psychometric properties of a brief self-administered scale as a screening tool for MRPs . METHODS This was a non-r and omized study utilizing question naires administered cross-sectionally . In Phase 1 , patients ( n = 394 ) at community pharmacies and outpatient clinics completed 78 items , provided to the study team by item authors , assessing perceived MRPs . These data were used to select items for further investigation as a brief , self-administered scale , and estimate the reliability and construct validity of the result ing instrument . In Phase 2 , a convenience sample of patients ( n = 200 ) at community pharmacies completed a nine-item , self-administered scale . After completion , they were engaged in a comprehensive medication review by their pharmacist who was blinded to question naire responses . The main outcome measure for estimating the criterion-related validity of the scale was the number of pharmacist-identified medication-related problems ( MRPs . ) Item statistics were computed as well as bivariate associations between scale scores and other variables with MRPs . A multivariate model was constructed to examine the influence of scale scores on MRPs after controlling for other significant variables . RESULTS Higher scores on the question naire were positively correlated with more pharmacist-identified MRPs ( r = 0.24 ; P = 0.001 ) and scores remained as a significant predictor ( P = 0.031 ) when controlling for other relevant variables in a multivariate regression model ( R(2 ) = 0.21 ; P < 0.001 ) . CONCLUSIONS Patient responses on the scale may have a modest role in predicting MRPs . The use of self-administered question naires such as this may supplement other available patient data in developing patient eligibility criteria for MTM , however , additional research is warranted BACKGROUND Treatment of diabetes mellitus ( DM ) is complex , requiring multifaceted lifestyle change or regulation and , for many , self-regulation of insulin levels in the blood . Historically , daily insulin treatment has been viewed as burdensome to patients , prompting newer formulations and improved delivery methods . OBJECTIVE This multicenter , clinical study was design ed to develop a conceptually sound , clinical ly meaningful , and psychometrically valid measure of insulin treatment satisfaction , applicable to a wide range of insulin therapies . METHODS A 3-phase iterative process was employed to develop and vali date the Insulin Treatment Satisfaction Question naire ( ITSQ ) : ( 1 ) conceptual development of items , ( 2 ) preliminary validation among patients with DM , and ( 3 ) confirmatory validation among patients with DM . RESULTS The ITSQ was vali date d with 170 patients in phase 2 and 402 patients in phase 3 . Confirmatory factor analysis produced a 5-factor , 22-item instrument assessing regimen inconvenience , lifestyle flexibility , glycemic control , hypoglycemic control , and satisfaction with the insulin delivery device . Results for reliability and construct validity of the final version were consistent in both sample s of patients treated with insulin , with different data collection methods . Internal consistency ( using Cronbach alpha coefficient ) of the subscales ranged from 0.79 to 0.91 . Test-retest reliability ( using Spearman rank correlation coefficients ) ranged from 0.63 to 0.94 . ITSQ scores showed moderate to high correlation with related measures of treatment burden . The ITSQ differentiated among insulin delivery methods , glycosylated hemoglobin values , the number of times the patient required assistance administering insulin , and insulin adherence . CONCLUSION In our study sample s , the ITSQ appeared to be conceptually and psychometrically sound and applicable to a wide range of insulin therapies Objective : To review literature on instruments available for assessing the physical and cognitive ability to take medications as prescribed , which serve as a way to rule out reasons for nonadherence . Data Sources : A PubMed search ( 1950–February 2008 ) was conducted to identity relevant articles . Additional references were obtained from cross-referencing the bibliographies of selected articles . Only journals containing English- language articles were selected for review . Study Selection and Data Extraction : Articles that described a simulated assessment of medication management were obtained , irrespective of whether the assessment also contained data about medication adherence or was focused on older adults . Data Synthesis : Fifteen instruments were identified . Six instruments required 5 minutes or less to administer . 5 required 6–30 minutes , and 4 had no administration time data reported . A possible advantage of 3 of the instruments is that they use a subject 's own medications and may therefore provide a more authentic assessment . Only 2 instruments have been tested by subjects other than the drug developers and only one has been used in 2 different population s , thereby affording soma insight into generalizability . These studies have used a variety of other vali date d surveys/ assessment s to provide an indication of construct validity , including neuropsychological batteries , caregiver reports , prospect i ve outcomes , instrumental activities of daily living , and levels of care . One instrument determined whether Individuals could tell if refills existed , whom to contact , and re sources to obtain medications . Three assessed numeracy literacy . Conclusions : Five instruments that measure medication management capacity should be compared for potential further use , including Beckman 's tasks , due to their brevity and assessment of numeracy literacy ; the Medication Management Ability Assessment , Drug Regimen Unassisted Grading Scale , and Hopkins Medication Schedule because of the evidence supporting their use ; and the Medication Management Instrument for Deficiencies In the Elderly because it includes an assessment of the patient 's knowledge of how to obtain more medications . No brief tool is available for the primary care setting to identify individuals with medication management problems or to guide the type and amount of support required to manage medications BACKGROUND Attention needs to be paid to comparing and st and ardizing methods for measuring patient satisfaction with consultations in primary care . OBJECTIVES To compare the Medical Interview Satisfaction Scale ( MISS ) and the Consultation Satisfaction Question naire ( CSQ ) in terms of acceptability , distribution of responses , reliability and gather evidence of validity . In addition , to compare the scores of patients completing the question naires immediately after the consultation in the general practitioners ' surgeries with those completing the question naires later at home . METHODS The two question naires were bound as a single instrument with order determined at r and om . This was given to patients immediately after their consultations in eight practice s in South Glamorgan . RESULTS One hundred and ninety-eight of 316 ( 63 % ) patients completed and returned question naires . The distributions of patient satisfaction scores for the two question naires were very similar . For the MISS : mean 76.6 % ( SD 11.4 ) ; for the CSQ mean 7.2 % ( SD 12.6 ) . Correlations between sub-scales ranged from 0.58 - 0.84 for the MISS and from 0.40 - 0.79 for the CSQ . The correlation between the overall scales was 0.82 . Levels of reliability for the scales and sub-scales were fair to good ranging from 0.78 - 0.96 for the MISS and from 0.73 - 0.94 for the CSQ . CONCLUSIONS The study does not identify one scale as being superior in psychometric terms , however by demonstrating consistency of responses it provides support for the scales as measures of patient satisfaction for use in primary care . The level of inter-correlation suggests that the sub-scales may not be clearly independent of each other and suggests that total scores may be preferred . Lower levels of satisfaction are expressed if patients complete question naires at home rather than in general practitioners ' surgeries |
10,513 | 26,968,880 | A trough concentration > 3.0 mg/L is associated with increased hepatotoxicity , particularly for the Asian population , and > 4.0 mg/L is associated with increased neurotoxicity | OBJECTIVES The optimum trough concentration of voriconazole for clinical response and safety is controversial .
The objective of this review was to determine the optimum trough concentration of voriconazole and evaluate its relationship with efficacy and safety . | Arbekacin ( ABK ) was approved and widely used in Japan for treatment of patients infected with MRSA , and TDM was introduced in clinical practice . The Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring decided to develop a clinical practice guidelines for TDM of ABK for the following reasons . First , although the daily dose of 150e200 mg was approved in Japan , recent PK- PD studies revealed that higher serum concentration is required to achieve better clinical efficacy and several findings concerning the usefulness of higher dosage regimen have obtained recently . Second , although maximal concentrations that obtained immediately after the end of administration ( Cmax ) w as generally adopted , the serum concentration at 1 h after initiation of administration ( peak serum con- centration ( Cpeak ) ) proved to be more suitable as an efficacy indicator of aminoglycosides . Lastly , as ABK is approved only in Japan , no international practice guideline for TDM has not been available in ABK to date . This guideline evaluated the scientific data associated with serum ABK monitoring and provided rec- ommendations based on the available evidence . Potential limitations of this guideline , however , include the findings that few prospect i ve clinical trials of TDM of ABK are available in the treatment of MRSA infections and that most of the published literature describes observational studies BACKGROUND Voriconazole is a triazole agent with excellent antifungal activity against Aspergillus species . However , despite its potential advantages , the occurrence of unpredictable toxicities might be critical in immunocompromised patients . The aim of this study was to analyze risk factors for voriconazole-related severe adverse events ( SAEs ) . METHODS This prospect i ve observational study was conducted in Korean patients with hematological malignancies and invasive aspergillosis on intravenous voriconazole therapy between June 2008 and April 2009 . RESULTS Of the 25 patients enrolled , eight ( 32 % ) showed voriconazole-related SAEs , which included hepatotoxicities ( n=5 ) , cardiac tachyarrhythmias ( n=2 ) , and neurotoxicity ( n=1 ) . Sex , age , underlying hematological malignancies , voriconazole dose , the co-administration of a proton pump inhibitor , and CYP2C19 genotype were not found to be related to the occurrence of SAEs . However , trough plasma concentrations of voriconazole were found to be significantly higher in the patients with an SAE : median 6.32 mg/l ( interquartile range ( IQR ) 2.86 - 9.71 mg/l ) vs. median 2.15 mg/l ( IQR 0.92 - 4.00 mg/l ) ; p=0.011 . Receiver operating characteristic curve analysis identified a cut-off trough concentration for SAEs of 5.83 mg/l ( sensitivity 62.5 % and specificity 94.1 % ) . Furthermore , multivariate analysis showed that a trough concentration of ≥ 5.83mg/l was the only significant independent risk factor of an SAE . CONCLUSIONS This study shows that therapeutic drug monitoring is indicated in patients with a voriconazole-related SAE and that dose adjustment is required if the trough concentration of voriconazole exceeds 5.83 mg/l Seventy-one allograft recipients receiving voriconazole , in whom complete clinical , microbiologic and pharmacokinetic data were available , were studied to determine the efficacy of voriconazole in preventing fungal infections . The length of voriconazole therapy was 6–956 days ( median 133 ) . The total number of patient-days on voriconazole was 13 805 ( ∼38 years ) . A total of 10 fungal infections were seen in patients on voriconazole ( 18 % actuarial probability at 1 year ) : C and ida glabrata ( n=5 ) , C and ida krusei ( n=1 ) , Cunninghamella ( n=1 ) , Rhizopus ( n=2 ) and Mucor ( n=1 ) . Two of the four zygomycosis cases were preceded by short duration s of voriconazole therapy , but prolonged itraconazole prophylaxis . The plasma steady-state trough voriconazole levels around the time the infection occurred were < 0.2 , < 0.2 , 0.33 , 0.55 , 0.63 and 1.78 μg/ml in the six c and idiasis cases . Excluding the four zygomycosis cases , all the six c and idiasis cases were seen among the 43 patients with voriconazole levels of ⩽2 μg/ml and none among the 24 with levels of > 2 μg/ml ( P=0.061 ) . We conclude that voriconazole is effective at preventing aspergillosis . However , breakthrough zygomycosis is seen in a small proportion of patients . The role of therapeutic voriconazole monitoring with dose adjustment to avoid breakthrough infections with fungi that are otherwise susceptible to the drug needs to be explored prospect ively BACKGROUND Blood levels of voriconazole , a first line therapy for invasive aspergillosis , may correlate with adverse events and treatment response . However , no r and omized controlled studies have been conducted to evaluate the clinical utility of routine therapeutic drug monitoring ( TDM ) of voriconazole . This study aim ed to determine whether routine TDM of voriconazole reduces drug adverse events or improves treatment response in invasive fungal infections . METHODS This was a r and omized , assessor-blinded , controlled , single center trial . One hundred ten adult patients were r and omly assigned to TDM or non-TDM groups . In the TDM group , voriconazole dosage was adjusted ( target range , 1.0 - 5.5 mg/L ) according to the serum trough level measured on the fourth day after initiation of voriconazole . The non-TDM group received a fixed , st and ard dosage . Voriconazole-related adverse events were monitored , and treatment response was assessed three months after the initiation of therapy . RESULTS Baseline characteristics including the CYP2C19 genotype were comparable between the two groups . While the incidence of adverse events was not different between the TDM group and the non-TDM group ( both 42 % ; P = .97 ) , the proportion of voriconazole discontinuation due to adverse events was significantly lower in the TDM group than in the non-TDM group ( 4 % vs 17 % ; P = .02 ) . A complete or partial response was observed in 81 % ( 30 of 37 ) of patients in the TDM group compared to 57 % ( 20 of 34 ) in the non-TDM group ( P = .04 ) . CONCLUSIONS Routine TDM of voriconazole may reduce drug discontinuation due to adverse events and improve the treatment response in invasive fungal infections . CLINICAL TRIAL REGISTRATION NCT00890708 ABSTRACT Voriconazole prophylaxis is common following lung transplantation , but the value of therapeutic drug monitoring is unknown . A prospect i ve , observational study of lung transplant recipients ( n = 93 ) receiving voriconazole prophylaxis was performed . Serum voriconazole troughs ( n = 331 ) were measured by high-pressure liquid chromatography . The median initial and subsequent troughs were 1.91 and 1.46 μg/ml , respectively . The age of the patient directly correlated with initial troughs ( P = 0.005 ) . Patients that were ≥60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs , respectively . In 95 % ( 88/93 ) of patients , ≥2 troughs were measured . In 28 % ( 25/88 ) and 32 % ( 28/88 ) of these patients , all troughs were ≤1.5 μg/ml or > 1.5 μg/ml , respectively . Ten percent ( 10/93 ) and 27 % ( 25/93 ) of the patients developed invasive fungal infection ( tracheobronchitis ) and fungal colonization , respectively . The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 μg/ml ( P = 0.07 ) . Invasive fungal infections or colonization were more likely with troughs of ≤1.5 μg/ml ( P = 0.01 ) and among patients with no trough of > 1.5 μg/ml ( P = 0.007 ) . Other cutoff troughs correlated less strongly with microbiologic outcomes . Troughs correlated directly with aspartate transferase levels ( P = 0.003 ) , but not with other liver enzymes . Voriconazole was discontinued due to suspected toxicity in 27 % ( 25/93 ) of the patients . The troughs did not differ at the times of suspected drug-induced hepatotoxicity , central nervous system ( CNS ) toxicity , or nausea/vomiting and in the absence of toxicity . Voriconazole prophylaxis was most effective at troughs of > 1.5 μg/ml . A cutoff for toxicity was not identified , but troughs of > 4 μg/ml were rare . The data support a target range of > 1.5 to 4 μg/ml There are limited data on the relationship between voriconazole levels and clinical outcomes relative to invasive aspergillosis ( IA ) . We therefore analyzed the association between initial voriconazole trough blood levels and clinical responses of IA in patients with hematologic malignancies . All adult patients treated with voriconazole in a tertiary care hospital in Seoul , South Korea , between August 2009 and April 2011 were identified from pharmacy records . Initial voriconazole trough levels were routinely measured 1 week after therapy and patient responses were classified as success ( complete or partial response ) or failure ( stable response , progression of disease , or death ) at 2 weeks post-therapy . Fifty-two patients , involving 2 ( 4 % ) proven , 29 ( 56 % ) probable , and 21 ( 40 % ) possible IA infections , were included . Of these , 11 ( 21 % ) had initial voriconazole levels of ≤ 2 mg/l and the remaining 41 ( 79 % ) had > 2 mg/l . There were slightly fewer successful responses ( 45 % , 5/11 ) in the patients with initial voriconazole levels ≤ 2 mg/l than in those with voriconazole levels > 2 mg/l ( 51 % , 21/41 ) , but the difference was not statistically significant ( P= 0.73 ) . Neutropenia ( OR 0.1 , P= 0.008 ) and immunosuppression ( OR 0.1 , P= 0.004 ) were independently associated with 2-week successful response after voriconazole therapy . In conclusion , initial voriconazole trough levels may not significantly affect clinical outcomes of IA at 2 weeks after voriconazole therapy in patients with hematologic malignancies . Further studies of prospect i ve design are needed to establish the optimal procedure for voriconazole drug monitoring Background Genetic polymorphisms of cytochrome P450 enzymes , especially CYP2C19 influence voriconazole pharmacokinetics . However , the impact of CYP2C19 genetic polymorphisms on the therapeutic efficacy and toxicity of voriconazole therapy are not well established . Material s and Methods In this prospect i ve observational study , we analyzed all consecutive adult patients with hematologic diseases who were treated for invasive aspergillosis ( IA ) with voriconazole between January 2011 and June 2012 . CYP2C19 genotype and routine therapeutic drug monitoring of voriconazole were performed . The target range for voriconazole trough levels was 1 - 5.5 mg/L. Results A total of 104 consecutive patients were enrolled , including 39 homozygous extensive metabolizers ( EMs , 38 % ) , 50 heterozygous extensive metabolizers ( HEMs , 48 % ) , and 15 poor metabolizers ( PMs , 14 % ) . The initial voriconazole trough levels were 1.8 , 2.7 , and 3.2 mg/L in EMs , HEMs , and PMs , respectively ( P = 0.068 ) . Out-of-range initial trough levels were most frequently observed in EMs ( 46 % ) followed by HEMs ( 26 % ) and PMs ( 0 % ) ( P = 0.001 ) . The frequency of initial trough levels < 1 mg/L but not > 5.5 mg/L differed significantly among the 3 groups ( P = 0.005 ) . However , treatment response , all-cause and IA-attributable mortality , and the occurrence of voriconazole-related adverse events did not differ significantly among the 3 groups ( P = 0.399 , P = 0.412 , P = 0.317 , and P = 0.518 , respectively ) . Conclusions While none of the initial voriconazole trough levels in PMs was outside the target range , subtherapeutic initial trough levels were frequent in EMs . Although there was no significant relationship between CYP2C19 genotype and either the clinical outcomes of IA or toxicity of voriconazole , further large-scale multicenter studies using clinical data from homogeneous population s are required The aim of this study was to determine an optimum voriconazole target concentration , to study the influence of CYP2C19 gene status on metabolism of voriconazole and to identify a dose-adjustment strategy for voriconazole according to CYP2C19 polymorphism in patients with invasive fungal infections . A total of 328 voriconazole trough plasma concentrations ( C(min ) ) were collected and monitored from 144 patients . Information on efficacy and safety was obtained . Voriconazole therapy was effective in 81.9 % of patients ( 118/144 ) , and 12.5 % ( 18/144 ) exhibited signs of hepatotoxicity . The relationships between voriconazole C(min ) and clinical response and hepatotoxicity were explored using logistic regression , and a target clinical C(min ) range of 1.5 - 4 mg/L was identified . Values of voriconazole C(min ) and the ratio of C(min ) to concentration of voriconazole-N-oxide ( C(min)/C(N ) ) of poor metabolisers ( PMs ) were significantly higher than extensive metabolisers and intermediate metabolisers . Model-based simulations showed that PM patients could be safely and effectively treated with 200 mg twice daily orally or intravenously , and non-PM patients with 300 mg twice daily orally or 200 mg twice daily intravenously . This study highlighted that voriconazole C(min ) and C(min)/C(N ) are strongly influenced by CYP2C19 polymorphism , and gene-adjusted dosing is important to achieve therapeutic levels that maximise therapeutic response and minimise hepatotoxicity To evaluate the efficacy and safety of voriconazole in acute invasive aspergillosis ( IA ) , an open , noncomparative multicenter study was conducted . Immunocompromised patients with IA were treated with intravenously administered voriconazole 6 mg/kg twice a day ( b.i.d . ) twice and then 3 mg/kg b.i.d . for 6 - 27 days , followed by 200 mg b.i.d . administered orally for up to 24 weeks . Response was assessed by clinical and radiographic change . A total of 116 patients were assessable . IA was proven in 48 ( 41 % ) and probable in 68 patients . Voriconazole was given as primary therapy in 60 ( 52 % ) . Good responses were seen in 56 ( 48 % ) ; 16 ( 14 % ) showed complete response and 40 ( 34 % ) partial response . A stable response was seen in 24 patients ( 21 % ) , and 36 ( 31 % ) of the infections failed to respond to therapy . Good responses were seen in 60 % of those with pulmonary or tracheobronchial IA ( n=84 ) , 16 % with cerebral IA ( n=19 ) , 58 % with hematologic disorders ( n=67 ) , and 26 % of allogeneic stem cell transplant recipients ( n=23 ) . Voriconazole is efficacious in treating acute IA In this study we present the results of a therapeutic drug monitoring retrospective analysis involving 14 patients with several underlying diseases who were receiving voriconazole for the treatment of fungal infections . A simple high performance liquid chromatography assay with ultraviolet detection was used in the drug monitoring . We report here that serum concentrations were highly variable and unpredictable in most patients . We also found that lack of response was more frequent in patients with levels persistently lower than 1 mg/l . The number of sample s with voriconazole concentrations below 1 mg/l was significantly higher in patients who exhibited therapeutic failures ( 88 % versus 27 % ; P < 0.001 ) . In addition , the period of time in which voriconazole concentrations were maintained below 1 mg/l was slightly higher in patients in the failure group . We suggest that serum concentration should be individually quantified for patients receiving voriconazole therapy . Further prospect i ve studies are needed to clarify the potential benefit of the individualization of treatment ABSTRACT The aim of this study was to investigate the pharmacokinetics , safety , and tolerability of voriconazole following intravenous-to-oral switch regimens used with immunocompromised Japanese pediatric subjects ( age 2 to < 15 years ) at high risk for systemic fungal infection . Twenty-one patients received intravenous-to-oral switch regimens based on a recent population pharmacokinetic modeling ; they were given 9 mg/kg of body weight followed by 8 mg/kg of intravenous ( i.v . ) voriconazole every 12 h ( q12h ) , and 9 mg/kg ( maximum , 350 mg ) of oral voriconazole q12h ( for patients age 2 to < 12 or 12 to < 15 years and < 50 kg ) or 6 mg/kg followed by 4 mg/kg of i.v . voriconazole q12h and 200 mg of oral voriconazole q12h ( for patients age 12 to < 15 years and ≥50 kg ) . The steady-state area under the curve over the 12-h dosing interval ( AUC0–12,ss ) was calculated using the noncompartmental method and compared with the predicted exposures in Western pediatric subjects based on the abovementioned modeling . The geometric mean ( coefficient of variation ) AUC0–12,ss values for the intravenous and oral regimens were 51.1 μg · h/ml ( 68 % ) and 45.8 μg · h/ml ( 90 % ) , respectively ; there was a high correlation between AUC0–12,ss and trough concentration . Although the average exposures were higher in the Japanese patients than those in the Western pediatric subjects , the overall voriconazole exposures were comparable between these two groups due to large interindividual variability . The exposures in the 2 cytochrome P450 2C19 poor metabolizers were among the highest . Voriconazole was well tolerated . The most common treatment-related adverse events were photophobia and abnormal hepatic function . These recommended doses derived from the modeling appear to be appropriate for Japanese pediatric patients , showing no additional safety risks compared to those with adult patients . ( This study has been registered at Clinical Trials.gov under registration no. NCT01383993 . |
10,514 | 25,422,259 | Sirolimus was associated with a reduction in the risk of malignancy and non-melanoma skin cancer in transplant recipients .
The benefit was most pronounced in patients who converted from an established immunosuppressive regimen to sirolimus .
Given the risk of mortality , however , the use of this drug does not seem warranted for most patients with kidney transplant . | OBJECTIVE To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus . | AIMS To compare the pharmacokinetics of mycophenolic acid ( MPA ) and its metabolite ( MPAG ) when mycophenolate mofetil ( MMF ) is administered in combination with sirolimus or ciclosporin ( CsA ) in renal allograft recipients . Safety and efficacy ( biopsy-proven acute rejection ( BPAR ) ) were also assessed . METHODS Patients ( n = 45 ) were r and omized 2 : 1 to receive treatment with sirolimus ( n = 30 ; dosed to maintain trough concentrations of 10 - 25 ng ml(-1 ) until week 8 , and then 8 - 15 ng ml(-1 ) thereafter ) or CsA ( n = 15 ; administered as per centre practice ) both in combination with daclizumab , oral MMF and corticosteroids . Pharmacokinetic assessment s were performed at day 7 , week 4 , and months 3 and 6 post-transplant . The primary endpoint was the AUC(0,12 h ) for MPA and MPAG . The pharmacokinetics of sirolimus were also assessed . RESULTS MPA exposure was 39 - 50 % lower ( month 6 mean AUC(0,12 h ) ( 95%CI ) : 40.4 ( 33.8 , 47.0 ) vs. 68.5 ( 54.9 , 82.0 ) microg ml(-1 ) h ) and MPAG exposure was 25 - 52 % higher ( 722 ( 607 , 838 ) vs. 485 ( 402 , 569 ) microg ml(-1 ) h at month 6 ) in the presence of CsA compared with sirolimus across visits . BPAR was 40.0 % with sirolimus and 13.3 % with CsA. The incidence of hypertension , tremors and hirsutism was higher with CsA than with sirolimus , while the incidence of diarrhoea , hyperlipidaemia and impaired wound closure was higher with sirolimus . No deaths , malignancies or graft losses were reported . CONCLUSIONS Co-administration of sirolimus with MMF led to greater MPA exposure , but lower MPAG exposure , than co-administration with CsA. As rejection rates were higher in the absence of CsA , further study of calcineurin inhibitor-free regimens is required before general recommendations can be made BACKGROUND Acute rejection episodes after renal transplantation are an important clinical challenge , despite use of multidrug immunosuppressive regimens . We did a prospect i ve , multicentre , r and omised , double-blind trial to investigate the impact of the addition of sirolimus , compared with azathioprine , to a cyclosporin and prednisone regimen . METHODS 719 recipients of primary HLA-mismatched cadaveric or living-donor renal allografts who displayed initial graft function were r and omly assigned , after transplantation , sirolimus 2 mg daily ( n=284 ) or 5 mg daily ( n=274 ) , or azathioprine ( n=161 ) . We assessed the primary composite endpoint of efficacy failure , occurrence of biopsy-confirmed acute rejection episodes , graft loss , or death , and various secondary endpoints that characterise these episodes at 6 months and 12 months . Analyses were done by intention to treat . FINDINGS The rate of efficacy failure at 6 months was lower in the two sirolimus groups ( 2 mg 18.7 % , p=0.002 ; 5 mg 16.8 % , p<0.001 ) than in the azathioprine group ( 32.3 % ) . The frequency of biopsy-confirmed acute rejection episodes was also lower ( 2 mg 16.9 % , p=0.002 ; 5 mg 12.0 % , p<0.001 ; azathioprine 29.8 % ) . At 12 months , survival was similar in all groups for grafts ( 97.2 % , 96.0 % , and 98.1 % ) and patients ( 94.7 % , 92.7 % , and 93.8 % ) . Patients on sirolimus showed a delay in the time to first acute rejection episode and decreased frequency of moderate and severe histological grade s of rejection episodes and related antibody treatment , compared with the azathioprine group . Rates of infection and malignant disorders were similar in all groups . INTERPRETATION Use of sirolimus reduced occurrence and severity of biopsy-confirmed acute rejection episodes with no increase in complications . Further studies are needed to establish the optimum doses for the combined regimen We performed a prospect i ve r and omized trial comparing sirolimus/mycophenolate mofetil (MMF)/prednisone to cyclosporine/MMF/prednisone and selected induction therapy with basiliximab . Twenty patients received sirolimus ( 10 mg loading dose followed by 3 mg/m body surface area/day , keeping 24-hr trough levels at 10 - 15 ng/mL for six months and 5 - 10 ng/mL thereafter . Twenty-one patients began cyclosporine ( 4 to 8 mg/kg/day , keeping 12-hour trough levels at 150 - 300 ng/mL for 6 months and 100 - 200 ng/mL afterwards ) . Mean follow up was 15.8 months . One-year patient and graft survival was similar in both groups ( > 90 % ) . Acute rejection rate was 16.6 % in the sirolimus group and 5.2 % in the cyclosporine group ( P = NS ) . There were no differences in mean serum creatinine between groups . No patients who received basiliximab and had sirolimus target levels suffered acute rejection at one year . The sirolimus group had significantly higher cholesterol and triglycerides . A calcineurin inhibitor-free regimen using sirolimus produces comparable one-year transplant outcomes in living related kidney transplants compared to a calcineurin inhibitor regimen Calcineurin inhibitors have decreased acute rejection and improved early renal allograft survival , but their use has been implicated in the development of chronic nephrotoxicity . We performed a prospect i ve , r and omized trial in kidney transplantation comparing sirolimus‐MMF‐prednisone to tacrolimus‐MMF‐prednisone . Eighty‐one patients in the sirolimus group and 84 patients in the tacrolimus group were enrolled ( mean follow‐up = 33 months ; range 13–47 months ) . At 1 year , patient survival was similar in the groups ( 98 % with sirolimus , 96 % with tacrolimus ; p = 0.42 ) as was graft survival ( 94 % sirolimus vs. 92 % tacrolimus , p = 0.95 ) . The incidence of clinical acute rejection was 10 % in the tacrolimus group and 13 % in the sirolimus group ( p = 0.58 ) . There was no difference in mean GFR measured by iothalamate clearance between the tacrolimus and sirolimus groups at 1 year ( 61 ± 19 mL/min vs. 63 ± 18 mL/min , p = 0.57 ) or 2 years ( 61 ± 17 mL/min vs. 61 ± 19 mL/min , p = 0.84 ) . At 1 year , chronicity using the Banff schema showed no difference in interstitial , tubular or glomerular changes , but fewer chronic vascular changes in the sirolimus group . This study shows that a CNI‐free regimen using sirolimus‐MMF‐prednisone produces similar acute rejection rates , graft survival and renal function 1–2 years after transplantation compared to tacrolimus‐MMF‐prednisone Current immunosuppressive regimens in renal transplantation typically include calcineurin inhibitors ( CNIs ) and corticosteroids , both of which have toxicities that can impair recipient and allograft health . This 1‐year , r and omized , controlled , open‐label , exploratory study assessed two belatacept‐based regimens compared to a tacrolimus (TAC)‐based , steroid‐avoiding regimen . Recipients of living and deceased donor renal allografts were r and omized 1:1:1 to receive belatacept‐mycophenolate mofetil ( MMF ) , belatacept‐sirolimus ( SRL ) , or TAC‐MMF . All patients received induction with 4 doses of Thymoglobulin ( 6 mg/kg maximum ) and an associated short course of corticosteroids . Eighty‐nine patients were r and omized and transplanted . Acute rejection occurred in 4 , 1 and 1 patient in the belatacept‐MMF , belatacept‐SRL and TAC‐MMF groups , respectively , by Month 6 ; most acute rejection occurred in the first 3 months . More than two‐thirds of patients in the belatacept groups remained on CNI‐ and steroid‐free regimens at 12 months and the calculated glomerular filtration rate was 8–10 mL/min higher with either belatacept regimen than with TAC‐MMF . Overall safety was comparable between groups . In conclusion , primary immunosuppression with belatacept may enable the simultaneous avoidance of both CNIs and corticosteroids in recipients of living and deceased st and ard criteria donor kidneys , with acceptable rates of acute rejection and improved renal function relative to a TAC‐based regimen BACKGROUND Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients . This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens . METHODS We r and omly assigned 1645 renal-transplant recipients to receive st and ard-dose cyclosporine , mycophenolate mofetil , and corticosteroids , or daclizumab induction , mycophenolate mofetil , and corticosteroids in combination with low-dose cyclosporine , low-dose tacrolimus , or low-dose sirolimus . The primary end point was the estimated glomerular filtration rate ( GFR ) , as calculated by the Cockcroft-Gault formula , 12 months after transplantation . Secondary end points included acute rejection and allograft survival . RESULTS The mean calculated GFR was higher in patients receiving low-dose tacrolimus ( 65.4 ml per minute ) than in the other three groups ( range , 56.7 to 59.4 ml per minute ) . The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus ( 12.3 % ) than in those receiving st and ard-dose cyclosporine ( 25.8 % ) , low-dose cyclosporine ( 24.0 % ) , or low-dose sirolimus ( 37.2 % ) . Allograft survival differed significantly among the four groups ( P=0.02 ) and was highest in the low-dose tacrolimus group ( 94.2 % ) , followed by the low-dose cyclosporine group ( 93.1 % ) , the st and ard-dose cyclosporine group ( 89.3 % ) , and the low-dose sirolimus group ( 89.3 % ) . Serious adverse events were more common in the low-dose sirolimus group than in the other groups ( 53.2 % vs. a range of 43.4 to 44.3 % ) , although a similar proportion of patients in each group had at least one adverse event during treatment ( 86.3 to 90.5 % ) . CONCLUSIONS A regimen of daclizumab , mycophenolate mofetil , and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function , allograft survival , and acute rejection rates , as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with st and ard-dose cyclosporine without induction . ( Clinical Trials.gov number , NCT00231764 [ Clinical Trials.gov ] . ) The preliminary observation of marked erythrocyte microcytosis in patients treated with sirolimus ( SRL ) and mycophenolate mofetil ( MMF ) has been evaluated as part of a prospect i ve study comparing SRL and cyclosporin A ( CsA ) as a primary immunosuppressant . Normal risk de novo kidney recipients were r and omized either to SRL or to CsA. Additional immunosuppressants consisted of MMF and prednisone . In patients with erythrocyte microcytosis , iron deficiency was excluded by measuring serum ferritin and transferrin saturation rate . Fifty-nine patients ( 30 in SRL and 29 in CsA ) were included . Mean corpuscular volume ( MCV ) ( fl ) on day 7 was 91.7 + /- 4.8 in SRL group versus 91.4 + /- 4.2 in CsA group ( P = 0.77 ) , whereas mean MCV on day 183 post-transplant was 78.5 + /- 3.8 in SRL group versus 88.4 + /- 3.4 in CsA group ( P < 0.0001 ) . Hemoglobin concentration ( g/dl ) was not significantly different . Only two patients in SRL group presented decreased transferrin saturation rate . Marked erythrocyte microcytosis without persistent anemia was observed in patients treated with SRL and MMF Background . Chronic steroid therapy in kidney transplantation has myriad side effects and steroid avoidance has become feasible . This prospect i ve study compared the safety and efficacy of steroid avoidance in tacrolimus (TAC)/mycophenolate mofetil ( MMF ) and TAC/sirolimus ( SRL ) combinations in kidney transplantation . Methods . In all , 150 kidney recipients were analyzed : 75 each in TAC/MMF and TAC/SRL groups . The primary endpoint was acute rejection . Surveillance biopsies were completed to analyze sub clinical acute rejection ( SCAR ) and chronic allograft nephropathy ( CAN ) . Acute rejection and SCAR were treated by methylprednisolone . Two-year patient and graft survival , renal function , and adverse effects were monitored . Results . Acute rejection was seen in 12 % of TAC/MMF and 8 % of TAC/SRL patients . Two-year actuarial patient survival was 95 % and 97 % , and graft survival 90 % and 90 % in TAC/MMF and TAC/SRL groups , respectively . Surveillance biopsy showed cumulative incidence of SCAR was 27 % in TAC/MMF and 16 % in TAC/SRL groups at 2 years ( P=0.04 ) . Overall , 33 % of recipients in TAC/MMF and 20 % in TAC/SRL received methylprednisolone for acute rejection/SCAR . Moderate/severe CAN was 10 % in TAC/SRL group and 22 % in TAC/MMF group(P=0.06 ) . New-onset diabetes mellitus ( NODM ) was 4 % each in both groups . All recipients remain free of maintenance steroid therapy . Conclusions . Steroid avoidance in tacrolimus-based immunosuppression with MMF or SRL provides equivalent 2-year patient and graft survival with a low incidence of acute rejection and NODM . SCAR and CAN are lower in TAC/SRL compared to TAC/MMF group . The impact of decreased SCAR and CAN in TAC/SRL group on longer-term graft survival and function is to be evaluated BACKGROUND Sirolimus maintenance therapy with Thymoglobulin induction is a promising regimen that may preserve renal function . Data are lacking , however , about the immunologic effects of combined Thymoglobulin-sirolimus . METHODS In a 12-month , prospect i ve , r and omised , open-label , single-centre pilot study , de novo deceased-donor kidney transplant patients were r and omised to receive cyclosporine or sirolimus , with Thymoglobulin induction , mycophenolate mofetil and corticosteroids . Flow cytometry analysis of peripheral blood was used to evaluate immune reconstitution . RESULTS Nineteen patients were recruited ( sirolimus 9 , cyclosporine 10 ) . Reconstitution of the CD4(+ ) T-lymphocyte subset was significantly lower with sirolimus versus cyclosporine over year 1 , but CD8(+ ) reconstitution did not differ significantly between groups . The proportion of naïve CD4(+ ) T-lymphocytes showed an initial decrease with sirolimus versus cyclosporine . Naïve CD8(+ ) T-lymphocytes increased versus baseline in the cyclosporine cohort at months 1 and 3 , but remained unchanged with sirolimus . Memory CD4(+ ) T-lymphocytes occurred more frequently in sirolimus- versus cyclosporine-treated patients during year 1 . The proportion of memory CD8(+ ) T-lymphocytes decreased at months 1 and 3 compared to baseline in the CsA arm , but did not change in the sirolimus cohort . By month 12 , the proportion of both naïve and memory CD4(+ ) and CD8(+ ) T-lymphocytes had become similar with sirolimus or cyclosporine . There were fewer naïve B-lymphocytes in the sirolimus cohort and more CD19(-)IgD(+/-)CD27(+ ) memory B-lymphocytes . CONCLUSIONS In this small population , homeostatic reconstitution after Thymoglobulin induction showed disproportionately high recovery of memory T-lymphocyte subsets during sirolimus therapy , which may explain the higher rejection rate seen with sirolimus versus cyclosporine following kidney transplantation OBJECTIVES This prospect i ve study was design ed to develop a steroid and calcineurin inhibitor-free regimen for kidney transplants using alemtuzumab . MATERIAL S AND METHODS A single dose of alemtuzumab ( 30 mg ) was given preoperatively . Phase 1 : Twenty-one patients were r and omized into 2 groups ; the tacrolimus ( n=11 ) and the sirolimus groups ( n=10 ) . Steroids were given for 5 days . Azathioprine ( 1 mg/kg ) was added when white blood cells ≥ 4000 cells/cm(3 ) . Mean follow-up was 48 ± 2.8 and 48.2 ± 1.6 months for the tacrolimus and sirolimus groups . Phase 2 : Twenty patients were included and the study design was modified . Tacrolimus was given for 2 months , and was replaced by sirolimus thereafter . The mean follow-up was 28.3 ± 2.1 months . RESULTS Phase 1 : Acute rejection episodes were encountered in 5 patients of the tacrolimus versus 2 cases in the sirolimus group ( P = .44 ) . Antibody-mediated rejection was diagnosed in 2 recipients in each group . Four patients were switched from sirolimus to tacrolimus owing to resistant rejection , significant proteinuria , persistent thrombocytopenia , lymphocele , and urinary leakage . One patient was shifted from tacrolimus to sirolimus owing to Kaposi sarcoma . Glomerular filtration rate was significantly higher in the sirolimus group . Currently , 14 patients ( 8 tacrolimus , and 6 sirolimus ) are steroid-free . One patient died from the tacrolimus group owing to fulminant hepatitis . Two grafts were lost in the sirolimus group versus 1 graft in the tacrolimus group . Phase 2 : Five patients developed successfully treated borderline changes with no antibody-mediated rejection . Mean serum creatinine was 114.9 ± 17.7 µmol/L. Currently , 17 patients are steroid free and 15 of them are calcineurin inhibitor-free as well . In this phase , only 1 patient died with a functioning graft . CONCLUSIONS This clinical trial provides a good insight into a potentially effective steroid and calcineurin inhibitor-free protocol with the use of alemtuzumab induction in combination with sirolimus BACKGROUND Transplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers . Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed . METHODS In this multicenter trial , we r and omly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell carcinoma either to receive sirolimus as a substitute for calcineurin inhibitors ( in 64 patients ) or to maintain their initial treatment ( in 56 ) . The primary end point was survival free of squamous-cell carcinoma at 2 years . Secondary end points included the time until the onset of new squamous-cell carcinomas , occurrence of other skin tumors , graft function , and problems with sirolimus . RESULTS Survival free of cutaneous squamous-cell carcinoma was significantly longer in the sirolimus group than in the calcineurin-inhibitor group . Overall , new squamous-cell carcinomas developed in 14 patients ( 22 % ) in the sirolimus group ( 6 after withdrawal of sirolimus ) and in 22 ( 39 % ) in the calcineurin-inhibitor group ( median time until onset , 15 vs. 7 months ; P=0.02 ) , with a relative risk in the sirolimus group of 0.56 ( 95 % confidence interval , 0.32 to 0.98 ) . There were 60 serious adverse events in the sirolimus group , as compared with 14 such events in the calcineurin-inhibitor group ( average , 0.938 vs. 0.250 ) . There were twice as many serious adverse events in patients who had been converted to sirolimus with rapid protocol s as in those with progressive protocol s. In the sirolimus group , 23 % of patients discontinued the drug because of adverse events . Graft function remained stable in the two study groups . CONCLUSIONS Switching from calcineurin inhibitors to sirolimus had an antitumoral effect among kidney-transplant recipients with previous squamous-cell carcinoma . These observations may have implication s concerning immunosuppressive treatment of patients with cutaneous squamous-cell carcinomas . ( Funded by Hospices Civils de Lyon and others ; TUMORAPA Clinical Trials.gov number , NCT00133887 . ) Delayed graft function ( DGF ) has long been identified as one of the main correlates of poor graft survival in cadaveric renal transplantation , but the factors that affect its onset and duration are not fully eluci date d. The impact of two immunosuppressive protocol s on the incidence and length of DGF among kidney transplant recipients of a suboptimal organ was evaluated . Patients were r and omly treated with corticosteroids ( CS ) ; low-dose cyclosporine ( CsA ) and sirolimus ( SRL ; group 1 ; n = 42 ) ; or CS , full-dose CsA , and mycophenolate mofetil ( group 2 ; n = 48 ) . All recipients received immunoprophylaxis with basiliximab . After 3 mo , group 1 discontinued CsA and continued with SRL , whereas group 2 continued the same treatment . The incidence of DGF was similar in the two groups ( group 1 = 52.4 % ; group 2 = 58.3 % ) , whereas its duration was significantly higher in the group 1 ( 19.0 + /- 6.0 versus 10.3 + /- 3.2 d ; P = 0.001 ) . Both groups showed 100 % actuarial graft and patient survival at 1-yr . Among DGF patients , serum creatinine ( sCr ) at discharge was significantly worse in group 1 ( sCr , 3.0 + /- 1.0 versus 1.5 + /- 0.2 mg/dl ; calculated creatinine clearance , 31.2 + /- 9.3 versus 61.1 + /- 10 ml/min ; P = 0.001 ) . During the first year , the former group displayed a significant improvement of graft function , such that at 1-yr , no difference could be measured between groups ( sCr , 1.8 + /- 0.5 versus 1.7 + /- 0.4 mg/dl ; calculated creatinine clearance , 51.5 + /- 10.2 versus 53.3 + /- 9.4 ml/min ) . In conclusion , in de novo renal transplanted patients , the administration of SRL , in combination with low-dose CsA , is associated with a delayed recovery from DGF but does not worsen 1-yr graft function In a multicenter trial , renal transplant recipients were r and omized to tacrolimus with fixed-dose sirolimus ( Tac/SRL , N = 318 ) or tacrolimus with MMF ( Tac/MMF , N = 316 ) . Targeted tacrolimus trough levels were lower in the Tac/SRL group after day 14 . The primary endpoint was renal function at 6 months using creatinine clearance ( Cockcroft-Gault ) and was comparable at 66.4 mL/min ( SE 1.4 ) with Tac/SRL and at 65.2mL/min ( SE 1.3 ) with Tac/MMF ( completers ) . Biopsy-confirmed acute rejection was 15.1 % ( Tac/SRL ) and 12.3 % ( Tac/MMF ) . In both groups , graft survival was 93 % and patient survival was 99.0 % . Premature withdrawal due to an adverse event was twice as high in the Tac/SRL group , 15.1 % versus 6.3 % . Hypercholesterolemia incidence was higher with Tac/SRL ( P < .05 ) while CMV , leukopenia , and diarrhea incidences were higher with Tac/MMF ( P < .05 ) . The incidence of any antidiabetic treatment for > 30 consecutive days in previously nondiabetic patients was 17.8 % , Tac/SRL , and 24.8 % , Tac/MMF . Evaluation at 6 months showed comparable renal function using tacrolimus/sirolimus and tacrolimus/MMF regimens OBJECTIVE This study examines the outcomes of de novo kidney transplants treated by a sequential protocol , design ed to target the succession of immunologic events following engraftment . SUBJECTS A total of 113 sequential live-donor recipients were r and omized into 2 arms . Patients in arm A received prednisolone , cyclosporine , and sirolimus for 3 months ( phase 1 ) , followed by replacement of cyclosporine with mycophenolate mofetil ( phase 2 ) . Those in arm B ( controls ) received prednisolone/cyclosporine/mycophenolate mofetil throughout the study . The primary endpoints were patient and graft survival rates at 2 years . Secondary endpoints included biopsy-proven acute rejection , early and late graft function , hypertension , and adverse reactions . RESULTS The 2-year intent-to-treat patient and graft survival rates ( 95.8 % vs 91.4 % and 94.6 % vs 90.2 % ) were numerically but not significantly higher in arm A. The overall incidence of biopsy-proven acute rejection was numerically lower ( 13.5 % vs 18.9 % ) , yet it occurred exclusively with cyclosporine C2 levels below 770 ng/mL ( P = .28 ) . Mean time for serum creatinine to reach 132 micromol/L was significantly longer in arm A ( 7.3 vs 2.9 days ) . Graft function at 2 years ( eGFR , 70.2 vs 55.9 mL/min ) and number of drugs needed to control blood pressure ( mean 1.7 vs 2.25 ) were significantly more favorable in group A. Significant adverse effects for patients in arm A included proteinuria ( 36.8 % vs 18.6 % ) , hyperlipidemia ( peak cholesterol > 7.75 mmol/L in 32.9 % vs 23.7 % of patients ) and thrombocytopenia ( platelet count < 100 x 109/L in 32.9 % vs 13.5 % of patients ) . CONCLUSIONS The described protocol reduced the incidence of biopsy-proven acute rejection in patients after kidney transplant , particularly in those with adequate cyclosporine blood levels . Despite the significantly higher incidence of certain adverse effects ( ie , delayed graft function , proteinuria , hyperlipidemia , and transient thrombocytopenia ) , patient and graft survival rates at 2 years were numerically , though not statistically , improved in patients in arm A. At 2-year analysis , compared with patients in the control arm ( arm B ) , graft function significantly improved in patients in arm A , and the number of drugs needed to control blood pressure was significantly lower INTRODUCTION Sirolimus is the one of new immunosuppressants that may be a substitute to traditional drugs such as cyclosporine . We present our investigation on sirolimus-based immunosuppression in kidney transplant recipients as compared with cyclosporine-based immunosuppression . MATERIAL S AND METHODS We enrolled 100 patients in an open-labeled r and omized clinical trial at Shahid Labbafinejad Medical Center . The patients were assigned to one of the immunosuppressive groups to receive either sirolimus or cyclosporine in combination with mycophenolate mofetil and steroids . All kidney transplant recipients were followed up by for serum creatinine and glomerular filtration rate for 4 years . RESULTS There was no significant differences between the two groups regarding serum creatinine level and GFR until for years posttransplant ; however , serum creatinine levels were significantly lower and the GFRs were higher in the sirolimus group after 3 and 4 years . The mean serum creatinine was 1.24 ± 0.28 mg/dL in the sirolimus group and 1.57 ± 0.33 mg/dL in the cyclosporine group at 4 years posttransplant ( P = .02 ) . Also , GFR was 79.8 ± 22.3 mL/min/1.73 m2 in the sirolimus group and 70.3 ± 23.6 mL/min/1.73 m2 in the cyclosporine group B ( P = .04 ) . Acute rejection was 1.7-fold higher in the cyclosporine group than in the sirolimus group . CONCLUSIONS Our study demonstrated that sirolimus in the immunosuppressive regimen of kidney transplant recipients had better outcomes regarding graft and patient survival . The effectiveness of sirolimus for kidney allograft recipients should be further assessed to be implemented from the first day after transplantation Background . To define the role of mammalian target of rapamycin inhibitors in kidney transplantation , we compared efficacy and safety of two immunosuppressive regimens — a calcineurin inhibitor-free regimen with depletive induction versus a calcineurin inhibitor-based regimen . Methods . De novo renal allograft recipients were r and omized before transplantation to receive sirolimus ( SRL ; n=71 , group A ) or tacrolimus ( n=70 , group B ) . All patients received mycophenolate mofetil and corticosteroids . In group A , patients received rabbit antithymocyte globulin induction . In group B , antithymocyte globulin therapy could be given in case of delayed graft function . The estimated glomerular filtration rate ( GFR ) ( Nankivell 's formula ) at month 12 was the primary endpoint . Results . GFR showed no significant difference at month 12 , with 56.1 in group A versus 58.4 mL/min/1.73 m2 in group B. In functioning grafts , renal function was significantly better in the SRL group , with higher GFR values at months 1 , 2 , 3 , 6 , and 9 ( P<0.05 ) . At month 12 , patient survival and incidence of biopsy-proven rejection were not different between groups ( 95.8 % vs. 97.1 % , and 16.9 % vs. 12.9 % , respectively ) . However , proportion of graft loss was higher with SRL at months 6 and 12 ( 11.3 % vs. 0.0 % , P=0.004 ; 14.1 % vs. 4.3 % , P=0.044 , respectively ) . Adverse events and premature withdrawals were more frequent with SRL ( P<0.001 and P<0.05 , respectively ) , whereas cytomegalovirus infections were more frequent with tacrolimus ( P<0.001 ) . Conclusion . Patients treated with induction plus SRL , mycophenolate mofetil , and corticosteroids may obtain good renal function but have a higher risk of adverse events , drug withdrawal , and graft loss Abstract : Background : The ability of sirolimus ( SRL ) , in combination with reduced exposure of cyclosporine , was investigated to prevent acute rejection and associated side effects To evaluate the efficacy and tolerance of a calcineurin inhibitor (CNI)‐free regimen , 145 renal recipients were prospect ively r and omized to receive either sirolimus ( n = 71 ) or cyclosporine ( CsA ; n = 74 ) . All patients received polyclonal antilymphocyte antibodies , mycophenolate mofetil ( MMF ) and steroids ( 6 months ) . The primary endpoint , estimated glomerular filtration rate ( eGFR ) was not significantly different at 12 months comparing sirolimus‐ and CsA‐treated patients ( 60 ± 27 vs. 57 ± 21 mL/min ) . At 12 months , patient and graft survival , incidence of biopsy‐proven rejection and rates of steroid withdrawal were not statistically different ( 97 % vs. 97 % ; 90 % vs. 93 % ; 14.3 % vs. 8.6 % and 82.8 % vs. 84.1 % , respectively ) . Delayed and slow graft function ( SGF ) was not significantly different ( 18.6 % vs. 12.3 % and 11.4 % vs. 13.7 % , respectively ) . In patients who remained on treatment according to protocol at 12 months , eGFR was significantly higher with sirolimus ( 69 ± 19 vs. 60 ± 14 mL/min , p = 0.01 ) . Overall study drug discontinuation rates were 28.2 % with sirolimus and 14.9 % with CsA. Adverse events ( wound complications , mouth ulcers , diarrhea , hypokalemia , bronchopneumonia ) and proteinuria > 0.5 g/24h ( 38.8 % vs. 5.6 % , p < 0.001 ) were significantly more frequent in sirolimus‐treated patients . Cytomegalovirus ( CMV ) infections were significantly less frequent with sirolimus ( 6 % vs. 23 % , p < 0.01 ) . A CNI‐free regimen using sirolimus‐MMF can achieve excellent renal function , but patients on sirolimus experienced a high rate of adverse events and study drug discontinuation Background . This is the 1-year report of a r and omized , multicenter , clinical trial comparing the combination of sirolimus or mycophenolate mofetil ( MMF ) with tacrolimus-based immunosuppression in kidney transplantation . Methods . Prior to transplantation , recipients were r and omized to receive tacrolimus plus corticosteroids with either sirolimus ( n=185 ) or MMF ( n=176 ) . The incidence of biopsy-confirmed acute rejection at 6 months was the primary endpoint of the study . Patient and graft survival , renal function , study drug dosing and discontinuations were evaluated at 1 year . Results . At 1 year , there was no difference in patient survival ( 95.7 % sirolimus vs. 97.2 % MMF ; P=0.45 ) or graft survival ( 90.8 % sirolimus vs. 94.3 % MMF ; P=0.22 ) . Patients without delayed graft function ( DGF ) receiving MMF had significantly better graft survival ( 99 % vs. 93 % ; P=0.01 ) . Patients receiving a transplant from a live donor had a trend towards better graft survival with MMF as compared to sirolimus ( 98 % vs. 91 % ; P=0.07 ) . Patients receiving sirolimus had a significantly higher incidence of study drug discontinuation ( 26.5 % vs. 14.8 % MMF ; P=0.006 ) . Patients receiving MMF had significantly better renal function as shown by median serum creatinine levels ( 1.3 mg/dL vs. 1.5 mg/dL ; P=0.03 ) and a trend towards higher calculated creatinine clearance ( CrCl ) , ( 58.4 ml/min vs. 54.3 ml/min ; P=0.06 ) . More patients in the sirolimus group had a serum creatinine > 2.0 mg/dL , ( 20.4 % vs. 11.0 % ; P=0.02 ) . Conclusions . Tacrolimus is safe and effective in live and deceased donor kidney transplantation when given in combination with sirolimus or MMF . Patient and graft survival were excellent in both arms . Renal function is superior for patients treated with tacrolimus + MMF combination BACKGROUND Sirolimus has been promoted as an agent to provide immunosuppression for kidney transplant recipients that , in contrast to calcineurin inhibitors , would not be nephrotoxic . However , several reports have observed proteinuria in patients treated with sirolimus , ranging from low grade to nephrotic range . Accordingly , we compared markers of tubular and glomerular damage in an ancillary study of a r and omized trial comparing sirolimus and cyclosporine . STUDY DESIGN Single-center , open-label , r and omized , prospect i ve trial . SETTING & PARTICIPANTS Patients undergoing cadaveric or living donor kidney transplant at the University Hospital in Basel , Switzerl and , between January 2001 and July 2004 . INTERVENTION Immunosuppression regimen consisting of cyclosporine , mycophenolate mofetil , and prednisone versus sirolimus , mycophenolate mofetil , and prednisone . OUTCOMES The primary outcome was kidney function , assessed using serum creatinine level . Secondary outcomes included patient and graft survival , number of rejections , and evidence of kidney damage , assessed using glomerular and tubular urine biomarker levels . MEASUREMENTS Urine and serum were collected at 0 , 7 , 30 , and 90 days . Kidney function was estimated using serum creatinine level . Urinary markers included alpha(1)-microglobulin and retinol-binding protein ( tubular ) , transferrin and albumin ( glomerular ) , and semiquantitative assessment of glucosuria . Protocol kidney biopsies were performed at days 90 and 180 . RESULTS There were 63 patients r and omly assigned to cyclosporine-based regimens , and 64 , to sirolimus-based regimens . Kidney function was similar in both groups , whereas levels of markers associated with glomerular damage ( albumin , 19.5 vs 8.96 mg/mmol creatinine ; P < 0.001 ; transferrin , 13.1 vs 5.7 mg/mmol creatinine ; P < 0.001 ) and those associated with tubular damage ( alpha(1)-microglobulin , 11 vs 7.6 mg/mmol creatinine ; P = 0.004 ; retinol-binding protein , 19.6 vs 9.6 mg/mmol creatinine ; P = 0.002 ) were higher beginning at day 7 in patients r and omly assigned to sirolimus therapy , with similar findings through day 90 . Glucosuria incidence was higher in patients r and omly assigned to sirolimus therapy beginning by day 30 ( 65 % vs 30 % on day 30 ; P = 0.002 ; 51 % vs 22 % on day 90 ; P < 0.001 ) . On histologic examination , the overall severity of tubular lesions was significantly higher in patients r and omly assigned to sirolimus therapy . LIMITATIONS Small sample size , short-term follow-up likely insufficient to appreciate calcineurin-associated nephropathy . CONCLUSION Compared with a cyclosporine-based immunosuppression regimen , a sirolimus-based regimen is associated with de novo low- grade glomerular proteinuria , increased excretion of markers associated with tubular damage , and evidence of tubular damage on kidney biopsy In an effort to mitigate progression of IF/TA associated with chronic renal allograft injury , we hypothesize that adjuvant immunosuppression with sirolimus ( SRL ) will delay progression compared with MMF . Subjects 5 - 17 yr old , > 1-yr post-transplant with mild or moderate IF/TA ( Banff criteria ) and tacrolimus dose minimization were r and omized to continue MMF or convert to SRL and followed for two yr . For the entire cohort ( n = 20 ) , there was significant progression of % GGS , ci , ct , cv , and ah scores over the follow-up period ( p < 0.05 ) . There was no difference in rates of progression of Banff scores , % GGS , or % IF over two yr between the two groups , though power was low . Both groups exhibited similar rates of eGFR decline ( MMF : -12.3 vs. SRL : -11.8 mL/min/1.73 m²/yr ) , which was correlated with ct score ( p < 0.05 ) . The SRL group had more episodes of acute allograft dysfunction and oral ulcers . Proteinuria at 24 months was significantly increased in the SRL group ( 6/9 subjects ) but was not correlated with eGFR or % GGS . We conclude that neither MMF nor SRL , combined with low-dose tacrolimus , was effective at mitigating progressive histological changes or functional decline associated with chronic renal allograft injury Tacrolimus combined with mycophenolate mofetil ( MMF ) is an effective regimen in kidney transplantation . This study compared the efficacy of combining tacrolimus and two different dosages of sirolimus with an established tacrolimus‐MMF regimen . Each day in addition to tacrolimus , 325 patients received 2 mg sirolimus ( TAC‐SRL2 mg ) , 325 patients received 0.5 mg sirolimus ( TAC‐SRL0.5 mg ) and 327 patients 1 g MMF ( TAC‐MMF ) . The initial tacrolimus dose was 0.2 mg/kg/day . Sirolimus patients received loading doses of 6 or 1.5 mg , and daily doses of 2 or 0.5 mg thereafter . Steroid administration was identical for all groups . The incidence of biopsy‐proven acute rejection was lower in the TAC‐SRL2 mg group ( 15.7 % ) compared with the TAC‐SRL0.5 mg ( 25.2 % , p = 0.003 ) and the TAC‐MMF groups ( 22.3 % , p = 0.036 ) . Six‐month graft survival was 91.0 % ( TAC‐SRL2 mg ) , 92.6 % ( TAC‐SRL0.5 mg ) and 92.4 % ( TAC‐MMF ) ; the respective values for patient survival were 98.1 % , 97.8 % and 97.9 % . Thirty‐four patients ( 10.5 % ) , 19 patients ( 5.8 % ) and 16 patients ( 4.9 % ) in the TAC‐SRL2 mg , TAC‐SRL0.5 mg and TAC‐MMF groups , respectively , discontinued the study because of adverse events . Hyperlipemia was reported more often in the TAC‐SRL2 mg group ( 24.0 % ) compared with 19.4 % ( TAC‐SRL0.5 mg ) and 11.0 % ( TAC‐MMF ; p < 0.05 ) . Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection , but a higher incidence of adverse events A 6-month , open-label , multicenter prospect i ve pilot study was conducted to evaluate the effects of sirolimus ( SRL ) versus cyclosporine ( CsA ) in recipients of kidneys from exp and ed criteria donors . All patients also received antithymocyte globulins induction , mycophenolate mofetil , and steroids . Sixty-nine patients ( 33 SRL , 36 CsA ) were r and omized . More patient were withdrawn in the SRL group ( 16 vs. 6 , P<0.01 ) , because of delayed graft function and surgical complications . Delayed graft function tended to be more frequent with SRL than with CsA ( 45.4 % vs. 30.6 % , P=0.22 ) . Graft survival was numerically lower in the SRL group ( 87.5 % vs. 97 % , P=0.19 ) . At 6 months , there were no significant differences in biopsy-proven acute rejection or calculated creatinine clearance ( SRL 12.1 % vs. CsA 8.3 % ; P=0.7 and 44.7±16.6 vs. 41.9±15.2 mL/min ; P=0.54 respectively ) . These results do not support the use of SRL immediately after transplantation in exp and ed criteria donor recipients The optimal long-term regimen for immunosuppression for kidney transplant recipients is unknown . We conducted a r and omized trial involving 150 kidney transplant recipients to compare tacrolimus/sirolimus , tacrolimus/mycophenolate mofetil ( MMF ) , and cyclosporine/sirolimus . All patients received daclizumab induction and maintenance corticosteroids . Median follow-up was 8 yr post-transplant . Acute rejection ( AR ) occurred significantly less often among those treated with tacrolimus/MMF ( 12 % ) than among those treated with tacrolimus/sirolimus ( 30 % ) or cyclosporine/sirolimus ( 28 % ) . Mean estimated GFR was consistently higher in the tacrolimus/MMF arm , especially after controlling for donor age in a multivariable model during the first 36 mo ( P ≤ 0.008 ) . The rate of dying with a functioning graft was significantly higher among those treated with tacrolimus/sirolimus ( 26 % ) than among those treated with tacrolimus/MMF ( 12 % ) or cyclosporine/sirolimus ( 4 % ) . We did not observe significant differences in actuarial graft survival at 8 yr post-transplant between the groups . Patient noncompliance seemed responsible for 45 % ( 13/29 ) of observed graft failures , with 11 of these occurring after 36 mo . Significantly more viral infections , protocol violations , and need for antilipid therapy occurred among patients receiving sirolimus , but we did not observe differences between the groups with regard to infections requiring hospitalization or new-onset diabetes . Taken together , these results suggest that maintenance therapy with tacrolimus/MMF is more favorable than either tacrolimus/sirolimus or cyclosporine/sirolimus Morbidity and mortality due to cardiovascular disease are major problems after renal transplantation . The effects of three immunosuppressive protocol s on cardiovascular end points were investigated in a single-center , r and omized , parallel ( 1 - 1 - 1 ) group . Acute rejection was a secondary safety endpoint . Groups were as follows : group one , tacrolimus+sirolimus ; group two , tacrolimus+mycophenolate mofetil ( MMF ) ; group three , sirolimus+MMF+daclizumab . All groups received two days methylprednisolone only . The Ethical Committee dem and ed an interim analysis when 50 % of the patients were included . In this analysis , 54 patients with a median follow-up of 9.2 months were studied . The Kaplan-Meyer analysis showed a difference in rejection free survival between group one ( 82 % ) and group three ( 34 % , P=0.03 ) and between groups one and two ( tacrolimus-based , 76 % ) and group three ( calcineurin-free , 34 % , P=0.04 ) . Calcineurin-free immunosuppression with two days of steroids only showed an unacceptable high incidence of acute rejection and re-rejection , and the study had to be stopped BACKGROUND The novel agent sirolimus ( SRL ; Rapamune ; rapamycin ) inhibits the immune response by a mechanism distinct from those of calcineurin antagonists or antimetabolites . This r and omized , controlled , multicenter , single blind , phase II trial examined the combination of SRL , steroids , and full versus reduced doses of cyclosporine ( CsA ) for prophylaxis of acute renal allograft rejection . METHODS A total of 149 recipients of mismatched cadaveric- or living-donor primary renal allografts were r and omized into six groups . Three groups received placebo or 1 or 3 mg/m2/day SRL , as well as steroids and full-dose CsA ( S and immune ) . Three groups received steroids , reduced-dose CsA ( target trough level 50 % of full-dose range ) , and 1 , 3 , or 5 mg/m2/day SRL . RESULTS The incidence of biopsy-proven acute rejection episodes within the first 6 months after transplant was reduced from 32.0 % in the control group to 8.5 % in patients receiving SRL ( 1 or 3 mg/m2/day ) and full-dose S and immune CsA ( P=0.018 ) . Similar low rates of acute rejection episodes were observed among non-African-Americans , but not African-Americans , treated with SRL and reduced-dose S and immune CsA. Despite the augmented immunosuppression , 1-year patient and graft survival rates did not differ significantly across groups . Adverse effects attributable to CsA , including hypertension and new-onset diabetes mellitus , were not exacerbated by SRL . Except for an increased incidence of pneumonia among patients receiving full-dose CsA and 3 mg/m2/day SRL , the incidences of opportunistic infections were similar in all treatment groups . Although SRL produced more frequent , but reversible , hematological and lipid abnormalities , it had no apparent nephrotoxic effects to exacerbate CsA-induced renal dysfunction . CONCLUSIONS SRL in combination with CsA and steroids not only lowers the incidence of biopsy-proven acute renal allograft rejection episodes , but also may permit CsA sparing , at least among Caucasian patients , without an increased risk of rejection BACKGROUND Sirolimus ( rapamycin ) is a potent immunosuppressant with a mechanism of action different from cyclosporine ( CsA ) or tacrolimus . METHODS In 11 European centers , first cadaveric renal allograft recipients were r and omized to CsA ( n=42 ) or sirolimus ( n=41 ) . Dosing of these agents was concentration-controlled and open-labeled . All patients received corticosteroids and azathioprine . RESULTS At 12 months , graft survival ( 98 % sirolimus vs. 90 % CsA ) , patient survival ( 100 % vs. 98 % ) , and incidence of biopsy-confirmed acute rejection ( 41 % vs. 38 % ) were similar . Serum creatinine was lower with sirolimus , significantly ( P < or = 0.05 ) so at 3 and 4 months , and serum uric acid and magnesium were normal . Laboratory abnormalities reported significantly more often with sirolimus included hypertriglyceridemia ( 51 % vs. 12 % ) , hypercholesterolemia ( 44 % vs. 14 % ) , thrombocytopenia ( 37 % vs. 0 % ) , leukopenia ( 39 % vs. 14 % ) , and , of lesser importance , increased liver enzymes and hypokalemia . These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/ml . Occurrence of cytomegalovirus was comparable ( 14 % vs. 12 % ) ; incidences of herpes simplex ( 24 % vs. 10 % , P=0.08 ) and pneumonia ( 17 % vs. 2 % , P=0.03 ) were higher with sirolimus . No gingival hyperplasia was seen with sirolimus , tremor was rare , and hypertension was less frequent ( 17 % vs. 33 % ) . Two malignancies were observed with CsA and none with sirolimus . CONCLUSIONS Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection , and has a safety profile that differs from Background . Overexposure to cyclosporine is a risk factor for chronic allograft nephropathy ( CAN ) and dose reduction has been advocated . The purpose of this study was to determine the impact of adding the non-nephrotoxic immunosuppressant , rapamycin , after cyclosporine dose reduction in renal-allograft recipients with CAN . Methods . Thirty-one patients with biopsy-confirmed CAN were prospect ively r and omized to receive a 40 % cyclosporine dose reduction with ( rapamycin , n=16 ) or without ( control , n=15 ) the addition of rapamycin 2 mg/day . Renal function and side-effect parameters were assessed . Patients had renal allograft biopsies taken at recruitment and after 6 months . Glomeruli were isolated from these and underwent total mRNA extraction followed by RT-PCR-ELISA to assess transforming growth factor-&bgr;1 , collagen III , TIMP-1 , TIMP-2 , and matrix metalloproteinase-2 expression . Sample s were also stained with Sirius red and the percentage interstitial volume fraction quantified by computerized histomorphometric analysis . Data are presented as mean ( ±SD ) . Results . Patient characteristics and cyclosporine trough levels after dose reduction ( rapamycin 68 [ ±21 ] vs. control 56 [ ±19 ] ng/mL , P = NS ) were similar in both groups . Rapamycin patients had a significant fall in Cr-51 radioisotope glomerular filtration rate ( 31.6 [ ±8.9 ] to 27.3 [ ±8.6 ] mL/min , P < 0.01 ) that was not significant in controls ( 29.5 [ ±10.4 ] to 27.0 [ ±8.0 ] mL/min , P = NS ) . Transforming growth factor-&bgr;1 expression fell over time in control but remained constant in rapamycin patients . Conversely collagen III expression increased over the 6-month follow-up in rapamycin patients but not in controls . Both had comparable increases in TIMP-1 and matrix metalloproteinase-2 but only rapamycin patients developed a significant increase in TIMP-2 . Sirius red-stained interstitial volume fraction fell over the study in controls ( 15.3–11.2 % , P = 0.06 ) but not in rapamycin patients ( 16.2–16.3 % , P = NS ) . Conclusion . Rapamycin ( 2 mg/day ) did not improve functional , molecular , or histological outcome in patients with CAN after cyclosporine dose reduction . Further studies involving larger numbers of patients are necessary to confirm these findings INTRODUCTION A previous trial in renal transplantation comparing sirolimus ( rapamycin ) to cyclosporine ( CsA ) in a triple-drug therapy regimen with azathioprine and corticosteroids found that the incidence of acute rejection was similar ( approximately 40 % ) with a trend for better renal function with sirolimus . METHODS In 14 European centers , first cadaveric renal allograft recipients were r and omized to receive sirolimus ( n = 40 ) or CsA ( n = 38 ) in an open-label design . All patients received corticosteroids and mycophenolate mofetil 2 g/day . Sirolimus and CsA were concentration controlled ; trough levels of mycophenolic acid and prednisolone were also measured . RESULTS At 12 months , graft survival ( 92.5 % sirolimus vs. 89.5 % CsA ) , patient survival ( 97.5 % sirolimus vs. 94.7 % CsA ) , and the incidence of biopsy-proven acute rejection ( 27.5 % sirolimus vs. 18.4 % CsA ) were not statistically different . The use of antibodies to treat suspected rejection episodes was also similar ( 7.5 % sirolimus vs. 5.3 % CsA ) . More sirolimus patients received bolus steroid therapy ( 20 vs. 11 , P = 0.068 ) . From month 2 onward , the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients . The adverse events reported more frequently with sirolimus were thrombocytopenia ( 45 % vs. 8 % ) and diarrhea ( 38 % vs. 11 % ) . In the CsA group , increased creatinine ( 18 % vs. 39 % ) , hyperuricemia ( 3 % vs. 18 % ) , cytomegalovirus infection ( 5 % vs. 21 % ) , and tremor ( 5 % vs. 21 % ) were observed significantly more often . DISCUSSION Patient and graft survival and the incidence of biopsy-proven acute rejection at 12 months were comparable between sirolimus and CsA , whereas safety profiles were different . These data suggest that sirolimus may be used as primary therapy for the prevention of acute rejection Background . De novo sirolimus in calcineurin inhibitor-free regimens , although potentially useful to improve early renal function , are complicated by various drug-related side effects . Methods . We report a prospect i ve open-label , multicenter , r and omized trial to evaluate early conversion from a CsA-based to a sirolimus (SRL)-based regimen 10 to 24 days after renal transplantation . Of the 196 patients , 141 patients with a low-to-moderate immunological risk were eligible to be converted to SRL or to continue CsA. All patients received antithymocyte globulin-F single-bolus induction , mycophenolate mofetil , and steroids . Results . The primary endpoint , renal function determined by S-creatinine and estimated glomerular filtration rate calculated by Nankivell formula at 12 months was significantly better in the SRL group ( 1.51±0.59 vs. 1.87±0.98 mg/dL or 64.5±25.2 vs. 53.4±18.0 mL/min/1.73 m2 ) . Patient survival , graft survival , and incidence of biopsy-proven acute rejection after conversion were not statistically different . Drug discontinuations were significantly higher in the SRL group ( 36.2 % vs. 19.7 % ) . Significantly , more patients in the SRL group reported acne , aphtous , and temporary hyperlipidemia , whereas cytomegalovirus viremia was significantly decreased ( 7.3 % vs. 28.2 % ) . Conclusions . Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function . The identification of appropriate c and i date s and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts , which currently limit the broad applicability of this protocol Renal transplant recipients ( RTR ) have a 50–200‐fold higher risk for nonmelanoma‐skin cancer ( NMSC ) causing high rates of morbidity and sometimes mortality . Cohort‐ studies gave evidence that a sirolimus‐based immunosuppression may inhibit skin tumor growth . This single‐center , prospect i ve , assessor‐blinded , r and omized trial investigated if switching to sirolimus treatment inhibits the progression of premalignancies and moreover how many new NMSC occur compared to continuation of the original immunosuppressive therapy . Forty‐four RTR ( mean age 59.9 years , mean duration of immunosuppression 229.5 months ) with skin lesions were r and omized to sirolimus or continuation of their original immunosuppression . Blinded dermatological assessment at month 6 and 12 by the same dermatologist evaluated the clinical change compared to baseline . Biopsy was performed in suspected malignancy . Already the 6‐month‐ assessment showed significant superiority of sirolimus‐therapy : a stop of progression , even regression of preexisting premalignancies ( p < 0.0005 ) . This effect was increased at month 12 ( p < 0.0001 ) . Nine patients developed histologically confirmed NMSC : one in the sirolimus group , eight in the control group , p = 0.0176 . Sirolimus‐based immunosuppression in RTR , even when established many years after transplantation , can delay the development of premalignancies , induce regression of preexisting lesions and decelerate the incidence of new NMSC It is not known how different steroid‐free immunosuppressive combinations affect renal graft survival and long‐term kidney transplant function . Here we sought to compare the impact on graft survival and long‐term graft function of two tacrolimus (Tac)‐based , prednisone‐free maintenance immunosuppressive protocol s : Tac/Mycophenolate Mofetil ( MMF ) vs. Tac/Sirolimus ( SRL ) . Renal transplant patients given induction therapy with IL2‐RA and methylprednisolone on days 0 , 1 and 2 post‐transplant were prospect ively r and omized to two maintenance immunosuppressive regimens with Tac/MMF ( n = 45 ) or Tac/SRL ( n = 37 ) . During the 3‐year follow‐up the following data were collected : patient survival , renal allograft survival , incidence of acute rejection and glomerular filtration rate ( GFR ) at different time‐points post‐transplant . Cumulative graft survival was significantly different in the two groups : one kidney loss in the Tac/MMF vs. six kidney losses in the Tac/SRL ( log‐rank test p = 0.04 ) . GFR at different time‐points post‐transplant was consistently and statistically better in the Tac/MMF than in the Tac/SRL group . The slope of GFR decline per month was flatter in the Tac/MMF than in the Tac/SRL group . This study showed that renal graft survival and graft function were significantly lower in the combination of Tac/SRL than Tac/MMF Chronic allograft nephropathy ( CAN ) represents the main cause of renal allograft loss after 1 yr of transplantation . Calcineurin inhibitor ( CNI ) use is associated with increased graft expression of profibrotic cytokines , whereas rapamycin inhibits fibroblast proliferation . The aim of this r and omized , prospect i ve , open-label , single-center study was to evaluate the histologic and clinical effect of rapamycin on biopsy-proven CAN . Eighty-four consecutive patients who had biopsy-proven CAN and received a transplant were r and omized to receive either a 40 % CNI reduction plus mycophenolate mofetil ( group 1 ; 50 patients ) or immediate CNI withdrawal and rapamycin introduction with a loading dose of 0.1 mg/kg per d and a maintaining dose aim ing at through levels of 6 to 10 ng/ml ( group 2 ; 34 patients ) . The follow-up period was 24 mo . At the end of follow-up , 25 patients ( group 1 , 10 patients ; group 2 , 15 patients ) underwent a second biopsy . CAN lesions were grade d according to Banff criteria . alpha-Smooth muscle actin ( alpha-SMA ) protein expression was evaluated in all biopsies as a marker of fibroblast activation . Graft function and Banff grading were superimposable at r and omization . Graft survival was significantly better in group 2 ( P = 0.0376 , chi2 = 4.323 ) . CAN grading worsened significantly in group 1 , whereas it remained stable in group 2 . After 24 mo , all group 1 biopsies showed an increase of alpha-SMA expression at the interstitial and vascular levels ( P < 0.001 ) ; on the contrary , alpha-SMA expression was dramatically reduced in group 2 biopsies ( P = 0.005 ) . This study demonstrates that rapamycin introduction /CNI withdrawal improves graft survival and reduces interstitial and vascular alpha-SMA expression , slowing down the progression of allograft injury in patients with CAN Background . The efficacy and safety of converting maintenance renal transplant recipients from calcineurin inhibitors ( CNIs ) to sirolimus ( SRL ) was evaluated . Methods . Eight hundred thirty renal allograft recipients , 6 to 120 months posttransplant and receiving cyclosporine or tacrolimus , were r and omly assigned to continue CNI ( n=275 ) or convert from CNI to SRL ( n=555 ) . Primary endpoints were calculated Nankivell glomerular filtration rate ( GFR ; stratified at baseline : 20–40 vs. > 40 mL/min ) and the cumulative rates of biopsy-confirmed acute rejection ( BCAR ) , graft loss , or death at 12 months . Enrollment in the 20 to 40 mL/min stratum was halted prematurely because of a higher incidence of safety endpoints in the SRL conversion arm . Results . Intent-to-treat analyses at 12 and 24 months showed no significant treatment difference in GFR in the baseline GFR more than 40 mL/min stratum . On-therapy analysis of this cohort showed significantly higher GFR at 12 and 24 months after SRL conversion . Rates of BCAR , graft survival , and patient survival were similar between groups . Median urinary protein-to-creatinine ratios ( UPr/Cr ) were similar at baseline but increased significantly after SRL conversion . Malignancy rates were significantly lower at 12 and 24 months after SRL conversion . Post hoc analyses identified a subgroup with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11 , whose risk-benefit profile was more favorable after conversion than that for the overall SRL conversion cohort . Conclusions . At 2 years , SRL conversion among patients with baseline GFR more than 40 mL/min was associated with excellent patient and graft survival , no difference in BCAR , increased urinary protein excretion , and a lower incidence of malignancy compared with CNI continuation . Superior renal function was observed among patients who remained on SRL through 12 to 24 months , particularly in the subgroup of patients with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11 Background . In kidney transplant recipients with alemtuzumab induction maintained on mycophenolate mofetil ( MMF ) immunosuppression , sirolimus ( SRL ) promotes significant expansion of circulating CD4+CD25high regulatory T cells ( Treg ) . This might translate into more effective protection against chronic graft injury compared to cyclosporin A ( CsA ) , which , in the same clinical setting , does not affect Treg . Methods . To assess this hypothesis , in the extension of a single-center , prospect i ve , r and omized , open , blind endpoint study aim ed to assess the effect of low-dose SRL or CsA on circulating Treg , we compared the outcomes of renal transplant recipients on SRL ( n=11 ) or CsA ( n=10 ) by per- protocol biopsies and serial measurements of glomerular filtration rate ( GFR ) , renal plasma flow ( RPF ) , and 24-hour proteinuria over 30 months posttransplant . Results . Despite 4-fold higher CD4+CD25high Treg counts ( 22.1±12.2 % vs. 5.7±4.2 % of CD3+CD4 + T cells ) , SRL-treated patients , compared to CsA-treated patients , had a significantly higher tubular C4d staining score ( 1.1±0.6 vs. 0.2±0.3 , P<0.01 ) , with nonsignificant trends to higher chronic allograft damage index score ( 5.6±2.4 vs. 3.7±3.3 ) , faster GFR ( −2.92±0.33 vs. −0.28±0.44 ml/min/1.73m2 per year ) , and RPF ( −10.80±5.45 vs. −1.86±3.09 ml/min/1.73 m2 per year ) decline , and more clinical proteinuria ( n=6 vs. 4 ) . There was no significant correlation between Treg counts and any considered outcome variable in the study group as a whole and within each cohort . Conclusions . These data suggest that , despite enhanced Treg expression , low-dose SRL combined to alemtuzumab induction and MMF-based steroid-free maintenance therapy , does not appreciably protect renal transplant recipients from chronic allograft injury and dysfunction Background . Chronic allograft nephropathy ( CAN ) represents the most common cause of late graft loss . Nephrotoxicity from chronic use of calcineurin inhibitors ( CNI ) has the potential to contribute to CAN . The present investigation aim ed to evaluate the impact of early CNI withdrawal on kidney graft function and structure at 1 year in sirolimus (SRL)-treated patients . Methods . Forty consecutive kidney transplant recipients were initially treated with corticosteroids , cyclosporine A ( CsA ) , and SRL ( 2 mg/day ) . After 3 months , patients were r and omly assigned to either continue the same treatment ( group I ) or to withdraw CsA and continue SRL ( group II ) . All patients underwent kidney graft biopsy immediately after graft reperfusion ( 0-hr biopsy ) and 12 months after engraftment . Results . Baseline graft biopsy showed a higher degree of renal damage in group II patients ( total score , 4±1.6 vs. 2±0.9;P < 0.05 ) . Twelve months after engraftment , CAN was diagnosed in 55 % of all patients , of whom 64 % were in group I and 36 % in group II . CAN lesions were scored as moderate to severe in 90 % of group I patients but only 32 % of group II patients ( P < 0.05 ) . A vascular score greater than or equal to 2 occurred in 90 % of group I patients and in 38 % of group II patients ( P < 0.05 ) . At 1 year , group I patients showed a significantly worse kidney graft function ( serum creatinine , 2.0±0.3 vs. 1.3±0.3 mg/dL ; creatinine clearance , 54±14 vs. 66±17 mL/min ; both P < 0.002 ) . Conclusions . These results suggest that early withdrawal of CsA is a safe option , which allows a significant reduction of chronic histologic damage , particularly vascular injury , of cadaveric kidney allografts Induction and maintenance immunosuppression protocol s with or without long-term steroid therapy in kidney transplant recipients are variable and are transplant center-specific . The aim of this prospect i ve r and omized pilot study was to compare 5-year outcomes in kidney recipients maintained on 4 different calcineurin inhibitor (CNI)-based immunosuppression protocol s without long-term steroid therapy . Two hundred consenting patients who received kidney transplants between June 2000 and October 2004 were enrolled in 4 immunosuppression protocol groups , with 50 patients in each group : cyclosporine (CSA)/mycophenolate mofetil ( MMF ) , CSA/sirolimus ( SRL ) , tacrolimus (TAC)/MMF , and TAC/SRL . Induction therapy was done with basiliximab and methylprednisolone . Steroids were withdrawn on post-transplant day 2 , and long-term steroid therapy was not used . Demographic characteristics among the four groups were comparable ; approximately 50 % of the recipients were African American and > or = 80 % of the kidneys transplanted were from deceased donors . Clinical acute rejection ( CAR ) was confirmed by biopsy and treated with intravenous pulse steroid therapy . Steroid-unresponsive CAR was treated with Thymoglobulin . Surveillance biopsies were performed at 1 , 6 , 12 , 24 , 36 , 48 , and 60 months to evaluate sub clinical acute rejection ( SCAR ) , chronic allograft injury ( CAI ) , and other pathological changes per the Banff 2005 schema . The primary end point was CAR , and secondary end points were 5-year patient and graft survival rates , renal function , SCAR , CAI , and adverse events . In the first year post-transplant , the incidence of CAR was 18 % in the CSA/MMF group , 8 % in the CSA/SRL group , 14 % in the TAC/MMF group , and 4 % in the TAC/SRL group ( CSA/MMF vs. TAC/SRL ; p=0.05 ) . The incidence of SCAR was 22 % in the CSA/MMF group , 8 % in the CSA/SRL group , 16 % in the TAC/MMF group , and 6 % in the TAC/SRL group ( CSA/MMF vs. CSA/SRL and TAC/SRL ; p=0.05 ) . After the first year , the incidences of CAR and SCAR decreased and were comparable in all 4 groups . At 5 years post-transplant , cumulative CAI due to interstitial fibrosis/tubular atrophy ( IF/TA ) , hypertension ( HTN ) , and chronic calcineurin inhibitor ( CNI ) toxicity was observed in 54 % , 48 % , and 8 % of the CSA/MMF group vs. 16 % , 36 % , and 12 % of the CSA/SRL group vs. 38 % , 24 % and 6 % of the TAC/MMF group vs. 14 % , 25 % and 12 % of the TAC/SLR group ( IF/TA : CSA/MMF vs. CSA/SRL and TAC/SRL ; p=0.04 , HTN : CSA/MMF vs. TAC/MMF and TAC/SRL ; p=0.05 , CNI toxicity : TAC/SRL and CSA/SRL vs. TAC/MMF ; p=0.05 ) . Five-year patient and graft survival rates were 82 % and 60 % in the CSA/MMF group , 82 % and 60 % in the CSA/SRL group , 84 % and 62 % in the TAC/MMF group , and 82 % and 64 % in the TAC/SRL group ( p=0.9 ) . Serum creatinine levels and creatinine clearances at 5 years were comparable among the groups . Our data show that the rates of CAR and SCAR in the first year post-transplant were significantly lower in the CSA/SRL and TAC/SRL groups and that cumulative CAI rates due to IF/TA and HTN at 5 years were significantly lower in the TAC/MMF , TAC/SRL , and CSA/SRL groups than in the CSA/MMF group . Despite significant differences in the incidences of CAR and SCAR and prevalence of different types of CAI at 5 years , renal function and patient and graft survival rates at 5 years were comparable among kidney recipients maintained on 4 different immunosuppression protocol s without long-term steroid therapy Background . Despite the various immunosuppressive regimens presently in use , acute rejection in the early postoperative period continues to occur in 20 to 40 % of renal transplant patients . In a double-blind , multicentred study , we investigated the ability of two different doses of sirolimus ( rapamycin , RAPAMUNE ) , a new class of immunosuppressant that blocks cell cycle progression , to prevent acute rejection in recipients of primary mismatched renal allografts when added to a regimen of cyclosporine ( cyclosporin A , CsA ) and corticosteroids . Methods . Between October 1996 and September 1997 , 576 recipients of primary mismatched cadaveric or living donor renal allografts were r and omly assigned in a 2:2:1 ratio ( before the transplant operation ) to receive an initial loading dose of either 6 or 15 mg of orally administered sirolimus , followed by a daily dose of either 2 or 5 mg/day , or to receive a matched placebo . All groups received cyclosporine ( microemulsion formula , CsA ) and corticosteroids . The primary endpoint was a composite of first occurrence of biopsy-confirmed acute rejection , graft loss , or death during the first 6 months after transplantation . Safety data were monitored by an independent drug safety monitoring board . Results . Based on an intention-to-treat analysis of 576 patients , there were no significant differences in patient demographic or baseline characteristics among treatment groups . The overall rate of the primary composite endpoint for the 6-month period after transplantation was 30.0 % ( 68/227 ) in the 2 mg/day sirolimus group and 25.6 % ( 56/219 ) in the 5 mg/day sirolimus group , significantly lower than the 47.7 % ( 62/130 ) in the placebo group ( P = 0.002 , P < 0.001 , respectively ) . During this period , the incidence of biopsy-confirmed acute rejection was 24.7 % ( 56/227 ) in the 2 mg/day sirolimus group and 19.2 % ( 42/219 ) in the 5 mg/day sirolimus group , compared with 41.5 % ( 54/130 ) in the placebo group ( P = 0.003 , P < 0.001 , respectively ) , representing a significant reduction in acute rejection of 40.5 and 53.7 % , respectively . The need for antibody therapy to treat the first episode of biopsy-confirmed acute rejection was significantly reduced in the 5 mg/day sirolimus group ( 3.2 % ) compared to the placebo group ( 8.5%;P = 0.044 ) . The results 1 year after transplantation were similar for the efficacy parameters studied . Adverse events and infections occurred in all groups . Conclusions . The addition of either 2 mg/day sirolimus or 5 mg/day sirolimus to CsA/corticosteroid therapy significantly reduces the incidence of acute rejection episodes in primary mismatched renal allograft recipients , without an increase in immunosuppressant-related side effects , including infections and malignancy , at 6 months and at 1 year after transplantation As part of the Spare-the-Nephron trial , we evaluated the combination mycophenolate mofetil ( MMF ) and sirolimus ( SRL ) as a calcineurin inhibitor (CNI)-free regimen for the preservation of renal function in renal allograft recipients . This 2-year , open-label , multicenter trial r and omized 299 patients of which 151 were maintained on MMF and a CNI , 148 on MMF plus SRL ( n=120 , tacrolimus ; n=31 , cyclosporine ) . Baseline characteristics including measured ( iothalamate ) glomerular filtration rate ( GFR ) were similar between groups . After 1 year , the mean percentage change from baseline in the primary end point of measured GFR was significantly higher in the MMF/SRL group compared with the MMF/CNI group . After 2 years , the change was indistinguishable . Calculated creatinine clearance and GFR were significantly greater with MMF/SRL at 2 years within which biopsy-proven acute rejection ( BPAR ) occurred in 14 MMF/SRL-treated patients ( 3 graft losses ) and in 17 receiving the MMF/CNI ( 6 graft losses ) . Significantly , no patients receiving MMF/SRL but five treated with MMF/CNI died . Thus , compared with MMF/CNI treatment , a 2-year regimen of MMF/SRL result ed in similar measures of renal function but with fewer deaths and a trend to less BPAR and graft loss We compared three maintenance immunosuppressive regimens in a rapid discontinuation of prednisone protocol . From March 1 , 2001 , through December 31 , 2003 , 239 first and second kidney transplant recipients ( 166 LD ; 73 DD ) were r and omized . All recipients were treated with Thymoglobulin ; all received steroids intraoperatively and for 5 days postoperatively . R and omization was to cyclosporine – mycophenolate mofetil ( n = 85 ) ; high‐level tacrolimus ( TAC ) ( 8–12 ng/mL)–low‐level sirolimus ( SRL ) ( 3–7 ng/mL ) ( n = 72 ) ; or low‐level TAC ( 3–7 ng/mL)–high‐level SRL ( 8–12 ng/mL ) ( n = 82 ) . We found no difference at 24 months between groups in patient , graft , death‐censored graft , or acute rejection‐free graft survival , or in kidney function Vascular disease and chronic allograft nephropathy have prompted re-evaluation of steroids and calcineurin inhibitors ( CNIs ) in renal transplantation . Sirolimus ( SRL ) can facilitate early CNI withdrawal . We report on the Early CNI and Steroid Elimination in Leeds ( ECSEL ) study , which was terminated early due to poor tolerability of SRL . Basiliximab/methylprednisolone induction was used , then 2 months of tacrolimus ( TAC ) and mycophenolate mofetil ( MMF ) treatment . A total of 51 patients were r and omized to continue TAC/MMF or switch to SRL/MMF . In ECSEL1 , patients were switched at 2 months ( n=10 ) . In ECSEL2 , SRL was introduced at months 4–6 and TAC was tapered ( n=13 ) . Median overall follow up was 701 days . All 10 ECSEL1 and 10 of 13 ( 77 % ) ECSEL2 patients discontinued SRL due to adverse events , including leucopenia , rash , mucosal ulceration , arthralgia , and possible pneumonitis . Mean end-of- study creatinine was comparable in all groups . Sirolimus should be used with caution in complete CNI and steroid withdrawal , due to the result ant intolerable adverse event profile Background . We report the 5-year outcomes from a r and omized prospect i ve trial in primary adult renal allograft recipients , design ed to evaluate calcineurin inhibitor (CNI)-free immunosuppression on kidney transplant function . Methods . Sixty-one patients were r and omized to either sirolimus ( n=31 ) or cyclosporine ( n=30 ) after basiliximab induction and mycophenolate mofetil ( MMF ) with steroids . Sirolimus was concentration controlled at 10–12 ng/mL for at least 6 months . Results . After 5 years , sirolimus-MMF-steroids compared to cyclosporine-MMF-steroids provides similar patient survival ( 87.1 vs. 90 % , P=0.681 ) , acute rejection rates ( 12.9 vs. 23.3 % , P=0.22 ) , total cholesterol ( 209.1 vs. 204.3 mg/dL , P=0.973 ) , urine protein/creatinine ratios ( 0.398 vs. 0.478 mg/dL , P=0.72 ) , and overall medical and surgical morbidity ( P = NS ) . Although unadjusted patient survival was similar , sirolimus based CNI-free patients had longer death censored graft survival ( 96.4 vs. 76.7 % , P=0.0265 ) , higher glomerular filtration rate ( GFR ) by the abbreviated Modified Diet in Renal Disease ( 66.7 vs. 50.7 cc/min , P=0.0075 ) , and fewer graft losses from chronic allograft nephropathy . The Banff chronic scores at two years were strong predictors of 5-year GFR . At 5 years , there were six de novo ( three solid organ , three skin ) cancers in the CNI group and only two de novo ( one skin , one leukemia , no solid organ ) cancers in the sirolimus group ( P = NS ) . Conclusions . This study of low to moderate risk patients demonstrates that excellent 5-year kidney transplant outcomes can be achieved without CNI drugs , when therapeutic drug monitoring of sirolimus is employed . The application of CNI drug avoidance protocol s to high-risk recipients ( retransplants , highly sensitized , etc . ) , extrarenal allograft recipients , or alternative drug regimens such as steroid or MMF elimination should be subjected to controlled trials Background . Recently , sirolimus ( SRL ) was introduced as an immunosuppressant in solid-organ transplantation . This study evaluated combinations of SRL and tacrolimus ( Tac ) . Methods . This 6-month study investigated the safety and efficacy of Tac and steroids in combination with three different doses of SRL in renal-transplant recipients . A total of 104 patients were r and omized in four groups : one group received Tac and steroids ( control n=28 ) , and three groups also received the following daily SRL doses : 0.5 mg ( TacSRL0.5 , n=25 ) , 1 mg ( TacSRL1 , n=25 ) , or 2 mg ( TacSRL2 , n=26 ) . Tac doses were adjusted to whole-blood trough levels . Steroids were tapered from 20 mg per day to 5 mg per day . The SRL groups underwent a second r and omization to discontinue SRL at either month 3 or 5 . Results . At month 6 , patient survival rates were 100 % , 100 % , 96.0 % , and 100 % , and graft survival rates were 96.4 % , 84.0 % , 88.0 % , and 84.6 % , respectively . The overall safety profile was similar in all groups . The incidences of infections during months 1 to 3 were similar in all groups ( control 46.4 % , TacSRL0.5 32.0 % , TacSRL1 56.0 % , TacSRL2 46.2 % ) . The 3-month incidences of hypercholesteremia ( cholesterol > 240 mg/dL or low-density lipoprotein cholesterol > 160 mg/dL ) were 21.4 % , 36.0 % , 48.0 % , and 50.0 % ( P = 0.019 ) . Lipid levels improved after withdrawal of SRL . The 3-month incidences of biopsy-proven acute rejection were 28.6 % ( control ) , 8.0 % ( TacSRL0.5 ) , 8.0 % ( TacSRL1 ) , and 3.8 % ( TacSRL2 ) ( P = 0.014 ) . Conclusion . Tac in combination with low doses of SRL provides a very effective and safe regimen Background Despite a decreased incidence of acute rejection and early renal allograft loss due to calcineurin inhibitors ( CNIs ) in transplant recipients , nephrotoxicity associated with long-term CNI use remains an important issue . This study evaluated whether a CNI-free regimen , including sirolimus , mycophenolate mofetil , corticosteroids , and anti – interleukin-2 receptor antibody induction , results in improved long-term renal function . Methods This open-label , r and omized , parallel group , comparative study in primary de novo renal transplant recipients was planned for 48 months but terminated early because of high acute rejection rates in the sirolimus arm . Results Enrollment was stopped after ≈12 months , with 475 transplanted patients r and omized ( 2:1 ) to sirolimus ( n=314 ) or cyclosporine A ( CsA ) treatment ( n=161 ) . Mean length of follow-up after transplantation was 190 days ; this article focuses on available data through 6 months . Mean±SD on-therapy Nankivell-calculated glomerular filtration rate was not significantly different between the sirolimus ( 69.1±18.7 mL/min ) and CsA ( 66.0±15.2 mL/min ) treatment groups . Occurrence and length of delayed graft function was not significantly different between groups . Patients in the sirolimus group experienced numerically lower survival rates ( 96.9 % vs. 99.4 % ; P=0.14 ) , with nine deaths reported with sirolimus and one with CsA ; higher rates of biopsy-confirmed acute rejection ( 21.4 % vs. 6.1 % ; P<0.001 ) ; and higher rates of discontinuations due to adverse events ( 17.4 % vs. 6.8 % ; P=0.001 ) . Conclusion A sirolimus-based , CNI-free immunosuppressive regimen , when used with mycophenolate mofetil , corticosteroids , and anti – interleukin-2 receptor antibody induction , was associated with high rates of biopsy-confirmed acute rejection compared with CsA-based immunosuppression and is not recommended Background . Calcineurin-inhibitor therapy is a contributing factor to the origin of interstitial fibrosis and tubular atrophy ( IFTA ) . Methods . We conducted a prospect i ve r and omized trial of conversion of tacrolimus to sirolimus at 1-month posttransplant in kidney transplant recipients on rapid steroid withdrawal . We compared the chronic changes ( IFTA and sum of Banff chronic scores — Total Score ) on protocol biopsies at 1 month , 1 year , and 2 years in all r and omized patients . We compared the outcomes between treatment groups and analyzed the impact of previous rejection on the chronic changes . Results . We r and omized 122 patients , 62 to sirolimus and 60 to tacrolimus . The 1-year biopsy was performed in 54 patients ( 90 % ) of the tacrolimus group and 56 patients ( 90 % ) of the sirolimus group . The proportion of biopsies with IFTA more than or equal to 2 and the Total Score more than 2 increased over the 2 years but were not different between the study groups at any time point . On the 1-year biopsy , there was more IFTA , and the fraction with Total Score more than 2 was higher in the tacrolimus group with previous rejection . In the cohort without rejection , there was a significant progression of the IFTA and Total Score between 1 and 2 years in both the sirolimus and tacrolimus groups . Conclusion . Conversion from tacrolimus to sirolimus at 1-month posttransplant in kidney transplant recipients on rapid steroid withdrawal does not decrease the progression of chronic changes on protocol biopsies during the first 2 years even in those patients without previous acute rejection INTRODUCTION With the introduction of new immunosuppressive medicines , it has become possible to determine the extent to which nephrotoxic medicines contribute to CAN . The aim of this study is to compare the safety and efficacy of calcineurin inhibitor ( CI ) free immunosuppression in a prospect i ve , r and omized trial comparing sirolimus-mycophenolate mofetil (MMF)-prednisone to tacrolimus- MMF-prednisone . METHODS Patients are r and omized at the time of transplant to receive either tacrolimus ( target level 12 to 15 ng/mL in the first month ) or sirolimus ( target level 12 to 18 ng/mL in the first month ) . All patients also receive MMF ( 750 mg bid ) and prednisone tapered to 10 mg/d by 3 months and thymoglobulin induction ( 1.5 mg/kg/d on days 0 , 1 , 2 , 4 and 6 ) . RESULTS At this point we have 4-month follow-up in 85 patients . The acute rejection rate is 7.5 % ( 3/40 ) in the tacrolimus group and 6.7 % ( 3/45 ) in the sirolimus group . We have discontinued sirolimus in eight patients so far , with wound complications being the most common indication . Renal function appears to be better in the sirolimus group at 1 month after transplantation , but the difference is not statistically significant . CONCLUSIONS While longer follow-up is needed , these results demonstrate that total avoidance of CI can be achieved with extremely low acute cellular rejection rates using sirolimus-based immunosuppression in combination with thymoglobulin , MMF , and prednisone Safety and efficacy of two sirolimus (SRL)‐based regimens were compared with tacrolimus ( TAC ) and mycophenolate mofetil ( MMF ) . Renal transplantation recipients were r and omized to Group 1 ( SRL+TAC ; week 13 TAC elimination [ n = 152 ] ) , Group 2 ( SRL + MMF [ n = 152 ] ) or Group 3 ( TAC + MMF [ n = 139 ] ) . Group 2 , with higher‐than‐expected biopsy‐confirmed acute rejections ( BCARs ) , was sponsor‐terminated ; therefore , Group 2 two‐year data were limited . At 1 and 2 years , respectively , graft ( Group 1 : 92.8 % , 88.5 % ; Group 2 : 90.6 % , 89.9 % ; Group 3 : 96.2 % , 95.4 % ) and patient ( Group 1 : 97.3 % , 94.4 % ; Group 2 : 95.2 % , 94.5 % ; Group 3 : 97.0 % , 97.0 % ) survival rates were similar . One‐ and 2‐year BCAR incidence was : Group 1 , 15.2 % , 17.4 % ; Group 2 , 31.3 % , 32.8 % ; Group 3 , 8.2 % , 12.3 % ( Group 2 vs. 3 , p < 0.001 ) . Mean 1‐ and 2‐year modified intent‐to‐treat glomerular filtration rates ( mL/min ) were similar . Primary reason for discontinuation was adverse events ( Group 1 , 34.2 % ; Group 2 , 33.6 % ; Group 3 , 22.3 % ; p < 0.05 ) . In Groups 1 and 2 , delayed wound healing and hyperlipidemia were more frequent . One‐year post hoc analysis of new‐onset diabetes posttransplantation was greater in TAC recipients ( Groups 1 and 3 vs. 2 , 17 % vs. 6 % ; p = 0.004 ) . Between‐group malignancy rates were similar . The SRL‐based regimens were not associated with improved outcomes for kidney transplantation patients Sirolimus ( SRL ) allows to minimize the use of cyclosporine ( CsA ) , but de novo administration after transplantation is associated with various complications . We report a prospect i ve , open‐label , multicenter r and omized study to evaluate conversion from a CsA‐based regimen to a SRL‐based regimen 3 months after transplantation . One hundred ninety‐two of a total of 237 patients were eligible at 3 months to be converted to SRL ( n = 95 ) or to continue CsA ( n = 97 ) . All patients were also given mycophenolate mofetil ( MMF ) and oral steroids , planned to be discontinued at month 8 . The primary endpoint , the clearance estimated according to Cockcroft and Gault at week 52 , was significantly better in the SRL group ( 68.9 vs. 64.4 mL/min , p = 0.017 ) . Patient and graft survival were not statistically different . The incidence of acute rejection episodes , mainly occurring after withdrawal of steroids , was numerically but not statistically higher in the SRL group ( 17 % vs. 8 % , p = 0.071 ) . Sixteen patients discontinued SRL , mainly for adverse events ( n = 11 ) , and seven patients discontinued CsA for renal failure or acute rejection . Significantly , more patients in the SRL group reported aphthous , diarrhea , acne and high triglyceride levels . Conversion CsA to SRL 3 months after transplantation combined with MMF is associated with improvement in renal function Sirolimus has antineoplastic effects and may reduce skin cancer rates in kidney transplant patients . This prospect i ve , multicenter , r and omized , open‐label , controlled trial r and omized 86 kidney transplant recipients ( ≥1 year posttransplant ) with history of nonmelanoma skin cancer ( NMSC ) to continue calcineurin inhibitor ( CNI ) or convert to sirolimus . Patients were stratified by number of NMSC lesions ( 0–5 , 6–20 ) in previous year . Primary end point was number of biopsy‐confirmed new NMSC lesions per patient‐year . Yearly NMSC rate was significantly lower with sirolimus ( 1.31 vs. 2.48 lesions/patient‐year ; p = 0.022 ) . Squamous cell carcinoma occurred at a lower rate in the sirolimus versus CNI group ( p = 0.038 ) ; basal cell carcinoma rate was similar in both . A lower proportion of patients receiving sirolimus developed new or recurrent NMSC ( 56.4 % vs. 80.9 % ; p = 0.015 ) or new squamous cell carcinoma ( 41.0 % vs. 70.2 % ; p = 0.006 ) . No sirolimus patients and one CNI continuation patient experienced acute rejection . Incidence of treatment‐emergent adverse events was similar between groups ; however , discontinuation rates related to adverse events were significantly higher with sirolimus ( 46.2 % vs. 0 % ; p < 0.001 ) . In kidney transplant recipients with history of NMSC , conversion from CNI to sirolimus reduced rates of NMSC , without increasing acute rejection risk |
10,515 | 28,544,303 | The authors suggest eleven findings from research areas of emotion recognition , cognitive mediation , discriminating between thoughts , feelings and behaviours , linking events and emotions that have implication s for the design of CBT programmes and future research for this population | BACKGROUND Cognitive behavioural therapy ( CBT ) is being increasingly adapted for use with people who have an intellectual disability .
However , it remains unclear whether inherent cognitive deficits that are present in adults who have an intellectual disability preclude the use of cognitive-based therapies .
This review aims to systematic ally examine " cognitive therapy skills " in adults who have an intellectual disability that assist engagement in CBT . | BACKGROUND Evaluation of complex interventions , including st and ardisation of the intervention , types of outcomes selected and measures of change , is a fairly novel concept in the field of intellectual disabilities . Our aim was to explore these issues in a feasibility study of Manualised Individual Cognitive Behaviour Treatment ( M-iCBT ) compared to the treatment as usual alone ( TAU ) . METHODS Service users with mild to moderate intellectual disability experiencing a mood disorder or symptoms of depression and /or anxiety ( mini PAS-ADD total score > 10 or 7 respectively ) were r and omly assigned to either . RESULTS In total , 32 participants were r and omly assigned to 16 sessions of M-iCBT ( n=16 ) in addition to TAU or TAU alone ( n=16 ) . We explored recruitment and accrual rates , willingness to participate , acceptability of the intervention and suitability of assessment tools . Mean change ( 95 % CI ) in the Beck Depression Inventory-Youth ( BDI-Y ) score from baseline to the 16 week endpoint ( primary variable ) was 0.10 ( 95 % CI : -8.56 , 8.76 ) and in the Beck Anxiety Inventory-Youth ( BAI-Y ) 2.42 ( 95 % CI : -5.27 , 10.12 ) in favour of TAU . However , there was a clear trend in favour of CBT in depressed participants with or without anxiety . LIMITATIONS The intervention targeted both depression and anxiety following a transdiagnostic model . This may have impacted the anticipated size of change in the primary outcome . The precise impact of cognitive limitations on ability to use therapy effectively is not fully understood . CONCLUSIONS This study demonstrates that it is feasible to carry out a pragmatic r and omised controlled trial of M-iCBT for people with mild to moderate intellectual disability . However , uncertainties about its clinical and cost effectiveness can only be fully answered by further examination of its superiority against other treatments BACKGROUND Many people with intellectual disabilities find it hard to control their anger and this often leads to aggression which can have serious consequences , such as exclusion from mainstream services and the need for potentially more expensive emergency placements . AIMS To evaluate the effectiveness of a cognitive-behavioural therapy ( CBT ) intervention for anger management in people with intellectual disabilities . METHOD A cluster-r and omised trial of group-based 12-week CBT , which took place in day services for people with intellectual disabilities and was delivered by care staff using a treatment manual . Participants were 179 service users identified as having problems with anger control r and omly assigned to either anger management or treatment as usual . Assessment s were conducted before the intervention , and at 16 weeks and 10 months after r and omisation ( trial registration : IS RCT N37509773 ) . RESULTS The intervention had only a small , and non-significant , effect on participants ' reports of anger on the Provocation Index , the primary outcome measure ( mean difference 2.8 , 95 % CI -1.7 to 7.4 at 10 months ) . However , keyworker Provocation Index ratings were significantly lower in both follow-up assessment s , as were service-user ratings on another self-report anger measure based on personally salient triggers . Both service users and their keyworkers reported greater usage of anger coping skills at both follow-up assessment s and keyworkers and home carers reported lower levels of challenging behaviour . CONCLUSIONS The intervention was effective in improving anger control by people with intellectual disabilities . It provides evidence of the effectiveness of a CBT intervention for this client group and demonstrates that the staff who work with them can be trained and supervised to deliver such an intervention with reasonable fidelity OBJECTIVE To determine if cues help young children discriminate among thoughts , feelings and behaviours . PARTICIPANTS Ninety-six children aged 4 - 7 years from three schools in Norwich , UK . DESIGN Within each age b and ( 4 , 5 , 6 , 7 ) , children were r and omised to the cue or the no cue condition on a stratified basis ensuring that equal numbers of boys and girls from each school were in each of the eight cells ( cue condition x age ) . Cues were glove puppets and post boxes . The effect of IQ was controlled . MEASURES A discrimination task , in which children were asked to identify a thought , a feeling and a behaviour from each of six brief stories , and a brief IQ assessment were administered to children individually . RESULTS There was a significant effect of age and cue condition on performance ; older children and those who were presented with the cue performed better . There were no gender differences and no interaction between cue condition and age . CONCLUSION Many young children discriminated among thoughts , feelings and behaviours suggesting that they may be able to engage in this aspect of cognitive behaviour therapy . Simple cues ( puppets and posting boxes ) improved children 's performance and these may be useful therapeutic tools with young children AIMS Training has been shown to improve the ability of people with intellectual disabilities ( IDs ) to perform some cognitive behavioural therapy ( CBT ) tasks . This study used a computerised training paradigm with the aim of improving the ability of people with IDs to : a ) discriminate between behaviours , thoughts and feelings , and b ) link situations , thoughts and feelings . METHODS Fifty-five people with mild-to-moderate IDs were r and omly assigned to a training or attention-control condition in a single-blind mixed experimental design . Computerised tasks assessed the participants ' skills in : ( a ) discriminating between behaviours , thoughts and feelings ( separately and pooled together ) , and ( b ) cognitive mediation by selecting appropriate emotions as consequences to given thoughts , and appropriate thoughts as mediators of given emotions . RESULTS Training significantly improved ability to discriminate between behaviours , thoughts and feelings pooled together , compared to the attention-control condition , even when controlling for baseline scores and IQ . Large within-group improvements in the ability to identify behaviours and feelings were observed for the training condition , but not the attention-control group . There were no significant between-group differences in ability to identify thoughts , or on cognitive mediation skills . CONCLUSIONS A single session of computerised training can improve the ability of people with IDs to underst and and practise CBT tasks relating to behaviours and feelings . There is potential for computerised training to be used as a " primer " for CBT with people with IDs to improve engagement and outcomes , but further development on a specific computerised cognitive mediation task is needed BACKGROUND People with intellectual disabilities ( ID ) experience similar or even higher rates of mental health problems than the general population and there is a need to develop appropriate treatments . Cognitive behaviour therapy ( CBT ) is effective for a wide range of disorders in the general population . However , there is some evidence that people with ID may lack the cognitive skills needed to take part in CBT . AIMS To test if people with ID can learn skills required for CBT , specifically the ability to distinguish between thoughts , feelings , and behaviours and to link thoughts and feelings ( cognitive mediation ) . METHOD A r and omized independent groups design was used to examine the effect of training in CBT on two tasks measuring CBT skills . Thirty-four adults with ID were r and omly allocated to the experimental condition ( N=18 ) or to the control condition ( N=16 ) . CBT skills were assessed blind at baseline and after the intervention . RESULTS The training led to significant improvements in participants ' ability to link thoughts and feelings , and this skill was generalized to new material . There was no effect of training on participants ' ability to distinguish amongst thoughts , feelings , and behaviours . People with ID can , therefore , learn some skills required for CBT . This implies that preparatory training for CBT might be useful for people with ID . The results might be applicable to other groups who find aspects of CBT difficult AIMS The aim was to examine whether specific skills required for cognitive behavioural therapy ( CBT ) could be taught using a computerised training paradigm with people who have intellectual disabilities ( IDs ) . Training aim ed to improve : a ) ability to link pairs of situations and mediating beliefs to emotions , and b ) ability to link pairs of situations and emotions to mediating beliefs . METHOD Using a single-blind mixed experimental design , sixty-five participants with IDs were r and omised to receive either computerised training or an attention-control condition . Cognitive mediation skills were assessed before and after training . RESULTS Participants who received training were significantly better at selecting appropriate emotions within situation-beliefs pairs , controlling for baseline scores and IQ . Despite significant improvements in the ability of those who received training to correctly select intermediating beliefs for situation-feelings pairings , no between-group differences were observed at post-test . CONCLUSIONS The findings indicated that computerised training led to a significant improvement in some aspects of cognitive mediation for people with IDs , but whether this has a positive effect upon outcome from therapy is yet to be established |
10,516 | 24,876,956 | Many studies found no quantitative gender-related differences in barriers and delays limiting access to TB services .
When differences were identified , women experienced greater barriers and longer delays than men | Background .
Tuberculosis ( TB ) remains a global public health problem with known gender-related disparities .
We review ed the quantitative evidence for gender-related differences in accessing TB services from symptom onset to treatment initiation . | Background Delayed diagnosis and treatment of tuberculosis ( TB ) results in severe disease and a higher mortality . It also leads to an increased period of infectivity in the community . The objective of this study was to determine the length of delays , and analyze the factors affecting the delay from onset of symptoms of pulmonary tuberculosis ( PTB ) until the commencement of treatment . Methods In r and omly selected TB management units ( TBMUs ) , i.e. government health institutions which have diagnosing and treatment facilities for TB in Amhara Region , we conducted a cross sectional study from September 1-December 31/2003 . Delay was analyzed from two perspectives , 1 . Period between onset of TB symptoms to first visit to any health provider ( health seeking period ) , and from the first health provider visit to initiation of treatment ( health providers ' delay ) , and 2 . Period between onset of TB symptoms to first visit to a medical provider ( patients ' delay ) , and from this visit to commencement of anti-TB treatment ( health systems ' delay ) . Patients were interviewed on the same date of diagnosis using a semi-structured question naire . Logistics regression analysis was applied to analyze the risk factors of delays . Results A total of 384 new smear positive PTB patients participated in the study . The median total delay was 80 days . The median health-seeking period and health providers ' delays were 15 and 61 days , respectively . Conversely , the median patients ' and health systems ' delays were 30 and 21 days , respectively . Taking medical providers as a reference point , we found that forty eight percent of the subjects delayed for more than one month . Patients ' delays were strongly associated with first visit to non-formal health providers and self treatment ( P < 0.0001 ) . Prior attendance to a health post/clinic was associated with increased health systems ' delay ( p < 0.0001 ) . Conclusion Delay in the diagnosis and treatment of PTB is unacceptably high in Amhara region . Health providers ' and health systems ' delays represent the major portion of the total delay . Accessing a simple and rapid diagnostic test for TB at the lowest level of health care facility and encouraging a dialogue among all health providers are imperative interventions Background One of the main strategies to control tuberculosis ( TB ) is to find and treat people with active disease . Unfortunately , the case detection rates remain low in many countries . Thus , we need interventions to find and treat sufficient number of patients to control TB . We investigated whether involving health extension workers ( HEWs : trained community health workers ) in TB control improved smear-positive case detection and treatment success rates in southern Ethiopia . Methodology /Principal Finding We carried out a community-r and omized trial in southern Ethiopia from September 2006 to April 2008 . Fifty-one kebeles ( with a total population of 296 , 811 ) were r and omly allocated to intervention and control groups . We trained HEWs in the intervention kebeles on how to identify suspects , collect sputum , and provide directly observed treatment . The HEWs in the intervention kebeles advised people with productive cough of 2 weeks or more duration to attend the health posts . Two hundred and thirty smear-positive patients were identified from the intervention and 88 patients from the control kebeles . The mean case detection rate was higher in the intervention than in the control kebeles ( 122.2 % vs 69.4 % , p<0.001 ) . In addition , more females patients were identified in the intervention kebeles ( 149.0 vs 91.6 , p<0.001 ) . The mean treatment success rate was higher in the intervention than in the control kebeles ( 89.3 % vs 83.1 % , p = 0.012 ) and more for females patients ( 89.8 % vs 81.3 % , p = 0.05 ) . Conclusions / Significance The involvement of HEWs in sputum collection and treatment improved smear-positive case detection and treatment success rate , possibly because of an improved service access . This could be applied in setting s with low health service coverage and a shortage of health workers . Trial Registration Clinical Trials.gov 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 A cross-sectional study was made of 500 patients and 500 health care workers r and omly selected from 250 primary health care centres throughout Iraq to evaluate knowledge , attitudes and practice s towards tuberculosis ( TB ) . Using structured question naire interviews , the study showed 64.4 % of patients had good knowledge , while 54.8 % had negative attitudes and practice s towards TB . The 2 most important sources of patient information about TB were physicians and television . Of health care workers , 95.5 % had good knowledge about TB and this was significantly associated with age and job duration . By contrast , health care workers ' practice was poor : only 38.2 % h and led suspected TB cases correctly . The national TB programme in Iraq has had a good impact on knowledge of TB patients and health care workers OBJECTIVE To assess an active case-finding strategy for the identification of smear-positive pulmonary tuberculosis ( TB ) in a rural district of Amhara Region , Ethiopia . METHODS Study kebeles ( smallest administrative units ) were r and omly selected in a cross-sectional study . House-to-house visits involving individuals aged > or=15 years in all households of the kebeles were conducted . The heads of households were asked to identify subjects with TB symptoms . Identified suspects were asked to provide three sputum sample s for smear microscopy . RESULTS Among the 47,478 individuals living in households that were screened , 1006 TB suspects and 38 cases were detected . This result ed in 38 cases of smear-positive TB , i.e. , 80 per 100,000 population , using cluster sampling . The ratio of active vs. passive case detection was 2.5:1 , indicating 2.5 undetected TB cases in the community for every smear-positive TB case receiving treatment during the survey period . A higher proportion of female patients was detected by the survey . CONCLUSION The study revealed a very high proportion of undiagnosed TB . This indicates that the potential for a large infectious pool and significant transmission of TB in the community is high . The expansion of diagnostic facilities and the active involvement of health extension workers is necessary to expedite early detection , timely referral and treatment of TB Background Optimally , exp and ed HIV testing programs should reduce barriers to testing while attracting new and high-risk testers . We assessed barriers to testing and HIV risk among clients participating in mobile voluntary counseling and testing ( MVCT ) campaigns in four rural villages in the Kilimanjaro Region of Tanzania . Methods Between December 2007 and April 2008 , 878 MVCT participants and 506 r and omly selected community residents who did not access MVCT were surveyed . Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics , HIV exposure risk , testing histories , HIV related stigma , and attitudes toward testing between MVCT participants and community residents who did not access MVCT . Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics , HIV exposure risk , testing histories , HIV related stigma , and attitudes toward testing , between the two groups . Results MVCT clients reported greater HIV exposure risk ( OR 1.20 [ 1.04 to 1.38 ] for males ; OR 1.11 [ 1.03 to 1.19 ] for females ) . Female MVCT clients were more likely to report low household expenditures ( OR 1.47 [ 1.04 to 2.05 ] ) , male clients reported higher rates of unstable income sources ( OR 1.99 [ 1.22 to 3.24 ] ) . First-time testers were more likely than non-testers to cite distance to testing sites as a reason for not having previously tested ( OR 2.17 [ 1.05 to 4.48 ] for males ; OR 5.95 [ 2.85 to 12.45 ] for females ) . HIV-related stigma , fears of testing or test disclosure , and not being able to leave work were strongly associated with non-participation in MVCT ( ORs from 0.11 to 0.84 ) . Conclusions MVCT attracted clients with increased exposure risk and fewer economic re sources ; HIV related stigma and testing-related fears remained barriers to testing . MVCT did not disproportionately attract either first-time or frequent repeat testers . Educational campaigns to reduce stigma and fears of testing could improve the effectiveness of MVCT in attracting new and high-risk population Background The CONSORT statement is intended to improve reporting of r and omised controlled trials and focuses on minimising the risk of bias ( internal validity ) . The applicability of a trial ’s results ( generalisability or external validity ) is also important , particularly for pragmatic trials . A pragmatic trial ( a term first used in 1967 by Schwartz and Lellouch ) can be broadly defined as a r and omised controlled trial whose purpose is to inform decisions about practice . This extension of the CONSORT statement is intended to improve the reporting of such trials and focuses on applicability . Methods At two , two-day meetings held in Toronto in 2005 and 2008 , we review ed the CONSORT statement and its extensions , the literature on pragmatic trials and applicability , and our experiences in conducting pragmatic trials . Recommendations We recommend extending eight CONSORT checklist items for reporting of pragmatic trials : the background , participants , interventions , outcomes , sample size , blinding , participant flow , and generalisability of the findings . These extensions are presented , along with illustrative examples of reporting , and an explanation of each extension . Adherence to these reporting criteria will make it easier for decision makers to judge how applicable the results of r and omised controlled trials are to their own conditions . Empirical studies are needed to ascertain the usefulness and comprehensiveness of these CONSORT checklist item extensions . In the meantime we recommend that those who support , conduct , and report pragmatic trials should use this extension of the CONSORT statement to facilitate the use of trial results in decisions about health care . Pragmatic trials are design ed to inform decisions about practice , but poor reporting can reduce their usefulness . The CONSORT and Practihc groups describe modifications to the CONSORT guidelines to help readers assess the applicability of the SETTING Bangladesh national tuberculosis control programme districts supported by the Damien Foundation ( population 18 million ) . OBJECTIVE To determine whether the observed gender difference is epidemiologically true or whether it is due to accessibility barriers for women . DESIGN Two-stage r and om sampling population survey . People were interviewed by teams composed of one male and one female volunteer about the presence of symptoms suggestive of tuberculosis . One early morning sputum specimen of all thus identified tuberculosis suspects was examined by Ziehl-Neelsen technique . RESULTS A total of 266189 people were surveyed , among whom 223 936 ( 84.1 % ) could be interviewed . This led to the identification of 7001 tuberculosis suspects ( 2406 females and 4595 males ) and 64 confirmed TB cases ( 16 females and 48 males ) . The female/male ratio ( 0.33:1 ) of cases found during the survey was not higher than that observed through routine diagnosis ( 0.42:1 ) . The routine case-notification rate of sputum-positive cases during 2000 was about twice the rate observed during the survey ( 44.3 vs. 24.0 per 100 000 population ) . CONCLUSIONS The gender difference observed in routine tuberculosis diagnosis is real , and is not due to lesser accessibility of women to the health services . The routine notification rate compares favourably with the detection of previously unknown cases found during the survey Background Tuberculosis ( TB ) is a global health concern . Inadequate case finding and case holding has been cited as major barrier to the control of TB . The TB literature is written almost entirely from a biomedical perspective , while recent studies show that it is imperative to underst and lay perception to determine why people seek treatment and may stop taking treatment . The Eastern Cape is known as a province with high TB incidence , prevalence and with one of the worst cure rates of South Africa . Its inhabitants can be considered lay experts when it comes to TB . Therefore , we investigated knowledge , perceptions of ( access to ) TB treatment and adherence to treatment among an Eastern Cape population . Methods An area-stratified sampling design was applied . A total of 1020 households were selected r and omly in proportion to the total number of households in each neighbourhood . Results TB knowledge can be considered fairly good among this community . Respondents ' perceptions suggest that stigma may influence TB patients ' decision in health seeking behavior and adherence to TB treatment . A full 95 % of those interviewed believe people with TB tend to hide their TB status out of fear of what others may say . Regression analyses revealed that in this population young and old , men and women and the lower and higher educated share the same attitudes and perceptions . Our findings are therefore likely to reflect the actual situation of TB patients in this population . Conclusions The lay experts ' perceptions suggests that stigma appears to effect case holding and case finding . Future interventions should be directed at improving attitudes and perceptions to potentially reduce stigma . This requires a patient-centered approach to empower TB patients and active involvement in the development and implementation of stigma reduction programs This study aim ed to determine the psychosocial factors associated with delayed test-seeking among tuberculosis patients . The duration of symptoms before seeking medical care was assessed by interview for 108 newly diagnosed pulmonary tuberculosis patients in the city of Iquitos in the Peruvian Amazon , which has high tuberculosis incidence . Beliefs associated with test-seeking behavior and delay was assessed in these patients . The median delay from symptom onset to seeking diagnostic testing was 61 days ( inter-quartile range 30 - 91 days ) . The belief that tuberculosis is curable was associated with a 100 % longer test-seeking delay ; the perception that tuberculosis was common was associated with a 57 % longer delay ; male gender was associated with a 48 % longer delay ; and education less than complete secondary schooling was associated with a 44 % longer delay . In conclusion , current health promotion activities that emphasize tuberculosis curability and high prevalence may paradoxically increase test-seeking delay and therefore require prospect i ve evaluation Summary Background Control of tuberculosis in setting s with high HIV prevalence is a pressing public health priority . We tested two active case-finding strategies to target long periods of infectiousness before diagnosis , which is typical of HIV-negative tuberculosis and is a key driver of transmission . Methods Clusters of neighbourhoods in the high-density residential suburbs of Harare , Zimbabwe , were r and omised to receive six rounds of active case finding at 6-monthly intervals by either mobile van or door-to-door visits . R and omisation was done by selection of discs of two colours from an opaque bag , with one disc to represent every cluster , and one colour allocated to each intervention group before selection began . In both groups , adult ( ≥16 years ) residents volunteering chronic cough ( ≥2 weeks ) had two sputum specimens collected for fluorescence microscopy . Community health workers and cluster residents were not masked to intervention allocation , but investigators and laboratory staff were masked to allocation until final analysis . The primary outcome was the cumulative yield of smear-positive tuberculosis per 1000 adult residents , compared between intervention groups ; analysis was by intention to treat . The secondary outcome was change in prevalence of culture-positive tuberculosis from before intervention to before round six of intervention in 12 % of r and omly selected households from the two intervention groups combined ; analysis was based on participants who provided sputum in the two prevalence surveys . This trial is registered , number IS RCT N84352452 . Findings 46 study clusters were identified and r and omly allocated equally between intervention groups , with 55 741 adults in the mobile van group and 54 691 in the door-to-door group at baseline . HIV prevalence was 21 % ( 1916/9060 ) and in the 6 months before intervention the smear-positive case notification rate was 2·8 per 1000 adults per year . The trial was completed as planned with no adverse events . The mobile van detected 255 smear-positive patients from 5466 participants su bmi tting sputum compared with 137 of 4711 participants identified through door-to-door visits ( adjusted risk ratio 1·48 , 95 % CI 1·11–1·96 , p=0·0087 ) . The overall prevalence of culture-positive tuberculosis declined from 6·5 per 1000 adults ( 95 % CI 5·1–8·3 ) to 3·7 per 1000 adults ( 2·6–5·0 ; adjusted risk ratio 0·59 , 95 % CI 0·40–0·89 , p=0·0112 ) . Interpretation Wide implementation of active case finding , particularly with a mobile van approach , could have rapid effects on tuberculosis transmission and disease . Funding Wellcome Trust SETTING The study was carried out at Delhi State , New Delhi . OBJECTIVES 1 . To assess the effect of social stigma in TB patient 's treatment , their personality , emotions , feelings , changes in their thinking process and behaviour of their family members , friends . 2 . To study the relationship of gender and to what extent social stigma affects their lives . DESIGN It was a prospect i ve study . A total of 1977 newly diagnosed and registered cases under Revised National TB Control Programme for treatment during the period of March 2009 to May 2009 were included in the study . Out of a total population of 170 lacs , a proportion of 31 lacs of Delhi , distributed among five chest clinics of Delhi , comprised the study population . All the patients were interviewed according to a pre- design ed & pre-tested question naire after taking informed consent of the patients . The data was collected and analysed after processing into MS excel sheets for statistical analysis . RESULTS There was an immense stigma observed at society level with 60 % of the patients hiding their disease ( p<0.05 ) from friends and neighbours . Stigma was observed more among middle and upper middle class when compared to lower middle class and lower class ( p<0.05 ) . Gender-wise further it was observed that stigma was more among females ( p<0.05 ) than in males . CONCLUSION The study has demonstrated that despite good performance of Revised National TB Control Programme the stigma in tuberculosis still remains a problem and we need to supplement the efforts in advocacy , communication and social mobalization for reducing the stigma problem among TB patients in effective control of tuberculosis In a prospect i ve study of gender and TB outcomes , 552 newly diagnosed smear-positive patients throughout the Syrian Arab Republic were interviewed at recruitment ( from January 2002 to July 2002 ) and followed until the end of treatment . Delay in diagnosis was significantly longer among males . Significant differences between males and females were noted in relation to the place they usually use to seek care . Gender did not seem to affect knowledge and attitudes of TB patients . Although the women reported more barriers to seeking care , compliance with treatment tended to be higher and the treatment success rate was significantly higher among females than males . Multivariate analysis showed that male sex was a significant predictor of a negative treatment outcome , after controlling for other significant sociodemographic and health care related variables BACKGROUND In many population s there is an excess of tuberculosis in young women and older men . We explored possible explanations for these patterns , concentrating on human immunodeficiency virus ( HIV ) status , pregnancy , smoking , cooking smoke exposure , contact with tuberculosis cases within the household or outside , and gender differences in health service usage and diagnostic delay . DESIGN Case control study in Karonga District , Malawi . METHODS Cases were new tuberculosis patients with bacteriological or histological evidence of tuberculosis . Controls were selected in the community using field-based r and om sampling . RESULTS The study included 598 tuberculosis cases and 992 controls , with an excess of tuberculosis in young females and older males . This was more marked in HIV-positive individuals . HIV infection was a similarly strong risk factor for tuberculosis in both men and women . Tuberculosis was associated with having a family or household contact with tuberculosis for both men and women . For women , but not men , contacts outside the close family and household were also a risk factor for tuberculosis . Tuberculosis was not associated with current or recent pregnancy , or with smoking or smoke exposure . There were no differences between men and women in health service usage or delay . CONCLUSIONS In this population , HIV infection and contacts with known tuberculosis patients are important determinants of the gender distribution of cases Background Health care seeking is a dynamic process that is influenced by socio-demographic , cultural and other factors . In Ethiopia , there are limited studies regarding the health seeking behaviour of tuberculosis ( TB ) suspects and TB patients . However , a thorough underst and ing of patients ' motivation and actions is crucial to underst and ing TB and the treatment of disease . Such insights would conceivably help to reduce delay in diagnosis , improve treatment adherence and thereby reduce transmission of TB in the community . The objective of this study was to describe and analyze health care seeking among TB suspects and pulmonary TB ( PTB ) cases in a rural district of the Amhara Region in Ethiopia . Methods Study kebeles were r and omly selected in a cross-sectional study design . House-to-house visits were conducted in which individuals aged 15 years and above in all households of the kebeles were included . Subjects with symptoms suggestive of TB were interviewed about their health seeking behaviour , socio-demographic and clinical factors using a semi-structured question naire . Logistics regression analysis was employed to assess associations between the independent and outcome variables . Results The majority , 787 ( 78 % ) , TB suspects and 33 ( 82.5 % ) PTB cases had taken health care actions for symptoms from sources outside their homes . The median delay before the first action was 30 days . In logistics regression , women ( AOR 0.8 , 95 % CI 0.6 , 0.9 ) were found to be less likely to visit a medical health provider than men . Those with a long duration of cough ( AOR 1.5 , 95 % CI 1.03 , 2.1 ) and those with a previous history of TB ( AOR 1.5 , 95 % CI 1.03 , 2.3 ) were more likely to visit a medical health provider compared to those with a shorter duration of cough and with no history of TB . Conclusion The majority of TB suspects and PTB cases had already taken health care actions for their symptoms at the time of the survey . The availability of a simple and rapid diagnostic TB test for use at the lowest level of health care and the involvement of all health providers in case finding activities are imperative for early TB case detection Background In Ethiopia , where HIV and tuberculosis ( TB ) are very common , little is known about the prejudice and misconceptions of rural communities towards People living with HIV/AIDS ( PLHA ) and TB . Methods We conducted a cross sectional study in Gilgel Gibe Field Research area ( GGFRA ) in southwest Ethiopia to assess the prejudice and misconceptions of rural and urban communities towards PLHA and TB . The study population consisted of 862 r and omly selected adults in GGFRA . Data were collected by trained personnel using a pretested structured question naire . To triangulate the findings , 8 focus group discussion s among women and men were done . Results Of the 862 selected study participants , 750(87 % ) accepted to be interviewed . The mean age of the respondents was 31.2 ( SD ± 11.0 ) . Of the total interviewed individuals , 58 % of them were females . More than half of the respondents did not know the possibility of transmission of HIV from a mother to a child or by breast feeding . For fear of contagion of HIV , most people do not want to eat , drink , and share utensils or clothes with a person living with HIV/AIDS . A higher proportion of females [ OR = 1.5 , ( 95 % CI : 1.0 , 2.2 ) ] , non-literate individuals [ OR = 2.3 , ( 95%CI : 1.4 , 3.6 ) ] , rural residents [ OR = 3.8 , ( 95%CI : 2.2 , 6.6 ) ] , and individuals who had poor knowledge of HIV/AIDS [ OR = 2.8 , ( 95%CI : 1.8 , 2.2 ) ] were more likely to have high prejudice towards PLHA than respectively males , literates , urban residents and individuals with good knowledge . Exposure to cold air was implicated as a major cause of TB . Literates had a much better knowledge about the cause and methods of transmission and prevention of TB than non-literates . More than half of the individuals ( 56 % ) had high prejudice towards a patient with TB . A larger proportion of females [ OR = 1.3 , ( 95 % CI : 1.0 , 1.9 ) ] and non-literate individuals [ OR = 1.4 , ( 95 % CI : 1.1 , 2.0 ) ] had high prejudice towards patients with TB than males and literate individuals . Conclusion TB/HIV control programs in collaboration with other partners should invest more in social mobilization and education of the communities to rectify the widespread prejudice and misconceptions BACKGROUND In several setting s , women with suspected tuberculosis are less likely to test smear positive than are men . Su bmi ssion of poor- quality sputum specimens by women might be one reason for the difference between the sexes . We did a pragmatic r and omised controlled trial to assess the effect of sputum-su bmi ssion instructions on female patients . METHODS 1494 women and 1561 men with suspected tuberculosis attending the Federal Tuberculosis Centre in Rawalpindi , Pakistan , were r and omly assigned between May and July , 2005 either to receive sputum-su bmi ssion guidance before specimen su bmi ssion or to su bmi t specimens without specific guidance , according to prevailing practice . Of enrolled patients , 133 ( 4 % ) declined to participate . The primary outcome measure was the proportion of instructed and non-instructed women testing smear positive . Intention-to-treat analysis was undertaken on the basis of treatment allocation . This study is registered with the International St and ard R and omised Controlled Trial number 34123170 . FINDINGS Instructed women were more likely to test smear positive than were controls ( Risk ratio 1.63 [ 95 % CI 1.19 - 2.22 ] ) . Instructions were associated with a higher rate of smear-positive case detection ( 58 [ 8 % ] in controls vs 95 [ 13 % ] in the intervention group ; p=0.002 ) , a decrease in spot-saliva su bmi ssion ( p=0.003 ) , and an increase in the number of women returning with an early-morning specimen ( p=0.02 ) . In men , instructions did not have a significant effect on the proportion testing smear positive or specimen quality . INTERPRETATION In the Federal Tuberculosis Centre in Rawalpindi , lower smear positivity in women than in men was mainly a function of poor- quality specimen su bmi ssion . Smear positivity in women was increased substantially by provision of brief instructions . Sputum-su bmi ssion guidance might be a highly cost-effective intervention to improve smear-positive case detection and reduce the disparity between the sexes in tuberculosis control in low-income countries SETTING Kigali University Hospital , the main referral centre for TB in Rw and a. OBJECTIVE To evaluate delays in the diagnosis and treatment of tuberculosis ( TB ) and associated risk factors . DESIGN Prospect i ve data collection of patients treated for pulmonary TB ( PTB ) or extra-pulmonary TB ( EPTB ) between June and September 2006 . RESULTS Of 104 patients with a mean age of 35 years ( range 17 - 84 ) recruited into the study , 62 % were HIV-positive . EPTB was diagnosed in 60 cases . The median total , health care and patient delays were respectively 57 , 28 and 25 days . The health system delay before referral was significantly longer than the delay at our institution ( 18 vs. 6 days , P<0.0001 ) . Risk factors for a longer health system delay at our institution were smear-negative PTB or EPTB ( OR 5.12 ) and a trial of antibiotics ( OR 2.96 ) . The latter was also found to significantly prolong total delay ( OR 2.85 ) , as did rural residence ( OR 4.86 ) . No significant association was found between patient delay and age , sex , profession or health insurance status . CONCLUSION Smear-negative PTB and EPTB were associated with longer health system delays . A trial of antibiotics significantly increased the health system delay . Its use , recommended by the World Health Organization in case of smear-negative TB and EPTB in developing countries , needs validation at the tertiary health care level SETTING Pakistan ranks eighth among the world 's highest tuberculosis ( TB ) burden countries , and Punjab province accounts for 60 % of TB cases nationally . OBJECTIVE To explore knowledge , attitudes and practice s regarding TB in the general population of two districts of Punjab province , and the effect of socio-economic determinants . DESIGN In a cross-sectional survey , subjects aged > or = 20 years were r and omly selected using multistage cluster sampling and interviewed . A knowledge score was formulated based on nine questions . Bivariate analysis using the chi(2 ) test was employed to independently correlate socio-economic factors with underst and ing of disease and information sources . Attitudes , practice s and information sources were also compared with TB knowledge . RESULTS Forty-two per cent of the surveyed population had good knowledge about TB , which was associated with better education , high income and good housing ( all P < 0.001 ) . Despite the fact that the majority ( 82.2 % ) knew about correct treatment , less than half ( 48.8 % ) were aware that diagnosis and treatment were free . Intended health-seeking behaviour was determined by better education ( P = 0.011 ) , good housing ( P = 0.004 ) and good knowledge about TB ( P < 0.001 ) . Television ( 69.4 % ) and health workers ( 43.6 % ) were the main sources of information . CONCLUSION Socio-economic factors should be considered when design ing communication strategies and prioritising TB prevention and control interventions SETTING Study conducted in 23 r and omly selected districts in four provinces of Vietnam . OBJECTIVE To describe and compare health seeking behaviour between men and women and to measure delays in tuberculosis ( TB ) diagnosis . DESIGN All patients ( n = 1027 ) aged 15 - 49 years with new smear-positive pulmonary TB detected in the selected districts during 1996 were interviewed using a structured question naire . RESULTS Mean total delay to TB diagnosis was 13.3 weeks ( 95 % confidence interval [ CI ] 11.5 , 15.1 ) for women and 11.4 weeks ( 95 % CI 10.6 , 12.2 ) for men , including a patient 's delay of 7.9 weeks ( 95 % CI 6.5 , 9.3 ) and 7.6 weeks ( 95 % CI 6.9 , 8.3 ) respectively . Doctor 's delay was significantly longer among women ( 5.4 weeks , 95 % CI 4.2 , 6.6 ) than among men ( 3.8 weeks , 95 % CI 3.3 , 4.3 ) . Women did not start seeking care later than men , nor did they have a different health seeking pattern . Women visited more health care providers than men ( 1.7 and 1.5 providers , respectively , P = 0.02 ) . CONCLUSION Patient 's delay is unacceptably long for both men and women . Women do not receive a diagnosis of TB by doctors or other health care providers as quickly as men once they seek health care . The reasons for this gender difference warrant further investigations SETTING A large , impoverished squatters ' settlement ( favela ) , Rio de Janeiro , Brazil . OBJECTIVE To assess the community impact of active case finding for tuberculosis ( TB ) compared to an enhanced case-finding strategy . DESIGN A pair-matched , cluster-r and omized trial comparing household symptom screening and spot sputum collection ( Arm 1 ) vs. distribution of an educational pamphlet ( Arm 2 ) was performed in a large Brazilian favela . We compared TB case-notification rates , time from symptom onset to treatment start and treatment completion proportions between arms . Fourteen neighborhoods ( estimated population 58,587 ) were pair-matched by prior TB case rates and r and omly allocated to one of two interventions . TB was diagnosed using acid-fast bacilli smears . New TB cases were interviewed and clinic records were review ed . RESULTS A total of 193 TB cases were identified in the 14 study neighborhoods ( incidence proportion 329 per 100,000 population ) . The case identification rate in Arm 1 was 934/100,000 person-years ( py ) vs. 604/100,000 py in Arm 2 ( RR 1.55 , 95%CI 1.10 - 1.99 ) . No significant differences were found in time from cough onset to treatment start or proportion completing treatment . CONCLUSIONS A door-to-door case-finding campaign was more effective ( while ongoing ) at detecting prevalent cases and influencing people to come for care than leafleting , but no differences were seen in time to treatment start or treatment completion Background Treatment delay is an important indicator of access to tuberculosis diagnosis and treatment . Analyses of patient delay ( i.e. time interval between onset of symptoms and first consultation of a health care provider ) and health care delay ( i.e. time interval between first consultation and start of treatment ) can inform policies to improve access . This study assesses the patient , health care provider and total delay in diagnosis and treatment of new smear-positive pulmonary tuberculosis patients , and the risk factors for long delay , in Vietnam . Methods A cross-sectional survey of new patients treated by the National Tuberculosis Control Programme was conducted in 70 r and omly selected districts in Vietnam . All consecutively registered patients in one quarter of 2002 were interviewed using a pre-coded structured question naire . Results Median ( range ) delay was 4 weeks ( 1–48 ) for total , 3 ( 1–48 ) weeks for patient and 1 ( 0–25 ) week for health care delay . Patients with long total delay ( ≥ 12 weeks , 15 % ) accounted for 49 % of the cumulative number of delay-weeks . Independent risk factors ( p < 0.05 ) for long total delay were female sex , middle age , remote setting , residence in the northern or central area , and initial visit to the private sector . For long patient delay ( ≥ 6 weeks ) this was female sex , belonging to an ethnic minority , and living at > 5 km distance from a health facility or in the northern area . For long health care delay ( ≥ 6 weeks ) this was urban setting , residence in the central area and initial visit to a communal health post , TB hospital or the private sector . Conclusion Analyses of patient and treatment delays can indicate target groups and areas for health education and strengthening of the referral system , in particular between the private sector and the NTP This study was carried out in Ilala and Kinondoni Municipalities in Tanzania to explore the perceptions of Tuberculosis ( TB ) , and treatment seeking behaviour , among patients attending healthcare facilities . The study was conducted in four r and omly selected health facilities providing directly observed treatment ( DOT ) . Exit interviews were administered to 69 r and omly selected TB patients . The mean age of the respondents was 33.2 years ( range = 11 - 72 years ) . Forty-six ( 66.7 % ) of the patients had primary school education . Fifty-nine ( 84.1 % ) patients had good knowledge on the transmission of TB . Majority ( 75 % ) of the respondents were of the opinion that the incidence of TB was on the increase and this was mainly associated with HIV/AIDS epidemic . All respondents knew that TB was a curable disease if one complies with the treatment . Sixty-four ( 60 % ) respondents had good knowledge on the correct duration of tuberculosis treatment . The median duration before seeking treatment from a health facility was 1.5 months . The majority of the patients 47 ( 68 % ) visited public health facilities for treatment as their first action . Overall , 83.8 % ( 57/68 ) respondents said females comply better with treatment than male patients . The majority of the respondents lived within a walking distance to a healthcare facility . Only 18.8 % ( 13/69 ) had to spend an average of US$ 0.2 - 0.3 as travel costs to the healthcare facility . Most of the respondents ( 57.8 % ) said they were well attended by service providers . Half ( 21/42 ) and 59.3 % ( 16/27 ) of the males and females , respectively , mentioned good patient-service provider relationship as an important reason for satisfaction of the service ( chi2 = 0.57 , df = 1 , P > 0.005 ) . Twenty-nine ( 42 % ) of respondents were of the opinion that female TB patients conformed better to treatment than males and a similar number thought that both of them equally conformed to treatment . Findings from this study indicate that a large population in urban setting s are aware that health facilities play a major role in TB treatment . In conclusion , there is a need to further explore how this information could potentially be used to enhance early seeking of appropriate services among TB patients in the era of rapid urbanization . Strategies in the control of TB and other diseases should focus on advocacy in seeking appropriate care PURPOSE This study aim ed to explore perceptions of TB , and health care seeking pathways , among poor rural communities in Inner Mongolia . METHODOLOGY Twenty focus group discussion s ( FGDs ) were held and 105 farmers were included . Six hundred and fourteen r and omly selected respondents were surveyed through interview question naire , in three poor rural counties with a high TB prevalence . MAIN FINDINGS A substantial proportion of community members were unclear or misinformed as to how TB was transmitted . Sixty percent of respondents identified prolonged cough as a main symptom of TB , while only 40 % perceived TB to be caused by ' close interaction with TB patient ' . In addition , 70 % could not afford TB treatment and fell into debt as a result of having to seek medical care . Social stigma associated with TB influenced marriage prospect s and impeded important social interactions within the community . Respondents ' perceptions of TB were associated with their socio-economic status . Women , young people , low-income groups and those with less education tended to be less knowledgeable about TB . All farmers in the study reported only seeking health care after they failed to treat themselves ; and most of them then sought care from less qualified village level health care providers . Less educated people , low-income groups and old people were identified as less likely to seek care , or more likely to seek care at village level where it is cheaper . Both financial and structural barriers were found to stop farmers seeking health care . CONCLUSIONS AND POLICY IMPLICATION S : Perceptions of TB and social stigma associated with the disease , together with socio-economic factors , shape the health seeking behaviour of poor farmers . Accessibility and affordability of TB health care issues should be dealt with through a multi-pronged approach , including health promotion in addition to expansion of the DOTS strategy and rural health insurance schemes BACKGROUND Although case detection is above 70 % in Tamil Nadu after DOTS implementation , an assessment of the timeliness of patient diagnosis and treatment is still needed . OBJECTIVE To study the health-seeking behaviour of new smear-positive pulmonary tuberculosis ( PTB ) patients treated at government facilities . METHODS New smear-positive patients diagnosed and treated between January and March 2003 in government facilities of r and omly selected blocks in Tamil Nadu were interviewed using a semi-structured interview schedule . RESULTS Of 601 patients interviewed , 65 % contacted a provider within 28 days . The first contact was governmental for 47 % and non-governmental for 53 % . Median total , patient and provider delays were respectively 62 , 28 and 28 days ; provider delay was 9 days with government and 50 with private provider . In multivariate analysis , patient delay was significantly associated with smoking ( P < 0.001 ) and mode of travel ( P < 0.01 ) , and provider delay with first consultation with a private provider ( P < 0.001 ) and distance > 5 km from the health facility ( P < 0.01 ) . Twenty-five per cent of patients took more than two actions before diagnosis . CONCLUSION Community awareness of TB needs to be increased . Greater private sector involvement in the Revised National Tuberculosis Control Programme is essential to reduce provider delay . Referral and sputum transportation to the diagnostic facility should be given priority INTRODUCTION Delayed diagnosis of tuberculosis ( TB ) can lead to an increased period of infectivity in the community , a delay in treatment and a severe form of the disease . The objective of this study was to determine the length of delay , and factors linking the delay from the onset of symptoms of pulmonary tuberculosis ( PTB ) until the commencement of treatment in Sarawak , Malaysia . METHODS An institution based cross-sectional study was conducted in 10 TB clinics in r and omly selected divisions in Sarawak from June 2003 to May 2004 . Delay was analyzed from two perspectives : ( 1 ) period between the onset of TB symptoms to any first medical consultation ( patients ' delay ) ; and ( 2 ) period between the first medical consultation to the diagnosis of TB ( diagnosis delay ) . Patients were interviewed on diagnosis or within the admission period using a semi-structured question naire . RESULTS A total of 316 new smear-positive PTB patients participated in the study . The median patient interval was 30 days . Gender was found to be significantly associated with patient delay . The median diagnosis interval was 22 days . Respondents ' incomes , health-care professional first consulted and actions taken by the health-care providers during the first consultation were significantly associated with diagnosis delay . The medium treatment interval was 0 days . CONCLUSION Both patients and health providers played a role in delaying TB diagnosis . Females appeared to have longer delay . Respondents living above the poverty line had diagnosis delay as they made more visits to GPs or different government clinics without proper investigations for TB . A mechanism is needed to increase all health-care providers ' suspicion of TB so that proper investigations can be done during first consultation A multistage r and om sampling method was used to select the community sample in the district of Kudat , Sabah . A total of 205 respondents from 210 selected houses were interviewed using a st and ardised question naire to ascertain their knowledge and attitude towards tuberculosis . Generally the knowledge about tuberculosis was poor . The well known symptoms that the respondents knew were coughing blood ( 46.2 % ) , cough ( 37.1 % ) , loss of weight ( 34.5 % ) , and loss of appetite ( 32.0 % ) . Only 51 % thought that the disease was caused by germs and it was transmitted by air . TB sufferers were thought to be dirty ( 22 % ) and the majority ( 51 % ) were not keen to mix with TB patients . Although more than 90 % of the respondents considered TB as socially acceptable within their family and community , a large proportion ( 41 % ) expressed that getting TB was embarrassing , 4 % said it was a disgrace to the family , and 16 % said that it was too sensitive to discuss about it . These behaviours suggest that at the private level , the respondents were still perceived negative social attitudes towards tuberculosis OBJECTIVE To examine access to and utilization of primary healthcare services with respect to gender . Greater family and child-rearing responsibilities are possible barriers to healthcare access and utilization for women with HIV infection . METHODS This study was part of a prospect i ve , r and omized , controlled trial evaluating primary care for HIV-infected patients at Duke University Medical Center ( DUMC ) , a tertiary care medical center . Subjects were 214 HIV-infected , uninsured or publicly insured participants . Ambulatory care visits , emergency room utilization , hospitalization rates , length of stay , preventive and screening measures , and antiretroviral use were the outcome measures . RESULTS Women ( n = 83 ) and men ( n = 131 ) enrolled in the study were similar with respect to race , educational level , marital status , and employment status . Women with HIV were more likely than men to have children ( 80 % vs. 25 % , p = 0.001 ) and spend their time as primary caregivers for their children ( 22 % vs. 0.8 % , p = 0.001 ) . Women had higher CD4(+ ) cell counts ( 378 + /- 287 vs. 243 + /- 252 cells/microl , p = 0.0002 ) , and a smaller proportion of women than men had AIDS at baseline ( 41 % vs. 62 % , p = 0.002 ) . Women and men had similar numbers of primary care visits , emergency room visits , annual admission rates , and lengths of stay for hospitalizations . Pneumocystis carinii pneumonia prophylaxis , pneumococcal vaccination , and tuberculosis screening were also similar between women and men . Women were more likely than men to have ever been prescribed an antiretroviral agent ( 88.0 % vs. 71.8 % , p = 0.005 ) . CONCLUSIONS Women had greater familial responsibilities than men , but this was not a barrier to access or utilization of healthcare services . Despite less advanced HIV disease , women received similar care and had similar utilization of health services OBJECTIVES To describe the TB knowledge in the general population and to analyze which methods and tools should be used for health education in community . METHODS A population -based cross-sectional survey was carried out within a demographic surveillance site in a rural district in Vietnam . A r and om sample of 12,143 adults was included . RESULTS The average knowledge score was 4.3+/-2.1 ( maximum=8 ) . Men had a significantly higher knowledge score than women ( 4.8 vs. 4.0 ) . More than half of the respondents thought TB was hereditary . In a multivariate analysis , gender , occupation , economic status , education , and sources of information were significantly associated with level of TB knowledge . Commonly , reported sources of information included television ( 64.6 % ) and friends/relatives ( 42.7 % ) . Sources of information differed between men and women . Commonly , television and loudspeakers were suggested as good ways of supplying information ( 70.4 % and 55.1 % ) . CONCLUSIONS A large proportion of general population had limited knowledge of TB , especially among women . Traditional beliefs such as a hereditary cause of TB persists in the population , despite many years of health education on TB . Access to information should be taken into consideration when choosing methods and channels for health education programmes OBJECTIVE To assess predictors for tuberculosis hospitalization and treatment outcome in Tajikistan . METHODS Stratified , single stage cluster sample survey of 1495 adult patients with pulmonary TB during 2 calendar years ( 2005 - 2006 ) from the registries of 10 TB centres chosen by simple r and om sampling . The primary outcome was referral to hospital . Logistic regression was conducted to test associations with the study outcome using linearization and a variance formula . RESULTS Prevalence of hospitalization for tuberculosis was 58 % . The odds of patients with smear-positive tuberculosis being referred were three times those of smear-negative patients [ OR 2.99 ( 95 % CI 1.81 - 4.96 ) ] . Other predictors for hospitalization were the availability of TB hospital beds within the same district [ OR 2.15 ( 95 % CI 1.22 - 3.76 ) ] and male gender [ OR 1.46 ( 95 % CI 1.07 - 2.48 ) ] . The overall treatment success was 80 % . CONCLUSIONS Hospitalization of patients with pulmonary tuberculosis was determined by positive sputum smear , supply of hospital beds , and gender . Reducing hospitalization with support of national guidelines is not expected to have a negative impact on treatment outcome and spread of disease , but could lead to improved efficiency and effectives of health service delivery for pulmonary tuberculosis in Tajikistan |
10,517 | 24,955,902 | A timely and adequate h and hygiene and an appropriate cleaning of the environment have been uniformly recommended by different guidelines as non-specific prevention measures against respiratory infections . | INTRODUCTION Attending a day care center is a risk factor for respiratory infections .
The objective of this study is to review which nonspecific prevention measures are recommended for day care centers and the evidence of their usefulness in this setting . | Objective . To study the effect of an educationally oriented intervention programme , with the recommendations from the National Board of Health and Welfare as a base . Design . A prospect i ve intervention study . Setting . Six day-care centres in Växjö , Sweden . Three centres comprised the intervention group and three constituted the control group . Subjects and main outcome measures . The parents and personnel completed a question naire on their views concerning information about infectious diseases . During a nine-month period , parents of all children reported every episode of absence , the number of days absent , the cause of absence , and any contact with doctors or prescription of antibiotics . Results . The guidelines were implementable in routine child day-care . Parents found regular information valuable and felt better informed about infectious diseases . Multilevel analyses showed no statistically significant results of the intervention . “ Infection-prone ” children had more sickness absence , doctor 's consultations , and antibiotic prescriptions than those not “ infection-prone ” . Conclusion . It is possible to implement an educationally oriented intervention programme directed against infectious diseases in child day-care . No significant effect of the intervention was found , which is why a larger intervention study is needed The objective of this study was to assess the effectiveness of a hygiene program in reducing the incidence of respiratory and diarrheal diseases in toddlers attending day care centers . A r and omized field trial was conducted in 52 day care centers in Quebec , Canada , between September 1 , 1996 and November 30 , 1997 . Absences for any reasons and the daily occurrence of colds and /or diarrhea in toddlers were recorded on calendars by the educators . The number of fecal coliforms on children 's h and s and on educators ' h and s was measured during three unannounced visits . Overall , 1,729 children were followed in 47 day care centers for a total of 153,643 child-days . The incidence rate of diarrhea was considerably reduced by the effect of monitoring ( IRR = 0.73 , 95 % CI = 0.54,0.97 ) , and the intervention reduced the incidence rate of upper respiratory tract infections ( IRR = 0.80 , 95 % CI = 0.68,0.93 ) . Monitoring alone also had an important effect in reducing the level of bacterial contamination on children 's and educators ' h and s. The results indicate that both an intervention program and monitoring alone play a role in reducing infections in children attending day care centers OBJECTIVE To evaluate the effectiveness of alcohol-based h and rubs ( ABH ) in reducing acute diarrheal diseases ( ADD ) and acute respiratory infections ( ARI ) among children 1 - 5 years of age in childcare centers with limited tap water . METHODS This was the first cluster-r and omized controlled trial in a developing country . The study took place at 42 childcare centers with sporadic and limited water availability in six towns in Colombia . Participants were r and omly assigned to use ABH as a complement to h and washing ( intervention arm : 21 centers/794 children ) ; or to continue existing h and washing practice s ( control arm : 21 centers/933 children ) . ADD and ARI cases were identified through teacher-reported signs and symptoms of illness . Adverse events were monitored . Hazard ratios ( HR ) were obtained using Cox proportional hazards multivariate regression shared frailty models . RESULTS Child-days of surveillance totaled 336 038 . Loss to follow up was 14.5 % . For both ADD and ARI , there were no differences in hazard ratios during the first trimester of the study . In the second and third trimesters , significant reductions in the risk of ADD were found in the intervention compared to control arm ( HR = 0.55 , P < 0.001 and HR = 0.44 , P < 0.001 , respectively ) . There were also significant risk reductions for ARI in the second trimester ( HR = 0.80 , P < 0.05 ) and in the third trimester ( HR = 0.69 , P < 0.001 ) . No adverse events occurred . CONCLUSIONS ABH effectively prevent ADD and ARI , and are safe . Colombia 's national public health policies for prevention of these diseases should include use of ABH , especially in setting s where h and washing with soap and water is limited by water availability OBJECTIVE Child care outside the home increases children 's infections substantially . We have to evaluate the possibilities for reducing the transmission of infections by an infection prevention program . DESIGN AND METHODS A 15-month r and omized controlled trial involving 20 day-care centers was conducted to evaluate the efficacy of an infection prevention program . The program was introduced in 10 centers and the other matched 10 centers served as controls . Records were made of the occurrence of infections and absences from care or work because of infections among the children , their parents and the personnel of the day-care centers . RESULTS Both the children and the personnel in the program centers had significantly fewer infections than those in the control centers , the reduction being 9 % [ 95 % confidence interval ( 95 % CI ) , 4 to 16 % , P < 0.002 ] among 3-year-old children and 8 % ( 95 % CI 0 to 14 % , P = 0.049 ) among the older children . The children at the program centers received 24 % fewer prescriptions of antimicrobials ( 95 % CI 22 to 27 % , P < 0.001 ) . Likewise there were 2.5 man-year fewer absences from work on the part of parents because of a child 's illness during 1 year in the program centers , a 24 % difference ( 95 % CI 18 to 29 % , P < 0.001 ) . CONCLUSIONS Effective prevention of infections is possible in child day-care centers , and this can benefit both the families and the personnel . Such a program is cost-effective even if a specialist nurse implements it Background . Acute upper respiratory infections are common in children who attend child care , and preventing transmission of disease in this setting depends on actions by child care staff . We set out to discover whether transmission of respiratory infections in child care could be reduced by improved infection control procedures . Methods . We performed a cluster , r and omized , controlled trial of an infection control intervention conducted in child care centers in 1 city in Australia . The intervention was training of child care staff about transmission of infection , h and washing , and aseptic nosewiping technique . Implementation of the intervention was recorded by an observer . Illness was measured by parent report in telephone interviews every 2 weeks . Results . There were 311 child-years of surveillance for respiratory symptoms . By multivariable analysis , there was no significant reduction in colds in intervention center children across the full age range . However , a significant reduction in respiratory illness was present in children 24 months of age and younger . When compliance with infection control practice s was high , colds in these children were reduced by 17 % . Conclusions . This trial supports the role of direct transmission of colds in young children in child care . The ability of infection control techniques to reduce episodes of colds in children in child care was limited to children 24 months of age and under Abstract . Background : The occurrence of contagious diseases among children attending day care centers ( DCCs ) is high . The possibility of reducing absences due to infections with an infection prevention program was investigated . Material s and Methods : The intervention study was conducted as an open , controlled cluster study . It included 60 municipal DCCs in one of the seven districts of the City of Helsinki ; 228 DCCs in the other six districts served as controls . The main indicator was the occurrence of absences due to upper respiratory tract infections , otitis media , eye infection and diarrhea per child-month . Results : The intervention reduced the absences due to infections by 26 % among under 3-year olds , but not among older children . The same phenomenon was observed when similar paired r and om control DCCs were compared with the intervention DCCs . Conclusion : Effective prevention of absences due to infections is possible among under 3-year olds by implementing a simple and inexpensive infection control program |
10,518 | 27,460,828 | Conclusions Current estimates of the lifetime medical care costs and the QALYs associated with smoking are date d and do not reflect the latest evidence on the health effects of smoking , nor the current costs and benefits of smoking cessation and prevention . | Background Estimated medical costs ( “ T ” ) and QALYs ( “ Q ” ) associated with smoking are frequently used in cost-utility analyses of tobacco control interventions .
The goal of this study was to underst and how research ers have addressed the method ological challenges involved in estimating these parameters . | 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 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 PURPOSE To evaluate the incremental effectiveness and cost-effectiveness of a staged-based , computerized smoking cessation intervention relative to st and ard care in an urban managed care network of primary care physicians . DESIGN Decision-analytic model based on results of a r and omized clinical trial . METHODOLOGY Patient outcomes and cost estimates were derived from clinical trial data . Effectiveness was measured in terms of 7-day point-prevalence abstinence at 6 months post-intervention . Quality -adjusted life years ( QALYs ) and cost-effectiveness ( CE ) were calculated , with CE measured as cost per patient per life year saved and per quality -adjusted life years saved . CE estimates were adjusted to account for partial behavior change as measured in terms of progression in stage of readiness to quit . Sensitivity analyses were conducted to evaluate the robustness of key model assumptions . PRINCIPAL FINDINGS Intervention patients were 1.77 times more likely to be smoke-free at 6 months follow-up than those in st and ard care ( p=.078 ) . The intervention generated an additional 3.24 quitters per year . Annualized incremental costs were $ 5,570 per primary care practice , and $ 40.83 per smoker . The mean incremental cost-effectiveness ratio was $ 1,174 per life year saved ( $ 869 per QALY ) . When the intervention impact on progression in stage of readiness to quit was also considered , the mean incremental cost-effectiveness ratio declined to $ 999 per life year saved ( $ 739 per QALY ) . CONCLUSIONS From a physician 's practice perspective , the stage-based computer tailored intervention was cost-effective relative to st and ard care . Incorporation of partial behavior change into the model further enhanced favorability of the cost-effectiveness ratio BACKGROUND As many as 70 % of smokers with acute myocardial infa rct ion ( AMI ) continue to smoke after hospital discharge despite high rates of inpatient smoking cessation counseling . Supportive contact after discharge improves quit rates but is rarely used . METHODS Using data from a meta- analysis of r and omized trials of smoking cessation interventions and other published sources , we developed a Monte Carlo model to project health and economic outcomes for a hypothetical US cohort of 327,600 smokers hospitalized with AMI . We compared routine care , consisting of advice to quit smoking , with counseling with supportive follow-up , consisting of routine care and follow-up telephone calls from a nurse after discharge . Primary outcomes were number of smokers , AMIs , and deaths averted ; health care and productivity costs ; cost per quitter ; and cost per quality -adjusted life-year . RESULTS Implementation of smoking cessation counseling with follow-up contact for the 2010 cohort of hospitalized smokers would create 50,230 new quitters , cost $ 27.3 million in nurse wages and material s , and prevent 1380 nonfatal AMIs and 7860 deaths . During a 10-year period , it would save $ 22.1 million in reduced hospitalizations but increase health care costs by $ 166.4 million , primarily through increased longevity . Productivity costs from premature death would fall by $ 1.99 billion and nonmedical expenditures would increase by $ 928 million , for a net positive value to society of $ 894 million . The program would cost $ 540 per quitter considering only intervention costs . Cost-effectiveness would be $ 5050 per quality -adjusted life-year . Results were sensitive to the utility and incidence of nonfatal AMI and the potential effect of pharmacotherapies . CONCLUSION Smoking cessation counseling with supportive contact after discharge is potentially cost-effective and may reduce the incidence of smoking and its associated adverse health events and social costs Introduction : A r and omized trial has demonstrated that lung cancer screening reduces mortality . Identifying participant and program characteristics that influence the cost-effectiveness of screening will help translate trial results into benefits at the population level . Methods : Six U.S. cohorts ( men and women aged 50 , 60 , or 70 years ) were simulated in an existing patient-level lung cancer model . Smoking histories reflected observed U.S. patterns . We simulated lifetime histories of 500,000 identical individuals per cohort in each scenario . Costs per quality -adjusted life-year gained ( $ /QALY ) were estimated for each program : computed tomography screening ; st and -alone smoking cessation therapies ( 4–30 % 1-year abstinence ) ; and combined programs . Results : Annual screening of current and former smokers aged 50 to 74 years costs between $ 126,000 and $ 169,000/QALY ( minimum 20 pack-years of smoking ) or $ 110,000 and $ 166,000/QALY ( 40 pack-year minimum ) , when compared with no screening and assuming background quit rates . Screening was beneficial but had a higher cost per QALY when the model included radiation-induced lung cancers . If screen participation doubled background quit rates , the cost of annual screening ( at age 50 years , 20 pack-year minimum ) was below $ 75,000/QALY . If screen participation halved background quit rates , benefits from screening were nearly erased . If screening had no effect on quit rates , annual screening costs more but provided fewer QALYs than annual cessation therapies . Annual combined screening/cessation therapy programs at age 50 years costs $ 130,500 to $ 159,700/QALY , when compared with annual st and -alone cessation . Conclusions : The cost-effectiveness of computed tomography screening will likely be strongly linked to achievable smoking cessation rates . Trials and further modeling should explore the consequences of relationships between smoking behaviors and screen participation There is a lack of evidence of the relative cost-effectiveness of proactive telephone counseling ( PTC ) and Web-based delivery of smoking cessation services in conjunction with pharmacotherapy . We calculated the differential cost-effectiveness of three behavioral smoking cessation modalities with varenicline treatment in a r and omized trial of current smokers from a large health system . Eligible participants were r and omized to one of three smoking cessation interventions : Web-based counseling ( n = 401 ) , PTC ( n = 402 ) , or combined PTC-Web counseling ( n = 399 ) . All participants received a st and ard 12-week course of varenicline . The primary outcome was a 7-day point prevalent nonsmoking at the 6 month follow-up . The Web intervention was the least expensive followed by the PTC and PTC-Web groups . Costs per additional 6-month nonsmoker and per additional lifetime quitter were $ 1,278 and $ 2,601 for Web , $ 1,472 and $ 2,995 for PTC , and $ 1,617 and $ 3,291 for PTC-Web . Cost per life-year ( LY ) and quality -adjusted life-year ( QALY ) saved were $ 1,148 and $ 1,136 for Web , $ 1,320 and $ 1,308 for PTC , and $ 1,450 and $ 1,437 for PTC-Web . Based on the cost per LY and QALY saved , these interventions are among the most cost-effective life-saving medical treatments . Web , PTC , and combined PTC-Web treatments were all highly cost-effective , with the Web treatment being marginally more cost-effective than the PTC or combined PTC-Web treatments OBJECTIVES To determine the differential cost effectiveness of 2 dosing regimens of bupropion sustained release ( SR ) in combination with behavioral interventions of minimal intensity ( tailored mailings [ TM ] ) or moderate intensity ( proactive telephone calls [ PTC ] ) for smoking cessation in an actual practice setting . STUDY DESIGN Open-label , r and omized trial , with 1-year follow-up , conducted in a large health system based in Seattle , Washington . METHODS A total of 1524 adult smokers interested in quitting smoking were r and omly assigned to receive 150 mg bupropion SR daily and PTC ( n = 382 ) , 150 mg bupropion SR daily and TM ( n = 381 ) , 300 mg bupropion SR daily and PTC ( n = 383 ) , or 300 mg bupropion SR daily and TM ( n = 378 ) . Sufficient medication for 8 weeks of dosing was provided to patients . The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 12 months after the target quit date . RESULTS Although the 300-mg dose was associated with a higher 12-month nonsmoking rate relative to the 150-mg dose with both PTC and TM , the additional cost result ed in lower cost effectiveness . The PTC behavioral intervention was more expensive than TM , but the additional effectiveness result ed in almost equivalent cost effectiveness at the 150-mg dose . Costs per additional 12-month nonsmoker ( above that expected for placebo ) for the 150-mg dose groups averaged 950 dollars and per additional lifetime quitter averaged 1508 dollars ; for the 300-mg groups these costs were 1342 dollars and 2129 dollars , respectively . Cost per life-year and quality -adjusted life-years ( QALYs ) saved varied substantially by age and treatment , but were no greater than 1100 dollars for all treatment groups when averaged across the age and sex distribution for the study population . CONCLUSIONS Although the cost per life-year and QALYs saved were sufficiently low for all doses to rate these smoking cessation interventions as among the most cost effective of life-saving medical treatments , within the regimens tested 150 mg bupropion combined with either PTC or TM was the most cost effective OBJECTIVES We assess the cost-effectiveness of smoking relapse prevention interventions design ed to keep quitters from resuming the use of cigarettes . Because relapse prevention is complementary to smoking cessation efforts , the appropriate test of its cost-effectiveness is whether it reduces the incremental cost-effectiveness ratio ( ICER ) of smoking cessation . The major goal of the study is to carry out such a test . METHODS Data from a r and omized trial that ascertained the effectiveness of alternative modes of smoking relapse prevention are combined with ICER estimates of smoking cessation to assess whether relapse prevention is cost-effective . RESULTS The trial produced convincing evidence that relapse prevention yields statistically significant reductions in the proportion of quitters who are smoking at 24 months postquit . The intervention effects are substantial enough to raise the denominator terms of the smoking cessation ICER and , thereby , offset the amount relapse prevention adds to cost numerator terms . In this sense , smoking relapse prevention tends to pay for itself . CONCLUSIONS Smoking relapse prevention is a highly cost-effective addition to current efforts to curb cigarette consumption . Complementary health interventions of this sort should be assessed by different methods than those commonly found in the cost-effectiveness literature |
10,519 | 22,007,320 | In conclusion , this review suggests that both safeguard interventions and educational training programs are effective in reducing the risk of having needlestick injuries . | Needlestick injuries frequently occur among healthcare workers , introducing high risk of bloodborne pathogen infection for surgeons , assistants , and nurses .
This systematic review aims to explore the impact of both educational training and safeguard interventions to reduce needlestick injuries . | Surgeons have the highest risk of contact with patients ' blood and body fluids , and breaches in gloving material may expose operating room staff to risk of infections . This prospect i ve r and omised study was done to assess the effectiveness of the practice of double gloving compared with single gloving in decreasing finger contamination during surgery . In 66 consecutive surgical procedures studied , preoperative skin abrasions were detected on the h and s of 17.4 % of the surgeons . In the double gloving pattern , 32 glove perforations were observed , of which 22 were in the outer glove and 10 in the inner glove . Only four outer glove perforations had matching inner glove perforations , thus indicating that in 82 % of cases when the outer glove is perforated the inner glove will protect the surgeon 's h and from contamination . The presence of visible skin contamination was also higher in perforation with the single gloving pattern ( 42.1 % ) than with the double gloving pattern ( 22.7 % ) . An overwhelming majority of glove perforations ( 83.3 % ) went unnoticed . Double gloving was accepted by the majority of surgeons , especially with repeated use . It is recommended that double gloves are used routinely in all surgical procedures in view of the significantly higher protection it provides OBJECTIVE : To compare the rate of glove perforation as a proxy for needlestick injuries between blunt and sharp needles used during cesarean-delivery closure and to survey physician satisfaction with blunt needles . METHODS : Patients requiring cesarean delivery were assigned r and omly to receive closure with either blunt ( study group ) or sharp needles ( control group ) . Patient demographics , operator experience , and other clinical variables were collected . Physicians reported any percutaneous injuries and were surveyed regarding satisfaction with the assigned needles . Glove perforation was determined using a vali date d water-test method . Differences between patient groups were tested using & khgr;2 and Fisher exact test for categorical variables and Student t-test or Wilcoxon rank-sum test for continuous variables . RESULTS : There were 194 patients enrolled in the trial : 97 in the control group and 97 in the study group . There were no statistical differences between groups in patient demographics . There were no differences between groups in clinical variables , type of cesarean delivery , or experience level of the surgeon . There was a significant reduction in total glove perforation rate for the primary surgeon with blunt needles ( 7.2 % ) compared with sharp needles ( 17.5 % ) ( relative risk [ RR ] 0.66 , 95 % confidence interval [ CI ] 0.49–0.89 ) as well as for the assistant surgeon ( RR 0.54 , 95 % CI 0.41–0.71 ) . There was poor correlation between reported perforations and those detected by water test ( R2=0.3 ) . Physicians reported that they were not as satisfied with blunt needles compared with sharp needles ( P=.001 ) . CONCLUSION : There was a significant decrease in the rate of glove perforation for surgeons and assistants performing cesarean-delivery closure with blunt needles . Assistant surgeons had the greatest reduction in glove perforations . However , physicians reported decreased satisfaction performing the surgery with blunt needles . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00844636 LEVEL OF EVIDENCE : The double gloving indicator underglove system ( IUS ) is based on a colored detection of the outer glove perforation . Our objective was to determine the IUS efficiency to detect outer glove perforations and to reduce the risks of blood and body fluids exposure , warning the surgeon before the breach of the surgeon – patient barrier ( SPB ) . A series of 100 visceral surgical procedures were r and omly assigned to either double ( IUS ) or single gloving . The noticed glove perforations ( using the water test method ) and the IUS efficiency were analyzed in 99 procedures . In 49 single-gloving procedures , 19 perforations were noticed : one was immediately perceived ( perceived accidental exposure , PAE ) ; 3 were discovered as the gloves were being removed , and 15 were undetected before the water test ( unperceived prolonged contact , UPC ) . In 50 double-gloving procedures ( IUS ) , 16 perforations were noticed , all of them involving only the outer glove : the IUS allowed immediate detection of 3 perforations without any blood exposure ; 13 other perforations went undetected but without any UPC . In conjunction with the protective quality of double gloving , the IUS allows detection of significant breaches of the outer glove before the breach of the SPB Glove perforation frequently occurs during the course of surgical procedures , introducing risks for both surgeons and patients . The aim of this study was to compare the use of blunt tapered and “ sharp ” needles during abdominal wall closure with respect to the incidence of glove perforation and the convenience of needle h and ling . A series of 200 patients undergoing laparotomy in a 6-month period for general surgical disorders were r and omized to two groups ; in one , the abdominal fascia was closed with a blunt tapered needle ; in the other , a sharp needle was used . The main outcome measures were glove perforation and convenience of h and ling the needle . Univariate and multivariate analyses were performed . In all , 56 glove perforations occurred during 40 ( 20 % ) surgical procedures .Perforation rates differed significantly : 12 % for the blunt ( n = 100 ) tapered needle and 28 % ( n = 100 ) for the sharp needle ( p = 0.003 ) . Only in 12 cases ( 21 % ) was the glove perforation detected at surgery . The type of needle ( odds ratio 0.35 , p = 0.006 ) and time taken to close the fascia ( odds ratio 1.001 , p = 0.05 ) significantly affected the risk of glove perforation . At multivariate logistic regression analysis the type of needle ( odds ratio 0.23 , p = 0.004 ) and the visual analog linear scale ( VAS ) for ease of needle h and ling ( odds ratio 1.18 , p = 0.019 ) were important predictive factors for glove perforation . With the blunt tapered needle , the VAS was significantly ( p = 0.0003 ) higher at primary laparotomy than at relaparotomy . Use of the blunt tapered needle reduces the incidence of glove perforation . Laborious closure predicts glove perforation . Blunt tapered needles are less convenient in closing a scarred abdominal fascia To assess the value of double‐gloving in gynaecological surgery OBJECTIVE To investigate the incidence of glove perforations during various types of gastrointestinal surgery , to record the incidence of blood contamination of the h and s , and to evaluate the protective effect of double gloving . DESIGN R and omised prospect i ve trial . SETTING University hospital , Denmark . MATERIAL 566 pairs of gloves tested on surgeons , assistants , and scrub nurses . INTERVENTIONS The participants were allocated to wear either single gloves or Indicator double gloves . MAIN OUTCOME MEASURES The number of glove perforations and the incidence of blood contamination of the h and s. RESULTS The perforation rate in single gloves was 53/306 ( 17 % ) , and that of both outer and inner Indicator gloves at corresponding sites was 6/260 ( 2 % ) ( p < 0.0001 ) . Double gloving reduced the rate of blood contamination of the h and s among surgeons from 15/115 ( 13 % ) to 2/98 ( 2 % ) ( p < 0.005 ) . CONCLUSION The use of Indicator double gloves is recommended in gastrointestinal surgery because of the appreciable protection against blood contamination that they offer BACKGROUND There is increased tendency towards double-gloving by general surgeons in our practice , due probably to awareness of the risk of contamination with blood or other body fluids during surgery . The aim of the study was to compare the relative frequency of glove puncture in single-glove versus double glove sets in general surgical procedures , and to determine if duration of surgery affects perforation rate . METHOD Surgeons at r and om do single or double gloves at their discretion , for general surgical procedures . All the gloves used by the surgeons were assessed immediately after surgery for perforation . RESULTS A total of 1120 gloves were tested , of which 880 were double-glove sets and 240 single-glove sets . There was no significant difference in the overall perforation rate between single and double glove sets ( 18.3 % versus 20 % ) . However , only 2.3 % had perforations in both the outer and inner gloves in the double glove group . Therefore , there was significantly greater risk for blood-skin exposure in the single glove sets ( p < 0.01 ) . The perforation rate was also significantly greater during procedures lasting an hour or more compared to those lasting less than an hour ( p < 0.01 ) . CONCLUSION Double-gloving reduces the risk of blood-skin contamination in all general surgical procedures , and especially so in procedures lasting an hour or more OBJECTIVE The purpose of this study was to compare the relative frequency of glove perforations in double-glove versus single-glove sets . STUDY DESIGN In this prospect i ve cohort study , surgeons single or double-gloved for pelvic surgery procedures at their own discretion . Gloves were collected at the end of each procedure and evaluated for perforations . RESULTS We tested 1000 sets of gloves : 675 double-glove sets and 325 single-glove sets . The highest rate of perforation ( 19 % ) occurred during major gynecologic procedures . Surgical nurses were the most likely member of the surgical team to sustain a glove injury . There was no significant difference in the total perforation rate between double and single glove sets ( 10 % vs 11 % ) . However , there was a significantly greater potential for blood-skin exposure in the single glove sets . Eleven percent of single glove sets contained a perforation , whereas only 2 % of double glove sets contained a corresponding defect in the inner and outer gloves ( P < .01 ) . CONCLUSION Surgeons should double-glove for all pelvic surgery procedures PURPOSE This study was conducted to comparatively evaluate , in a prospect i ve and r and omized manner , 2 techniques for providing double-gloving protection during arch bar placement for intermaxillary fixation . MATERIAL S AND METHODS A total of 42 consecutive patients in whom application of an Erich bar was indicated for intermaxillary fixation were equally divided into 2 groups . In group 1 , 2 sterile surgical gloves were used ; in group 2 , a nonsterile disposable inner glove was used under a sterile surgical glove . Wilcoxon , Mann-Whitney , Kruskal-Wallis , and binomial statistical tests were used to analyze the findings . RESULTS A total of 103 perforations were found in the outer gloves ( 47 in group 1 and 56 in group 2 ) , along with 5 perforations in inner gloves in both groups ( alpha = .01 ) . No significant statistical difference was found between groups in terms of inner glove perforations ( alpha = .05 ) . The nondominant h and presented with 70.9 % of the perforations , statistically significant to 1 % . CONCLUSIONS Both double-gloving techniques were found to provide effective clinician protection . The use of a nonsterile disposable glove under the surgical glove is possible for less-invasive procedures , offering the same safety as using 2 sterile surgical gloves while decreasing operational costs . This method does not eliminate the need to change gloves when a perforation is suspected or noted during the surgery , however BACKGROUND In surgery , intact gloves protect the surgeon from bloodborne pathogens and the surgical wound from microorganisms on the skin of the surgeon . However , glove perforation is very common , and puncture rates as high as 61 % are published in the literature . One objective of this study was to compare puncture rates between a unique double-gloving puncture indication system and single-use gloves , and another was to determine the extent to which glove perforations remain undetected during surgery . METHODS The study material comprised all gloves used in surgical operations at our hospital for a period of 2 months . The analysis was made by the glove type in a prospect i ve and r and omized manner . Gloves were tested immediately after the surgical procedure using the approved st and ardized water-leak method for 2 minutes to detect any holes . The gloves used in this study were either a double-gloving puncture indication system or the st and ard glove used at our hospital . RESULTS In 885 operations altogether , 2,462 gloves were tested ; 1,020 single gloves , 1,148 double-glove systems , and 294 combination gloves were studied . The overall perforation rate was 192 out of 2,462 gloves ( 7.80 % ) , and 162 out of 885 operations ( 18.3 % ) . The detection of perforation during surgery was 28 out of 76 ( 36.84 % ) with single gloves , 77 out of 89 with the double-gloving system ( 86.52 % ) , and 9 out of 27 with combination gloves ( 33.33 % ; P < 0.001 ) . The inner glove of the double-gloving system was punctured in 6 out of 88 outer glove perforations ( 6.82 % ) . CONCLUSIONS In view of the critical importance of safety at work by having a sterile barrier between surgeon and patient , it is very important to use a double-gloving puncture indication system , at least in operations where there is a high risk of glove perforation AIMS AND OBJECTIVES To determine the frequency of needlestick injuries and barriers of reporting such injuries amongst Iranian nurses . BACKGROUND Exposure to blood-borne pathogens because of needlestick injuries in particular is a potential risk for healthcare workers , including clinical nurses . The burden of sharp injuries sustained by healthcare workers is still unclear , primarily because of underreporting . DESIGN A cross-sectional study was undertaken amongst 111 clinical nurses working in five major teaching hospitals in Tehran/Iran during 2007 - 2008 who were r and omly selected . METHODS A vali date d self-reported question naire containing demographic characteristics and history of experiences with contaminated needlesticks as well as probably reason/s for underreporting such injuries was used . RESULTS More than half of the enrolled nurses ( 54.1 % , n = 60 ) had no experience of contaminated injuries , while the rest of 45.9 % ( n = 51 ) had experienced at least one contaminated needlestick injuries during their clinical performance . More than one-third ( 34.0 % , n = 38 ) had experienced a mean of 58 contaminated needlestick injuries during the past 12 months ( crude incidence : 0.52 NSI/nurse/year ) . Only 14 nurses ( 36.8 % ) with needlestick injuries experiences had officially reported their experiences . The major reasons for not reporting needlestick injuries were dissatisfaction with follow-up investigations by officials after reporting the events ( 33.3 % ) and safe/low risk considering of source patients ( 29.2 % ) . CONCLUSIONS Increased frequency and underreporting of needlestick injuries amongst Iranian nurses is going to be a major concern . As a preventive strategy , further interventions such as constant staff training , life-long learning and st and ardising postexposure procedures are recommended . RELEVANCE TO CLINICAL PRACTICE Determining the prevalence , burden and reasons for underreporting needlestick injuries by clinical nurses are required for establishing a preventive strategy to decrease hospital infections OBJECTIVE The objective of the study was to compare the rate of glove perforation for blunt and sharp needles used during obstetrical laceration repair . A secondary aim was to assess physician satisfaction with blunt needles . STUDY DESIGN This was an institutional review board-approved , r and omized , prospect i ve trial . Patients with obstetric lacerations were r and omized to repair with either blunt or sharp needles . Patient demographics , operator experience , and other clinical variables were collected . Physicians reported any percutaneous injuries and were surveyed regarding satisfaction with the assigned needles . Glove perforation was determined using a vali date d water test method . RESULTS There were 438 patients enrolled in the trial : 221 in the control group and 217 in the study group . There was no statistical difference between groups in patient demographics , clinical variables , severity of laceration , or experience level of the surgeon . There was no difference in the glove perforation rate between blunt and sharp needles ( risk ratio , 0.79 ; 95 % confidence interval , 0.2 - 2.95 ) . There was poor correlation between reported perforations and those detected by water test ( R(2 ) = 0.33 ) . The physicians reported that blunt needles were more difficult to use than sharp needles ( P = .0001 ) . CONCLUSION There was no difference in the rate of surgical glove perforation for blunt , compared with sharp , needles used during vaginal laceration repair . Physicians also reported increased difficulty performing the repair with blunt needles |
10,520 | 26,581,833 | Conclusions The available evidence suggests that CWI can be slightly better than passive recovery in the management of muscle soreness .
The results also demonstrated the presence of a dose – response relationship , indicating that CWI with a water temperature of between 11 and 15 ° C and an immersion time of 11–15 min can provide the best results | Background Cold water immersion ( CWI ) is a technique commonly used in post-exercise recovery .
However , the procedures involved in the technique may vary , particularly in terms of water temperature and immersion time , and the most effective approach remains unclear .
Objectives The objective of this systematic review was to determine the efficacy of CWI in muscle soreness management compared with passive recovery .
We also aim ed to identify which water temperature and immersion time provides the best results . | PURPOSE The authors investigated the efficacy of a single exposure to 14 min of cold-water immersion ( COLD ) and contrast water therapy ( CWT ) on posttraining recovery in Australian football ( AF ) . METHOD Fourteen AF players participated in 3 wk of st and ardized training . After week 1 training , all players completed a passive recovery ( PAS ) . During week 2 , COLD or CWT was r and omly assigned . Players undertook the opposing intervention in week 3 . Repeat-sprint ability ( 6 × 20 m ) , countermovement and squat jumps , perceived muscle soreness , and fatigue were measured pretraining and over 48 h posttraining . RESULTS Immediately posttraining , groups exhibited similar performance and psychometric declines . At 24 h , repeat-sprint time had deteriorated by 4.1 % for PAS and 1.0 % for CWT but was fully restored by COLD ( 0.0 % ) . At 24 and 48 h , both COLD and CWT attenuated changes in mean muscle soreness , with COLD ( 0.6 ± 0.6 and 0.0 ± 0.4 ) more effective than CWT ( 1.9 ± 0.7 and 1.0 ± 0.7 ) and PAS having minimal effect ( 5.5 ± 0.6 and 4.0 ± 0.5 ) . Similarly , after 24 and 48 h , COLD and CWT both effectively reduced changes in perceived fatigue , with COLD ( 0.6 ± 0.6 and 0.0 ± 0.6 ) being more successful than CWT ( 0.8 ± 0.6 and 0.7 ± 0.6 ) and PAS having the smallest effect ( 2.2 ± 0.8 and 2.4 ± 0.6 ) . CONCLUSIONS AF training can result in prolonged physical and psychometric deficits persisting for up to 48 h. For restoring physical-performance and psychometric measures , COLD was more effective than CWT , with PAS being the least effective . Based on these results the authors recommend that 14 min of COLD be used after AF training In the last years , phototherapy has becoming a promising tool to improve skeletal muscle recovery after exercise , however , it was not compared with other modalities commonly used with this aim . In the present study we compared the short-term effects of cold water immersion therapy ( CWIT ) and light emitting diode therapy ( LEDT ) with placebo LEDT on biochemical markers related to skeletal muscle recovery after high-intensity exercise . A r and omized double-blind placebo-controlled crossover trial was performed with six male young futsal athletes . They were treated with CWIT ( 5 ° C of temperature [ SD ±1 ° ] ) , active LEDT ( 69 LEDs with wavelengths 660/850 nm , 10/30 mW of output power , 30 s of irradiation time per point , and 41.7 J of total energy irradiated per point , total of ten points irradiated ) or an identical placebo LEDT 5 min after each of three Wingate cycle tests . Pre-exercise , post-exercise , and post-treatment measurements were taken of blood lactate levels , creatine kinase ( CK ) activity , and C-reactive protein ( CRP ) levels . There were no significant differences in the work performed during the three Wingate tests ( p > 0.05 ) . All biochemical parameters increased from baseline values ( p < 0.05 ) after the three exercise tests , but only active LEDT decreased blood lactate levels ( p = 0.0065 ) and CK activity ( p = 0.0044 ) significantly after treatment . There were no significant differences in CRP values after treatments . We concluded that treating the leg muscles with LEDT 5 min after the Wingate cycle test seemed to inhibit the expected post-exercise increase in blood lactate levels and CK activity . This suggests that LEDT has better potential than 5 min of CWIT for improving short-term post-exercise recovery Abstract This study investigated the effects of two different hydrostatic pressures ( seated or st and ing ) during cold water immersion at attenuating the deleterious effects of strenuous exercise on indices of damage and recovery . Twenty four male well-trained games players ( age 23 ± 3 years ; body mass 81.4 ± 8.7 kg : O2max 57.5 ± 4.9 ml∙kg−1∙min−1 ) completed the Loughborough Intermittent Shuttle Test ( LIST ) and were r and omly assigned to either a control , seated cold water immersion or a st and ing cold water immersion ( 14 min at 14 ° C ) . Maximal isometric voluntary contraction , counter-movement jump , creatine kinase , C-reactive protein , interleukin-6 and delayed onset muscle soreness ( DOMS ) were measured before and up to 72 h following the LIST . All dependent variables showed main effects for time ( P < 0.05 ) following the LIST , indicating physiological stress and muscle damage following the exercise . There were no significant group differences between control and either of the cold water immersion interventions . Seated cold water immersion was associated with lower DOMS than st and ing cold water immersion ( effect size = 1.86 ; P = 0.001 ) . These data suggest that increasing hydrostatic pressure by st and ing in cold water does not provide an additional recovery benefit over seated cold water immersion , and that both seated and st and ing immersions have no benefit in promoting recovery following intermittent sprint exercise The aim of this investigation was to eluci date the reductions in muscle , skin and core temperature following exposure to −110 ° C whole body cryotherapy ( WBC ) , and compare these to 8 ° C cold water immersion ( CWI ) . Twenty active male subjects were r and omly assigned to a 4-min exposure of WBC or CWI . A minimum of 7 days later subjects were exposed to the other treatment . Muscle temperature in the right vastus lateralis ( n = 10 ) ; thigh skin ( average , maximum and minimum ) and rectal temperature ( n = 10 ) were recorded before and 60 min after treatment . The greatest reduction ( P<0.05 ) in muscle ( mean ± SD ; 1 cm : WBC , 1.6±1.2 ° C ; CWI , 2.0±1.0 ° C ; 2 cm : WBC , 1.2±0.7 ° C ; CWI , 1.7±0.9 ° C ; 3 cm : WBC , 1.6±0.6 ° C ; CWI , 1.7±0.5 ° C ) and rectal temperature ( WBC , 0.3±0.2 ° C ; CWI , 0.4±0.2 ° C ) were observed 60 min after treatment . The largest reductions in average ( WBC , 12.1±1.0 ° C ; CWI , 8.4±0.7 ° C ) , minimum ( WBC , 13.2±1.4 ° C ; CWI , 8.7±0.7 ° C ) and maximum ( WBC , 8.8±2.0 ° C ; CWI , 7.2±1.9 ° C ) skin temperature occurred immediately after both CWI and WBC ( P<0.05 ) . Skin temperature was significantly lower ( P<0.05 ) immediately after WBC compared to CWI . The present study demonstrates that a single WBC exposure decreases muscle and core temperature to a similar level of those experienced after CWI . Although both treatments significantly reduced skin temperature , WBC elicited a greater decrease compared to CWI . These data may provide information to clinicians and research ers attempting to optimise WBC and CWI protocol s in a clinical or sporting setting The purpose of this study was to determine the effect of cryotherapy on the inflammatory response to muscle-damaging exercise using a r and omized trial . Twenty recreationally active males completed a 40-min run at a −10 % grade to induce muscle damage . Ten of the subjects were immersed in a 5 ° C ice bath for 20 min and the other ten served as controls . Knee extensor peak torque , soreness rating , and thigh circumference were obtained pre- and post-run , and 1 , 6 , 24 , 48 , and 72 h post-run . Blood sample s were obtained pre- and post-run , and 1 , 6 and 24 h post-run for assay of plasma chemokine lig and 2 ( CCL2 ) . Peak torque decreased from 270 ± 57 Nm at baseline to 253 ± 65 Nm post-run and increased to 295 ± 68 Nm by 72 h post-run with no differences between groups ( p = 0.491 ) . Soreness rating increased from 3.6 ± 6.0 mm out of 100 mm at baseline to 47.4 ± 28.2 mm post-run and remained elevated at all time points with no differences between groups ( p = 0.696 ) . CCL2 concentrations increased from 116 ± 31 pg mL−1 at baseline to 293 ± 109 pg mL−1 at 6 h post-run ( control ) and from 100 ± 27 pg mL−1 at baseline to 208 ± 71 pg mL−1 at 6 h post-run ( cryotherapy ) . The difference between groups was not significant ( p = 0.116 ) , but there was a trend for lower CCL2 in the cryotherapy group at 6 h ( p = 0.102 ) , though this measure was highly variable . In conclusion , 20 min of cryotherapy was ineffective in attenuating the strength decrement and soreness seen after muscle-damaging exercise , but may have mitigated the rise in plasma CCL2 concentration . These results do not support the use of cryotherapy during recovery OBJECTIVES To compare the localized skin-cooling effects of 2 cryotherapy modalities and to review the clinical relevance of the results . DESIGN R and omized controlled trial with repeated measures . SETTING Laboratory experiment . PARTICIPANTS Convenience sample of 20 volunteers ( 13 women , 7 men ) , ages 21.3 to 44 years ( mean , 31.3 + /- 6.8 y ) . INTERVENTIONS A flexible frozen gel pack , a 454 g packet of frozen peas , or a control applied to the anterior thigh . No blinding was undertaken . MAIN OUTCOME MEASURE Surface skin temperature under the modality at baseline and 10 and 20 minutes after application . RESULTS Significant effects were recorded for modality ( F(2 ) = 290.56 , P < .0001 ) , time ( F(1.27 ) = 1868.07 , P < .0001 ) , and their interaction ( F(2.09 ) = 305.47 , P < .0001 ) . After 20 minutes , frozen peas produced the lowest mean skin temperature + /- st and ard deviation of 10.8 degrees C + /- 2.28 degrees C compared with 14.4 degrees C + /- 2.53 degrees C from the gel pack and 26.1 degrees C + /- 1.75 degrees C from the control . Skin temperature fell between both time periods with the application of frozen peas but stabilized after 10 minutes of gel pack and control application . CONCLUSIONS Application of frozen peas produced mean skin temperatures adequate to induce localized skin analgesia , to reduce nerve conduction velocity , and to reduce metabolic enzyme activity to clinical ly relevant levels . Flexible frozen gel packs did not cool skin sufficiently to achieve these levels Abstract The aim of this study was to assess the effects of a single session of cold or thermoneutral water immersion after a one-off match on muscular dysfunction and damage in soccer players . Twenty-male soccer players completed one match and were r and omly divided into cryotherapy ( 10 min cold water immersion , 10 ° C , n = 10 ) and thermoneutral ( 10 min thermoneutral water immersion , 35 ° C , n = 10 ) groups . Muscle damage ( creatine kinase , myoglobin ) , inflammation ( C-reactive protein ) , neuromuscular function ( jump and sprint abilities and maximal isometric quadriceps strength ) , and delayed-onset muscle soreness were evaluated before , within 30 min of the end , and 24 and 48 h after the match . After the match , the players in both groups showed increased plasma creatine kinase activity ( 30 min , 24 h , 48 h ) , myoglobin ( 30 min ) and C-reactive protein ( 30 min , 24 h ) concentrations . Peak jump ability and maximal strength were decreased and delayed-onset muscle soreness increased in both groups . However , differential alterations were observed between thermoneutral water and cold water immersion groups in creatine kinase ( 30 min , 24 h , 48 h ) , myoglobin ( 30 min ) , C-reactive protein ( 30 min , 24 h , 48 h ) , quadriceps strength ( 24 h ) , and quadriceps ( 24 h ) , calf ( 24 h ) and adductor ( 30 min ) delayed-onset muscle soreness . The results suggest that cold water immersion immediately after a one-off soccer match reduces muscle damage and discomfort , possibly contributing to a faster recovery of neuromuscular function BACKGROUND Cold Water Immersion ( CWI ) is commonly used to manage delayed onset muscle soreness ( DOMS ) result ing from exercise . Scientific evidence for an optimal dose of CWI is lacking and athletes continue to use a range of a treatment protocol s and water temperatures . OBJECTIVES To compare the effectiveness of four different water immersion protocol s and a passive control intervention in the management of DOMS . DESIGN R and omised controlled trial with blinded outcome assessment . SETTING University Research Laboratory . PARTICIPANTS 50 healthy participants with laboratory induced DOMS r and omised to one of five groups : Short contrast immersion ( 1 min 38 ° C/1 min 10 ° C × 3 ) , Short intermittent CWI ( 1 min × 3 at 10 ° C ) ; 10 min CWI in 10 ° C ; 10 min CWI in 6 ° C ; or control ( seated rest ) . MAIN OUTCOME MEASURES muscle soreness , active range of motion , pain on stretch , muscle strength and serum creatine kinase . RESULTS 10 min of CWI in 6 ° C was associated with the lowest levels of muscle soreness and pain on stretch however values were not statistically different to any of the other groups . There were no statistically significant differences between groups for any other outcomes . CONCLUSION Altering the treatment duration , water temperature or dosage of post exercise water immersion had minimal effect on outcomes relating to DOMS UNLABELLED Cold water immersion ( CWI ) has become a popular means of enhancing recovery from various forms of exercise . However , there is minimal scientific information on the physiological effects of CWI following cycling in the heat . PURPOSE To examine the safety and acute thermoregulatory , cardiovascular , metabolic , endocrine , and inflammatory responses to CWI following cycling in the heat . METHODS Eleven male endurance trained cyclists completed two simulated approximately 40-min time trials at 34.3 + /- 1.1 degrees C. All subjects completed both a CWI trial ( 11.5 degrees C for 60 s repeated three times ) and a control condition ( CONT ; passive recovery in 24.2 + /- 1.8 degrees C ) in a r and omized cross-over design . Capillary blood sample s were assayed for lactate , glucose , pH , and blood gases . Venous blood sample s were assayed for catecholamines , cortisol , testosterone , creatine kinase , C-reactive protein , IL-6 , and IGF-1 on 7 of the 11 subjects . Heart rate ( HR ) , rectal ( Tre ) , and skin temperatures ( Tsk ) were measured throughout recovery . RESULTS CWI elicited a significantly lower HR ( CWI : Delta 116 + /- 9 bpm vs. CONT : Delta 106 + /- 4 bpm ; P = .02 ) , Tre ( CWI : Delta 1.99 + /- 0.50 degrees C vs. CONT : Delta 1.49 + /- 0.50 degrees C ; P = .01 ) and Tsk . However , all other measures were not significantly different between conditions . All participants subjectively reported enhanced sensations of recovery following CWI . CONCLUSION CWI did not result in hypothermia and can be considered safe following high intensity cycling in the heat , using the above protocol . CWI significantly reduced heart rate and core temperature ; however , all other metabolic and endocrine markers were not affected by CWI This study examined the effects of cold therapy ( COLD ) on recovery of voluntary and evoked contractile properties following high-intensity , muscle-damaging and fatiguing exercise . Ten resistance-trained males performed 6 × 25 maximal concentric/eccentric muscle contractions of the dominant knee extensors ( KE ) followed by a 20-min recovery ( COLD v control ) in a r and omized cross-over design . Voluntary and evoked neuromuscular properties of the right KE , ratings of perceived muscle soreness ( MS ) and pain , and blood markers for muscle damage were measured pre- and post-exercise , and immediately post-recovery , 2 , 24 and 48-h post-recovery . Exercise result ed in decrements in voluntary and evoked torque , increased MS and elevated muscle damage markers ( p < 0.05 ) . Measures of maximal voluntary contraction ( MVC ) or voluntary activation ( VA ) were not significantly enhanced by COLD ( p > 0.05 ) . Activation of right KE decreased post-exercise with increased activation of biceps femoris ( BF ) ( p < 0.05 ) . However , no significant differences were evident between conditions of activation of KE and hamstrings at any time point ( p > 0.05 ) . No significant differences were observed between conditions for creatine kinase or asparate aminotransferase ( p > 0.05 ) . However , perceptual ratings of pain were significantly ( p < 0.05 ) lower following COLD compared to control . In conclusion , following damage to the contractile apparatus , COLD did not significantly hasten the recovery of peripheral contractile trauma . Despite no beneficial effect of COLD on recovery of MVC , perceptions of pain were reduced following COLD PURPOSE The efficacy of a single exposure to 14 min of contrast water therapy ( CWT ) or cold-water immersion ( COLD ) on recovery postmatch in elite professional footballers was investigated . METHOD Twenty-four elite footballers participated in a match followed by 1 of 3 recovery interventions . Recovery was monitored for 48 h postmatch . Repeat-sprint ability ( 6 × 20-m ) , static and countermovement jump performance , perceived soreness , and fatigue were measured prematch and immediately , 24 h , and 48 h after the match . Soreness and fatigue were also measured 1 h postmatch . Postmatch , players were r and omly assigned to complete passive recovery ( PAS ; n = 8) , COLD ( n = 8) , or CWT ( n = 8) . RESULTS Immediately postmatch , all groups exhibited similar psychometric and performance decrements , which persisted for 48 h only in the PAS group . Repeat-sprinting performance remained slower at 24 and 48 h for PAS ( 3.9 % and 2.0 % ) and CWT ( 1.6 % and 0.9 % ) but was restored by COLD ( 0.2 % and 0.0 % ) . Soreness after 48 h was most effectively attenuated by COLD ( ES 0.59 ± 0.10 ) but remained elevated for CWT ( ES 2.39 ± 0.29 ) and PAS ( ES 4.01 ± 0.97 ) . Similarly , COLD more successfully reduced fatigue after 48 h ( ES 1.02 ± 0.72 ) than did CWT ( ES 1.22 ± 0.38 ) and PAS ( ES 1.91 ± 0.67 ) . Declines in static and countermovement jump were ameliorated best by COLD . CONCLUSIONS An elite professional football match results in prolonged physical and psychometric deficits for 48 h. COLD was more successful at restoring physical performance and psychometric measures than CWT , with PAS being the poorest Abstract The aim of this study was to assess the effects of cold-water immersion ( cryotherapy ) on indices of muscle damage following a bout of prolonged intermittent exercise . Twenty males ( mean age 22.3 years , s = 3.3 ; height 1.80 m , s = 0.05 ; body mass 83.7 kg , s = 11.9 ) completed a 90-min intermittent shuttle run previously shown to result in marked muscle damage and soreness . After exercise , participants were r and omly assigned to either 10 min cold-water immersion ( mean 10 ° C , s = 0.5 ) or a non-immersion control group . Ratings of perceived soreness , changes in muscular function and efflux of intracellular proteins were monitored before exercise , during treatment , and at regular intervals up to 7 days post-exercise . Exercise result ed in severe muscle soreness , temporary muscular dysfunction , and elevated serum markers of muscle damage , all peaking within 48 h after exercise . Cryotherapy administered immediately after exercise reduced muscle soreness at 1 , 24 , and 48 h ( P < 0.05 ) . Decrements in isometric maximal voluntary contraction of the knee flexors were reduced after cryotherapy treatment at 24 ( mean 12 % , s x = 4 ) and 48 h ( mean 3 % , s x = 3 ) compared with the control group ( mean 21 % , s x = 5 and mean 14 % , s x = 5 respectively ; P < 0.05 ) . Exercise-induced increases in serum myoglobin concentration and creatine kinase activity peaked at 1 and 24 h , respectively ( P < 0.05 ) . Cryotherapy had no effect on the creatine kinase response , but reduced myoglobin 1 h after exercise ( P < 0.05 ) . The results suggest that cold-water immersion immediately after prolonged intermittent shuttle running reduces some indices of exercise-induced muscle damage OBJECTIVE To determine if ice-water immersion after eccentric quadriceps exercise minimises the symptoms of delayed-onset muscle soreness ( DOMS ) . DESIGN A prospect i ve r and omised double-blind controlled trial was undertaken . 40 untrained volunteers performed an eccentric loading protocol with their non-dominant leg . INTERVENTIONS Participants were r and omised to three 1-min immersions in either ice water ( 5+/-1 degrees C ) or tepid water ( 24 degrees C ) . MAIN OUTCOME MEASURES Pain and tenderness ( visual analogue scale ) , swelling ( thigh circumference ) , function ( one-legged hop for distance ) , maximal isometric strength and serum creatine kinase ( CK ) recorded at baseline , 24 , 48 and 72 h after exercise . Changes in outcome measures over time were compared to determine the effect of group allocation using independent t tests or Mann-Whitney U tests . RESULTS No significant differences were observed between groups with regard to changes in most pain parameters , tenderness , isometric strength , swelling , hop-for-distance or serum CK over time . There was a significant difference in pain on sit-to-st and at 24 h , with the intervention group demonstrating a greater increase in pain than the control group ( median change 8.0 vs 2.0 mm , respectively , p = 0.009 ) . CONCLUSIONS The protocol of ice-water immersion used in this study was ineffectual in minimising markers of DOMS in untrained individuals . This study challenges the wide use of this intervention as a recovery strategy by athletes The purpose of this study was to examine the effectiveness of a single bout of cold-water immersion on recovery from exercise-induced muscle damage . Eighteen physically active female volunteers ( age 19.9 ( ±0.97 years ) , height 1.66 ( ±0.05 m ) , mass 63.7 ( ±10 kg ) , completed 10 sets of 10 counter-movement jumps to induce muscle damage and were r and omly allocated to a control or treatment group . The treatment group was given a single 10-min bout of lower limb cold-water immersion therapy at 10 ° C immediately following damage-inducing exercise . Indicators of muscle damage ( plasma creatine kinase activity , perceived soreness and maximal voluntary contraction of the quadriceps ) were assessed immediately prior to counter-movement jumps , and at 1 , 24 , 48 , 72 and 96 h , following the damaging exercise . Significant ( p = 0.05 ) time effects were recorded on all indicators of muscle damage , but there were no significant group or group × time interaction effects found on any of the measured variables . The results indicate that a single bout of cold-water immersion after a damaging bout of exercise has no beneficial effects on the recovery from exercise-induced muscle damage The present study investigated the effects of three hydrotherapy interventions on next day performance recovery following strenuous training . Twelve cyclists completed four experimental trials differing only in 14-min recovery intervention : cold water immersion ( CWI ) , hot water immersion ( HWI ) , contrast water therapy ( CWT ) , or passive recovery ( PAS ) . Each trial comprised five consecutive exercise days of 105-min duration , including 66 maximal effort sprints . Additionally , subjects performed a total of 9-min sustained effort ( time trial - TT ) . After completing each exercise session , athletes performed one of four recovery interventions ( r and omly assigned to each trial ) . Performance ( average power ) , core temperature , heart rate ( HR ) , and rating of perceived exertion ( RPE ) were recorded throughout each session . Sprint ( 0.1 - 2.2 % ) and TT ( 0.0 - 1.7 % ) performance were enhanced across the five-day trial following CWI and CWT , when compared to HWI and PAS . Additionally , differences in rectal temperature were observed between interventions immediately and 15-min post-recovery ; however , no significant differences were observed in HR or RPE regardless of day of trial/intervention . Overall , CWI and CWT appear to improve recovery from high-intensity cycling when compared to HWI and PAS , with athletes better able to maintain performance across a five-day period BACKGROUND Many strategies are in use with the intention of preventing or minimising delayed onset muscle soreness and fatigue after exercise . Cold-water immersion , in water temperatures of less than 15 ° C , is currently one of the most popular interventional strategies used after exercise . OBJECTIVES To determine the effects of cold-water immersion in the management of muscle soreness after exercise . SEARCH METHODS In February 2010 , we search ed the Cochrane Bone , Joint and Muscle Trauma Group Specialised Register , the Cochrane Central Register of Controlled Trials ( The Cochrane Library ( 2010 , Issue 1 ) , MEDLINE , EMBASE , Cumulative Index to Nursing and Allied Health ( CINAHL ) , British Nursing Index and archive ( BNI ) , and the Physiotherapy Evidence Data base ( PEDro ) . We also search ed the reference lists of articles , h and search ed journals and conference proceedings and contacted experts . In November 2011 , we up date d the search es of CENTRAL ( 2011 , Issue 4 ) , MEDLINE ( up to November Week 3 2011 ) , EMBASE ( to 2011 Week 46 ) and CINAHL ( to 28 November 2011 ) to check for more recent publications . SELECTION CRITERIA R and omised and quasi-r and omised trials comparing the effect of using cold-water immersion after exercise with : passive intervention ( rest/no intervention ) , contrast immersion , warm-water immersion , active recovery , compression , or a different duration /dosage of cold-water immersion . Primary outcomes were pain ( muscle soreness ) or tenderness ( pain on palpation ) , and subjective recovery ( return to previous activities without signs or symptoms ) . DATA COLLECTION AND ANALYSIS Three authors independently evaluated study quality and extracted data . Some of the data were obtained following author correspondence or extracted from graphs in the trial reports . Where possible , data were pooled using the fixed-effect model . MAIN RESULTS Seventeen small trials were included , involving a total of 366 participants . Study quality was low . The temperature , duration and frequency of cold-water immersion varied between the different trials as did the exercises and setting s. The majority of studies failed to report active surveillance of pre-defined adverse events . Fourteen studies compared cold-water immersion with passive intervention . Pooled results for muscle soreness showed statistically significant effects in favour of cold-water immersion after exercise at 24 hour ( st and ardised mean difference ( SMD ) -0.55 , 95 % CI -0.84 to -0.27 ; 10 trials ) , 48 hour ( SMD -0.66 , 95 % CI -0.97 to -0.35 ; 8 trials ) , 72 hour ( SMD -0.93 ; 95 % CI -1.36 to -0.51 ; 4 trials ) and 96 hour ( SMD -0.58 ; 95 % CI -1.00 to -0.16 ; 5 trials ) follow-ups . These results were heterogeneous . Exploratory subgroup analyses showed that studies using cross-over design s or running based exercises showed significantly larger effects in favour of cold-water immersion . Pooled results from two studies found cold-water immersion groups had significantly lower ratings of fatigue ( MD -1.70 ; 95 % CI -2.49 to -0.90 ; 10 units scale , best to worst ) , and potentially improved ratings of physical recovery ( MD 0.97 ; 95 % CI -0.10 to 2.05 ; 10 units scale , worst to best ) immediately after the end of cold-water immersion . Five studies compared cold-water with contrast immersion . Pooled data for pain showed no evidence of differences between the two groups at four follow-up times ( immediately , 24 , 48 and 72 hours after treatment ) . Similar findings for pooled analyses at 24 , 48 and 72 hour follow-ups applied to the four studies comparing cold-water with warm-water immersion . Single trials only compared cold-water immersion with respectively active recovery , compression and a second dose of cold-water immersion at 24 hours . AUTHORS ' CONCLUSIONS There was some evidence that cold-water immersion reduces delayed onset muscle soreness after exercise compared with passive interventions involving rest or no intervention . There was insufficient evidence to conclude on other outcomes or for other comparisons . The majority of trials did not undertake active surveillance of pre-defined adverse events . High quality , well reported research in this area is required The aim of the present study was to investigate the potential benefits of cold water immersion ( CWI ) and active recovery ( AR ) on blood lactate concentration ( [ Lac ] ) and heart rate variability ( HRV ) indices following high-intensity exercise . 20 male subjects were recruited . On the first visit , an incremental test was performed to determine maximal oxygen consumption and the associated speed ( MAS ) . The remaining 3 visits for the performance of constant velocity exhaustive tests at MAS and different recovery methods ( 6 min ) were separated by 7-day intervals [ r and omized : CWI , AR or passive recovery ( PR ) ] . The CWI and AR lowered [ Lac ] ( p<0.05 ) at 11 , 13 and 15 min after exercise cessation in comparison to PR . There was a ' time ' and ' recovery mode ' interaction for 2 HRV indices : st and ard deviation of normal R-R intervals ( SDNN ) ( partial eta squared=0.114 ) and natural log of low-frequency power density ( lnLF ) ( partial eta squared=0.090 ) . CWI presented significantly higher SDNN compared to PR at 15 min of recovery ( p<0.05 ) . In addition , greater SDNN values were found in CWI vs. AR during the application of recovery interventions , and at 30 and 75 min post-exercise ( p<0.05 for all differences ) . The lnLF during the recovery interventions and at 75 min post-exercise was greater using CWI compared with AR ( p<0.05 ) . For square root of the mean of the sum of the squares of differences between adjacent R-R intervals ( RMSSD ) and natural log of high-frequency power density ( lnHF ) , a moderate effect size was found between CWI and PR during the recovery interventions and at 15 min post-exercise . Our findings show that AR and CWI offer benefits regarding the removal of [ Lac ] following high-intensity exercise . While limited , CWI results in some improvement in post-exercise cardiac autonomic regulation compared to AR and PR . Further , AR is not recommended if the aim is to accelerate the parasympathetic reactivation The purpose was to assess whether body cooling between 2 bouts of exercise in the heat enhances performance during the second exercise session . Using a r and om , crossover design , 15 subjects ( 3 women , 12 men ; 28 ± 2 years , 180 ± 2 cm , 69 ± 2.3 kg ) participated in all 3 trials . Subjects ran 90 minutes on hilly trails in a hot environment ( approximately 278C ) before 12 minutes of either cold water immersion ( CWI ; 13.98 ° C ) , ice water immersion ( IWI ; 5.23 ° C ) , or a mock treatment ( MT ) of sitting in a tub with no water ( 29.50 ° C ) . After immersion , subjects ran a 2-mile race . CWI had faster ( p < 0.05 ) performance time ( 725 seconds ) than MT ( 769 seconds ) . CWI and IWI had significantly ( p < 0.05 ) lower rectal temperatures postimmersion than MT as well as postrace ( p < 0.05 ) . Heart rate also remained significantly lower ( p < 0.05 ) during the CWI and IWI trials for the first half of the race . In conclusion , CWI enhances performance ( 6 % improvement in race time ) in the second bout of exercise , supporting its potential role as an ergogenic aid in athletic performance |
10,521 | 30,124,517 | Recent findings Focal therapy reduces the rate of cancer progression and conversion to radical therapy in men on active surveillance for prostate cancer .
Although long-term oncological outcomes remain lacking , focal therapy has a low complication rate , minimal impact on urinary continence and a moderate impact on erectile function .
Summary With the appropriate expertise in imaging , targeted biopsy and targeted ablation , focal therapy is a good option in men with low – intermediate risk cancer who are willing to maximize their urinary and sexual function . | Purpose of review Prostate focal therapy has the potential to preserve urinary and sexual function while eliminating clinical ly significant cancer in a subset of men with low-volume , organ-confined prostate cancer .
This systematic review aims to examine current evidence to determine the efficacy and safety of focal therapy for st and ard clinical application .
As a strategy , success in focal therapy is heavily dependent on the use of imaging and targeted biopsies .
Despite advances in these areas , there remains a small but significant risk of under-detecting clinical ly significant cancer .
Similarly , under-estimation of tumor volume may contribute to infield recurrences and close attention must be paid to the ablation margin . | 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 . ) Background : Contemporary screening for prostate cancer frequently identifies small volume , low- grade lesions . Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions . To identify which patients might benefit from focal ablative techniques , we analysed the surgical specimens of a large sample of population -detected men undergoing radical prostatectomy as part of a r and omised clinical trial . Methods : Surgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume , location and grade . These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately . Results : Solitary cancers were found in prostatectomy specimens from 19 % ( 100 out of 525 ) of men . In addition , 73 out of 425 ( 17 % ) men had multiple cancers with a solitary significant tumour focus . Thus , 173 out of 525 ( 33 % ) men had tumours potentially suitable for focal therapy . The majority of these were small , well-differentiated lesions that appeared to be pathologically insignificant ( 38–66 % ) . Criteria used to select patients for focal prostatic ablation underestimated the cancer 's significance in 26 % ( 34 out of 130 ) of men and result ed in overtreatment in more than half . Only 18 % ( 24 out of 130 ) of men presumed eligible for focal therapy , actually had significant solitary lesions . Conclusion : Focal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer . Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone . Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression INTRODUCTION Focal therapy for localized prostate cancer has the potential for oncological control without the side effects of radical therapies . However , there is currently no vali date d method for monitoring treatment success . We assessed the diagnostic performance of prostate-specific antigen ( PSA ) parameters and MRI compared to histological outcomes following focal therapy . PATIENTS AND METHODS Patients from 3 Ethics Review Board approved prospect i ve studies of focal high intensity-focused ultrasound ( HIFU ) ( Sonablate 500 ) for localized prostate cancer ( T1c-T3a , Gleason grade ≤4 + 3 , and PSA≤20 ) . Post-HIFU PSA nadir , 6-month PSA , PSA density , and early ( < 3wk ) and late ( 6mo ) MRI ( T2-weighted , dynamic contrast-enhanced±diffusion-weighted ) was assessed for predictive accuracy of cancer on postoperative biopsy , using receiver operating characteristic ( ROC ) analysis and sensitivity , specificity , and positive and negative predictive estimates . ROC areas for MRI and PSA were compared . Calculations for statistical significance ( P≤0.05 ) were obtained in a subset of patients comparing area under ROC for 6-month MRI and PSA criteria , across 4 different histological definitions of disease significance . RESULTS Of 118 men , 111 underwent at least 1 postoperative biopsy ( median 6 cores ) , with an overall positive biopsy rate of 37 % ( 41/118 ) , over a mean follow-up period of 716 days post-HIFU . Areas under ROC for early and late MRI were ( depending on definition of significant disease ) 0.65 to 0.76 and 0.77 to 0.85 , respectively , with sensitivity , specificity , and negative predictive values of 68 % to 91 % , 52 % to 55 % , and 85 % to 98 % ( early MRI ) , and 63 % to 80 % , 67 % to 73 % , and 86 % to 97 % ( late MRI ) . The area under the ROC curve was statistically significantly higher for late MRI than 6 months and nadir PSA for residual disease > 3 mm or any Gleason 4 tumor . CONCLUSIONS Early and late MRI performed better than PSA measurements in the detection of residual tumor after focal therapy Purpose The design , conduct and completion of r and omized trials for curative prostate cancer ( PCa ) treatments are challenging . To evaluate the effect of robot-assisted radical prostatectomy ( RARP ) versus focal irreversible electroporation ( IRE ) on patient-reported quality of life ( QoL ) and early oncological control using propensity-scored matching . Methods Patients with T1c – cT2b significant PCa ( high-volume ISUP 1 or any 2/3 ) who received unifocal IRE were pair-matched to patients who received nerve-sparing RARP . Patient-reported outcomes were prospect ively assessed using the Exp and ed Prostate Cancer Index Composite ( EPIC ) , AUA symptom score and Short Form of Health Survey ( SF-12 ) physical and mental components . Oncological failure was defined as biochemical recurrence ( RARP ) or positive follow-up biopsies ( IRE ) . Generalized mixed-effect models were used to compare IRE and RARP . Results 50 IRE patients were matched to 50 RARP patients by propensity score . IRE was significantly superior to RARP in preserving pad-free continence ( UC ) and erections sufficient for intercourse ( ESI ) . The absolute differences were 44 , 21 , 13 , 14 % for UC and 32 , 46 , 27 , 22 % for ESI at 1.5 , 3 , 6 , and 12 months , respectively . The EPIC summary scores showed no statistically significant differences . Urinary symptoms were reduced for IRE and RARP patients at 12 months , although IRE patient initially had more complaints . IRE patients experienced more early oncological failure than RARP patients . Conclusions These data demonstrated the superior preservation of UC and ESI with IRE compared to RARP up to 12 months after treatment . Long-term oncological data are warranted to provide ultimate proof for or against focal therapy Purpose : We evaluated focal therapy with high intensity focused ultrasound hemiablation in a prospect i ve trial . Material s and Methods : We performed a prospect i ve , multicenter , single arm study in patients with unilateral low/intermediate risk prostate cancer who were treated from April 2013 through March 2016 in Germany in AUO ( Arbeitsgemeinschaft Urologische Onkologie ) Study Protocol AP 68/11 . Unilateral prostate cancer was assessed by transrectal ultrasound guided biopsy and multiparametric magnetic resonance imaging . Hemiablation was done using the Ablatherm ® or the Focal One ® device . The oncologic outcome was assessed by the salvage treatment rate , multiparametric magnetic resonance imaging and rebiopsy at 12 months . Functional outcome , quality of life , anxiety and depression were measured by vali date d question naires at baseline and every 3 months . Results : Of the 54 recruited patients 51 completed 12‐month or greater visits . Mean ± SD followup was 17.4 ± 4.5 months . Mean prostate specific antigen decreased from 6.2 ± 2.0 to 2.9 ± 1.9 ng/ml at 12 months ( p < 0.001 ) . Biopsy at 12 months was positive for any prostate cancer and for clinical ly significant prostate cancer in 13 ( 26.5 % ) and 4 ( 8.2 % ) of the 49 patients , respectively . Posttreatment multiparametric magnetic resonance imaging had limited 25 % sensitivity for clinical ly significant prostate cancer . Ten patients ( 19.6 % ) underwent salvage treatment . Potency was maintained in 21 of the 30 men who were potent preoperatively . There was no increase in incontinence . Quality of life , anxiety and depression did not change postoperatively . The study was limited by a short followup and the lack of a control arm . Conclusions : Focal therapy hemiablation is safe with little alteration of functional outcome . The oncologic outcome is acceptable on short‐term followup . Followup multiparametric magnetic resonance imaging performed poorly and should not replace repeat biopsy . Focal therapy has no impact on posttreatment anxiety and depression Purpose To report the safety profile and 2-year functional outcomes of in-bore magnetic resonance (MR)-guided focused ultrasound on single cancer foci in men with prostate cancer . Material s and Methods Ethics approval was obtained from the central ized institutional review board for this prospect i ve single-arm study , and patients provided informed consent . Patients with untreated low-volume low- grade prostate cancer ( clinical stage T2a or lower ; Gleason score , 3 + 3 ; index tumor ≤10 mm3 ) underwent MR-guided focused ultrasound between July 2011 and February 2013 . All patients underwent robotic transperineal mapping biopsy and multiparametric MR imaging . Only those with a maximum of two lesions smaller than 10 mm at mapping biopsy were included . Target areas were sonicated with real-time MR thermometry monitoring , excluding critical areas from the beam path . Serum prostate-specific antigen ( PSA ) and Exp and ed Prostate Index Composite ( EPIC ) scores were obtained at baseline and at 1 , 3 , 6 , 12 , 18 , and 24 months and were plotted to observe their trend . Mean EPIC subdomain score changes at each serial time point were compared with the baseline score by using paired t tests ( level of significance , P < .007 ) . Repeat transperineal biopsy was performed at 6 and 24 months . Results Fourteen men ( mean age , 62.8 years ; median PSA level , 8.3 ng/mL ) underwent treatment , with 12 men completing 2-year follow-up . A median reduction of PSA level by 2.9 ng/mL was observed at 6 months . Seven men had Clavien-Dindo grade 1 - 2 complications . There was a slight insignificant deterioration of EPIC urinary symptom score ( mean increase of 7.8 points compared with baseline , P = .012 ) noted at 1 month , but it returned to baseline by 3 months . There was a trend to deterioration in sexual function score ( mean decrease , 4.4 points ; P = .04 [ not significant ] ) that normalized at 3 months . There was no significant change in EPIC subdomain scores from baseline over the 24 months . At 6-month template biopsy , one man had cancer with a Gleason score greater than 6 ; at 24 months , three men had cancer with a Gleason score greater than 6 . Conclusion MR-guided focused ultrasound is technically feasible for focal prostate ablation and appears to have a favorable early safety and functional profile . Further clinical trials are necessary to establish oncologic efficacy . © RSNA , 2017 Online supplemental material is available for this article BACKGROUND In selected patients with unilateral , organ-confined prostate cancer ( PCa ) , hemiablation of the affected lobe might be feasible to achieve acceptable cancer control with fewer complications . OBJECTIVES To assess the oncologic and functional outcomes of focal high-intensity focused ultrasound ( HIFU ) hemiablation in unilateral organ-confined PCa . DESIGN , SETTING AND PATIENTS Single-center prospect i ve evaluation of HIFU hemiablation for unilateral organ-confined PCa was performed from July 2009 through December 2013 . INTERVENTION Cancer localization was done with transrectal ultrasound-guided biopsy and multiparametric magnetic resonance imaging followed by HIFU hemiablation . OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS Oncologic outcomes were analyzed with control biopsies and prostate-specific antigen ( PSA ) measurement . Functional outcomes were assessed with vali date d question naires for genitourinary symptoms . RESULTS AND LIMITATIONS Of 71 HIFU hemiablation patients , 67 completed the study protocol . The mean age was 70.2 yr ( st and ard deviation : 6.8 yr ) , and median PSA was 6.1 ng/ml ( interquartile range [ IQR ] : 1.6 - 15.5 ng/ml ) . Median maximum cancer-core length was 3 mm ( IQR : 2 - 10 mm ) , and total cancer length was 6.5 mm ( IQR : 2 - 24 mm ) . Gleason score was 6 ( 3 + 3 ) in 58 patients ( 86.6 % ) and 7 ( 3 + 4 ) in 9 patients ( 13.4 % ) . Median follow-up was 12 mo ( IQR : 6 - 50 mo ) , and at 12 mo , 56 of 67 patients had a negative control biopsy in the treated lobe . At 3 mo , all patients were continent , and potency was maintained in 11 of 21 preoperatively potent patients ( confidence interval , 0.18 - 0.69 ) . Complications included 8 % Clavien-Dindo grade 2 and 2.8 % grade 3 events . CONCLUSIONS Focal HIFU hemiablation appears to achieve acceptable oncologic outcomes with low morbidity and minimal functional changes . Longer follow-up will establish future considerations . PATIENT SUMMARY This study showed that high-intensity focused ultrasound hemiablation in selected patients with unilateral organ-confined prostate cancer can be used for satisfactory cancer control with minimal effect on genitourinary functions Purpose : Focal laser ablation is a potential treatment in some men with prostate cancer . Currently focal laser ablation is performed by radiologists in a magnetic resonance imaging unit ( in bore ) . We evaluated the safety and feasibility of performing focal laser ablation in a urology clinic ( out of bore ) using magnetic resonance imaging‐ultrasound fusion for guidance . Material s and Methods : A total of 11 men with intermediate risk prostate cancer were enrolled in this prospect i ve , institutional review board approved pilot study . Magnetic resonance imaging‐ultrasound fusion was used to guide laser fibers transrectally into regions of interest harboring intermediate risk prostate cancer . Thermal probes were inserted for real‐time monitoring of intraprostatic temperatures during laser activation . Multiparametric magnetic resonance imaging ( 3 Tesla ) was done immediately after treatment and at 6 months along with comprehensive fusion biopsy . Results : Ten of 11 patients were successfully treated while under local anesthesia . Mean procedure time was 95 minutes ( range 71 to 105 ) . Posttreatment magnetic resonance imaging revealed a confined zone of nonperfusion in all 10 men . Mean zone volume was 4.3 cc ( range 2.1 to 6.0 ) . No CTCAE grade 3 or greater adverse events developed and no changes were observed in urinary or sexual function . At 6 months magnetic resonance imaging‐ultrasound fusion biopsy of the treatment site showed no cancer in 3 patients , microfocal Gleason 3 + 3 in another 3 and persistent intermediate risk prostate cancer in 4 . Conclusions : Focal laser ablation of prostate cancer appears safe and feasible with the patient under local anesthesia in a urology clinic using magnetic resonance imaging‐ultrasound fusion for guidance and thermal probes for monitoring . Further development is necessary to refine out of bore focal laser ablation and additional studies are needed to determine appropriate treatment margins and oncologic efficacy PURPOSE We ascertained the feasibility and safety of image guided targeted photothermal focal therapy for localized prostate cancer . MATERIAL S AND METHODS Twelve patients with biopsy proven low risk prostate cancer underwent interstitial photothermal ablation of the cancer . The area of interest was confirmed and targeted using magnetic resonance imaging . Three-dimensional ultrasound was used to guide a laser to the magnetic resonance to ultrasound fused area of interest . Target ablation was monitored using thermal sensors and real-time Definity contrast enhanced ultrasound . Followup was performed with a combination of magnetic resonance imaging and prostate biopsy . Vali date d quality of life question naires were used to assess the effect on voiding symptoms and erectile function , and adverse events were solicited and recorded . RESULTS Interstitial photothermal focal therapy was technically feasible to perform . Of the patients 75 % were discharged home free from catheter the same day with the remainder discharged home the following day . The treatment created an identifiable hypovascular defect which coincided with the targeted prostatic lesion . There were no perioperative complications and minimal morbidity . All patients who were potent before the procedure maintained potency after the procedure . Continence levels were not compromised . Based on multicore total prostate biopsy at 6 months 67 % of patients were free of tumor in the targeted area and 50 % were free of disease . CONCLUSIONS Image guided focal photothermal ablation of low risk and low volume prostate cancer is feasible . Early clinical , histological and magnetic resonance imaging responses suggest that the targeted region can be ablated with minimal adverse effects . It may represent an alternate treatment approach to observation or delayed st and ard therapy in carefully selected patients . Further trials are required to demonstrate the effectiveness of this treatment concept PURPOSE To evaluate the long-term efficacy of prostate cancer control and complication rates , in the elderly , after focal therapy with high-intensity focused ultrasound ( HIFU ) . MATERIAL S AND METHODS Between June 1997 and March 2000 , patients with localized prostate cancer were included into a focal therapy protocol . Inclusion criteria were : PSA ≤ 10 ng/mL , ≤ 3 positive biopsies with only 1 lobe involved , clinical stage ≤ T2a , Gleason score ≤ 7 ( 3 + 4 ) , negative CT scan and bone scan . Hemi-ablation of the prostate was performed with the Ablatherm ® device . Survival , complication rates and urinary continence were evaluated . Control biopsies were performed at 1 year . Treatment failure was defined as a positive biopsy or need for salvage therapy . RESULTS Twelve patients with a mean age 70 years were included . Median follow-up was 10 years . Control prostate biopsies were negative in 11/12 ( 91 % ) patients . Overall survival was 83 % ( 10/12 ) and cancer specific survival was 100 % at 10 years . Two patients died from other causes . Recurrence free survival was 90 % ( 95 % CI ; 0.71 - 1 ) at 5 years , and 38 % ( 95 % CI ; 0.04 - 0.73 ) at 10 years . Five patients had salvage therapy with repeat HIFU ( n = 1 ) or hormonal therapy ( n = 4 ) and all salvage patients were alive at 10 years . No patients developed lymph node or bone metastasis . No patients suffered from urinary incontinence . International Prostate Symptom Score was stable at 1 year . Complications included two urinary tract infections and one episode of acute urinary retention . CONCLUSIONS Hemi-prostate ablation with HIFU can be safely performed in selected elderly patients with adequate long-term cancer control and low complication rates . Results from larger prospect i ve studies using improved imaging techniques and extensive biopsy protocol s are awaited PURPOSE The biology of prostate cancer may be influenced by the index lesion . The definition of index lesion volume is important for appropriate decision making , especially for image guided focal treatment . We determined the accuracy of magnetic resonance imaging for determining index tumor volume compared with volumes derived from histopathology . MATERIAL S AND METHODS We evaluated 135 patients ( mean age 59.3 years ) with a mean prostate specific antigen of 6.74 ng/dl who underwent multiparametric 3 T endorectal coil magnetic resonance imaging of the prostate and subsequent radical prostatectomy . Index tumor volume was determined prospect ively and independently by magnetic resonance imaging and histopathology . The ellipsoid formula was applied to determine histopathology tumor volume , whereas manual tumor segmentation was used to determine magnetic resonance tumor volume . Histopathology tumor volume was correlated with age and prostate specific antigen whereas magnetic resonance tumor volume involved Pearson correlation and linear regression methods . In addition , the predictive power of magnetic resonance tumor volume , prostate specific antigen and age for estimating histopathology tumor volume ( greater than 0.5 cm(3 ) ) was assessed by ROC analysis . The same analysis was also conducted for the 1.15 shrinkage factor corrected histopathology data set . RESULTS There was a positive correlation between histopathology tumor volume and magnetic resonance tumor volume ( Pearson coefficient 0.633 , p < 0.0001 ) , but a weak correlation between prostate specific antigen and histopathology tumor volume ( Pearson coefficient 0.237 , p = 0.003 ) . On linear regression analysis histopathology tumor volume and magnetic resonance tumor volume were correlated ( r(2 ) = 0.401 , p < 0.00001 ) . On ROC analysis AUC values for magnetic resonance tumor volume , prostate specific antigen and age in estimating tumors larger than 0.5 cm(3 ) at histopathology were 0.949 ( p < 0.0000001 ) , 0.685 ( p = 0.001 ) and 0.627 ( p = 0.02 ) , respectively . Similar results were found in the analysis with shrinkage factor corrected tumor volumes at histopathology . CONCLUSIONS Magnetic resonance imaging can accurately estimate index tumor volume as determined by histology . Magnetic resonance imaging has better accuracy in predicting histopathology tumor volume in tumors larger than 0.5 cm(3 ) than prostate specific antigen and age . Index tumor volume as determined by magnetic resonance imaging may be helpful in planning treatment , specifically in identifying tumor margins for image guided focal therapy and possibly selecting better active surveillance c and i date PURPOSE To assess long-term outcomes of men with favorable-risk prostate cancer in a prospect i ve , active-surveillance program . METHODS Curative intervention was recommended for disease reclassification to higher cancer grade or volume on prostate biopsy . Primary outcomes were overall , cancer-specific , and metastasis-free survival . Secondary outcomes were the cumulative incidence of reclassification and curative intervention . Factors associated with grade reclassification and curative intervention were evaluated in a Cox proportional hazards model . RESULTS A total of 1,298 men ( median age , 66 years ) with a median follow-up of 5 years ( range , 0.01 to 18.00 years ) contributed 6,766 person-years of follow-up since 1995 . Overall , cancer-specific , and metastasis-free survival rates were 93 % , 99.9 % , and 99.4 % , respectively , at 10 years and 69 % , 99.9 % , and 99.4 % , respectively , at 15 years . The cumulative incidence of grade reclassification was 26 % at 10 years and was 31 % at 15 years ; cumulative incidence of curative intervention was 50 % at 10 years and was 57 % at 15 years . The median treatment-free survival was 8.5 years ( range , 0.01 to 18 years ) . Factors associated with grade reclassification were older age ( hazard ratio [ HR ] , 1.03 for each additional year ; 95 % CI , 1.01 to 1.06 ) , prostate-specific antigen density ( HR , 1.21 per 0.1 unit increase ; 95 % CI , 1.12 to 1.46 ) , and greater number of positive biopsy cores ( HR , 1.47 for each additional positive core ; 95 % CI , 1.26 to 1.69 ) . Factors associated with intervention were prostate-specific antigen density ( HR , 1.38 per 0.1 unit increase ; 95 % CI , 1.22 to 1.56 ) and a greater number of positive biopsy cores ( HR , 1.35 for one additional positive core ; 95 % CI , 1.19 to 1.53 ) . CONCLUSION Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention PURPOSE Patients currently diagnosed with low risk prostate cancer are often overtreated and experience complications , result ing in detriment to quality of life . Targeted focal therapy is a minimally invasive procedure design ed to ablate tumor foci while minimizing collateral damage to maintain quality of life . MATERIAL S AND METHODS This institutional review board approved , prospect i ve study was done to assess the safety and efficacy of targeted focal therapy using cryotherapy in men 40 to 85 years old diagnosed with low risk , organ confined prostate cancer at our institution between 2006 and 2009 . Low risk , organ confined prostate cancer was defined as Gleason score 7 or less ( 3 + 4 ) on transrectal ultrasound biopsy , tumor burden 50 % or less and prostate specific antigen less than 10 ng/dl . Patients were evaluated for eligibility after undergoing 3-dimensional mapping biopsy . Median followup was 28 months ( IQR 26 - 31 ) . RESULTS A total of 62 men with low risk disease met study inclusion criteria . At 1 year biopsy was negative in 50 of 62 patients ( 81 % ) . All 12 men who tested positive on repeat biopsy had a Gleason score of 3 + 3 = 6 with 1 or 2 positive cores . The median prostate specific antigen change was a 3.0 ng/dl decrease ( p < 0.01 ) . The median American Urological Association symptom score change was a 1.5-point decrease ( p < 0.01 ) . No significant change was observed in Sexual Health Inventory for Men score ( p = 0.6 ) . No urinary incontinence episodes and no severe side effects were noted . CONCLUSIONS Targeted focal therapy in carefully selected patients provides a feasible , practical option for treating low risk prostate cancer with minimal impact on quality of life Background : Focal therapy is an emerging mini-invasive treatment modality for localized prostate cancer aim ed to reduce the morbidity associated with radical therapy while maintaining optimal cancer control . We report the mid-term oncological and functional results of primary hemiablation high-intensity focused ultrasound ( HIFU ) in a prospect i ve cohort of patients . Methods : Over 8 years , hemiablation HIFU was primarily performed in 50 selected patients with biopsy-proven clinical ly localized unilateral , low – intermediate risk prostate cancer in complete concordance with the prostate cancer lesions identified by magnetic resonance imaging with precise loci matching on multimodal approach . Post-treatment follow-up included regular serial PSA measurements . Biochemical recurrence was reported using Stuttgart and Phoenix criteria . The latter was used as a threshold to offer whole-gl and biopsies . Results : Complete follow-up was available for all patients and the median follow-up was 39.5 months ( range : 6–94 ) . Mean nadir PSA value was 1.6 ng ml−1 , which represents 72 % reduction compared with initial PSA pre-treatment value ( P<0.001 ) . Median time to achieve PSA nadir was 3 months . Biochemical recurrence , according to Phoenix and Stuttgart definition , occurred in 28 and 36 % of patients , respectively . The 5-year actuarial metastases-free survival , cancer-specific survival and overall survival rates were 93 , 100 and 87 % , respectively . Out of the eight patients undergoing biopsy , six patients had a positive biopsy for cancer occurring in the untreated contralateral ( n=3 ) or treated ipsilateral lobe ( n=1 ) or bilaterally ( n=2 ) . A Clavien – Dindo grade 3b complication occurred in two patients . Complete continence ( no pads ) and erection sufficient for intercourse were documented in 94 or 80 % of patients , respectively . Conclusion : Hemiablation HIFU therapy , delivered with intention to treat , for carefully selected patients affords mid-term promising functional and oncological outcomes . The effectiveness of this technique should be now compared with whole-gl and radical therapy BACKGROUND The use of breast sparing surgery , i.e. , " lumpectomy " , revolutionized management of breast cancer . Lumpectomy confirmed that quality of life issues can successfully be addressed without compromising treatment efficacy . Complications of prostate cancer treatment , including impotence and incontinence , affect the male self image no less than the loss of a breast does a woman . Traditional thinking held that prostate cancer was multifocal and therefore not amenable to a focal treatment approach . Recent pathology literature indicates , however , that up to 25 % of prostate cancers are solitary and unilateral . This raises the question of whether these patients can be identified and treated with a limited " lumpectomy " or focal cancer treatment . METHODS Focal cryoablation was planned to encompass the area of known tumor based on staging biopsies . PSAs were obtained every 3 months for 2 years and then every 6 months thereafter . RESULTS Forty-eight patients with at least 2-year follow-up had focal cryoablation . Follow-up ranged from 2 years 10 years with a mean of 4.5 years ; 45 of 48 patients ( 94 % ) have stable PSAs [ American Society of Therapeutic Radiology and Oncology ( ASTRO ) criteria ] with no evidence for cancer , despite 25 patients being medium to high risk for recurrence . Of the 24 patients with stable PSAs who were routinely biopsied ( n = 24 ) all were negative . No local recurrences were noted in areas treated . Potency was maintained to the satisfaction of the patient in of 36 of 40 patients who were potent preoperatively . Of the 48 , all were continent . CONCLUSION These preliminary results indicate a " male lumpectomy " in which the prostate tumor region itself is destroyed , appears to preserve potency in a majority of patients and limits other complications ( particularly incontinence ) , without compromising cancer control . If confirmed by further studies and long-term follow-up , this treatment approach could have a profound effect on prostate cancer management To assess oncological ( biochemical and histological recurrence ) and functional ( urinary and potency ) outcomes in patients with unilateral low‐risk organ‐confined prostate cancer ( PCa ) treated with focal cryoablation ( FC ) Purpose : Irreversible electroporation has attractive attributes for focal ablation , namely nonthermal effect , precise demarcation of treatment and tissue selectivity . We report a prospect i ve development study investigating focal irreversible electroporation . Material s and Methods : A total of 20 men with certain characteristics were recruited for study , including a visible index lesion on anterior magnetic resonance imaging that was concordant with transperineal targeted and template prostate mapping biopsy , absent clinical ly significant disease noted elsewhere ( University College London definition 2 ) and prostate specific antigen 15 ng/ml or less . Our primary objective was to determine the side effect profile at 12 months . Secondary objectives included the domain specific toxicity profile using patient reported outcomes and early disease control using magnetic resonance imaging targeted biopsy . Results : A total of 19 patients with median age of 60 years ( IQR 53–66 ) and median prostate specific antigen 7.75 ng/ml ( IQR 5.5–10.03 ) were treated . Of the patients 16 were available for estimating the first outcome as 1 was lost to followup and 2 had received another form of treatment by study end . All 16 men had pad‐free/leak‐free continence at 12 months . The proportion of men with erection sufficient for penetration decreased from 12 of 16 ( 75 % ) to 11 of 16 ( 69 % ) . No serious adverse events were recorded . There was a statistically significant improvement in urinary symptoms according to changes in UCLA‐EPIC ( UCLA Exp and ed Prostate Cancer Index Composite ) and I‐PSS ( International Prostate Symptom Score ) ( p = 0.039 and 0.001 , respectively ) . Erectile function remained stable according to the change in IIEF‐15 ( 15‐Item International Index of Erectile Function ) ( p = 0.572 ) . Median prostate specific antigen significantly decreased to 1.71 ng/ml ( p = 0.001 ) . One man refused followup biopsy . No residual disease was found in 11 patients ( 61.1 % ) . One man ( 5.6 % ) harbored clinical ly insignificant disease and the remaining 6 ( 33.3 % ) harbored clinical ly significant disease . Conclusions : Focal irreversible electroporation has low genitourinary toxicity . Additional studies are needed to optimize patient selection and treatment parameters To determine the safety , quality of life ( QoL ) and short‐term oncological outcomes of primary focal irreversible electroporation ( IRE ) for the treatment of localized prostate cancer ( PCa ) , and to identify potential risk factors for oncological failure PURPOSE Magnetic resonance imaging guided focal laser ablation is an investigational strategy for the treatment of prostate cancer . MATERIAL S AND METHODS This phase II evaluation of focal laser ablation included men with stage T1c-T2a , prostate specific antigen less than 15 ng/ml or prostate specific antigen density less than 0.15 ng/ml3 , Gleason 7 or less in 25 % or less of biopsies and magnetic resonance imaging with 1 or 2 lesions concordant with biopsy detected cancer . At 3 months all patients underwent magnetic resonance imaging with biopsy of ablation zone(s ) . At 12 months all underwent magnetic resonance imaging and systematic biopsy . I-PSS ( International Prostate Symptom Score ) and SHIM ( Sexual Health Inventory for Men ) scores were collected before focal laser ablation , and at 1 , 3 and 12 months . The primary end point was no cancer on the 3-month ablation zone biopsy . Secondary end points were safety , 12-month biopsy , and urinary and sexual function . RESULTS In the 27 men median age was 62 years and mean prostate specific antigen was 4.4 ng/ml . Biopsy Gleason score was 6 in 23 patients ( 85 % ) and Gleason 7 in 4 ( 15 % ) . Seven men ( 26 % ) had low volume Gleason 6 disease outside the intended ablation zone(s ) . At 3 months 26 patients ( 96 % ) had no evidence of cancer on magnetic resonance imaging guided biopsy of the ablation zone . No significant I-PSS changes were observed ( each p > 0.05 ) . SHIM was lower at 1 month ( p = 0.03 ) , marginally lower at 3 months ( p = 0.05 ) and without a significant difference at 12 months ( p = 0.38 ) . At 12-month biopsy cancer was identified in 10 patients ( 37 % ) , including in the ablation zone(s ) in 3 ( 11 % ) and outside the ablation zone(s ) in 8 ( 30 % ) with cancer in and outside the ablation zone in 1 . CONCLUSIONS In select men with localized prostate cancer and visible magnetic resonance imaging lesions focal laser ablation has an acceptable morbidity profile and is associated with encouraging short-term oncologic outcomes . Significantly longer followup is m and atory to fully assess this novel treatment OBJECTIVE The purpose of this study is to investigate the accuracy of multiparametric MRI with endorectal coil and Partin tables in predicting organ-confined ( OC ) prostate cancer in a contemporary cohort undergoing radical prostatectomy ( RP ) and to assess the possible added value of radiologic staging based on multiparametric MRI to the predictive accuracy of Partin tables . MATERIAL S AND METHODS One hundred fifty-eight consecutive subjects underwent 3-T multiparametric MRI with endorectal coil before RP between November 2010 and November 2013 . Data were r and omly split 60 % and 40 % into derivation ( n = 95 ) and validation ( n = 62 ) data sets . Multiparametric MRI was used to assess the radiologic stage , and logistic regression models were created using the derivation data set and were fit on the independent validation data set using multiparametric MRI staging alone and with prostate-specific antigen ( PSA ) level as the covariate . The probability of each patient to harbor OC disease was calculated using an up date d version of Partin tables , using either clinical staging from digital rectal examination ( DRE ) or radiologic staging ( multiparametric MRI ) . The AUC was calculated to evaluate accuracy of these predictive methods . RESULTS The accuracy of multiparametric MRI to predict OC disease on pathologic analysis was greater ( AUC , 0.88 ) than that of Partin tables ( AUC , 0.70 ) and improved when multiparametric MRI was combined with PSA level ( AUC , 0.91 ) . The accuracy of Partin nomograms to predict OC disease decreased ( AUC , 0.63 ) when staging was based on multiparametric MRI versus DRE . CONCLUSION The superior predictive accuracy of multiparametric MRI compared with Partin tables to predict OC disease vali date s the results of smaller previously published studies . Although there is no added benefit of substituting multiparametric MRI stage for clinical stage when using Partin tables , multiparametric MRI staging information is valuable as a st and -alone test PURPOSE Active surveillance is increasingly accepted as a treatment option for favorable-risk prostate cancer . Long-term follow-up has been lacking . In this study , we report the long-term outcome of a large active surveillance protocol in men with favorable-risk prostate cancer . PATIENTS AND METHODS In a prospect i ve single-arm cohort study carried out at a single academic health sciences center , 993 men with favorable- or intermediate-risk prostate cancer were managed with an initial expectant approach . Intervention was offered for a prostate-specific antigen ( PSA ) doubling time of less than 3 years , Gleason score progression , or unequivocal clinical progression . Main outcome measures were overall and disease-specific survival , rate of treatment , and PSA failure rate in the treated patients . RESULTS Among the 819 survivors , the median follow-up time from the first biopsy is 6.4 years ( range , 0.2 to 19.8 years ) . One hundred forty-nine ( 15 % ) of 993 patients died , and 844 patients are alive ( censored rate , 85.0 % ) . There were 15 deaths ( 1.5 % ) from prostate cancer . The 10- and 15-year actuarial cause-specific survival rates were 98.1 % and 94.3 % , respectively . An additional 13 patients ( 1.3 % ) developed metastatic disease and are alive with confirmed metastases ( n = 9 ) or have died of other causes ( n = 4 ) . At 5 , 10 , and 15 years , 75.7 % , 63.5 % , and 55.0 % of patients remained untreated and on surveillance . The cumulative hazard ratio for nonprostate-to-prostate cancer mortality was 9.2:1 . CONCLUSION Active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame . In our cohort , 2.8 % of patients have developed metastatic disease , and 1.5 % have died of prostate cancer . This mortality rate is consistent with expected mortality in favorable-risk patients managed with initial definitive intervention PURPOSE We assessed the outcome of a watchful-waiting protocol with selective delayed intervention by using clinical prostate-specific antigen ( PSA ) , or histologic progression as treatment indications for clinical ly localized prostate cancer . PATIENTS AND METHODS This was a prospect i ve , single-arm , cohort study . Patients were managed with an initial expectant approach . Definitive intervention was offered to those patients with a PSA doubling time of less than 3 years , Gleason score progression ( to 4 + 3 or greater ) , or unequivocal clinical progression . Survival analysis and Cox proportional hazard model were applied to the data . Results A total of 450 patients have been observed with active surveillance . Median follow-up was 6.8 years ( range , 1 to 13 years ) . Overall survival was 78.6 % . The 10-year prostate cancer actuarial survival was 97.2 % . Overall , 30 % of patients have been reclassified as higher risk and have been offered definitive therapy . Of 117 patients treated radically , the PSA failure rate was 50 % , which was 13 % of the total cohort . PSA doubling time of 3 years or less was associated with an 8.5-times higher risk of biochemical failure after definitive treatment compared with a doubling time of more than 3 years ( P < .0001 ) . The hazard ratio for nonprostate cancer to prostate cancer mortality was 18.6 at 10 years . CONCLUSION We observed a low rate of prostate cancer mortality . Among the patients who were reclassified as higher risk and who were treated , PSA failure was relatively common . Other-cause mortality accounted for almost all of the deaths . Additional studies are warranted to improve the identification of patients who harbor more aggressive disease despite favorable clinical parameters at diagnosis Purpose : The prospect i ve PCM301 trial r and omized 413 men with low risk prostate cancer to partial gl and ablation with vascular targeted photodynamic therapy in 207 and active surveillance in 206 . Two‐year outcomes were reported previously . We report 4‐year rates of intervention with radical therapy and further assess efficacy with biopsy results . Material s and Methods : Prostate biopsies were m and ated at 12 and 24 months . Thereafter patients were monitored for radical therapy with periodic biopsies performed according to the st and ard of care at each institution . Ablation efficacy was assessed by biopsy results overall and in field in the treated lobe or the lobe with index cancer . Results : Conversion to radical therapy was less likely in the ablation cohort than in the surveillance cohort , including 7 % vs 32 % at 2 years , 15 % vs 44 % at 3 years and 24 % vs 53 % at 4 years ( HR 0.31 , 95 % CI 0.21–0.46 ) . Radical therapy triggers were similar in the 2 arms . Cancer progression rates overall and by grade were significantly lower in the ablation cohort ( HR 0.42 , 95 % CI 0.29–0.59 ) . End of study biopsy results were negative throughout the prostate in 50 % of patients after ablation vs 14 % after surveillance ( risk difference 36 % , 95 % CI 28–44 ) . Gleason 7 or higher cancer was less likely for ablation than for surveillance ( 16 % vs 41 % ) . Of the in field biopsies 10 % contained Gleason 7 cancer after ablation vs 34 % after surveillance . Conclusions : In this r and omized trial of partial ablation of low risk prostate cancer photodynamic therapy significantly reduced the subsequent finding of higher grade cancer on biopsy . Consequently fewer cases were converted to radical therapy , a clinical ly meaningful benefit that lowered treatment related morbidity BACKGROUND Although localised prostate cancer is multifocal in most instances , the index lesion might be responsible for disease progression . OBJECTIVE To determine the early genitourinary functional and cancer control outcomes of index lesion ablation . DESIGN , SETTING , AND PARTICIPANTS This was a single-centre prospect i ve development study in which 56 men were treated ( July 2009-January 2011 ) . The mean age was 63.9 yr ( st and ard deviation 5.8 ) and median prostate-specific antigen ( PSA ) was 7.4 ng/ml ( interquartile range [ IQR ] 5.6 - 9.5 ) . There were seven ( 12.5 % ) low-risk , 47 ( 83.9 % ) intermediate-risk , and two ( 3.6 % ) high-risk cancers . INTERVENTION Multiparametric magnetic resonance imaging ( mpMRI ) and prostate biopsies to localise disease , followed by index lesion ablation using high-intensity focused ultrasound . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary outcomes were genitourinary side effects measured using vali date d question naires . Secondary outcomes included absence of clinical ly significant disease at 12 mo . RESULTS AND LIMITATIONS The composite of leak-free , pad-free continence , and erections sufficient for penetration decreased from a baseline frequency of 40/56 ( 71.4 % ) to 33/56 ( 58.9 % ) at 12 mo . Pad-free and leak-free , pad-free continence was preserved in 48/52 ( 92.3 % ) and 46/50 ( 92.0 % ) patients , respectively . Erections sufficient for intercourse were preserved in 30/39 ( 76.9 % ) patients . The median PSA nadir decreased to 2.4 ng/ml ( IQR 1.6 - 4.1 ) . At 12 mo , 42/52 ( 80.8 % ) patients had histological absence of clinical ly significant cancer and 85.7 % ( 48/56 ) had no measurable prostate cancer ( biopsy and /or mpMRI ) . Two ( 3.6 % ) patients had clinical ly significant disease in untreated areas not detected at baseline . The main study limitation is the short follow-up duration . CONCLUSIONS Index lesion ablation had low rates of genitourinary side effects and acceptable short-term absence of clinical ly significant cancer . Comparative effectiveness trials are required to assess cancer control outcomes against radical therapy . PATIENT SUMMARY In this study we looked at whether it is possible to treat the largest and highest- grade tumour in men who have more than one known prostate tumour . We show that the side effects of targeted ablation were low , with acceptable rates of early cancer control . Larger studies with longer follow-up are needed . TRIAL REGISTRATION NCT00988130 BACKGROUND Robust data on patient-reported outcome measures comparing treatments for clinical ly localized prostate cancer are lacking . We investigated the effects of active monitoring , radical prostatectomy , and radical radiotherapy with hormones on patient-reported outcomes . METHODS We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment ( ProtecT ) trial who completed question naires before diagnosis , at 6 and 12 months after r and omization , and annually thereafter . Patients completed vali date d measures that assessed urinary , bowel , and sexual function and specific effects on quality of life , anxiety and depression , and general health . Cancer-related quality of life was assessed at 5 years . Complete 6-year data were analyzed according to the intention-to-treat principle . RESULTS The rate of question naire completion during follow-up was higher than 85 % for most measures . Of the three treatments , prostatectomy had the greatest negative effect on sexual function and urinary continence , and although there was some recovery , these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial . The negative effect of radiotherapy on sexual function was greatest at 6 months , but sexual function then recovered somewhat and was stable thereafter ; radiotherapy had little effect on urinary continence . Sexual and urinary function declined gradually in the active-monitoring group . Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat , except for the increasing frequency of bloody stools ; bowel function was unchanged in the other groups . Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months . Effects on quality of life mirrored the reported changes in function . No significant differences were observed among the groups in measures of anxiety , depression , or general health-related or cancer-related quality of life . CONCLUSIONS In this analysis of patient-reported outcomes after treatment for localized prostate cancer , patterns of severity , recovery , and decline in urinary , bowel , and sexual function and associated quality of life differed among the three groups . ( Funded by the U.K. National Institute for Health Research Health Technology Assessment Program ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) BACKGROUND Up to a third of patients with localized prostate cancer have unilateral disease that may be suitable for partial treatment with hemiablation . OBJECTIVE To evaluate the ability of high intensity focused ultrasound ( HIFU ) to achieve local control of the tumor in patients with unilateral localized prostate cancer . DESIGN , SETTING , AND PARTICIPANTS The French Urological Association initiated a prospect i ve IDEAL multi-institutional study ( 2009 - 2015 ) , to evaluate HIFU-hemiablation as a primary treatment . INTERVENTION Multiparametric magnetic resonance imaging and biopsy were used for unilateral cancer diagnosis and control , and HIFU-hemiablation . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary : absence of clinical ly significant cancer ( CSC ) on control biopsy at 1 yr ( CSC : Gleason score ≥ 7 or cancer core length>3 mm regardless of grade or > 2 positive cores ) . Secondary : presence of any cancer on biopsy , biochemical response , radical treatment free survival , adverse events , continence ( no pad ) , erectile function ( International Index of Erectile Function-5 ≥ 16 ) , and quality of life ( European Organization for Research and Treatment of Cancer QLQ-C28 ) question naires . RESULTS AND LIMITATIONS One hundred and eleven patients were treated ( mean age : 64.8 yr [ st and ard deviation 6.2 ] ; mean prostate-specific antigen : 6.2 ng/ml [ st and ard deviation 2.6 ] ; 68 % low risk , 32 % intermediate risk ) . Of the 101 patients with control biopsy , 96 ( 95 % ) and 94 ( 93 % ) had no CSC in the treated and contralateral lobes , respectively . Mean prostate-specific antigen at 2 yr was 2.3 ng/ml ( st and ard deviation 1.7 ) . The radical treatment-free survival rate at 2 years was 89 % ( radical treatments : six radical prostatectomies , three radiotherapies , and two HIFU ) . Adverse events were Grade 3 in 13 % . At 12 mo continence and erectile functions were preserved in 97 % and 78 % . No significant decrease in quality of life score was observed at 12 mo . One limitation is the number of low-risk patients included in this study . CONCLUSIONS At 1 yr , HIFU-hemiablation was efficient with 95 % absence of clinical ly significant cancer associated with low morbidity and preservation of quality of life . Radical treatment-free survival rate was 89 % at 2 yr . PATIENT SUMMARY This report shows that high intensity focused ultrasound half-gl and treatment of unilateral prostate cancer provides promising results with high cancer control and low morbidity |
10,522 | 28,387,802 | Cardiac cycle length and equivalence were more important than the number of beats averaged .
Conclusion With careful selection of appropriate cardiac cycles , echocardiography is a valid tool to identify diastolic dysfunction in AF , and E/e ' is an independent marker of clinical status and adverse prognosis . | Aims Echocardiography is vital in the routine assessment and management of atrial fibrillation ( AF ) .
We performed a systematic review of the validity and reproducibility of echocardiographic left ventricular systolic and diastolic function in AF , and optimal acquisition methods . | The reproducibility of a variety of Doppler indexes of diastolic function in an epidemiologic setting and in atrial fibrillation have not been reported . This study examined the reproducibility of left ventricular inflow in subjects in sinus rhythm ( n = 80 ) and atrial fibrillation ( n = 12 ) , r and omly selected from the original cohort of the Framingham Heart Study . The following Doppler indexes were assessed for all subjects : peak and integral of early ( E ) diastolic inflow velocity , acceleration slope and time , deceleration slope and time , and pressure half-time . For subjects in sinus rhythm , the following parameters also were measured : the peak and integral of late ( A ) diastolic inflow velocity , ratios of peak velocities and integrals E/A , and atrial filling fraction . Intraobserver and interobserver variability were evaluated by statistical methods including Student 's t test of the systematic differences ( bias ) , percent bias , correlation coefficients , measurement precision , and percent precision . In subjects in sinus rhythm , although the interobserver bias was statistically significant for most of the parameters , it was < 10 % for all but 1 parameter ( acceleration time ) . For the peak and integral measures , the intra- and interobserver correlations were > or = 0.89 , with intra- and interobserver percent precision measures within 2.2 to 13.0 % of the corresponding mean values . The acceleration , deceleration and pressure half-time measures had somewhat lower correlations ( interobserver correlations ranging from 0.59 to 0.96 ) , with percent precision measures further from the corresponding means ( interobserver percent precision ranging from 10.1 to 19.5 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS Background — There is a paucity of international data on the various types of atrial fibrillation ( AF ) outside the highly selected population s from r and omized trials . This study aim ed to describe patient characteristics , risk factors , comorbidities , symptoms , management strategy , and control of different types of AF in real-life practice . Methods and Results — Real-life global survey evaluating patients with atrial fibrillation ( RealiseAF ) was a contemporary , large-scale , cross-sectional international survey of patients with AF who had ≥1 episode in the past 12 months . Investigators were r and omly selected to avoid bias . Among 9816 eligible patients from 831 sites in 26 countries , 2606 ( 26.5 % ) had paroxysmal , 2341 ( 23.8 % ) had persistent , and 4869 ( 49.6 % ) had permanent AF . As AF progressed from paroxysmal to persistent and permanent forms , the prevalence of comorbidities , such as heart failure ( 32.9 % , 44.3 % , and 55.6 % ) , coronary artery disease ( 30.0 % , 32.9 % , and 34.3 % ) , cerebrovascular disease ( 11.7 % , 10.8 % , and 17.6 % ) , and valvular disease ( 16.7 % , 21.2 % , and 35.8 % ) , increased , and the prevalence of lone AF decreased . Similarly , there was an increase in mean CHADS2 [ cardiac failure , hypertension , age , diabetes , stroke ( doubled ) ] score ( 1.7 , 1.8 , and 2.2 ) , and more than half of patients ( 51.0 % , 56.7 % , and 67.3 % ) qualified for oral anticoagulants . Almost 90 % of patients received ≥1 antiarrhythmic drug , but > 60 % had European Heart Rhythm Association symptom scores from II to IV . Furthermore , 40.7 % of persistent and 49.8 % of permanent AF patients were still in AF with a heart rate > 80 beats per minute . Conclusions — This survey disclosed high cardiovascular risks and an unmet need in daily practice for patients with any type of AF , especially those with the permanent form BACKGROUND Doppler echocardiography is frequently used to predict filling pressures in normal sinus rhythm , but it is unknown whether it can be applied in sinus tachycardia , with merging of E and A velocities . Tissue Doppler imaging ( TDI ) can record the mitral annular velocity . The early diastolic velocity ( Ea ) behaves as a relative load-independent index of left ventricular relaxation , which corrects the influence of relaxation on the transmitral E velocity . METHODS AND RESULTS We evaluated 100 patients 64+/-12 years old with simultaneous Doppler and invasive hemodynamics . Mitral inflow was classified into 3 patterns : complete merging of E and A velocities ( pattern A ) , discernible velocities with A dominance ( B ) , or E dominance ( C ) . The Doppler data were analyzed at the mitral valve tips for E , acceleration and deceleration times of E , and isovolumic relaxation time . In patterns B and C , the A velocity , E/A ratio , and atrial filling fraction were derived . Pulmonary venous flow velocities were also measured , and TDI was used to acquire Ea and Aa . Weak significant relations were observed between pulmonary capillary wedge pressure ( PCWP ) and sole parameters of mitral flow , pulmonary venous flow , and annular measurements . These were better for patterns A and C. E/Ea ratio had the strongest relation to PCWP [ r=0.86 , PCWP=1.55 + 1.47(E/Ea ) ] , irrespective of the pattern and ejection fraction . This equation was tested prospect ively in 20 patients with sinus tachycardia . A strong relation was observed between catheter and Doppler PCWP ( r=0.91 ) , with a mean difference of 0.4+/-2.8 mm Hg . CONCLUSIONS The ratio of transmitral E velocity to Ea can be used to estimate PCWP with reasonable accuracy in sinus tachycardia , even with complete merging of E and A velocities Background —Conventional Doppler measurements have limitations in the prediction of left atrial pressure ( LAP ) in patients with mitral valve disease ( MVD ) , given the confounding effect of valve area , left ventricular ( LV ) relaxation , and stiffness . However , the time interval between the onset of early diastolic mitral inflow velocity ( E ) and annular early diastolic velocity ( Ea ) by tissue Doppler imaging ( TDI ) , TE−Ea , which is well related to the time constant of LV relaxation ( & tgr ; ) in canine and clinical studies , is not subject to these variables . We therefore undertook this study to test its usefulness in a patient population . Methods and Results —Two-dimensional Doppler and TDI echocardiography were performed simultaneously with right-heart catheterization in 51 consecutive patients ( mean±SD age , 64±11 years ) with MVD : 35 with moderately severe to severe mitral regurgitation ( MR ) and 16 with moderate to severe mitral stenosis ( MS ) . Among several Doppler measurements , only the mitral E/A ratio , isovolumetric relaxation time ( IVRT ) , and pulmonary venous Ar duration had significant relations with mean pulmonary capillary wedge pressure ( PCWP ) . The ratio of IVRT to TE−Ea ( for MR , r=−0.92 ; for MS , r=−0.88 ; both P<0.001 ) and the ratio of IVRT to & tgr ; ( for MR , r=−0.74 ; for MS , r=−0.85 ; both P<0.001 ) had the best correlations with PCWP . In 54 repeat studies , including those performed after MV repair or replacement , these ratios tracked well the changes in PCWP and readily identified changes in mean PCWP by ≥5 mm Hg . A similar correlation was noted in 13 patients with atrial fibrillation ( r=−0.92 , P<0.01 ) and in a prospect i ve group of 14 patients with MR ( r=−0.93 , P<0.001 ) . Conclusions —The ratio of IVRT to TE−Ea or to & tgr ; can be readily applied for estimating mean PCWP in patients with MVD and can track changes in PCWP after valve surgery BACKGROUND It is traditionally difficult to estimate left ventricular ( LV ) systolic function in atrial fibrillation ( AF ) . The aim of this study was to vali date the use of an index beat , the beat after the nearly equal preceding ( RR1 ) and pre-preceding ( RR2 ) intervals , for the measurement of LV peak longitudinal systolic strain ( PLSS ) . The difference between RR1 and RR2 intervals of the index beat must be < 60 msec . LV PLSS measured from the index beat ( PLSSindex ) was compared with LV PLSS measured from the conventional but time-consuming method of averaging multiple cardiac cycles ( PLSSavg ) . METHODS Ninety-eight patients with persistent or permanent AF and resting ventricular rates ≤ 105 beats/min were prospect ively included . LV PLSSindex and LV PLSSavg were obtained from two-dimensional speckle-tracking echocardiography . RESULTS LV PLSSindex had a highly significant correlation with LV PLSSavg ( r = 0.970 , P < .001 ) . Bl and -Altman analysis showed only small bias of 0.01 % , and the 95 % limits of agreement were + 1.64 % to -1.62 % . Compared with those with lower risk scores of stroke indicated by CHADS(2 ) scores < 2 or CHA(2)DS(2)-VASc scores < 2 , patients with higher risk scores of stroke indicated by CHADS(2 ) scores ≥ 2 or CHA(2)DS(2)-VASc scores ≥ 2 had lower PLSSavg and PLSSindex ( P ≤ .012 ) . CONCLUSIONS LV PLSSindex was a good alternative to LV PLSSavg in patients with AF . Use of the index beat to measure LV longitudinal systolic strain in patients with AF was as accurate as the time-consuming method of averaging multiple cardiac cycles Single-beat determination of left ventricular systolic function at a beat with equal subsequent cardiac cycles has been proposed as an accurate method in atrial fibrillation . However , there has still been substantial variability between the values calculated from beats with equal subsequent cycles . Therefore , some refinement on the single-beat method is needed . In 100 patients with atrial fibrillation , Doppler aortic flow time-velocity integral was determined for at least 20 consecutive cardiac cycles . The values at beats with equal subsequent cardiac cycles were chosen and compared with the average values over all cardiac cycles . The values at beats with cycle lengths shorter than 500 milliseconds were usually far below the average values over all cardiac cycles . Bl and -Altman agreement analysis revealed improved accuracy by gradually narrowing the range of the limits of agreement when 2 or 3 beats with equal subsequent cycles and cycle lengths longer than 500 milliseconds were used for evaluation OBJECTIVES We sought to obtain a noninvasive estimation of mean pulmonary wedge pressure ( MPWP ) in patients with chronic atrial fibrillation ( AF ) . BACKGROUND It has previously been demonstrated that MPWP can be reliably estimated from Doppler indexes of mitral and pulmonary venous flow ( PVF ) in patients with sinus rhythm . Doppler estimation of MPWP has not been vali date d in patients with AF . METHODS MPWP was correlated with variables of mitral and pulmonary venous flow velocity as assessed by Doppler transthoracic echocardiography in 35 consecutive patients . The derived algorithm was prospect ively tested in 23 additional patients . RESULTS In all patients the mitral flow pattern showed only a diastolic forward component . A significant but relatively weak correlation ( r = -0.50 ) was observed between MPWP and mitral deceleration time . In 12 ( 34 % ) of 35 patients , the pulmonary vein flow tracing demonstrated only a diastolic forward component ; a diastolic and late systolic forward flow was noted in the remaining 23 patients ( 66 % ) . A strong negative correlation was observed between MPWP and the normalized duration of the diastolic flow ( r = -0.80 ) and its initial deceleration slope time ( r = -0.91 ) . Deceleration time > 220 ms predicted MPWP < or = 12 mm Hg with 100 % sensitivity and 100 % specificity . When estimating MPWP by using the equation MPWP = -94.261 PVF deceleration time -9.831 Interval QRS to onset of diastolic PVF -16.337 Duration of PVF + 44.261 , the measured and predicted MPWP closely agreed with a mean difference of -0.85 mm Hg . The 95 % confidence limits were 4.8 and -6.1 mm Hg . CONCLUSIONS In patients with chronic AF , MPWP can be estimated from transthoracic Doppler study of PVF velocity signals Although exercise intolerance is a major symptom of patients with atrial fibrillation ( AF ) , the factors limiting these patients ' exercise capacity remains uncertain . This study evaluated the correlation of clinical and echocardiographic parameters with exercise capacity of patients with AF . In all , 73 patients ( 61 men and 12 women ; mean age 61 years ) with chronic AF were included in this study . Those patients with primary valvular diseases were excluded . St and ard 2-dimensional and Doppler echocardiography was performed , and we averaged 10 consecutive measurements of each variable . Patients then underwent a symptom-limited treadmill exercise testing . We also measured patients ' plasma levels of B-type natriuretic peptide before exercise testing . Of all clinical and echocardiographic parameters we assessed , age ( r = -0.45 , P = .006 ) , ratio of early mitral inflow velocity to mitral annular velocity ( r = -0.35 , P = .032 ) , and baseline heart rate were independent predictors of exercise capacity on multivariate regression analysis . In conclusion , patient 's age , averaged ratio of early mitral inflow velocity to mitral annular velocity , and baseline heart rate provided useful information on exercise intolerance for patients with AF . Ratio of early mitral inflow velocity to mitral annular velocity , a noninvasive tool for estimating left ventricular filling pressure , may especially have important value for predicting functional capacity in this population as it has in individuals with in sinus rhythm BACKGROUND Although several risk factors for stroke have been reported in patients with atrial fibrillation ( AF ) , the relation of LV diastolic dysfunction to stroke is still uncertain in these patients . We evaluated the relationship between tissue Doppler-derived index , E/E ' , as well as other clinical and echocardiographic parameters and ischemic stroke by this cross-sectional study . METHODS Three hundred thirty patients with persistent AF who had preserved LV ejection fraction were included from 6 centers . Clinical data were obtained and st and ard transthoracic echocardiography was performed . Patients without a history of ischemic stroke ( n=280 ) were compared with patients with this complication ( n=50 ) . Potential determinants of ischemic stroke were identified by logistic regression analyses . RESULTS In univariate analyses , age , history of hypertension , diabetes mellitus , hyperlipidemia and symptomatic heart failure , plasma brain natriuretic peptide ( BNP ) level , early mitral inflow velocity ( E ) , diastolic mitral annular velocity ( E ' ) , and E/E ' ratio were significantly correlated to ischemic stroke . Multivariate regression analyses identified two significant variables that were independently associated with ischemic stroke : hypertension ( odds ratio=6.03 , p=0.008 ) , and E/E ' ( odds ratio=1.21 , p=0.002 ) . CONCLUSIONS These findings may have clinical implication s that LV diastolic dysfunction , reflected by E/E ' , is a significant determinant of ischemic stroke in AF . A larger prospect i ve data is needed to confirm the value of E/E ' in risk stratification for ischemic stroke in this population OBJECTIVES This study sought to determine the accuracy of Doppler echocardiography and tissue Doppler imaging ( TDI ) measurements in detecting elevated left atrial pressure ( LAP ) in ambulant subjects with chronic heart failure using directly measured LAP as the reference . BACKGROUND Echocardiographic indexes including the ratio of transmitral to annular early diastolic velocities ( E/e ' ) may identify raised invasively measured left ventricular filling pressures when tested in cross-sectional studies in some population s. The accuracy of these indexes when measured sequentially remains untested . We determined the accuracy of Doppler echocardiography and TDI measurements in detecting elevated directly measured LAP in ambulant subjects with stable chronic heart failure . METHODS Fifteen patients with New York Heart Association functional class II to III heart failure and a permanently implanted direct LAP monitoring device underwent serial echocardiography . Simultaneous resting mean LAP , Doppler mitral inflow , mitral annular TDI , and pulmonary venous inflow velocities were obtained on each occasion . Receiver-operator characteristic curve analysis was used to compare the accuracy of the Doppler variables to detect an elevated device LAP ≥15 and ≥20 mm Hg . RESULTS The patients ( 13 men , mean age : 71 years , mean left ventricular ejection fraction : 32 ± 12 % ) underwent 60 simultaneous echocardiographic studies and LAP measurements with a median of 4 ( 1 to 7 ) studies per patient . Mean LAP was 16.9 ( range 5 to 39 mm Hg ) at echocardiography ( n = 60 ) . E/e ' had the greatest accuracy for detection of LAP ≥15 mm Hg with an area beneath the receiver-operator characteristic curve > 0.9 . In comparison , area under the curve for mitral E velocity and mitral E/A were 0.77 and 0.76 , respectively ( p < 0.008 vs. E/e ' medial and average ) . CONCLUSIONS Single and serial measurements of mitral inflow and mitral annular TDI velocities ( E/e ' ) can reliably detect raised directly measured LAP in ambulant subjects with compensated chronic heart failure . ( Hemodynamically Guided Home Self-Therapy in Severe Heart Failure Patients [ HOMEOSTASIS ] ; NCT00547729 ) OBJECTIVE The aim of this prospect i ve study was to evaluate the contribution of an initially shortened deceleration time of mitral inflow E velocity ( E-wave DT ) to predict survival in patients with left-ventricular ( LV ) systolic dysfunction in atrial fibrillation ( AF ) and in sinus rhythm ( SR ) . BACKGROUND To date , few data are available concerning the prognostic value of Doppler mitral profile in patients with AF , particularly in the presence of LV systolic dysfunction . METHODS We studied the outcome of 140 consecutive patients with LV ejection fraction less than 40 % . Complete history , physical examination and echocardiography were performed . RESULTS Chronic AF was present in 40 ( 29 % ) patients . Over a mean follow-up of 25+/-11 months , 54 ( 39 % ) patients died , 18 in the AF group and 36 in the SR group . Ejection fraction was similar in the two groups ( 31 % versus 32 % , respectively ) . Survival curves indicated a significantly poorer prognosis for shortened E-wave DT less than 150 ms in the AF group and in the SR group ( both p < or=0.01 ) . Using multivariable Cox analysis , shortened E-wave DT was identified as an independent predictor of mortality in the AF group ( exponential of coefficient : 0.97 ; chi-square : 5.82 ; p=0.01 ) and in the SR group ( exponential of coefficient : 0.98 ; chi-square : 5.82 ; p=0.001 ) . CONCLUSION In patients with LV systolic dysfunction , a shortened deceleration time E-wave on Doppler examination appears to predict a similar poor prognosis in patients with AF as with SR BACKGROUND The time interval between the onset of early transmitral flow velocity ( E ) and that of early diastolic mitral annular velocity ( e ' ) ( T(E-e ' ) ) is a good predictor of elevated left ventricular ( LV ) filling pressure in patients with sinus rhythm . Although the evaluation of LV filling pressure using E/e ' has been challenging in atrial fibrillation ( AF ) , the usefulness of T(E-e ' ) is unknown . METHODS AND RESULTS E and e ' were simultaneously recorded using dual Doppler echocardiography in 45 AF patients ( 30 men ; mean age , 69 ± 9 years ) . E/e ' and T(E-e ' ) were calculated and compared with the pulmonary capillary wedge pressure ( PCWP ) , which was measured invasively . E/e ' and T(E/e ' ) correlated with PCWP ( E/e ' , r=0.57 , P<0.001 ; T(E-e ' ) , r=0.77 , P<0.001 ) . Using receiver operating characteristic analysis , the optimal cut-off for T(E-e ' ) was 34 ms ( sensitivity , 95 % ; specificity , 88 % ) and that for E/e ' was 14.6 ( sensitivity , 50 % ; specificity , 84 % ) in order to predict > 12-mmHg PCWP . When the combined cut-offs of T(E-e ' ) > 34 ms and E/e ' > 14.6 were used , the sensitivity and specificity of predicting elevated PCWP were improved to 100 % and 88 % , respectively . CONCLUSIONS In AF patients , the simultaneous recording of E and e ' using dual Doppler echocardiography and the analysis of T(E-e ' ) , in addition to E/e ' , improved the accuracy of evaluation of LV filling pressure OBJECTIVES To develop and vali date a new risk-of-bias tool for nonr and omized studies ( NRSs ) . STUDY DESIGN AND SETTING We developed the Risk of Bias Assessment Tool for Nonr and omized Studies ( RoBANS ) . A validation process with 39 NRSs examined the reliability ( interrater agreement ) , validity ( the degree of correlation between the overall assessment s of RoBANS and Method ological Index for Nonr and omized Studies [ MINORS ] , obtained by plotting the overall risk of bias relative to effect size and funding source ) , face validity with eight experts , and completion time for the RoBANS approach . RESULTS RoBANS contains six domains : the selection of participants , confounding variables , the measurement of exposure , the blinding of the outcome assessment s , incomplete outcome data , and selective outcome reporting . The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial . There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS . The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies . The mean time required to complete RoBANS was approximately 10 min . The external experts who were interviewed evaluated RoBANS as a " fair " assessment tool . CONCLUSIONS RoBANS shows moderate reliability , promising feasibility , and validity . The further refinement of this tool and larger validation studies are required BACKGROUND Accurate assessment of left ventricular ( LV ) function in patients with atrial fibrillation ( AF ) remains difficult , mainly because of the beat-to-beat variability of many echocardiographic parameters . The aim of this study was to assess the hypothesis that LV function can be estimated from an index-beat echocardiographic assessment in patients with AF using myocardial strain and strain rate . METHODS A prospect i ve study was conducted to assess 25 patients with AF ( mean age , 66 ± 10 years ) . Peak systolic longitudinal strain ( LS ) and peak diastolic longitudinal strain rate ( dSR ) were measured using two different methods : ( 1 ) mean LS and dSR , the averages of instantaneous LS and dSR over 10 sec , and ( 2 ) index-beat LS and dSR , calculated when the ratio of the preceding ( RR1 ) to the pre-preceding ( RR2 ) interval was 1 ( range , 0.96 - 1.04 ) . These variables were compared with simultaneously measured LV pressure parameters using Millar catheters . RESULTS There was a positive linear relationship between mean LS and index-beat LS at RR1/RR2 = 1 ( r = 0.94 , P < .001 ) and a positive linear relationship between mean dSR and index-beat dSR ( r = 0.69 , P < .001 ) . Index-beat LS was correlated with the maximal positive derivative of LV pressure ( peak + dP/dt ) ( r = -0.73 , P < .001 ) . Index-beat dSR was correlated with the time constant of isovolumic LV pressure decay ( τ ) ( r = -0.63 , P < .001 ) . To investigate the independent predictors of τ , a stepwise multilinear regression analysis showed that index-beat dSR was the best predictor of τ . CONCLUSIONS Index-beat parameters accurately reflect the mean values of parameters in patients with AF . These noninvasively obtained index-beat parameters are useful to assess surrogate LV function even in patients with AF |
10,523 | 24,972,265 | Compared with placebo , patients treated with heparins had a similar risk of mortality , revascularization , recurrent angina , and thrombocytopenia .
However , those treated with heparins had a decreased risk of myocardial infa rct ion and a higher incidence of minor bleeding . | BACKGROUND Non-ST elevation acute coronary syndromes ( NSTEACS ) represent a spectrum of disease including unstable angina and non-ST segment myocardial infa rct ion ( NSTEMI ) .
Despite treatment with aspirin , beta-blockers and nitroglycerin , unstable angina/NSTEMI is still associated with significant morbidity and mortality .
Although evidence suggests that low molecular weight heparin ( LMWH ) is more efficacious compared to unfractionated heparin ( UFH ) , there is limited data to support the role of heparins as a drug class in the treatment of NSTEACS .
This is an up date of a review last published in 2008 .
OBJECTIVES To determine the effect of heparins ( UFH and LMWH ) compared with placebo for the treatment of patients with non-ST elevation acute coronary syndromes ( unstable angina or NSTEMI ) . | BACKGROUND The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion . In unstable angina due to a restenotic lesion , smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation . Therefore , the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina . METHODS AND RESULTS We r and omized 200 patients hospitalized for unstable angina within 6 months after angioplasty ( excluding those with intracoronary stents ) to double-blind administration of intravenous nitroglycerin , heparin , their combination , or placebo for 63+/-30 hours . Recurrent angina occurred in 75 % of patients in the placebo and heparin-alone groups , compared with 42.6 % of patients in the nitroglycerin-alone group and 41.7 % of patients in the nitroglycerin-plus-heparin group ( P<0.003 ) . Refractory angina requiring angiography occurred in 22.9 % , 29.2 % , 4 . 3 % , and 4.2 % of patients , respectively ( P<0.002 ) . The odds ratios for being event free were 0.24 ( 95 % CI , -0.13 to 0.45 , P=0.0001 ) for nitroglycerin versus no nitroglycerin and 0.98 ( 95 % CI , -0.55 to 1 . 73 , P = NS ) for heparin versus no heparin . No patient died or suffered myocardial infa rct ion . CONCLUSIONS Intravenous nitroglycerin is highly effective in preventing adverse ischemic events ( recurrent or refractory angina ) in patients with unstable angina secondary to restenosis , whereas heparin has no effect CONTEXT Despite many therapeutic advances , mortality in patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) remains high . The role of additional antithrombotic agents is unclear , especially among patients not receiving reperfusion therapy . OBJECTIVE To evaluate the effect of fondaparinux , a factor Xa inhibitor , when initiated early and given for up to 8 days vs usual care ( placebo in those in whom unfractionated heparin [ UFH ] is not indicated [ stratum 1 ] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [ stratum 2 ] ) in patients with STEMI . DESIGN , SETTING , AND PARTICIPANTS R and omized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12,092 patients with STEMI from 447 hospitals in 41 countries ( September 2003-January 2006 ) . From day 3 through day 9 , all patients received either fondaparinux or placebo according to the original r and omized assignment . MAIN OUTCOME MEASURES Composite of death or reinfa rct ion at 30 days ( primary ) with secondary assessment s at 9 days and at final follow-up ( 3 or 6 months ) . RESULTS Death or reinfa rct ion at 30 days was significantly reduced from 677 ( 11.2 % ) of 6056 patients in the control group to 585 ( 9.7 % ) of 6036 patients in the fondaparinux group ( hazard ratio [ HR ] , 0.86 ; 95 % confidence interval [ CI ] , 0.77 - 0.96 ; P = .008 ) ; absolute risk reduction , 1.5 % ; 95 % CI , 0.4%-2.6 % ) . These benefits were observed at 9 days ( 537 [ 8.9 % ] placebo vs 444 [ 7.4 % ] fondaparinux ; HR , 0.83 ; 95 % CI , 0.73 - 0.94 ; P = .003 , and at study end ( 857 [ 14.8 % ] placebo vs 756 [ 13.4 % ] fondaparinux ; HR , 0.88 ; 95 % CI , 0.79 - 0.97 ; P = .008 ) . Mortality was significantly reduced throughout the study . There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use . However , there was no benefit in those undergoing primary percutaneous coronary intervention . In other patients in stratum 2 , fondaparinux was superior to unfractionated heparin in preventing death or reinfa rct ion at 30 days ( HR , 0.82 ; 95 % CI , 0.66 - 1.02 ; P = .08 ) and at study end ( HR , 0.77 ; 95 % CI , 0.64 - 0.93 ; P = .008 ) . Significant benefits were observed in those receiving thrombolytic therapy ( HR , 0.79 ; P = .003 ) and those not receiving any reperfusion therapy ( HR , 0.80 ; P = .03 ) . There was a tendency to fewer severe bleeds ( 79 for placebo vs 61 for fondaparinux ; P = .13 ) , with significantly fewer cardiac tamponade ( 48 vs 28 ; P = .02 ) with fondaparinux at 9 days . CONCLUSION In patients with STEMI , particularly those not undergoing primary percutaneous coronary intervention , fondaparinux significantly reduces mortality and reinfa rct ion without increasing bleeding and strokes . TRIAL REGISTRATION Clinical Trials.gov Identifier NCT00064428 Background Antiplatelet therapy with aspirin and antithrombotic therapy with heparin both prevent the complications of unstable angina ; however , no definitive data exist on the relative clinical efficacy of the two drugs . Methods and Results Aspirin ( 325 mg bid ) or heparin ( 5000-U intravenous bolus followed by a perfusion titrated to the APTT ) were compared in a double-blind r and omized trial of 484 patients in two cohorts enrolled sequentially . The study was initiated at admission to hospital at a mean of 8.3±7.8 hours after the last episode of pain . End points were assessed 5.7±3.3 days later , when the decision for long-term management was made . Myocardial infa rct ion occurred in 2 ( 0.8 % ) of the 240 patients r and omized to heparin and in 9 ( 3.7 % ) of the 244 r and omized to aspirin ( P=.035 ) , an odds ratio of 0.22 and a risk difference of 2.9%o ( 95 % confidence limits , 0.3 % to 5.6 % ) with heparin . The only death result ed from a myocardial infa rct ion in an aspirin patient . Survival curves with Cox logistic regression analysis showed that the improvement in survival without myocardial infa rct ion with heparin ( P=.035 ) was independent of other baseline characteristics . Conclusions This study documents that heparin prevents myocardial infa rct ion better than aspirin during the acute phase of unstable angina Platelet glycoprotein IIb/IIIa inhibitors have been extensively studied in the treatment of patients with ischemic heart disease . Data regarding the use of these agents in the absence of concomitant intravenous heparin have been conflicting . We sought to determine , using propensity analysis , whether the benefit of eptifibatide , a IIb/IIIa inhibitor , in the treatment of acute coronary syndromes is affected by the concurrent administration of heparin . By trial design , patients were r and omized to either eptifibatide or placebo , whereas use of intravenous heparin was left to the discretion of treating physicians . The effect of eptifibatide on the 30-day composite end point of death or myocardial infa rct ion was studied in patients who received heparin and those who did not . Propensity analysis methods were used to control for confounding and presumed selection biases . Among 5,576 patients who were receiving heparin when the bolus dose of the study drug was administered , eptifibatide was associated with a reduced composite end point rate ( 13 % ) compared with that of placebo ( 14.5 % vs 16.6 % , p = 0.03 ) . In contrast , among 1,441 patients who were not receiving heparin , there was no difference in 30-day event rates with eptifibatide compared with placebo ( 13.7 % vs 13.1 % , p > 0.7 ) . After a propensity score for use of heparin was developed , however , use of heparin did not affect the reduced risk associated with eptifibatide ( adjusted relative risk [ RR ] for heparin-eptifibatide interaction term 0.90 , 95 % confidence interval [ CI ] 0.61 to 1.32 , p > 0.5 ) , but the propensity for heparin use was a strong predictor of events ( adjusted RR 1.76 , 95 % CI 1.42 to 2.17 , p < 0.001 ) . The use of eptifibatide independently predicted a lower risk of events ( adjusted RR 0.31 , 95 % CI 0.10 to 0.93 , p = 0.04 ) . Thus , the apparent positive impact of heparin on the benefits of eptifibatide therapy was largely due to confounding and bias Heparin , aspirin with dipyridamole or placebo were given to 266 patients with pre-infa rct ion angina treated with isosorbide dinitrate , beta blockers and nifedipidine . The number of patients who developed acute myocardial infa rct ion ( MI ) in the next 72 hours was comparable in all 3 groups . However , patients on heparin developed only 3.2 % ( 2 out of 61 ) Q MI compared with 20 % ( 20 out of 100 , p = 0.005 ) taking dipyridamole with aspirin and 19 % ( 20 out of 105 on placebo , p = 0.006 ) . Infa rct ions of patients treated with heparin as assessed by peak of serum creatine kinase ( CK ) were also smaller ( 810 + /- 538 IU/1 ) than in groups taking antiplatelets ( 1229 + /- 829 IU/1 , p = 10.048 ) or placebo ( 1417 + /- 919 IU/1 , p = 0.009 ) . We defined a subgroup at high risk patients who had prolonged chest pain longer than 45 min and ECG changes with ST segment depression more than 1 mm within 6 hours of admission : 55 % of these patients developed acute infa rct ion in the following 72 hours . Aggressive management including coronary angiography and fibrinolysis should be considered in well equipped centers for patients with evolving coronary thrombus in a general hospital , heparin infusion should be part of routine treatment as patients on heparin developed smaller infa rct ions OBJECTIVES The aims of the Safety and Efficacy of Subcutaneous Enoxaparin Versus Intravenous Unfractionated Heparin and Tirofiban Versus Placebo in the Treatment of Acute ST-Segment Elevation Myocardial Infa rct ion Patients Ineligible for Reperfusion ( TETAMI ) study were to demonstrate that enoxaparin was superior to unfractionated heparin ( UFH ) and that tirofiban was better than placebo in patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) who do not receive timely reperfusion . BACKGROUND An optimal treatment strategy has not been identified for the many STEMI patients ineligible for acute reperfusion . METHODS A total of 1224 patients were enrolled in 91 centers in 14 countries between July 1999 and July 2002 . Patients with STEMI ineligible for reperfusion were r and omized to enoxaparin , enoxaparin plus tirofiban , UFH , or UFH plus tirofiban . All patients received oral aspirin . The primary efficacy end point was the 30-day combined incidence of death , reinfa rct ion , or recurrent angina ; the primary analysis was the comparison of the pooled enoxaparin and UFH groups . RESULTS The incidence of the primary efficacy end point was 15.7 % enoxaparin versus 17.3 % for UFH ( odds ratio 0.89 [ 95 % confidence interval CI = 0.66 to 1.21 ] ) and 16.6 % for tirofiban versus 16.4 % for placebo ( odds ratio 1.02 [ 95 % CI 0.75 to 1.38 ] ) . The Thrombolysis In Myocardial Infa rct ion ( TIMI ) major hemorrhage rate was 1.5 % for enoxaparin versus 1.3 % for UFH ( odds ratio 1.16 [ 95 % CI 0.44 to 3.02 ] ) and 1.8 % versus 1 % for tirofiban versus placebo ( odds ratio 1.82 [ 95 % CI 0.67 to 4.95 ] ) . CONCLUSIONS This study did not show that enoxaparin significantly reduced the 30-day incidence of death , reinfa rct ion , and recurrent angina compared with UFH in non-reperfused STEMI patients . However , enoxaparin appears to have a similar safety and efficacy profile to UFH and may be an alternative treatment . Additional therapy with tirofiban did not appear beneficial BACKGROUND Heparin is an effective , widely used treatment for unstable angina . Among patients enrolled in a double-blind , r and omized , placebo-controlled trial comparing intravenous heparin , aspirin , both treatments , and neither during the acute phase of unstable angina , we encountered patients in whom unstable angina was reactivated after heparin was discontinued . METHODS The study population included 403 of the original 479 patients in the trial who had completed six days of blinded therapy without refractory angina or myocardial infa rct ion . After the discontinuation of therapy , clinical events , including reactivation of unstable angina and myocardial infa rct ion occurring within 96 hours after hospitalization , were closely monitored . RESULTS Early reactivation occurred in 14 of the 107 patients who received heparin alone , as compared with only 5 patients in each of the other three study groups ( P less than 0.01 ) . These reactivations required urgent intervention ( thrombolysis , angioplasty , or coronary-bypass surgery ) in 11 patients treated with heparin alone , but in only 2 patients in the other groups combined ( P less than 0.01 ) . Four of the six patients who had a myocardial infa rct ion during a reactivation of their disease were in the heparin group . Reactivations in this group occurred in a cluster a mean ( + /- SD ) of 9.5 + /- 5 hours after the discontinuation of the study drug but were r and omly distributed over the initial 96 hours in the other three groups . CONCLUSIONS Although heparin is beneficial in treating unstable angina , the disease process may be reactivated within hours of the discontinuation of this drug . Concomitant therapy with aspirin may prevent this withdrawal phenomenon The FRISC II study addressed two key questions in the management of acute coronary syndromes : is it beneficial to extend low‐molecular‐weight heparin ( LMWH ) therapy with dalteparin beyond the initial period of acute treatment ; and , is a strategy of early invasive therapy , including angioplasty and surgical revascularization , preferable to a more conservative strategy ? The study focused on patients with unstable coronary artery disease ( UCAD ) , that is , angina and non‐ST‐segment‐elevation myocardial infa rct ion ( MI ) . Patients were allocated in a r and omized , factorial study design to either an invasive or a conservative management strategy . Within each of these groups , patients were further r and omized to receive either 3 months of extended treatment with dalteparin or placebo , following at least 5 days ' treatment with open‐label dalteparin . After 1 year , patient survival and MI‐free survival were significantly higher in the invasive therapy group than in the noninvasive group . Patients who received extended dalteparin treatment had a significantly reduced probability of death or MI after 1 month ( relative risk reduction 47 % ; p = 0.002 ) , a benefit still evident after 60 days , but after 3 months there was no longer any significant clinical advantage compared with placebo . There was , however , a significant reduction in the combined incidence of death , MI , or revascularization at 3 months in the extended dalteparin treatment group ( relative risk reduction 13 % ; p = 0.031 ) . The benefits of extended dalteparin treatment were particularly marked in patients with elevated troponin‐T or ST‐segment depression . A subgroup analysis of conservatively managed patients who underwent revascularization in the first 45 days revealed that the probability of death or MI at 1 year was significantly lower among patients who received extended dalteparin treatment ( relative risk reduction 35 % ; p = 0.02 ) . Extended dalteparin treatment is , however , associated with a small increase in bleeding risk . in conclusion , early invasive therapy ( following combined treatment with aspirin and dalteparin ) is recommended in a majority of patients with UCAD . Furthermore , extended dalteparin treatment for up to 45 days is efficacious and well tolerated , and therefore provides a useful “ bridge ” to revascularization when early revascularization is not immediately available BACKGROUND Short-term treatment with subcutaneous low-molecular-mass heparin in addition to aspirin is effective in unstable coronary-artery disease . We assessed the efficacy of long-term treatment with dalteparin in patients managed with a non-invasive treatment strategy . METHODS 2267 patients from three Sc and inavian countries ( median age 67 years , 68 % men ) with unstable coronary-artery disease were r and omly assigned to continue double-blind subcutaneous dalteparin twice daily or placebo for 3 months , after at least 5 days ' treatment with open-label dalteparin . The composite primary endpoint was death or myocardial infa rct ion . Analysis was by intention to treat . FINDINGS During the 3 months of double-blind treatment , there was a non-significant decrease in the composite endpoint of death or myocardial infa rct ion of 6.7 % and 8.0 % in the dalteparin and placebo groups , respectively ( risk ratio 0.81 [ 95 % CI 0.60 - 1.10 ] , p=0.17 ) . At 30 days , this decrease was significant ( 3.1 vs 5.9 % , 0.53 [ 0.35 - 0.80 ] ; p=0.002 ) . In the total cohort there was at 3 months a decrease in death , myocardial infa rct ion , or revascularisation ( 29.1 vs 33.4 % , 0.87 [ 0.77 - 0.99 ] ; p=0.031 ) . The initial benefits were not sustained at 6-month follow-up . INTERPRETATION Long-term dalteparin lowers the risk of death , myocardial infa rct ion , and revascularisation in unstable coronary-artery disease at least during the first month of therapy . These early protective effects could be used to lower the risk of events in patients waiting for invasive procedures PURPOSE To assess the efficacy of heparin in preventing the abrupt closure after coronary angioplasty in low risk patients for this phenomenon . METHODS In the last 4 years , 525 patients successfully dilated were r and omized to receive intravenous heparin ( n = 264 ) or not ( n = 261 ) after the angioplasty . The excluding criteria were contraindications for heparin and risk for abrupt closure ( refractory unstable angina , primary coronary angioplasty in acute myocardial infa rct ion , evidence of intracoronary thrombus , intimal tear after the procedure and cases of chronic total occlusions ) . Both heparin and non heparin groups were similar in respect to female sex ( 15 % x 17 % ; p = NS ) , age over 70 years old ( 7 % x 9 % ; p = NS ) , previous myocardial infa rct ion ( 26 % x 24 % ; p = NS ) , multi-vessel procedures ( 4 % x 7 % ; p = NS , stable angina ( 40 % x 46 % ; p = NS ) , unstable angina ( 52 % x 48 % ; p = NS ) and angioplasty after thrombolytic therapy ( 8 % x 6 % ; p = NS ) . RESULTS The overall incidence of abrupt closure was 2/525 ( 0.4 % ) , with one case ( 0.4 % ) in each group . The in-hospital mortality was 1/525 ( 0.2 % ) , which occurred in a non-heparin patient , due to a anterior myocardial infa rct ion . Major complications occurred similarly in heparin and non-heparin groups ( 0.4 % ) . Bleeding complications were observed more frequently in the heparin group ( 7 % x 2 % ; p = 0.002 ) . All of them were in the catheterization site and none required blood transfusion . Severe systemic bleeding were not observed . CONCLUSION In patients regarded as low risk for abrupt closure , the incidence of this complication was really low ( 0.4 % ) and heparin probably do not prevent it Increased thrombin generation is frequently associated with an increase in anginal activity . A cross-over , single-blind , completely r and omized study was planned in order to evaluate whether the control of thrombin generation affected the increase in anginal activity . After discharge from the hospital , 24 patients ( 18 men and 6 women , aged 40 to 69 years ) suffering from spontaneous angina were followed up to 12 months and were alternatively treated during two consecutive 6-month periods with calcium heparin , 12,500 IU by the subcutaneous route , or with placebo by the intramuscular route , in addition to the usual antianginal medications . Thrombin generation and clinical activity of angina were assessed every 15 days by measuring fibrinopeptide A ( FPA ) plasma levels and by grading in three classes ( symptomless , mildly symptomatic , and severely symptomatic ) the anginal activity on the basis of the number and the time concentration of the ischemic attacks and ECG changes . Low-dose heparin treatment significantly reduced both the FPA plasma level ( from 4.1 + /- 3.7 to 2.3 + /- 1.8 ng/ml , p less than 0.001 ) and the clinical activity of angina . During heparin treatment , the frequency of the observations in the severely and mildly symptomatic classes decreased , respectively , by 53 % and by 30 % , whereas that in the symptomless class increased by 23 % ( p less than 0.001 ) in comparison with the period on placebo . Present results indicate that the control of thrombin generation obtained by low-dose heparin treatment favorably affects the degree of anginal activity in patients with spontaneous angina OBJECTIVES This study compared the effects of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina . BACKGROUND Transient myocardial ischemia occurring in patients with unstable angina is associated with an adverse prognosis . Heparin and aspirin are two drugs used frequently in the treatment of this condition , but the effect of combination therapy versus aspirin alone on transient myocardial ischemia is unknown . METHODS Two hundred eighty-five consecutive patients with unstable angina were r and omized to receive either intravenous heparin plus oral aspirin ( 150 mg once daily ) ( Group H + A ) or aspirin alone ( Group A ) . Patients also received a beta-adrenergic blocking agent , diltiazem and intravenous nitrates . ST segment monitoring was performed for the 1st 48 h of treatment . Patients were followed up for the duration of their in-hospital stay . RESULTS One hundred fifty-four patients ( 30 women , mean [ + /- SEM ] age 58.3 + /- 0.8 years ) received heparin and aspirin ( Group H + A ) , and 131 patients ( 26 women , mean age 60.6 + /- 0.8 years ) received aspirin only ( Group A ) . ST segment monitoring ( 11,622 h ) yielded 244 episodes of transient myocardial ischemia of a total duration of 7,819 min . There were no significant differences between the two treatment arms in the number of patients with transient myocardial ischemia ( 27 [ 18 % ] in Group H + A vs. 31 [ 24 % ] in Group A ) , number of episodes ( 96 in Group H + A vs. 148 in Group A ) or total duration of transient myocardial ischemia ( 2,911 min in Group H + A vs. 4,908 min in Group A ) . The incidence of in-hospital myocardial infa rct ion or death was significantly higher in patients with transient myocardial ischemia ( 53 % vs. 22 % , p < 0.0001 ) . Five of the six deaths occurred in patients with transient myocardial ischemia . Event-free survival from myocardial infa rct ion or death was similar in both treatment groups . Preadmission therapy with aspirin was associated with a lower in-hospital infa rct ion rate ( 19 % vs. 34 % , p = 0.01 ) . CONCLUSIONS The presence of transient myocardial ischemia in patients with unstable angina is associated with a significantly higher incidence of myocardial infa rct ion or death in hospital . Combined therapy with heparin and aspirin compared with aspirin alone makes no difference in the development of these events , nor does it reduce the development of transient myocardial ischemia BACKGROUND The purpose of this study was to compare combination antithrombotic therapy with aspirin plus anticoagulation versus aspirin alone , when added to conventional antianginal therapy in patients with unstable rest angina or non-Q-wave myocardial infa rct ion who were nonprior aspirin users . METHODS AND RESULTS Two hundred fourteen patients were r and omized ; 109 were r and omized to receive aspirin alone ( 162.5 mg daily ) and 105 to receive a combination of aspirin plus anticoagulation , ie , aspirin 162.5 mg daily plus heparin ( activated partial thromboplastin time , two times control ) followed by aspirin 162.5 mg daily plus warfarin ( international normalized ratio , 2 to 3 ) . Trial therapy was begun by 9.5 + /- 8.8 hours of qualifying pain and was continued for 12 weeks . Primary end points were recurrent angina with ECG changes , myocardial infa rct ion , and /or death . Analysis by intention to treat of primary events at 12 weeks was performed . At 14 days , there was a significant reduction in total ischemic events in the combination group versus aspirin alone ( 10.5 % versus 27 % , P = .004 ) . An efficacy analysis of primary events at 12 weeks also revealed a large reduction in total ischemic events in the combination group versus aspirin alone ( 13 % versus 25 % , P = .06 ) . Bleeding complications were slightly more common with combination therapy . CONCLUSIONS In nonprior aspirin users , combination antithrombotic therapy with aspirin plus anticoagulation significantly reduces recurrent ischemic events in the early phase of unstable angina Background —A reactivation of ischemia after the discontinuation of intravenous heparin in acute coronary syndromes has been described . The effect of glycoprotein IIb/IIIa blockade on heparin rebound is unknown . Methods and Results — Patients with acute coronary syndromes who received heparin therapy but not initial revascularization in the Platelet IIb/IIIa in Unstable angina : Receptor Suppression Using Integrilin Therapy ( PURSUIT ) trial were analyzed . Rates of death or myocardial (re)infa rct ion while on heparin therapy and in 12-hour periods in the 2 days after heparin discontinuation were compared between eptifibatide and placebo . There was no difference between study groups in event rates during heparin infusion . In the 12 hours after heparin discontinuation , there was a 2.5-fold increase in all events , an 8-fold increase in death , and a 2-fold increase in myocardial infa rct ion . However , in the 12 hours after heparin discontinuation , there was a significantly lower rate of events ( 1.68 % versus 2.53 % , P = 0.03 ) and death ( 0.77 % versus 0.21 % , P = 0.002 ) in the eptifibatide group compared with the placebo group . When only considering patients who were on study drug at the time of heparin discontinuation , the reduction in the combined end point was marginally significant , but the difference in the rate of death remained significant ( 0.68 % versus 0.06 % , P = 0.004 ) . In logistic regression analyses , the multivariate predictors of rebound events were the duration of heparin therapy , age , North American site , and lack of eptifibatide treatment . Conclusions —An increase in death or myocardial infa rct ion occurs in the 12 hours after heparin discontinuation in patients with acute coronary syndromes . This rebound is attenuated by glycoprotein IIb/IIIa inhibition with eptifibatide BACKGROUND Despite current treatments , patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events . We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients . METHODS We r and omly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel ( 300 mg immediately , followed by 75 mg once daily ) ( 6259 patients ) or placebo ( 6303 patients ) in addition to aspirin for 3 to 12 months . RESULTS The first primary outcome --a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or stroke -- occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group ( relative risk with clopidogrel as compared with placebo , 0.80 ; 95 percent confidence interval , 0.72 to 0.90 ; P<0.001 ) . The second primary outcome --the first primary outcome or refractory ischemia -- occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group ( relative risk , 0.86 ; 95 percent confidence interval , 0.79 to 0.94 ; P<0.001 ) . The percentages of patients with in-hospital refractory or severe ischemia , heart failure , and revascularization procedures were also significantly lower with clopidogrel . There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group ( 3.7 percent vs. 2.7 percent ; relative risk , 1.38 ; P=0.001 ) , but there were not significantly more patients with episodes of life-threatening bleeding ( 2.2 percent [ corrected ] vs. 1.8 percent ; P=0.13 ) or hemorrhagic strokes ( 0.1 percent vs. 0.1 percent ) . CONCLUSIONS The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation . However , the risk of major bleeding is increased among patients treated with clopidogrel It has been demonstrated in animal experiments that heparin accelerates the coronary collateral development induced by repeated coronary occlusion . We used this effect of heparin for the treatment of patients with stable effort angina . In 10 patients , treadmill exercise was performed according to st and ard Bruce protocol twice a day for 10 days . A single intravenous dose of heparin ( 5000 IU ) was given 10 to 20 min before each exercise period . Exercise with heparin pretreatment increased the total exercise duration from 6.3 + /- 1.9 ( SD ) to 9.1 + /- 2.2 min ( p less than .001 ) and the maximal double product ( DP ) from 18,900 + /- 5100 to 25,500 + /- 6800 mm Hg.beats/min ( p less than .001 ) . The DP at the onset of angina was also increased by 35 % ( p less than .01 ) and the DP at which ST depression ( 0.1 mV ) first appeared was 19 % ( p less than .05 ) greater after treatment . Repeat coronary cineangiography revealed an increase in the extent of opacification of collaterals to the jeopardized myocardium . In an additional six patients , treadmill exercise was performed with no medication twice a day for 10 days . All of the above-mentioned variables of treadmill capacity remained unchanged , despite 20 exercise periods without heparin pretreatment . Thus , heparin accelerates exercise-induced coronary collateral development by promoting angiogenesis . The development of such a therapeutic modality will open a new field for the treatment of patients with ischemia Although the efficacy of long-term administration of antithrombotic agents in unstable angina has been established , short-term effects on myocardial ischemia are unknown . A retrospective analysis was performed in 47 patients undergoing three-channel continuous ST segment monitoring as part of a multicenter trial using esmolol in unstable angina , in which 20 patients received a continuous heparin infusion during the initial assessment of chest pain . Concomitant medications included calcium channel blockers , beta-adrenergic blockers , nitrates , and aspirin in the majority of patients . Clinical variables between the heparin and no heparin groups were similar , except for fewer males and fewer total artery occlusions in the heparin group . No significant differences in the incidence or duration of ischemia were found in a 36 + /- 16 hour monitoring period . Forty percent of the heparin group had 35 episodes of ischemia with a mean of 11 + /- 10 minutes per episode and a total ischemic time of 48 + /- 39 minutes per patient with ischemia . Forty-four percent of the no heparin group had 47 episodes of ischemia with a mean of 13 + /- 13 minutes per episode and a total ischemic time of 58 + /- 47 minutes per patient with ischemia . Multiple linear regression analysis to adjust for intergroup differences did not alter the results . Eighty-five percent of all episodes were asymptomatic . Clinical events , such as episodes of chest pain , emergency coronary arteriography , or coronary revascularization , were also similar between groups . Thus the short-term administration of heparin did not alter the incidence or duration of ischemia in patients with unstable angina . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Everolimus-eluting and paclitaxel-eluting stents , compared with bare metal stents , reduced the risk of restenosis in clinical trials with strict inclusion and exclusion criteria . We compared the safety and efficacy of the second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice . METHODS We r and omly assigned 1800 consecutive patients ( aged 18 - 85 years ) undergoing percutaneous coronary intervention at one centre to treatment with everolimus-eluting or paclitaxel-eluting stents . The primary endpoint was a composite of safety and efficacy ( all-cause mortality , myocardial infa rct ion , and target vessel revascularisation ) within 12 months . Patients were not told which stent they had been allocated . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT01016041 . FINDINGS Follow-up was completed in 1797 patients . The primary endpoint occurred in 56 ( 6 % ) of 897 patients in the everolimus-eluting stent group versus 82 ( 9 % ) of 903 in the paclitaxel-eluting stent group ( relative risk 0.69 [ 95 % CI 0.50 - 0.95 ] , p value for superiority=0.02 ) . The difference was attributable to a lower rate of stent thrombosis ( 6 [ < 1 % ] vs 23 [ 3 % ] , 0.26 [ 0.11 - 0 - 64 ] , p=0.002 ) , myocardial infa rct ion ( 25 [ 3 % ] vs 48 [ 5 % ] , 0.52 [ 0.33 - 0.84 ] , p=0.007 ) , and target vessel revascularisation ( 21 [ 2 % ] vs 54 [ 6 % ] , 0.39 [ 0.24 - 0.64 ] , p=0.0001 ) . Cardiac death , non-fatal myocardial infa rct ion , or target lesion revascularisation occurred in 44 [ 5 % ] patients in the everolimus-eluting stent group versus 74 [ 8 % ] patients in the paclitaxel-eluting stent group , p value for superiority was 0.005 . INTERPRETATION The everolimus-eluting stent is better than the second generation paclitaxel-eluting stent in unselected patients in terms of safety and efficacy . On the basis of our results , we suggest that paclitaxel-eluting stents should no longer be used in everyday clinical practice . FUNDING Unrestricted grants from Abbott Vascular and Boston Scientific PURPOSE To evaluate the clinical efficacy and safety of subcutaneous ( SC ) low molecular weight heparin ( LMWH ) compared to intravenous ( IV ) non fractioned heparin ( NFH ) in unstable angina , acute myocardial infa rct ion and post-percutaneous transluminal coronary angioplasty . METHODS From September/92 to April/94 , 314 patients were r and omized in two groups . Group I-- 154 patients treated with SC LMWH , using in the 1st phase SC LMWH with a dosage of 160 UaXa IC/kg/day ( group IA--92 patients ) , and in the 2nd , a dosage of 320 UaXa IC/kg/day ( group IB--62 patients ) . Group II--160 patients treated with IV NFH 100UI/kg ( bolus ) , followed by 1000UI/h with adjusted dosage by activated partial thromboplastin time . RESULTS There was not a statistically significant difference among the three groups in relation to cardiac events , hemorrhagic complications and deaths . CONCLUSION The clinical efficacy and safety of SC LMWH in patients with unstable angina , acute myocardial infa rct ion and post-percutaneous transluminal coronary angioplasty were similar to IV NFH with the dosages used in this study The Fragmin and /or Early Revascularisation during Instability in Coronary Artery Disease ( FRISC II ) trial will , in a prospect i ve multicenter factorially r and omized study , compare the efficacy of 3 months continuation of subcutaneous treatment with the low-molecular-weight heparin dalteparin ( Fragmin ) with that of placebo and will also compare a direct invasive strategy with a stepwise selective approach with regard to the utilization of coronary angiography and revascularization in patients with unstable coronary artery disease . The primary endpoints are death or myocardial infa rct ion after 3 and 6 months respectively . Secondary endpoints are the same events after 12 - 24 months and also cardiac symptoms , exercise capacity , and /or signs of myocardial ischemia , readmission , and costs . Analyses will also be made of subgroups based on inclusion diagnosis , initial elevation of biochemical markers of myocardial damage , elevation of fibrinogen or C-reactive protein , signs of ischemia in electrocardiography at rest or at continuous 24-hour ischemia monitoring , and left ventricular function at echocardiography . Altogether , 3,100 patients will be recruited in 65 - 70 Sc and inavian centers . Completion of follow-up is anticipated in the second half of 1998 . The FRISC II study will further eluci date new alternatives for antithrombotic , invasive , and individually tailored treatment of unstable coronary syndromes AIMS At least one quarter of ST-segment elevation myocardial infa rct ion ( STEMI ) patients do not receive reperfusion therapy , and these patients are at high risk for new ischaemic events . We evaluated fondaparinux treatment vs. usual care , i.e. placebo or unfractionated ( UF ) heparin , in a pre-specified subgroup of 2867 ( out of 12 092 ) patients not receiving reperfusion treatment in the OASIS-6 trial . METHODS In all , 1458 patients were r and omized to fondaparinux 2.5 mg once daily subcutaneously up to 8 days and 1409 patients to usual care ( control ) . R and omization was stratified by indication for UF heparin ( stratum II , n = 1226 ) or not ( stratum I , n = 1641 ) based on the investigator 's judgment . RESULTS The proportion of patients who suffered death or myocardial re-infa rct ion at 30 days ( primary outcome ) was 12.2 % in the fondaparinux vs. 15.1 % in the control group , hazard ratio ( HR ) 0.80 ; 95 % confidence interval ( CI ) 0.65 - 0.98 . There was no increase in severe bleedings , HR 0.82 ; CI 0.44 - 1.55 , or strokes , HR 0.62 ; CI 0.29 - 1.33 . Consequently , the composite of death , myocardial re-infa rct ion , or severe bleeding were significantly reduced at 30 days , HR 0.81 ; CI 0.67 - 0.99 . Reductions in death or myocardial re-infa rct ion at 30 days were consistent in stratum I with fondaparinux vs. placebo , HR 0.88 ; 95 % CI 0.65 - 1.19 , and in stratum II with fondaparinux vs. UF heparin infusion for 24 - 48 h ( n = 806 ) , HR 0.74 ; CI 95 % 0.57 - 0.97 , P = 0.41 for heterogeneity . CONCLUSION In STEMI patients not receiving reperfusion treatment , fondaparinux reduces the composite of death or myocardial re-infa rct ion without an increase in severe bleedings or strokes as compared to placebo or UF heparin BACKGROUND Although coronary thrombosis plays a critical role in the pathogenesis of unstable angina and non-Q-wave myocardial infa rct ion ( NQMI ) , the effects of thrombolytic therapy in these disorders is not clear . Also , the role of routine early coronary arteriography followed by revascularization has not been established . METHODS AND RESULTS Patients ( n = 1473 ) seen within 24 hours of ischemic chest discomfort at rest , considered to represent unstable angina or NQMI , were r and omized using a 2 x 2 factorial design to compare ( 1 ) TPA versus placebo as initial therapy and ( 2 ) an early invasive strategy ( early coronary arteriography followed by revascularization when the anatomy was suitable ) versus an early conservative strategy ( coronary arteriography followed by revascularization if initial medical therapy failed ) . All patients were treated with bed rest , anti-ischemic medications , aspirin , and heparin . The primary end point for the TPA-placebo comparison ( death , myocardial infa rct ion , or failure of initial therapy at 6 weeks ) occurred in 54.2 % of the TPA-treated patients and 55.5 % of the placebo-treated patients ( P = NS ) . Fatal and nonfatal myocardial infa rct ion after r and omization ( reinfa rct ion in NQMI patients ) occurred more frequently in TPA-treated patients ( 7.4 % ) than in placebo-treated patients ( 4.9 % , P = .04 , Kaplan-Meier estimate ) . Four intracranial hemorrhages occurred in the TPA-treated group versus none in the placebo-treated group ( P = .06 ) . The end point for the comparison of the two strategies ( death , myocardial infa rct ion , or an unsatisfactory symptom-limited exercise stress test at 6 weeks ) occurred in 18.1 % of patients assigned to the early conservative strategy and 16.2 % of patients assigned to the early invasive strategy ( P = NS ) . In the latter , the average length of initial hospitalization , incidence of rehospitalization within 6 weeks , and days of rehospitalization all were significantly lower . CONCLUSIONS In the overall trial , patients with unstable angina and NQMI were managed with low rates of mortality ( 2.4 % ) and myocardial infa rct ion or reinfa rct ion ( 6.3 % ) at the time of the 6-week visit . These results can be achieved using either an early conservative or early invasive strategy , the latter result ing in a reduced incidence of days of hospitalization and of rehospitalization and in the use of antianginal drugs . The addition of a thrombolytic agent is not beneficial and may be harmful OBJECTIVES This study was design ed to test the hypothesis that low molecular weight heparin may lessen the severity of ischemic events in patients with unstable angina . BACKGROUND Unstable angina is a thrombotic process that requires intensive medical treatment . Although current treatments can reduce the number of complications , serious bleeding continues to occur . Nadroparin calcium , a low molecular weight heparin , seems to be a safe therapeutic agent that does not require laboratory monitoring . METHODS A total of 219 patients with unstable angina entered the study at a mean time of 6.17 h after the last episode of rest pain . Patients were r and omized to receive aspirin ( 200 mg/day [ group A ] ) , aspirin plus regular heparin ( 400 IU/kg body weight per day intravenously and titered by activated partial thromboplastin time [ group B ] ) and aspirin plus low molecular weight heparin ( 214 UIC/kg anti-Xa twice daily subcutaneously [ group C ] ) . The major end points determined for the in-hospital period were 1 ) recurrent angina , 2 ) myocardial infa rct ion , 3 ) urgent revascularization , 4 ) major bleeding , and 5 ) death . Minor end points were 1 ) silent myocardial ischemia , and 2 ) minor bleeding . Event rates were tested by chi-square analysis . RESULTS Recurrent angina occurred in 37 % , 44 % and 21 % of patients in groups A , B and C , respectively , and was significantly less frequent in group C than in either group A ( odds ratio 2.26 , 95 % confidence interval [ CI ] 1 to 5.18 , p = 0.03 ) or group B ( odds ratio , 3.07 , 95 % CI 1.36 to 7.00 , p = 0.002 ) . Nonfatal myocardial infa rct ion was present in seven patients in group A , four in group B and none in group C ( group B vs. A , p = 0.5 ; group C vs. A , p = 0.01 ) . Urgent revascularization was performed in nine patients in group A , seven in group B and one in group C ( C vs. A , p = 0.01 ) . Two episodes of major bleeding occurred in group B. Silent myocardial ischemia was present in 38 % , 41 % and 25 % of patients in groups A , B and C , respectively , and was significantly less frequent in group C than group B ( odds ratio 2.12 , 95 % CI 0.97 to 4.69 , p = 0.04 ) . Minor bleeding was detected in 10 patients in group B , 1 patient in group C ( B vs. C , p = 0.01 ) and no patient in group A ( A vs. B , p = 0.003 ) . CONCLUSIONS In this study , treatment with aspirin plus a high dose of low molecular weight heparin during the acute phase of unstable angina was significantly better than treatment with aspirin alone or aspirin plus regular heparin We studied the therapeutic effect of st and ard heparin ( HS ) compared with low-molecular-weight ( HBPM ) in two homogeneous groups of 14 patients heparin selected at r and om , with clinical history and electrocardiographic signs of unstable angina pectoris . Patients received the conventional treatment with platelets ' inhibitors , nitrates , adrenergic beta-blockers or calcium antagonists . Both heparins , separately , showed statistical therapeutic effect on the symptoms and signs of unstable angina pectoris . They decreased to zero the number and duration of symptomatic myocardial ischemic events observed by ambulatory electrocardiogram ( EKG-Holter ) . The symptoms of the angina pectoris disappeared at the same elapsed time : in 51.9 + /- 20.2 min . for the HS , and in 48.14 + /- 20.7 min . for the HBPM . They decreased the frequency of the silent myocardial ischemia observed at the EKG-Holter : 9 events decreased to 4 with the HS , and 8 events decreased to 3 with the HBPM . They decreased the total elapsed time of the silent ischemia from 52 min . to 15 min . , and the mean elapsed time of the silent ischemia decreased from 3.71 + /- 3.29 min . to 1.07 + /- 1.81 min . with the HS ( P < 0.001 ) . With HBPM it decreased the total elapsed time of the silent ischemia from 60 min to 10 min , and the mean elapsed time of the silent ischemia decreased from 4.28 + /- 4.49 min . to 0.71 + /- 1.43 min . ( P < 0.02 ) . Both heparins considerably decreased the frequency of the lethal arrhythmias . Although in this study we did not find statistical differences in the therapeutic action of either heparins , HBPM reduced rapidly angina symptoms and the events associated to angina pectoris , cardiac arrhythmias , specially lethal extrasystolia , conduction defects and atrial paroxysmal tachycardia . Compared to HS , HBPM is easily applied , does not produce side effects on coagulation or bleeding time We conducted a multicenter , double-blind , placebo-controlled r and omized trial of aspirin treatment ( 324 mg in buffered solution daily ) for 12 weeks in 1266 men with unstable angina ( 625 taking aspirin and 641 placebo ) . The principal end points were death and acute myocardial infa rct ion diagnosed by the presence of creatine kinase MB or pathologic Q-wave changes on electrocardiograms . The incidence of death or acute myocardial infa rct ion was 51 per cent lower in the aspirin group than in the placebo group : 31 patients ( 5.0 per cent ) as compared with 65 ( 10.1 per cent ) ; P = 0.0005 . Nonfatal acute myocardial infa rct ion was 51 per cent lower in the aspirin group : 21 patients ( 3.4 per cent ) as compared with 44 ( 6.9 per cent ) ; P = 0.005 . The reduction in mortality in the aspirin group was also 51 per cent--10 patients ( 1.6 per cent ) as compared with 21 ( 3.3 per cent)--although it was not statistically significant ; P = 0.054 . There was no difference in gastrointestinal symptoms or evidence of blood loss between the treatment and control groups . Our data show that aspirin has a protective effect against acute myocardial infa rct ion in men with unstable angina , and they suggest a similar effect on mortality The benefit of using subcutaneous low molecular weight heparin for the treatment of acute myocardial infa rct ion is not known . The aim of this study was to determine the efficacy of a low molecular weight heparin ( dalteparin sodium ) for the treatment of acute myocardial infa rct ion in patients not treated with thrombolytic therapy . Twenty-nine cardiological centres from leading hospitals in India participated in this prospect i ve , multicentre , double-blind , placebo-controlled study in two phases which included 1128 patients with acute myocardial infa rct ion . In the acute phase ( between day 1 and 3 of admission ) all the patients received a weight-adjusted dose of subcutaneous dalteparin ( 120 IU/kg twice daily ) . In the second , double-blind phase of acute myocardial infa rct ion , patients were r and omised to receive a fixed dose of dalteparin ( 7,500 IU ) or an identical placebo injection for 30 days . A composite primary endpoint of death , reinfa rct ion , recurrence of angina and emergency revascularisation was used . All the 1128 patients with acute myocardial infa rct ion were included in the trial . In the acute phase , the composite primary endpoint was observed in 58 ( 5.1 % ) patients . Of 1037 paients who were r and omly assigned to receive a fixed dose of dalteparin ( n=519 ) or placebo ( n=518 ) , the composite primary event rate was 6.7 percent and 7.0 percent , respectively ( RR 0.97 ; 95 % CI 0.62 - 1.52 ; p=0.90 ) . To conclude , treatment with dalteparin administered subcutaneously in a weight-adjusted dose of 120 IU/kg twice daily result ed in a lower than expected mortality during the acute phase of myocardial infa rct ion . A lower fixed once daily dose of 7,500 IU during the chronic phase did not confer additional protection The administration of heparin during the first 48 hours following acute myocardial infa rct ion is widely practised . Heparin treatment is also recommended for acute coronary insufficiency on the grounds that it may prevent development of an impending myocardial infa rct ion . These measures had been accepted without support of a controlled clinical trial . By r and om selection , 101 patients hospitalized with a provisional diagnosis of acute myocardial infa rct ion received heparin ( 100 mg . intravenously every eight hours for 48 hours ) and 105 patients were assigned to a control group . Both groups of patients received bishydroxycoumarin ( Dicumarol ) . The mortality in the heparin series was 30 % and in the control group , 28 % . A significantly large number of the heparin-treated patients developed clinical and laboratory proof of recent myocardial infa rct ion . It is concluded that early intermittent intravenous heparin treatment does not lower the mortality in patients with acute myocardial infa rct ion nor does it prevent impending myocardial infa rct ion in patients with acute coronary insufficiency Heparin therapy improves clinical outcomes in patients with thromboembolic disorders [ 1 - 4 ] , but the determination of appropriate heparin dosing is often problematic . Physicians ' dosing decisions vary widely , as do their therapeutic goals [ 5 ] . Practice audits reveal frequent underdosing , with delays in achieving therapeutic anticoagulation leading to suboptimal clinical outcomes [ 6 , 7 ] . Recent research offers hope that clarification of treatment goals and specific dosing guidelines may improve outcomes . Hull and colleagues [ 3 ] reported that rapidly exceeding a therapeutic threshold ( APTT , 1.5 times the control ) reduced the rate of recurrent thromboembolism from 25 % to 2 % , a finding confirmed in other studies [ 4 , 8 - 12 ] . In addition , a retrospective analysis suggested that an initial heparin infusion dose of 1000 units per hour is often insufficient [ 13 ] , and the most recent American College of Chest Physicians Consensus Conference on Antithrombotic Therapy recommends an initial infusion of at least 1250 units per hour [ 14 , 15 ] . Finally , dosing nomogramswhich specify heparin dose adjustments in response to any given APTT levelhave shown promising results [ 16 , 17 ] . Despite these advances , uncertainties remain . R and omized controlled studies have not compared higher initial heparin doses with 1000 units per hour , and many physicians continue to follow this clinical tradition [ 5 ] . Because the relation between bleeding complications and excessive APTT values is controversial [ 3 , 10 , 16 , 18 - 24 ] , so is the optimal upper limit of the therapeutic range [ 5 , 14 , 25 ] . For this reason , Hull and colleagues [ 14 ] and Hirsh [ 25 ] have recently de-emphasized the value of the therapeutic range and have stressed the need to minimize recurrent thromboembolism by rapidly exceeding the therapeutic threshold . Measured against that st and ard , Hull 's nomogram succeeded in 98 % of patients ; however , heparin infusions were routinely started at 1670 units per hour and nearly half of the patients had excessive APTT levels that persisted for 24 hours or more [ 16 ] . The generalizability of this nomogram is limited by its dependence on an APTT test reagent that yields markedly prolonged APTT compared with reagents commonly used in the United States [ 16 , 17 , 26 , 27 ] . ( Activated partial thromboplastin times vary greatly depending on laboratory method used [ 14 - 16 , 25 - 27 ] , analogous to the variability of prothrombin times that prompted development of the International Normalized Ratio . ) We agree with Hull and colleagues that heparin nomograms relentlessly direct the heparin dosage and drive the APTT into the therapeutic range [ 16 ] . We hypothesized that a patient-specific nomogram , based on total body weight ( the single best predictor of individual heparin requirements [ 28 , 29 ] ) would achieve high success rates without the need for prescribing excessive heparin doses . Our study , using the most generalizable APTT test system in North America , compares the performance of our weight-based heparin nomogram with another nomogram reflecting a prevalent st and ard of practice . Our report is the first to describe a weight-based heparin nomogram , the first to compare two nomograms prospect ively , and the first nomogram study to have easily generalizable results . Methods Study Design In a r and omized , controlled trial , we compared two nomograms for intravenous heparin dosing in patients with venous thromboembolism , unstable angina , or arterial thromboembolism . During the first 48 hours of anticoagulation , the appropriate nomogram determined all dosing decisions ( Tables 1 , 2 ) , and warfarin was withheld . We defined two primary outcomes . The first was the time elapsed between initiating heparin therapy and surpassing the therapeutic threshold ( APTT , 1.5 times the control ) , considered the minimum acceptable level of anticoagulation . The second was the time elapsed before achieving therapeutic range ( APTT , 1.5 to 2.3 times the control ) , the optimal goal for intravenous anticoagulation . Table 1 . St and ard Care Nomogram Table 2 . Weight-based Nomogram We did our study simultaneously at two community teaching hospitals : a 700-bed regional referral center in Phoenix , Arizona , and a 250-bed , inner-city hospital in Rochester , New York . Both hospitals are major teaching affiliates of university medical schools , and each maintains a large , accredited internal medicine residency program . Patients Patients admitted between May 1991 and January 1992 were deemed eligible if they were to receive intravenous heparin for one of the following indications : 1 ) pulmonary embolism , diagnosed clinical ly and confirmed by a high-probability lung scan or pulmonary arteriography ; 2 ) proximal deep vein thrombosis , confirmed by ascending venography , impedance plethysmography , or Doppler ultrasonography ; 3 ) unstable angina , diagnosed clinical ly by an attending cardiologist using the Braunwald criteria [ 30 ] ; or 4 ) acute noncoronary arterial ischemia . Exclusion criteria included 1 ) anticoagulant or thrombolytic therapy in the previous 7 days , 2 ) active hemorrhage , 3 ) acute major cerebral vascular event , 4 ) history of heparin-induced thrombocytopenia , and 5 ) known allergy to heparin . A power analysis revealed that a total study size of 100 patients would have 90 % power ( with a type I error of 0.05 ) to detect a 6-hour difference in the mean time needed to achieve the primary outcomes . The Nomograms The st and ard practice nomogram ( Table 1 ) was based on the mode for each of the responses to a survey of 61 internists at our hospitals regarding their usual practice s of heparin administration [ 5 ] . The initial bolus and infusion doses were identical to those recommended by the American College of Chest Physicians at the time the study was done [ 13 ] , and dose adjustments in response to APTT results were similar to those of subsequently published nomograms [ 16 , 17 ] . We constructed the weight-based nomogram Table 2 after we review ed the literature and did a preliminary dosing study . Many reports have described bolus doses ranging from 50 to 150 units per kg body weight and infusion doses from 15 to 25 units per kg per hour [ 8 , 28 , 29 , 31 , 37 ] . In one study , 78 % of patients achieved therapeutic goals rapidly after receiving a bolus of 75 units per kg and an initial infusion of 17 units per kg per hour [ 34 ] . In our preliminary dosing study , the mean dose of heparin required to achieve two consecutive therapeutic APTT values in 24 patients with unstable angina was 17.3 4.0 units per kg per hour [ 38 ] . The initial heparin doses we chose for our weight-based nomogram ( bolus , 80 units per kg ; infusion , 18 units per kg per hour ) supplied 511 units per kg per day , consistent with reports that daily heparin requirements in venous thromboembolism range from 480 to 600 units per kg [ 7 , 39 , 40 ] . Subsequent infusion adjustments in the nomogram were design ed to minimize delay in attaining the therapeutic range . All doses in the weight-based nomogram were calculated based on actual body weight rather than ideal weight . Intervention After informed consent was obtained , patients were r and omized to one of the two nomograms , and preprinted orders for implementation of the appropriate nomogram were charted . Staff nurses , who were not blinded , weighed each patient , calculated doses , and adjusted the infusion rate accordingly . Although the nurses could not influence the results of APTT measurements , several indices of nomogram implementation were monitored to detect any unintended co- interventions . Patients r and omized to st and ard heparin therapy received a 5000-unit bolus of intravenous heparin followed by an infusion dose of 1000 units per hour . Patients in the weight-based heparin group received an intravenous bolus of 80 units per kg , followed by an infusion dose of 18 units per kg per hour . At both hospitals , heparin sodium ( pork derived , Schein Pharmaceuticals Inc. ; New York , New York ) was diluted in 5 % dextrose solution and administered with infusion pumps . Stat APTT levels were drawn every 6 hours . ( This interval approximates four half-lives of heparin , the time required to achieve steady-state kinetics . ) When the staff nurses received the APTT results , they consulted the nomogram and adjusted the heparin dose . No adjustments were made if blood for the APTT was drawn less than 4 hours after the last heparin dose adjustment was made . Measurements All blood specimens for APTT were collected in siliconized Vacutainer tubes ( Bectin-Dickinson Company ; Rutherford , New Jersey ) containing buffered citrate . Both our hospital laboratories use plain Dade actin thromboplastin ( Baxter Healthcare Corporation , Dade Division ; Miami , Florida ) and automated coagulation systems ( MLA Electra 700 and 1000 series , Medical Laboratory Automation Inc. ; Pleasantville , New York ) to determine APTT values . The correlation coefficient for APTT performed with plain Dade actin thromboplastin on these two automated systems , using mean values reported for all plasma sample s in the 1992 College of American Pathologists ' data [ 27 ] , is 0.999 . The normal range for APTT ( mean APTT 2 SD in patients having no known coagulopathy and not receiving anticoagulants ) at both hospitals was 20 to 30 seconds . In the absence of published consensus regarding the definition of control APTT , we used the upper limit of the normal range ( 30 seconds ) as our control APTT in all patients , assuming that 97.5 % of patients ' individual APTT control values would be 30 seconds or less . The primary outcome variables were elapsed time from initiation of heparin therapy until achievement of the two primary outcomes : an APTT value exceeding the therapeutic threshold of 45 seconds ( 1.5 times the control APTT ) and an APTT within the therapeutic range of 46 to 70 seconds ( 1.5 to 2.3 times the control APTT ) . This therapeutic range is consistent with others published [ 2 , 7 , 10 , 13 , 16 , 25 ] and correlates with heparin levels of 0.38 to 0.57 by anti-factor Xa activity ( performed at the University of BACKGROUND Unstable angina is an active thrombotic process that involves thrombus formation and platelets . It requires a rapid and intensive treatment with anticoagulants and antiplatelets . HYPOTHESIS The aim of the present study was to compare the efficacy of a very low molecular weight heparin , OP 2000 , with st and ard heparin in the treatment of unstable angina . Tolerance and safety were also assessed . METHODS The study population included 120 consecutive hospitalized patients with unstable angina r and omized for treatment with very low molecular weight heparin or with st and ard heparin . The dosage of the study drug was 200 mg intramuscular ( i.m . ) the first day followed by 150 mg IM/day . The control drug was st and ard heparin starting at a dosage of 5,000 UI/ml intravenously ( i.v . ) and followed by continuous infusion at an activated partial thromboplastin time-adjusted dosage . The primary end points were death , acute myocardial infa rct ion , urgent revascularization , and recurrence of angina . Tolerability was assessed using bleeding parameters , thrombocytopenia , and allergic reactions . RESULTS Fourteen clinical events were reported in the study group compared with 25 events in the control group ( p < 0.05 ) . No adverse events were reported in either group . CONCLUSION During the acute phase of unstable angina , treatment with a very low molecular weight heparin plus aspirin was more effective than treatment with st and ard heparin plus aspirin Patients with unstable coronary artery disease were r and omly treated either with a combination therapy consisting of nitrates and calcium-channel blockers without or with addition of clinical grade heparin administered subcutaneously ; in order to evaluate the effect of heparin treatment on the fibrinolytic system , tissue plasminogen activator ( t-PA ) and plasminogen activator inhibitor-1 ( PAI-1 ) plasma levels were related to the clinical course of the disease . In heparinized patients thrombin time was prolonged more than 3-fold the normal range indicating effective heparin treatment . Heparinization led to a significant increase in t-PA antigen plasma levels ( p less than 0.0001 ) within approximately four hours while PAI-1 activities remained unaltered . However , the measurable increase of the anticoagulant and pro-fibrinolytic activities of heparin did not result in a short-term benefit for the heparinized patients because the number of further ischemic attacks per patient during the observation period of three days was not different between the two study groups OBJECTIVES We report mortality , infa rct ion , revascularization and repeat hospital admission events for 1 year after enrollment and r and omization in the Thrombolysis in Myocardial Ischemia ( TIMI ) IIIB clinical trial . BACKGROUND The purpose of this trial was to investigate the role of a thrombolytic agent added to conventional medical therapies and to compare an early invasive management strategy to a more conservative early strategy in patients with unstable angina and non-Q wave myocardial infa rct ion . METHODS There were 1,473 patients enrolled , and they received conventional anti-ischemic medical therapies . They were r and omized to therapy with either tissue-type plasminogen activator ( t-PA ) or placebo and also to an early invasive management strategy with coronary arteriography at 18 to 48 h , followed by revascularization as soon as possible if appropriate , or , alternatively , to an early conservative strategy with arteriography and revascularization reserved for failure of initial therapy to prevent recurrent ischemia . The primary end point was a composite outcome variable and was assessed at 42 days . Patients were then managed entirely at the discretion of their treating physician . Follow-up contacts were made at 1 year . RESULTS The incidence of death or nonfatal infa rct ion for the t-PA- and placebo-treated groups was similar after 1 year ( 12.4 % vs. 10.6 % , p = 0.24 ) . The incidence of death or nonfatal infa rct ion was also similar after 1 year for the early invasive and early conservative strategies ( 10.8 % vs. 12.2 % , p = 0.42 ) . A trial of this size should be able to detect differences in relative risk for death or infa rct ion > or = 1.81 with a power of 80 % at a significance level ( alpha ) of 0.01 . Revascularization by 1 year was common , but was slightly more common with the early invasive than the early conservative strategy ( 64 % vs. 58 % , p < 0.001 ) . This result was related entirely to a small difference in angioplasty rates ( 39 % vs. 32 % , p < 0.001 ) inasmuch as rates of bypass grafting by 1 year were equivalent ( 30 % in each group , p = 0.50 ) . The high rate of revascularization in both strategies was accompanied by comparable clinical status at the 1-year follow-up contact . CONCLUSIONS In this large study of unstable angina and non-Q wave myocardial infa rct ion , the incidence of death and nonfatal infa rct ion or reinfa rct ion was low but not trivial after 1 year ( 4.3 % mortality , 8.8 % nonfatal infa rct ion ) . An early invasive management strategy was associated with slightly more coronary angioplasty procedures but equivalent numbers of bypass surgery procedures than a more conservative early strategy of catheterization and revascularization only for signs of recurrent ischemia . The incidence of death or nonfatal infa rct ion , or both , did not differ after 1 year by strategy assignment , but fewer patients in the early invasive strategy group underwent later repeat hospital admission ( 26 % vs. 33 % , p < 0.001 ) . Either strategy is appropriate for patient management ; differences in hospital admissions and revascularization procedures , with their attendant costs , are likely to be minimal Intravenous heparin has been used in the control of myocardial ischaemia in patients with unstable angina . We set out to assess the efficacy of subcutaneous heparin in reducing myocardial ischaemia in patients with unstable angina . 343 of 399 patients with unstable angina were monitored for 24 h and 108 were refractory to conventional antianginal treatment and were entered into a r and omised multicentre trial . 37 patients were assigned to heparin infusion ( partial thromboplastin time 1.5 - 2 times baseline ) , 35 to subcutaneous heparin ( adjusted dose with partial thromboplastin time 1.5 - 2 times baseline ) , and 36 to aspirin ( 325 mg daily ) . All had additional conventional antianginal therapy . After the run-in patients were monitored for 3 days . The primary endpoint was reduced myocardial ischaemia assessed by the number of anginal attacks , silent ischaemic episodes , and duration of ischaemia per day . At 1 week and 1 month we accounted for anginal attacks and other clinical events ( myocardial infa rct ion , revascularisation procedures , and death ) . Aspirin did not significantly affect the incidence of myocardial ischaemia . On the first 3 days , infused and subcutaneous heparin significantly decreased the frequency of angina ( on average by 91 % and 86 % , respectively ) , episodes of silent ischaemia ( by 56 % and 46 % ) , and the overall duration of ischaemia ( 66 % and 61 % ) versus run-in day and aspirin ( p < 0.001 for all variables ) . The favourable effects of heparin therapy remained evident during follow-up . Only minor bleeding complications occurred . Subcutaneous heparin is effective in the control of myocardial ischaemia in patients with unstable angina Patients with acute myocardial infa rct ion ( AMI ) who do not receive early reperfusion therapy are at high risk of reinfa rct ion or death , and the efficacy and safety of antithrombotic therapy in this group of patients has not been evaluated . Enoxaparin is a low-molecular-weight heparin ( LMWH ) that has previously been shown to reduce the incidence of ischemic events in patients with unstable angina or non – Q-wave MI . The principal aims of the TETAMI study are to investigate the efficacy and safety of treatment with enoxaparin or tirofiban ( a glycoprotein IIb/IIIa receptor antagonist ) alone or in combination for 2 to 8 days in patients with AMI who are not eligible for early reperfusion therapy . In this 2 by 2 factorial design study approximately 900 patients will be r and omly assigned , in a blinded manner , to one of four treatments : enoxaparin alone , enoxaparin plus tirofiban , unfractionated heparin ( UFH ) , or UFH plus tirofiban , with appropriate matched placebos . The primary end point is the composite of death , recurrent AMI , and recurrent angina , analyzed at 30 days after AMI . The design and methods of the TETAMI study are described in this article 399 out of 474 in patients with unstable angina were monitored for 48 h and 97 of these were found to be refractory to conventional antianginal treatments and entered a r and omised double-blind study . With the initial protocol heparin infusion or bolus were compared with aspirin ; with a modified protocol , heparin infusion , the best of these three treatments , was compared with alteplase . Patients were monitored for 3 days after starting treatment and then observed clinical ly for 4 more days . On the first days of treatment heparin infusion significantly decreased the frequency of angina ( by 84 - 94 % ) , episodes of silent ischaemia ( by 71 - 77 % ) , and the overall duration of ischaemia ( by 81 - 86 % ) . Heparin bolus and aspirin were not effective . Alteplase caused small ( non-significant ) reductions on the first day only . Only minor bleeding complications occurred CONTEXT Although reperfusion therapy , aspirin , beta-blockers , and angiotensin-converting enzyme inhibitors reduce mortality when used early in patients with acute myocardial infa rct ion ( MI ) , mortality and morbidity remain high . No antithrombotic or newer antiplatelet drug has been shown to reduce mortality in acute MI . OBJECTIVE To evaluate the effects of reviparin , a low-molecular-weight heparin , when initiated early and given for 7 days in addition to usual therapy on the primary composite outcome of death , myocardial reinfa rct ion , or strokes at 7 and 30 days . DESIGN , SETTING , AND PATIENTS A r and omized , double-blind , placebo-controlled trial ( Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infa rct ion Treatment Evaluation [ CREATE ] ) of 15,570 patients with ST-segment elevation or new left bundle-branch block , presenting within 12 hours of symptom onset at 341 hospitals in India and China from July 2001 through July 2004 . INTERVENTION Reviparin or placebo subcutaneously twice daily for 7 days . MAIN OUTCOME MEASURE Primary composite outcome of death , myocardial reinfa rct ion , or stroke at 7 and 30 days . RESULTS The primary composite outcome was significantly reduced from 854 ( 11.0 % ) of 7790 patients in the placebo group to 745 ( 9.6 % ) of 7780 in the reviparin group ( hazard ratio [ HR ] , 0.87 ; 95 % CI , 0.79 - 0.96 ; P = .005 ) . These benefits persisted at 30 days ( 1056 [ 13.6 % ] vs 921 [ 11.8 % ] patients ; HR , 0.87 ; 95 % CI , 0.79 - 0.95 ; P = .001 ) with significant reductions in 30-day mortality ( 877 [ 11.3 % ] vs 766 [ 9.8 % ] ; HR , 0.87 ; 95 % CI , 0.79 - 0.96 ; P = .005 ) and reinfa rct ion ( 199 [ 2.6 % ] vs 154 [ 2.0 % ] ; HR , 0.77 ; 95 % CI , 0.62 - 0.95 ; P = .01 ) , and no significant differences in strokes ( 64 [ 0.8 % ] vs 80 [ 1.0 % ] ; P = .19 ) . Reviparin treatment was significantly better when it was initiated very early after symptom onset at 7 days ( < 2 hours : HR , 0.70 ; 95 % CI , 0.52 - 0.96 ; P = .03 ; 30/1000 events prevented ; 2 to < 4 hours : HR , 0.81 ; 95 % CI , 0.67 - 0.98 ; P = .03 ; 21/1000 events prevented ; 4 to < 8 hours : HR , 0.85 ; 95 % CI , 0.73 - 0.99 ; P = .05 ; 16/1000 events prevented ; and > or = 8 hours : HR , 1.06 ; 95 % CI , 0.86 - 1.30 ; P = .58 ; P = .04 for trend ) . There was an increase in life-threatening bleeding at 7 days with reviparin and placebo ( 17 [ 0.2 % ] vs 7 [ 0.1 % ] , respectively ; P = .07 ) , but the absolute excess was small ( 1 more per 1000 ) vs reductions in the primary outcome ( 18 fewer per 1000 ) or mortality ( 15 fewer per 1000 ) . CONCLUSIONS In patients with acute ST-segment elevation or new left bundle-branch block MI , reviparin reduces mortality and reinfa rct ion , without a substantive increase in overall stroke rates . There is a small absolute excess of life-threatening bleeding but the benefits outweigh the risks In a prospect i ve pilot trial of antithrombotic therapy in the acute coronary syndromes ( ATACS ) of resting and unstable angina pectoris or non-Q-wave myocardial infa rct ion , 3 different antithrombotic regimens in the prevention of recurrent ischemic events were compared for efficacy . Ninety-three patients were r and omized to receive aspirin ( 325 mg/day ) , or full-dose heparin followed by warfarin , or the combination of aspirin ( 80 mg/day ) plus heparin and then warfarin . Trial antithrombotic therapy was added to st and ardized antianginal medication and continued for 3 months or until an end point was reached . Analysis , by intention-to-treat , of the 3-month end points , revealed the following : recurrent ischemia occurred in 7 patients ( 22 % ) after aspirin , in 6 patients ( 25 % ) after heparin and warfarin , and in 16 patients ( 43 % ) after aspirin combined with heparin and then warfarin ; coronary revascularization occurred in 12 patients ( 38 % ) after aspirin , in 12 patients ( 50 % ) after heparin and warfarin , and in 22 patients ( 60 % ) after aspirin combined with heparin and then warfarin ; myocardial infa rct ion occurred in 1 patient ( 3 % ) after aspirin , in 3 patients ( 13 % ) after heparin and warfarin , and in no patient after aspirin combined with heparin and then warfarin ; no deaths occurred after aspirin or after aspirin combined with heparin and then warfarin , but 1 patient ( 4 % ) died after warfarin alone ; major bleeding occurred in 3 patients ( 9 % ) after aspirin , in 2 patients ( 8 % ) after heparin and warfarin , and in 3 patients ( 8 % ) after aspirin combined with heparin and then warfarin . Recurrent myocardial ischemia occurred at 3 + /- 3 days after r and omization . ( ABSTRACT TRUNCATED AT 250 WORDS |
10,524 | 24,360,321 | The present study indicated that selected patients who underwent extended P/D had lower perioperative morbidity and mortality with similar , if not superior , long-term survival compared to EPP , in the context of multi-modality therapy .
This may represent an important paradigm shift in the surgical management of MPM | BACKGROUND Malignant pleural mesothelioma ( MPM ) is an aggressive disease of the pleural lining with a dismal prognosis .
Surgical treatments of MPM with a curative intent include extrapleural pneumonectomy and extended pleurectomy/decortication ( P/D ) . | BACKGROUND Trimodality therapy seems to be the best treatment for malignant pleural mesothelioma ( MPM ) . A large experience served to evaluate the efficacy of surgery followed by adjuvant chemo-radiotherapy . Trimodality therapy results have led us to test induction chemotherapy followed by EPP and adjuvant radiotherapy in stages I-III of MPM . The aim of our study was to evaluate the feasibility of this protocol and to estimate survival . METHODS From 2000 to 2003 , 21 patients with MPM ( 14 males and 7 females , median age 59 years ) were enrolled in the prospect i ve study . Induction chemotherapy consisted of Carboplatin ( AUC 5mg/mL/min on Day 1 ) and Gemcitabine ( 1000mg/m(2 ) on Days 1 , 8 , 15 ) for three to four cycles . EPP was performed 3 - 5 weeks after induction therapy , while post-operative RT was given 4 - 6 weeks after operation . RESULTS Ten patients received three cycles of chemotherapy , 10 patients received four cycles and 1 patient had two cycles . Grade s 3 - 4 haematological toxicity occurred in eight ( 38.1 % ) patients . Chemotherapy response rate was : complete 0 % , partial 33.3 % and stable disease 66.7 % . Seventeen ( 80.9 % ) out of 21 patients underwent EPP with no intra or post-operative mortality with an overall major and minor morbidity rate at 52.4 % . Median survival was 25.5 months , with an overall 1 , 3 and 5-year survival rate of 71 , 33 and 19 % , respectively . CONCLUSIONS In MPM , the combined modality approach using the Carboplatin/Gemcitabine combination as induction chemotherapy is feasible , with good results in terms of survival and morbidity . Our results are similar to those of other studies using a heavier modality treatment The first report of the Mesothelioma and Radical Surgery ( MARS ) trial appeared in the Journal of Thoracic Oncology [ 1 ] . The objective of MARS was to establish the possibility of allocating patients , at r and om , to have either extrapleural pneumonectomy ( EPP ) or no surgical resection . The target — 50 r and omised patients — was reached in late 2008 . Outcomes are not yet available ; however , the trial was not powered to prove effectiveness but to address the question of feasibility . In the MARS trial protocol ( Fig. 1 ) , patients were allocated to either trimodality therapy ( chemotherapy , EPP and radical hemithoracic radiotherapy ) or identical chemotherapy followed by any non-surgical treatment thought appropriate . The trial employed a two-stage consent process . Patients consented to participate in the study for completion of staging , chemotherapy and other work-up ( N = 112 ) . The 2—3 months required for chemotherapy between the first and second consent allowed patients and teams to come to terms with r and omisation as a means of unbiased allocation . Of the 112 patients , 50 ( 45 % ) were eventually r and omised . MARS has shown that unbiased allocation to surgery versus no surgery is not impossible — but it is far from easy . The story of MARS goes back 5 years . Cl aims were being made that EPP had the potential to prolong life [ 2 ] . The data were derived from follow-up studies of multimodality therapy ; one could not discern the effect attributable to surgery . There were no data concerning the denominator from which the cases were drawn , and it is likely that the EPP series include fitter patients with slower progressing cancer . Then , if only patients completing treatment are reported , it follows that these patients must be sufficiently well to receive the second and thirdmodalities of treatment , further biasing the interpretation of outcome . These are some of the pitfalls in the reporting of follow-up studies [ 3 ] . It was against that background that the cancer epidemiologist Julian Peto urged European surgeons to put the question of radical surgery for mesothelioma to the test in the form of a r and omised trial [ 4 ] . While MARS has been recruiting , cl aims for the benefit of EPP have moderated . The Boston group have raised a caution ary note in reporting the high burden of complications occurring in over 60 % of patients [ 5 ] . This was echoed in the Mayo clinic follow-up study in which the authors report The European Organisation for Research and Treatment of Cancer ( EORTC ; protocol 08031 ) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma ( with a severity of cT3N1M0 or less ) . Induction chemotherapy consisted of three courses of cisplatin 75 mg·m−2 and pemetrexed 500 mg·m−2 . Nonprogressing patients underwent extrapleural pneumonectomy followed by post-operative radiotherapy ( 54 Gy , 30 fractions ) . Our primary end-point was “ success of treatment ” and our secondary end-points were toxicity , and overall and progression-free survival . 59 patients were registered , one of whom was ineligible . Subjects ’ median age was 57 yrs . The subjects ’ TNM scores were as follows : cT1 , T2 and T3 , 36 , 16 and six patients , respectively ; cN0 and N1 , 57 and one patient , respectively . 55 ( 93 % ) patients received three cycles of chemotherapy with only mild toxicity . 46 ( 79 % ) patients received surgery and 42 ( 74 % ) had extrapleural pneumonectomy with a 90-day mortality of 6.5 % . Post-operative radiotherapy was completed in 37 ( 65 % ) patients . Grade 3–4 toxicity persisted after 90 days in three ( 5.3 % ) patients . Median overall survival time was 18.4 months ( 95 % CI 15.6–32.9 ) and median progression-free survival was 13.9 months ( 95 % CI 10.9–17.2 ) . Only 24 ( 42 % ) patients met the definition of success ( one-sided 90 % CI 0.36–1.00 ) . Although feasible , trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary BACKGROUND The aim of this multicenter trial was to prospect ively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy ( EPP ) and radiotherapy , including quality of life as outcome . PATIENTS AND METHODS Eligible patients had malignant pleural mesothelioma of all histological types , World Health Organization performance status of zero to two and clinical stage T1-T3 , N0 - 2 , M0 disease considered completely resectable . Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP . Postoperative radiotherapy was considered for all patients . RESULTS In all , 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy . Forty-five patients ( 74 % ) underwent EPP and in 37 patients ( 61 % ) the resection was complete . Postoperative radiotherapy was initiated in 36 patients . The median survival of all patients was 19.8 months [ 95 % confidence interval ( CI ) 14.6 - 24.5 ] . For the 45 patients undergoing EPP , the median survival was 23 months ( 95 % CI 16.6 - 32.9 ) . Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82 % ( N = 36 ) at baseline and 76 % ( N = 26 ) at 3 months after surgery ( P = 0.5 ) . CONCLUSIONS The observed rate of operability is promising . A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery . This approach was not associated with an increase in psychological distress BACKGROUND Malignant pleural mesothelioma ( MPM ) is an aggressive form of cancer arising from the pleural mesothelium . Trimodality therapy ( TMT ) involving extrapleural pneumonectomy with neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy is a recognized treatment option with a curative intent . Despite encouraging results from institutional studies , TMT in the treatment of MPM remains controversial . The present systematic review aims to assess the safety and efficacy of TMT in the current literature . METHODS A systematic review was performed using five electronic data bases from 1 January 1985 to 1 October 2012 . Studies were selected independently by two review ers according to predefined selection criteria . The primary endpoint was overall survival . Secondary endpoints included disease-free survival , disease recurrence , perioperative morbidity and length of stay . RESULTS Sixteen studies were included for quantitative assessment , including one r and omized controlled trial and five prospect i ve series . Median overall survival ranged from 12.8 - 46.9 months . Disease-free survival ranged from 10 - 16.3 months . Perioperative mortality ranged from 0 - 12.5 % . Overall perioperative morbidity ranged from 50 - 82.6 % and the average length of stay was 9 - 14 days . CONCLUSIONS Outcomes of patients who underwent TMT in the current literature appeared to be inconsistent . Four prospect i ve series involving a st and ardised treatment regimen with neoadjuvant chemotherapy indicated encouraging results based on intention-to-treat analysis . However , a small study assessing the feasibility of conducting a r and omized controlled trial for TMT versus conservative treatment reported poor short- and long-term outcomes for patients who underwent pneumonectomy . Overall , results of the present systematic review suggest TMT may offer acceptable perioperative outcomes and long-term survival in selected patients treated in specialized centers Hypothesis : The effectiveness of extrapleural pneumonectomy ( EPP ) to extend quality -adjusted survival in malignant pleural mesothelioma within multimodality treatment should be proven in a r and omized controlled trial if this radical surgery is to be regarded as the st and ard of care . The question was whether r and omization to surgery versus no surgery would be possible . Methods : The Mesothelioma and Radical Surgery trial was planned to r and omize 50 patients to test feasibility . There was a two-stage consent process . At first consent , the patients who were possible c and i date s for radical surgery were registered into the trial for completion of assessment and staging . All received platinum-based chemotherapy . If still eligible , they completed a second consent to be r and omized to have either EPP followed by radical hemithorax radiotherapy or to have continued best care . Results : Patients were recruited through 11 collaborating centers in the United Kingdom . One hundred twelve potentially eligible patients gave informed consent to enter the registration phase and undergo chemotherapy . One died , 27 progressed , five were inoperable , four were treated off trial , and 18 withdrew either during or after chemotherapy but before final review . Additionally six were deemed inoperable at review after completing chemotherapy and one more patient withdrew . The remaining 50 were r and omized ; 24 to EPP and 26 to continued best care . Conclusions : In this study , 50/112 ( 45 % ) of patients entering the evaluation and induction phase of the trial went on to be r and omized . We have shown that this r and omization between surgery and no surgery is feasible . This was the primary aim of the Mesothelioma and Radical Surgery trial Introduction : To compare the outcomes of two different multimodality regimens involving neoadjuvant chemotherapy , extrapleural pneumonectomy ( EPP ) and adjuvant radiotherapy versus pleurectomy/decortication ( P/D ) , hyperthermic pleural lavage with povidone-iodine , and adjuvant chemotherapy in patients with malignant pleural mesothelioma . Methods : Nonr and omized prospect i ve study of patients treated by multimodality therapy and operated on between January 2004 and June 2011 . Second-line treatments were administered when appropriate . Survival and prognostic factors were analyzed by the Kaplan Meier method , log rank test , and Cox regression analysis . Results : Twenty-five consecutive patients received neoadjuvant chemotherapy , 22 underwent EPP , and 17 received adjuvant radiotherapy . Over the same period , 54 consecutive patients underwent P/D and hyperthermic pleural lavage and received prophylactic radiotherapy and adjuvant chemotherapy . The 30-day mortality rate was 4.5%in the EPP group and nil in the P/D group . Fifteen patients ( 68 % ) in the EPP group and 15 ( 27.7 % ) in the P/D group experienced complications . There were no differences between the EPP and P/D groups for age , sex , histology , pathologic stage , and nodal status . Trimodality therapy was completed by 68%of the patients in the EPP group and 100%in the P/D group . Survival was significantly better in the P/D group : median survival was 23 months versus 12.8 months , 2-year survival was 49%versus 18.2 % , and 5-year survival was 30.1%versus 9 % , respectively ( p = 0.004 ) . At multivariate analysis , epithelioid histology , P/D , and completeness of resection were independent prognostic factors . Conclusions : In our experience , P/D , hyperthermic pleural lavage with povidone-iodine , and adjuvant chemotherapy were superior to neoadjuvant chemotherapy , EPP , and adjuvant radiotherapy OBJECTIVE This study was undertaken to determine maximum tolerated dose and toxicity of intraoperative intracavitary hyperthermic cisplatin perfusion with amifostine after extrapleural pneumonectomy for malignant pleural mesothelioma . METHODS Patients with mesothelioma were prospect ively enrolled . Those with resectable disease received amifostine and 1-hour hyperthermic cisplatin perfusion of ipsilateral hemithorax and abdomen . Morbidity , recurrence , and survival were recorded . RESULTS Forty-two patients were enrolled ; 29 underwent resection ( operative mortality 7 % , 2/29 ) . Median age was 57 years . Eighteen were in pathologic stage I or II ; 11 were in stage III . Median hospitalization was 15 days . Common complications were atrial fibrillation ( 66 % , 19 patients ) , deep venous thrombosis ( 31 % , 9 patients ) , and grade 3 + renal toxicity ( 31 % , 9 patients ) . Feasibility was determined . Renal toxicity was unrelated to cisplatin dose , with no maximum tolerated dose determined . Overall median survival was 17 months ( resected 20 months , unresected 10 months ) . Median survivals were 26 months for patients receiving higher cisplatin doses and 16 months for those receiving lower doses ( P = .35 ) . Survival was significantly longer with negative extrapleural nodes ( 31 vs 14 months , P = .0115 ) and early stage ( all resected 35 months for stage I-II vs 14 months for stage III , P = .0022 , epithelial 39 months for stage I-II vs 15 months for stage III , P = .0072 ) . CONCLUSION Early stage and negative extrapleural lymph nodes were associated with prolonged survival . Single-dose amifostine did not protect adequately against cisplatin-induced renal toxicity . Additional cytoprotective strategies are needed to allow determination of cisplatin maximum tolerated dose PURPOSE Neoadjuvant pemetrexed plus cisplatin was administered , followed by extrapleural pneumonectomy ( EPP ) and hemithoracic radiation ( RT ) , to assess the feasibility and efficacy of trimodality therapy in stage I to III malignant pleural mesothelioma . PATIENTS AND METHODS Requirements included stage T1 - 3 N0 - 2 disease , no prior surgical resection , adequate organ function ( including predicted postoperative forced expiratory volume in 1 second > or = 35 % ) , and performance status 0 to 1 . Patients received pemetrexed 500 mg/m(2 ) plus cisplatin 75 mg/m(2 ) for four cycles . Patients without disease progression underwent EPP followed by RT ( 54 Gy ) . The primary end point was pathologic complete response ( pCR ) rate . RESULTS Seventy-seven patients received chemotherapy . All four cycles were administered to 83 % of patients . The radiologic response rate was 32.5 % ( 95 % CI , 22.2 to 44.1 ) . Fifty-seven patients proceeded to EPP , which was completed in 54 patients . Three pCRs were observed ( 5 % of EPP ) . Forty of 44 patients completed irradiation . Median survival in the overall population was 16.8 months ( 95 % CI , 13.6 to 23.2 months ; censorship , 33.8 % ) . Patients completing all therapy had a median survival of 29.1 months and a 2-year survival rate of 61.2 % . Radiologic response of complete or partial response was associated with a median survival of 26.0 months compared with 13.9 months for patients with stable disease or progressive disease ( P = .05 ) . CONCLUSION This multicenter trial showed that trimodality therapy with neoadjuvant pemetrexed plus cisplatin is feasible with a reasonable long-term survival rate , particularly for patients who completed all therapy . Radiologic response to chemotherapy , but not sex , histology , disease stage , or nodal status , was associated with improved survival |
10,525 | 22,033,830 | Results indicate that BPD does not appear to be independently associated with increased risk of violence in the general population .
History of childhood maltreatment , history of violence or criminality , and comorbid psychopathy or antisocial personality disorder appear to be predictors of violence in patients with BPD .
This review concludes that the current evidence suggests that patients with BPD are not more violent than individuals in the general population . | This article aim ed to systematic ally review the current literature regarding elevated risk of aggression in borderline personality disorder ( BPD ) and to review factors that differentiate aggressive from nonaggressive individuals with BPD . | Impulsivity has been repeatedly identified as a key construct in BPD ; however , its precise definition seems to vary especially regarding the overlap with aggression . The term impulsive-aggression , also generally seen as central to an underst and ing of BPD , seems to address itself to the interface between the two , but has itself been used inconsistently in the literature , sometimes having reference to a unitary phenotypic dimension , and at other times suggesting some combination of distinct traits . This study examined the relationship between multiple measures of impulsivity , aggression , and impulsive-aggression in a BPD sample ( N = 92 ) in order to clarify the relationship between these measured constructs in this clinical population . Results show little relationship between measures of aggression and impulsivity in BPD , with measures of impulsive-aggression correlating strongly with measures of aggression only . Implication s of the present results for future research and clinical work with BPD are discussed OBJECTIVE A community-based , longitudinal prospect i ve study was conducted to investigate whether personality disorders during adolescence are associated with elevated risk for violent behavior during adolescence and early adulthood . METHOD A community-based sample of 717 youths from upstate New York and their mothers were interviewed in 1983 , 1985 - 1986 , and 1991 - 1993 . Axis I and II disorders were assessed in 1983 and 1985 - 1986 . Antisocial personality disorder was not assessed because most participants were less than 18 years of age in 1983 and 1985 - 1986 . Violent behavior was assessed in 1985 - 1986 and 1991 - 1993 . RESULTS Adolescents with a greater number of DSM-IV cluster A or cluster B personality disorder symptoms were more likely than other adolescents in the community to commit violent acts during adolescence and early adulthood , including arson , assault , breaking and entering , initiating physical fights , robbery , and threats to injure others . These associations remained significant after controlling for the youths ' age and sex , for parental psychopathology and socioeconomic status , and for co-occurring psychiatric disorders during adolescence . Paranoid , narcissistic , and passive-aggressive personality disorder symptoms during adolescence were independently associated with risk for violent acts and criminal behavior during adolescence and early adulthood after the covariates were controlled . CONCLUSIONS Cluster A and cluster B personality disorders and paranoid , narcissistic , and passive-aggressive personality disorder symptoms during adolescence may increase risk for violent behavior that persists into early adulthood OBJECTIVE The purpose of the study was to identify risk factors and correlates of violence committed by patients in an acute adult psychiatric inpatient unit in a district general hospital of the United Kingdom 's National Health Service . METHODS Incidents of violence committed by in patients over a one-year period in 1997 - 1998 were retrospectively analyzed . The clinical characteristics of 49 violent patients were compared with those of all patients admitted to the unit during the study period ( N=474 ) and with a r and om sample of nonviolent patients ( N=140 ) . Logistic regression analysis was used to identify clinical variables that predicted violent behavior . RESULTS Violence was not positively associated with schizophrenia or negatively associated with depression . Frequent medication change , high use of sedative drugs , past violent behavior , an ICD-10 diagnosis of dissocial personality disorder or emotionally unstable personality disorder ( DSM-IV antisocial personality disorder or borderline personality disorder ) , and long hospitalization were the most powerful predictors of violence . Together these variables had a sensitivity of 76 percent , a specificity of 97 percent , and a positive predictive value of 90 percent in predicting which patients became violent . Compulsory ( involuntary ) admission , comorbid diagnoses , past self-harm , and nonalcohol drug abuse were also associated with violent behavior . CONCLUSIONS Clinicians ' judgment about an inpatient 's potential for violence may be augmented by knowledge of the risk factors identified in this study . Medication variables could be especially useful predictors , particularly when information about other risk factors is not available . Factors other than mental illness per se may be crucial determinants of violence in acute inpatient setting OBJECTIVE The study of personality pathology in adolescence is in its infancy . This article examined the applicability and limits of DSM-IV axis II personality disorder diagnoses in adolescents , assessed the validity of a method for assessing adolescent personality pathology , and began to develop an empirically grounded classification . METHOD A total of 296 r and omly selected clinicians described a patient age 14 - 18 in treatment for maladaptive personality patterns using axis II ratings scales and the Shedler-Westen Assessment Procedure-200 for Adolescents ( SWAP-200-A ) , a Q-sort instrument for assessing adolescent personality pathology . After examining the nature and frequency of axis II disorders in the sample , the authors used Q-factor analysis to identify naturally occurring groupings of patients on the basis of shared personality features . RESULTS Axis II diagnoses in adolescents resembled those in adults , although application of DSM-IV criteria appeared to overdiagnose antisocial and avoidant personality disorder in adolescents . Q analysis with the SWAP-200-A isolated five personality disorders ( antisocial-psychopathic , emotionally dysregulated , avoidant-constricted , narcissistic , and histrionic ) and one personality style . Patients ' dimensional scores on each diagnostic prototype showed predictable associations with ratings of current axis II disorders , measures of adaptive functioning , and symptoms assessed with the Child Behavior Checklist . CONCLUSIONS With some exceptions , personality pathology in adolescence resembles that in adults and is diagnosable in adolescents ages 14 - 18 . Categories and criteria developed for adults may not be the optimal way of diagnosing adolescents . Data from sample s of adolescents may prove useful in developing an empirically and clinical ly grounded classification of personality pathology in adolescents Violence associated with personality disorders is usually best viewed separately from psychiatric diagnosis , as a syndrome of violence rather than a syndrome of diagnosis . The authors describe eight categories of violence associated with personality disorders that may help clinicians choose treatment or management techniques : purpose ful , instrumental violence ; purpose ful , non-instrumental violence ; purpose ful , targeted , defensive violence ; targeted , impulsive violence ; nontargeted , impulsive violence incidental to emotional escape ; r and om but purpose ful violence ; violence related to perceived or feared loss or ab and onment ; and violence related to chronic paranoia or related misconceptions . The categories are not completely mutually exclusive , nor do they represent a " decision tree . " We also point out three important principles about the relationship between personality disorders and violence : 1 ) Personality disorders are rarely ego dystonic ; 2 ) Most patients and violent situations that come to clinical attention involve comorbid conditions . 3 ) Violence and violence risk are often associated with intoxication The Life History of Aggression ( LHA ) assessment was administered to up to 252 subjects . In addition to a total LHA score , subscale scores for Aggression , Social Consequences and Antisocial Behavior , and Self-directed Aggression were calculated . Test-retest stability , interrater agreement , and internal consistency reliability were excellent both for the LHA Total score and the LHA Aggression subscore . There were moderately strong correlations between these scores and both self-reports of aggressive tendency ( Buss-Durkee Hostility Inventory : n = 214 ) and recent overt aggression ( Overt Aggression Scale-Modified for Out- patients : n = 61 ) . LHA Total scores were highest among subjects with Antisocial or Borderline Personality Disorder . These results support the use of the LHA assessment , and especially the LHA Aggression subscore , as a measure of life history of aggressive behavior Theorists and clinicians have long believed that personality psychopathology is a risk factor for aggressive behavior . Previous investigations in this area , however , have provided mixed results . In this study , the relationship between personality psychopathology and aggressive behavior was examined in 137 research volunteers . The influences of gender and coexisting major mental disorders were statistically controlled . Aggressive behavior was associated with criteria for 7 of the 11 personality disorders listed in the Diagnostic and Statistical Manual of Mental Disorders ( 3rd ed . , rev . ) . Except for schizoid criteria , all relationships with aggressive behavior were in the positive direction . When all personality disorders were considered simultaneously , paranoid and passive-aggressive criteria were significant predictors of aggressive behavior |
10,526 | 29,121,285 | Conclusions The literature is not conclusive on whether the use of NSAIDs is associated with anastomotic leaks after gastrointestinal cancer surgery .
Also , the current evidence is equivocal regarding the effects of short-term NSAIDs on cancer recurrence after major cancer surgery .
There are no registered RCTs that are testing the hypothesis of whether the perioperative use of NSAIDs increases the rate of anastomotic leaks | Background Non-steroidal anti-inflammatory drugs ( NSAIDs ) are effective analgesic drugs .
Recent studies have indicated a potential beneficial effect on long-term survival outcomes after cancer surgery but a negative impact on anastomotic leaks .
The objective of this study was to objective ly assess the implication s of the perioperative NSAIDs use on anastomotic leaks and cancer recurrence . | Background Non-steroid anti-inflammatory drugs ( NSAIDs ) have been proposed as part of a multimodal postoperative analgesia in patients operated for colorectal cancer . However , whether these drugs are prescribed and taken by the patients have not been evaluated . The aim of this study was to quantify the postoperative use of NSAIDs in these patients . Methods Data from patients operated for colorectal cancer between January 1 , 2006 and December 31 , 2009 were collected from the Danish Colorectal Cancer Group ’s ( DCCG ) prospect i ve data base . From the electronically registered medical records , data for the use of the two NSAIDs diclofenac and ibuprofen were recorded . The data from six colorectal departments in eastern Denmark were compared . Results Of the 2,754 patients analyzed overall , 40.6 % received NSAIDs as part of their analgesic treatment . The percentage of the patients receiving NSAIDs , receiving a pre-defined dosage as a minimum and receiving NSAIDs as p.r.n . medication , and the type of NSAID were significantly different both between department and within departments . The median dose of ibuprofen and diclofenac were 1200 mg ( 400–2,400 mg ) and 100 mg ( 50–200 mg ) , respectively . Conclusions The large variation between and within the departments points to an inconsistency in the use of multimodal post-operative pain treatments . This may be a result of insufficient evidence on procedure specific pain treatments and possibly a lack of compliance to existing guidelines . High- quality large-scale studies are warranted to form the basis for guidelines for postoperative analgesic treatment Cancer cells treated with the cyclooxygenase-2 inhibitor celecoxib show growth inhibition and induced apoptosis . This study was conducted to determine if the same processes are relevant to celecoxib 's effects on human colorectal adenocarcinomas treated in vivo . A cohort of 23 patients with primary colorectal adenocarcinomas was r and omised to receive a 7-d course of celecoxib ( 400 mg b.i.d . ) or no drug prior to surgical resection . Gene expression profiling was performed on resected adenocarcinomas from the cohort of patients . Using fold change ( > 1.5 ) and p-value ( < 0.05 ) cut-offs , 190 genes were differentially expressed between adenocarcinomas from patients receiving celecoxib and those that did not . The celecoxib pre-treated sample s showed decreased expression levels in multiple genes involved in cellular lipid and glutathione metabolism ; changes associated with diminished cellular proliferation . Celecoxib pre-treatment for 7 d in vivo is associated with alterations in colorectal adenocarcinoma gene expression which are suggestive of diminished cellular proliferation OBJECTIVE To evaluate the impact of preemptive local analgesia at the incision site in reducing pain in women undergoing abdominal hysterectomy for a benign myomatous uterus . STUDY DESIGN In this prospect i ve , r and omized , double-blinded , placebo-controlled study , 20 mL of 1 % lidocaine or 0.9 % saline was injected at the abdominal incision site prior to the performance of the hysterectomy . Thirty-two women were enrolled in the study , 16 received preemptive analgesia while 14 were treated by placebo ; 2 were excluded . All operations were performed under general anesthesia . The st and ard postoperative pain treatment consisted of oral analgesia with ibuprofen ( 400 mg ) in liquid-filled capsules . Morphine ( 10 mg ) was used for rescue analgesia . Pain intensity was self-evaluated with the use of a 100 mm visual analog scale . RESULTS Compared to the placebo group , women who received preemptive analgesia with lidocaine 1 % perceived a significant reduction in postoperative pain in the first hours after surgery ( 2 h : 50.1+/-27.9 versus 70.6+/-22.6 , p=0.043 ; 5 h : 42.5+/-25.2 versus 64.6+/-28.3 , p=0.043 ; 8 h : 31.2+/-22.4 versus 53.3+/-30.3 , p=0.031 ) . CONCLUSION Preemptive analgesia with lidocaine 1 % is a simple , cheap and efficient mode to reduce pain in the first hours after hysterectomy Purpose During cancer surgery , prostagl and in-mediated inflammation may promote and activate micrometastatic disease with a consequent increase in long-term cancer recurrence . Cyclooxygenase-2 inhibitors , known to have anti-proliferative properties , may offset such perioperative perturbation . We investigated the effectiveness of these agents to minimize inflammatory changes during cancer surgery . Methods Following ethics approval , 32 patients who were to undergo major intracavity cancer surgery were enrolled in this prospect i ve , r and omized , clinical trial . The treatment group received 400 mg celecoxib preoperatively followed by five 200 mg 12-hourly doses . The control group received no anti-inflammatory agents . Inflammatory and immunomodulatory end points were measured serially . The primary end points were the measured plasma and urinary prostagl and in E metabolite ( PGEM ) levels 48 hours following surgery . Secondary endpoints included interleukin levels , leucocyte profile , and clinical end points . Results No differences in the 48-hr plasma or urinary PGEM levels were observed between the celecoxib and control groups . Linear mixed modeling , used to accommo date differences in baseline PGEM levels , showed that celecoxib ( cf . control ) administration lowered plasma PGEM over the entire 48-hr period following surgery ( β-coefficient = −0.38 pg.ml−1 ; 95 % confidence interval : −0.69 to −0.06 ; P = 0.021 ) . Celecoxib administration also lowered postoperative pain scores . Discussion St and ard dosing of the cyclooxygenase-2 inhibitor celecoxib slightly reduced perioperative cyclooxygenase activity during cancer surgery . Given cyclooxygenase ’s role in cancer pathways , we recommend dose-finding studies be undertaken before prospect i ve clinical trials are conducted testing the currently unsubstantiated hypothesis that perioperative anti-inflammatory administration improves long-term cancer outcomes . This trial was registered at : Australian New Zeal and Clinical Trial Registry : ACTRN12615000041550 ; www.anzctr.org.auRésuméObjectifPendant les chirurgies du cancer , l’inflammation médiée par les prostagl and ines pourrait favoriser et activer une maladie micrométastatique avec une augmentation conséquente de la récurrence du cancer à long terme . Les inhibiteurs de la cyclo-oxygénase-2 , do nt on connaît les propriétés antiprolifératives , pourraient compenser une telle perturbation périopératoire . Nous avons étudié l’efficacité de ces agents pour minimiser les changements inflammatoires pendant les chirurgies du cancer . MéthodeAprès avoir obtenu le consentement du Comité d’éthique , 32 patients devant subir une chirurgie ouverte majeure pour un cancer ont été enrôlés dans cette étude clinique prospect i ve et r and omisée . Le groupe traitement a reçu 400 mg de célécoxib avant l’opération , puis cinq doses de 200 mg aux 12 heures . Le groupe témoin n’a reçu aucun agent anti-inflammatoire . Les critères d’évaluation d’inflammation et d’immunomodulation ont été mesurés en série . Les critères d’évaluation principaux étaient les taux de métabolites des prostagl and ines E ( PGEM ) mesurés dans le plasma et dans l’urine 48 h après la chirurgie . Les critères d’évaluation secondaires comprenaient les taux d’interleukine , le profil leucocytaire ainsi que des critères d’évaluation cliniques . RésultatsAucune différence n’a été observée dans les taux de PGEM dans le plasma ou l’urine à 48 h entre le groupe célécoxib et le groupe témoin . Un modèle linéaire mixte , utilisé pour tenir compte des différences dans les taux de base de PGEM , a démontré que l’administration de célécoxib réduisait les PGEM dans le plasma tout au long de la période de 48 h suivant la chirurgie ( coefficient β = −0,38 ; intervalle de confiance 95 % : −0,69 à −0,06 ; P = 0,021 ) . L’administration de célécoxib a également réduit les scores de douleur postopératoires . Discussion Une posologie st and ard de l’inhibiteur de cyclo-oxygénase 2 qu’est le célécoxib a légèrement réduit l’activité périopératoire de la cyclo-oxygénase pendant une chirurgie du cancer . Étant donné le rôle de la cyclo-oxygénase dans les voies de développement du cancer , nous recomm and ons de tester l’hypothèse , actuellement non vérifiée , selon laquelle l’administration périopératoire d’anti-inflammatoires améliorerait les pronostics oncologiques à long terme , avant de réaliser des études cliniques prospect ives . Cette étude est enregistrée au : Registre australien et néozél and ais des études cliniques : ACTRN12615000041550 ; OBJECTIVE To determine pre-/intraoperative risk factors for anastomotic leak after colon resection for cancer and to create a practical instrument for predicting anastomotic leak risk . BACKGROUND Anastomotic leak is still the most dreaded complication in colorectal surgery . Many risk factors have been identified to date , but multicentric prospect i ve studies on anastomotic leak after colon resection are lacking . METHODS Fifty-two hospitals participated in this prospect i ve , observational study . Data of 3193 patients , operated for colon cancer with primary anastomosis without stoma , were included in a prospect i ve online data base ( September 2011-September 2012 ) . Forty-two pre-/intraoperative variables , related to patient , tumor , surgical procedure , and hospital , were analyzed as potential independent risk factors for anastomotic leak ( 60-day follow-up ) . A nomogram was created to easily predict the risk of anastomotic leak for a given patient . RESULTS The anastomotic leak rate was 8.7 % , and widely varied between hospitals ( variance of 0.24 on the logit scale ) . Anastomotic leak significantly increased mortality ( 15.2 % vs 1.9 % in patients without anastomotic leak , P < 0.0001 ) and length of hospitalization ( median 23 vs 7 days in uncomplicated patients , P < 0.0001 ) . In the multivariate analysis , the following variables were independent risk factors for anastomotic leak : obesity [ P = 0.003 , odds ratio ( OR ) = 2.7 ] , preoperative serum total proteins ( P = 0.03 , OR = 0.7 per g/dL ) , male sex ( P = 0.03 , OR = 1.6 ) , ongoing anticoagulant treatment ( P = 0.05 , OR = 1.8 ) , intraoperative complication ( P = 0.03 , OR = 2.2 ) , and number of hospital beds ( P = 0.04 , OR = 0.95 per 100 beds ) . CONCLUSIONS Anastomotic leak after colon resection for cancer is a frequent , relevant complication . Patients , surgical technique , and hospital are all important determining factors of anastomotic leak risk BACKGROUND : Nonsteroidal anti-inflammatory drugs have become an important component of narcotic-sparing postoperative pain management protocol s. However , conflicting evidence exists regarding the adverse association of nonsteroidal anti-inflammatory drug use with intestinal anastomotic healing in colorectal surgery . OBJECTIVE : This study compares patients receiving nonsteroidal anti-inflammatory drugs on postoperative day 1 with patients who did not receive nonsteroidal anti-inflammatory drugs with regard to the occurrence of anastomotic leaks . DESIGN : This is a retrospective study from a protocol -driven prospect ively collected statewide data base . A propensity score model was used to adjust for differences between the groups in patient demographics , characteristics , comorbidities , and laboratory values . SETTING S : The multicenter data set used in this analysis represents a variety of academic and community hospitals within the state of Michigan from July 2012 through February 2014 . PATIENTS : Nonpregnant patients over the age of 18 who underwent colon and rectal surgery with bowel anastomosis were selected . MAIN OUTCOME MEASURES : Occurrence of anastomotic leak , composite surgical site infection , sepsis , and death within 30 days of surgery were the primary outcomes measured . RESULTS : A total of 4360 patients met inclusion criteria , of which 1297 ( 29.7 % ) received nonsteroidal anti-inflammatory drugs and 3063 ( 70.3 % ) did not receive nonsteroidal anti-inflammatory drugs . There was no statistically significant difference between the 2 groups in the proportion of cases with anastomotic leak ( OR , 1.33 ; CI , 0.86–2.05 ; p = 0.20 ) , composite surgical site infection ( OR , 1.26 ; CI , 0.96–1.66 ; p = 0.09 ) , or death within 30 days ( OR , 0.58 ; CI , 0.28–1.19 ; p = 0.14 ) . There was a significantly greater risk of sepsis for patients given nonsteroidal anti-inflammatory drugs than for those patients not given nonsteroidal anti-inflammatory drugs ( OR , 1.47 ; CI , 1.05–2.06 ; p = 0.03 ) . LIMITATIONS : This is a nonr and omized study performed retrospectively , and it is based on data collected only within a subset of hospitals in the state of Michigan . CONCLUSIONS : No statistically significant increase in the proportion of patients with anastomotic leak was observed when prescribing nonsteroidal anti-inflammatory drugs for analgesia in the early postoperative period for patients undergoing elective colorectal surgery . Unexpectedly , there was an increased risk of sepsis that warrants further investigation ( see video , Supplemental Digital Content 1 , http://links.lww.com/DCR/A192 , for a synopsis of this study ) BACKGROUND Anastomotic leakage is one of serious complications of colorectal surgery . Research is inconsistent about whether non-steroidal anti-inflammatory drugs influence the healing of colorectal anastomoses and increase the incidence of anastomotic leakage . OBJECTIVE To study the influence of NSAIDs on the healing of rat colonic anastomoses . DESIGN This was an animal r and omized-control trial . This study was approved by the ethical committee of Yangpu Hospital , Tongji University . INTERVENTION 90 healthy Sprague-Dawley rats were r and omly divided into 6 groups of 15 rats/group . Trail was performed in C ( cotrol group ) with no drugs , group M with morphine for analgesia , group F with flurbiprofen axeil , group L with lornoxicam , and group P with parecoxib sodium . MAIN OUTCOME MEASURES The main outcomes measures were serological indexes including vascular endothelial growth factor , prostagl and in E2 , hydroxyproline , and C reactive protein ; histological specimens from the anastomotic stoma tissue including the collagen proportion , and hydroxyproline , cycloxygenase-2 , and vascular endothelial growth factor content ; physical indicators , including stoma fracture pressure , fracture strength and anastomotic leakage . RESULTS No significant difference was observed among the indices of each group ( P > 0.05 ) . A significant difference occurred after operation ( P < 0.05 ) , with the data for groups K and M being dramatically higher than those for group F. LIMITATION The study was nonblinded . CONCLUSION The postoperative usages of non-steroidal anti-inflammatory drugs can decrease the strength of anastomotic tissue , and increase the incidence of anastomotic leakage BACKGROUND Analgesics are commonly used to provide pain relief after surgery . These drugs produce some extended depression of immunity . A prospect i ve r and omized controlled trial was design ed to observe expressions of T-lymphocyte subsets ( CD3(+ ) , CD3(+)CD4(+ ) and CD3(+)CD8(+ ) ) , natural-killer cells ( CD3(-)CD16(+)CD56(+ ) ) , and activated T-lymphocytes ( CD3(+)CD25(+ ) ) of patients undergoing gastric cancer surgeries and receiving patient-controlled intravenous analgesia ( PCIA ) . METHODS Forty-five patients undergoing elective gastric cancer surgeries under general anesthesia were r and omly allocated into 3 groups . Group I received PCIA using morphine after surgery , group II using tramadol , and group III using tramadol with lornoxicam . The analgesic efficacy was evaluated by visual analog scale ( VAS ) and Bruggrmann comfort scale ( BCS ) . Expressions of CD3(+ ) , CD3(+)CD4(+ ) , CD3(+)CD8(+ ) , CD3(-)CD16(+)CD56(+ ) , and CD3(+)CD25(+ ) were measured as percentages of total lymphocytes by flow cytometer at 5 time points . RESULTS There was no significant difference in analgesic efficacy and the baselines of CD3(+ ) , CD3(+)CD4(+ ) , CD3(+)CD8(+ ) , CD3(-)CD16(+)CD56(+ ) , and CD3(+)CD25(+ ) in all groups . Compared with the baseline , CD3(+)CD8(+ ) had no changes in all groups at any time point . Ninety minutes after incision , CD3(+ ) , CD3(+)CD4(+ ) , CD3(-)CD16(+)CD56(+ ) , and CD3(+)CD25(+ ) were lower in all groups ( P<0.05 ) . 24 h after surgery , CD3(+ ) , CD3(+)CD4(+ ) , CD3(-)CD16(+)CD56(+ ) , and CD3(+)CD25(+ ) were lower in group I and group II ( P<0.05 ) ; meanwhile CD3(+ ) , CD3(+)CD4(+ ) , and CD3(+)CD25(+ ) returned to the baseline but CD3(-)CD16(+)CD56(+ ) was still low ( P<0.05 ) in group III . 48 h after surgery , CD3(+ ) , CD3(+)CD4(+ ) , CD3(-)CD16(+)CD56(+ ) , and CD3(+)CD25(+ ) returned to the baseline in group II and group III , but not in group I ( P<0.05 ) . 72 h after surgery , CD3(+ ) , CD3(+)CD4(+ ) , CD3(+)CD4(+)/CD3(+)CD8(+ ) returned to the baseline , but CD3(+)CD25(+ ) and CD3(-)CD16(+)CD56(+ ) were still low in group I ( P<0.05 ) . CONCLUSION PCIA using lornoxicam with tramadol has the same good analgesic efficacy and less immunity depression than PCIA using morphine or tramadol BACKGROUND : In this r and omized study , we compared intrathecal ( IT ) morphine with or without clonidine and IV postoperative patient-controlled analgesia ( PCA ) morphine for analgesia after radical retropubic prostatectomy . METHODS : Fifty patients were r and omly divided into three groups . They were allocated to receive IT morphine ( 4 & mgr;g/kg ) ( M group ) , IT morphine and clonidine ( 1 & mgr;g/kg ) ( MC group ) , or PCA ( PCA group ) . Each patient was given morphine PCA for postoperative analgesia . The primary objective was the quantity of morphine required during the first 48 postoperative hours . The first request for morphine , numeric pain score at rest and on coughing , the time of tracheal decannulation and adverse effects ( pruritus , postoperative nausea and vomiting , respiratory depression ) were recorded . RESULTS : Morphine consumption in the first 48 h was decreased in the M and MC groups . The numeric pain score at rest and on coughing were lower in the M group until the 18th postoperative hour and until the 24th postoperative hour in the MC group . The first requests for PCA were delayed in these two groups . The need for intraoperative sufentanil was significantly lower in the MC group . CONCLUSION : IT morphine provided a significant reduction in morphine requirement during the first 48 postoperative hours after a radical prostatectomy . The addition of clonidine to IT morphine reduced intraoperative sufentanil use , prolonged time until first request for PCA rescue , and further prolonged analgesia at rest and with coughing Background : Retrospective studies have drawn attention to possible detrimental effects of non-steroidal anti-inflammatory drugs ( NSAIDs ) on the anastomotic leakage rate after colorectal resection . In this study , we examined the effects of the NSAID diclofenac on the breaking strength of an experimental colonic anastomosis and a skin incision as well as subcutaneous collagen accumulation . Methods : This was a r and omized , blinded , placebo-controlled experimental study in 60 male Wistar rats treated with diclofenac 4 mg/kg/day or placebo . In each rat , a colonic anastomosis was performed and an exp and ed polytetrafluoroethylene ( ePTFE ) tube was placed subcutaneously . Incisional and anastomotic wound breaking strength and hydroxyproline content in the ePTFE tubes were measured 7 days after the operation . Results : We found no significant differences in any of the breaking strength measurements , but showed a median 38 % reduction in hydroxyproline deposition as a result of diclofenac treatment ( p = 0.03 ) . In the placebo group , subcutaneous collagen deposition tended to correlate positively with skin incisional but negatively with anastomotic bio-mechanical strength . Conclusion : Postoperative diclofenac treatment significantly inhibited collagen deposition in subcutaneous granulation tissue . Anastomotic strength and skin wound strength were not significantly affected . The ePTFE model is suitable for assessing the effect of various drugs on collagen formation and thus on wound healing Background : Recently , many studies have suggested a possible adjuvant role of aspirin in colorectal cancer , reporting a positive prognostic effect with its use in patients with established disease . The aim of this study was to investigate the anticancer effect of aspirin use during preoperative chemoradiation for rectal cancer . Methods : Two hundred and forty-one patients with stage II – III rectal cancer and c and i date s for chemoradiation ( CRT ) were selected and assigned to two groups : group 1 , patients taking aspirin at the time of diagnosis , and group 2 , all others . Treatment and oncological outcomes were explored . Results : Aspirin use was associated with a higher rate of tumour downstaging ( 67.6 % vs 43.6 % , P=0.01 ) , good pathological response ( 46 % vs 19 % ; P<0.001 ) , and a slightly , although not significant , higher rate of complete pathological response ( 22 % vs 13 % ; P=0.196 ) . Aspirin use was also associated with a better 5-year progression-free survival ( 86.6 % vs 67.1 % ; hazard rate (HR)=0.20 ; 95 % CI=0.07–0.60 ) and overall survival ( 90.6 % vs 73.2 % ; HR=0.21 ; 95 % CI=0.05–0.89 ) . Although chance of local relapse was similar ( HR=0.6 ; 95 % CI=0.06–4.5 ) , aspirin use was associated with a lower risk of developing metastasis ( HR=0.30 ; 95 % CI=0.10–0.86 ) . Conclusions : Aspirin might have anticancer activity against rectal cancer during preoperative CRT . This finding could be clinical ly relevant and should be further investigated with r and omised trials PURPOSE Laboratory and case-control studies suggest a pivotal role for the cyclooxygenase-2 ( COX-2 ) pathway in colorectal carcinogenesis . The purpose of this study was to test whether the COX-2 inhibitor rofecoxib could reduce recurrence and improve survival when administered in the adjuvant setting of colorectal cancer ( CRC ) . PATIENTS AND METHODS Patients who had undergone potentially curative surgery and completion of adjuvant therapy for stage II and III CRC were r and omly assigned to receive rofecoxib ( 20 mg daily ) or placebo . The primary end point was overall survival ( OS ) . Where formalin-fixed paraffin-embedded tumor tissue sample s were available , COX-2 expression was evaluated by immunohistochemistry and correlated with clinical outcome . RESULTS Two thous and four hundred thirty-four patients were entered onto the study . The trial was terminated early because of the worldwide withdrawal of rofecoxib . At this point , 1,167 patients had received rofecoxib and 1,160 patients had received placebo for median treatment duration s of 7.4 and 8.2 months , respectively . For the rofecoxib and placebo arms , median follow-up times were 4.84 and 4.85 years , with 241 and 246 deaths and 297 and 329 recurrences , respectively . No difference was demonstrated in OS ( hazard ratio [ HR ] = 0.97 ; 95 % CI , 0.81 to 1.16 ; P = .75 ) or recurrence ( HR = 0.89 ; 95 % CI , 0.76 to 1.04 ; P = .15 ) comparing the two groups . Tumor COX-2 expression by immunohistochemistry was assessed for 871 patients , but neither prognostic nor predictive effects were observed . CONCLUSION In this study of abbreviated therapy in the adjuvant setting of CRC , rofecoxib did not improve OS or protect from recurrence in unselected patients . In addition , COX-2 expression did not correlate with prognosis overall or predict effectiveness of COX-2 inhibitors BACKGROUND An association between the use of non-steroidal anti-inflammatory drugs ( NSAIDs ) and better outcome after mastectomy and lung surgery for cancer has been recently suggested . In a retrospective analysis , we investigated the association between intraoperative NSAIDs use in conservative breast cancer surgery and breast cancer disease-free survival ( DFS ) . Similarly , we also evaluated the association between breast cancer DFS and preoperative neutrophil : lymphocyte ratio ( NLR ) . METHODS A retrospective analysis of a single-centre cohort was performed in breast cancer patients ( n=720 ) with uni- and multivariate analyses , using a Cox regression model . RESULTS In conservative breast cancer surgery , the intraoperative use of NSAIDs ( ketorolac or diclofenac ) was associated with an improved DFS { hazard ratio (HR)=0.57 [ 95 % confidence interval ( CI ) : 0.37 - 0.89 ] , P=0.01 } and an improved overall survival ( OS ) [ HR=0.35 ( 95 % CI : 0.17 - 0.70 ) , P=0.03 ] . In these patients , an NLR > 3.3 ( identified by a receiver-operating characteristic curve ) was associated with a shorter DFS [ HR=1.99 ( 95 % CI : 1.16 - 3.41 ) , P=0.01 ] and OS [ HR=2.35 ( 95 % CI : 1.02 - 5.43 ) , P=0.046 ] . CONCLUSIONS Intraoperative NSAIDs and higher preoperative NLR are associated with improved outcome in conservative breast cancer surgery . Prospect i ve , r and omized trials to evaluate if these associations are causal are warranted Pre clinical studies have demonstrated that opioid receptor agonists increase the rate of non‐small cell lung cancer ( NSCLC ) growth and metastasis . Following institutional review board approval , we retrieved data on 901 patients who underwent surgery for NSCLC at MD And erson Cancer Center . Comprehensive demographics , intraoperative data , and recurrence‐free survival ( RFS ) and overall survival ( OS ) at 3 and 5 years were obtained . Cox proportional analyses were conducted to assess the association between intraoperative opioid exposure and RFS and OS . The median intraoperative fentanyl equivalents dosage was 10.15 μg/kg . The multivariate analysis by stage indicated that a trend toward significance for opioid consumption as a risk factor in stage I patients ( P = 0.053 ) . No effect was found on RFS for stage II or III patients . Alternatively , opioid consumption was a risk factor for OS for stage I patients ( P = 0.036 ) , whereas no effect was noted for stage II or III patients . Intraoperative opioid use is associated with decreased OS in stage I but not stage II – III NSCLC patients . Until r and omized controlled studies explore this association further , opioids should continue to be a key component of balanced anesthesia Objective : The purpose of this study was to identify patient , clinical , and surgical factors that may predispose patients to anastomotic leak ( AL ) after large bowel surgery . Background : Anastomotic leak is still one of the most devastating complications following colorectal surgery . Knowledge about factors predisposing patients to AL is vital to its early detection , decision making for surgical time , managing preoperative risk factors , and postoperative complications . Methods : This was a prospect i ve observational , quality improvement study in a cohort of 616 patients undergoing colorectal resection in a single institution with the main outcome being AL within 30 days postoperatively . Some of the predictor variables were age , sex , Charlson Comorbidity Index ( CCI ) , radiation and chemotherapy , immunomodulator medications , albumin , preoperative diagnoses , surgical procedure(s ) , surgical technique ( laparoscopic vs open ) , anastomotic technique ( staple vs h and sewn ) , number of major arteries ligated at surgery , surgeon 's experience , presence of infectious condition at surgery , intraoperative adverse events , and functional status using 36-Item Short Form General Health Survey . Results : Of the 616 patients , 53.4 % were female . The median age of the patients was 63 years and the mean body mass index was 25.9 kg/m2 . Of them , 80.3 % patients had laparoscopic surgery and 19.5 % had open surgery . AL occurred in 5.7 % ( 35 ) patients . In multivariate analysis , significant independent predictors for leak were anastomoses less than 10 cm from the anal verge , CCI of 3 or more , high inferior mesenteric artery ligation ( above left colic artery ) , intraoperative complications , and being of the male sex . Conclusions : Multiple risk factors exist that predispose patients to ALs . These risk factors should be considered before and during the surgical care of colorectal patients Introduction Non-steroidal anti-inflammatory drugs ( NSAIDs ) decrease postoperative pain and opioid consumption . The objective of the study was to determine if postoperative NSAIDs were associated with anastomotic leaks following elective colorectal surgery . Material s and Methods We used a matched nested case-control study design . Using a prospect ively collected data base , we identified all patients having elective colorectal surgery between January 2001 and June 2012 . Cases and matched controls were identified based on the occurrence of a postoperative anastomotic leak . The primary and secondary exposure variables were , respectively , use of any NSAID and use of ketorolac specifically . Conditional logistic regression was used to determine the unadjusted and adjusted odds ratio . Results A total of 262 patients were included ( 65.6 % inflammatory bowel disease , 34.4 % cancer ) . Use of any NSAID was associated with a non-significant increase in anastomotic leaks ( odds ratio ( OR ) 1.81 , 95 % confidence interval ( CI ) 0.98–3.37 , p = 0.06 ) . Use of ketorolac was associated with a significant increase in anastomotic leaks ( OR 2.09 , 95 % CI 1.12–3.89 , p = 0.021 ) . There was no significant association between anastomotic leaks and cumulative NSAID dose . Conclusion These data suggest that there may be an association between NSAIDs and risk of anastomotic leaks after colorectal surgery . Further research is needed to better eluci date this relationship to clarify the implication s for patients BACKGROUND Vascular endothelial growth factor-C ( VEGF-C ) , tumor necrosis factor-α ( TNF-α ) , and interleukin-1ß(IL-1ß ) have been shown to be associated with the recurrence and metastasis of breast cancer after surgery . This study tested the hypothesis that patients undergoing surgery for breast cancer , who received postoperative analgesia with flurbiprofen axetil combined with small doses of fentanyl ( FA ) , exhibited reduced levels of VEGF-C , TNF-α , and IL-1ß compared with those patients receiving fentanyl alone ( F ) . METHOD Forty-women with primary breast cancer undergoing a modified radical mastectomy were r and omized to receive postoperative analgesia with flurbiprofen axetil combined with fentanyl or fentanyl alone . Venous blood was sample d before anesthesia , at the end of surgery , and at 48 hours after surgery , and the serum was analyzed . The primary endpoint was changes in the VEGF-C concentrations in serum . RESULTS Group FA patients reported similar analgesic effects as group F patients at 2 , 24 , and 48 hours . At 48 hours , mean postoperative concentrations of VEGF-C in group F patients were higher than in group FA patients , 730.9 versus . 354.1 pg/mL ( P = 0.003 ) , respectively . The mean postoperative concentrations of TNF-α in group F patients were also higher compared with group FA patients 27.1 vs. 15.8 pg/mL ( P = 0.005 ) . Finally , the mean postoperative concentrations of IL-1ß in group F were also significantly higher than in group FA 497.5 vs. 197.7 pg/mL ( P = 0.001 ) . CONCLUSION In patients undergoing a mastectomy , postoperative analgesia with flurbiprofen axetil , combined with fentanyl , were associated with decreases in serum concentrations of VEGF-C , TNF-α , and IL-1ß compared with patients receiving doses of only fentanyl OBJECTIVE Acute pain can lead to immune dysfunction , which can be partly ameliorated by successful pain management . Opioids , which are widely used for analgesia , can result in the deterioration of immune function . This study aim ed to investigate the influence of morphine with or without flurbiprofen as post-operative analgesics on the immune systems of patients undergoing gastric cancer surgery . METHODS 60 patients undergoing gastric cancer surgery were equally r and omized into two groups . They received post-operative patient-controlled intravenous ( IV ) analgesia using morphine either with or without flurbiprofen . Visual analogue scale ( VAS ) scores , Bruggemann comfort scale ( BCS ) scores , morphine consumption , time of first flatus , incidence of nausea/vomiting , and T-lymphocyte subsets ( CD3⁺ , CD4⁺ , and CD8⁺ ) and natural killer cells ( CD3⁻CD16⁺CD56⁺ ) were evaluated . RESULTS No significant difference was observed in the VAS scores , BCS scores , and nausea/vomiting incidence between groups . Less morphine was consumed and the time of first flatus was earlier in patients receiving morphine with flurbiprofen than morphine alone . The expression of CD3⁺ , CD4⁺ , CD4⁺/CD8⁺ , and CD3⁻CD16⁺CD56⁺ decreased at 2 hours after incision and , except for CD3⁻CD16⁺CD56⁺ , returned to baseline at 120 hours after surgery . Moreover , the expression of CD3⁻CD16⁺CD56⁺ at 2 hours after incision and the expression of CD3⁺ , CD4⁺ , CD4⁺/CD8⁺ , and CD3⁻CD16⁺CD56⁺ at 24 hours after surgery were higher in patients receiving morphine with flurbiprofen than morphine alone . CONCLUSION The combination of morphine and flurbiprofen ameliorates the immune depression in Tlymphocyte subsets and natural killer cells and provides a similar analgesic efficacy to morphine alone in patients undergoing gastric cancer surgery Background The objective of this study was to determine if intravenous ketorolac can reduce ileus following laparoscopic colorectal surgery , thus shortening hospital stay . Methods This was a prospect i ve , r and omized , double-blind , placebo-controlled , clinical trial of patients undergoing laparoscopic colorectal resection and receiving morphine patient controlled analgesia ( PCA ) and either intravenous ketorolac ( group A ) or placebo ( group B ) , for 48 h after surgery . Daily assessment s were made by a blinded assistant for level of pain control . Diet advancement and discharge were decided according to strictly defined criteria . Results From October 2002 to March 2005 , 190 patients underwent laparoscopic colorectal surgery . Of this total , 84 patients were eligible for this study and 70 consented . Another 26 patients were excluded , leaving 22 patients in each group . Two patients who suffered anastomotic leaks in the early postoperative period were excluded from further analysis . Median length of stay for the entire study was 4.0 days , with significant correlation between milligrams of morphine consumed and time to first flatus ( r = 0.422 , p = 0.005 ) , full diet ( r = 0.522 , p < 0.001 ) , and discharge ( r = 0.437 , p = 0.004 ) . There we no differences between groups in age , body mass index , or operating time . Patients in group A consumed less morphine ( 33 ± 31 mg versus 63 ± 41 mg , p = 0.011 ) , and had less time to first flatus ( median 2.0 days versus 3.0 days , p < 0.001 ) and full diet ( median 2.5 days versus 3.0 days , p = 0.033 ) . The reduction in length of stay was not significant ( mean 3.6 days versus 4.5 days , median 4.0 days versus 4.0 days , p = 0.142 ) . Pain control was superior in group A. Three patients required readmission for treatment of five anastomotic leaks ( 4 in group A versus 1 in group B , p = 0.15 ) . Two of them underwent reoperation . Conclusions Intravenous ketorolac was efficacious in improving pain control and reducing postoperative ileus when anastomotic leaks were excluded . This simple intervention shows promise in reducing hospital stay , although the outcome was not statistically significant . The high number of leaks is inconsistent with this group ’s experience and is of concern PURPOSE To assess the biologic activity of celecoxib , a selective cyclooxygenase-2 inhibitor , in men with recurrent prostate cancer using change in prostate-specific antigen ( PSA ) doubling time ( PSADT ) as the primary outcome variable . PATIENTS AND METHODS Participants had histologically confirmed prostate cancer , no recent hormone therapy , rising serum PSA after radical prostatectomy and /or radiation therapy , and no radiographic evidence of metastases . Patients were r and omly assigned to celecoxib ( 400 mg by mouth twice daily ) or placebo . Treatment continued until disease progression or until adverse effects stopped treatment . A positive outcome was defined as post-treatment PSADT of more than 200 % baseline PSADT with no new metastases . RESULTS The study was terminated early after information about the cardiovascular safety of celecoxib prompted review of ongoing clinical studies . Before discontinuation of the study , 78 men were assigned r and omly to either celecoxib or placebo . Eight ( 20 % ) of 40 men in the placebo group and 15 ( 40 % ) of 38 men in the celecoxib group had post-treatment PSADT of more than 200 % of baseline PSADT with no new metastases ( P = .08 ) . Mean PSA velocity increased by 3.0 % for the placebo group and decreased by 3.4 % for the celecoxib group ( P = .02 ) . CONCLUSION Although the primary efficacy objective was not met , this study provides some evidence for biologic activity of celecoxib in prostate cancer . Compared with placebo , celecoxib significantly decreased mean PSA velocity and tended to increase the proportion of men who doubled their PSADT Introduction Recent evidence raises concern about the use of perioperative non-steroidal anti-inflammatory drug ( NSAID ) use after colorectal resection . The purpose of this retrospective cohort study was to investigate the relationship between perioperative ketorolac use and anastomotic leakage after colorectal surgery . Methods A retrospective review ( 2004–2011 ) was performed on patients who underwent elective colorectal surgery . Univariate analysis and multivariate logistic regression were used to evaluate the association between patients who did not receive any NSAIDs and those who received ketorolac within the first 5 days perioperatively and leak rate . Results A total of 731 patients were identified as having resection with primary anastomosis : 376 ( 51.4 % ) received no NSAIDs and 355 ( 48.6 % ) received ketorolac perioperatively within 5 days after their surgery . There were 24 ( 3.3 % ) leaks , with 12 in both the no NSAIDs ( 3.2 % ) and ketorolac ( 3.4 % ) groups , odds ratio ( OR ) 1.06 ( 0.43 , 2.62 ; p = 0.886 ) . Adjusting for smoking , steroid use , and age , there remained no significant difference between ketorolac use and leakage , OR 1.21 ( 0.52 , 2.84 ; p = 0.660 ) . In our multivariate model , only smoking was a significant predictor of postoperative leak , OR 3.34 ( 1.30 , 8.62 ; p = 0.021 ) . Conclusions There does not appear to be a significant association between perioperative ketorolac use and anastomotic leakage after colorectal surgery . However , further prospect i ve studies are needed to confirm our findings before definitive guidelines on NSAID use perioperatively can be recommended Purpose : Flurbiprofen axetil ( FA ) is a potent non-steroidal antiinflammatory drug ( NSAID ) . We examined the effects that perioperative intravenous administration of FA , combined with thoracic epidural anesthesia and postoperative patient-controlled epidural analgesia ( PCEA ) , have on bowel function , postoperative pain , and cytokine release , after open colorectal surgery . Methods : This was a prospect i ve , r and omized , double-blind , placebo-controlled study . Forty patients were r and omly assigned to one of two groups ( n=20 in each group ) . The FA group patients received FA 1 mg·kg−1iv , 30 min before and six hours after skin incision ; whereas the control group patients received an equal volume of intralipid . Blood cytokine levels were measured before FA administration , at the end of surgery , and six hours and 24 hr postoperatively . All patients received postoperative PCEA for pain control . Analgesic efficacy was evaluated for 72 hr postoperatively using visual analogue scale ( VAS ) pain scores both at rest and during coughing . Gastrointestinal motility was recorded . Temperature and leukocyte count were measured preoperatively , and 24 hr postoperatively . Results : The times to first bowel movement ( 87±23vs 105±19 hr , P=0.008 ) and first flatus ( 63±16vs 75±11 hr , P=0.01 ) were earlier in the FA group compared to the control group . For the first 24 hr , the pain scores in the FA group were also lower during coughing ( P<0.001 compared to control ) . The plasma concentrations of interleukin (IL)-6 and IL-8 in the FA group were lower , postoperatively ( P<0.01 and P<0.05 , respectively , compared to control ) . In contrast , the IL-10 levels were significantly increased at six hours , postoperatively , in the FA group ( P=0.009 ) . The total leukocyte count and the incidence of pyrexia were also lower in patients of the FA group ( P=0.001 0.001 and P=0.006 , respectively , compared to control ) . Conclusion : Flurbiprofen axetil may have an anti-inflammatory effect in major abdominal surgery . The combination of perioperative intravenous FA , intraoperative thoracic epidural anesthesia , and postoperative PCEA facilitated recovery of bowel function , enhanced analgesia , and attenuated the cytokine response . RésuméObjectif : Le flurbiprofène axétil ( FA ) est un agent antiinflammatoire non stéroïdien ( AINS ) puissant . Nous avons évalué les effets d’une administration intraveineuse périopératoire de FA , en présence d’une anesthésie péridurale thoracique et d’une analgésie péridurale contrôlée par le patient ( APCP ) postopératoire , sur la fonction intestinale , la douleur postopératoire et la libération de cytokines à la suite d’une chirurgie colorectale ouverte . Méthode : Nous avons mené une étude prospect i ve , r and omisée , à double insu et contrôlée par placebo . Quarante patients ont été r and omisés dans deux groupes ( n=20 dans chaque groupe ) . Les patients du groupe FA ont reçu du FA 1 mg·kg-1 iv 30 min avant et six heures après l’incision de la peau ; les patients du groupe témoin ont , quant à eux , reçu un volume équivalent d’Intralipide . Les niveaux de cytokines plasmatiques ont été mesurés avant l’administration de FA , à la fin de la chirurgie , et six et 24 h après l’opération . Tous les patients ont reçu une APCP pour le contrôle de la douleur . L’efficacité analgésique a été évaluée à 72 h après l’opération sur la base des scores de douleur sur une échelle visuelle analogue ( EVA ) au repos et à la toux . La motilité gastro-intestinale a été enregistrée . La température et la numération leucocytaire ont été mesurées avant l’opération et 24 h après l’opération . Résultats : Les temps jusqu’à la première défécation ( 87±23 vs 105±19 h , P=0,008 ) et jusqu’aux premières flatuosités ( 63±16 vs 75±11 h , P=0,01 ) étaient plus courts dans le groupe FA que dans le groupe témoin . Durant les 24 premières heures , les scores de douleur à la toux étaient également moindres dans le groupe FA ( P<0,001 par rapport au groupe témoin ) . Les concentrations plasmatiques d’interleukine (IL)-6 et IL-8 étaient plus basses dans le groupe FA après l’opération ( P<0,01 et P<0,05 , respectivement , par rapport au groupe témoin ) . En revanche , les niveaux IL-10 étaient significativement plus élevés à six heures après l’opération dans le groupe FA ( P=0,009 ) . La numération leucocytaire totale et l’incidence de pyrexie étaient également plus bas dans le groupe FA ( P=0,001 et P=0,006 , respectivement , par rapport au groupe témoin ) . Conclusion : Le flurbiprofène axétil pourrait avoir un effet antiinflammatoire lors de chirurgies abdominales majeures . La combinaison de FA intraveineux périopératoire , d’anesthésie péridurale thoracique peropératoire et d’APCP postopératoire a facilité le rétablissement de la fonction intestinale , amélioré l’analgésie , et atténué la sécrétion des cytokines BACKGROUND : Nonsteroidal antiinflammatory drugs have become increasingly popular as part of multimodal analgesic regimens for pain management in the ambulatory setting . We design ed this r and omized , double-blind , placebo-controlled study to evaluate the effect of postoperative administration of either a nonselective nonsteroidal antiinflammatory drug ( ibuprofen ) or the cyclooxygenase-2 selective inhibitor ( celecoxib when administered as part of a multimodal analgesic regimen ) on the severity of pain , the need for rescue analgesics , and clinical ly relevant patient outcomes after ambulatory surgery . The primary end point was the time to resumption of normal activities of daily living . METHODS : One hundred eighty patients undergoing outpatient surgery were r and omly assigned to 1 of 3 treatment groups : group 1 ( control ) received either 2 placebo capsules ( matching celecoxib ) or 1 placebo tablet ( matching ibuprofen ) in the recovery room and 1 placebo tablet at bedtime on the day of surgery , followed by 1 placebo capsule or tablet 3 times a day for 3 days after discharge ; group 2 ( celecoxib ) received celecoxib 400 mg ( 2 capsules ) orally in the recovery room and 1 placebo capsule and tablet at bedtime on the day of surgery , followed by celecoxib 200 mg ( 1 capsule ) twice a day + placebo capsule every day at bedtime for 3 days after surgery ; or group 3 ( ibuprofen ) received ibuprofen 400 mg ( 1 tablet ) orally in the recovery room and 400 mg orally at bedtime on the day of surgery , followed by 400 mg orally 3 times a day for 3 days after surgery . Recovery times , postoperative pain scores , and the need for rescue analgesics were recorded before discharge . Follow-up evaluations were performed at 24 hours , 48 hours , 72 hours , 7 days , and 30 days after surgery to assess postdischarge pain , analgesic requirements , resumption of normal activities , opioid-related side effects , as well as quality of recovery and patient satisfaction with their postoperative pain management using a 5-point verbal rating scale . RESULTS : The 3 groups did not differ with respect to their demographic characteristics . Compared with the placebo treatment , both celecoxib and ibuprofen significantly decreased the need for rescue analgesic medication after discharge ( P < 0.05 ) . The effect sizes ( celecoxib and ibuprofen versus control group ) were 0.73 to 1 and 0.3 to 0.8 , respectively . Quality of recovery scores and patient satisfaction with their postoperative pain management were also improved in the celecoxib and ibuprofen groups compared with the control group ( P < 0.05 , effect size [ vs control group ] = 0.67 ) . The incidence of postoperative constipation was significantly higher in the control group ( 28 % ) compared with the celecoxib ( 5 % ) and ibuprofen ( 7 % ) groups , respectively ( P < 0.05 ) . Both active treatments were well tolerated in the postdischarge period . However , the time to resumption of normal activities of daily living was similar among the 3 groups . CONCLUSIONS : Both ibuprofen ( 1200 mg/d ) and celecoxib ( 400 mg/d ) significantly decreased the need for rescue analgesic medication in the early postdischarge period , leading to an improvement in the quality of recovery and patient satisfaction with their pain management after outpatient surgery A number of interventions have been used to decrease the incidence of post‐operative paralytic ileus . A secondary outcome of a r and omized controlled study showed that COX‐2 inhibitors decreased the incidence of paralytic ileus . We sought to study a large cohort of patients undergoing major abdominal operations who were treated with a COX‐2 inhibitor Background : Over a period our department experienced an unexpected high frequency of anastomotic leakages . After diclofenac was removed from the postoperative analgesic regimen , the frequency dropped . This study aim ed to evaluate the influence of diclofenac on the risk of developing anastomotic leakage after laparoscopic colorectal surgery . Methods : This was a retrospective case-control study based on 75 consecutive patients undergoing laparoscopic colorectal resection with primary anastomosis . In period 1 , patients received diclofenac 150 mg/day . In period 2 , diclofenac was withdrawn and the patients received an opioid analgesic instead . The primary outcome parameter was clinical ly significant anastomotical leakage verified at reoperation . Results : 1/42 patients in the no-diclofenac group compared with 7/33 in the diclofenac group had an anastomotic leakage after operation ( p = 0.018 ) . In a multivariate regressional analysis , none of the recorded factors were significantly associated with the frequency of anastomotical leakages when diclofenac treatment was omitted from the model . Conclusions : We found an increased number of clinical ly significant anastomotic leakages in patients receiving oral diclofenac for postoperative analgesia . There is an urgent need to test our hypothesis in prospect i ve r and omized clinical trials and to examine whether our findings can be extended to open surgery and to other NSAIDs Objectives To evaluate the effect of postoperative use of non-steroidal anti-inflammatory drugs ( NSAIDs ) on anastomotic leakage requiring reoperation after colorectal resection . Design Cohort study based on data from a prospect i ve clinical data base and electronically registered medical records . Setting Six major colorectal centres in eastern Denmark . Participants 2766 patients ( 1441 ( 52 % ) men ) undergoing elective operation for colorectal cancer with colonic or rectal resection and primary anastomosis between 1 January 2006 and 31 December 2009 . Median age was 70 years ( interquartile range 62 - 77 ) . Intervention Postoperative use of NSAID ( defined as at least two days of NSAID treatment in the first seven days after surgery ) . Main outcome measures Frequency of clinical anastomotic leakage verified at reoperation ; mortality at 30 days . Results Of 2756 patients with available data and included in the final analysis , 1871 ( 68 % ) did not receive postoperative NSAID treatment ( controls ) and 885 ( 32 % ) did . In the NSAID group , 655 ( 74 % ) patients received ibuprofen and 226 ( 26 % ) received diclofenac . Anastomotic leakage verified at reoperation was significantly increased among patients receiving diclofenac and ibuprofen treatment , compared with controls ( 12.8 % and 8.2 % v 5.1 % ; P<0.001 ) . After unadjusted analyses and when compared with controls , more patients had anastomotic leakage after treatment with diclofenac ( 7.8 % ( 95 % confidence interval 3.9 % to 12.8 % ) ) and ibuprofen ( 3.2 % ( 1.0 % to 5.7 % ) ) . But after multivariate logistic regression analysis , only diclofenac treatment was a risk factor for leakage ( odds ratio 7.2 ( 95 % confidence interval 3.8 to 13.4 ) , P<0.001 ; ibuprofen 1.5 ( 0.8 to 2.9 ) , P=0.18 ) . Other risk factors for anastomotic leakage were male sex , rectal ( v colonic ) anastomosis , and blood transfusion . 30 day mortality was comparable in the three groups ( diclofenac 1.8 % v ibuprofen 4.1 % v controls 3.2 % ; P=0.20 ) . Conclusions Diclofenac treatment could result in an increased proportion of patients with anastomotic leakage after colorectal surgery . Cyclo-oxygenase-2 selective NSAIDs should be used with caution after colorectal resections with primary anastomosis . Large scale , r and omised controlled trials are urgently needed BACKGROUND : Cyclo-oxygenase 2 inhibitors can be used for pain treatment after colorectal surgery . OBJECTIVE : The aim of this study was to investigate whether the use of etoricoxib has negative effects on the perioperative outcome in colorectal surgery . DESIGN : Complication data from an advanced medical data base system were sample d prospect ively , and patient records were review ed retrospectively . PATIENTS : All patients with elective colorectal surgery within an enhanced recovery after surgery protocol from 2008 to 2009 were selected . INTERVENTION : The nonr and omized use of perioperative etoricoxib treatment was compared with a control group . MAIN OUTCOME MEASURES : The primary outcome measured was the number of patients with postoperative complications according to the Dindo-Clavien classification . RESULTS : One hundred one patients received etoricoxib treatment , whereas 104 did not . The patient groups were very comparable . We observed a significant increase in the number of patients with postoperative complications with etoricoxib treatment ( 43 vs 30 patients ; 42.6 % vs 28.8 % , p = 0.041 ) due to an increase in patients with a major complication ( Dindo-Clavien complication grade III – V : 22.8 % vs 9.6 % , p = 0.01 ) . Patients with etoricoxib treatment and a complication needed a longer recovery period than patients with a complication in the control group ( 18 ( 17 ; 20 ) vs 14 ( 13 ; 15 ) days , p = 0.05 ) . We observed an increased level of postoperative serum creatinine with etoricoxib treatment ( 105 ( 98 ; 112 ) vs 82 ( 78 ; 85 ) , p = 0.003 ) , which was more pronounced in patients with a complication ( 141 ( 127 ; 155 ) vs 91 ( 83 ; 98 ) , p = 0.002 ; 25 vs 8 patients with serum creatinine > 100 & mgr;mol/L , p = 0.008 ) . In multivariate analysis , etoricoxib was identified as an independent risk factor for experiencing a major complication with a risk increase of approximately 2.5-fold ( p = 0.03 ) . LIMITATIONS : This study was limited by the nonr and omized use of perioperative etoricoxib and the retrospective nature of its review of patient records . CONCLUSIONS : Etoricoxib increased the number of patients with postoperative complications and should be considered carefully in colorectal surgery Objectives Postoperative ileus ( PI ) is one of many common complications in major abdominal surgery . PI results in patient discomfort , increased gastrointestinal leakage , prolonged hospital stay , and increased medical expenses . In this study , we have investigated the morphine-sparing effects of ketorolac and its correlation with the duration of PI in patients with colorectal surgeries . Methods We collected data from 102 patients who had received elective colorectal resection . The patients were r and omly allocated into 2 groups and received intravenous patient-controlled analgesia ( IVPCA ) morphine ( M group ) or IVPCA morphine plus ketorolac ( M+K group ) . Time-scale morphine consumption ( per 12 h ) , recovery of bowel functions ( the first bowel movement and passage of flatus ) , pain scores , and opioid-related side effects were then recorded . Results Patients in the M+K group received 18.3 % less morphine than those in the M group within 72 postoperative hours . The maximal opioid-sparing effects of ketorolac appeared in 12 to 24 postoperative hours . The onset of the first bowel movement and passage of flatus was significantly less in the M+K group than in the M group . The M group showed a 5.25 times greater risk of inducing PI , a result comparable with the M+K group in colorectal surgery patients . Discussion The addition of ketorolac to IVPCA morphine has demonstrated a clear opioid-sparing effect and benefits in regards to the shortening of the duration of bowel immobility . We suggest that adding ketorolac to morphine IVPCA be included in the multimodal postoperative rehabilitation program for the early restoration of normal bowel function To study the possible effects of diclofenac sodium on intestinal anastomoses , 48 rabbits were su bmi tted to surgery consisting of two single-layer ileal anastomoses performed with separate propylene 5 - 0 sutures . The animals were divided at r and om into two groups ( test and control ) . The animals in the test group were given intramuscular injections of diclofenac sodium at the dose of 3 mg/ kg body weight at 24-hour intervals , and the control animals were given injections of an identical amount of 0.9 percent saline . The animals were sacrificed on the 3rd , 7th , and 14th postoperative days for macroscopic evaluation of the peritoneal cavity and of the anastomoses , tensile strength measurement , hydroxyproline determination , and histopathologic examination . The following results were observed : anastomotic dehiscence followed by peritonitis and death in five test animals ( 20.83 percent ) and no control animals ; decreased anastomotic tensile strength on the 7th day in test animals ( P<0.05 ) ; delayed acute inflammatory response and onset of fibroblast proliferation in the test group ; and similar hydroxyproline levels in both groups . On the basis of the results obtained , we conclude that diclofenac sodium had a negative effect on intestinal anastomotic healing Background : Postoperative ileus ( PI ) is the transient impairment of bowel motility due to surgical trauma and the associated physiological responses . Postoperative ileus results in patient discomfort , increases gastrointestinal risks , prolongs hospital stay and increases medical expenses . In this study , we investigated the effect of patient‐controlled analgesia ( PCA ) morphine with or without ketorolac on bowel functions in patients after colorectal surgeries Background : Aspirin , nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and selective COX-2 inhibitors may improve outcomes in breast cancer patients . We investigated the association of aspirin , NSAIDs , and use of selective COX-2 inhibitors with breast cancer recurrence . Methods : We identified incident stage I – III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry , who were diagnosed during 1996–2008 . Prescriptions for aspirin ( > 99 % low-dose aspirin ) , NSAIDs , and selective COX-2 inhibitors were ascertained from the National Prescription Registry . Follow-up began on the date of breast cancer primary surgery and continued until the first of recurrence , death , emigration , or 1 January 2013 . We used Cox regression models to compute hazard ratios ( HR ) and corresponding 95 % confidence intervals ( 95 % CI ) associating prescriptions with recurrence , adjusting for confounders . Results : We identified 34,188 breast cancer patients with 233,130 person-years of follow-up . Median follow-up was 7.1 years ; 5,325 patients developed recurrent disease . Use of aspirin , NSAIDs , or selective COX-2 inhibitors was not associated with the rate of recurrence ( HRadjusted aspirin = 1.0 , 95 % CI = 0.90 , 1.1 ; NSAIDs = 0.99 , 95 % CI = 0.92 , 1.1 ; selective COX-2 inhibitors = 1.1 , 95 % CI = 0.98 , 1.2 ) , relative to nonuse . Prediagnostic use of the exposure drugs was associated with reduced recurrence rates ( HRaspirin = 0.92 , 95 % CI = 0.82 , 1.0 ; HRNSAIDs = 0.86 , 95 % CI = 0.81 , 0.91 ; HRsCOX-2inhibitors = 0.88 , 95 % CI = 0.83 , 0.95 ) . Conclusions : This prospect i ve cohort study suggests that post diagnostic prescriptions for aspirin , NSAIDs , and selective COX-2 inhibitors have little or no association with the rate of breast cancer recurrence . Prediagnostic use of the drugs was , however , associated with a reduced rate of breast cancer recurrence Surgical stress and inflammatory response induce the release of catecholamines and PGs , which may be key factors in facilitating cancer recurrence through immunosuppression . Animal studies have suggested the efficacy of perioperative blockades of catecholamines and PGs in reducing immunosuppression . In this study , to our knowledge , we present the first report of the effects of perioperative propranolol and /or parecoxib on peripheral regulatory T cells ( Tregs ) in breast cancer patients . Patients were r and omly assigned to control , propranolol , parecoxib , and propranolol plus parecoxib groups . We demonstrated that levels of circulating epinephrine , norepinephrine , and PGE2 increased in response to surgery . Meanwhile , peripheral FOXP3 mRNA level and Treg frequencies were elevated on postoperative day 7 . Propranolol administration , rather than parecoxib , attenuated such elevation of Tregs , indicating the critical roles for catecholamines in surgery-induced promotion of Tregs . Besides , propranolol plus parecoxib treatment demonstrated no additive or synergistic effects . Furthermore , a study of Treg activity on CD4 + T cell responses to specific tumor Ags was performed in the control and propranolol groups . Propranolol abrogated the increased Treg activity and accompanying suppression of CD4 + T cell responses after surgery . Finally , we conducted ex vivo experiments on the effects of varying concentrations of epinephrine and /or propranolol on Treg proliferation over P BMC s from breast cancer patients , to provide further direct evidence strengthening our clinical observations . Epinephrine markedly promoted Treg proliferation , whereas propranolol prevented such enhancement effect . In conclusion , our study highlights beneficial roles for propranolol in inhibiting Treg responses in vivo and in vitro , and demonstrates that propranolol could alleviate surgical stress – induced elevation of Tregs in breast cancer patients |
10,527 | 25,134,954 | RESULTS The results showed that GLP-1 agent treatment in patients with T2DM and /or CVD led to significantly improved regional left ventricular contractile parameters ( including peak left systolic tissue velocity and strain ) and global left ventricular performance ( including stroke volume , ejection fraction , and left ventricular chambers ) compared with patients receiving placebo .
GLP-1 agent treatment in T2DM and /or CVD patients is associated with a modest but significant increase in the odds of left ventricular contractile parameters and left ventricular performance compared with patients having received placebo , which may be indicative of additional cardiovascular benefits for these patients | BACKGROUND The cardiovascular safety of many glucagon-like peptide-1 agents ( GLP-1 agents ) is unclear .
In this study , we assess the effects of the GLP-1 agents on left ventricular function in patients with type 2 diabetes ( T2DM ) and /or cardiovascular disease ( CVD ) . | GLP-1 stimulates insulin secretion , suppresses glucagon secretion , delays gastric emptying , and inhibits small bowel motility , all actions contributing to the anti-diabetogenic peptide effect . Endothelial dysfunction is strongly associated with insulin resistance and type 2 diabetes mellitus and may cause the angiopathy typifying this debilitating disease . Therefore , interventions affecting both endothelial dysfunction and insulin resistance may prove useful in improving survival in type 2 diabetes patients . We investigated GLP-1 's effect on endothelial function and insulin sensitivity ( S(I ) ) in two groups : 1 ) 12 type 2 diabetes patients with stable coronary artery disease and 2 ) 10 healthy subjects with normal endothelial function and S(I ) . Subjects underwent infusion of recombinant GLP-1 or saline in a r and om crossover study . Endothelial function was measured by postischemic FMD of brachial artery , using ultrasonography . S(I ) [ in ( 10(-4 ) dl.kg(-1).min(-1))/(muU/ml ) ] was measured by hyperinsulinemic isoglycemic clamp technique . In type 2 diabetic subjects , GLP-1 infusion significantly increased relative changes in brachial artery diameter from baseline FMD(% ) ( 3.1 + /- 0.6 vs. 6.6 + /- 1.0 % , P < 0.05 ) , with no significant effects on S(I ) ( 4.5 + /- 0.8 vs. 5.2 + /- 0.9 , P = NS ) . In healthy subjects , GLP-1 infusion affected neither FMD(% ) ( 11.9 + /- 0.9 vs. 10.3 + /- 1.0 % , P = NS ) nor S(I ) ( 14.8 + /- 1.8 vs. 11.6 + /- 2.0 , P = NS ) . We conclude that GLP-1 improves endothelial dysfunction but not insulin resistance in type 2 diabetic patients with coronary heart disease . This beneficial vascular effect of GLP-1 adds yet another salutary property of the peptide useful in diabetes treatment BACKGROUND Exenatide , an incretin mimetic for adjunctive treatment of type 2 diabetes ( T2DM ) , reduced hemoglobin A(1c ) ( A1C ) and weight in clinical trials . The objective of this study was to evaluate the effects of > or = 3 years exenatide therapy on glycemic control , body weight , cardiometabolic markers , and safety . METHODS Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended , open-label clinical trial . Patients were r and omized to twice daily ( BID ) placebo , 5 mug exenatide , or 10 mug exenatide for 30 weeks , followed by 5 mug exenatide BID for 4 weeks , then 10 mug exenatide BID for > or = 3 years of exenatide exposure . Patients continued metformin and /or sulfonylureas . RESULTS 217 patients ( 64 % male , age 58 + /- 10 years , weight 99 + /- 18 kg , BMI 34 + /- 5 kg/m(2 ) , A1C 8.2 + /- 1.0 % [ mean + /- SD ] ) completed 3 years of exenatide exposure . Reductions in A1C from baseline to week 12 ( -1.1 + /- 0.1 % [ mean + /- SEM ] ) were sustained to 3 years ( -1.0 + /- 0.1 % ; p < 0.0001 ) , with 46 % achieving A1C < or = 7 % . Exenatide progressively reduced body weight from baseline ( -5.3 + /- 0.4 kg at 3 years ; p < 0.0001 ) . Patients with elevated serum alanine aminotransferase ( ALT ) at baseline ( n = 116 ) had reduced ALT ( -10.4 + /- 1.5 IU/L ; p < 0.0001 ) and 41 % achieved normal ALT . Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline ( -6.1 + /- 0.6 kg vs. -4.4 + /- 0.5 kg ; p = 0.03 ) , however weight change was minimally correlated with baseline ALT ( r = -0.01 ) or ALT change ( r = 0.31 ) . Homeostasis Model Assessment B ( HOMA-B ) , blood pressure , and aspartate aminotransferase ( AST ) all improved . A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis ( n = 151 ) . Triglycerides decreased 12 % ( p = 0.0003 ) , total cholesterol decreased 5 % ( p = 0.0007 ) , LDL-C decreased 6 % ( p < 0.0001 ) , and HDL-C increased 24 % ( p < 0.0001 ) . Exenatide was generally well tolerated . The most frequent adverse event was mild-to-moderate nausea . The main limitation of this study is the open-label , uncontrolled nature of the study design which does not provide a placebo group for comparison . CONCLUSION Adjunctive exenatide treatment for > or = 3 years in T2DM patients result ed in sustained improvements in glycemic control , cardiovascular risk factors , and hepatic biomarkers , coupled with progressive weight reduction Background — The incretin hormone glucagon-like peptide-1 ( GLP-1 ) has been shown to have cardioprotective properties in animal models of ischemia and infa rct ion due to promotion of myocardial glucose uptake and suppression of apoptosis . We investigated whether GLP-1 protected the heart from dysfunction caused by supply ischemia during percutaneous coronary intervention ( PCI ) . Methods and Results — Twenty patients with normal left ventricular ( LV ) function and single-vessel coronary disease within the left anterior descending artery undergoing elective PCI were studied . A conductance catheter was placed into the LV through the femoral artery , and pressure-volume loops were recorded at baseline and during a 1-minute low-pressure balloon occlusion at the site of the stenosis . The patients were r and omized to receive an infusion of either GLP-1(7–36 ) amide at 1.2 pmol/kg per minute or saline immediately after the first balloon occlusion . Coronary balloon occlusion caused LV stunning in the control group with cumulative LV dysfunction on subsequent occlusion that was not seen in the GLP-1 group . GLP-1 improved recovery of LV systolic and diastolic function at 30 minutes after balloon occlusion compared with control ( delta dP/dtmax from baseline , −1.6 % versus −12.2 % ; P=0.02 ) and reduced the LV dysfunction after the second balloon occlusion ( delta dP/dtmax , −13.1 % versus −25.3 % ; P=0.01 ) . Conclusions — In this pilot study , infusion of GLP-1 has been demonstrated to reduce ischemic LV dysfunction after supply ischemia during coronary balloon occlusion in humans and mitigates stunning . The findings require confirmation in a larger scale clinical trial . Clinical Trial Registration — URL : http://www.is rct n.org . Unique identifier : IS RCT N 77442023 BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents , including saxagliptin , a dipeptidyl peptidase 4 ( DPP-4 ) inhibitor , are unclear . METHODS We r and omly assigned 16,492 patients with type 2 diabetes who had a history of , or were at risk for , cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years . Physicians were permitted to adjust other medications , including antihyperglycemic agents . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . RESULTS A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group ( 7.3 % and 7.2 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio with saxagliptin , 1.00 ; 95 % confidence interval [ CI ] , 0.89 to 1.12 ; P=0.99 for superiority ; P<0.001 for noninferiority ) ; the results were similar in the " on-treatment " analysis ( hazard ratio , 1.03 ; 95 % CI , 0.91 to 1.17 ) . The major secondary end point of a composite of cardiovascular death , myocardial infa rct ion , stroke , hospitalization for unstable angina , coronary revascularization , or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group ( 12.8 % and 12.4 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio , 1.02 ; 95 % CI , 0.94 to 1.11 ; P=0.66 ) . More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure ( 3.5 % vs. 2.8 % ; hazard ratio , 1.27 ; 95 % CI , 1.07 to 1.51 ; P=0.007 ) . Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups ( acute pancreatitis , 0.3 % in the saxagliptin group and 0.2 % in the placebo group ; chronic pancreatitis , < 0.1 % and 0.1 % in the two groups , respectively ) . CONCLUSIONS DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events , though the rate of hospitalization for heart failure was increased . Although saxagliptin improves glycemic control , other approaches are necessary to reduce cardiovascular risk in patients with diabetes . ( Funded by AstraZeneca and Bristol-Myers Squibb ; SAVOR-TIMI 53 Clinical Trials.gov number , NCT01107886 . ) OBJECTIVE The gut hormone glucagon-like peptide 1 ( GLP-1 ) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity . The effect of a single subcutaneous injection is brief because of rapid degradation . We therefore sought to evaluate the effect of infusion of GLP-1 for 48 h in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We infused GLP-1 ( 2.4 pmol.kg-1.min-1 ) or saline subcutaneously for 48 h in r and omized order in six patients with type 2 diabetes to evaluate the effect on appetite during fixed energy intake and on plasma glucose , insulin , glucagon , postpr and ial lipidemia , blood pressure , heart rate , and basal metabolic rate . RESULTS The infusion result ed in elevations of the plasma concentrations of intact GLP-1 similar to those observed after intravenous infusion of 1.2 pmol.kg-1.min-1 , previously shown to lower blood glucose effectively in type 2 diabetic patients . Fasting plasma glucose ( day 2 ) decreased from 14.1 + /- 0.9 ( saline ) to 12.2 + /- 0.7 mmol/l ( GLP-1 ) , P = 0.009 , and 24-h mean plasma glucose decreased from 15.4 + /- 1.0 to 13.0 + /- 1.0 mmol/l , P = 0.0009 . Fasting and total area under the curve for insulin and C-peptide levels were significantly higher during the GLP-1 administration , whereas glucagon levels were unchanged . Neither triglycerides nor free fatty acids were affected . GLP-1 administration decreased hunger and prospect i ve food intake and increased satiety , whereas fullness was unaffected . No side effects during GLP-1 infusion were recorded except for a brief cutaneous reaction . Basal metabolic rate and heart rate did not change significantly during GLP-1 administration . Both systolic and diastolic blood pressure tended to be lower during the GLP-1 infusion . CONCLUSIONS We conclude that 48-h continuous subcutaneous infusion of GLP-1 in type 2 diabetic patients 1 ) lowers fasting as well as meal-related plasma glucose , 2 ) reduces appetite , 3 ) has no gastrointestinal side effects , and 4 ) has no negative effect on blood pressure CONTEXT Glucagon-like peptide-1 ( GLP-1 ) and GLP-1 receptor agonists provide beneficial cardiovascular effects by protecting against ischemia and reperfusion injury . Type 2 diabetes mellitus patients have reduced glycolysis in the heart . OBJECTIVE We hypothesized that cardioprotection by GLP-1 is achieved through increased glucose availability and utilization and aim ed to assess the effect of exenatide , a synthetic GLP-1 receptor agonist , on myocardial glucose uptake ( MGU ) , myocardial glucose transport , and myocardial blood flow ( MBF ) . DESIGN AND METHODS We conducted a r and omized , double-blinded , placebo-controlled crossover study in eight male , insulin-naive , type 2 diabetes mellitus patients without coronary artery disease . Positron emission tomography was used to determine the effect of exenatide on MGU and MBF during a pituitary-pancreatic hyperglycemic clamp with (18)F-fluorodeoxyglucose and (13)N-ammonia as tracers . RESULTS Overall , exenatide did not alter MGU . However , regression analysis revealed that exenatide altered initial clearance of glucose over the membrane of cardiomyocytes and MGU , depending on the level of insulin resistance ( P = 0.017 and 0.010 , respectively ) . Exenatide increased MBF from 0.73 ± 0.094 to 0.85 ± 0.091 ml/g · min ( P = 0.0056 ) . Except for an increase in C-peptide levels , no differences in circulating hormones or metabolites were found . CONCLUSIONS The action of exenatide as an activator or inhibitor of the glucose transport and glucose uptake in cardiomyocytes is dependent on baseline activity of glucose transport and insulin resistance . Exenatide increases MBF without changing MGU Background Cardiovascular effects of glucose-lowering agents are of increasing interest . Our aim was to assess the effects of the glucagon-like peptide-1 receptor agonist exenatide on heart rate ( HR ) and blood pressure ( BP ) in subjects with type 2 diabetes mellitus ( T2DM ) . Methods In this double-blind , placebo-controlled trial , subjects with T2DM on metformin and /or a thiazolidinedione were r and omized to receive exenatide ( 5 μg for 4 weeks followed by 10 μg ) or placebo BID for 12 weeks . Heart rate and BP were assessed with 24-hour ambulatory BP monitoring . The primary measure was change from baseline in mean 24-hour HR . Results Fifty-four subjects ( 28 exenatide , 26 placebo ) were r and omized and comprised the intent-to-treat population . Baseline values ( exenatide and placebo ) were ( mean ± SE ) 74.4 ± 2.1 and 74.5 ± 1.9 beats/minute for HR , 126.4 ± 3.2 and 119.9 ± 2.8 mm Hg for systolic BP ( SBP ) , and 75.2 ± 2.1 and 70.5 ± 2.0 mm Hg for diastolic BP ( DBP ) . At 12 weeks , no significant change from baseline in 24-hour HR was observed with exenatide or placebo ( LS mean ± SE , 2.1 ± 1.4 versus -0.7 ± 1.4 beats/minute , respectively ; between treatments , p = 0.16 ) . Exenatide therapy was associated with trends toward lower 24-hour , daytime , and nighttime SBP ; changes in DBP were similar between groups . No changes in daytime or nighttime rate pressure product were observed . With exenatide , body weight decreased from baseline by -1.8 ± 0.4 kg ( p < 0.0001 ; treatment difference -1.5 ± 0.6 kg , p < 0.05 ) . The most frequently reported adverse event with exenatide was mild to moderate nausea . Conclusions Exenatide demonstrated no clinical ly meaningful effects on HR over 12 weeks of treatment in subjects with T2DM . The observed trends toward lower SBP with exenatide warrant future investigation . Trial registration Background Ingestion of a meal increases the blood flow to the gastrointestinal organs and affects the heart rate ( HR ) , blood pressure and cardiac output ( CO ) , although the mechanisms are not known . The aim of this study was to evaluate the effect of endogenously released glucose , insulin , glucagon-like peptide 1 ( GLP-1 ) , ghrelin on CO , HR , stroke volume ( SV ) , and blood pressure . Methods Eleven healthy men and twelve healthy women ( ( mean ± SEM ) aged : 26 ± 0.2 y ; body mass index : 21.8 ± 0.1 kg/m2 ) ) were included in this study . The CO , HR , SV , systolic and diastolic blood pressure , antral area , gastric emptying rate , and glucose , insulin , GLP-1 and ghrelin levels were measured . Results The CO and SV at 30 min were significantly higher , and the diastolic blood pressure was significantly lower , than the fasting in both men and women ( P < 0.05 ) . In men , significant correlations were found between GLP-1 level at 30 min and SV at 30 min ( P = 0.015 , r = 0.946 ) , and between ghrelin levels and HR ( P = 0.013 , r = 0.951 ) at 110 min . Significant correlations were also found between the change in glucose level at 30 min and the change in systolic blood pressure ( P = 0.021 , r = -0.681 ) , and the change in SV ( P = 0.008 , r = -0.748 ) relative to the fasting in men . The insulin 0 - 30 min AUC was significantly correlated to the CO 0 - 30 min AUC ( P = 0.002 , r = 0.814 ) in men . Significant correlations were also found between the 0 - 120 min ghrelin and HR AUCs ( P = 0.007 , r = 0.966 ) in men . No statistically significant correlations were seen in women . Conclusions Physiological changes in the levels of glucose , insulin , GLP-1 and ghrelin may influence the activity of the heart and the blood pressure . There may also be gender-related differences in the haemodynamic responses to postpr and ial changes in hormone levels . The results of this study show that subjects should not eat immediately prior to , or during , the evaluation of cardiovascular interventions as postpr and ial affects may affect the results , leading to erroneous interpretation of the cardiovascular effects of the primary intervention . Trial registration Background —Glucose-insulin-potassium infusions are beneficial in uncomplicated patients with acute myocardial infa rct ion ( AMI ) but are of unproven efficacy in AMI with left ventricular ( LV ) dysfunction because of volume requirements associated with glucose infusion . Glucagon-like peptide-1 ( GLP-1 ) is a naturally occurring incretin with both insulinotropic and insulinomimetic properties that stimulate glucose uptake without the requirements for concomitant glucose infusion . Methods and Results —We investigated the safety and efficacy of a 72-hour infusion of GLP-1 ( 1.5 pmol/kg per minute ) added to background therapy in 10 patients with AMI and LV ejection fraction ( EF ) < 40 % after successful primary angioplasty compared with 11 control patients . Echocardiograms were obtained after reperfusion and after the completion of the GLP-1 infusion . Baseline demographics and background therapy were similar , and both groups had severe LV dysfunction at baseline ( LVEF=29±2 % ) . GLP-1 significantly improved LVEF ( from 29±2 % to 39±2 % , P < 0.01 ) , global wall motion score indexes ( 1.94±0.11→1.63±0.09 , P < 0.01 ) , and regional wall motion score indexes ( 2.53±0.08→2.02±0.11 , P < 0.01 ) compared with control subjects . The benefits of GLP-1 were independent of AMI location or history of diabetes . GLP-1 was well tolerated , with only transient gastrointestinal effects . Conclusions —When added to st and ard therapy , GLP-1 infusion improved regional and global LV function in patients with AMI and severe systolic dysfunction after successful primary angioplasty Glucagon-like peptide-1 ( GLP-1 ) , an incretin , which is used to treat diabetes mellitus in humans , inhibited vagal activity and activated nitrergic pathways . In rats , GLP-1 also increased sympathetic activity , heart rate , and blood pressure ( BP ) . However , the effects of GLP-1 on sympathetic activity in humans are unknown . Our aims were to assess the effects of a GLP-1 agonist with or without alpha(2)-adrenergic or -nitrergic blockade on autonomic nervous functions in humans . In this double-blind study , 48 healthy volunteers were r and omized to GLP-1-(7 - 36 ) amide , the nitric oxide synthase ( NOS ) inhibitor N(G)-monomethyl-l-arginine acetate ( l-NMMA ) , the alpha(2)-adrenergic antagonist yohimbine , or placebo ( i.e. , saline ) , alone or in combination . Hemodynamic parameters , plasma catecholamines , and cardiac sympathetic and parasympathetic modulation were measured by spectral analysis of heart rate . Thereafter , the effects of GLP-1-(7 - 36 ) amide on muscle sympathetic nerve activity ( MSNA ) were assessed by microneurography in seven subjects . GLP-1 increased ( P = 0.02 ) MSNA but did not affect cardiac sympathetic or parasympathetic indices , as assessed by spectral analysis . Yohimbine increased plasma catecholamines and the low-frequency ( LF ) component of heart rate power spectrum , suggesting increased cardiac sympathetic activity . l-NMMA increased the BP and reduced the heart rate but did not affect the balance between sympathetic and parasympathetic activity . GLP-1 increases skeletal muscle sympathetic nerve activity but does not appear to affect cardiac sympathetic or parasympathetic activity in humans Background Patients with type 2 diabetes and heart failure are considered to be at high risk for hypoglycaemic complications . There is a considerable uncertainty with respect to the appropriate choice of antidiabetic pharmacotherapy in patients with type 2 diabetes and comorbid heart failure . Little is known about comorbidity , hypoglycaemia rates and selected pharmacotherapy in diabetic patients with heart failure in clinical practice . Methods DiaRegis is a prospect i ve registry in Germany including 3,810 patients with type 2 diabetes receiving antidiabetic treatment with oral mono or oral dual combination therapy in 2009/2010 . Only patients for which adjustment of pharmacotherapy ( including the introduction of insulin and GLP-1 analogues ) was deemed necessary were enrolled . We examined the differences in comorbidity , hypoglycaemia and choice of anti-diabetic pharmacotherapy between diabetics with and without clinical heart failure in clinical practice in Germany . Results For 3,746 patients , data on the presence of heart failure were available , median ( IQR ) age 65.9 ( 57.6–72.8 ) years and 46.8 % were female . Patients with heart failure ( n = 370 ; 9.9 % ) were older , had a higher BMI , were less physically active , and had more cardiovascular risk factors and a substantial comorbidity . Glycaemic control was comparable between groups . Of the patients with heart failure , 76.8 % received metformin , 32.7 % sulfonylureas , 2.2 % glucosidase inhibitors , 4.3 % glinides , 6.2 % glitazones and 7.3 % DPP-4 inhibitors at baseline before adjustment of therapy . In multivariate analyses , patients with heart failure received less metformin ( odds ratio ( OR ) 0.58 , 95 % confidence interval ( CI ) 0.43–0.79 ) and sulfonylureas ( OR 0.70 , 95%CI 0.52–0.95 ) but not thiazolidinediones ( OR 1.22 , 95%CI 0.82–1.81 ) or other antidiabetic drugs . Hypoglycaemia was considerably more frequent in diabetic patients with heart failure than in those without ( OR 1.96 , 95%CI 1.47–2.61 ) . Conclusion Patients with type 2 diabetes and heart failure had a substantially increased comorbidity burden compared to patients without heart failure . They more often suffered from episodes of hypoglycaemia , especially those requiring medical assistance . The diagnosis of heart failure did not impact the choice of antidiabetic pharmacotherapy in patients with type 2 diabetes . There was no differential use of thiazolidinediones despite evidence discouraging their use in patients with heart failure . ZusammenfassungHintergrundPatienten mit Typ-2-Diabetes und Herzinsuffizienz haben ein erhöhtes Risiko für Hypoglykämien . I m klinischen Alltag besteht häufig Unsicherheit bezüglich einer adäquaten antidiabetischen Therapie bei Patienten mit zusätzlicher Herzinsuffizienz , und es existieren nur wenig Date n zur Komorbidität , zu Hypoglykämieraten sowie zur gewählten antidiabetischen Therapie von Patienten mit Diabetes und Herzinsuffizienz . Method ikDiaRegis ist ein deutsches prospektives Register . Von 313 niedergelassenen Ärzten wurden in den Jahren 2009/2010 insgesamt 3810 ambulant beh and elte Patienten mit Typ-2-Diabetes und antidiabetischer oraler Monotherapie oder oraler dualer Kombinationstherapie eingeschlossen , bei denen der beh and elnde Arzt bei Aufnahme in das Register eine Anpassung der antidiabetischen Therapie vornahm ( inklusive der Gabe von Insulin oder GLP-1Analoga ) . Wir untersuchten Unterschiede in der Komorbidität , der Hypoglykämierate sowie der antidiabetischen Pharmakotherapie bei Patienten mit und ohne klinische Zeichen einer Herzinsuffizienz i m klinischen Alltag in Deutschl and .ErgebnisseBei 3746/3810 Patienten lagen Date n zur Herzinsuffizienz vor . Das mediane Alter betrug 65,9 Jahre ( Interquartilenabst and 57,6–72,8 ) ; 46,8 % der Patienten waren Frauen . Eine Herzinsuffizienz war bei 370 Patienten ( 9,9 % ) vorbeschrieben . Diese Patienten waren älter , hatten einen höheren BMI , waren körperlich weniger aktiv und hatten signifikant mehr kardiovaskuläre Risikofaktoren sowie deutlich mehr Begleiterkrankungen . Es f and en sich keinerlei Unterschiede in der Blutzuckerkontrolle , gemessen als HbA1c , Nüchtern- oder postpr and iale Plasmaglukose , zwischen Patienten mit bzw . ohne Herzinsuffizienz . Die Rate der Hypoglykämien in den 12 Monaten vor Einschluss in das Register war bei Patienten mit Herzinsuffizienz signifikant erhöht ( OR 1,96 ; 95%-KI 1,47–2,61 ) . Die Pharmakotherapie des Diabetes war bei Patienten mit Herzinsuffizienz zum Zeitpunkt des Einschlusses in das Register vor Therapieanpassung dominiert von Metformin ( 76,8 % ) , gefolgt von Sulfonylharnstoffen ( 32,7 % ) , Glukosidaseinhibitoren ( 2,2 % ) , Gliniden ( 4,3 % ) , Glitazonen ( 6,2 % ) und DPP-4-Inhibitoren ( 7,3 % ) . Nach Korrektur für die Unterschiede in den Patientencharakteristika mittels multivariater Analyse erhielten Patienten mit Herzinsuffizienz seltener Metformin ( OR 0,58 ; 95%-KI 0,43–0,79 ) und Sulfonylharnstoffe ( OR 0,70 ; 95%-KI 0,52–0,95 ) . Keine Unterschiede zu Patienten ohne Herzinsuffizienz f and en sich bei Einsatz der and eren antidiabetischen Therapien , insbesondere auch nicht für Thiazolidindione ( OR 1,22 ; 95%-KI 0,82–1,81).SchlussfolgerungenIm klinischen Alltag in Deutschl and waren Patienten mit Typ-2-Diabetes und Herzinsuffizienz i m Vergleich zu Diabetikern ohne Herzinsuffizienz durch eine deutlich größere Komorbidität geprägt . Trotz gleicher HbA1c-Einstellung hatten diese Patienten signifikant mehr Hypoglykämien , insbesondere solche , die medizinische Hilfe benötigten , als Patienten ohne Herzinsuffizienz . Die Herzinsuffizienz hatte keinerlei Einfluss auf die Auswahl der antidiabetischen Therapie des Typ-2-Diabetes i m Alltag in Deutschl and . Insbesondere Thiazolidindione wurden bei Patienten mit Herzinsuffizienz trotz der Hinweise aus r and omisierten Studien auf eine erhöhte Ereignisrate gleichermaßen eingesetzt AIMS Exenatide , a glucagon-like-peptide-1 analogue , increases myocardial salvage in experimental setting s with coronary occlusion and subsequent reperfusion . We evaluated the cardioprotective effect of exenatide at the time of reperfusion in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) treated with primary percutaneous coronary intervention ( pPCI ) . METHODS AND RESULTS A total of 172 patients with STEMI and Thrombolysis in Myocardial Infa rct ion flow 0/1 were r and omly assigned to exenatide or placebo ( saline ) intravenously . Study treatment was commenced 15 min before intervention and maintained for 6 h after the procedure . The primary endpoint was salvage index calculated from myocardial area at risk ( AAR ) , measured in the acute phase , and final infa rct size measured 90 ± 21 days after pPCI by cardiac magnetic resonance ( CMR ) . In 105 patients evaluated with CMR , a significantly larger salvage index was found in the exenatide group than in the placebo group ( 0.71 ± 0.13 vs. 0.62 ± 0.16 ; P= 0.003 ) . Infa rct size in relation to AAR was also smaller in the exenatide group ( 0.30 ± 0.15 vs. 0.39 ± 0.15 ; P= 0.003 ) . In a regression analysis , there was a significant correlation between the infa rct size and the AAR for both treatment groups and an analysis of covariance showed that data points in the exenatide group lay significantly lower than for the placebo group ( P= 0.011 ) . There was a trend towards smaller absolute infa rct size in the exenatide group ( 13 ± 9 vs. 17 ± 14 g ; P= 0.11 ) . No difference was observed in left ventricular function or 30-day clinical events . No adverse effects of exenatide were observed . CONCLUSION In patients with STEMI undergoing pPCI , administration of exenatide at the time of reperfusion increases myocardial salvage Increasing evidence suggests that tight glycemic control improves clinical outcomes after coronary artery bypass grafting ( CABG ) . However , the risk for hypoglycemia with insulin often results in less aggressive glycemic control . Glucagon-like peptide-1 ( GLP-1 ) is a naturally occurring peptide whose insulinotropic effects are predicated on the glucose concentration , minimizing the risk for hypoglycemia . This study was conducted to examine whether perioperative treatment with GLP-1 would affect glycemic control and improve hemodynamic recovery after CABG . Twenty patients with coronary heart disease and preserved left ventricular function who were scheduled to undergo CABG were r and omized to receive st and ard therapy at the discretion of the surgeon or treatment with GLP-1 ( 1.5 pmol/kg/min ) as a continuous infusion beginning 12 hours before CABG and continuing for 48 hours . Perioperative hemodynamics , the left ventricular ejection fraction , plasma glucose , and requirements for insulin drips and inotropic support were monitored . There were no differences between groups in the preoperative , postoperative , or 7-day left ventricular ejection fraction ( GLP-1 61 + /- 4 % , control 59 + /- 3 % ) or cardiac index at 18 hours ( GLP-1 3.0 + /- 0.2 L/min/m(2 ) , control 3.3 + /- 0.4 L/min/m(2 ) ) . However , the control group required greater use of inotropic and vasoactive infusions during the 48 hours after the operation to achieve the same hemodynamic result . There were also more frequent arrhythmias requiring antiarrhythmic agents in the control group . GLP-1 result ed in better glycemic control in the pre- and perioperative periods ( GLP-1 95 + /- 3 mg/dl , control 140 + /- 10 mg/dl , p < /=0.02 ) , with 45 % less insulin requirements to achieve the same glycemic control in the postoperative period ( GLP-1 139 + /- 4 mg/dl , control 140 + /- 3 mg/dl ) . In conclusion , the perioperative use of GLP-1 achieves better glycemic control and comparable hemodynamic recovery without the requirements for high-dose insulin or inotropes Background Glucagon-like peptide-1 ( GLP-1 ) is an incretin hormone which has been shown to promote myocardial glucose uptake . Its pharmacological properties as a cardioprotective agent are attractive because it has a short half-life and there is minimal risk of hypoglycaemia . Objective To assess the hypothesis that intravenous infusion of GLP-1 would protect the heart from ischaemic left ventricular ( LV ) dysfunction during dobutamine stress echocardiography ( DSE ) in patients with coronary artery disease ( CAD ) . Design R and omised crossover study . Patients and Interventions 14 patients with CAD and good LV function awaiting revascularisation underwent two DSE scans in a r and omised order . GLP-1 was infused intravenously at 1.2 pmol/kg/min starting 30 min before the DSE for one of the scans and the other scan acted as a control . Main outcome measurements Global and regional wall LV function assessed using tissue Doppler imaging at rest , peak stress and 30 min into recovery . Results Global LV function was greater at peak stress during GLP-1 infusion compared with control ( ejection fraction 77.0±4.4 vs 70.8±5.0 % , p<0.0001 ; mitral annular systolic velocity 12.18±3.10 vs 11.31±3.11 cm/s , p=0.0004 ) . GLP-1 infusion improved regional wall LV function in 12 non-apical segments assessed by velocity , strain and strain rate . This beneficial effect was predominantly seen in ischaemic segments . In recovery , infusion of GLP-1 mitigated the post-ischaemic stunning seen in the control scan . Conclusion Intravenous infusion of GLP-1 protects the heart from ischaemic LV dysfunction induced by dobutamine stress in patients with CAD . Clinical trial registration URL : http://is rct n.org . Registration number IS RCT N 69686930 |
10,528 | 26,627,042 | Conclusions The minor allele of rs13181 polymorphism may confer a protect effect against radiotoxicity . | Background The relationship between ERCC2 polymorphisms and the risk of radiotoxicity remains inconclusive .
The aim of our study is to systematic ally evaluate the association between ERCC2 polymorphisms and the risk of radiotoxicity . | PURPOSE To identify single nucleotide polymorphisms ( SNPs ) associated with development of erectile dysfunction ( ED ) among prostate cancer patients treated with radiation therapy . METHODS AND MATERIAL S A 2-stage genome-wide association study was performed . Patients were split r and omly into a stage I discovery cohort ( 132 cases , 103 controls ) and a stage II replication cohort ( 128 cases , 102 controls ) . The discovery cohort was genotyped using Affymetrix 6.0 genome-wide arrays . The 940 top ranking SNPs selected from the discovery cohort were genotyped in the replication cohort using Illumina iSelect custom SNP arrays . RESULTS Twelve SNPs identified in the discovery cohort and vali date d in the replication cohort were associated with development of ED following radiation therapy ( Fisher combined P values 2.1 × 10(-5 ) to 6.2 × 10(-4 ) ) . Notably , these 12 SNPs lie in or near genes involved in erectile function or other normal cellular functions ( adhesion and signaling ) rather than DNA damage repair . In a multivariable model including nongenetic risk factors , the odds ratios for these SNPs ranged from 1.6 to 5.6 in the pooled cohort . There was a striking relationship between the cumulative number of SNP risk alleles an individual possessed and ED status ( Sommers ' D P value=1.7 × 10(-29 ) ) . A 1-allele increase in cumulative SNP score increased the odds for developing ED by a factor of 2.2 ( P value=2.1 × 10(-19 ) ) . The cumulative SNP score model had a sensitivity of 84 % and specificity of 75 % for prediction of developing ED at the radiation therapy planning stage . CONCLUSIONS This genome-wide association study identified a set of SNPs that are associated with development of ED following radiation therapy . These c and i date genetic predictors warrant more definitive validation in an independent cohort There is increasing evidence supporting the role of genetic variants in the development of radiation-induced toxicity . However , previous c and i date gene association studies failed to eluci date the common genetic variation underlying this phenotype , which could emerge years after the completion of treatment . We performed a genome-wide association study on a Spanish cohort of 741 individuals with prostate cancer treated with external beam radiotherapy ( EBRT ) . The replication cohorts consisted of 633 cases from the UK and 368 cases from North America . One locus comprising TANC1 ( lowest unadjusted P value for overall late toxicity = 6.85 × 10−9 , odds ratio ( OR ) = 6.61 , 95 % confidence interval ( CI ) = 2.23–19.63 ) was replicated in the second stage ( lowest unadjusted P value for overall late toxicity = 2.08 × 10−4 , OR = 6.17 , 95 % CI = 2.25–16.95 ; Pcombined = 4.16 × 10−10 ) . The inclusion of the third cohort gave unadjusted Pcombined = 4.64 × 10−11 . These results , together with the role of TANC1 in regenerating damaged muscle , suggest that the TANC1 locus influences the development of late radiation-induced damage Purpose Germline genetic variations may partly explain the clinical observation that normal tissue tolerance to radiochemotherapy varies by individual . Our objective was to evaluate the association between single-nucleotide polymorphisms ( SNPs ) in radiation/platinum pathways and serious treatment-related toxicity in subjects with esophageal adenocarcinoma who received cisplatin-based preoperative radiochemotherapy . Methods In a multicenter clinical trial ( E1201 ) , 81 eligible treatment-naïve subjects with resectable esophageal adenocarcinoma received cisplatin-based chemotherapy concurrent with radiotherapy , with planned subsequent surgical resection . Toxicity endpoints were defined as grade ≥3 radiation-related or myelosuppressive events probably or definitely related to therapy , occurring during or up to 6 weeks following the completion of radiochemotherapy . SNPs were analyzed in 60 subjects in pathways related to nucleotide/base excision- or double str and ed break repair , or platinum influx , efflux , or detoxification . Results Grade ≥3 radiation-related toxicity ( mostly dysphagia ) and myelosuppression occurred in 18 and 33 % of subjects , respectively . The variant alleles of the XRCC2 5′ flanking SNP ( detected in 28 % of subjects ) and of GST-Pi Ile-105-Val ( detected in 65 % of subjects ) were each associated with higher odds of serious radiation-related toxicity compared to the major allele homozygote ( 47 % vs. 9 % , and 31 % vs. 0 % , respectively ; P = 0.005 ) . No SNP was associated with myelosuppression . Conclusions This novel finding in a well-characterized cohort with robust endpoint data supports further investigation of XRCC2 and GST-Pi as potential predictors of radiation toxicity PURPOSE Clinical radiosensitivity varies considerably among patients , and radiation-induced side effects developing in normal tissue can be therapy limiting . Some single nucleotide polymorphisms ( SNPs ) have been shown to correlate with hypersensitivity to radiotherapy . We conducted a prospect i ve study of 87 female patients with breast cancer who received radiotherapy after breast surgery . We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes : XRCC1 ( Arg399Gln and Arg194Trp ) , XRCC3 ( Thr241Met ) , XPD ( Asp312Asn and Lys751Gln ) , MSH2 ( gIVS12 - 6T > C ) , MLH1 ( Ile219Val ) , MSH3 ( Ala1045Thr ) , MGMT ( Leu84Phe ) , and in damage-detoxification GSTM1 and GSTT1 genes ( allele deletion ) . METHODS AND MATERIAL S Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms . The development of severe acute skin reaction ( moist desquamation or interruption of radiotherapy due to toxicity ) associated with genetic polymorphisms was modeled using Cox proportional hazards , accounting for cumulative biologically effective radiation dose . RESULTS Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3 - 241Met allele ( hazard ratio [ HR ] unquantifiably high ) , MSH2 gIVS12 - 6nt-C allele ( HR=53.36 ; 95 % confidence intervals [ 95 % CI ] , 3.56 - 798.98 ) , and MSH3 - 1045Ala allele ( HR unquantifiably high ) . Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity ( HR=38.26 ; 95 % CI , 1.19 - 1232.52 ) . CONCLUSIONS To our knowledge , this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients . Our findings suggest the hypothesis that mismatch repair mechanisms may be involved in cellular response to radiotherapy . Genetic polymorphisms may be promising c and i date s for predicting acute radiosensitivity , but further studies are necessary to confirm our findings Purpose : Several DNA repair gene polymorphisms have been described , which affect DNA repair capacity and modulate cancer susceptibility . We evaluated the association of six polymorphisms in the DNA repair genes : XRCC1 ( Arg194Trp , Arg280His , and Arg399Gln ) , APE1 ( Asp148Glu ) , and XPD ( Lys751Gln and Asp312Asn ) , with the risk of acute skin reactions following radiotherapy . Design : We conducted a prospect i ve study of 446 female patients with breast cancer who received radiotherapy after breast-conserving surgery . Individual genetic polymorphisms were determined using melting point analysis of sequence-specific hybridization probes . The development of acute skin reactions ( moist desquamation ) associated with DNA repair gene polymorphisms was modeled using Cox proportional hazards , accounting for cumulative biologically effective radiation dose . Results : Overall , the development of acute toxicity , which presented in 77 patients , was not associated with the genetic variants studied , although the hazard ratios ( HR ) were generally below 1 . Risks were however differential by body mass index . Among normal-weight patients only , both carriers of the APE1 148Glu and the XRCC1 399Gln alleles had decreased risk of acute skin reactions after radiotherapy ( HR , 0.49 and 0.51 , respectively ) . The results for XRCC1 were confirmed by haplotype analysis . When considering joint effects , we observed that compared with homozygote carriers of the wild-type allele in both genes , the risk was most strongly reduced in carriers of both APE1 148Glu and XRCC1 399Gln alleles with normal weight [ HR , 0.19 ; 95 % confidence interval ( 95 % CI ) , 0.06 - 0.56 ] but not in those with overweight ( HR , 1.39 ; 95 % CI , 0.56 - 3.45 ; Pinteraction = 0.009 ) . Conclusion : The XRCC1 399Gln or APE1 148Glu alleles may be protective against the development of acute side effects after radiotherapy in patients with normal weight Radiotherapy is associated with a board spectrum of early and late normal tissue injury . It is a basic clinical observation that even within a group of identically treated patients large variability exists in the incidence and severity of radiation sequelae . Although this is partly a result of the r and om nature of radiation-induced cell killing , there are at least two additional phenomena involved . One is that certain cofactors influence the expression of radiation damage . These include for example , age of the patient , hemoglobin level , and smoking habits . Another type of predisposing factors are related to coexisting morbidity , like collagen vascular disease , diabetes mellitus , hypertension , and infections . The influence of these factors on the expression of normal tissue injury is critically review ed and some of the method ological problems involved in this field are discussed . The other phenomenon , that probably contributes to the patient-to-patient variability in the expression of normal tissue reactions , is the variability in intrinsic cellular radiosensitivity that has been shown among individuals . Clinical studies have shown that patients who express a given type of normal tissue injury in one treated area are more likely also to express this injury in another treated area . On the other h and , different normal tissue reactions seem to have a very limited , if any , intrapatient correlation . A number of genetic syndromes are associated with hypersensitivity to radiation , both clinical ly and in vitro . Also , studies have shown that highly selected patients who express an unusually strong response to radiotherapy , are likely to have in vitro radiosensitivities in the lower normal range . Recently , two studies on otherwise unselected patients support the hypothesis that in vitro radiosensitivity of normal human skin fibroblasts correlated with clinical normal tissue reactions BACKGROUND Several studies have reported associations between radiation toxicity and single nucleotide polymorphisms ( SNPs ) in c and i date genes . Few associations have been tested in independent validation studies . This prospect i ve study aim ed to vali date reported associations between genotype and radiation toxicity in a large independent data set . METHODS 92 ( of 98 attempted ) SNPs in 46 genes were successfully genotyped in 1613 patients : 976 received adjuvant breast radiotherapy in the Cambridge breast IMRT trial ( IS RCT N21474421 , n=942 ) or in a prospect i ve study of breast toxicity at the Christie Hospital , Manchester , UK ( n=34 ) . A further 637 received radical prostate radiotherapy in the MRC RT01 multicentre trial ( IS RCT N47772397 , n=224 ) or in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer ( CHHiP ) trial ( IS RCT N97182923 , n=413 ) . Late toxicity was assessed 2 years after radiotherapy with a vali date d photographic technique ( patients with breast cancer only ) , clinical assessment , and patient question naires . Association tests of genotype with overall radiation toxicity score and individual endpoints were undertaken in univariate and multivariable analyses . At a type I error rate adjusted for multiple testing , this study had 99 % power to detect a SNP , with minor allele frequency of 0·35 , associated with a per allele odds ratio of 2·2 . FINDINGS None of the previously reported associations were confirmed by this study , after adjustment for multiple comparisons . The p value distribution of the SNPs tested against overall toxicity score was not different from that expected by chance . INTERPRETATION We did not replicate previously reported late toxicity associations , suggesting that we can essentially exclude the hypothesis that published SNPs individually exert a clinical ly relevant effect . Continued recruitment of patients into studies within the Radiogenomics Consortium is essential so that sufficiently powered studies can be done and method ological challenges addressed . FUNDING Cancer Research UK , The Royal College of Radiologists , Addenbrooke 's Charitable Trust , Breast Cancer Campaign , Cambridge National Institute of Health Research ( NIHR ) Biomedical Research Centre , Experimental Cancer Medicine Centre , East Midl and s Innovation , the National Cancer Institute , Joseph Mitchell Trust , Royal Marsden NHS Foundation Trust , Institute of Cancer Research NIHR Biomedical Research Centre for Cancer BACKGROUND AND PURPOSE We have performed a case-control study among prostate cancer patients treated with three-dimensional conformational radiotherapy ( 3D-CRT ) in order to investigate the association between single nucleotide polymorphisms ( SNPs ) , treatment and patient features with gastrointestinal and genitourinary acute toxicity . MATERIAL AND METHODS A total of 698 patients were screened for 14 SNPs located in the ATM , ERCC2 , LIG4 , MLH1 and XRCC3 genes . Gastrointestinal and genitourinary toxicities were recorded prospect ively using the Common Terminology Criteria for Adverse Events v3.0 . RESULTS The XRCC3 SNP rs1799794 ( G/G OR=5.65 ; 95 % CI : 1.95 - 16.38 ; G/A OR=2.75 ; 95 % CI : 1.25 - 6.05 ; uncorrected p-value=2.8 × 10(-03 ) ; corrected p-value=0.03 ; FDR q-value=0.06 ) as well as the mean dose received by the rectum ( OR=1.06 ; 95 % CI : 1.02 - 1.1 ; uncorrected p-value=2.49 × 10(-03 ) ; corrected p-value=0.03 ; FDR q-value=0.06 ) were significantly associated with gastrointestinal toxicity after correction for multiple testing . Those patients who undergone previous prostatectomy were less prone to develop genitourinary toxicity ( OR=0.38 ; 95 % CI : 0.18 - 0.71 ; uncorrected p-value=4.95 × 10(-03 ) ; corrected p-value=0.03 ; FDR q-value=0.08 ) . Our study excludes the possibility of a > 2-fold risk increase in genitourinary acute toxicity being due to rs1801516 ATM SNP , the rs1805386 and rs1805388 LIG4 markers , as well as all the SNPs evaluated in the ERCC2 , MLH1 and XRCC3 genes . CONCLUSIONS The XRCC3 rs1799794 SNP and the mean dose received by the rectum are associated with the development of gastrointestinal toxicity after 3D-CRT |
10,529 | 23,763,635 | This article provides a systematic evaluation of the scientific evidence of the efficacy of cosmetic products in cellulite reduction and supports a moderate efficacy in thigh circumference reduction | BACKGROUND The number of original articles investigating the efficacy of cosmetic products in cellulite reduction increased rapidly in the last decade ; however , to our knowledge , no systematic review and meta- analysis has been performed so far .
OBJECTIVE We conducted a systematic review of in vivo studies on humans adopting the PRISMA guidelines .
Moreover , we used a meta-analytic approach to estimate the overall effect of cosmetic creams in cellulite treatment from controlled trials with more than 10 patients per arm , using thigh circumference reduction as the outcome measure . | Gynoid lipodystrophy , also known as cellulite , is a common multifactorial entity that affects millions of women around the world . There have been few scientific articles dealing with its physiology and treatment in the past few years , and vascular changes seem to play an important role in its pathophysiology . Skin microvascular alterations can be observed noninvasively with a new method called orthogonal polarization spectral imaging , which was used to evaluate the effectiveness of an anticellulite drug composed mainly of a 7 % caffeine solution . Microcirculatory parameters evaluated were functional capillary density ( FCD ; number of flowing capillaries per unit area ) , diameter of the dermic papilla ( DPD ) , and capillary diameter ( CD ) . The clinical parameters analyzed were centimetrical measurements of thighs and hips and the influence of tobacco , alcohol , and physical activities on the efficacy of the treatment . After 1 month of treatment , statistical application of chi-squared and Z approximation tests showed , in treated patients , statistically significant reduction of thigh circumferences in more than 80 % of the cases and reduction of hip circumference in 67.7 % . FCD , DPD , and CD did not change significantly after treatment . Smoking as well as alcohol consumption and regular physical activity were not significantly related to the centimetrical reduction observed in treated thighs and hips The aim of this study was to determine how worthwhile it would be to combine a newly developed topical slimming product with customized dietary habits not based on calorie restriction , so as to improve the cellulite appearance of the skin . At the beginning of the study , a nutritionist recorded the dietary habits of each participant and gave recommendations to each of them according to their food consumption . The chosen methodology was a right/left comparison , one thigh and hip being treated with the new topical slimming product and the other one left untreated to serve as a r and om control . Objective evaluations were performed by blind assessors . Control of food intake improved the cellulite score after 4 weeks when compared with the base value , but this reduction was significantly greater and earlier on the treated side than on the untreated side , indicating an objective additional benefit derived from the new slimming cream . This result corroborated the slimming effect assessed by measurement in centimetres of the circumference of the upper thighs and the reconstructed volume of the thigh between two fixed horizontal slices . Furthermore , skin tonicity , a major component of cellulite visibility , was also significantly improved on the treated side after only 2 weeks CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs Background CONSORT ( Consoli date d St and ards for Reporting Trials ) guidelines were constructed to ensure optimal reporting quality of r and omized controlled trials ( RCTs ) . Three studies were performed to investigate the mechanism of action and evaluate the efficacy of a topical cosmetic slimming product combining tetrahydroxypropyl ethylenediamine , caffeine , carnitine , forskolin and retinol . The Ex vivo study on skin explants showed that caffeine and forskolin both stimulated glycerol release and demonstrates for the first time that retinol and carnitine in combination synergistically stimulated keratinocyte proliferation , which leads to an increase epidermal thickness . The double-blind , r and omized , placebo-controlled clinical study associating circumference measurements on five selected parts of the body , cutaneous hydration measurements as well as blinded expert grading of skin aspect was conducted on 78 women who applied the product or placebo twice daily for 12 consecutive weeks . After 4 weeks of twice-daily application of the product , significant reductions in circumference of abdomen , hips-buttocks and waist were already observed . Improvements concerned all the measured body parts after 12 weeks . Orange peel and stubborn cellulite decreased significantly from 4 weeks of treatment and tonicity improved from 8 weeks , demonstrating that the product improved skin aspect . At the end of the study , eight parameters of the thirteen evaluated were significantly improved in the active group and compared with placebo INTRODUCTION Cellulite is the unsightly dimpling and nodularity found on the thighs and buttocks of many postadolescent women . Unfortunately , poor underst and ing of its pathophysiology coupled with very few scientifically based studies have left us with limited treatment options that are tolerable and effective . PURPOSE To review current concepts of the etiology and nature of cellulite and summarize available treatment options . To evaluate a novel , pathophysiologically based , topical agent for treatment . MATERIAL S AND METHODS A total of 40 women with a moderate degree of cellulite ( 20 from each of the two research centers ) entered a double-blinded , r and omized trial where an anticellulite cream was applied on a nightly basis to the affected sites for four continuous weeks . Each subject was r and omized to receive active cream on either the right or left leg , with the contralateral side serving as placebo control . Bioceramic-coated neoprene shorts were worn overnight to enhance penetration of the topical agents by occlusion . High- quality digital photography was taken before treatment and after 4 weeks , with tangential full-spectrum lighting . Five blinded , independent physician review ers assessed the photographs for improvement . Subject question naires were completed to assess tolerability and efficacy . RESULTS Of the 34 subjects who completed the study , 62 % ( 21/34 ) noticed an overall improvement in their cellulite , with 62 % ( 13/21 ) reporting greater improvement in the thigh that received active product . All 34 subjects found the shorts and creams easy and pleasant to use . Overall , the average measured decrease in thigh circumference was 1.9 cm ( range : 0.1 - 4.5 ) with active product , and 1.3 cm ( range : 0.1 - 3.0 ) with placebo . Upon review of the pre- and post study photographs , dermatologist evaluators found thighs treated with active product showed greater improvement than thighs treated with placebo in 68 % of subjects . CONCLUSIONS The active topical agent used in this study was found to be effective in reducing the appearance of cellulite . All subjects tolerated the formulation well with no adverse effects . The success of this research vali date s the pathophysiologic concepts used to formulate the topical compound . This study both increases our underst and ing of the nature of cellulite and establishes a tolerable , effective product to treat it Numerous manufacturers are marketing topical creams , cl aim ing that they improve or eliminate unwanted fat or cellulite in a short period of time . The active ingredient in most of these creams is theophylline , and cl aims have been made that it initiates lipolysis by binding to adipocyte beta-adrenergic receptors . The creams are applied with vigorous massage to facilitate absorption and apply mechanical stress to the fat cells . The efficacy of these creams is largely untested . This prospect i ve r and omized study was conducted to determine whether there is scientific evidence that application of these creams alone can eliminate unwanted fat or cellulite . Eleven women with normal body weight as defined by insurance tables applied either Skinny Dip(TM ) or a placebo to one thigh and one half of the abdomen for 8 weeks . Each subject was examined , photographed , weighed , and measured by a study monitor on a weekly basis . There were no statistically significant differences in appearance , abdominal circumference , thigh circumference , or skin fold measurements among subjects using the active agent ( Skinny Dip(TM ) ) or the placebo . This study failed to support the efficacy of topically applied lipolytic creams in eliminating unwanted fat manifesting as a localized bulge or cellulite presenting as a dimpling of the skin A double-blind , r and omized , placebo-controlled study was conducted with 46 healthy female volunteers in order to test an anti-cellulite product containing retinol , caffeine and ruscogenine . An evaluation of different parameters related to cellulite appearance , i.e. , the skin macrorelief , the dermal and hypodermal structures , the skin mechanical characteristics , and the cutaneous flowmetry was assessed using several non-invasive methods . This combination of different evaluation methods result ed in the demonstration of significant activity of the anti-cellulite product versus baseline and showed its superiority versus the placebo in skin macrorelief ( decrease of the " orange peel " effect ) and an increase in cutaneous microcirculation . By using a combination of methods , it was possible to detail the activity of an anti-cellulite product and to show superiority of the product in comparison with the placebo Cellulite is a common phenomenon that particularly affects the thighs and buttocks of women . Little scientific evidence exists to support any of the many advertised treatments for it . A total of 52 of 69 women , who were divided into three groups , completed a 12-week , r and omized , controlled trial in which the effectiveness of two different treatments for cellulite was assessed . The patients acted as their own controls . The treatments investigated were twice-daily application of aminophylline cream and twice-weekly treatment with Endermologie ES1 . Group 1 ( double blind ) received aminophylline to one thigh/buttock and a placebo cream to the other . Group 2 ( singly blind ) received Endermologie to one thigh/buttock . Group 3 received Endermologie to both sides and used the same cream regimen as group 1 . Results were assessed subjectively by the patient and by clinical examination and photographic assessment by the surgeon ( before and after the trial ) . Morphologic assessment included body mass index , thigh girth at two points , and thigh fat depth measurement by ultrasound . No statistical difference existed in measurements between legs for any of the treatment groups ( paired t test , p > 0.4 ) . The best subjective assessment , by the patients themselves , revealed that only 3 of 35 aminophylline-treated legs and 10 of 35 Endermologie-treated legs had their cellulite appearance improved . The authors do not believe that either of these two treatments is effective in improving the appearance of cellulite BACKGROUND The development of ultrasonography allowed for skin imaging used in dermatology and esthetic medicine . By means of classic and high-frequency ultrasonographies , changes within the dermis and subcutaneous tissue can be presented . OBJECTIVE The aim of this study was to show the possibilities of applying classic and high-frequency ultrasonographies in esthetic dermatology based on monitoring various types of anti-cellulite therapies . METHODS Sixty-one women with cellulite were assigned to two smaller groups . One group was using anti-cellulite cream and the second group was a placebo group . The ultrasound examination was carried out before the initiation and after the completion of the treatment and evaluated epidermal echoes , the thickness of the subcutaneous tissue and the dermis , dermis echogenicity , the length and surface area of the subcutaneous tissue fascicles growing into the dermis , and the presence or absence of edemas . RESULTS After the completion of the treatment , a statistically significant difference was observed . The most useful parameters were as follows : the thickness of the subcutaneous tissue , echogenicity , the surface area and length of the subcutaneous tissue , as well as the presence of edemas . The discussed changes were not observed in the placebo group . CONCLUSION Classic and high-frequency ultrasonographies are useful methods for monitoring anti-cellulite therapies BACKGROUND Excessive subcutaneous adipose tissue is typically treated by physically removing the fat through liposuction , but cost and accessibility have popularized alternative treatments for reducing adipose tissue thickness . OBJECTIVE The purpose of this study was to test the absolute and relative effectiveness of a liposome-encapsulated caffeine-based cream in modifying subcutaneous adipose tissue . METHODS Forty-one patients consented and completed the double-blind , single-center , placebo-controlled study . Caliper measurements , tape measurements , and photographs were taken over a 2-month period . RESULTS Both concentrations of the cream were found to significantly reduce the thickness of the adipose tissue in all areas of the body . In addition , the more concentrated cream was significantly more effective than the less concentrated cream in the areas of the hips and the triceps . CONCLUSION The caffeine-based liposome-encapsulated cream significantly reduced the thickness of the subcutaneous fat over a 2-month period Beta-adrenergic stimulation and alpha 2-adrenergic inhibition increase lipolysis from fat cells . Twenty-eight obese women were placed on a calorie-restricted diet and one of five treatments was applied to one thigh three to five times per week for four weeks : ( 1 ) isoproterenol injections ; ( 2 ) cream containing colforsin ( forskolin ) , aminophylline , and yohimbine ; ( 3 ) yohimbine cream ; ( 4 ) colforsin cream ; or ( 5 ) aminophylline cream . The opposite thigh was treated with a placebo ( injection or cream ) . The treated thighs lost significantly more girth after treatment , both by injection and by cream . No adverse reactions were attributable to either the cream or the injections . It is concluded that local fat reduction from the thigh can be safely accomplished Background Cellulite occurs to varying degrees on the thighs and buttocks of many otherwise healthy women . Among the many purported treatments for cellulite , only a h and ful have been tested in clinical trials . Objective The aim of this study was to critically explore the reputed effect of topical retinol in the treatment of cellulite . Material s and Methods The study compared the effect of topical retinol to a placebo formulation in a left-right r and omized trial in order to eliminate the massage-effect . The study was conducted in 15 women aged from 26 to 44 years who had requested liposuction to improve mild to moderate cellulite . Results After 6-months of treatment , skin elasticity was increased by 10.7 % while viscosity was decreased by 15.8 % at the retinol-treated site . Such an effect on the tensile properties of skin was more prominent where the mattress phenomenon was the only evidence of cellulite . The lumpy-bumpy appearance of the skin showed either little response or was not responsive to the treatment . Although gross microanatomical differences were not disclosed between the comparative sites at completion of the study , evidence for a shift in the phenotype of connective tissue cells was obtained . The main retinol-related change consisted of a 2- to 5-fold increase in the number of factor XIIIa+ dendrocytes both in the dermis and fibrous str and s of the hypodermis . Conclusions We hypothesize that the functional and phenotypic changes seen in this study were linked and represent the result of a direct or indirect modulating effect of retinol on cellulite . Such features ultimately improve the resting tensions inside the skin which should in turn smooth the skin surface Cellulite is thought to affect 80 - 90 % of postpubertal women , and is considered much of a cosmetic concern by the large majority of them . In this study , the objective was to assess the efficacy of a topical cosmetic product containing various active ingredients of botanical origin on cellulite blemishes on female volunteers affected by fat accumulations , as well as by slight-to-moderate cellulite in the lower limbs . The assessment was performed by means of various objective evaluations , including contact thermography , morphometric measures of thigh circumference , and microcirculation evaluation . The obtained results indicate that the use of synergistic botanical st and ardized extracts , through the exploitation of different mechanisms of action and acting on different biological targets , provides visible and measurable results in the improvement of cellulite signs and symptoms |
10,530 | 26,045,716 | The collected evidence suggests that genetic polymorphisms in CYP2E1 , GSTM1 , NQO1 , NAT2 , MDR1 , and XRCC1 are capable of modulating leukaemia risk , mainly when associated with environmental exposures , such as domestic pesticides and insecticides , smoking , trihalomethanes , alcohol consumption , and x-rays .
More recently , genome wide association studies identified significant associations between genetic polymorphisms in ARID5B e IKZF1 and acute lymphoblastic leukaemia , but only a few studies have replicated these results until now .
In conclusion , genetic susceptibility contributes to the risk of childhood leukaemia through the effects of gene-gene and gene-environment interactions | Acute leukaemias ( AL ) correspond to 25 - 35 % of all cancer cases in children .
The aetiology is still sheltered , although several factors are implicated in causality of AL subtypes .
Childhood acute leukaemias are associated with genetic syndromes ( 5 % ) and ionising radiation as risk factors .
Somatic genomic alterations occur during fetal life and are initiating events to childhood leukaemia .
Genetic susceptibility has been explored as a risk factor , since environmental exposure of the child to xenobiotics , direct or indirectly , can contribute to the accumulation of somatic mutations .
Hence , a systematic review was conducted in order to underst and the association between gene polymorphisms and childhood leukaemia risk . | Polymorphisms of glutathione S-transferase ( GST ) enzymes have been correlated with altered risk of several cancers , as well as altered response and toxicity from cancer chemotherapy . We report a low cost , highly reproducible and specific PCR-based high-throughput assay for genotyping different GSTs design ed for use in large clinical trials . In comparison to an alternative genotyping method ( single nucleotide extension ) , the sensitivity and specificity of the high throughput assay was shown to be 92 and 97 % , respectively , depending on the source of genomic DNA . Using the high-throughput assay , we demonstrate by multivariate analysis an increased risk of acute lymphoblastic leukemia , glial brain tumors , and osteosarcoma for patients carrying nonnull alleles of GSTM1 and /or GSTT1 Abstract — A model for childhood leukemia proposes that characteristic chromosomal translocations can arise in utero and that for most cases a second hit occurring postnatally will be necessary . Possible causal mechanisms for leukemias are environmental factors such as ionizing radiation from x rays and inherited susceptibility from polymorphisms in DNA repair genes . We performed a case-control study of childhood acute lymphoblastic leukemia measuring reported postnatal x rays in 701 cases aged 0–14 y and in as many population -based controls matched on age and sex . In addition we performed a case-only study in 207 cases to evaluate the interaction between x ray exposure and polymorphisms in DNA repair genes . There was an increase in risk of leukemia with number of x rays : the adjusted odds ratio for two or more x rays vs. none was 1.48 ( 95 % confidence interval : 1.11–1.97 ) . That risk was slightly higher among girls ( odds ratio = 1.67 ) . A polymorphism in the APE gene ( ex 5 ) involved in the base excision repair system was suggestive of an increased risk among boys and a reduced risk among girls . HMLH1 ( ex 8) , a mismatch repair gene , was associated with reduction of risk among girls . Results from the genetic data are still preliminary and must be interpreted with caution especially because of the relatively small number of genotyped cases . However , ionizing radiation from x rays as well as polymorphisms in DNA repair genes are plausible risk factors for childhood leukemia and should be studied more The aldo-keto reductase 1C3 ( AKR1C3 ) gene located on chromosome 10p15-p14 , a regulator of myeloid cell proliferation and differentiation , represents an important c and i date gene for study ing human carcinogenesis . In a prospect ively enrolled population -based case-control study of Han Chinese conducted in Kaohsiung in southern Taiwan , a total of 114 leukemia cases and 221 controls < 20 years old were recruited between November 1997 and December 2005 . The present study set out to evaluate the association between childhood leukemia and both maternal and offspring 's genotypes . To do so , we conducted a systematic assessment of common single-nucleotide polymorphisms ( SNPs ) at the 5 ' flanking 10 kb to 3 ' UTR of AKR1C3 gene . Gln5His and three tagSNPs ( rs2245191 , rs10508293 and rs3209896 ) and one multimarker ( rs2245191 , rs10508293 and rs3209896 ) were selected with average 90 % coverage of untagged SNPs by using the HapMap II data set . Odds ratios and 95 % confidence intervals were adjusted for age and gender . After correcting for multiple comparisons , we observed that risk of developing childhood leukemia is significantly associated with rs10508293 polymorphism on intron 4 of the AKR1C3 gene in both offspring alone and in the combined maternal and offspring genotypes ( nominal P < 0.0001 , permutation P < 0.005 ) . The maternal methylenetetrahydrofolate reductase A1298C polymorphism was found to be an effect modifier of the maternal intron 4 polymorphism of the AKR1C3 gene ( rs10508293 ) and the childhood leukemia risk . In conclusion , this study suggests that AKR1C3 polymorphisms may be important predictive markers for childhood leukemia susceptibility |
10,531 | 22,632,754 | The studies reported conflicting results or no statistically significant associations between the use of non-aspirin NSAIDs and risk of lung , ovary , bladder , prostate , skin , and head and neck cancers .
We did not find sufficient evidence to support the use of the non-aspirin NSAIDs for the primary chemoprevention of a wide variety of non-gastrointestinal cancers . | BACKGROUND There is evidence that aspirin is effective for the chemoprevention of colorectal cancer .
Due to their similar pharmacodynamics , the use of other non-steroidal anti-inflammatory drugs ( NSAIDs ) has been suggested for other cancer sites .
Although this possibility has been discussed in the literature , uncertainty remains about the actual effects of NSAIDs other than aspirin in nongastrointestinal cancer .
OBJECTIVE To summarize the best available evidence of the primary chemopreventive effects of non-aspirin NSAIDs for nongastrointestinal cancer . | Inflammation and gonadotropins are hypothesized to influence ovarian carcinogenesis . In a prospect i ve study , we evaluated ovarian cancer risk associated with self-reported use of medications that influence inflammation or gonadotropin levels . The Breast Cancer Detection Demonstration Project Follow-Up Study enrolled 61,431 women in 1979 and used telephone interviews and 3 mailed question naires through 1998 to up date risk factor information and identify incident ovarian cancers . The 1992 - 95 question naire ascertained medication use , including duration and frequency of use for aspirin , acetaminophen , other nonsteroidal anti-inflammatory drugs ( NSAIDs ) , tranquilizers and histamine-receptor antagonists . A Poisson regression analysis generated rate ratios ( RRs ) and 95 % confidence intervals ( CIs ) for the 31,364 women who were at risk of ovarian cancer and responded to the question naire that queried regular medication use . One hundred sixteen women developed ovarian cancer during follow-up . None of the anti-inflammatory medications was associated with ovarian cancer , but the RR for more than 1 aspirin per day for 1 year or longer was 0.56 ( 95 % CI 0.20 - 1.5 ) and the RR for more than 5 years of regular " other NSAID " use was 2.0 ( 95 % CI 0.95 - 4.2 ) . Regular tranquilizer use was not associated with ovarian cancer , but histamine-receptor antagonists used regularly for more than 5 years ( RR = 3.6 , 95 % CI 1.4 - 9.1 ) or more than once daily ( RR = 3.1 , 95 % CI 1.5 - 6.5 ) appeared to increase risk . In our study , neither anti-inflammatory medications nor anti-psychotic medications were associated with ovarian cancer . Potential associations with histamine-receptor antagonists may warrant further study Objective : We sought to evaluate the association between ovarian cancer risk and use of aspirin and nonsteroidal anti-inflammatories . Methods : We prospect ively assessed use of aspirin , nonsteroidal anti-inflammatories ( NSAIDs ) , and acetaminophen use in relation to ovarian cancer risk among 76,821 participants in the Nurses ' Health Study who had no history of cancer other than non-melanoma skin cancer . Women reported known and suspected ovarian cancer risk factors in biennial mailed question naires from 1976 to 1996 , along with new diagnoses of ovarian cancer . Aspirin use was assessed in 1980 , 1982 , 1984 , and 1988–1994 . We assessed NSAID use in 1980 , and both NSAID and acetaminophen use in 1990 , 1992 , and 1994 . During 16 years of follow-up and 1,222,412 person-years , 333 cases of invasive epithelial ovarian cancer were confirmed . We used pooled logistic regression to control for age , body mass index , oral contraceptive use , smoking history , parity , postmenopausal hormone use , tubal ligation , and other potential ovarian cancer risk factors . Results : Aspirin use was not associated with ovarian cancer risk overall ( RR for users compared with nonusers , 1.00 , 95 % confidence interval ( CI 0.80–1.25 ) . We found no association between aspirin dose ( in number of weekly tablets ) and ovarian cancer risk ( RR for those taking 15 or more tablets weekly compared with nonusers , 0.98 , 95 % CI 0.63–1.52 ) . Similarly , duration of aspirin use was not associated with risk ( RR for aspirin use of 20 or more years , 0.99 , 95 % CI 0.69–1.43 ) . In separate models assessing the relation between NSAID use and ovarian cancer risk we found a 40 % reduction in risk among NSAID users versus nonusers ( RR 0.60 , 95 % CI 0.38–0.95 ) . However , when we examined this relationship in terms of days of NSAID use per month , we did not observe a dose – response with increasing NSAID use . Conclusions : We observed no association between aspirin use , dose , or duration and epithelial ovarian cancer risk . Although we found a modest reduction in risk associated with NSAID use , there was no dose – effect Background : Several epidemiologic studies have shown inverse associations between use of nonsteroidal anti-inflammatory drugs ( NSAID ) and incident ovarian cancer , but the results are inconsistent . There have been only a few studies examining possible links between NSAIDs and endometrial cancer risk . We investigated associations between use of NSAIDs and incident ovarian and endometrial cancers in a prospect i ve cohort of about 20,000 women with ages from 58 to 76 years in 1992 . Participants were asked how often they used aspirin and nonaspirin NSAIDs . Over 15 years , 311 endometrial and 167 ovarian incident malignancies were identified . Multivariate-adjusted hazard ratios were estimated using Cox proportional regression . Results : Compared with women who reported no use of aspirin , the relative risks for ovarian cancer for those who used aspirin < 2 , 2 to 5 times , and ≥6 times per week were 0.83 , 0.77 , and 0.61 , respectively ( P trend = 0.04 ) . We did not observe any association between nonaspirin NSAIDs use and ovarian cancer risk . Neither did we find associations between aspirin or nonaspirin NSAIDs use and risk for endometrial cancer . Conclusions : Our results suggest a possible inverse association between frequency of aspirin use and risk for ovarian cancer . Cancer Epidemiol Biomarkers Prev ; 19(2 ) ; Background : Previous studies have suggested that use of aspirin or other nonsteroidal anti-inflammatory drugs ( NSAIDs ) may be associated with reduced risk of lung cancer , but the data are inconsistent and are limited particularly with respect to the effects of aspirin , separate from other NSAIDs . Methods : The Iowa Women 's Health Study is a prospect i ve cohort of 41,836 Iowa women ages 55 to 69 years old at baseline in 1986 . NSAID use was assessed in 1992 . Over 10 years of follow-up , 403 incident cases of lung cancer were identified . The association of incident lung cancer with current use of aspirin or non-aspirin NSAIDs was analyzed after adjustment for lung cancer risk factors . Hazard ratios ( HR ) were estimated using multivariate COX proportional hazards regression . Results : There were 27,162 women in the analytic cohort . After controlling for age , education , alcohol intake , pack-years , smoking status , body mass index , and total fruit intake , the RR of women taking six or more aspirin weekly was 1.21 ( 95 % confidence interval , 0.92 - 1.59 ) . The HR was 1.23 for women taking six or more non-aspirin NSAIDs weekly ( 95 % confidence interval , 0.92 - 1.65 ) . There was no statistically significant trend by frequency of use for either aspirin ( Ptrend = 0.22 ) or non-aspirin NSAIDs ( Ptrend = 0.53 ) . Analyses by histologic type and smoking status yielded similar null results . Information on dosage and duration of use were not available for this analysis . Conclusion : These findings do not suggest that aspirin or other NSAIDs reduce risk of lung cancer in this cohort of postmenopausal women . ( Cancer Epidemiol Biomarkers Prev 2006;15(11):2226–31 Inflammation is postulated to play an important role in ovarian carcinogenesis . Prostagl and in endoperoxide synthase 2 ( PTGS2 ) is responsible for the conversion of arachidonic acid to prostagl and ins in response to inflammation . In a pooled analysis of two population -based studies , the Hawaii Ovarian Cancer Case – Control Study and the New Engl and Case – Control Study , including 1,025 women with invasive ovarian carcinoma and 1,687 cancer-free controls , the association of ovarian cancer risk with the PTGS2 rs5275 polymorphism and the use of nonsteroidal antiinflammatory drugs ( NSAIDs ) were examined . Odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) were estimated using unconditional logistic regression . In the pooled analysis , the CC genotype was associated with a reduced risk of nonserous ovarian carcinoma ( OR = 0.66 ; CI : 0.44–0.98 ) . In addition , the lowest risk was observed among carriers of the CC genotype who were users of only nonaspirin NSAIDs ( OR = 0.43 ; CI:0.20–0.93 ) in all women combined . The association of PTGS2 rs5275 with nonserous ovarian carcinoma and possible effect modification by NSAID use needs further validation , preferably in prospect i ve studies BACKGROUND Epidemiological evidence suggests that chronic inflammation may influence ovarian carcinogenesis . The study objective was to examine the association between the commonly used anti-inflammatory drug aspirin and epithelial ovarian cancer . METHODS The authors conducted a case-control study based in the New York University Women 's Health Study cohort enrolled between 1985 and 1991 in New York City . After a median follow-up period of 12 years , 68 incident cases of epithelial ovarian cancer were identified . Data about regular aspirin use were collected during the 1994 - 1996 follow-up question naire . Using a case-control study design , 10 controls per case were r and omly selected among study participants who matched the case by age and menopausal status . Conditional logistic regression analysis was used to study the relationships between aspirin and epithelial ovarian cancer by generating odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) . RESULTS Relative to no aspirin use , the OR for epithelial ovarian cancer among women who reported aspirin use three or more times per week for a period of at least 6 months was 0.60 ( 95 % CI 0.26 , 1.38 ) , after adjustment for age at menarche , parity , oral contraceptive use , and first-degree family history of breast cancer before age 50 . Among recent , within the previous 5 years , users of aspirin , the adjusted OR was 0.36 ( 95 % CI 0.11 , 1.18 ) . CONCLUSION Although confidence intervals included unity , the observed risk estimates seem to be compatible with previous studies suggesting that regular aspirin use could be inversely associated with risk of epithelial ovarian cancer Chronic inflammation may play an etiologic role in endometrial cancer . Nonsteroidal anti-inflammatory drugs ( NSAIDs ) reduce inflammatory activity by inhibiting the proinflammatory cyclooxygenase enzymes and , therefore , may decrease cancer risk . However , few studies have examined the association between NSAID use and endometrial cancer . We conducted a prospect i ve study among 72,524 women in the NIH-AARP Diet and Health Study . Women completed a question naire in 1996–1997 on lifestyle and health-related factors , including type and frequency of NSAID use within the past year , and were followed through 2003 by linkages to cancer registries and vital status data bases . During 488,261 person-years of follow-up , there were 732 incident endometrial cancers . NSAID use , compared with nonuse of NSAIDs , was not significantly associated with endometrial cancer risk [ relative risk ( RR ) , 0.90 ; 95 % confidence interval ( 95 % CI ) , 0.74–1.09 ] . Null associations were also observed by type of NSAID use [ aspirin only : RR , 0.88 ; 95 % CI , 0.70–1.11 ; nonaspirin NSAID ( NA-NSAID ) only : RR , 1.01 ; 95 % CI , 0.79–1.29 ; both aspirin and NA-NSAIDs : RR , 0.85 ; 95 % CI , 0.68–1.06 ] . Generally , results were not statistically significant by frequency of use for aspirin or NA-NSAIDs . Results did not change when women with a history of heart disease , hypertension , or diabetes were excluded to minimize the potential for confounding by indication . Overall , our data do not support an association between aspirin or NA-NSAID use and endometrial cancer risk To date , no prospect i ve studies have explored the relationship between the use of aspirin , other nonsteroidal anti-inflammatory medications ( NSAID ) , and acetaminophen and endometrial adenocarcinoma . Of the 82,971 women enrolled in a prospect i ve cohort study , 747 developed medical record-confirmed invasive endometrial cancer over a 24-year period . Use of aspirin was ascertained from 1980 to 2004 , and for other NSAIDs and acetaminophen , from 1990 to 2004 . Cox regression models calculated multivariate relative risks ( MV RR ) , controlling for body mass index ( BMI ) , postmenopausal hormone ( PMH ) use , and other endometrial cancer risk factors . Currency , duration , and quantity of aspirin were not associated with endometrial cancer risk overall [ current use : MV RR , 1.03 ; 95 % confidence interval ( CI ) 0.83 - 1.27 ; > 10 years of use : MV RR , 1.01 ; 95 % CI , 0.78 - 1.30 ; and cumulative average > 7 tablets per week : ( MV RR , 1.10 ; 95 % CI , 0.84 - 1.44 ) ] . However , stratified analyses showed that a lower risk of endometrial cancer among obese ( BMI , > or=30 kg/m(2 ) ) women was seen with current aspirin use ( MV RR , 0.66 ; 95 % CI , 0.46 - 0.95 ) . The greatest risk reduction for current aspirin users was seen in postmenopausal obese women who had never used PMH ( MV RR , 0.43 ; 95 % CI , 0.26 - 0.73 ) . The use of other NSAIDs or acetaminophen was not associated with endometrial cancer . Our data suggest that use of aspirin or other NSAIDs does not play an important role in endometrial cancer risk overall . However , risk was significantly lower for current aspirin users who were obese or who were postmenopausal and had never used PMHs ; these subgroup findings require further confirmation Epidemiologic data on the association between nonsteroidal antiinflammatory drugs ( NSAIDs ) and ovarian cancer risk have been inconsistent . The authors prospect ively examined the association between regular use of aspirin and nonaspirin NSAIDs and ovarian cancer incidence among 197,486 participants of the Nurses ' Health Study ( NHS ) and the Nurses ' Health Study -II ( NHS-II ) over 24 and 16 years of follow-up , respectively . Information on aspirin was initially assessed in 1980 ( NHS ) and 1989 ( NHS-II ) and on nonaspirin NSAIDs and acetaminophen in 1990 ( NHS ) and 1989 ( NHS-II ) and up date d throughout follow-up . The authors used Cox proportional hazards models adjusting for ovarian cancer risk factors . A total of 666 confirmed cases of epithelial ovarian cancer were identified over 2,790,986 person-years of follow-up . The hazard ratios associated with regular use of aspirin , nonaspirin NSAIDs , and acetaminophen were 1.11 ( 95 % confidence interval ( CI ) : 0.92 , 1.33 ) , 0.81 ( 95 % CI : 0.64 , 1.01 ) , and 1.14 ( 95 % CI : 0.92 , 1.43 ) , respectively . The authors did not observe a dose-response relation with increased frequency or duration of regular use of any of these medications and ovarian cancer incidence . The results did not differ substantially by tumor histology . In this large prospect i ve study , the authors found no compelling evidence to support an association between regular use of aspirin , nonaspirin NSAIDs , or acetaminophen and ovarian cancer incidence PURPOSE Observational studies have reported significant negative associations between sporadic non-steroidal anti-inflammatory drug ( NSAID ) use and keratinocyte carcinoma ( KC ) while reporting null results for regular use . This pattern may be partially explained by the operational expression of NSAID exposure and analytic model assumptions . Our goals were to quantify the association between NSAIDs and KC and to explore the impact of exposure metrics and modeling assumptions on observed associations . METHODS We conducted a prospect i ve cohort study by linking data from the Veterans Affairs Topical Tretinoin Chemoprevention Trial and the VA Pharmacy Benefits Management data base . NSAID use was categorized according to cyclooxygenase selectivity , timing of initiation , and frequency of use . Data were analyzed using time-varying and time-fixed multivariable-adjusted Cox proportional hazard models [ Correction made here after initial online publication ] . Simulated null data were generated and analyzed to explore potential biases introduced by the models and the exposure metrics . RESULTS During a median follow-up time of 2 years for basal cell carcinoma and 2.5 years for squamous cell carcinoma , 472 occurrences of BCC and 309 occurrences of SCC were observed . Time-fixed analyses of NSAID exposure metrics produced significant negative associations , whereas time-varying analyses produced null results . Analysis of simulated null data revealed the potential for strong bias in the time-fixed analyses . CONCLUSIONS This study did not identify a negative association between NSAIDs and KC . The disparity between the time-fixed and the time-varying analyses highlights the extent to which operational definitions of drug exposures and reliance on time-fixed methods may introduce bias Background Pre clinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers . We evaluated the efficacy and safety of celecoxib , a cyclooxygenase 2 inhibitor , as a chemopreventive agent for actinic keratoses , the premalignant precursor of nonmelanoma skin cancers , and for nonmelanoma skin cancers , including cutaneous squamous cell carcinomas ( SCCs ) and basal cell carcinomas ( BCCs ) . Methods A double-blind placebo-controlled r and omized trial involving 240 subjects aged 37–87 years with 10–40 actinic keratoses was conducted at eight US academic medical centers . Patients were r and omly assigned to receive 200 mg of celecoxib or placebo administered orally twice daily for 9 months . Subjects were evaluated at 3 , 6 , 9 ( ie , completion of treatment ) , and 11 months after r and omization . The primary endpoint was the number of new actinic keratoses at the 9-month visit as a percentage of the number at the time of r and omization . In an intent-to-treat analysis , the incidence of actinic keratoses was compared between the two groups using t tests . In exploratory analyses , we evaluated the number of nonmelanoma skin cancers combined and SCCs and BCCs separately per patient at 11 months after r and omization using Poisson regression , after adjustment for patient characteristics and time on study . The numbers of adverse events in the two treatment arms were compared using χ2 or Fisher exact tests . All statistical tests were two-sided . Results There was no difference in the incidence of actinic keratoses between the two groups at 9 months after r and omization . However , at 11 months after r and omization , there were fewer nonmelanoma skin cancers in the celecoxib arm than in the placebo arm ( mean cumulative tumor number per patient 0.14 vs 0.35 ; rate ratio [ RR ] = .43 , 95 % confidence interval [ CI ] = 0.24 to 0.75 ; P = .003 ) . After adjusting for age , sex , Fitzpatrick skin type , history of actinic keratosis at r and omization , nonmelanoma skin cancer history , and patient time on study , the number of nonmelanoma skin cancers was lower in the celecoxib arm than in the placebo arm ( RR = 0.41 , 95 % CI = 0.23 to 0.72 , P = .002 ) as were the numbers of BCCs ( RR = 0.40 , 95 % CI = 0.18 to 0.93 , P = .032 ) and SCCs ( RR = 0.42 , 95 % CI = 0.19 to 0.93 , P = .032 ) . Serious and cardiovascular adverse events were similar in the two groups . Conclusions Celecoxib may be effective for prevention of SCCs and BCCs in individuals who have extensive actinic damage and are at high risk for development of nonmelanoma skin cancers Experimental studies have consistently shown a protective effect of nonsteroidal antiinflammatory drugs ( NSAIDs ) against nonmelanoma skin cancers ( NMSC ) . However , little human epidemiological research has been done in this regard . We used data from the Skin Cancer Chemoprevention Study to explore the association of NSAID use and with the risk of basal‐cell carcinoma ( BCC ) and squamous‐cell carcinoma ( SCC ) . 1,805 subjects with a recent history of NMSC were r and omized to placebo or 50 mg of daily β‐carotene . Participants were asked about their use of over‐the‐counter and prescription medications at baseline and every 4 months during the trial . Skin follow‐up examinations were scheduled annually with a study dermatologist ; confirmed lesions were the endpoints in the study . We used a risk set approach to the analysis of grouped times survival data and unconditional logistic regression to compute odds ratios [ ORs ] for various exposures to NSAIDs . The use of NSAIDs was reported in over 50 % of question naires . For BCC , NSAIDs exhibited a weak protective effect in crude analyses , which attenuated markedly after adjustment . For SCC , the use of NSAIDs in the year previous to diagnosis reduced the odds by almost 30 % ( adjusted OR= 0.71 , 95 % CI 0.48–1.04 ) . When we accounted for frequency of use , results for BCC were not striking , and there were inconsistent suggestions of an inverse association with SCC . There were some indications of a modest , nonsignificant reduction on the number of BCCs and SCCs with NSAID use . Our data suggest a weak and inconsistent chemopreventive effect of NSAIDs on BCC and SCC . © 2006 Wiley‐Liss , We investigated the risk of basal cell carcinoma ( BCC ) in relation to a number of single nucleotide polymorphisms in genes involved in the inflammatory response . A case-control study including 322 BCC cases and a similar number of controls was nested in a population -based prospect i ve study of 57,053 individuals ( aged 50 - 64 at inclusion ) in Denmark . NSAID use was associated with a slightly decreased risk of BCC ( IRR=0.85 , 95 % CI=0.66 - 1.10 ) . We found that two polymorphisms in COX-2 , COX-2 A-1195 G and T8473C were associated with risk of BCC . Carriers of the variant allele of COX-2 A-1195 G had lower risk of BCC than homozygous wild type carriers ( IRR=0.54 , 95 % CI=0.47 - 0.89 ) . Homozygous carriers of the variant allele of COX-2 T8473C were at 2.27-fold higher risk of BCC ( 95 % CI=1.31 - 3.92 ) than homozygous wild type allele carriers . The polymorphisms IL6 G-174C , IL8 T-251A , PPARgamma2 Pro(12)Ala , IL1beta T-31C , and IL10 C-592A were not associated with risk of BCC . We found no statistically significant interaction between polymorphisms and NSAID use in relation to risk of BCC . While it can not be ruled out that the present findings are due to chance , the results indicate that high COX-2 expression may increase risk of BCC while NSAID use may be protective BACKGROUND Aspirin , other non-steroidal anti-inflammatory drugs ( NSAIDs ) , and statins have been associated with lower risk of prostate cancer and its progression , though results have been inconsistent . METHODS Data from 140 men with prostate cancer enrolled in a Phase 2 clinical trial of selenium to prevent prostate cancer progression were analyzed to determine association between aspirin , other NSAIDs , or statin use with baseline serum prostate-specific antigen ( PSA ) levels and PSA velocity ( rate of PSA change over time ) using repeated measures over an average follow-up time of 3.2 years . Multiple linear regression and mixed effects models were used to model the association of medication use with PSA at baseline and with PSA velocity , respectively . RESULTS Baseline PSA levels were significantly lower in aspirin users compared to non-users ( 5.17 ng/ml vs. 7.58 ng/ml , P = 0.001 ) . This association was statistically significant in never smokers ( aspirin users vs. non-users : 4.19 ng/ml vs. 8.24 ng/ml , P = 0.004 ) but not in ever smokers ( aspirin users vs. non-users : 5.52 ng/ml vs. 7.3 ng/ml , P = 0.101 ) . Statin and other NSAID use was not associated with baseline PSA . Aspirin , statin , or other NSAID use at baseline demonstrated a non-significant negative association with PSA velocity . CONCLUSION These findings support an effect of aspirin use on PSA , particularly among never smokers . However , they do not suggest a protective effect on the disease and support previous findings that aspirin use may mask accurate measurement of PSA warranting consideration of washout procedures prior to testing |
10,532 | 25,478,803 | Placebo response was significant at the earliest time period ( 15 - 30 minutes ) .
There was no significant evidence of placebo response at any of the other time periods .
PERSPECTIVE In this meta- analysis of placebo responses in r and omized controlled trials in long-st and ing CRPS , published during 1966 to 2013 , we found no evidence for placebo analgesia , except at very early time points . | UNLABELLED The typical placebo response ( ie , the nonspecific effects in the placebo group including benign natural course , regression to the mean , expectation/conditioning effects , and others ) in r and omized trials in complex regional pain syndrome ( CRPS ) is unknown .
We recently observed a surprising near-absence of placebo response in a r and omized controlled trial we conducted on patients with long-st and ing ( ≥6 months ) CRPS . | The microcirculation appears to be impaired in cold chronic complex regional pain syndrome ( CRPS ) . This double-blind , placebo-controlled , r and omized trial investigated the effect of the nitric oxide ( NO ) donor isosorbide dinitrate ( ISDN ) on the peripheral blood flow in patients with chronic CRPS . Twenty-four patients received 1 % ISDN in Vaseline or a placebo ointment applied to the dorsum of the affected h and four times daily for 10 weeks . The patients participated in a physical therapy program to improve activity . The primary outcome measure was blood distribution in the affected extremity , which was determined by measuring the skin temperature using videothermography . We also measured NO and endothelin-1 concentrations in blister fluid , pain using the visual analog scale , and activity limitations using an upper limb activity monitor and the Disabilities of Arm Shoulder and H and Question naire . ISDN failed to produce a significant improvement in temperature asymmetry in chronic cold CRPS patients , and it did not result in the expected reduction in pain and increase in activity compared with placebo either . There may be other central or peripheral factors contributing to the disturbed vasodynamics in cold chronic CRPS that are not influenced by NO substitution . This study does not show an improvement of the regional blood distribution by ISDN in the involved extremity of patients with cold-type CRPS Background Placebo treatment can significantly influence subjective symptoms . However , it is widely believed that response to placebo requires concealment or deception . We tested whether open-label placebo ( non-deceptive and non-concealed administration ) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome ( IBS ) . Methods Two-group , r and omized , controlled three week trial ( August 2009-April 2010 ) conducted at a single academic center , involving 80 primarily female ( 70 % ) patients , mean age 47±18 with IBS diagnosed by Rome III criteria and with a score ≥150 on the IBS Symptom Severity Scale ( IBS-SSS ) . Patients were r and omized to either open-label placebo pills presented as “ placebo pills made of an inert substance , like sugar pills , that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes ” or no-treatment controls with the same quality of interaction with providers . The primary outcome was IBS Global Improvement Scale ( IBS-GIS ) . Secondary measures were IBS Symptom Severity Scale ( IBS-SSS ) , IBS Adequate Relief ( IBS-AR ) and IBS Quality of Life ( IBS-QoL ) . Findings Open-label placebo produced significantly higher mean ( ±SD ) global improvement scores ( IBS-GIS ) at both 11-day midpoint ( 5.2±1.0 vs. 4.0±1.1 , p<.001 ) and at 21-day endpoint ( 5.0±1.5 vs. 3.9±1.3 , p = .002 ) . Significant results were also observed at both time points for reduced symptom severity ( IBS-SSS , p = .008 and p = .03 ) and adequate relief ( IBS-AR , p = .02 and p = .03 ) ; and a trend favoring open-label placebo was observed for quality of life ( IBS-QoL ) at the 21-day endpoint ( p = .08 ) . Conclusion Placebos administered without deception may be an effective treatment for IBS . Further research is warranted in IBS , and perhaps other conditions , to eluci date whether physicians can benefit patients using placebos consistent with informed consent . Trial Registration Clinical Trials.gov OBJECTIVES Complex regional pain syndrome ( CRPS ) , formerly known as reflex sympathetic dystrophy ( RSD ) , is a painful , disabling disorder for which treatment is difficult . The aim of this study was to determine the efficacy of pamidronate in a double-blind r and omized placebo-controlled trial . METHODS Patients referred to our regional multidisciplinary pain management center who fulfilled the International Association for the Study of Pain criteria for CRPS Type I were enrolled in the study over a 2-year period . Patients were administered , intravenously , either pamidronate , 60 mg as a single dose , or normal saline . Patients ' pain scores , global assessment of disease severity scores , and functional assessment ( SF-36 ) scores were documented at baseline and at 1 and 3 months . RESULTS Twenty-seven patients ( 18 female , 9 male ; average age 45 years ) were recruited , of whom 14 received pamidronate and 13 received placebo . Overall improvements in pain score , patient 's global assessment of disease severity score , and physical function ( SF-36 ) score were noted in the pamidronate group at 3 months , and improvements in role physical ( SF-36 ) score were noted at 1 and 3 months . There was variability in pamidronate response among individuals . CONCLUSIONS Pamidronate may be a useful treatment option in the management of patients with CRPS Type I. Although treatment response was variable , the majority of patients improved . Early administration in t and em with other treatment measures is recommended Background . Complex regional pain syndrome type 1 ( CRPSt1 ) of the upper limb is a painful and debilitating condition , frequent after stroke , and interferes with the rehabilitative process and outcome . However , treatments used for CRPSt1 of the upper limb are limited . Objective . This r and omized controlled study was conducted to compare the effectiveness on pain and upper limb function of mirror therapy on CRPSt1 of upper limb in patients with acute stroke . Methods . Of 208 patients with first episode of unilateral stroke admitted to the authors ’ rehabilitation center , 48 patients with CRPSt1 of the affected upper limb were enrolled in a r and omized controlled study , with a 6-month follow-up , and assigned to either a mirror therapy group or placebo control group . The primary end points were a reduction in the visual analogue scale score of pain at rest , on movement , and brush-induced tactile allodynia . The secondary end points were improvement in motor function as assessed by the Wolf Motor Function Test and Motor Activity Log . Results . The mean scores of both the primary and secondary end points significantly improved in the mirror group ( P < .001 ) . No statistically significant improvement was observed in any of the control group values ( P > .001 ) . Moreover , statistically significant differences after treatment ( P < .001 ) and at the 6-month follow-up were found between the 2 groups . Conclusions . The results indicate that mirror therapy effectively reduces pain and enhances upper limb motor function in stroke patients with upper limb CRPSt1 OBJECTIVE Complex regional pain syndrome type I ( CRPS-I ) is a severely disabling pain syndrome for which no definite treatment has been established . The aim of this multi-centre , r and omized , double-blind placebo-controlled trial was to test the efficacy of the amino-bisphosphonate neridronate in patients with CRP-I. METHODS Eighty-two patients with CRP-I at either h and or foot were r and omly assigned to i.v . infusion of 100 mg neridronate given four times over 10 days or placebo . After 50 days the former placebo patients were given open label the same regimen of neridronate . RESULTS Within the first 20 days , visual analogue scale ( VAS ) score decreased significantly more in the neridronate group . In the following 20 days , VAS remained unchanged in the placebo group and further decreased in the active group by 46.5 mm ( 95 % CI -52.5 , -40.5 ) vs 22.6 mm ( 95 % CI -28.8 , -16.3 ) for placebo group ( P < 0.0001 ) . Significant improvements vs placebo were observed also for a number of other indices of pain and quality of life . During the open-extension phase in the formerly placebo group the results of treatment were superimposable on those seen during the blind phase in the active group . A year later none of the patients was referring symptoms linked to CRPS-I. CONCLUSION In patients with acute CRPS-I , four i.v . infusions of neridronate 100 mg are associated with clinical ly relevant and persistent benefits . These results provide conclusive evidence that the use of bisphosphonates , at appropriate doses , is the treatment of choice for CRPS-I. TRIAL REGISTRATION EU Clinical Trials Register , https://www . clinical trialsregister.eu/ , 2007 - 003372 - 18 Background Complex Regional Pain Syndrome type one ( CRPS I ) or formerly Reflex Sympathetic Dystrophy ( RSD ) is a disabling syndrome , in which a painful limb is accompanied by varying symptoms . Neuropathic pain is a prominent feature of CRPS I , and is often refractory to treatment . Since gabapentin is an anticonvulsant with a proven analgesic effect in various neuropathic pain syndromes , we sought to study the efficacy of the anticonvulsant gabapentin as treatment for pain in patients with CRPS I. Methods We did a r and omized double blind placebo controlled crossover study with two three-weeks treatment periods with gabapentin and placebo separated by a two-weeks washout period . Patients started at r and om with gabapentin or placebo , which was administered in identical capsules three times daily . We included 58 patients with CRPS type 1 . Results Patients reported significant pain relief in favor of gabapentin in the first period . Therapy effect in the second period was less ; finally result ing in no significant effect combining results of both periods . The CRPS patients had sensory deficits at baseline . We found that this sensory deficit was significantly reversed in gabapentin users in comparison to placebo users . Conclusions Gabapentin had a mild effect on pain in CRPS I. It significantly reduced the sensory deficit in the affected limb . A sub population of CRPS patients may benefit from gabapentin UNLABELLED To assess the effects of intravenous administration of the free radical scavenger mannitol 10 % on complaints associated with complex regional pain syndrome Type I ( CRPS I ) , a r and omized , placebo-controlled , double-blinded trial was performed . Forty-one CRPS I patients according to the Bruehl et al diagnostic criteria , were included in 2 outpatient pain clinics of 2 university medical centers and r and omly assigned to receive either 10 % mannitol iv in 1 L 0.9 % NaCL in 4 hours for 5 consecutive days or equal volumes of 0.9 % NaCL ( placebo ) . Patients in both groups received physical therapy according to protocol and rescue pain medication if required . Complaints on impairment and disability level and quality of life were assessed up to 9 weeks after baseline , with primary measurement points at 2 , 6 , and 9 weeks . Monitoring of pain using the visual analogue scale took place continuously during the course of the trial . Except for a significant improvement on a subscale of the Jebsen-Taylor h and function test , no significant differences were found between mannitol and placebo treatment . Changes in both groups in the course of the trial were small and clinical ly irrelevant on all measurement indices . We conclude that intravenous administration of 10 % mannitol is not more effective than placebo in reducing complaints for CRPS I patients and provides no addition to already-established interventions for CRPS I. Whether 10 % mannitol can provide beneficial effects for subgroups of CRPS I patients with a pathophysiological profile more closely fitting the presumed mode of action for this intervention remains to be established . PERSPECTIVE This article addresses the efficacy of the intravenous administration of the free radical scavenger mannitol for treatment of CRPS type 1 . This intervention is not more effective than placebo in reducing complaints for CRPS I patients and provides no addition to already-established interventions for CRPS Background This double-blind , r and omized , controlled trial investigated the effect of the phosphodiesterase-5 inhibitor tadalafil on the microcirculation in patients with cold Complex Regional Pain Syndrome ( CRPS ) in one lower extremity . Methods Twenty-four patients received 20 mg tadalafil or placebo daily for 12 weeks . The patients also participated in a physical therapy program . The primary outcome measure was temperature difference between the CRPS side and the contralateral side , determined by measuring the skin temperature with videothermography . Secondary outcomes were : pain measured on a Visual Analogue Scale , muscle force measured with a MicroFet 2 dynamometer , and level of activity measured with an Activity Monitor ( AM ) and walking tests . Results At the end of the study period , the temperature asymmetry was not significantly reduced in the tadalafil group compared with the placebo group , but there was a significant and clinical ly relevant reduction of pain in the tadalafil group . Muscle force improved in both treatment groups and the AM revealed small , non-significant improvements in time spent st and ing , walking , and the number of short walking periods . Conclusion Tadalafil may be a promising new treatment for patients that have chronic cold CRPS due to endothelial dysfunction , and deserves further investigation . Trial Registration The registration number in the Dutch Trial Register is IS RCT N60226869 ABSTRACT Complex Regional Pain Syndrome Type 1 ( CRPS‐1 ) responds poorly to st and ard pain treatment . We evaluated if the N‐methyl‐d‐aspartate receptor antagonist S(+)‐ketamine improves pain in CRPS‐1 patients . Sixty CRPS‐1 patients ( 48 females ) with severe pain participated in a double‐blind r and omized placebo‐controlled parallel‐group trial . Patients were given a 4.2‐day intravenous infusion of low‐dose ketamine ( n = 30 ) or placebo ( n = 30 ) using an individualized stepwise tailoring of dosage based on effect ( pain relief ) and side effects ( nausea/vomiting/psychomimetic effects ) . The primary outcome of the study was the pain score ( numerical rating score : 0–10 ) during the 12‐week study period . The median ( range ) disease duration of the patients was 7.4 ( 0.1–31.9 ) years . At the end of infusion , the ketamine dose was 22.2 ± 2.0 mg/h/70 kg . Pain scores over the 12‐week study period in patients receiving ketamine were significantly lower than those in patients receiving placebo ( P < 0.001 ) . The lowest pain score was at the end of week 1 : ketamine 2.68 ± 0.51 , placebo 5.45 ± 0.48 . In week 12 , significance in pain relief between groups was lost ( P = 0.07 ) . Treatment did not cause functional improvement . Patients receiving ketamine more often experienced mild to moderate psychomimetic side effects during drug infusion ( 76 % versus 18 % , P < 0.001 ) . In conclusion , in a population of mostly chronic CRPS‐1 patients with severe pain at baseline , a multiple day ketamine infusion result ed in significant pain relief without functional improvement . Treatment with ketamine was safe with psychomimetic side effects that were acceptable to most patients OBJECTIVE To assess the effects of intravenous administration of magnesium on complex regional pain syndrome type 1 ( CRPS-1 ) , a r and omized double-blind placebo-controlled trial was performed . METHODS Fifty-six patients with CRPS-1 ( International Association for the Study of Pain Orl and o criteria ) received MgSO(4 ) 70 mg/kg or placebo ( NaCl 0.9 % ) in 4 hours over 5 consecutive days . Pain ( BOX-11 and McGill ) , the level of impairment ( Impairment level Sum Score [ ISS ] ) , functional limitations ( Radboud Skills Question naire , Walking Skills Question naire/ question naire rising and sitting down ) , participation ( Impact on Participation and Autonomy [ IPA ] ) , and quality of life ( Short Form-36 , EuroQol , IPA ) were evaluated at baseline and at 1 , 3 , 6 , and 12 weeks . RESULTS No significant differences were found between MgSO(4 ) and placebo on the BOX-11 and ISS at different time points during the trial on intention-to-treat and per- protocol analysis . A significant improvement on the BOX-11 was found after the first week of the trial in both groups ( mean 0.7 ; st and ard deviation 1.1 ) . For the MgSO(4 ) group , a clinical ly relevant and statistically significant improvement on the ISS at 1 week ( median 5 , interquartile range [ IQR ] -1 to 8) and a significant improvement on the McGill up to 6 weeks ( median 2 words , IQR 0 - 4.5 ) were found compared with baseline , which were not found in the placebo group . Significant improvement in perceived job participation was found for the MgSO(4 ) group at 12 weeks ( median improvement 1.44 - 1.17 ; P = 0.01 ) . ISS improved significantly more in patients with a low Hospital Anxiety and Depression Scale ( HADS ) score ( ≤10 ) in the MgSO(4 ) group ( mean 4.4 vs mean -3.1 ; P = 0.02 ) . CONCLUSION Administration of the physiological competitive N-methyl-D-aspartate receptor antagonist magnesium in chronic CRPS provides insufficient benefit over placebo . Future research should focus on patients with acute CRPS and early signs and symptoms of central sensitization ABSTRACT Since glycinergic neurotransmission plays an important inhibitory role in the processing of sensory and motor information , intrathecal glycine ( ITG ) administration may be a potential therapy for both pain and movement disorders in patients with complex regional pain syndrome ( CRPS ) . Aims of the current study , which is the first report on ITG in humans , were to evaluate its safety and efficacy . ITG treatment during 4 weeks was studied in CRPS patients with dystonia in the period before they received intrathecal baclofen treatment . Twenty patients were assessed and after exclusion of one patient , the remaining 19 patients were r and omized in a double‐blind placebo‐controlled crossover study . Safety was assessed by clinical evaluation , blood examinations and electrocardiograms . Efficacy measures involved pain ( numeric rating scale , McGill pain question naire ) , movement disorders ( Burke – Fahn – Marsden dystonia rating scale , unified myoclonus rating scale , tremor research group rating scale ) , activity ( Radboud skills question naire , walking ability question naire ) , and a clinical global impression ( CGI ) and patient 's global impression score ( PGI ) . Treatment‐emergent adverse events were generally mild to moderate and not different from placebo treatment . During ITG treatment growth hormone levels were slightly increased . Although there was a trend to worsening on the CGI and PGI during ITG treatment , there were no significant differences between ITG and placebo treatment in any of the outcomes . ITG given over 4 weeks was ineffective for pain or dystonia in CRPS . Although no serious adverse events occurred , further studies are required to rule out potential neurotoxicity of ITG UNLABELLED The treatment of dystonia related to complex regional pain syndrome ( CRPS ) remains unsatisfactory , raising the need of alternative targets for intervention . In dystonia , pathologic muscle changes may occur , which contributes to stiffness . Because magnesium sulphate may act as a muscle relaxant through its actions on the neuromuscular junction and muscle , we performed an explanatory study of the muscle relaxant effect and safety of intramuscular magnesium sulphate ( IMMG ) in CRPS patients with dystonia . In a double-blind r and omized placebo-controlled crossover study , 30 patients were assigned to 3-week treatments of IMMG and placebo . Treatments were separated by a 1-week washout period . The daily dose of IMMG was 1,000 mg in week 1 , 1,500 mg in week 2 , and 2,000 mg in week 3 . The primary outcome measure was the difference in change in Burke-Fahn-Marsden scores after 3 weeks of treatment between both interventions . Secondary outcomes involved severity of dystonia , myoclonus , tremor , and pain , and functional activity . Data of 22 patients available for the explanatory analysis revealed no significant differences between IMMG and placebo treatment in any of the outcomes . In conclusion , we found no indication of efficacy of IMMG in a daily dose of 2,000 mg as a muscle relaxant in CRPS-related dystonia . PERSPECTIVE In this double-blind placebo-controlled crossover study there was no evidence found of a muscle relaxant effect of intramuscular magnesium sulphate in dystonia related to CRPS . Consequently , there is insufficient support for new studies evaluating the efficacy of other routes of MG administration in CRPS-related dystonia & NA ; The course of pain associated with temporom and ibular disorders ( TMD ) and other chronic pain conditions is typically episodic . Its expression may influence when a person seeks treatment , for example , when the level of pain flares up or exceeds its characteristic severity . Improvement in pain status subsequent to entering treatment may be due to : ( 1 ) specific effects of treatment ; ( 2 ) non‐specific effects of treatment ( ‘ placebo effects ’ ) ; or ( 3 ) regression to the mean . Due to regression to the mean , uncontrolled evaluation of treatment in persons self‐selected by a pain flare‐up may lead to erroneous conclusions concerning effects of treatment by patients , providers , and /or research ers . For this report , the magnitude of regression to the mean due to self‐ selection for treatment is estimated by comparing subjects who sought treatment for TMD pain ( n = 147 ) to a r and om sample of subjects with TMD pain not seeking treatment ( n = 95 . Among subjects seeking treatment , a significant 14.7‐point reduction in VAS pain intensity was observed at 1‐year follow‐up . A control group of TMD subjects not seeking treatment showed no mean reduction in pain intensity but reported lower pain intensity at baseline than the group seeking care . When both groups of subjects were stratified on baseline VAS pain values , the reduction in pain increased as the baseline pain level increased , but no differences between comparable treated and untreated cases in the extent of improvement were observed . The before‐after differences in both groups may be attributed to regression to the mean . We conclude that before‐after differences in pain intensity can be large and that such improvement may be largely due to regression to the mean . This suggests the need for research which differentiates change due to regression to the mean ( due to homeostatic processes , r and om within‐subject variation , or measurement error ) from change due to specific and non‐specific effects of treatment . In clinical practice , the personal experience of patients and clinicians who observe improvement after initiation of treatment should be regarded as an unreliable guide to treatment efficacy due to regression to the mean . This phenomenon may contribute to the proliferation and continued use of treatments of unproven efficacy for pain management and suggests caution in the use of costly or risky pain treatments the efficacy of which is unknown Background / Aim : Short-term fluctuation of gastrointestinal symptoms in the general population is largely unknown . We aim ed to determine gastrointestinal symptom fluctuation in an r and om adult population using a vali date d question naire assessing gastrointestinal symptoms . Methods : A representative sample ( n = 2,860 ) of the population ( n = 21,610 , 20–81 years of age ; mean age 50.4 years ) in Northern Sweden was studied . The subjects were asked to complete the question naire on two occasions [ mean 2.5 months ( range 1–6 ) ] , firstly via mail and secondly at a visit to the clinic . An upper endoscopy was performed after the last assessment of symptoms . Results : 2,122 individuals ( 74.2 % ) completed the initial question naire ; 1,001 of these ( mean age 54.1 years , 48.8 males ) completed the second question naire . On the first occasion , 40 % of the subjects were symptom-free ( 20.2 % ) or could not be classified according to their symptom pattern , of those with symptoms 39 % reported troublesome reflux symptoms , 40 % dyspeptic symptoms and 30 % irritable bowel symptoms . Symptom overlap occurred in more than two thirds of the subjects . At the second visit 75 % of the subjects who had reported dyspeptic complaints still reported such complaints . Conclusions : In this population -based study , gastrointestinal symptoms were common . Some symptom fluctuation occurred in the shorter term , but troublesome gastrointestinal complaints remained in approximately 90 % of subjects over a 1–6-month period A number of pharmacologic treatments examined in recent r and omized clinical trials ( RCTs ) have failed to show statistically significant superiority to placebo in conditions in which their efficacy had previously been demonstrated . Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies , such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo ( “ assay sensitivity ” ) . Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development . Therefore , an Initiative on Methods , Measurement , and Pain Assessment in Clinical Trials consensus meeting was convened in which the assay sensitivity of chronic pain trials was review ed and discussed . On the basis of this meeting and subsequent discussion s , the authors recommend consideration of a number of patient , study design , study site , and outcome measurement factors that have the potential to affect the assay sensitivity of RCTs of chronic pain treatments . Increased attention to and research on method ological aspects of clinical trials and their relationships with assay sensitivity have the potential to provide the foundation for an evidence ‐based approach to the design of analgesic clinical trials and expedite the identification of analgesic treatments with improved efficacy and safety Activated immune cells in the spinal cord may play an important role in the development and maintenance of neuropathic pain , such as occurs in response to peripheral inflammation or tissue injury . Immune activation may therefore serve as a therapeutic target for immune modulating drugs like corticosteroids . This double-blind r and omized placebo-controlled parallel-group trial aim ed to investigate the efficacy and safety of a single intrathecal administration of 60 mg methylprednisolone ( ITM ) in chronic patients with complex regional pain syndrome ( CRPS ) . The primary outcome measure was change in pain ( pain intensity numeric rating scale ; range 0 - 10 ) after 6 weeks . With 21 subjects per group the study had a 90 % power to detect a clinical ly relevant difference ( > or = 2 points ) . After 21 patients ( 10 on ITM ) were included , the trial was stopped prematurely after the interim analysis had shown that ITM had no effect on pain ( difference in mean pain intensity numeric rating scale at 6 weeks 0.3 , 95 % confidence interval -0.7 to 1.3 ) or any other outcome measure . We did not find any difference in treatment-emergent adverse events between the ITM and placebo group . We conclude that a single bolus administration of ITM is not efficacious in chronic CRPS patients , which may indicate that spinal immune activation does not play an important role in this phase of the syndrome Background Intraspinally administered α2-adrenerglc agonists may relieve pain in sympathetically maintained pain ( SMP ) syndromes , such as reflex sympathetic dystrophy ( RSD ) , by spinal , peripheral , and central nervous system actions . This study examined analgesic efficacy and side effects of epidurally administered clonidine in patients with severe , refractory RSD . Methods Twenty-six patients with severe chronic pain consistent with RSD were studied in a r and omized , blinded , placebo-controlled design . Cervical or lumbar epidural catheters were inserted for patients with upper or lower extremity RSD , respectively , and patients received , in r and om order on three consecutive days , epidural injection of clonidine , 300 or 700 μg , or placebo . Pain ( by visual analog score ( VAS ) and McGill Pain Question naire ) , sedation , blood pressure , and heart rate were monitored at specified Intervals for 6 h after injection . Patients who responded to clonidine , but not placebo , then entered a trial of open-label , continuous epidural infusion of clonidine ( 10–50 μg/h ) . Results Clonidine , but not placebo , caused pain relief , sedation , and decreased blood pressure and heart rate after bolus epidural injection . The smaller clonidine dose ( 300 μg ) , produced pain relief and decreases in blood pressure and heart rate similar to those of the 700 μg dose , but with less sedation . Epidural clonidine was infused for a mean of 43 days in 19 patients at a mean rate of 32 μg/h for sustained analgesia . Conclusions Transdermal clonidine has been demonstrated to produce analgesia in the area surrounding its application site in patients with SMP . The current study indicates that extensive analgesia may be obtained by epidural administration . Sedation and hypotension may limit bolus epidural clonidine administration for RSD . The role for chronic epidural Infusion of clonidine has not yet been established This double-blind , r and omized study was design ed to compare the effectiveness of intravenous regional sympatholysis using guanethidine , reserpine and normal saline . Twenty-one patients with reflex sympathetic dystrophy of an upper or lower extremity were enrolled and received intravenous regional blockade ( IVRB ) with one of the three medications . There was significant pain relief in all three groups at 30 min . There were no significant differences among the three groups in the degree of pain relief , the number of patients obtaining pain relief in the 30 min after the block , or the number of patients reporting more than 50 % pain relief for more than 24 hr . The saline group 's high rate of pain relief could be partially due to a mechanism of tourniquet-induced analgesia In complex regional pain syndrome ( CRPS ) many clinical symptoms suggest involvement of the central nervous system . Neuropathic pain as the leading symptom is often resistant to therapy . In the present study we investigated the analgesic efficiency of repetitive transcranial magnetic simulation ( rTMS ) applied to the motor cortex contralateral to the CRPS-affected side . Seven out of ten patients reported decreased pain intensities . Pain relief occurred 30 s after stimulation , whereas the maximum effect was found 15 min later . Pain re-intensified increasingly 45 min after rTMS . In contrast , sham rTMS did not alter pain perception . These findings provide evidence that in CRPS I pain perception can be modulated by repetitive motor cortex stimulation Ketanserin , a selective S2 serotonergic antagonist , was assessed against placebo in a double-blind cross-over study of 16 patients with chronic peripheral burning pain . Nine of these had signs of reflex sympathetic dystrophy ( RSD ) . All patients underwent 4 intravenous regional treatments , 2 with ketanserin ( 10 mg for upper limb pain , 20 mg for lower limb pain ) and 2 with placebo . In those patients with RSD ketanserin and not placebo provided significant ( P less than 0.05 ) sustained pain relief as assessed by linear analogue scales . In patients who did not fulfil the criteria for RSD no significant relief was seen with placebo or ketanserin . Following tourniquet release , drowsiness , shakiness and faintness were reported at a higher ( P less than 0.05 ) frequency after ketanserin than after placebo . All side effects were mild and transient , and no changes occurred in heart rate or blood pressure following ketanserin that were significantly different from those seen following placebo . A role for serotonin in the pathogenesis of RSD is proposed OBJECTIVE Pain-relieving effects of lidocaine/bupivicaine local anesthetic ( LA ) and saline ( S ) block of sympathetic ganglia ( stellate block , 4 patients ; lumbar sympathetic block , 3 patients ) were compared in 7 complex regional pain syndrome ( CRPS ) patients on a double-blind crossover basis to evaluate the diagnostic and therapeutic value of local anesthetic sympathetic blocks . DESIGN Patients rated their pain on a visual analog scale before and after blocks and were tested for mechanical allodynia one-half hour after blocks . Thereafter , they rated their pain intensity in diaries four times a day for 7 days . Each patient received two blocks , S and LA , and served as his own control . RESULTS Both S and LA injections of sympathetic ganglia produced large reductions in pain intensity in 6 of 7 patients 30 minutes after block . These large reductions were accompanied by the reversal of mechanical allodynia in both S and LA . The mean difference between initial peak reduction in pain intensity produced by saline ( 68.7 % ) and active local anesthetic ( 74.4 % ) did not approach statistical significance . In striking contrast , the mean duration of pain relief was reliably longer in the case of LA ( 3 days , 18 hours ) as compared with S ( 19.9 hours ) , a difference that occurred in all 7 patients . In a larger sample of 41 CRPS patients , signs of sympathetic efferent blockade , including Homer ' s syndrome or skin surface temperature change , were not predictive of initial peak magnitude of pain relief from sympathetic blockade but were predictive of duration of pain reduction . CONCLUSION The combination of these results provides evidence that duration of pain relief is affected by injection of local anesthetics into sympathetic ganglia . These results indicate that both magnitude and duration of pain reduction should be closely monitored to provide optimal efficacy in procedures that use local anesthetics to treat CRPS Background Pain Exposure Physical Therapy is a new treatment option for patients with Complex Regional Pain Syndrome type 1 . It has been evaluated in retrospective as well as in prospect i ve studies and proven to be safe and possibly effective . This indicates that Pain Exposure Physical Therapy is now ready for clinical evaluation . The results of an earlier performed pilot study with an n = 1 design , in which 20 patients with Complex Regional Pain Syndrome type 1 were treated with Pain Exposure Physical Therapy , were used for the design and power calculation of the present study .After completion and evaluation of this phase III study , a multi-centre implementation study will be conducted . The aim of this study is to determine whether Pain Exposure Physical Therapy can improve functional outcomes in patients with Complex Regional Pain Syndrome type 1 . Methods / design This study is design ed as a single-blinded , r and omized clinical trial . 62 patients will be r and omized with a follow-up of 9 months to demonstrate the expected treatment effect . Complex Regional Pain Syndrome type 1 is diagnosed in accordance with the Bruehl/International Association for the Study of Pain criteria . Conventional therapy in accordance with the Dutch guideline will be compared with Pain Exposure Physical Therapy . Primary outcome measure is the Impairment level SumScore , restricted version . Discussion This is the first r and omized controlled study with single blinding that has ever been planned in patients with Complex Regional Pain Syndrome type 1 and does not focus on a single aspect of the pain syndrome but compares treatment strategies based on completely different pathophysiological and cognitive theories . Trial registration Clinical trials NCT00817128 ; National Trial Register |
10,533 | 20,589,513 | Data suggest that EL performs better in establishing a final diagnosis after admission , but the lack of uniform information does not allow for the recommendation of EL as a routine strategy in clinical practice . | Background Patients with nonspecific abdominal pain ( NSAP ) are frequently seen in emergency departments .
Different studies have suggested that early laparoscopy ( EL ) could be an adequate tool to accelerate diagnosis and therapy .
The aim of this study was to assess the effectiveness of EL in terms of diagnosis , persistence of NSAP , mortality , morbidity , cost , hospital stay , and quality of life relative to observation in NSAP . | BACKGROUND The aim of this study was to compare the outcome and cost-effectiveness of laparoscopic ( LA ) and open appendectomy ( OA ) . METHODS Forty consecutive patients were r and omized to either the LA ( n = 19 ) or OA ( n = 21 ) group . RESULTS The medians of operative times in the LA and OA groups were 31.5 and 41 min , respectively . The total operation room times were 91 and 82 min , respectively . There was no significant difference in postoperative pain or fatigue , but return to normal life was faster in the LA group ( 14 versus 26 . 5 days ) . The median hospital costs per patient were 8,538 and 6,788 FIM ( $ 1 US = 4.6 FIM ) in the LA and OA groups , respectively ; but the total costs among working patients were lower in the LA group ( 20 , 963 versus 27,778 FIM ) due to faster return to work . CONCLUSIONS Laparoscopic appendectomy is as safe as open appendectomy . The hospital costs are higher , but LA offers significant cost savings to the payer for working patients Background A prospect i ve study including 272 patients with suspected appendicitis was performed . The aims were to evaluate the representativity of the study group and to compare diagnostic and therapeutic laparoscopy with conventional appendicectomy Aim : To see whether laparoscopy improves the accuracy of a clinical diagnosis of acute appendicitis in women of reproductive age , and to determine what the long-term sequelae are of not removing an appendix deemed at laparoscopy to be normal . Method : The initial part of the study was undertaken during 1991–1992 . Female patients between 16 and 45 years were eligible for inclusion once a clinical decision had been made to perform an appendicectomy for suspected acute appendicitis . Following consent , patients were r and omized into two groups . One group had open appendicectomy , as planned . The other group had laparoscopy , followed by open appendicectomy only if the appendix was seen to be inflamed or was not visualized . The end points for the study were the clinical outcomes of all patients , and the results of histology , where appropriate . An attempt was made to contact all patients at 10 years to determine whether they had had a subsequent appendicectomy , or had been diagnosed with another abdominal condition that might be relevant to the initial presentation in 1991–1992 . Results : Laparoscopic assessment was correct in all cases in which the appendix was visualized . Diagnostic accuracy was improved from 75 % to 97 % . Laparoscopy was associated with no added complications , no increase in hospital stay in patients who went on to appendicectomy , and a reduction in hospital stay for those who underwent laparoscopy alone . No patients developed a problem over the 10-year follow-up period from having a normal-looking appendix not removed at laparoscopy . Conclusion : Laparoscopic assessment of the appendix is reliable , and to leave a normal-looking appendix at laparoscopy does not appear to cause any long-term problems AIM The aim of this study was to determine whether it is safe and cost-effective to discharge nonspecific abdominal pain ( NSAP ) patients from the Emergency Department ( ED ) and re-evaluate diagnosis later . METHODS Patients aged between 18 and 65 years were enrolled into the study . They had been admitted to the ED for acute abdominal pain with an indefinitive diagnosis after clinical examination and base-line investigations . The patients were r and omly assigned into two groups : 1 ) active clinical observation ( ACO ) , comprising those admitted to the ED observation room ; 2 ) outpatient group ( OG ) , comprising those discharged and asked to return for re-evaluation at 8 - 12 hours intervals over the following three days . Each patient was examined by an ED physician and a consultant general surgeon . Demographics , blood tests , morbidity and mortality , number of operations , together with 6-month follow-up results were noted . Finally , a patient satisfaction question naire was administered . RESULTS A total of 105 patients were enrolled into the study ; 50 were r and omized to the ACO group and 55 to the OG . There were no statistically significant differences in demographics and blood parameters between the two groups . Overall agreement of ED diagnosis with final diagnosis was 91.4 % . Total morbidity was 10 % in the ACO group and 7.2 % in the OG . There were no statistically differences in morbidities and usage of diagnostic imaging modalities between the two groups ( P>0.05 ) . No deaths occurred in either group during the study period . The patients in the ACO group were more keen on returning for re-evaluation and willing to recommend our hospital services to other people ( P < or = 0.05 ) . CONCLUSION Outpatient evaluation of patients with an ED diagnosis of NSAP may be an option , seems to be safe , is not accompanied by an increased incidence of complications and is efficient if patients are selected properly INTRODUCTION The aim of the study is to analyse the own data and try to discuss if laparoscopic appendectomy offers any advantages in treating young women suffering from pain in right lower abfdominal quadrant . MATERIAL S AND METHODS The study was conducted on 148 patients admitted from October 1993 to December 1998 with diagnosis of of pain in right iliac fossa and operated on with a laparoscopic ( LA group : 75 cases ) or open approach ( OA group : 73 cases ) . Patients were prospect ively r and omized on the surgical approach adopted , following a r and omized list . RESULTS The operative time in LA group was significantly ( p < 0.001 ) longer ( 87.2 minutes ) than for OA group ( 65.2 minutes ) . In 2 patients ( 2.7 % ) the operation had to be converted . Diagnosis had remained unknown in 16 patients ( 21.9 % ) of OA group , in spite of only one case ( 1.4 % ) with laparoscopic technique . We did n't observed intraoperative complications . Pain in the first and second postoperative days , evaluated on the use of pain medication , was significantly less in patients in group LA ( p < 0.01 ) . There were no deaths . Postoperative complications occurred in 4 patients ( 5.5 % ) of group LA , and in 8 patients ( 10.9 % ) of group OA . Hospital stay was significantly shorter for those having laparoscopic appendectomy ( p < 0.001 ) . DISCUSSION The main advantages of laparoscopic appendectomy consist more in diagnostic accuracy , than in less postoperative pain , less hospital stay and less postoperative complications . CONCLUSION Laparoscopic appendectomy is a safe and accurate approach BACKGROUND Clinical diagnosis of acute appendicitis is most difficult in fertile-age women . In this patient group up to 50 % of open appendectomies are negative for appendicitis . We conducted a r and omized study to compare laparoscopic and open appendectomy in young female patients with suspected acute appendicitis . METHODS Fifty female patients between the ages of 16 and 40 years presenting with acute right lower abdominal pain were r and omized , 25 to laparoscopy and 25 to an open appendectomy . Diagnostic accuracy , rate of negative appendectomies , safety , and final outcome were compared in the two groups . RESULTS Diagnosis was established in 96 % of patients in the laparoscopic group and in 72 % in the open group . There were 11 ( 44 % ) unnecessary appendectomies in the open group , but only one ( 4 % ) in the laparoscopic group ( p < 0.0005 ) . CONCLUSIONS In young women with right lower abdominal pain , laparoscopy can give precise diagnosis and reduce the rate of negative appendectomies The benefits of laparoscopic appendectomy appear to be controversial . Since 1994 , several abdominal procedures have been completed by using the needlescopic technique , but there appear to be no prospect i ve studies to demonstrate the perceived benefits of needlescopic appendectomy . The authors compared open , laparoscopic , and needlescopic appendectomy in a r and omized fashion with regard to duration of surgery , length of hospitalization , analgesic dosage , and surgery-associated complications . From March to July 1998 , 75 patients admitted at the emergency station of the authors ' hospital with a final diagnosis of acute appendicitis without tumor formation were r and omized to receive one of the three treatment categories : open ( OA ) , laparoscopic ( LA ) , and needlescopic ( nLA ) appendectomy . Laparoscopic and needlescopic appendectomy were performed by using a three-port technique , although the size of the trocar used varied . There were 26 patients in the OA group , 23 in the LA group , and 26 in the nLA group . The mean operation duration s for the OA , LA , and nLA groups were 55.4 ± 28.0 minutes , 69.1 ± 48.8 minutes , and 62.3 ± 26.3 minutes , respectively , and these were not significantly different from one another . The mean number of the analgesic doses ( Pethidine 1 mg/kg ) required was 1.3 ± 1.2 mg/kg , 0.5 ± 0.8 mg/kg , and 0.2 ± 0.6 mg/kg , respectively . Significant differences were noted when comparing the OA with the LA or nLA groups ( OA vs. LA , P = 0.02 ; OA vs. nLA , P = 0.0002 ; LA vs. nLA , P = 0.06 ) . The mean oral intake duration s were 32.2 ± 16.9 hours , 21.0 ± 14.6 hours , and 20.8 ± 16.4 hours , respectively , after surgery for the OA , LA , and nLA groups , and the between-group differences were statistically significant for the OA versus LA group ( P = 0.004 ) and for the OA versus nLA group ( P = 0.003 ) . The mean duration s of hospitalization for the OA , LA , and nLA groups were 3.6 ±1.8 days , 2.8 ± 1.4 days , and 2.4 ± 0.9 days , and difference was detected between the OA and the nLA groups ( P = 0.02 ) . The OA group rendered a greater wound-complication rate and ileus than did the other two groups , but the differences were not detected between the three categories ( P = 0.065 , 0.6935 ) . The result of the current study confirmed that the nLA procedure is a feasible and safe one . The nLA procedure provided substantial advantages over the OA procedure in the context s of diminished postoperative pain and shorter hospital stay without significant increases in postoperative complication rate or surgical time BACKGROUND Laparoscopic appendectomy is feasible , but whether it confers any advantage to patients with acute appendicitis is not known . We performed a r and omized controlled trial to compare results of laparoscopic and open appendectomy in patients with signs and symptoms suggesting acute appendicitis who were seen by one surgical team . METHODS Sixty-two consecutive patients were r and omized , 30 to laparoscopy and 32 to a classical open appendectomy . Postoperative recovery , complications , and return to normal activities were compared in the two groups . RESULTS The laparoscopy group were discharged earlier ( 2.5 vs 3.8 days , p less than 0.01 ) . Postoperative complications were more frequent after open appendectomy . Follow-up showed less pain , shorter bed stay at home , and faster return to work and sport after laparoscopic appendectomy . CONCLUSIONS This prospect i ve r and omized study shows that laparoscopic appendectomy is superior to open appendectomy in terms of hospital stay , postoperative complications , and return to normal activities and is recommended as the approach of choice in the management of acute appendicitis Background The aim of this study was to study the value of diagnostic laparoscopy prospect ively in fertile women scheduled for acute appendectomy . Methods For this study , 110 women , with acute abdominal pain ages 15 to 47 years , in whom the surgeon had decided to perform an appendectomy , were r and omized to either open appendectomy or diagnostic laparoscopy , then open appendectomy if necessary . Results Appendicitis was diagnosed in 66 % of the women after open surgery , and in 73 % after laparoscopy . During laparoscopy , was appendicitis misdiagnosed in only 7 % of the women , from whom the appendix unnecessarily removed , whereas 34 % in the open surgery group had a healthy appendix removed . No appendicitis was missed in the laparoscopic group . The relative risk of removing a healthy appendix in open surgery was 6.6 relative risk ( range , 2–21 C.I. ) as compared with laparoscopy . Among the women with a healthy appendix , a gynecologic diagnosis was found in 73 % after laparoscopy , as compared with 17 % after open surgery . Conclusions Laparoscopy reduces unnecessary appendectomies and improves diagnosis in fertile women Laparoscopy in patients with a clinical suspicion of acute appendicitis has not gained wide acceptance , and its use remains controversial Background The role of laparoscopy in the management of patients with suspected acute appendicitis remains controversial . It has been suggested that laparoscopy is useful mainly in young women of reproductive age because of the high incidence of wrong diagnosis in these patients . Methods Different management protocol s for patients with suspected acute appendicitis were prospect ively used in male and female patients ; women of reproductive age were treated laparoscopically , while men were r and omised to open or laparoscopic appendectomy . Results From September 2002 to September 2005 , 132 patients —54 women and 78 men — with suspected acute appendicitis were treated according to the protocol . The incidence of wrong diagnosis in female patients was high ( 26 % and the conversion rate low ( 5.5 % ) . In contrast , in the laparoscopic male subgroup , these rates showed a reverse relationship ( 5.2 % and 18.5 % , respectively ) . Morbidity did not differ between female and male patients or between the 2 arms of the male group . Laparoscopic appendectomy took longer to perform without affecting significantly the needs for postoperative analgesia , the duration of hospital stay and the time to return to normal activities when compared with open appendectomy in men . Conclusion Laparoscopic appendectomy is at least as safe as the open procedure in the male population , although it does not appear to offer any obvious advantage over the open procedure . The diagnostic advantage that laparoscopy offers to fertile women makes the procedure attractive for this population In a prospect i ve study of 230 patients followed up for 5 years after hospital admission for acute non-specific abdominal pain , 21 patients ( 9 patients ) could not be traced , and 11 ( 5 percent ) had died . Only one death was related to symptoms from the first admission . Of the remaining 198 patients , 77 percent were healthy and free of any symptoms during the observation period . Fourteen patients ( 7 percent ) had been hospitalized once more due to acute abdominal pain ; 5 had acute appendicitis . The others had diagnosed recurrences of nonspecific abdominal pain . Sixteen percent complained of continuing of intermittent abdominal symptoms , mainly of benign colonic or gynecologic origin , while malignant disease developed in 1 percent ( or 4 percent of patients over 50 years of age ) . It is concluded that control of these patients is generally unnecessary , but when symptoms recur further examinations , especially for colonic or gynecologic disease , should be carried out . In patients over 50 years old , the possibility of malignant disease should be kept in mind OBJECTIVE To compare the costs and effectiveness of early laparoscopy with those of conventional diagnostic methods based on clinical and para clinical observation and diagnostic images for ascertaining the cause of non-specific acute low abdominal pain ( NSALAP ) in females of reproductive age from the third-party payers ' ( TPP ) point of view . METHODS POPULATION 110 reproductive aged females suffering from NSALAP . PLACE Instituto Materno Infantil , perinatal and maternal attention referral hospital in Bogotá , Colombia . RESEARCH DESIGN cost-effectiveness study of a controlled clinical trial carried out in 1998 and 1999 . Outcomes to be measured : effectiveness , direct medical costs ( in Colombian pesos and their equivalent in US dollars ( USD-December 2004 ) from length of hospital stay , diagnostic procedures carried out , medical visits and managing complications . ANALYSIS Cost-effectiveness incremental ratio , analysing sensitivity in five different scenarios . RESULTS Early diagnostic laparoscopy was more cost-effective in 4 out of the 5 possible scenarios . Savings varying from dollar 21.875 to dollar 69.834 ( USD 9.42 and USD 30.1 ) were made per unit of increased effectiveness . CONCLUSION Early diagnostic laparoscopy was cost-effective in 4 out of 5 scenarios dealing with managing NSALAP in reproductive aged females Background We set out to investigate the potential benefits of routine diagnostic laparoscopy ( DL ) in cases of acute abdomen . Methods A prospect i ve study of 120 DL in acute abdominal cases was performed in comparison with 310 similar acute abdominal cases treated without DL . The diagnostic accuracy , hospital stay , therapeutic delay , and convalescence time were then evaluated . Results DL established the indications for intervention in 96 % of cases , yielded a diagnosis in 90 % , and changed the treatment in 14 % . The sensitivity achieved was 99.3 % , specificity was 83.3 % , and accuracy was 88.6 % . There were two false positives , one false negative , and three results insufficient to make a diagnosis . Morbidity was one ( 0.8 % ) , and mortality was one ( 0.8 % ) . Seventy-nine patients ( 66 % ) were managed by laparoscopy and 24 by open interventions . The hospital stay in DL groups was shorter ( median , 5 days vs 6 days in controls , p<0.0003 ) , as was the effective treatment time ( median , 5 days vs 6 days , p<0.0012 ) . The convalescence time was also shorter in DL groups ( median , 14 days vs 14 days , p<0.04 ) . Therapeutic delay occurred in 16 % of the control group cases , doubling the morbidity rate , increasing mortality by 50 % , and prolonging hospital stay ( median , 9 days vs 6 days , p>0.3 ( NS ) . Conclusions DL in the acute abdomen is a safe and accurate procedure that enables laparoscopic interventions and helps avoid nontherapeutic surgery . DL and appropriate treatment reduces hospital stay , therapeutic delay , and convalescence time Abstract Background : There are acute abdominal conditions in which it is difficult to establish an indicative diagnosis before laparotomy . A diagnosis is important in planning the right abdominal incision or to avoid an unnecessary laparotomy . Diagnostic noninvasive procedures such as X-ray studies do not always appear conclusive . Diagnostic laparoscopy is the only technique which can visualize the abdomen and , by establishing an adequate diagnosis , permits the surgeon to plan the right abdominal approach . Methods : In a prospect i ve study , 65 patients with a generalized acute abdomen ( no intestinal obstruction or perforation ) underwent a diagnostic laparoscopy under general anesthesia previous to the planned median laparotomy . Results : In 46 patients ( 70 % ) diagnostic laparoscopy permitted the establishment of an adequate diagnosis , whereas in seven patients ( 10 % ) no cause for the acute abdomen could be found and an explorative laparotomy was avoided . In another 12 patients ( 20 % ) insufficient information was obtained during laparoscopy and an explorative laparotomy was performed . Conclusions : A conclusive diagnosis was established in 53 patients . This information led to a change in the surgical approach in 38 patients ( e.g. , limited , well-placed approach , laparoscopically , or avoidance of an unnecessary laparotomy ) . Diagnostic laparoscopy in this category of patients is a useful technique with important therapeutic consequences OBJECTIVE To assess the value of laparoscopy in the accurate diagnosis of appendicitis in women of child-bearing age . DESIGN Prospect i ve r and omised trial . SETTING University hospital , Kuwait . SUBJECTS 100 patients who fulfilled the inclusion criteria between July 1988 and March 1990 . INTERVENTIONS 50 patients were r and omised to have diagnostic laparoscopy followed by appendicectomy if necessary , and the other 50 to have immediate appendicectomy . MAIN OUTCOME MEASURES Avoidance of unnecessary appendicectomy , length of operating time , and length of stay in hospital . RESULTS 19 of 50 patients in the study group did not require appendicectomy ( 38 % ) . One patient required an emergency operation for an ectopic pregnancy . Of the remaining 30 , only 4 of the removed appendixes showed no histological abnormality ( 13 % ) . There were no complications of laparoscopy . CONCLUSION Laparoscopy is a safe and effective way of diagnosing acute appendicitis and should be used more often Abstract Background : The aggressive surgical approach to patients suspected of having acute appendicitis for fear of perforation , and the inaccuracy of available diagnostic methods lead to an unacceptably high negative appendicectomy rate , especially in young women , in whom gynecological disorders frequently mimic appendicitis . Our objectives were to determine the value of diagnostic laparoscopy in women of child-bearing age to reduce the number of negative laparotomies and establish the correct diagnosis to allow prompt and appropriate treatment . Methods : 161 consecutive adult female patients under 50 years of age with a clinical diagnosis of acute appendicitis underwent diagnostic laparoscopy prior to the planned appendicectomy . If an inflamed appendix was found , appendicectomy was usually done through a muscle-splitting McBurney incision . Other diagnoses were treated accordingly . A normal appendix was not removed . Results were compared to a group of 42 similar patients in whom the laparoscopy was omitted for various reasons , to 23 postmenopausal women , and to all 137 male adults , directly operated by the McBurney approach . Results : After laparoscopy , 55 % of the patients required appendicectomy for appendicitis while in 23 % a gynecological diagnosis was made in spite of previous examination by a gynecologist . Fourteen percent had a negative laparoscopy . There were no false-negative results . The negative appendicectomy rate after laparoscopy was 5 % due to two false positives and eight laparoscopy failures . In the group of fertile females who escaped laparoscopy the negative appendicectomy rate was 38 % . The respective rates for postmenopausal women and men were 4 % and 8 % . Conclusions : All women of child-bearing age suspected of having acute appendicitis should undergo diagnostic laparoscopy prior to the planned appendicectomy , regardless of the certainty of the preoperative diagnosis . This is currently the only way to reduce the negative appendicectomy rate and establish a correct diagnosis allowing prompt and appropriate treatment . In male patients and postmenopausal women one may proceed directly to emergency appendicectomy In a series of 187 patients with acute abdominal pain syndrome , 65 young women reported non specific pain in right iliac or pelvic area . A controlled study compared 33 patients with immediate laparoscopy and 32 explored with a laboratory contrast or imaging approach . In the laparoscopic group , an exact diagnosis was made in 97 % of the patients , allowing in 2/3 of cases the endoscopic treatment . Only 28 % in the second group had an exact diagnosis . Hospital stay was shorter in the laparoscopic group ( 4.18 vs 6.16 days ; p = 0.01 ) decreasing the hospital cost . The authors suggest that immediate laparoscopy should be performed in young women presenting with non-specific abdominal pain OBJECTIVES To assess the utility of laparoscopic versus conventional surgical exploration in premenopausal women with suspected acute appendicitis . METHOD Female patients aged 15 - 45 years in whom an independent decision to undertake surgical exploration had been made , were r and omised to laparoscopic or open procedures . Comparison of patient groups was conducted on an intention-to-treat basis . RESULTS Eighteen patients underwent laparoscopic exploration , with 1 procedure requiring conversion to lower midline laparotomy . Open surgical exploration was performed primarily in 16 patients . Postoperative complications ( 3 patients versus 1 patient ) and diagnostic errors ( 5 patients versus 1 patient ) were more frequent in patients undergoing open surgical procedures . Laparoscopic procedures tended to be of longer duration than open operations , but were generally associated with slightly more favourable indices of postoperative recovery ( analgesic requirement , postoperative hospitalisation , return to normal activity , return to work ) . In patients found not to have acute appendicitis , the difference in mean postoperative hospitalisation following laparoscopic intervention ( 2.6 days ) and conventional surgery ( 3.4 days ) approached statistical significance ( p < 0.1 ) . CONCLUSIONS Laparoscopy may carry some diagnostic advantage over open surgery in premenopausal women with suspected acute appendicitis . Patients found not to have acute appendicitis have a marginally shorter period of hospitalisation after laparoscopic intervention . The outcome following laparoscopic appendicectomy for confirmed acute appendicitis is at least equivalent to that achieved with conventional appendicectomy . Laparoscopic exploration is an acceptable option in premonopausal women requiring surgery for suspected acute appendicitis Aims : To evaluate , in a prospect i ve , r and omized , single-institution trial , the role of early laparoscopy in the management of nonspecific abdominal pain ( NSAP ) in young women . Patients and Methods : Women aging from 13 to 45 years , admitted for NSAP at the emergency department , were included in the study . Exclusion criteria were pregnancy , previous appendectomy , contraindications to laparoscopy , diagnosis of malignancy , or chronic disease . NSAP was defined as an abdominal pain in right iliac or hypogastric area lasting more than 6 hours and less than 8 days , without fever , leukocytosis , or obvious peritoneal signs and uncertain diagnosis after physical examination and baseline investigations including abdominal sonography . Patients were r and omly assigned to early ( < 12 hours from admission ) laparoscopy group ( LAP ) or to clinical observation group ( OBS ) . After discharge a follow-up was carried out . Results : From January 2001 to February 2004 , 508 female patients without previous abdominal surgery were evaluated in admitting area for acute right iliac or hypogastric abdominal pain , in 373 patients diagnosis was established for obvious signs or with baseline investigations . Of the remaining 135 patients , 31 were excluded from study for various reasons , 53 patients were r and omly assigned to LAP and 51 to OBS . Groups were similar for age , mean BMI , white blood cell count , and duration of pain . During hospitalization diagnosis was established in 83.4 % of the LAP and in 45.1 % of OBS ( P < 0.05 ) . Twenty patients of OBS ( 39.2 % ) were operated during observation because of worsening of symptoms or appearance of peritoneal sign . Diagnoses in LAP were appendicitis in 16 patients ( 30.1 % ) , pelvic inflammatory disease in 7 ( 13.2 % ) , carcinoid in 1 ( 1.9 % ) , other in 18 ( 33.9 % ) , no diagnosis in 11 ( 20.7 % ) ; diagnoses in OBS were appendicitis in 3 patients ( 5.8 % ) , pelvic inflammatory disease in 8 ( 15.6 % ) , other in 12 ( 23.5 % ) , and no diagnosis in 28 ( 54.9 % ) . Mean length of hospital stay was 3.7 ± 0.8 days in LAP and 4.7 ± 2.4 days in OBS ( P < 0.05 ) ; no differences were found regarding mortality , morbidity , radiation dose , and analgesia . Mean follow-up time was 29.3 months ( range , 12–60 months ) for LAP and 30.6 months for OBS ( range , 12–60 months ) . After 3 months from discharge , 20 % of patients in LAP and 52 % in OBS had recurrent abdominal pain ( P < 0.05 ) ; after 12 months , 16 % in LAP and 25 % in OBS ( P = not significant ) . Six patients in OBS required readmission for surgery . Conclusions : Compared with active clinical observation , early laparoscopy did not show a clear benefit in women with NSAP . A higher number of diagnosis and a shorter hospital stay in the LAP group did not led to a significant reduction in symptoms recurrences at 1 year R and omised assessment of new laparoscopic surgical techniques is difficult . Surgeons need time to become experienced with the methods and tend , when they have experience , to favour one or other approach . We have carried out a prospect i ve r and omised comparison of laparoscopic and conventional appendicectomy done by surgeons of comparable experience in patients with suspected acute appendicitis . Postoperative management decisions were made by surgeons other than the operating surgeon . 140 patients were r and omly assigned to open ( OA ) or laparoscopic ( LA ) appendicectomy ( 70 each ) . The age , sex ratio , duration of symptoms , and proportion of patients with histologically confirmed appendicitis was similar in the two groups . Operating time was longer for LA than for OA ( mean 70.3 [ SD 21.9 ] vs 46.5 [ 25.9 ] min ; p < 0.001 ) . There were no major intraoperative complications in either group . 14 ( 20 % ) patients in the LA group required conversion to an open operation . No significant differences between the groups were found postoperatively for pain score , analgesic requirement , time to re introduction of diet , or hospital stay . 46 LA patients and 42 OA patients attended follow-up 3 weeks after surgery . Similar proportions had returned to work ( 36 [ 79 % ] vs 31 [ 74 % ] ) . The frequency of wound complications and wound pain after leaving hospital was lower after LA but not significantly so . We conclude that the postoperative course after LA and conventional OA does not differ significantly BACKGROUND / AIMS Acute abdomen accounts for 13 - 40 % of all emergency surgical admissions . The aim of this prospect i ve r and omized controlled study was to examine the role of early laparoscopy in the management of acute abdomen compared with the more traditional active observation . METHODOLOGY From July 1993 to August 2004 , 522 patients consecutively , admitted with " acute abdomen " , were r and omized to either early laparoscopy ( 260 patients ) ( group 1 ) or active observation and non-invasive investigation ( 262 patients ) ( group 2 ) . Baseline investigations included a full blood count , a pregnancy test in women of reproductive age , chest and /or abdominal radiograph if indicated clinical ly . RESULTS Sixty-two patients in the laparoscopy group underwent a total of 116 radiological investigations compared with a total of 558 investigations in all patients in the observation group ( P < 0.05 ) . In the observation group 34.7 % of patients remained without a clear diagnosis compared with 4.2 % of patients in the early laparoscopic group ( P < 0.0001 ) . The morbidity rate was 1.1 % in group 1 and 27 % in group 2 ( P < 0.0001 ) . The duration of hospital stay was significantly shorter in group 1 ( 3.1 vs. 7.3 days ) ( P < 0.01 ) . Eight patients in group 1 required readmission ( total readmission 46 days ) compared with 58 patients in group 2 who stayed a total of 201 days ( P < 0.05 ) . CONCLUSIONS Early laparoscopy is valuable in the management of acute abdomen . It provides a significantly higher diagnostic accuracy and a better improvement in quality of life than the more traditional approach observation A study was carried out of 137 patients with a diagnosis of acute appendicitis who were r and omized to either laparoscopic or open appendicectomy . Patients found to have perforated or normal appendices at histological examination were excluded . Fifty‐two patients undergoing laparoscopic appendicectomy and those receiving 57 open procedures were analysed . Laparoscopic appendicectomy took no longer than the open procedure ( mean 43 versus 40 min ) . The number of doses of pethidine ( 1 mg per kg body‐weight ) required in the immediate postoperative period did not differ between the two groups but the mean number of doses of oral analgesic ( naproxen sodium 550 mg twice daily ) required was less in patients undergoing laparoscopic appendicectomy ( 2·8 versus 5·0 , P < 0·05 ) . There was no significant difference between time to resumption of fluid and diet intake and length of hospital stay . There were five ( 9 per cent ) wound infections after open appendicectomy compared with none after the laparoscopic operation ( P < 0·01 ) . Patients who underwent laparoscopy returned to full home ( 17 versus 30 days , P < 0·01 ) and social ( 19 versus 32 days , P < 0·05 ) activities earlier than those who underwent open operation . Laparoscopic appendicectomy may allow reduction in the number of wound infections and earlier return to normal activities OBJECTIVES To compare the accuracy of laparoscopy performed within 24 h of admission and the conventional method based on clinical observation in the etiological diagnosis of non-specific acute lower abdominal pain ( NSLAP ) in women of reproductive age . METHODS A total of 110 patients who met the selection criteria and were seen from November 1997 to June 2000 at the Instituto Materno Infantil , a referral hospital for maternal and perinatal care in Bogotá , were r and omly divided into two groups . The effectiveness of each method was evaluated according to number of diagnoses reached , length of in-patient stay before diagnosis , complications , and diagnostic accuracy when compared with a st and ard given by microbiological and histopathological findings as well as clinical course . RESULTS The early laparoscopy group did not experience more accurate diagnoses ( 85 % vs. 79 % , P=0.61 ) or a greater number of complications ( 11 % vs. 9 % , P=0.48 ) , although the patients ' stay was shorter ( 1.3 vs. 2.3 days , P=0.008 ) than the stay of the conventional-diagnosis group . Sensitivity analysis showed more accurate judgements with laparoscopy in four of the five NSLAP causes , but only in two of the cases did this greater accuracy have clinical significance . CONCLUSIONS Early laparoscopy did not show a clear benefit in women with NSLAP Abdominal pain of uncertain aetiology ( non‐specific abdominal pain ; NSAP ) is the commonest reason for emergency surgical admission . The aim of this study was to examine the role of early laparoscopy in the management of NSAP |
10,534 | 23,996,821 | A broad range of educational interventions have been conducted to improve prescribing competency .
The WHO Guide to Good Prescribing has the largest body of evidence to support its use and is a promising model for the design of targeted prescribing courses . | OBJECTIVE To review the literature on educational interventions to improve prescribing and identify educational methods that improve prescribing competency in both medical and non-medical prescribers . | The priority of the National Health System in South Africa is primary health care ( PHC ) . The approach involves a health system led by PHC services and includes personal and curative services for acute minor ailments delivered by PHC nurses . The nurses are also responsible for the treatment of these ailments with essential drugs according to protocol s as proposed in the Essential Drugs List . A before-after experimental research design was used to evaluate the effect of a competency-based primary care drug therapy ( PCDT ) training programme for PHC nurses in the treatment of acute minor ailments . An experimental group ( n = 35 ) and control group ( n = 31 ) consisting of registered nurses undergoing training in PHC at Gold Fields Nursing College were r and omly selected . The results showed a significant increase in prescribing outcomes and medicine utilisation OBJECTIVE The study was carried out to evaluate short term effects of one to one educational intervention approach , conducted with 40 drug sellers in order to improve the private sector 's practice s , compliance and performance in using the national treatment guidelines for malaria and other common childhood ( diarrhoea , acute respiratory tract infection-ARI ) illnesses in Kibaha district-Tanzania . METHODS The training took place one month after baseline data collection . Data collection was undertaken eight months after training and the effects of training was evaluated . The 40 drug stores were divided into 20 intervention and 20 control facilities . Trained nurses were used as clients who posed as caretakers of sick under-five children needing medication . The drug dispensers/sellers knowledge of anti-malarials and other drugs and their dispensing practice s was assessed . RESULTS The intervention seemed to have had a significant impact on knowledge pattern for prescribing and dispensing practice s of drug stores for some common childhood illnesses but not in other control drug stores/shops . About 90 % ( n=18 ) of shops prescribed to clients , the approved first-line anti-malarial drug for uncomplicated malaria ( sulfadoxine-pyrimethamine ) , as compared to only 55 % ( n=11 ) of the control shops . CONCLUSION Changing the private sectors ' knowledge , behaviour and practice s/performance may be a slow and difficult process . The intervention approach applied in this study seems to be feasible at district-level . This strategy can be applied in all districts of Tanzania with the aim of achieving significant improvements in knowledge , behaviour , compliance , improving performance and practice s of drug sellers in drug stores/shops . However , other alternative strategies are needed to influence drug sellers'/dispensers ' compliance and performance . Thus , the overall impact on performance and practice s in these facilities will remain at moderate level for quite sometime unless national policies , other programs and stakeholders are involved actively WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Medication errors , and particularly prescribing errors , are common in UK hospitals . Junior doctors make the majority of prescribing errors . Deficiencies in prescribing education and training have been closely linked to the high frequency of medication errors . WHAT THIS STUDY ADDS Focussed prescribing teaching can lead to an improvement in prescribing ability . Prescribing confidence can be significantly improved through education . Education is insufficient alone in eradicating prescribing errors . AIM To assess the impact of prescribing teaching on final year medical students . METHODS Students r and omly allocated to two hospitals completed a prescribing assessment . Prescribing teaching was delivered to the intervention group while no additional teaching was provided for the control group . All students then completed a second prescribing assessment . RESULTS Teaching improved the assessment score : mean assessment 2 vs. 1 , 70 % vs. 62 % , P= 0.007 ; allergy documentation : 98 % vs. 74 % , P= 0.0001 ; and confidence . However , 30 % of prescriptions continued to include prescribing errors . CONCLUSION Medical students make significant errors in prescribing . Teaching improves ability and confidence but is insufficient alone in eradicating errors OBJECTIVE To identify and analyse factors underlying intern prescribing errors to inform development of specific medication-safety interventions . DESIGN A prospect i ve qualitative study that involved face-to-face interviews and human-factor analysis . SETTING A tertiary referral teaching hospital , Brisbane , Queensl and , February-June , 2004 . PARTICIPANTS Fourteen intern prescribers involved in 21 errors . METHOD A structured question naire was used to identify factors causing the errors . Transcripts were analysed on the basis of human-error theory to identify underlying themes . MAIN OUTCOME MEASURES Factors underlying prescribing errors . RESULTS Errors were multifactorial , with a median of 4 ( range , 2 - 5 ) different types of performance-influencing factors per error . Lack of drug knowledge was not the single causative factor in any incident . The factors in new-prescribing errors included team , individual , patient and task factors . Factors associated with errors in represcribing were environment , task and number of weeks into the term . Defences against error , such as other clinicians and guidelines , were porous , and supervision was inadequate or not tailored to the patient , task , intern or environment . Factors were underpinned by an underlying culture in which prescribing is seen as a repetitive low-risk chore . CONCLUSION To reduce the risk of prescribing errors , a range of strategies addressing patient , task , individual , team and environment factors must be introduced OBJECTIVE To evaluate the effect of an educational intervention on rational drug use amongst Primary Health Care workers in two Local Government Areas ( LGAs ) , Mushin and Ikeja , in Lagos State . METHODS Mushin was r and omly selected as the intervention LGA while Ikeja was selected as the control L.G.A. A structured educational intervention design ed to improve prescribing practice s was carried in Mushin LGA for four weeks . Drug use indicators were measured before , at two weeks and three months post intervention . RESULTS At baseline , most of the drug-use indicators in the intervention LGA were significantly worse ( p < 0.05 ) than the control LGA . However , at the two-week evaluation , the educational programme achieved a significant reduction in the average number of drugs in the intervention LGA from 7.3 + 2.8 to 6.3 + 2.3 ( p=0.000 ) compared to the control LGA where there was no significant change ( from 4.9 + to 4.8 + 2.2 , p=0.647 ) . There was also a significant increase in the percentage of patients rationally managed from 18 % to 30 % ( p=0.0005 ) in the intervention LGA unlike the control LGA ( from 33 % to 31%,p=0.693 . ) . The rate of change in the average number of drugs prescribed was significantly higher in the intervention LGA ( + 14 % ) compared to the control LGA ( + 2%,p=0.0000 ) . The improvements were not sustained at the three-month evaluation , as most of the indicators were similar to values obtained at the baseline . CONCLUSION The intervention programme significantly improved rational drug use in the short-term period only . Other cost effective and sustainable intervention models for improving prescribing practice s should be developed OBJECTIVE : To study the effectiveness of an intensive small group education and peer review programme aim ed at implementing national guidelines on asthma/chronic obstructive pulmonary disease ( COPD ) on care provision by general practitioners ( GPs ) and on patient outcomes . DESIGN : A r and omised experimental study with pre-measurement and post-measurement ( after one year ) in an experimental group and a control group in Dutch general practice . SUBJECTS AND INTERVENTION : Two groups of GPs were formed and r and omised . The education and peer review group ( 17 GPs with 210 patients ) had an intervention consisting of an interactive group education and peer review programme ( four sessions each lasting two hours ) . The control group consisted of 17 GPs with 223 patients ( no intervention ) . MAIN OUTCOME MEASURES : Knowledge , skills , opinion about asthma and COPD care , presence of equipment in practice ; actual performance about peakflow measurement , non-pharmacological and pharmacological treatment ; asthma symptoms ( Dutch Medical Research Council ) , smoking habits , exacerbation ratio , and disease specific quality of life ( QOL-RIQ ) . Data were collected by a written question naire for GPs , by self recording of consultations by GPs , and by a written self administered question naire for adult patients with asthma/ COPD . RESULTS : Data from 34 GP question naires , 433 patient question naires , and recordings from 934 consultations/visits and 350 repeat prescriptions were available . Compared with the control group there were only significant changes for self estimated skills ( + 16 % , 95 % confidence interval 4 % to 26 % ) and presence of peakflow meters in practice ( + 18 % , p < 0.05 ) . No significant changes were found for provided care and patient outcomes compared with the control group . In the subgroup of more severe patients , the group of older patients , and in the group of patients not using anti-inflammatory medication at baseline , no significant changes compared with the control group were seen in patient outcomes . CONCLUSION : Except for two aspects , intensive small group education and peer review in asthma and COPD care do not seem to be effective in changing relevant aspects of the provided care by GPs in accordance with guidelines , nor in changing patients ' health status Objective Medication errors are common , with junior doctors accounting for the majority in acute healthcare . Paediatrics is uniquely challenging , but the evidence base to guide prescribing education is limited . The authors set out to develop a short , educationally sound , low cost e-learning re source for paediatric prescribing to improve junior doctors ' prescribing skills and to evaluate its effectiveness . Design A non-blinded r and omised controlled trial . Setting North Western Deanery Foundation School , UK . Participants 162 volunteer foundation ( junior ) doctors r and omised into control ( 86 ) and intervention ( 76 ) groups . Interventions On study entry , participants were assessed on prescribing skill , prescribing habits and confidence . The intervention group completed the e-learning course design ed for the study , which took 1–2 h. At 1 and 3 months after the intervention , both groups were assessed on similar prescribing assessment s , habits and confidence . Main outcome measures Total score ( expressed as a percentage ) on prescribing assessment s , confidence and satisfaction scores . Results There were no preintervention differences in prescribing assessment s ( 67 % vs 67 % , p=0.56 ) . Postintervention , the e-learning group scored significantly higher than the control group ( 63 % vs 79 % , p<0.0001 ) . At 3 months , the e-learning group still scored significantly higher ( 69 % vs 79 % , p<0.0001 ) , with improved confidence scores ( p<0.0001 ) . Conclusions This short e-learning re source significantly improved the paediatric prescribing skills of junior doctors . Outcomes were maintained at 3 months , suggesting the utility of low cost , low fidelity , educationally sound e-learning interventions . However , the direct impact on patient outcomes following this intervention has yet to be determined BACKGROUND Antibiotics are a medication class for which inappropriate prescribing is frequently described . We sought to assess the effectiveness of a mailed intervention combining confidential prescribing feedback with targeted educational bulletins in increasing the use of less expensive , first-line antibiotics by practising physicians . METHODS The participants were 251 r and omly selected primary care physicians from southern Ontario who consented to participate ( 135 in the feedback group and 116 in the control group ) . Prescribing data were obtained from the cl aims data base of the Ontario Drug Benefit program , which covers all Ontarians over age 65 years for drugs selected from a minimally restrictive formulary . Confidentially prepared profiles of antibiotic prescriptions coupled with guidelines -based educational bulletins were mailed to the intervention group every 2 months for 6 months . The control group received no intervention until after completion of the study . The main outcome measures were change from baseline in physician 's median antibiotic cost and proportion of episodes of care in which a prespecified first-line antibiotic was used first . RESULTS The median prescription cost of about $ 11 remained constant in the feedback group but rose in the control group ( change of $ 0.05 v. $ 3.37 , p < 0.002 ) . First-line drug use increased in the feedback group but decreased in the control group ( change of 2.6 % v. -1.7 % , p < 0.01 ) . In a mailed survey of 100 feedback recipients ( response rate 76 % ) , 82 % indicated that they would participate readily in another , similar program . INTERPRETATION A simple program of confidential feedback and educational material s blunted cost increases , increased the use of first-line antibiotics and was highly acceptable to Ontario primary care physicians BACKGROUND Different methods have previously been tested to affect GPs ' prescribing habits . Attention has been drawn to benzodiazepines and antipsychotic drugs that are associated with several adverse effects in the elderly . OBJECTIVE To evaluate if educational outreach visits to GP practice s can affect the prescribing of benzodiazepines and antipsychotic drugs to the elderly and to evaluate the opinions of the participating GPs on such education . METHODS In the county of Skåne , Sweden , 41 GP practice s were invited to participate in educational outreach visits . Fifteen GP practice s accepted the invitation . Practice s were r and omised to active ( 8 practice s , 23 physicians ) and control group ( 7 practice s , 31 physicians ) . After the educational outreach visits prescribing of benzodiazepines and antipsychotic drugs to patients 65 years or older were measured for 1 year . The control group participated in the education after the study period . The opinions of GPs on educational outreach visits were evaluated . RESULTS One year after the educational outreach visits there were significant decreases in the active group compared to control group in the prescribing of medium- and long-acting benzodiazepines and total benzodiazepines but not so for antipsychotic drugs . CONCLUSIONS Educational outreach visits can be effective in modifying GPs ' prescribing habits . We have shown this to be so for prescribing of benzodiazepines to elderly patients in primary health care . Educational outreach visits are also very well appreciated by participating GPs OBJECTIVES To promote safe prescribing and administration of medicines in the pre- registration house officer ( PRHO ) year through a programme of structured teaching and assessment for final year medical students . DESIGN Forty final year medical students from two medical schools were r and omly allocated either to participate in a pharmacist facilitated teaching session or to receive no additional teaching . Teaching comprised five practical exercises covering seven skills through which students rotated in small groups . One month later , a r and om sample of 16 taught and 16 non-taught students participated in a nine-station objective structured clinical examination ( OSCE ) to assess the impact of the teaching . SETTING Manchester School of Medicine ( MSM ) , and Kings College School of Medicine and Dentistry ( KCSMD ) . PARTICIPANTS Final year medical student volunteers . MAIN OUTCOME MEASURES The need for teaching as indicated by student prior experience ; question naire rating of student acceptability of teaching and assessment ; self-rating of student confidence post- assessment , and student performance assessed by OSCE . RESULTS The study demonstrated that the taught group achieved higher scores in eight OSCE stations . Four of these were statistically significant ( P < or= 0.005 ) . Taught students felt more confident performing the skills on five stations . From 0 to 47.5 % students had prior experience of the skills taught . The post-teaching question naire evaluated exercises positively on several criteria , including provision of new information and relevance to future work . CONCLUSIONS Structured teaching provided an effective and acceptable method of teaching the medicines management skills needed in the PRHO year . The structured approach complemented variable precourse clinical experience Abstract Objective : This study aims to reveal whether a short training course of problem-based pharmacotherapy teaching , based on the World Health Organization 's ( WHO 's ) Guide to Good Prescribing and the Yemen Essential Drug List and St and ard Treatment Guidelines , will improve the competence of rational prescribing among medical and health assistant students in Yemen . Design : In a controlled pre/post-test study , 111 students from universities and health institutes participated on a voluntary basis . They were r and omly separated into a study and a control group . Students of the study group were taught to generate st and ard first-choice drugs for asthma or diarrhoea . The students were then taught how to apply this set of first-choice drugs to specific patient problems , using the WHO six-step problem-solving approach . Results : Students from the study group performed significantly better than those from control in all problems presented and also when compared with the results of the pre-test . The results of the pre-test also show that teaching students all basic knowledge about drugs does not guarantee rational prescribing in Yemen . Conclusion : It can be concluded from this study that proper training , i.e. ` immunising ' future doctors using problem-based pharmacotherapy teaching , is an efficient way of teaching rational prescribing in Yemen BACKGROUND In the paediatric emergency department ( ED ) trainees are more likely to commit prescribing errors . OBJECTIVE To determine whether a short educational intervention reduces the incidence of prescribing errors among trainees in a pediatric ED . METHODS A prospect i ve cohort study at the ED of a tertiary paediatric hospital . All fellows and residents arriving at the ED at the beginning of the academic year were invited to participate in a 30-minute tutorial focusing on appropriate methods for prescribing medications , followed by a written test . Eighteen days were selected r and omly during July 2001 . All the charts from these days were review ed for medication errors . Two review ers , blinded to whether or not a particular physician attended the tutorial , independently decided whether or not an error had occurred . The main outcome measure was the number of prescribing errors . RESULTS Twenty-two trainees worked in the ED during July 2001 . Of these , 13 trainees attended the tutorial . Eight hundred and ninety nine orders given by trainees were evaluated . We identified 66 ( 12.4 % ) errors in 533 orders given by those who attended tutorial , and 46 ( 12.7 % ) errors in 363 orders given by those who did not attend tutorial . The adjusted odds of a medication error was not significantly different between those who did not attend the tutorial and those who did ( OR : 1.07 95 % CI : 0.66 - 1.70 ) . CONCLUSIONS A short tutorial , followed by a written test , administered to trainees before entering their rotation in the paediatric ED , did not appear to reduce prescribing errors CONTEXT Avoidable drug-related problems ( DRPs ) cause substantial morbidity , mortality and costs . As most prescription errors are committed by recently graduated doctors , undergraduate training should specifically address DRPs . OBJECTIVES This study set out to investigate whether a DRP teaching module can reduce prescription errors made by advanced medical students in varying clinical context s. METHODS A total of 74 Year 5 medical students ( mean age 25 + /- 3 years ; 24 men , 50 women ) participated in a r and omised controlled crossover study . Students filled in patients ' prescription charts before and after a special DRP training module and a control intervention . The 1-week training module comprised a seminar on common prescription errors , a prescribing exercise with a st and ardised paper case patient , drafting of inoperative prescription charts for real patients and discussion s with a lecturer . During the observation points , prescription charts for st and ardised patient cases in different clinical context s had to be completed . These prescription charts were subsequently analysed by two independent raters using a checklist for common prescription errors . RESULTS Prior to training , students committed a mean of 69 + /- 12 % of the potential prescription errors . This decreased to 29 + /- 15 % after DRP training ( P < 0.001 ) . CONCLUSIONS Prescription errors can be significantly reduced in a relatively brief training time by implementing a specific DRP teaching module Abstract Objective : To determine whether an educational package could influence the management of menorrhagia , increase the appropriateness of choice of non-hormonal treatment , and reduce referral rates from primary to secondary care . Design : R and omised controlled trial . Setting : General practice s in East Anglia . Subjects : 100 practice s ( 348 doctors ) in primary care were recruited and r and omised to intervention ( 54 ) and control ( 46 ) . Interventions : An educational package based on principles of “ academic detailing ” with independent academics was given in small practice based interactive groups with a visual presentation , a printed evidence based summary , a graphic management flow chart , and a follow up meeting at 6 months . Outcome measures : All practice s recorded consultation details , treatments offered , and outcomes for women with regular heavy menstrual loss ( menorrhagia ) over 1 year . Results : 1001 consultation data sheets for menorrhagia were returned . There were significantly fewer referrals ( 20 % v 29 % ; odds ratio 0.64 ; 95 % confidence interval 0.41 to 0.99 ) and a significantly higher use of tranexamic acid ( odds ratio 2.38 ; 1.61 to 3.49 ) in the intervention group but no overall difference in norethisterone treatment compared with controls . There were more referrals when tranexamic acid was given with norethisterone than when it was given alone . Those practice s reporting fewer than 10 cases showed the highest increase in prescribing of tranexamic acid . Conclusions : The educational package positively influenced referral for menorrhagia and treatment with appropriate non-hormonal drugs Background : Continuing medical education ( CME ) is compulsory in Iran , and traditionally it is lecture-based , which is mostly not successful . Outcome -based education has been proposed for CME programs . Aim : To evaluate the effectiveness of an outcome -based educational intervention with a new approach based on outcomes and aligned teaching methods , on knowledge and skills of general physicians ( GPs ) working in primary care compared with a concurrent CME program in the field of “ Rational prescribing ” . Method : The method used was cluster r and omized controlled design . All GPs working in six cities in one province in Iran were invited to participate . The cities were matched and r and omly divided into an intervention arm for education on rational prescribing with an outcome -based approach , and a control arm for a traditional program on the same topic . Knowledge and skills were assessed using a pre- and post-test , including case scenarios . Results : In total , 112 GPs participated . There were significant improvements in knowledge and prescribing skills after the training in the intervention arm as well as in comparison with the changes in the control arm . The overall intervention effect was 26 percentage units . Conclusion : The introduction of an outcome -based approach in CME appears to be effective when creating programs to improve GPs ’ knowledge and skills Guidelines for the prescription of nonsteroidal anti-inflammatory drugs ( NSAIDs ) , drawn in the Health Ministry and published by the Drug Regulatory Agency , were introduced in the emergency department of a university hospital . The main objective was to determine , in this prospect i ve , before- and -after study , whether a teaching program could help doctors improve their NSAID prescribing practice s. Correct prescribing included limiting NSAIDs to their most admitted indications , avoiding their prescription to accident-prone patients , and reducing treatment duration and daily dosage . An overall reduction of NSAID prescriptions was also expected . Prescribing errors were divided into violations ( prescribing when unwarranted or against a contraindication ) and inadequacies ( if the compound or treatment schedule was not suited to the condition addressed ) . We measured the effect of the intervention 45 days after its initiation . Twenty-seven doctors participated in the two study phases ( 595 and 520 patients ) and wrote 50 NSAID prescriptions in each ( 8.4 % and 9.6 % of patients , respectively ; P = 0.44 ) . Prescribing errors decreased from 20 % to 14 % of cases ( P = 0.60 ) . There was a trend toward more prescriptions conforming to the Drug Regulatory Agency guidelines ( P = 0.08 ) . Treatment duration decreased from 10.4 ± 5.4 to 9.0 ± 4.0 days ( P = 0.03 ) . The teaching of guidelines has helped physicians to improve their NSAID prescribing practice s ; however , it did not succeed in curbing the overall prescription rate . Unrestricted lists that include soft indications may influence younger doctors into prescribing more NSAIDs Acute respiratory infections ( ARI ) , the leading class of ailments causing people to seek health care , rarely require antibiotics . Nevertheless , many physicians prescribe them needlessly . Hence , reducing the unnecessary use of antibiotics is one aim of any ARI control program . To help determine whether this aim might be achieved through a combination of refresher training for family physicians and public education campaigns , two 1991 interventions were carried out in four health areas ( design ated A , B , C , and D ) in the city of Havana , Cuba . In each area , 10 clinics staffed by family physicians were selected through simple r and om sampling . In two areas ( A and B ) , a refresher training program on ARI for health personnel was instituted at each clinic , while in areas A and C a community education program was set up . No intervention was carried out in area D. Simultaneously , from January through December 1991 trained individuals visited and administered a st and ard question naire every 15 days to 1,600 families ( 40 per clinic ) systematic ally selected by r and om sampling . The aim of this procedure was to record the number of ARI episodes occurring among children under 5 years old , the treatment chosen in these cases , and whether antibiotics were employed . The results showed that when the two interventions were initiated , antibiotics were prescribed for 26 % , 20 % , 11 % , and 19 % of the mild ARI cases occurring in areas A , B , C , and D respectively ( P > 0.05 ) . In the period immediately following the interventions , antibiotic prescription rates declined by 26 % and 63 % in areas A and B , while increasing by 2 % and 48 % in areas C and D. Overall , prescription of antibiotics in the intervention areas A and B combined decreased by 54 % ( 95 % CI : 31 - 69 % ) . These data suggest that a refresher training program for health personnel can rapidly reduce the unnecessary prescribing of antibiotics for ARI cases , but that public education alone does not appear effective Background : It has been estimated that 1–2 % of US in patients are harmed by medication errors , the majority of which are errors in prescribing . The UK Department of Health has recommended that serious errors in the use of prescribed drugs should be reduced by 40 % by 2005 ; however , little is known about the current incidence of prescribing errors in the UK . This pilot study sought to investigate their incidence in one UK hospital . Methods : Pharmacists prospect ively recorded details of all prescribing errors identified in non-obstetric in patients during a 4 week period . The number of medication orders written was estimated from a 1 in 5 sample of in patients . Potential clinical significance was assessed by a pharmacist and a clinical pharmacologist . Results : About 36 200 medication orders were written during the study period , and a prescribing error was identified in 1.5 % ( 95 % confidence interval ( CI ) 1.4 to 1.6 ) . A potentially serious error occurred in 0.4 % ( 95 % CI 0.3 to 0.5 ) . Most of the errors ( 54 % ) were associated with choice of dose . Error rates were significantly different for different stages of patient stay ( p<0.0001 ) with a higher error rate for medication orders written during the inpatient stay than for those written on admission or discharge . While the majority of all errors ( 61 % ) originated in medication order writing , most serious errors ( 58 % ) originated in the prescribing decision . Conclusions : There were about 135 prescribing errors identified each week , of which 34 were potentially serious . Knowing where and when errors are most likely to occur will be helpful in design ing initiatives to reduce them . The methods developed could be used to evaluate such initiatives Medical students have difficulty calculating drug doses correctly , but better teaching improves their performance in written tests . We conducted a blinded , r and omised , controlled trial to assess the benefit of online teaching on students ' ability to administer drugs in a simulated critical incident scenario , during which they were scored on their ability to administer drugs in solution presented as a ratio ( adrenaline ) or percentage ( lidocaine ) . Forty‐eight final year medical students were invited to participate ; 44 ( 92 % ) attended but only nine of the 20 students ( 45 % ) directed to the extra teaching viewed it . Nevertheless , the teaching module significantly improved the students ' ability to calculate the correct volume of lidocaine ( p = 0.005 ) and adrenaline ( p = 0.0002 ) , and benefited each student 's overall performance ( p = 0.0007 ) . Drug administration error is a very major problem and few interventions are known to be effective . We show that focusing on better teaching at medical school may benefit patient safety Purpose Although clinical - practice guidelines ( CPGs ) are implemented on the assumption that they will improve the quality , efficiency , and consistency of health care , they generally have limited effect in changing physicians ’ behavior . The purpose of this study was to design and implement an effective program for formulating , promulgating , and implementing CPGs to foster the development of an evidence -based culture in an Israeli HMO . Method The authors implemented a four-stage program of stepwise collaborative efforts with academic institutions composed of developing quantitative tools to evaluate prescribing patterns , updating CPGs , collecting MDs ’ input via focus groups and quantitative surveys , and conducting a r and omized controlled trial of a two-stage , multipronged intervention . The test case for this study was the development , dissemination , and implementation of CPG for the treatment of acute uncomplicated cystitis in adult women . Interventions in the form of a lecture at a conference and a letter with personalized feedback were implemented , both individually and combined , to improve physicians ’ rates of prescribing the first-line drug , nitrofurantoin , and , in the absence of nitrofurantoin , adhering to the recommended duration of three days of treatment with ofloxacin . Results The tools and data -generating capabilities design ed and constructed in Stage I of the project were integral components of all subsequent stages of the program . Personalized feedback alone was sufficient to improve the rate of adherence to the guidelines by 19.4 % ( 95 % CI = 16.7 , 22.1 ) . Conclusions This study provides a template for introducing the component of experimentation essential for cultivating an evidence -based culture . This process , composed of collaborative efforts between academic institutions and a managed care organization , may be beneficial to other health care systems In Tlaxcala State , Mexico , we determined that 80 % of children who died from diarrhoea or acute respiratory infections ( ARI ) received medical care before death ; in more than 70 % of the cases this care was provided by a private physician . Several strategies have been developed to improve physicians ' primary health care practice s but private practitioners have only rarely been included . The objective of the present study was to evaluate the impact of in-service training on the case management of diarrhoea and ARI among under-5-year-olds provided by private and public primary physicians . The training consisted of a five-day course of in-service practice during which physicians diagnosed and treated sick children attending a centre and conducted clinical discussion s of cases under guidance . Each training course was limited to six physicians . Clinical performance was evaluated by observation before and after the courses . The evaluation of diarrhoea case management covered assessment of dehydration , hydration therapy , prescription of antimicrobial and other drugs , advice on diet , and counselling for mothers ; that of ARI case management covered diagnosis , decisions on antimicrobial therapy , use of symptomatic drugs , and counselling for mothers . In general the performance of public physicians both before and after the intervention was better than that of private doctors . Most aspects of the case management of children with diarrhoea improved among both groups of physicians after the course ; the proportion of private physicians who had five or six correct elements out of six increased from 14 % to 37 % : for public physicians the corresponding increase was from 53 % to 73 % . In ARI case management , decisions taken on antimicrobial therapy and symptomatic drug use improved in both groups ; the proportion of private physicians with at least three correct elements out of four increased from 13 % to 42 % , while among public doctors the corresponding increase was from 43 % to 78 % . H and s-on training courses thus seemed to be effective in improving the practice of physicians in both the private and public sectors AIMS The impact of a short postgraduate course on rational pharmacotherapy planning behaviour of general practitioners ( GP ) was investigated via a face-to-face interview with 25 GPs working at health centres in Istanbul . METHODS GPs were r and omly allocated to control and intervention groups . Intervention group attended a 3-day-training program preceded and followed by a written exam to plan treatment for simulated cases with a selected indication . The participants ' therapeutic competence was also tested at the post-test for an unexposed indication to show the transfer effect of the course . In addition , patients treated by these GP 's were interviewed and the prescriptions were analysed regarding rational use of drugs ( RUD ) principles at the baseline , 2 weeks and 4 months after the course . RESULTS At the baseline there was not any significant difference between the control and intervention groups in terms of irrational prescribing habits . The question naires revealed that the GPs were not applying RUD rules in making their treatment plans and they were not educating their patients efficiently . Training produced a significant improvement in prescribing habits of the intervention group , which was preserved for 4 months after the course . However , very low scores of the pretest indicate the urgent necessity for solutions . CONCLUSIONS Training medical doctors on RUD not only at the under- but also at the postgraduate level deserves attention and should be considered by all sides of the problem including academia , health authorities and medical associations Objective To evaluate the effectiveness and costs of a multifaceted flexible educational programme aim ed at reducing antibiotic dispensing at the practice level in primary care . Design R and omised controlled trial with general practice s as the unit of r and omisation and analysis . Clinicians and research ers were blinded to group allocation until after r and omisation . Setting 68 general practice s with about 480 000 patients in Wales , United Kingdom . Participants 34 practice s were r and omised to receive the educational programme and 34 practice s to be controls . 139 clinicians from the intervention practice s and 124 from control practice s had agreed to participate before r and omisation . Practice level data covering all the clinicians in the 68 practice s were analysed . Interventions Intervention practice s followed the Stemming the Tide of Antibiotic Resistance ( STAR ) educational programme , which included a practice based seminar reflecting on the practice s ’ own dispensing and resistance data , online educational elements , and practising consulting skills in routine care . Control practice s provided usual care . Main outcome measures Total numbers of oral antibiotic items dispensed for all causes per 1000 practice patients in the year after the intervention , adjusted for the previous year ’s dispensing . Secondary outcomes included reconsultations , admissions to hospital for selected causes , and costs . Results The rate of oral antibiotic dispensing ( items per 1000 registered patients ) decreased by 14.1 in the intervention group but increased by 12.1 in the control group , a net difference of 26.1 . After adjustment for baseline dispensing rate , this amounted to a 4.2 % ( 95 % confidence interval 0.6 % to 7.7 % ) reduction in total oral antibiotic dispensing for the year in the intervention group relative to the control group ( P=0.02 ) . Reductions were found for all classes of antibiotics other than penicillinase-resistant penicillins but were largest and significant individually for phenoxymethylpenicillins ( penicillin V ) ( 7.3 % , 0.4 % to 13.7 % ) and macrolides ( 7.7 % , 1.1 % to 13.8 % ) . There were no significant differences between intervention and control practice s in the number of admissions to hospital or in reconsultations for a respiratory tract infection within seven days of an index consultation . The mean cost of the programme was £ 2923 ( € 3491 , $ 4572 ) per practice ( SD £ 1187 ) . There was a 5.5 % reduction in the cost of dispensed antibiotics in the intervention group compared with the control group ( −0.4 % to 11.4 % ) , equivalent to a reduction of about £ 830 a year for an average intervention practice . Conclusion The STAR educational programme led to reductions in all cause oral antibiotic dispensing over the subsequent year with no significant change in admissions to hospital , reconsultations , or costs . Trial registration IS RCT No 63355948 |
10,535 | 22,794,306 | Although all the predictive and confounding factors could not be controlled for , the results of this systematic review show a significant reduction of 47 % in the odds for miscarriage when dydrogesterone is compared to st and ard care indicating a real treatment effect | The objective of this systematic review was to assess whether the orally acting progestagen , dydrogesterone lowers the incidence of miscarriage in women with threatened miscarriage . | The objective of our study was to investigate the relationship between sonographic findings and the occurrence of abortion in pregnancies complicated by first-trimester bleeding in which fetal cardiac activity was documented upon admission . A prospect i ve study of transvaginal sonography was performed in 270 pregnant patients with bleeding between 5 and 12 weeks ' gestation . The study group included 149 cases in which a singleton fetus with cardiac activity was initially documented . The outcome variable was pregnancy loss prior to 20 weeks . The influence of sonographic findings on admission was studied by univariate analysis and logistic regression . The prevalence of abortion was 23/149 ( 15 % ) . A significant relationship ( p < 0.05 ) was found between the occurrence of abortion and the following : fetal bradycardia ( heart rate less than -1.2 SD from the mean ) , a discrepancy between the diameter of the gestational sac and crown-rump length less than -0.5 SD from the mean , and a discrepancy between menstrual and sonographic age of more than 1 week . According to the logistic regression equation that was obtained , the probability of abortion in first-trimester bleeding with documented fetal cardiac activity upon admission varied between a minimum of 6 % when none of the above risk factors were present and a maximum of 84 % when all were present . The presence of any of the above factors identified 84 % of all subsequent abortions Between 1983 and 1984 a double-blind r and omized study with progesterone substitution in threatened abortion was carried out . Fifty-six patients with vaginal bleeding during the first trimester of pregnancy , the internal cervical os being closed , were referred to the hospital . Twenty-five women ( 5th and 6th week of gestation ) with positive serum concentrations of beta-hCG were admitted to the study without regard to sonogram results . In other 25 women ( 7th-10th week of pregnancy ) and 6 women ( greater than or equal to 11th week of pregnancy ) fetal heart action and movement could be demonstrated by ultrasound . The patients were prescribed bed rest and vaginal suppositories twice daily , containing either 25 mg progesterone or only polyethylene glycol . The code was not broken until after completion of the study . Serial serum determinations of beta-hCG , estradiol-17 beta ( E2 ) , progesterone , and ultrasound were performed . Four patients had to be omitted from final analysis ( two tubal pregnancies , one intrauterine infection , one sectio parva ) . Three of 26 patients progesterone ( 11 % ) and five of 26 patients with placebo ( 19 % ) had an abortion , which represented no significant difference . Frequency of abortion was increased in women more than 30 years old , in women with previous abortions and after ovulation induction . Progesterone treatment result ed in a significant elevation of serum progesterone concentrations ( p less than 0.01 ) , while beta-hCG and E2 were unchanged . The results of this study confirm that pregnancy outcome is favorable in women with bleeding and normal hormone concentrations without hormonal treatment and unfavorable in women with reduced beta-hCG and E2-concentrations . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To assess the clinical value of a single serum CA-125 level in women presenting with symptoms of imminent abortion from 5 to 12 weeks ' gestation . STUDY DESIGN Two hundred women with symptoms of imminent abortion from 5 to 12 weeks ' gestation were allocated to 3 subgroups : group I ( n = 50 ) , abdominal pain only ; group II ( n = 80 ) , abdominal pain and vaginal bleeding of less than 3 days ' duration ; and group III ( n = 70 ) , abdominal pain and vaginal bleeding of > or = 3 days ' duration . The control group ( n = 55 ) was women undergoing a normal pregnancy of comparable gestational age . In all patients , CA-125 and beta-human chorionic gonadotropin ( beta-hCG ) levels were determined with commercially available enzymatic immunoassay tests . RESULTS A significant increase in serum CA-125 levels was observed in patients with vaginal bleeding ( groups II and III ) in comparison with the control group . In contrast to CA-125 , serum beta-hCG levels were significantly lower in patients who went on to miscarry . Receiver operating characteristic curve analysis revealed that all women with symptoms of imminent abortion who have a CA-125 level of > or = 43.1 U/mL should be considered as having a greater risk of miscarriage . Patients with bleeding of > or = 3 days should have a threshold value of 66.5 U/mL applied as a risk determinant . CONCLUSION A single serum CA-125 level determination is valuable in women with imminent abortion presenting with abdominal pain , vaginal bleeding or both OBJECTIVE To assess the diagnostic value of maternal CA 125 in patients with symptomatic first trimester pregnancy and to evaluate the prognostic significance of CA 125 versus beta-hCG in early pregnancies with intact fetal heartbeat , complicated by vaginal bleeding . STUDY DESIGN Two prospect i ve open-label studies with longitudinal follow-up in the second trial . SETTING Academic Department of Obstetrics and Gynecology , University of Cologne . PATIENTS Study 1 : 168 patients presenting between gestational weeks 6 and 12 with : extrauterine pregnancy , 29 ; missed abortion , 50 ; incomplete spontaneous abortion , 38 ; imminent abortion , 33 ; and normal pregnancy ( no history of endometriosis or ovarian mass ) , 18 . Study 2 : Fifty consecutive patients with vaginal bleeding during gestational weeks 6 - 12 all of whom having demostrable fetal heartbeat . Eighteen patients finally aborted whereas the remainder had normally continuing pregnancy until term . MAIN OUTCOME MEASURE Study 1 : Single serum determinations of CA 125 and beta-hCG were correlated with the different disorders observed . Study 2 : Two sequential measurements of serum CA 125 and beta-hCG performed within a 5 - 7 days interval were related to the outcome of pregnancy as indicated by changes of the ultrasound presentation , miscarriage , future hospitalization , or delivery . RESULTS Study 1 : Patients with vaginal bleeding generally had higher median CA 125 values ( 38 IU/ml ; range 1.3 - 540 ) compared to non-bleeding patients ( 17.8 IU/ml ; range 1.0 - 157 ) . No statistically significant differences in regard to median serum CA 125 levels between symptomatic and normal pregnancies occurred : normal pregnancy , 25.5 IU/ml ( range 3.2 - 97 ) ; ectopic pregnancy , 26 IU/ml ( range 1.3 - 157 ) ; missed abortion , 19.1IU/ml ( range 1 - 242 ) ; threatened abortion , 48 IU/ml ( range 5.2 - 540 ) ; spontaneous abortion , 40 IU/ml ( range 5.4 - 442 ) . Study 2 : Initial CA 125 levels did not differ significantly between both groups of patients with 27/32 non-aborters and 13/18 aborters showing concentrations below 65 IU/ml . After 5 - 7 days , CA 125 in all patients who eventually aborted remained high or increased whereas non-aborters all had constantly low or steeply declining CA 125 measures . beta-hCG increased in all non-aborters but also in 13/18 aborters during the 5 - 7 day interval . CONCLUSION Single serum measurements of CA 125 in symptomatic first trimester pregnant patients failed to discriminate spontaneous abortion , ectopic or normal pregnancies . However , sequential determinations of maternal CA 125 measurements appear to be a highly sensitive prognostic marker in patients with viable pregnancy at risk for abortion OBJECTIVE The purpose of this study was to determine whether patients with first-trimester threatened abortion are at increased risk for poor pregnancy outcome . STUDY DESIGN A large prospect i ve multicenter data base was studied . Subjects were divided into three groups : ( 1 ) no bleeding , ( 2 ) light bleeding , and ( 3 ) heavy bleeding . Univariate and multivariable logistic regression analyses were used . RESULTS The study comprised 16,506 patients : 14,160 patients without bleeding , 2094 patients with light bleeding , and 252 patients with heavy bleeding . Patients with vaginal bleeding , light or heavy , were more likely to experience a spontaneous loss before 24 weeks of gestation ( odds ratio , 2.5 and 4.2 , respectively ) and cesarean delivery ( odds ratio , 1.1 and 1.4 , respectively ) . Light bleeding subjects were more likely to have preeclampsia ( odds ratio , 1.5 ) , preterm delivery ( odds ratio , 1.3 ) , and placental abruption ( odds ratio , 1.6 ) . Heavy vaginal bleeding subjects were more likely to have intrauterine growth restriction ( odds ratio , 2.6 ) , preterm delivery ( odds ratio , 3.0 ) , preterm premature rupture of membranes ( odds ratio , 3.2 ) , and placental abruption ( odds ratio , 3.6 ) . CONCLUSION First-trimester vaginal bleeding is an independent risk factor for adverse obstetric outcome that is directly proportional to the amount of bleeding Problem The role of increased Th1 cytokine expression in pregnancy failure has been question ed recently . The therapeutic value of progestogens in threatened abortion ( TA ) is still debated . The aim of this prospect i ve study was to compare serum cytokine [ tumor necrosis factor (TNF)‐α , interleukin (IL)‐12 and IL‐10 ] concentrations in women with TA to those in women with normal pregnancy and to evaluate the impact of dydrogesterone supplementation in the former group on cytokine concentration OBJECTIVE To compare the influence of vaginal micronized progesterone and oral dydrogesterone supplementation on uteroplacental circulation in early pregnancy that is complicated by threatened abortion . DESIGN R and omized , parallel group , double-blind , double dummy-controlled study . SETTING Tertiary care university hospital . PATIENT(S ) Fifty-three patients with threatened abortion and a living embryo . INTERVENTION(S ) Three hundred milligrams of micronized vaginal progesterone or 30 mg of oral dydrogesterone daily supplementation for 6 weeks , serial transvaginal Doppler ultrasound measurement of pulsatility index , resistance index , and systolic/diastolic ratio of the spiral arteries , the uterine arteries , and the intrachorionic area . MAIN OUTCOME MEASURE(S ) Uteroplacental blood flow . RESULT ( S ) The study demonstrated that vaginal progesterone administration , but not oral dydrogesterone treatment , results in the decrease in the spiral artery pulsatility and resistance index and systolic/diastolic ratio . Insignificant decrease in pulsatility index and resistance index of the uterine artery was observed at > 9 weeks and was not associated with treatment regimen . Dydrogesterone treatment was only accompanied by the decrease in the uterine artery systolic/diastolic ratio . CONCLUSION ( S ) Vaginal progesterone and oral dydrogesterone supplementation have a different influence on the uteroplacental circulation in early pregnancy that is complicated by threatened abortion Abstract Objective : To estimate the miscarriage rate in a cohort of pregnant women and the final outcome of pregnancy . Design : Two year prospect i ve community study . Setting : Women registered with four semirural practice s at one health centre . Subjects : 626 pregnant women from a population 21 448 , 5140 of whom were women aged 15 - 44 years . Main outcome measures : Vaginal bleeding and outcome of pregnancy . Results : 76 of the 89 women with an unwanted pregnancy requested a termination . In the 550 ongoing pregnancies bleeding occurred before the 20th week in 117 ( 21 % ) , and 67 ( 12 % ) ended in miscarriage . The risk of miscarriage was not significantly increased after a miscarriage in the previous pregnancy ( 11 ( 15 % ) women had miscarriage v 55 ( 12 % ) women who had not had miscarriage ) who had previously had a live birth ) . Of the 117 women with bleeding , 64 were not admitted to hospital by the general practitioner ; 42 of these women had an ultrasound examination at the health centre and 19 subsequently miscarried at home . In hospital 41 of 46 women who miscarried had evacuation of the uterus . Conclusions : Bleeding occurred in one fifth of recognised pregnancies before the 20th week and over half of these miscarried . Treatment of women with miscarriage at home means current statistics on miscarriage in Britain are missing many cases . Key messages No national statistics for Britain are published on miscarriages Extrapolations from this survey indicate that in 1993 there may have been 70 000 - 90 000 miscarriages in Engl and and Wales Bleeding in early pregnancy is followed by a live birth in about half the affected pregnancies At least a quarter of all miscarriages were treated at home by general practitioners and would therefore not be recorded in any published statistics Women who had had a miscarriage did not have a significantly higher chance of a second consecutive INTRODUCTION The aim of this study was to determine whether dydrogesterone helps to preserve pregnancy in women with threatened miscarriage . METHODS 146 women who presented with mild or moderate vaginal bleeding during the first trimester of pregnancy were r and omised to receive oral dydrogesterone ( 10 mg b.i.d . ) ( n=86 ) or no treatment ( n=60 ) . Dydrogesterone was continued until 1 week after the bleeding had stopped . All women received st and ard supportive care . RESULTS The incidence of miscarriage was significantly lower in the dydrogesterone group than in the untreated group ( 17.5 % vs. 25 % ; p<0.05 ) . There were no statistically significant differences between the groups with respect to pregnancy complications or congenital abnormalities . CONCLUSION Dydrogesterone appears to have beneficial effects in women with threatened miscarriage OBJECTIVE To compare the efficacy of a vaginal progesterone preparation with our st and ard IM preparation within a donor egg program . DESIGN Prospect i ve r and omized trial . SETTING Donor egg program at a university assisted reproductive therapy program ( Jones Institute for Women 's Health ) . PATIENT(S ) Couples accepted into the donor egg program because of either premature ovarian failure or evidence of diminished ovarian reserve . INTERVENTION(S ) Women were r and omized into either a group receiving IM progesterone replacement or a group receiving vaginal progesterone replacement . Both groups underwent Estraderm patch/progesterone treatment in a mock cycle leading to an endometrial biopsy on day 26 followed by a second cycle in which ET was performed . Subjects with residual ovarian function received a GnRH agonist . In the IM treatment group , 100 mg was administered from cycle days 15 to 27 . In the vaginal treatment group , Crinone 8 % , a polycarbophil-based gel preparation containing 90 mg of micronized progesterone , was administered twice daily from the evening of day 14 . MAIN OUTCOME MEASURE(S ) Endometrial histology , serum levels of progesterone ( on days 13 , 17 , 20 , 24 , and 26 ) , the occurrence of pregnancy , implantation rate , and pregnancy outcome . RESULT ( S ) Fifty-four women r and omized into the vaginal progesterone treatment group and 18 women in the IM treatment group achieved ET . Mean serum progesterone levels were higher in the IM treatment group than in the Crinone group . Endometrial histology was " in phase " for all subjects in both groups . Clinical pregnancies were observed in 26 of 54 women and 5 of 18 women in the Crinone and IM progesterone groups , respectively . The ongoing pregnancy rate ( PR ) of 31 % ( 17/54 ) and implantation rate of 23 % in the subjects receiving Crinone was not statistically different from the IM progesterone group 's ongoing PR of 22 % ( 4/18 ) and implantation rate of 18 % . CONCLUSION Vaginal progesterone replacement with the polycarbophil gel preparation was as effective as IM progesterone in producing clinical and ongoing pregnancies within our donor egg program in the dosages administered INTRODUCTION Threatened miscarriage is a common problem during pregnancy . METHODS The aim of this prospect i ve , open , r and omised study was to determine whether dydrogesterone was more effective than conservative management alone in preventing miscarriage in women with vaginal bleeding up to week 16 of pregnancy . Women were excluded if they had a history of recurrent miscarriage . A total of 191 women were r and omised to dydrogesterone ( 40 mg stat followed by 10 mg twice daily ) or conservative management ( control group ) . The treatment was considered successful if the pregnancy continued beyond 20 weeks of gestation . RESULTS The success rate in the dydrogesterone group was statistically significantly higher than that in the control group ( 87.5 % vs. 71.6 % ; p<0.05 ) . Miscarriage occurred in 12.5 % of women in the dydrogesterone group compared with 28.4 % in the control group ( p<0.05 ) . There were no differences between the groups with regard to the incidence of Caesarean section , placenta praevia , antepartum haemorrhage , preterm labour ( weeks 28 - 36 ) , pregnancy-induced hypertension or low birth weight ( < 2500 g ) babies . There were no intrauterine deaths or congenital abnormalities in either group . CONCLUSION Compared with conservative management , dydrogesterone had beneficial effects on maintaining pregnancy in women with threatened miscarriage Many pregnancies are lost during early gestation , but clinicians still lack tools to recognize risk factors for miscarriage . Thus , the identification of risk factors for miscarriage during the first trimester in women with no obvious risk for a pregnancy loss was the aim of this prospect i ve cohort trial . A total of 1098 women between gestation weeks 4 and 12 in whom no apparent signs of a threatened pregnancy could be diagnosed were recruited . Demographic , anamnestic , psychometric and biological data were documented at recruitment and pregnancy outcomes were registered subsequently . Among the cases with sufficiently available data , 809 successfully progressing pregnancies and 55 subsequent miscarriages were reported . In this cohort , risk of miscarriage was significantly increased in women at higher age ( > 33 years ) , lower body mass index ( < or = 20 kg/ m(2 ) ) and lower serum progesterone concentrations ( < or = 12 ng/ml ) prior to the onset of the miscarriage . Women with subsequent miscarriage also perceived higher levels of stress/dem and s ( supported by higher concentrations of corticotrophin-releasing hormone ) and revealed reduced concentrations of progesterone-induced blocking factor . These risk factors were even more pronounced in the subcohort of women ( n = 335 ) recruited between gestation weeks 4 and 7 . The identification of these risk factors and development of an interaction model of these factors , as introduced in this article , will help clinicians to recognize pregnant women who require extra monitoring and who might benefit from therapeutic interventions such as progestogen supplementation , especially during the first weeks of pregnancy , to prevent a miscarriage UNLABELLED Pregnancy with visible fetal heart beat complicated by first trimester threatened abortion had significant increased risk of subsequent spontaneous abortion compared with normal pregnancy . OBJECTIVE To compare pregnancy outcomes in cases complicated by first trimester threatened abortion with those that were not . METHODS Prospect i ve cohort study of 255 cases of first trimester threatened abortions but with visible heart beat and 265 other normal pregnancies . RESULTS Spontaneous abortion rates of 5.5 % ( with relative abortal risk of 2.91 ) was found for study group , compared to 1.88 % for controls ( p < 0.05 ) . Preterm delivery was also higher , but was not statistically significant . CONCLUSIONS First trimester bleeding with visible fetal heart beat appears to associate significantly with higher subsequent spontaneous abortion rate than those without OBJECTIVE To determine whether therapy with dydrogesterone in threatened abortion during the first trimester of pregnancy will improve pregnancy outcome . DESIGN Prospect i ve open study . SUBJECTS Pregnant women presenting to the obstetric and gynaecology clinic admitting center with vaginal bleeding before 13 weeks gestation were evaluated for entry into the study . Women were excluded if they had a history of recurrent miscarriage . METHOD Eligible subjects were r and omized to receive either dydrogesterone 40 mg stat dose followed by 10 mg twice a day for one week or conservative therapy . RESULTS One hundred and 54 women were recruited . There was no statistically significant differences between the two groups with regard to pre-treatment status . The continuing pregnancy success rate was significantly ( p=0.037 ) higher in women treated with dydrogesterone ( 95.9 % ) compared with women who received conservative treatment ( 86.3 % ) . The odds ratio of the success rate between dydrogesterone treatment and non-treatment was 3.773 ( 95 % confidence interval : 1.009 - 14.108 ) . CONCLUSION Corpus luteal support with dydrogesterone has been shown to reduce the incidence of pregnancy loss in threatened abortion during the first trimester in women without a history of recurrent abortion OBJECTIVES To study the incidence of fetal loss in threatened abortion after detection of embryonic/fetal heart activity . METHODS A prospect i ve study was performed on pregnant women with clinical ly diagnosed threatened abortion between 6 and 14 weeks of gestation . All had a good menstrual history and the calculated gestational age using crown-rump length in the first trimester ultrasound was in agreement . Embryonic/fetal heart rate measurements were obtained by a 5 MHz vaginal probe using M-mode and real-time B mode imaging . All cases were followed up with respect to pregnancy outcomes . The data were analyzed using the SPSS computer program . RESULTS Eighty-seven pregnant women were included in the study . There were three pregnancies ( 3.4 % ) which result ed in fetal loss before 20 weeks of gestation . In viable pregnancies , the mean embryonic/fetal heart rate increased with advancing gestational age . The individual values of embryonic/fetal heart rate for fetal losses were within the reference range . CONCLUSIONS The incidence of fetal loss in threatened abortion after detection of embryonic/fetal heart activity was 3.4 % . There was no evident pattern of bradycardia or tachycardia that signaled the incipient of viability Fifty women with previous diagnosis of inadequate luteal phase and threatened abortion underwent a prospect i ve , r and omized , double-blind study in one medical center carried out with a parallel trial . The primary objective was to establish the effects of vaginal progesterone ( Crinone 8 % ) in reducing both pain and uterine contractions ( UCs ) . The gel with or without ( placebo ) vaginal progesterone was administered once a day since the diagnosis of threatened abortion and for 5 days . The efficacy on pain symptom amelioration was evaluated by a 5-score intensity gradation , while the UCs were evaluated by ultrasound . The secondary objective of the study was to evaluate the outcome of the pregnancies . The use of progesterone was effective both on pain relief and on the frequency of the UCs that decreased after 5 days of vaginal progesterone administration ( P < 0.005 ) . The evaluation of the ongoing pregnancy and spontaneous abortion in both study groups after 60 days showed that 4 patients of group A and 8 patients of group B miscarried ( P < 0.05 ) . In conclusion , patients with threatened abortion benefit from vaginal progesterone by a reduction of UCs and pain . The use of vaginal progesterone improved the outcome of pregnancies complicated by threatened abortion and previous diagnosis of inadequate luteal phase |
10,536 | 28,222,158 | Conclusions The addition of AAs to st and ard therapy in mOGC improves OS .
Improved efficacy was only observed in 2nd- or 3rd-line setting and not in 1st-line setting .
Consistent OS benefit was present across all geographical regions .
This benefit is at the expense of increased overall toxicity | Background Studies of anti-angiogenic agents ( AAs ) , combined with chemotherapy ( chemo ) or as monotherapy in metastatic oesophago-gastric cancer ( mOGC ) , have reported mixed outcomes .
We undertook systematic review and meta- analysis to determine their overall benefits and harms . | BACKGROUND VEGFR-2 has a role in gastric cancer pathogenesis and progression . We assessed whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with placebo plus paclitaxel . METHODS This r and omised , placebo-controlled , double-blind , phase 3 trial was done at 170 centres in 27 countries in North and South America , Europe , Asia , and Australia . Patients aged 18 years or older with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy ( platinum plus fluoropyrimidine with or without an anthracycline ) were r and omly assigned with a central ised interactive voice or web-response system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 , plus paclitaxel 80 mg/m(2 ) intravenously on days 1 , 8 , and 15 of a 28-day cycle . A permuted block r and omisation , stratified by geographic region , time to progression on first-line therapy , and disease measurability , was used . The primary endpoint was overall survival . Efficacy analysis was by intention to treat , and safety analysis included all patients who received at least one treatment with study drug . This trial is registered with Clinical Trials.gov , number NCT01170663 , and has been completed ; patients who are still receiving treatment are in the extension phase . FINDINGS Between Dec 23 , 2010 , and Sept 23 , 2012 , 665 patients were r and omly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel . Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group ( median 9·6 months [ 95 % CI 8·5 - 10·8 ] vs 7·4 months [ 95 % CI 6·3 - 8·4 ] , hazard ratio 0·807 [ 95 % CI 0·678 - 0·962 ] ; p=0·017 ) . Grade 3 or higher adverse events that occurred in more than 5 % of patients in the ramucirumab plus paclitaxel group versus placebo plus paclitaxel included neutropenia ( 133 [ 41 % ] of 327 vs 62 [ 19 % ] of 329 ) , leucopenia ( 57 [ 17 % ] vs 22 [ 7 % ] ) , hypertension ( 46 [ 14 % ] vs eight [ 2 % ] ) , fatigue ( 39 [ 12 % ] vs 18 [ 5 % ] ) , anaemia ( 30 [ 9 % ] vs 34 [ 10 % ] ) , and abdominal pain ( 20 [ 6 % ] vs 11 [ 3 % ] ) . The incidence of grade 3 or higher febrile neutropenia was low in both groups ( ten [ 3 % ] vs eight [ 2 % ] ) . INTERPRETATION The combination of ramucirumab with paclitaxel significantly increases overall survival compared with placebo plus paclitaxel , and could be regarded as a new st and ard second-line treatment for patients with advanced gastric cancer . FUNDING Eli Lilly and Company Background : This study aim ed to determine whether combination S-1 plus cisplatin ( CDDP ) therapy , the most widely used therapy for Japanese patients with advanced gastric cancer , and the novel oral antiangiogenic agent TSU-68 could contribute to gastric cancer treatment . Methods : Ninety-three patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers were r and omised into two groups : TSU-68 plus S-1/CDDP ( group A ) and S-1/CDDP ( group B ) groups . Both patient groups received identical S-1 and CDDP dosages . TSU-68 was orally administered for 35 consecutive days . Group B patients received S-1 orally twice daily for three consecutive weeks , followed by intravenous CDDP on day 8 . The primary endpoint was progression-free survival ( PFS ) . Results : Median PFS periods were 208 and 213 days in groups A and B , respectively ( P=0.427 ) . Median survival periods for groups A and B were 497.0 and 463.5 days , respectively ( P=0.219 ) . No statistically significant differences were noted for PFS , survival or the adverse event ( AE ) incidence rate . All AEs were expected according to previous reports for TSU-68 , TS-1 , and CDDP . Conclusion : Combination therapy involving TSU-68 , S-1 , and CDDP was safe and well tolerated in patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers . However , factors related to therapeutic efficacy should be investigated further PURPOSE We evaluated the activity of regorafenib , an oral multikinase inhibitor , in advanced gastric adenocarcinoma . PATIENTS AND METHODS We conducted an international ( Australia and New Zeal and , South Korea , and Canada ) r and omized phase II trial in which patients were r and omly assigned at a two-to-one ratio and stratified by lines of prior chemotherapy for advanced disease ( one v two ) and region . Eligible patients received best supportive care plus regorafenib 160 mg or matching placebo orally on days 1 to 21 of each 28-day cycle until disease progression or prohibitive adverse events occurred . The primary end point was progression-free survival ( PFS ) . Final analysis included data to December 31 , 2014 . RESULTS A total of 152 patients were r and omly assigned from November 7 , 2012 , to February 25 , 2014 , yielding 147 evaluable patients ( regorafenib , n = 97 ; placebo , n = 50 ) . Baseline characteristics were balanced . Median PFS significantly differed between groups ( regorafenib , 2.6 months ; 95 % CI , 1.8 to 3.1 and placebo , 0.9 months ; 95 % CI , 0.9 to 0.9 ; hazard ratio [ HR ] , 0.40 ; 95 % CI , 0.28 to 0.59 ; P < .001 ) . The effect was greater in South Korea than in Australia , New Zeal and , and Canada combined ( HR , 0.12 v 0.61 ; interaction P < .001 ) but consistent across age , neutrophil-to-lymphocyte ratio , primary site , lines of chemotherapy , peritoneal metastasis presence , number of metastatic sites , and plasma vascular endothelial growth factor A. A survival trend in favor of regorafenib was seen ( median , 5.8 months ; 95 % CI , 4.4 to 6.8 v 4.5 months ; 95 % CI , 3.4 to 5.2 ; HR , 0.74 ; P = .147 ) . Twenty-nine patients assigned to placebo received open-label regorafenib after disease progression . Regorafenib toxicity was similar to that previously reported . CONCLUSION In this phase II trial , regorafenib was effective in prolonging PFS in refractory advanced gastric adenocarcinoma . Regional differences were found , but regorafenib was effective in both regional groups . A phase III trial is planned BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche Background As a multi-targeted anti-angiogenic receptor tyrosine kinase ( RTK ) inhibitor sunitinib ( SUN ) has been established for renal cancer and gastrointestinal stromal tumors . In advanced refractory esophagogastric cancer patients , monotherapy with SUN was associated with good tolerability but limited tumor response . Methods This double-blind , placebo-controlled , multicenter , phase II clinical trial was conducted to evaluate the efficacy , safety and tolerability of SUN as an adjunct to second and third-line FOLFIRI ( NCT01020630 ) . Patients were r and omized to receive 6-week cycles including FOLFIRI plus sodium folinate ( Na-FOLFIRI ) once every two weeks and SUN or placebo ( PL ) continuously for four weeks followed by a 2-week rest period . The primary study endpoint was progression-free survival ( PFS ) . Preplanned serum analyses of VEGF-A , VEGF-D , VEGFR2 and SDF-1α were performed retrospectively . Results Overall , 91 patients were r and omized , 45 in each group ( one patient withdrew ) . The main grade ≥3 AEs were neutropenia and leucopenia , observed in 56 % /20 % and 27 % /16 % for FOLFIRI + SUN/FOLFIRI + PL , respectively . Median PFS was similar , 3.5 vs. 3.3 months ( hazard ratio ( HR ) 1.11 , 95 % CI 0.70–1.74 , P = 0.66 ) for FOLFIRI + SUN vs. FOLFIRI + PL , respectively . For FOLFIRI + SUN , a trend towards longer median overall survival ( OS ) compared with placebo was observed ( 10.4 vs. 8.9 months , HR 0.82 , 95 % CI 0.50–1.34 , one-sided P = 0.21 ) . In subgroup serum analyses , significant changes in VEGF-A ( P = 0.017 ) , VEGFR2 ( P = 0.012 ) and VEGF-D ( P < 0.001 ) serum levels were observed . Conclusions Although sunitinib combined with FOLFIRI did not improve PFS and response in chemotherapy-resistant gastric cancer , a trend towards better OS was observed . Further biomarker-driven studies with other anti-angiogenic RTK inhibitors are warranted . Trial registration This study was registered prospect ively in the NCT Clinical Trials Registry ( Clinical Trials.gov ) under NCT01020630 on November 23 , 2009 after approval by the leading ethics committee of the Medical Association of Rhinel and -Palatinate , Mainz , in coordination with the participating ethics committees ( see Additional file 2 ) on September 16 , 2009 PURPOSE The AVAGAST study showed that adding bevacizumab to chemotherapy in patients with advanced gastric cancer improves progression-free survival and tumor response rate but not overall survival . To examine the hypothesis that angiogenic markers may have predictive value for bevacizumab efficacy in gastric cancer , AVAGAST included a prospect i ve , m and atory biomarker program . PATIENTS AND METHODS Patients with previously untreated , locally advanced or metastatic gastric cancer were r and omly assigned to bevacizumab ( n = 387 ) or placebo ( n = 387 ) in combination with chemotherapy . Blood and tumor tissue sample s were collected at baseline . Prespecified biomarkers included plasma vascular endothelial growth factor-A ( VEGF-A ) , protein expression of neuropilin-1 , and VEGF receptors-1 and -2 ( VEGFR-1 and VEGFR-2 ) . Correlations between biomarkers and clinical outcomes were assessed by using a Cox proportional hazards model . RESULTS Plasma was available from 712 patients ( 92 % ) , and tumor sample s were available from 727 patients ( 94 % ) . Baseline plasma VEGF-A levels and tumor neuropilin-1 expression were identified as potential predictors of bevacizumab efficacy . Patients with high baseline plasma VEGF-A levels showed a trend toward improved overall survival ( hazard ratio [ HR ] , 0.72 ; 95 % CI , 0.57 to 0.93 ) versus patients with low VEGF-A levels ( HR , 1.01 ; 95 % CI , 0.77 to 1.31 ; interaction P = .07 ) . Patients with low baseline expression of neuropilin-1 also showed a trend toward improved overall survival ( HR , 0.75 ; 95 % CI , 0.59 to 0.97 ) versus patients with high neuropilin-1 expression ( HR , 1.07 ; 95 % CI , 0.81 to 1.40 ; interaction P = .06 ) . For both biomarkers , subgroup analyses demonstrated significance only in patients from non-Asian regions . CONCLUSION Plasma VEGF-A and tumor neuropilin-1 are strong biomarker c and i date s for predicting clinical outcome in patients with advanced gastric cancer treated with bevacizumab BACKGROUND Vascular endothelial growth factor ( VEGF ) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer . We aim ed to assess whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , prolonged survival in patients with advanced gastric cancer . METHODS We did an international , r and omised , double-blind , placebo-controlled , phase 3 trial between Oct 6 , 2009 , and Jan 26 , 2012 , at 119 centres in 29 countries in North America , Central and South America , Europe , Asia , Australia , and Africa . Patients aged 24 - 87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line platinum-containing or fluoropyrimidine-containing chemotherapy were r and omly assigned ( 2:1 ) , via a central interactive voice-response system , to receive best supportive care plus either ramucirumab 8 mg/kg or placebo , intravenously once every 2 weeks . The study sponsor , participants , and investigators were masked to treatment assignment . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00917384 . FINDINGS 355 patients were assigned to receive ramucirumab ( n=238 ) or placebo ( n=117 ) . Median overall survival was 5·2 months ( IQR 2·3 - 9·9 ) in patients in the ramucirumab group and 3·8 months ( 1·7 - 7·1 ) in those in the placebo group ( hazard ratio [ HR ] 0·776 , 95 % CI 0·603 - 0·998 ; p=0·047 ) . The survival benefit with ramucirumab remained unchanged after multivariable adjustment for other prognostic factors ( multivariable HR 0·774 , 0·605 - 0·991 ; p=0·042 ) . Rates of hypertension were higher in the ramucirumab group than in the placebo group ( 38 [ 16 % ] vs nine [ 8 % ] ) , whereas rates of other adverse events were mostly similar between groups ( 223 [ 94 % ] vs 101 [ 88 % ] ) . Five ( 2 % ) deaths in the ramucirumab group and two ( 2 % ) in the placebo group were considered to be related to study drug . INTERPRETATION Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy . Our findings vali date VEGFR-2 signalling as an important therapeutic target in advanced gastric cancer . FUNDING ImClone Systems |
10,537 | 24,976,964 | Generally no differences in attitudes or preference of eLearning over traditional learning were observed .
No clear trends were found in the comparison of different modes of eLearning .
Conclusions Our results suggest that offline eLearning is equivalent and possibly superior to traditional learning regarding knowledge , skills , attitudes and satisfaction . | Background The world is short of 7.2 million health – care workers and this figure is growing .
The shortage of teachers is even greater , which limits traditional education modes .
eLearning may help overcome this training need .
Offline eLearning is useful in remote and re source –limited setting s with poor internet access .
To inform investments in offline eLearning , we need to establish its effectiveness in terms of gaining knowledge and skills , students ’ satisfaction and attitudes towards eLearning . | OBJECTIVE To assess the impact of digital problem-based learning ( PBL ) cases on student learning in ophthalmology courses . METHODS Ninety students were r and omly divided into 3 classes ( 30 students per class ) . The first class studied under a didactic model . The other 2 classes were divided into 6 groups ( 10 students per group ) and received PBL teaching ; 3 groups studied via cases presented in digital form and the others studied via paper-form cases . The results of theoretical and case analysis examinations were analyzed using the chi(2 ) test . Student performance on the interval practice was analyzed using the Kruskal-Wallis test . Question naires were used to evaluate student and facilitator perceptions . RESULTS Students in the digital groups exhibited better performance in the practice procedures according to tutorial evaluations compared with the other groups ( P < .05 ) . The 2 PBL classes had significantly higher mean results of theoretical and case analysis examinations ( P < .001 ) , but there was no significant difference between the 2 PBL classes . Ninety-three percent of students in the digital groups ( vs 73 % in the paper groups ) noted that the cases greatly stimulated their interest . CONCLUSIONS Introducing PBL into ophthalmology could improve educational quality and effectiveness . Digital PBL cases stimulate interest and motivate students to further improve diagnosis and problem-h and ling skills Background / aim : Owing to the complex topographical aspects of ophthalmic surgery , teaching with conventional surgical videos has led to a poor underst and ing among medical students . A novel multimedia three dimensional ( 3D ) computer animated program , called “ Ophthalmic Operation Vienna ” has been developed , where surgical videos are accompanied by 3D animated sequences of all surgical steps for five operations . The aim of the study was to assess the effect of 3D animations on the underst and ing of cataract and glaucoma surgery among medical students . Method : Set in the Medical University of Vienna , Department of Ophthalmology , 172 students were r and omised into two groups : a 3D group ( n = 90 ) , that saw the 3D animations and video sequences , and a control group ( n = 82 ) , that saw only the surgical videos . The narrated text was identical for both groups . After the presentation , students were question ed and tested using multiple choice questions . Results : Students in the 3D group found the interactive multimedia teaching methods to be a valuable supplement to the conventional surgical videos . The 3D group outperformed the control group not only in topographical underst and ing by 16 % ( p<0.0001 ) , but also in theoretical underst and ing by 7 % ( p<0.003 ) . Women in the 3D group gained most by 19 % over the control group ( p<0.0001 ) . Conclusions : The use of 3D animations lead to a better underst and ing of difficult surgical topics among medical students , especially for female users . Gender related benefits of using multimedia should be further explored OBJECTIVE Nurses need to be competent and confident in performing drug calculations to ensure patient safety . The purpose of this study is to compare an interactive e-drug calculations package , developed using Cognitive Load Theory as its theoretical framework , with traditional h and out learning support on nursing students ' drug calculation ability , self-efficacy and support material satisfaction . DESIGN A cluster r and omised controlled trial comparing the e-package with traditional h and out learning support was conducted with a September cohort ( n=137 ) and a February cohort ( n=92 ) of second year diploma nursing students . Students from each cohort were geographically dispersed over 3 or 4 independent sites . MEASUREMENTS Students from each cohort were invited to participate , halfway through their second year , before and after a 12 week clinical practice placement . During their placement the intervention group received the e-drug calculations package while the control group received traditional ' h and out ' support material . Drug calculation ability and self-efficacy tests were given to the participants pre- and post-intervention . Participants were given the support material satisfaction scale post-intervention . RESULTS Students in both cohorts r and omised to e-learning were more able to perform drug calculations than those receiving the h and out ( September : mean 48.4 % versus 34.7 % , p=0.027 ; February : mean 47.6 % versus 38.3 % , p=0.024 ) . February cohort students using the e-package were more confident in performing drug calculations than those students using h and outs ( self-efficacy mean 56.7 % versus 45.8 % , p=0.022 ) . There was no difference in improved self-efficacy between intervention and control for students in the September cohort . Students who used the package were more satisfied with its use than the students who used the h and out ( mean 29.6 versus 26.5 , p=0.001 ) , particularly with regard to the package enhancing their learning ( p=0.023 ) , being an effective way to learn ( p=0.005 ) , providing practice and feedback ( p<0.001 ) , being accessible ( p=0.027 ) , user friendly ( p=0.02 ) and providing learning enjoyment ( p=0.022 ) . CONCLUSION It is essential that nurses are educated and supported to become , and remain , confident and competent in performing drug calculations . This study found the e-drug calculations package , based on Cognitive Load Theory , to be significantly more effective than a h and out in improving students ' drug calculation ability and self-efficacy , with students who used the package being significantly more satisfied with its use than students who used the h and out . This package could particularly be useful for the continuing professional development of any healthcare professional involved in drug calculations Purpose To compare , using a prospect i ve , r and omized controlled study , three methods of teaching a medical school parasitology course : computer-based instruction , traditional lecture-based instruction , and a combination of computer-based and lecture-based instruction . Method A single class of the University of Utah School of Medicine was r and omized into three study groups for the second-year parasitology course . The computer group ( n = 29 ) used a locally developed interactive parasitology computer program ; the lecture group ( n = 32 ) had traditional lectures , and the combined group ( n = 33 ) used both the computer program and lectures . Students ' knowledge was assessed using a pretest , a final examination , and a posttest administered four months after the course . Students also used logs to track the amounts of time they spent study ing . Their impressions and course evaluations were collected using a st and ardized course-evaluation form . Results The groups ' scores on the pretest , final examination , and posttest were not statistically significantly different . Students in the computer group averaged 26.8 hours of study ing over the two-week course compared with 32.1 hours in the lecture group and 32.7 hours in the combined group . The difference in study times between the computer and combined groups yielded a significant p value of 0.036 . Students were generally positive about the course and the computer program . Conclusion Students can learn parasitology from computer-based instruction as effectively as from traditional lecture-based instruction , and they can do so in less time BACKGROUND Curricular medical training on dementia at the Department of Psychiatry and Psychotherapy at the University of Erlangen comprises of a traditional lecture . This setting was compared with two different E-Learning formats using a r and omized study design . METHODS 104 students ( average age 26.3 + /- 3.6 years ) were r and omized into 3 groups : Interactive e-Learning ; virtual lecture ( slides and audio ) and st and ard lecture ( control group ; 90 minutes ) . RESULTS Overall , the response rate was 40.4 % . Assessment of formal knowledge using a multiple-choice test yielded no differences between the three groups . In the students ' evaluation , the interactive e-learning showed the best results ( 1.86 + /- 0.69 ) , followed by the st and ard lecture ( 2.0 + /- 0.71 ) and the virtual lecture ( 2.6 + /- 0.8 ) . Nevertheless , the students would not prefer e-learning to the st and ard lecture when both methods are directly compared . CONCLUSION Our findings suggest that e-learning is equivalent to a st and ard lecture when formal knowledge is assessed . Evaluation results are best for interactive e-learning formats . The detailed reasons for the preference of different learning styles should be further investigated OBJECTIVES To determine the long-term retention of a 3-dimentional ( 3-D ) educational computer model of the larynx to teach laryngeal anatomy and to compare it with st and ard written instruction ( SWI ) . DESIGN Prospect i ve r and omized controlled trial . SETTING University education program . PARTICIPANTS One hundred health care students . INTERVENTIONS For short-term assessment , 50 students were r and omized to the 3-D model and 50 to SWI and were tested using a 20- question laryngeal test . Six months later , the same students were invited to retake the laryngeal anatomy test to examine long-term retention . MAIN OUTCOME MEASURE The score on a 20-item Web-based test that assessed the students ' level of knowledge of laryngeal anatomy approximately 6 months after their initial exposure to the laryngeal anatomy teaching intervention . RESULTS Sixty-two students retook the test : 3-D ( n = 30 ) and SWI ( n = 32 ) . No significant difference was noted in mean scores ( P = .54 ) and change in scores ( P = .59 ) between short- and long-term retention on the laryngeal anatomy test . There was a trend toward an increase in 3-D scores in both groups ( P = .07 ) and a significant increase in 3-D scores in the 3-D group only ( P = .049 ) . CONCLUSIONS A low-fidelity model ( SWI ) is just as effective as a high-fidelity model ( 3-D ) in teaching laryngeal anatomy . The acquired knowledge from either educational intervention may last up to 6 months for long-term retention . This study is one of the few in medical education to examine long-term retention OBJECTIVES To explore medical students ' use of computer tutorials embedded in a busy clinical setting ; to demonstrate that such tutorials can increase knowledge gain over and above that attributable to the clinical rotation itself . METHODS Six tutorials were installed on a computer placed in a central area in an emergency department . Each tutorial was made up of between 33 and 85 screens of information that include text , graphics , animations , and questions . They were design ed to be brief ( 10 minutes ) , focused , interactive , and immediately relevant . The authors evaluated the intervention using quantitative research methods , including usage tracking , surveys of faculty and students , and a r and omized pretest-posttest study . RESULTS Over 46 weeks , 95 medical students used the tutorials 544 times , for an overall average of 1.7 times a day . The median time spent on completed tutorials was 11 minutes ( average [ SD ] , 14 [ + /-12 ] minutes ) . Seventy-four students completed the r and omized study . They completed 65 % of the assigned tutorials , result ing in improved examination scores compared with the control ( effect size , 0.39 ; 95 % confidence interval = 0.15 to 0.62 ) . Students were positively disposed to the tutorials , ranking them as " valuable . " Fifty-four percent preferred the tutorials to small group teaching sessions with a preceptor . The faculty was also positive about the tutorials , although they did not appear to integrate the tutorials directly into their teaching . CONCLUSIONS Medical students on rotation in a busy clinical setting can and will use appropriately presented computer tutorials . The tutorials are effective in raising examination scores BACKGROUND Computer-based video training ( CBVT ) provides flexible opportunities for surgical trainees to learn fundamental technical skills , but may be ineffective in self-directed practice setting s because of poor trainee self- assessment . This study examined whether CBVT is effective in a self-directed learning environment among novice trainees . METHODS Thirty novice trainees used CBVT to learn the 1-h and ed square knot while self-assessing their proficiency every 3 minutes . On reaching self-assessed skill proficiency , trainees were r and omized to either cease practice or to complete additional practice . Performance was evaluated with computer and expert-based measures during practice and on pretests , posttests , and 1-week retention tests . RESULTS Analyses revealed performance improvements for both groups ( all P < .05 ) , but no differences between the 2 groups ( all P > .05 ) on all tests . CONCLUSIONS CBVT for the 1-h and ed square knot is effective in a self-directed learning environment among novices . This lends support to the implementation of self-directed digital media-based learning within surgical curricula BACKGROUND We carried out a prospect i ve , r and omized , 4-arm study including control arm , blinding of examiners to determine effectiveness of computer-based video instruction ( CBVI ) and different types of expert feedback ( concurrent and summary ) on learning of a basic technical skill . METHODS Using bench models , participants were pre-tested on a suturing and instrument knot-tying skill after viewing an instructional video . The students were subsequently assigned r and omly to 4 practice conditions : no additional intervention ( control ) , self study with CBVI , expert feedback during practice trials ( concurrent feedback ) , and expert feedback after practice trials ( summary feedback ) . All participants underwent 19 trials of practice , over 1 hour , in their assigned training condition . The effectiveness of training was assessed both at an immediate post-test and 1 month later at a retention test . Performance was evaluated using both expert-based ( Global Rating Scores ) and computer-based assessment ( H and Motion Analysis ) . Data were analyzed using repeated- measures ANOVA . RESULTS There were no differences in GRS between groups at pre-test . The CBVI , concurrent feedback and summary feedback methods were equally effective initially for the instruction of this basic technical skill to naive medical students and displayed better performance than control ( control , 12.71 [ 10.79 to 14.62 ] ; CBVI , 16.39 [ 14.38 to 18.40 ] ; concurrent , 16.97 [ 15.79 to 18.15 ] ; summary , 16.09 [ 13.57 to 18.62 ] ; P < .001 each ) . At retention . however , only CBVI and summary feedback groups retained superior suturing and knot-tying performance versus control ( control , 8.13 [ 6.94 to 9.85 ] ; CBVI , 11.92 [ 10.19 to 14.99 ] P = .037 ; concurrent , 9.80 [ 8.55 to 13.45 ] P = .635 ; summary , 111.19 [ 10.27 to 14.29 ] P = .037 ) . H and motion data displayed a similar pattern of results . There were no group differences in the rate of learning ( P > .05 ) . CONCLUSION Our study showed that CBVI can be as effective as summary expert feedback in the instruction of basic technical skills to medical students . Thoughtfully incorporated into technical curricula , CBVI can make efficient use of faculty time and serve as a useful pedagogic adjunct for basic skills training . Additionally , our study provides evidence supporting an increased role of summary feedback to effectively train novices in technical skills Didactic teaching remains a core component of undergraduate education , but developing computer assisted learning ( CAL ) packages may provide useful alternatives . We compared the effectiveness of interactive multimedia-based tutorials with traditional , lecture-based models for teaching arterial blood gas interpretation to fourth year medical students . Participants were r and omized to complete a tutorial in either lecture or multimedia format containing identical content . Upon completion , students answered five multiple choice questions assessing post-tutorial knowledge , and provided feedback on their allocated learning method . Marks revealed no significant difference between either group . All lecture c and i date s rated their teaching as good , compared with 89 % of the CAL group . All CAL users found multiple choice questions assessment useful , compared with 83 % of lecture participants . Both groups highlighted the importance of interaction . CAL complements other teaching methods , but should be seen as an adjunct to , rather than a replacement for , traditional methods , thus offering students a blended learning environment Background e-learning re sources may be beneficial for complex or conceptually difficult topics . Leukaemia is one such topic , yet there are no reports on the efficacy of e-learning for leukaemia . This study compared the learning impact on senior medical students of a purpose -built e-learning module on leukaemia , compared with existing online re sources . Methods A r and omised controlled trial was performed utilising volunteer senior medical students . Participants were r and omly allocated to Study and Control groups . Following a pre-test on leukaemia administered to both groups , the Study group was provided with access to the new e-learning module , while the Control group was directed to existing online re sources . A post-test and an evaluation question naire were administered to both groups at the end of the trial period . Results Study and Control groups were equivalent in gender distribution , mean academic ability , pre-test performance and time study ing leukaemia during the trial . The Study group performed significantly better than the Control group in the post-test , in which the group to which the students had been allocated was the only significant predictor of performance . The Study group ’s evaluation of the module was overwhelmingly positive . Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort , compared with existing online re sources . We believe that the interactivity , dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact . This has implication s for e-learning design in medicine and other disciplines We intended to clarify the influence of student academic ability on the effectiveness of CAI , using data of a study to assess the effectiveness of a new type of CAI software , cyberPatient ( CP ) , at Kochi Medical School ( KMS ) . A total of 59 third-year students were r and omly assigned to four groups : Group-1 used a textbook for self-instruction , Group-2 used CP , Group-3 used both types of learning material s , and Group-4 did not learn . Learning performance was evaluated by multiple-choice examination and OSCE . In order to clarify the influence of students ' academic ability on the effectiveness of CAI , statistical analyses were conducted , assigning students as either high or medium or low performance students . High performance students from Group-1 , -2 and -3 did not differ significantly in test performance after self-instruction . However , low performance students in Group-1 scored significantly lower than those in Group-2 and -3 . All students in Group-2 and -3 reported that CP stimulated willingness to learn and assisted underst and ing . The present analysis suggested that effectiveness of CAI might be associated with the academic ability of students A prospect i ve study was performed to better define the role of computers in teaching radiology to medical students . Two hundred twenty-five 3rd-year students were r and omly assigned to one of four groups and exposed to 10 radiology cases as well as to a voluntary weekly radiology lecture . Group A used computer-based cases with interactive elements ; group B used computer-based cases without interactive elements ; group C used paper-based cases with interactive elements ; and group D was not exposed to the cases and served as a control group . On a multiple-choice question test , groups A , B , and C showed significant improvement ( + 11.2 % , + 15.1 % , and + 13.0 % , respectively ) , whereas group D did not ( + 0.6 % ) . On an image interpretation test , group A showed the most improvement ( + 15.7 % [ P < .001 ] ) , followed by group B ( + 15.1 % [ P < .01 ] ) and group C ( + 10.2 % [ P < .05 ] ) ; group D showed no significant improvement ( + 8.5 % ) . No significant differences in the learning outcome were found between the two interactive groups ( computer based and paper based ) . Computer-based teaching with case studies ( with or without interactivity ) improves students ' problem-solving ability in radiology This study was design ed to assess whether a self- study interactive computer program is more effective than weekly seminars for teaching fundamental skills of electrocardiographic interpretation to junior medical students . Forty-two students were assigned to the computer and 41 to the seminar group . A test was given to each participant at the beginning and end of each rotation . The computer group used a computer-assisted learning program , and the seminar group met weekly with a cardiologist to review electrocardiograms . Attendance at a minimum of 80 % of the seminars or completion of 80 % of the computer-assisted learning program was required for inclusion in the statistical analysis . The mean difference in test scores before and after study was 5.69 for the computer group and 4.36 for the seminar group ( P less than .02 by one-tailed t-test ) . These results indicate that the computer group performed significantly better than the seminar group . We believe this difference to be educationally important The purpose of this study was to compare the performance of students exposed to two different instructional modalities for dental anatomy wax carving : CAI ( computer-assisted instruction ) using DVD technology , or traditional laboratory instruction . Students ' self- assessment scores were also compared to faculty scores , and students ' perceptions of their teaching modality were analyzed . Seventy-three first-year dental students ( response rate 81 percent ) participated in this r and omized single blind trial , in which faculty grade rs were blinded to student group assignment . There were no statistical differences , as determined by the Wilcoxon non-parametric test and a t-test , between the faculty grade s on the wax carving from the two teaching methods the students experienced . The student self- assessment s revealed higher mean grade s ( 3.0 for the DVD-only group and 3.1 for the traditional group ) than the faculty actual mean grade s ( 2.2 for both the DVD-only group and the traditional group ) by almost one grade level on a 4.0 grade scale . Similar percentages of students in the traditional group had either favorable or unfavorable perceptions of their learning experience , while more students in the DVD-only group reported favorable perceptions . Students from both groups said they wanted more faculty feedback in the course . Based on these objective and subjective data , merging CAI and traditional laboratory teaching may best enhance student learning needs Tooth Morphology is a computer-assisted learning program design ed to teach the anatomy of the adult dentition . The purpose of this study was to test whether Tooth Morphology could teach dental anatomy to first-year dental students as well as the traditional lecture . A r and omized controlled trial was performed with forty-five first-year dental students . The students were r and omly assigned to either the Tooth Morphology group ( n=23 ) , which used the computer-assisted learning program and did not attend lecture , or the lecture group ( n=22 ) , which attended the traditional lecture and did not use Tooth Morphology . The Tooth Morphology group had a final exam average of 90.0 ( st and ard deviation=5.2 ) , and the lecture group had a final exam average of 90.9 ( sd=5.3 ) . Analysis showed that the two groups ' scores were statistically equivalent ( p<0.05 ) , with a priori equivalence bounds around the difference between the groups set at + /-5 points . It was concluded that Tooth Morphology taught the anatomy of the adult dentition as well as traditional lecture , as measured by exams . Based on the results of this study and student feedback , Tooth Morphology , in combination with interactive class meetings , has replaced the traditional dental anatomy lectures Background Tanzania , like many developing countries , faces a crisis in human re sources for health . The government has looked for ways to increase the number and skills of health workers , including using distance learning in their training . In 2008 , the authors review ed and assessed the country 's current distance learning programmes for health care workers , as well as those in countries with similar human re source challenges , to determine the feasibility of distance learning to meet the need of an increased and more skilled health workforce . Methods Data were collected from 25 distance learning programmes at health training institutions , universities , and non-governmental organizations throughout the country from May to August 2008 . Methods included internet research ; desk review ; telephone , email and mail-in surveys ; on-site observations ; interviews with programme managers , instructors , students , information technology specialists , preceptors , health care workers and Ministry of Health and Social Welfare representatives ; and a focus group with national HIV/AIDS care and treatment organizations . Results Challenges include lack of guidelines for administrators , instructors and preceptors of distance learning programmes regarding roles and responsibilities ; absence of competencies for clinical components of curricula ; and technological constraints such as lack of access to computers and to the internet . Insufficient funding result ed in personnel shortages , lack of appropriate training for personnel , and lack of material s for students . Nonetheless , current and prospect i ve students expressed overwhelming enthusiasm for scale-up of distance learning because of the unique financial and social benefits offered by these programs . Participants were retained as employees in their health care facilities , and remained in their communities and supported their families while advancing their careers . Space in health training institutions was freed up for new students entering in-residence pre-service training . Conclusions A blended print-based distance learning model is most feasible at the national level due to current re source and infrastructure constraints . With an increase in staffing ; improvement of infrastructure , coordination and curricula ; and de central ization to the zonal or district level , distance learning can be an effective method to increase both the skills and the numbers of qualified health care workers capable of meeting the health care needs of the Tanzanian population Objective : To evaluate whether computer-based learning ( CBL ) improves newly acquired knowledge and is an effective strategy for teaching prenatal ultrasound diagnostic skills to third-year medical students when compared with instruction by traditional paper-based methods ( PBM ) . Study Design : We conducted a r and omized , prospect i ve study involving volunteer junior ( 3rd year ) medical students consecutively rotating through the Obstetrics and Gynecology clerkship during six months of the 2005–2006 academic year . The students were r and omly assigned to permuted blocks and divided into two groups . Half of the participants received instruction in prenatal ultrasound diagnostics using an interactive CBL program ; the other half received instruction using equivalent material by the traditional PBM . Outcomes were evaluated by comparing changes in pre-tutorial and post instruction examination scores . Results : All 36 potential participants ( 100 % ) completed the study curriculum . Students were divided equally between the CBL ( n = 18 ) and PBM ( n = 18 ) groups . Pre-tutorial exam scores ( mean±s.d . ) were 44%±11.1 % for the CBL group and 44%±10.8 % for the PBL cohort , indicating no statistically significant differences ( p>0.05 ) between the two groups . After instruction , post-tutorial exam scores ( mean±s.d . ) were increased from the pre-tutorial scores , 74%±11 % and 67%±12 % , for students in the CBL and the PBM groups , respectively . The improvement in post-tutorial exam scores from the pre-test scores was considered significant ( p<0.05 ) . When post-test scores for the tutorial groups were compared , the CBL subjects achieved a score that was , on average , 7 percentage points higher than their PBM counterparts , a statistically significant difference ( p < 0.05 ) . Conclusion : Instruction by either CBL or PBM strategies is associated with improvements in newly acquired knowledge as reflected by increased post-tutorial examination scores . Students that received CBL had significantlyhigher post-tutorial exam scores than those in the PBM group , indicating that CBL is an effective instruction strategy in this setting Background Medical education is increasingly being conducted in community-based teaching sites at diverse locations , making it difficult to provide a consistent curriculum . We conducted a r and omized trial to assess whether students who viewed digital lectures would perform as well on a measure of cognitive knowledge as students who viewed live lectures . Students ' perceptions of the digital lecture format and their opinion as whether a digital lecture format could serve as an adequate replacement for live lectures was also assessed . Methods Students were r and omized to either attend a lecture series at our main campus or view digital versions of the same lectures at community-based teaching sites . Both groups completed the same examination based on the lectures , and the group viewing the digital lectures completed a feedback form on the digital format . Results There were no differences in performance as measured by means or average rank . Despite technical problems , the students who viewed the digital lectures overwhelmingly felt the digital lectures could replace live lectures . Conclusions This study provides preliminary evidence digital lectures can be a viable alternative to live lectures as a means of delivering didactic presentations in a community-based setting Background and objective Fibreoptic intubation is an essential skill in anaesthesiology that is challenging to learn in the clinical setting . The goal of this study was to evaluate ‘ virtual fibreoptic intubation ’ ( VFI ) software as an adjunct to the traditional fibreoptic intubation teaching . Methods After informed consent , 42 undergraduate medical students were r and omized into two groups . The ‘ control group ’ was taught conventionally by an expert bronchoscopist with a 1 h lecture . In addition to the didactic lecture by the expert , the ‘ VFI group ’ was given the VFI CD-ROM , and students self-trained with the software until they felt competent performing a virtual fibreoptic bronchoscopy on the normal patient models . Students were evaluated 2 weeks later on their first orotracheal fibreoptic intubation of an airway manikin . The primary endpoint was success , as evaluated by a staff anaesthesiologist blinded to the group of teaching . Fibreoptic intubation ability was the secondary endpoint . Results The fibreoptic intubation success rate was significantly higher in the VFI group than in the control group ( 81 versus 52 % , P < 0.05 ) . Among 10 failures in the control group , nine were due to oesophageal intubation as compared with only one out of four in the VFI group . Among four failures in the VFI group , three were because of taking longer than 4 min as compared with only one out of 10 in the control group . The VFI group tended towards better ability in the procedural skills of fibreoptic intubation than the control group . Conclusion Self-training in fibreoptic intubation with the VFI software may improve the acquisition of fibreoptic intubation skills Background : Well- design ed computer-assisted instruction ( CAI ) can potentially transform medical education . Yet little is known about whether specific design features such as direct manipulation of the content yield meaningful gains in clinical learning . We design ed three versions of a multimedia module on the abdominal exam incorporating different types of interactivity . Methods : As part of their physical diagnosis course , 162 second-year medical students were r and omly assigned ( 1:1:1 ) to Watch , Click or Drag versions of the abdominal exam module . First , students ’ prior knowledge , spatial ability , and prior experience with abdominal exams were assessed . After using the module , students took a posttest ; demonstrated the abdominal exam on a st and ardized patient ; and wrote structured notes of their findings . Results : Data from143 students were analyzed . Baseline measures showed no differences among groups regarding prior knowledge , experience , or spatial ability . Overall there was no difference in knowledge across groups . However , physical exam scores were significantly higher for students in the Click group . Conclusions : A mid-range level of behavioral interactivity was associated with small to moderate improvements in performance of clinical skills . These improvements were likely mediated by enhanced engagement with the material , within the bounds of learners ’ cognitive capacity . These findings have implication s for the design of CAI material s to teach procedural skills BACKGROUND Computerised learning clearly offers exciting potential for improving student learning , either as an aid to or as a replacement for traditional formats , or for the development of innovative approaches . However , rigorous evaluation of the utility of computer-aided learning ( CAL ) in enhancing student learning can be difficult . Many studies have compared CAL to more traditional learning formats , but there is little evidence to show which style of CAL leads to the best learning outcomes . AIM This study aim ed to test the hypothesis that a CAL tutorial , in which the learner actively interacts with the computer , will result in superior learning ( ability to apply and retain knowledge ) to that obtained in more passive CAL formats . METHODS Third year medical undergraduates at Adelaide University , South Australia were r and omly assigned to 4 groups . Following a pretest , only students in the " didactic " , " problem-based " and " free text " groups had 2 weeks of free access to a neuroradiology CAL tutorial in their assigned format . Tutorial access was denied to all students 2 weeks before post-testing . Learning was quantified by comparing the post- to pretest scores for each of the 4 groups . RESULTS After active interaction with the computer material , students in the free text group demonstrated a statistically significant improvement in their ability to apply and retain knowledge compared to the control group , but no advantage compared to the didactic group . CONCLUSIONS While users of an interactive CAL tutorial demonstrated significant learning gains compared to non-CAL users , these gains were not superior to those achieved from non-interactive CAL . When evaluating education interventions such as CAL packages , it is important to use a valid assessment tool to measure learning The purpose of this study was to develop and test a CD-ROM tutorial for nursing students to educate them on how the rules and regulations of the Health Insurance Portability and Accountability Act ( HIPAA ) affect them as they engage in patient care activities in hospitals . The project was completed in two parts , the first of which was production of a st and -alone , audio lecture , image and text self-instruction on CD-ROM to distribute to students as they began their clinical experience . The second part compared the effectiveness of learning the HIPAA content via CD-ROM to a text-directed , self study method . Students were pretested and r and omly assigned to one of the types of instruction based on their seminar group assignment . One group received the CD-ROM , Getting Started with HIPAA , along with a journal article on HIPAA , while the other ( control ) group received only the journal article . All students were instructed to prepare for a test on their underst and ing about HIPAA by the end of the clinical rotation . The test was analyzed , and items clarified to yield a reliable Web-based examination with 20 questions , 18 of which were used in the analysis . The students ' scores were analyzed before and after the instruction , and the methods of instruction were compared . The study findings demonstrated significant differences between experimental-group and control-group students ' performance on a knowledge test of HIPAA , as well as overall satisfaction with learning the material by CD-ROM among students who used it . The tutorial is now available for all students , and the Web-based examination provides automatic scoring to a preestablished competence level This study compared the effectiveness of three instructional intervention strategies for teaching nursing students about congenital heart disease ( CHD ) . They are : ( 1 ) computer-assisted instruction ( CAI ) , ( 2 ) traditional class room lecture ( TCL ) ; and ( 3 ) the combination of CAI and TCL . The subjects were associate degree nursing ( ADN ) students enrolled in a pediatric nursing course at the University of Cincinnati Raymond Walters College . Differences between pre- and post-scores on a 20-item multiple choice test were analyzed by analysis of variance . There was a significant improvement in scores for all groups but no significant difference in improvement in scores between the CAI group and the TCL group . The CAI/TCL group showed significant improvement in scores compared with the other two groups . The research er concluded that when teaching strategies are comparable , CAI is as effective as TCL . Used together , a significant improvement is seen in student performance than when either strategy is used alone A CD-ROM and printed material on San-Yin-Jiao pressure to lessen labor pain for women were developed as formal didactic instruction using the same content . A prospect i ve , r and omized , double-blind study was conducted to compare self-learning outcomes using the software and the printed material s. Eighty third-year student nurses were r and omly allocated to either the CD-ROM group or printed material group . A test was administered after 1 week of study time . A p value of < .05 was considered statistically significant . Results showed no significant differences between the two groups in self-learning measures . Text-based learning seems to be a convenient educational method because it can be used at any time in any place . However , with more time and facilities available , CD-ROMs may be as effective as traditional learning methods and can be an alternative tool PURPOSE This study aim ed to compare the effects of computer-assisted , text-based and computer- and -text learning conditions on the performances of 3 groups of medical students in the pre- clinical years of their programme , taking into account their academic achievement to date . A fourth group of students served as a control ( no- study ) group . METHOD Participants were recruited from the pre- clinical years of the training programmes in 2 medical schools in Japan , Jichi Medical School near Tokyo and Kochi Medical School near Osaka . Participants were r and omly assigned to 4 learning conditions and tested before and after the study on their knowledge of and skill in performing an abdominal examination , in a multiple-choice test and an objective structured clinical examination ( OSCE ) , respectively . Information about performance in the programme was collected from school records and students were classified as average , good or excellent . Student and faculty evaluations of their experience in the study were explored by means of a short evaluation survey . RESULTS Compared to the control group , all 3 study groups exhibited significant gains in performance on knowledge and performance measures . For the knowledge measure , the gains of the computer-assisted and computer-assisted plus text-based learning groups were significantly greater than the gains of the text-based learning group . The performances of the 3 groups did not differ on the OSCE measure . Analyses of gains by performance level revealed that high achieving students ' learning was independent of study method . Lower achieving students performed better after using computer-based learning methods . CONCLUSION The results suggest that computer-assisted learning methods will be of greater help to students who do not find the traditional methods effective . Explorations of the factors behind this are a matter for future research INTRODUCTION H and held computers ( PDAs ) uploaded with clinical decision support software ( CDSS ) have the potential to facilitate the adoption of evidence -based medicine ( EBM ) at the point-of-care among undergraduate medical students . Further evaluation of the usefulness and acceptability of these tools is required . METHODS All 169 Year 4 undergraduate medical students at the University of Hong Kong completed a post-r and omised controlled trial survey . Primary outcome measures were CDSS/PDA usefulness , satisfaction , functionality and utilisation . Focus groups were also conducted to derive complementary qualitative data on the students ' attitudes towards using such new technology . RESULTS Overall , the students found the CDSS/PDA useful ( mean score = 3.90 out of 6 , 95 % confidence interval ( CI ) = 3.78 , 4.03 ) . They were less satisfied with the functional features of the CDSS ( mean score = 3.45 , 95 % CI = 3.32 , 3.59 ) and the PDA ( mean score = 3.51 95 % CI = 3.40 , 3.62 ) . Utilisation was low , with the average frequency of use less than once per week . Although students reported a need for information in patient care at least once daily , they infrequently used the CDSS in a clinical setting ( 20.4 + /- 10.4 % of the time ) , with an average information retrieval success rate of 37.6 + /- 22.1 % requiring 63.7 + /- 86.1 seconds . Multivariable regression shows that higher perceived CDSS/PDA usefulness was associated with more supportive faculty attitudes , greater knowledge of EBM , better computer literacy skills and increased use in a clinical setting . Greater satisfaction with the CDSS/PDA was associated with increased use in a clinical setting and higher successful search rates . Qualitative results were consistent with these quantitative findings and yielded additional information on students ' underlying feelings that may explain the observations . CONCLUSIONS While PDAs uploaded with the CDSS are able to provide students with better access to high quality information , improvements in faculty attitudes , students ' knowledge of EBM and computer literacy skills , and having the CDSS specially design ed for undergraduate use are essential to increasing student adoption of such point-of-care tools & NA ; The purpose of this study was to compare the effectiveness of an interactive , multimedia CD‐ROM with traditional methods of teaching the skill of performing a 12‐lead ECG . A r and omized pre/posttest experimental design was used . Seventy‐seven baccalaureate nursing students in a required , senior‐level critical‐care course at a large midwestern university were recruited for the study . Two teaching methods were compared . The traditional method included a self‐ study module , a brief lecture and demonstration by an instructor , and h and s‐on experience using a plastic manikin and a real 12‐lead ECG machine in the learning laboratory . The second method covered the same content using an interactive , multimedia CD‐ROM embedded with virtual reality and supplemented with a self‐ study module . There were no significant ( p < .05 ) baseline differences in pretest scores between the two groups and no significant differences by group in cognitive gains , student satisfaction with their learning method , or perception of self‐efficacy in performing the skill . Overall results indicated that both groups were satisfied with their instructional method and were similar in their ability to demonstrate the skill correctly on a live , simulated patient . This evaluation study is a beginning step to assess new and potentially more cost‐effective teaching methods and their effects on student learning outcomes and behaviors , including the transfer of skill acquisition via a computer simulation to a real patient Discussing end-of-life decisions with cancer patients is a crucial skill for physicians . This article reports findings from a pilot study evaluating the effectiveness of a computer-based decision aid for teaching medical students about advance care planning . Second-year medical students at a single medical school were r and omized to use a st and ard advance directive or a computer-based decision aid to help patients with advance care planning . Students ' knowledge , skills , and satisfaction were measured by self-report ; their performance was rated by patients . 121/133 ( 91 % ) of students participated . The Decision-Aid Group ( n = 60 ) outperformed the St and ard Group ( n = 61 ) in terms of students ´ knowledge ( p < 0.01 ) , confidence in helping patients with advance care planning ( p < 0.01 ) , knowledge of what matters to patients ( p = 0.05 ) , and satisfaction with their learning experience ( p < 0.01 ) . Likewise , patients in the Decision Aid Group were more satisfied with the advance care planning method ( p < 0.01 ) and with several aspects of student performance . Use of a computer-based decision aid may be an effective way to teach medical students how to discuss advance care planning with cancer patients Background : Although animations may intuitively seem more effective than static graphics for teaching , there is no clear-cut evidence for the superiority of simple computer-based animations in medical education . Aims : We investigated whether simple animations are better than static graphics as an aid to medical students in learning home safety assessment , an important part of geriatric curriculum . Methods : We used two versions of an interactive online module , one that depicted common home safety issues in static graphics and the other in animations . We r and omized first-year medical students who agreed to participate into two groups . After the module , students completed a cognitive burden scale and a st and ardized competency assessment test in which they had to identify the salient home safety issues and give recommendations based on the hazards . We also captured time spent on task . Results and conclusions : We found no significant differences between the groups in the cognitive burden level , competency assessment scores , and time spent on task . The much cheaper-to-produce static graphics were equally effective as simple animations in this medical education scenario BACKGROUND High quality health care dem and s a nursing workforce with sound clinical skills . However , the clinical competency of newly qualified nurses continues to stimulate debate about the adequacy of current methods of clinical skills education and emphasises the need for innovative teaching strategies . Despite the increasing use of e-learning within nurse education , evidence to support its use for clinical skills teaching is limited and inconclusive . OBJECTIVES This study tested whether nursing students could learn and retain the theory and skill of h and washing more effectively when taught using computer-assisted learning compared with conventional face-to-face methods . DESIGN The study employed a two group r and omised controlled design . The intervention group used an interactive , multimedia , self-directed computer-assisted learning module . The control group was taught by an experienced lecturer in a clinical skills room . Data were collected over a 5-month period between October 2004 and February 2005 . Knowledge was tested at four time points and h and washing skills were assessed twice . SETTING AND PARTICIPANTS Two-hundred and forty-two first year nursing students of mixed gender ; age ; educational background and first language study ing at one British university were recruited to the study . Participant attrition increased during the study . RESULTS Knowledge scores increased significantly from baseline in both groups and no significant differences were detected between the scores of the two groups . Skill performance scores were similar in both groups at the 2-week follow-up with significant differences emerging at the 8-week follow-up in favour of the intervention group , however , this finding must be interpreted with caution in light of sample size and attrition rates . CONCLUSION The computer-assisted learning module was an effective strategy for teaching both the theory and practice of h and washing to nursing students and in this study was found to be at least as effective as conventional face-to-face teaching methods OBJECTIVES Computers are a part of everyday life and offer an exciting way of learning . The aim of our study was to determine the effectiveness of teaching undergraduate endocrinology using a Computer Assisted Learning ( CAL ) programme BACKGROUND The use of computer-based instruction ( CBI ) in physical therapy education is growing , but its effectiveness compared to lecture is undefined . This study compared CBI to lecture in an introductory neuroscience course for students in their first year of a 3 year professional program leading to the Doctor of Physical Therapy Degree . SUBJECTS Twenty-eight students participated in 2003 and 34 in 2004 . METHODS A r and omized , cross-over design was employed . The course was divided into two sections with an exam after each . Students in one group participated in CBI during the first half of the course and lecture during the second half with the order of participation reversed for the other group . A 6 months post-course review exam was also administered . Exam scores , study time , and student opinions regarding teaching methods were collected after each half of the course . Course development costs for both teaching approaches were also documented . RESULTS There were no statistically significant differences in exam scores between participant groups . CBI students spent less time study ing . Student did not distinguish a major preference for either instruction method . Many students preferred that CBI be used as a complementary rather than mutually exclusive instructional method . Lecture-based instruction was much less expensive than CBI . CONCLUSION Lecture-based instruction was more cost effective than CBI , but CBI was more time efficient in terms of student learning STUDY AIM The primary purpose of this study was to compare two , shorter , self-directed methods of cardiopulmonary resuscitation ( CPR ) education for healthcare professionals ( HCP ) to traditional training with a focus on the trainee 's ability to perform two-person CPR . METHODS First-year medical students with either no prior CPR for HCP experience or prior training greater than 5 years were r and omized to complete one of three courses : 1 ) HeartCode BLS System , 2 ) BLS Anytime , or 3 ) Traditional training . Only data from the adult CPR skills testing station was review ed via video recording by certified CPR instructors and the Laerdal PC Skill Reporter software program ( Laerdal Medical , Stavanger , Norway ) . RESULTS There were 180 first-year medical students who met inclusion criteria : 68 were HeartCode BLS System , 53 BLS Anytime group , and 59 traditional group Regarding two-person CPR , 57 ( 84 % ) of Heartcode BLS students and 43 ( 81 % ) of BLS Anytime students were able to initiate the switch compared to 39 ( 66 % ) of traditional course students ( p = 0.04 ) . There were no significant differences in the quality of chest compressions or ventilations between the three groups . There was a trend for a much higher CPR skills testing pass rate for the traditional course students . However , failure to " clear to analyze or shock " while using the AED was the most common reason for failure in all groups . CONCLUSION The self-directed learning groups not only had a high level of success in initiating the " switch " to two-person CPR , but were not significantly different from students who completed traditional training Abstract Background H and -held mobile learning technology provides opportunities for clinical ly relevant self-instructional modules to augment traditional bedside teaching . Using this technology as a teaching tool has not been well studied . We sought to evaluate medical students ’ case presentation performance and perception when viewing short , just-in-time mobile learning videos using the iPod touch prior to patient encounters . Methods Twenty-two fourth-year medical students were r and omized to receive or not to receive instruction by video , using the iPod Touch , prior to patient encounters . After seeing a patient , they presented the case to their faculty , who completed a st and ard data collection sheet . Students were surveyed on their perceived confidence and effectiveness after using these videos . Results Twenty-two students completed a total of 67 patient encounters . There was a statistically significant improvement in presentations when the videos were viewed for the first time ( p = 0.032 ) . There was no difference when the presentations were summed for the entire rotation ( p = 0.671 ) . The reliable ( alpha = 0.97 ) survey indicated that the videos were a useful teaching tool and gave students more confidence in their presentations . Conclusions Medical student patient presentations were improved with the use of mobile instructional videos following first time use , suggesting mobile learning videos may be useful in medical student education . If direct bedside teaching is unavailable , just-in-time iPod touch videos can be an alternative instructional strategy to improve first-time patient presentations by medical students We have developed a computer assisted learning package for teaching clinical medical students about familial breast cancer . It explains the principles of genetic predisposition to breast cancer , the association with other cancers , the principles of family history taking and confirmation , risk assessment and possible interventions . Clinical medical students were r and omised to either conventional teaching or CAL , 48 students attended the evaluation session . Students r and omised to conventional teaching received a 20 min mini-lecture , those r and omised to CAL completed the package with technical , but not academic support available . At the end of the intervention both groups of students completed a short written assessment of acceptability and knowledge and underst and ing of breast cancer genetics . There was no significant difference between the CAL and mini-lecture groups in terms of marks or acceptability . Thus CAL appears to be an acceptable and effective method of teaching clinical medical students about familial breast cancer . Although time consuming to develop , CAL can be used in a variety of setting s to increase curriculum flexibility . Methods of motivating students to complete the CAL , and of providing educational support are being explored PURPOSE The current model of undergraduate medical education is under debate since knowledge retention and student interest seem to be decreasing . To clarify this situation we developed and evaluated a computer aided learning program using a multimedia presentation about prostate cancer for undergraduate teaching in urology . MATERIAL S AND METHODS A total of 60 medical students from years 2 and 3 were divided into group 1 - 31 who used the multimedia program and group 2 - 29 who attended a st and ard lecture on the same subject . At the end the level of knowledge acquisition for the 2 groups was evaluated by a multiple choice test . Group 1 students also answered a question naire about subjective feelings on computer based teaching . RESULTS Test performance in groups 1 and 2 was similar ( 60 % vs 62 % correct answers , p > 0.05 ) . On the other h and , 23 of 31 students using the multimedia program believed that it did not adequately replace the instructor and interaction with a mentor still seems to be relevant . CONCLUSIONS According to this study computers and multimedia programs can be used for undergraduate education in urology , providing that direct contact with an instructor is concomitantly offered to students RATIONALE AND OBJECTIVE We sought to determine which is more effective in increasing skill in radiograph interpretation : a linear ( PowerPoint-style ) computer tutorial that locks the student into a fixed path through the material or a branched ( Web-style ) version that allows r and om access . MATERIAL S AND METHODS We prepared a computer tutorial for learning how to interpret cervical spine radiographs . The tutorial has 66 screens including radiographs or graphics on almost every page and five unknown radiographs for the student to interpret . One version ( linear ) presents the material in a linear sequence with the unknown radiographs heading up " chapters " detailing an important aspect of the task . In the second ( branched ) version , the same 66 screens were accessed through hyperlinks in a frame beside the unknown radiographs . One hundred thirty-nine medical students at two sites participated in a r and omized single-blinded controlled experiment . They interpreted cervical spine images as a pretest and then completed one of the two tutorial versions . Afterward , they did the same examination as a post-test . RESULTS The tutorial was successful , in both layouts , in improving the subjects ' ability to interpret cervical spine radiograph images ( effect size 2.1 ; 95 % confidence interval 1.7 - 2.5 ) . However , the layout did not make a difference to their gain in ability . Students in the linear group completed the tutorial in 17 % less time ( P < .001 ) but were slightly less likely to rate the tutorial as " valuable . " CONCLUSION For these novice learners , computer tutorial layout does not affect knowledge gain . Students may be more satisfied with the linear layout , but in time-pressured situations , the Web-style layout may be preferable because it is more efficient Advances in computer technology , such as the portable and affordable iPodTM , allow students to view lectures anywhere at any time . iPodsTM are of special interest for nurse educators who strive to meet dem and s posed by a critical nursing shortage . A mixed- methods pilot study was conducted to assess whether iPodTM could be an effective teaching tool for medical-surgical nursing lectures . In a r and omized study with 35 participants , together with eight students having their own iPodsTM , grade s of students given pre-recorded class lectures on iPodsTM were compared with grade s of those who attended lectures without iPodsTM . Learning styles , amount and use of students devoted to iPodTM lectures were considered as well as grade s. Most results were not significant , but there was some evidence that the control groups who attended classroom lectures received better grade s than iPodTM users , and individuals who used iPodTM more frequently before the final exam received lower grade s. These somewhat surprising results suggest the need for further research in the use of this technology as a re source for nursing education delivery OBJECTIVE To evaluate a novel method of teaching laryngeal anatomy . DESIGN Prospect i ve , r and omized , controlled trial . SETTING University educational program . METHODS Computer model development : A three-dimensional ( 3D ) educational computer model of the larynx was created from high-resolution computed tomography and magnetic resonance images of cadaveric necks using segmentation software ( Amira ) ( Visage Imaging , Inc. , Carlsbad , CA ) . E-learning authoring software ( Articulate , Articulate Global , Inc , New York , NY ) then was used to make the model interactive and multimedia . The model was launched on a Web-based platform . Model evaluation : One hundred students ( age 23.8 + /- 2.2 years ; 55 % male ) were r and omized to either the 3D computer model group ( 3D group ) ( n = 50 ) or the st and ard written instruction group ( SWI group ) ( n = 50 ) . MAIN OUTCOME MEASURES The primary outcome measure was the score on a 20- question laryngeal anatomy test ; the secondary outcome measure was a student opinion question naire . RESULTS The mean score on the laryngeal anatomy test was 14.2 + /- 2.8 ( 72.0 + /- 15.1 % ) . The mean score for the 3D group was 13.6 + /- 3.0 ( 67.0 + /- 16.1 % ) versus 14.8 + /- 2.5 ( 76.0 + /- 12.7 % ) for the SWI group ( t = 2.194 , df = 98 , p < .031 ) . A majority of students felt that the 3D model was effective , clear , user-friendly , and a preferred supplement to traditional methods of instruction . The 3D group rated the computer model more enjoyable than the SWI group . CONCLUSIONS A 3D educational computer model of the larynx was not shown to be superior to written lecture notes in its efficacy in teaching anatomy ; however , it was judged to be a preferred and valuable supplement to traditional teaching methods BACKGROUND Practice using computer-based video instruction ( CBVI ) leads to improvements in surgical skills proficiency . This study investigated the benefits of the introduction of ( a ) learner-directed , interactive video training and ( b ) the addition of expert instruction on the learning and retention of the basic surgical skills of suturing and knot-tying in medical students . METHODS Using bench models , students were pre-tested on a suturing and knot-tying skill after viewing an instructional video . The students were then r and omly assigned to three practice conditions : self- study with video ; self- study with interactive video ; or the combination of self- study with interactive video with the addition of subsequent expert instruction . All participants underwent 18 trials of practice in their assigned training condition . The effectiveness of training was assessed by an immediate post-test and a retention test one month later . Performance was evaluated using expert- and computer-based assessment s. Data were analyzed using repeated- measures ANOVA . RESULTS There were no differences in expert- and computer-based assessment s between groups at pre-test . Although all three groups demonstrated significant improvements on both measures between the pre- and post-tests as well as between pre-tests and retention-tests ( P < .01 ) , no significant differences were detected among the three groups . CONCLUSION This study shows that in surgical novices , neither the inclusion of expert instruction nor the addition of self-directed interaction with video leads to further improvements in skill development or retention . These findings further support the possible implementation of CBVI within surgical skills curricula In the study reported here , third-year medical students in an internal medicine clerkship were r and omly assigned to computer-assisted instruction ( CAI ) and to tutorials to compare the effectiveness of these methods in teaching hematology and oncology topics . A multiple-choice test was used to assess the students ' knowledge after instruction , and the students completed a 14-item question naire concerning their opinions of CAI . No statistically significant difference was found between the test scores of the students using CAI and those in the tutorials for oncology ; but in hematology the students in the tutorials had higher scores than those using CAI . The study design does not permit a definite explanation of the disparity in outcome for the two topics , but it is possible that the effectiveness of the presentations in the two sections was different . There was no statistically significant correlation between the time spent in the teaching setting and the score attained . The students did not consider CAI more effective than the tutorials but rather seemed to view it as a supplement to traditional teaching by lectures , textbooks , and study ing from notes BACKGROUND Computer-based teaching may allow effective teaching of important psychiatric knowledge and skills . AIMS To investigate the effectiveness and acceptability of computer-based teaching . METHOD A single-blind , r and omized , controlled study of 166 undergraduate medical students at the University of Leeds , involving an educational intervention of either a structured lecture or a computer-based teaching package ( both of equal duration ) . RESULTS There was no difference in knowledge between the groups at baseline or immediately after teaching . Both groups made significant gains in knowledge after teaching . Students who attended the lecture rated their subjective knowledge and skills at a statistically significantly higher level than students who had used the computers . Students who had used the computer package scored higher on an objective measure of assessment skills . Students did not perceive the computer package to be as useful as the traditional lecture format , despite finding it easy to use and recommending its use to other students . CONCLUSIONS Medical students rate themselves subjectively as learning less from computer-based as compared with lecture-based teaching . Objective measures suggest equivalence in knowledge acquisition and significantly greater skills acquisition for computer-based teaching AIM The aim of this study was to evaluate the place of computer-aided learning in a basic science course in the undergraduate medical curriculum at the University of Adelaide . METHODS A software program was written which would allow students to study the anatomy and physiology of the liver and biliary tree in three different styles . Identical content was produced , matched for each style ( problem-based , didactic and free text response ) and students r and omly allocated to one of four groups ( three computer and one control ) . Students were tested before and after access to the program . RESULTS Ninety second-year students completed the study . Those students who had access to the material in the problem-based and free text response styles did no better in the post- study test than the controls , whilst the group who had studied the didactically presented computer material performed significantly better than the other three groups . All three computer groups accessed the material on a similar number of occasions , but the group who had access to the free text entry program spent significantly less time on computer study . CONCLUSIONS If computer material s are to be provided as a learning re source for the basic medical sciences , provision must be made for the style of teaching of the course and the style of learning of the students attending that course AIM To determine whether the students enrolled in the computer-based teaching program would take the final examination in pathology earlier than those who studied according to the previous traditional program . METHODS The study included all medical students enrolled in the pathology course at the Zagreb University School of Medicine , Zagreb , Croatia , between 1995/96 and 2000/01 academic years . In the fall of 1998 , computer-based teaching program from the University of Kansas was implemented at the Zagreb University School of Medicine , with 48 of the class of 225 students ( 20 % ) r and omly enrolled in the program . The remaining 80 % of students of the same class were enrolled in the traditional teaching program used at the Zagreb University School of Medicine . We compared the success of these two groups of students at the final pathology examination in the first term . Following this initial observational period , all students in the next two years ( 1999/00 and 2000/01 ) , were enrolled in the computer-based teaching program . Pass rates of these students at the final examination taken in the first term were compared with the pass rates of students who studied according to the traditional teaching program during the period from 1995 to 1998 . RESULTS In 1998 , 58.3 % of students from the computer-based teaching program group chose to take the final examination in the first term , compared with only 32.2 % of students from the traditional teaching program group ( chi(2 ) (1)=10.97 , P<0.001 ) . Students in the computer based program had better final examination mean scores ( -/+ st and ard deviation ) than students in the traditional program ( 81.9-/+9.8 and 73.3-/+14.2 , respectively ; t=2.908 , P=0.005 ) . Upon the implementation of the computer-based teaching program for the entire class in 1999 and 2000 , the number of students taking the final examination in the first term increased more than we expected on the basis of the data from the academic years 1995 to 1998 ( chi(2 ) (5)=39.60 , P<0.001 ) . CONCLUSION The computer-based program introduced at the Zagreb University School of Medicine in 1998 had a positive effect on medical students , as evidence d by the fact that more students chose to take the final pathology examination in the first term and more of them passed the examination in the first attempt than those in the traditional teaching program OBJECTIVE To compare the teaching value of one session of computer-guided solo instruction in exposure therapy for phobias with that of one face-to-face small-group tutorial . DESIGN Non-blind , r and omized , controlled study . SETTING King 's College Hospital Medical School , London . PARTICIPANTS Thirty-seven third-year medical students and 11 behaviour therapists . MAIN OUTCOME MEASURES Seventy-five true/false multiple choice questions relating to ( b ) below answered at pre- and post-teaching by students and just once by behaviour therapists to obtain ' expert ' scores ; pre- and post-teaching ratings of interest in behaviour therapy and post-teaching ratings of educational and enjoyment value . EDUCATIONAL INTERVENTIONS : ( a ) All students had a 20-minute group lecture on basic concepts and historical aspects just before r and omization to : ( b ) 90 min of either solo computer or group face-to-face tutorial teaching . Computer instruction used a short version of ' FearFighter'- a self-help computer system for people suffering from phobias . RESULTS Solo computer instruction taught exposure therapy principles effectively but improved multiple choice question scores marginally less than did small-group tutorial teaching . Tutorial teaching required 5 times more teacher time but led to knowledge scores that did not differ significantly from those of behaviour therapists . Students clearly rated face-to-face small-group tutorial teaching as more enjoyable . CONCLUSION The knowledge gain from a solo computer session resembled that from a small-group face-to-face tutorial , and required far less teacher time , but was less enjoyable . Enjoyment might rise if the computer session was group-oriented and aim ed at students rather than patients . In general computer teaching might be best used to complement rather than replace conventional teaching OBJECTIVES To compare 2 educational programmes for teaching evidence -based medicine ( EBM ) . DESIGN Prospect i ve r and omised controlled trial accompanied by a qualitative evaluation . SETTING University of Oslo , Norway , 2002 - 03 . PARTICIPANTS A total of 175 students entered the study . All tenth semester medical students from 3 semesters were eligible for inclusion if they completed baseline assessment and consent forms and either attended teaching on the first day of the semester or gave reasons for their absence on the first day in advance . Interventions One intervention was based on computer-assisted , self-directed learning ( self-directed intervention ) , whilst the other was organised as workshops based on social learning theory ( directed intervention ) . Both educational interventions consisted of 5 half-day sessions . MAIN OUTCOME MEASURES The primary outcomes were knowledge about EBM and skills in critical appraisal . A secondary outcome measured attitudes to EBM . Outcomes were compared on an intention-to-treat basis using a stratified Wilcoxon rank-sum test . RESULTS There were no differences in outcomes for the 2 study groups in terms of EBM knowledge ( mean deviation 0.0 [ 95 % confidence interval - 1.0 , 1.0 ] , P = 0.8 ) , critical appraisal skills ( MD 0.1 [ 95 % CI - 0.9 , 1.1 ] , P = 0.5 ) , or attitudes to EBM ( MD - 0.3 [ 95 % CI - 1.4 , 0.8 ] , P = 0.5 ) . Follow-up rates were 96 % , 97 % and 63 % , respectively . CONCLUSIONS This trial and its accompanying qualitative evaluation suggest that self-directed , computer-assisted learning may be an alternative format for teaching EBM . However , further research is needed to confirm this and investigate alternative educational models OBJECTIVE To identify whether there was measurable impact of a specific computer-assisted learning ( CAL ) package , " Virtual Rheumatology , " on the learning of musculoskeletal examination skills by medical students . METHODS We conducted 2 parallel , cluster-r and omized controlled trials using undergraduate curricula at 2 locations : Newcastle and London , UK . Medical students attending a musculoskeletal rotation were allocated to the intervention ( Virtual Rheumatology CD ) or the control arm of the study by placement group . A formative 14-item objective structured clinical examination ( OSCE ) assessment on the examination of shoulder and /or knee joints was the main outcome measure at Newcastle . At London , a 17-item knee station formed part of the summative OSCE . We also used a question naire including a 15-item confidence log ( C-Log ) for self assessment of musculoskeletal examination skills and knowledge . Analysis was by intention to teach . RESULTS At Newcastle , there were 112 students in the CD allocated group and 129 in the non-CD group . The CD allocated group performed significantly better on the OSCE ( P = 0.002 ) and C-Log ( P = 0.005 ) than the non-CD group . At London , there were 48 students in the CD allocated group and 65 in the non-CD group . The CD allocated group performed better on the knee OSCE than the non-CD group ( adjusted P = 0.040 ) , but there was little difference in the change in C-Log scores from baseline to followup between the 2 groups ( P = 0.582 ) . CONCLUSION The Virtual Rheumatology CD has a positive impact on the acquisition of musculoskeletal examination skills in medical students . Further study is needed to see if similar advantages could be gained in other clinical specialities and how CAL re sources could be effectively integrated into the medical curriculum The purpose of this study was to determine if there was a significant difference in the diagnostic quality of the initial full-mouth series ( FMS ) exposed by first-year dental students after viewing a Computer Assisted Instruction ( CAI ) module on radiographic technique as compared to those who did not and to determine if students who used the CAI module expressed a preference to using it and would recommend its use prior to exposure . Fifty-nine first-year dental students were r and omly selected and assigned to two groups ( students who did not view a CAI CD and students who did ) before exposing their initial FMS on a Dental X-ray Training and Teaching Replica ( DXTTR ) . For each radiographic series , a radiology faculty member determined the total number of error points based on performance criteria . The Wilcoxon Rank Sum Test was used to determine significance between the two groups , p = .05 . After exposing the FMS , students in the second group completed a question naire to assess their preference for using the CAI CD . The Sign Rank Test was used to determine preference , p = .05 . No significant difference in error points were found to exist between the two groups . Dental students who review ed the CAI preferred using it and would recommend it to others before exposing their FMS To determine whether interactive-videodisc lessons can effectively replace some of the labor-intensive laboratories in human gross anatomy , pre-nursing and allied-medical-professions undergraduates at The Ohio State University were r and omly assigned to either a traditional cadaver-demonstration lab or an interactive-videodisc computer lab covering the same material . In a one-unit pilot study in the autumn quarter of 1989 ( involving 190 students ) and a full-quarter course in the spring quarter of 1991 ( 283 students ) , the performances of the computer-lab students were not significantly different from those of the students in the traditional cadaver-demonstration-lab groups Background : Assessing in undergraduate medical education the educational effectiveness of a short computer-based session , integrating a lecturer 's video with a st and ardized structure , for evidence based medicine ( EBM ) teaching , compared to a lecture-based teaching session of similar structure and duration . Method : A concealed , r and omized controlled trial of computer based session versus lecture of equal duration ( 40 minutes ) and identical content in EBM and systematic review s. The study was based at the Medical School , University of Birmingham , UK involving one hundred and seventynine year one medical students . The main outcome measures were change from pre to post-intervention score measured using a vali date d question naire assessing knowledge ( primary outcome ) and attitudes ( secondary outcome ) . Results : Participants ’ improvement in knowledge in the computer based group was equivalent to the lecture based group ( gain in score : 0.8 [ S.D = 3.2 ] versus 1.3 [ S.D = 2.4 ] ; p = 0.24 ) . Attitudinal gains were similar in both groups . Conclusion : Computer based teaching and typical lecture sessions have similar educational gains OBJECTIVES We have developed both a computer-assisted instruction ( CAI ) multimedia program and a textbook on arterial blood gas interpretation with the same content as formal didactic instruction . A prospect i ve , r and omized study was design ed to compare the outcomes of self-learning using the software and using the textbook . METHODS 80 third-year medical students were r and omly allocated to two groups : the CAI ( n=40 ) and text group ( n=40 ) . A 30-item , type-K examination was administered as the pre-test . After the pre-test , the volunteers in the CAI group studied the software program , whereas those in the text group spent their time reading the textbook covering the same material . The post-test was held immediately at the end of a full day of study , and 3 weeks later , the final test was performed without prior notice . A P value of < 0.05 was considered to be a statistically significant difference . RESULTS Students in the text group seemed to fulfil their assignments and improved their scores post-test better than those in the CAI group . After 3 weeks , the final test scores of both groups demonstrated a significant decrease , but showed an insignificant difference between the two groups . CONCLUSION Text-based learning seems to be a convenient method of education where time is limited . However , with more time available , use of software may be as good as the conventional learning method and can be an alternative tool . The computer-assisted instruction program seems to enhance the learning process AIM This study compared e-learning ( EL ) , face-to-face learning ( F2FL ) and blended learning ( BL ) with respect to their effectiveness and student attitudes towards them . It also evaluated the effect of the order in which the components ( EL and F2FL ) of blended learning are delivered . DESIGN This was a prospect i ve cluster r and omised trial comparing four parallel groups . METHOD Eight groups of fourth year dental undergraduate students were r and omly allocated to one of four intervention groups : EL , F2FL , BL1 or BL2 . These four groups were assessed for their baseline comparability of knowledge and skills . Each then received the same cephalometric tutorial but delivered by the allocated mode of learning . Effectiveness was immediately assessed with a MCQ which measured short-term recall of knowledge . Student attitudes were evaluated with a question naire followed by a focus group discussion . RESULTS Ninety ( 57 % ) students completed the study . Pearson 's chi-square test found no statistically significant difference between F2FL and BL ; EL alone was less effective ( P<0.05 ) for four MCQ questions but with no difference for the remaining six questions . Overall students were positive towards each learning modality , but a one-way analysis of variance found BL was the most and F2FL was the least accepted ( P=0.002 ) . EL was significantly ( P=0.028 ) less preferred . The order of the components in BL had no significant effects . CONCLUSION These results suggest that BL is more likely than either F2FL or EL alone , to be both effective and accepted when delivering cephalometric education to undergraduates BACKGROUND The effectiveness of e-learning for reporting of x-ray- findings in a prospect i ve , r and omized trial was tested . MATERIAL AND METHODS Twenty advanced medical students were r and omized into two groups . The test group practice d 4 - 6 hours with the newly developed software , the control group used conventional learning material . Afterwards , a test was carried out including 30 pathologic x-ray films that were r and omly spread through 200 non-pathologic images . The required time , the number of correctly appraised images and the frequency of falsely suspected pathologies were recorded . In addition , we asked for an assessment of the own capabilities in evaluating x-ray films and of passing the radiology training . RESULTS The test group showed a markedly improved efficiency in comparison to the control group in all parameters . The required time was 57.4 % shorter than in the control group ( p < 0.05 ) , 18.3 % more cases were evaluated correctly ( p < 0.05 ) . The frequency of falsely suspected pathologies decreased by 61 % ( p < 0.05 ) . There was no significant correlation of the objective abilities of a student with his/her self- assessment or of passing the radiology course . CONCLUSION This study shows that an effective st and ardized training of practical skills by means of e-learning is feasible and reasonable |
10,538 | 26,017,279 | Tapentadol extended release is associated with a reduction in pain intensity in comparison to placebo and oxycodone .
Tapentadol is associated with a more favourable safety profile and tolerability than oxycodone | BACKGROUND Chronic musculoskeletal pain is a prevalent condition and a major cause of disability and absence from the workplace worldwide .
Opioids are frequently used to treat chronic pain , although adverse effects often restrict their long-term benefits .
Tapentadol is an opioid and norepinephrine re-uptake inhibitor , which may cause a lower incidence ( and severity ) of adverse effects compared to other strong opioids .
OBJECTIVES To determine the efficacy , safety and tolerability of tapentadol extended release for moderate-to-severe pain for at least three months for any musculoskeletal cause . | OBJECTIVE The goals of this study were to examine agreement and estimate differences in sensitivity between pain assessment scales . DESIGN Multiple simultaneous pain assessment s by patients in acute pain after oral surgery were used to compare a four-category verbal rating scale ( VRS-4 ) and an 11-point numeric rating scale ( NRS-11 ) with a 100-mm visual analog scale ( VAS ) . The sensitivity of the scales ( i.e. , their ability [ power ] to detect differences between treatments ) was compared in a simulation model by sampling from true pairs of observations using varying treatment differences of predetermined size . RESULTS There was considerable variability in VAS scores within each VRS-4 or NRS-11 category both between patients and for repeated measures from the same patient . Simulation experiments showed that the VAS was systematic ally more powerful than the VRS-4 in all simulations performed . The sensitivity of the VAS and NRS-11 was approximately equal . CONCLUSIONS In this acute pain model , the VRS-4 was less sensitive than the VAS . The simulation results demonstrated similar sensitivity of the NRS-11 and VAS when comparing acute postoperative pain intensity . The choice between the VAS and NRS-11 can thus be based on subjective preferences & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies Introduction This open-label , phase 3b study evaluated the effectiveness and tolerability of oral tapentadol prolonged release ( PR ; 50–250 mg twice daily [ b.i.d . ] ) for managing severe , chronic low back pain in patients responding to World Health Organization ( WHO ) step III opioids but tolerating treatment poorly . Equianalgesic ratios for tapentadol to prior strong opioids were calculated . Methods Patients rotated directly from prior WHO step III opioids to tapentadol . Patients received tapentadol PR ( 50–250 mg b.i.d . ) during 5-week titration and 7-week maintenance periods . Tapentadol immediate release ( IR ) 50 mg ( ≤twice/day , ≥4 h apart ) was allowed ( total daily dose of tapentadol PR and IR ≤500 mg/day ) . The primary endpoint was responder rate 1 at week 6 ( percentage of patients with the same or less pain intensity [ 11-point numerical rating scale ( NRS ; 3-day average ) ] vs week −1 ) . Results Responder rate 1 at week 6 ( last observation carried forward [ LOCF ] ) was 80.9 % ( 76/94 ; P < 0.0001 vs. the null responder hypothesis rate [ < 60 % ] ) , result ing in a positive trial despite premature termination ( 136 recruited of 180 planned ) . Significant improvements from baseline in pain intensity and neuropathic pain symptoms were observed at weeks 6 and 12 with tapentadol PR ( P < 0.05 ) . Equianalgesic ratios were calculated for PR formulations alone and for PR and IR formulations combined for tapentadol to oxycodone , buprenorphine , fentanyl , morphine , and hydromorphone . The prevalences of adverse events reported as the reason for switching to tapentadol ( most commonly constipation and nausea ) decreased over time . Conclusions Tapentadol PR ( 50–250 mg b.i.d . ) provided at least comparable pain relief and improved tolerability versus prior strong opioids in patients with severe , chronic low back pain responding to WHO step III therapy . Conversion from strong opioids to tapentadol PR , with its two mechanisms of action , went smoothly considering overall effectiveness and tolerability outcomes . Equianalgesic ratios of tapentadol to oxycodone and other strong opioids were in line with other phase 3/3b studies Objective : To evaluate the efficacy and safety of tapentadol extended release ( ER ) for the management of moderate to severe chronic low back pain . Research design : Patients ( N = 981 ) were r and omized 1:1:1 to receive tapentadol ER 100 – 250 mg b.i.d . , oxycodone HCl controlled release ( CR ) 20 – 50 mg b.i.d . , or placebo over 15 weeks ( 3-week titration period , 12-week maintenance period ) . Main outcome measures : Efficacy was assessed as change from baseline in average pain intensity ( 11-point NRS ) at week 12 of the maintenance period and throughout the maintenance period ; last observation carried forward was used to impute missing pain scores . Adverse events ( AEs ) were monitored throughout the study . Results : Tapentadol ER significantly reduced average pain intensity versus placebo at week 12 ( least squares mean difference vs placebo [ 95 % confidence interval ] , −0.8 [ −1.22 , −0.47 ] ; p < 0.001 ) and throughout the maintenance period ( −0.7 [ −1.06,−0.35 ] ; p < 0.001 ) . Oxycodone CR significantly reduced average pain intensity versus placebo at week 12 ( −0.9 [ −1.24,−0.49 ] ; p < 0.001 ) and throughout the maintenance period ( −0.8 [ −1.16,−0.46 ] ; p < 0.001 ) . Tapentadol ER was associated with a lower incidence of treatment-emergent AEs ( TEAEs ) than oxycodone CR . Gastrointestinal TEAEs , including constipation , nausea , and vomiting , were among the most commonly reported TEAEs ( placebo , 26.3 % ; tapentadol ER , 43.7 % ; oxycodone CR , 61.9 % ) . The odds of experiencing constipation or the composite of nausea and /or vomiting were significantly lower with tapentadol ER than with oxycodone CR ( both p < 0.001 ) . Conclusions : Tapentadol ER ( 100 – 250 mg b.i.d . ) effectively relieved moderate to severe chronic low back pain over 15 weeks and had better gastrointestinal tolerability than oxycodone HCl CR ( 20 – 50 mg b.i.d . ) OBJECTIVE To establish basic epidemiological data on chronic pain ( duration > 3 months ) in a defined population . Relationships between age , gender , and social class were tested . DESIGN A survey of pain symptoms , including location , intensity , duration , and functional capacity , was conducted by means of a mail question naire . SETTING General population s in two Swedish primary health care districts . Medical care was provided in a state health system . SUBJECTS A r and om sample ( from the population register ) of 15 % of the population aged 25 - 74 ( n = 1,806 ) . The response rate was 90 % . OUTCOME MEASURES Descriptive epidemiologic data in relation to objectives of the study . RESULTS Without sex differences , 55 % ( 95 % confidence interval , 53 - 58 % ) of the population had perceived persistent pain for 3 months and 49 % for 6 months . Among individuals with chronic pain , 90 % localized their pain to the musculoskeletal system to a variable extent . Women experienced more multiple localizations of pain and had pain in the neck , shoulder , arm , and thigh to a greater extent than men . Prevalence of pain increased by age up to 50 - 59 years for both genders and then slowly decreased . The neck-shoulder area was the most common site of pain ( 30.2 % ) , followed by the lower back ( 23.2 % ) . Even in the youngest age groups more than one of four reported chronic pain . Blue-collar workers and employers ( including farmers ) reported chronic pain to a greater extent than other groups . In 13 % of the population , manifest pain problems were associated with reduced functional capacity . CONCLUSION Chronic pain symptoms are common but unevenly distributed in a general population . The results may influence planning and consultation in primary health care as well as warranting selective prevention activities BACKGROUND Tapentadol is a novel , central ly acting analgesic with 2 mechanisms of action : µ-opioid receptor agonism and norepinephrine reuptake inhibition . This r and omized , open-label phase 3 study ( Clinical Trials.gov Identifier : NCT00361504 ) assessed the long-term safety and tolerability of tapentadol extended release ( ER ) in patients with chronic knee or hip osteoarthritis pain or low back pain . METHODS Patients were r and omized 4:1 to receive controlled , adjustable , oral , twice-daily doses of tapentadol ER ( 100 to 250 mg ) or oxycodone HCl controlled release ( CR ; 20 to 50 mg ) for up to 1 year . Efficacy evaluations included assessment s at each study visit of average pain intensity ( 11-point numerical rating scale ) over the preceding 24 hours . Treatment-emergent adverse events ( TEAEs ) and discontinuations were monitored throughout the study . RESULTS A total of 1,117 patients received at least 1 dose of study drug . Mean ( st and ard error ) pain intensity scores in the tapentadol ER and oxycodone CR groups , respectively , were 7.6 ( 0.05 ) and 7.6 ( 0.11 ) at baseline and decreased to 4.4 ( 0.09 ) and 4.5 ( 0.17 ) at endpoint . The overall incidence of TEAEs was 85.7 % in the tapentadol ER group and 90.6 % in the oxycodone CR group . In the tapentadol ER and oxycodone CR groups , respectively , TEAEs led to discontinuation in 22.1 % and 36.8 % of patients ; gastrointestinal TEAEs led to discontinuation in 8.6 % and 21.5 % of patients . CONCLUSION Tapentadol ER ( 100 to 250 mg bid ) was associated with better gastrointestinal tolerability than oxycodone HCl CR ( 20 to 50 mg bid ) and provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis or low back pain for up to 1 year OBJECTIVE To evaluate via retrospective analysis the efficacy and tolerability of tapentadol extended release ( ER ; 100 - 250 mg bid ) based on patient-specific factors , including baseline pain intensity , prior opioid experience , gender , and body mass index ( BMI ) . DESIGN Data were pooled from three r and omized , double-blind phase III studies of similar design that evaluated the efficacy and tolerability of tapentadol ER for the management of moderate to severe , chronic osteoarthritis knee pain ( NCT00421928 , NCT00486811 ) or low back pain ( NCT00449176 ) . SETTING In the original trials , patients were recruited at primary , secondary , and tertiary care centers , institutional setting s , and private practice s in North America , Europe , Australia , and New Zeal and . PATIENTS Data were analyzed separately for groups of patients divided by baseline pain intensity , prior opioid experience , gender , and BMI . INTERVENTIONS Patients received twice-daily placebo , tapentadol ER ( 100 - 250 mg ) , or oxycodone HCl controlled release ( CR ; 20 - 50 mg ) for a 3-week titration and 12-week maintenance period . MAIN OUTCOME MEASURES Changes from baseline in average pain intensity ( 11-point numerical rating scale ) at week 12 of the maintenance period and for the overall maintenance period . RESULTS Efficacy and tolerability were evaluated in 2,968 and 2,974 patients , respectively . The efficacy of tapentadol ER was shown in sub population s divided by baseline pain intensity , prior opioid experience , gender , and BMI . Tapentadol ER was also shown to be well tolerated and associated with better gastrointestinal tolerability than oxycodone CR in the evaluated sub population s ( divided by prior opioid experience and gender ) . CONCLUSIONS Results suggest that tapentadol ER ( 100 - 250 mg bid ) provides similar pain relief and tolerability , regardless of baseline pain intensity , prior opioid experience , gender , or BMI ABSTRACT Objective : Nociceptive and neuropathic components both contribute to pain . Since these components require different pain management strategies , correct pain diagnosis before and during treatment is highly desirable . As low back pain ( LBP ) patients constitute an important subgroup of chronic pain patients , we addressed the following issues : ( i ) to establish a simple , vali date d screening tool to detect neuropathic pain ( NeP ) components in chronic LBP patients , ( ii ) to determine the prevalence of neuropathic pain components in LBP in a large-scale survey , and ( iii ) to determine whether LBP patients with an NeP component suffer from worse , or different , co-morbidities . Methods : In co-operation with the German Research Network on Neuropathic Pain we developed and vali date d the painDETECT question naire ( PD‐Q ) in a prospect i ve , multicentre study and subsequently applied it to approximately 8000 LBP patients . Results : The PD‐Q is a reliable screening tool with high sensitivity , specificity and positive predictive accuracy ; these were 84 % in a palm-top computerised version and 85 % , 80 % and 83 % , respectively , in a corresponding pencil- and -paper question naire . In an unselected cohort of chronic LBP patients , 37 % were found to have predominantly neuropathic pain . Patients with NeP showed higher ratings of pain intensity , with more ( and more severe ) co‐morbidities such as depression , panic/anxiety and sleep disorders . This also affected functionality and use of health-care re sources . On the basis of given prevalence of LBP in the general population , we calculated that 14.5 % of all female and 11.4 % of all male Germans suffer from LBP with a predominant neuropathic pain component . Conclusion : Simple , patient-based , easy-to-use screening question naires can determine the prevalence of neuropathic pain components both in individual LBP patients and in heterogeneous cohorts of such patients . Since NeP correlates with more intense pain , more severe co‐morbidity and poorer quality of life , accurate diagnosis is a milestone in choosing appropriate therapy Study Design This report gives the results of a population -based cross-sectional mailed question naire , with prospect i ve follow-up of survey responders and nonresponders . Objective To determine the 1-month period prevalence of low back pain in an adult population in the United Kingdom and to estimate the effect of nonresponse bias . Summary of Background Data Previous United Kingdom population studies have reported a 1-year period prevalence of low back pain of 37 % . However , the definitions of low back pain have varied , and the influence of nonresponse rarely has been reported . Methods The study population was made up of all 7669 adults ( 18 to 75 years old ) registered with two family practice s in a sociodemographically mixed suburban area . The question naire , including a pain drawing to identify the site of any pain , was mailed to the entire study population . Two repeat mailings were sent to nonresponders . Family practice consultations about low back pain by individuals from the study population were monitored over the following 12 months using computerized records of all surgery contacts . Results Of the study population , 4501 ( 59 % ) responded . The 1-month period prevalence of low back pain was 39 % ( 35 % in males , 42 % in females ) . The age distribution was unimodal , with peak prevalence in those aged 45 to 59 years old . Responders to the first mailing had a small but nonsignificant increase in prevalence compared with those who responded to the second or third mailing . Nonresponders had a subsequent consultation rate for low back pain that was 22 % lower than that for the survey responders . Conclusions After considering potential differences in nonresponders , the estimated 1-month prevalence of low back pain was between 35 % and 37 % . Prevalence figures in survey responders may overestimate the true population prevalence by a modest amount Abstract Background : Tapentadol is a novel , central ly acting analgesic with μ-opioid receptor agonist and norepinephrine reuptake inhibitor activity . Objective : To evaluate the efficacy and safety of tapentadol extended release ( ER ) compared with oxycodone controlled release ( CR ) for management of moderate to severe chronic osteoarthritis-related knee pain . Methods : This was a r and omized , double-blind , active- and placebo-controlled , parallel-arm , multicentre , phase III study during which patients received tapentadol ER , oxycodone CR or placebo for a 3-week titration period followed by a 12-week maintenance period . The study was carried out at sites in Australia , Canada , New Zeal and and the US . A total of 1030 patients with chronic osteoarthritis-related knee pain were r and omized to receive tapentadol ER 100–250 mg twice daily , oxycodone HCl CR 20–50 mg twice daily or placebo . Primary endpoints ( as determined prior to initiation of the study ) were the changes from baseline in average daily pain intensity ( rated by patients on an 11-point numerical rating scale ) over the last week of maintenance and over the entire 12-week maintenance period ; last observation carried forward was used to impute missing values after early treatment discontinuation . Results : Efficacy and safety were evaluated for 1023 patients . Tapentadol ER significantly reduced average pain intensity from baseline to week 12 of the maintenance period versus placebo ( least squares mean [ LSM ] difference [ 95 % CI ] , −0.7 [ −1.04 , −0.33 ] ) , and throughout the maintenance period ( −0.7 [ −1.00 , −0.33 ] ) . Oxycodone CR significantly reduced average pain intensity from baseline throughout the maintenance period versus placebo ( LSM difference [ 95 % CI ] , −0.3 [ −0.67 , −0.00 ] ) but not at week 12 ( −0.3 [ −0.68 , 0.02 ] ) . A significantly higher percentage of patients achieved ≥50 % improvement in pain intensity in the tapentadol ER group ( 32.0 % [ 110/344 ] ) compared with the placebo group ( 24.3 % [ 82/337 ] ; p = 0.027 ) , indicating a clinical ly significant improvement in pain intensity , while a significantly lower percentage of patients achieved ≥50 % improvement in pain intensity in the oxycodone CR group ( 17.3 % [ 59/342 ] ; p = 0.023 vs placebo ) . In the placebo , tapentadol ER and oxycodone CR groups , respectively , 61.1 % ( 206/337 ) , 75.9 % ( 261/344 ) and 87.4 % ( 299/342 ) of patients reported at least one treatment-emergent adverse event ( TEAE ) ; incidences of gastrointestinal-related TEAEs were 26.1 % ( 88/337 ) , 43.0 % ( 148/344 ) and 67.3 % ( 230/342 ) . Conclusion : Treatment with tapentadol ER 100–250 mg twice daily or oxycodone HCl CR 20–50 mg twice daily was effective for the management of moderate to severe chronic osteoarthritis-related knee pain , with substantially lower incidences of gastrointestinal-related TEAEs associated with treatment with tapentadol ER than with oxycodone CR . [ Trial registration number : NCT00421928 ( Clinical Trials.gov Identifier ) |
10,539 | 11,406,075 | Otherwise , there were no significant differences between groups for this outcome .
Oral prostagl and in was associated with vomiting across all comparison groups .
REVIEW ER 'S CONCLUSIONS Oral prostagl and in consistently result ed in more frequent gastrointestinal side effects , in particular vomiting , compared with the other treatments included in this review .
There were no clear advantages to oral prostagl and in over other methods of induction of labour | BACKGROUND This is one of a series of review s of methods of cervical ripening and labour induction using st and ardised methodology .
OBJECTIVES To determine the effects of oral prostagl and in E2 for third trimester induction of labour .
DATA COLLECTION AND ANALYSIS A strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction .
This involves a two-stage method of data extraction . | The effect of prostagl and in E2 ( PGE2 ) in ' ripening ' the cervix was studied in 33 patients who required surgical induction of labour . Patients included primigravidas and parous subjects between 36 and 42 weeks of gestation . Sixteen patients received a total oral dose of 5 mg PGE2 and 17 received 4 - 6 mg PGE2 intravaginally in the form of a gel . There was significant improvement in ' ripeness ' of the cervix in all groups , the intravaginal route giving slightly better results than the oral route . Ten patients remained unsuitable for induction because of inadequate dilatation of the cervix or a high fetal head . Four patients on oral therapy developed late decelerations of the fetal heart and 3 of these were delivered by immediate caesarean section . The implication s of this and the reasons for the inability to perform inductions after ' ripening ' are discussed OBJECTIVE To clarify the safety of elective induction of labor at 39 weeks of gestation . STUDY DESIGN Prospect i ve r and omized study . SUBJECTS AND METHODS Uncomplicated nulliparas ( N = 194 ) were r and omly assigned at 36 weeks of gestation . Labor was electively induced in 63 women at 39 weeks of gestation in the active management group ( I group , N = 98 ) . Spontaneous labor onset was expected with semi-weekly nonstress test ( NST ) and amniotic fluid index ( AFI ) by 42 weeks of gestation in the expectant group ( E group , N = 96 ) . Perinatal events were compared between the 2 groups . RESULTS A significantly higher incidence of meconium-stained amnios ( 19.4 % vs 3.2 % ) and fetal resuscitation ( 16.7 % vs 4.8 % ) was found in the E group than in the I group . Also , although a significantly higher incidence of epidural analgesia was noted in the I group ( 89 % ) than in the E group ( 54 % ) ( labor onset > or = 39 weeks , N = 72 ) , the duration of the 1st stage was shorter in I group and the duration of the 2nd stage was not significantly different . No other significant difference was noted between the 2 groups in terms of the rate of C-section , blood loss , incidence of pathological FHR , birth weight , Apgar score , umbilical arterial pH , or admission to NICU . CONCLUSION Active management of labor at 39 weeks could be made as safely as expectant management with modified biophysical profile monitoring Abstract . The efficacy of oral PGE2 tablets and buccal demoxytocin ( resoriblets ) for the induction of labor in cases of premature rupture of the membranes ( PROM ) after the 37th week of gestation has been evaluated in a prospect i ve , r and omized investigation of 193 women . PGE2 tablets ( Pro‐stinR ) were given to 109 parturients and demoxytocin resoriblets ( S and opartR ) to 84 . The former were given in increasing doses from an initial 0.5 mg to a maximum of 1.5 mg every hour . The demoxytocin was administered at a constant dosage of 50 I.U. every 30 min The use of prostagl and in E2 for the induction of labor with intact membranes is described and its effectiveness is compared to intravenous syntocinon . 40 primigravida and 60 multigravid patients with previous medical and obstetrical histories were studied . The patients were numbered as they entered the trial , with the odd numbers in each group being given oral prostagl and in and the even numbers intravenous syntocinon . In no case was the pregnancy less than 38 weeks maturity . No patient was in labor prior to being given either drug . Prostagl and in E2 ( PGE2 ) was supplied in ampoules containing 5 milligrams in 0.5 milliliter of ethanol . This was added to 49.5 milliliters of sterile water to produce a concentration of the drug of 0.1 milligrams per ml . The syntocinon infusion was prepared by putting 20 units of syntocinon into 1 liter of 5 % dextrose in water to produce a solution concentration of 20 mu/ml . The accepted criteria for diagnosing established labor for both groups of patients was the presence of uterine contractions occurring once every 3 minutes , associated with progressive dilatation of the cervix . For both groups of patients it was decided that cervical dilatation should be at least 6 cm within 18 hours of the infusion starting . Using this criterion there was only 1 failure , occurring in the 1st primigravid patient given PGE2 , the labor in this instance being completed with intravenous syntocinon . A further 8 patients failed to complete the trial as they had to be delivered by cesarian section . Syntocin was considerably more efficient than PGE2 in inducing labor in the remaining 91 patients particularly in primigravida . This was the case whether judged by the length of labor or by the induction delivery interval . Toco-dynamometric studies showed that the contractions produced by prostagl and in more closely resembled those of normal labor and were less painful Labor was induced for medical reasons at or near term in altogether 200 patients . The women were r and omly assigned to low amniotomy and either oral PGE2 or intravenous infusion of oxytocin . The initial PGE2 dose was 0.5 mg , followed by 1.0 mg every hour for up to 24 hours . Oxytocin was given as an intravenous pump infusion , starting with 5 mIU/min and rising stepwise to 20 mIU/min . Uterine contractility and fetal heart rate ( FHR ) were recorded by cardiotocography in 61 women receiving oxytocin and in 63 given prostagl and in E2 . A detailed analysis of the contractility pattern was performed in 16 women , eight from each group In a prospect i ve study of neonatal jaundice 739 infants , delivered vaginally , in the vertex presentation , and without major complications , were examined . Labour was induced or stimulated after r and om allocation of the mothers to one of three oxytocics ( prostagl and in E2 orally , oxytocin intravenously , or demoxytocin buccally ) . Oxytocics were unnecessary after primary amniotomy in 91 women . A linear logistic statistical analysis showed that gestational age has a highly significant influence on the risk of jaundice ( defined by maximum serum level of bilirubin greater than or equal to 205 mumol/l ) . An apparent influence of birthweight could be explained by the correlation between birthweight and gestational age . The influence of the three oxytocic agents was not significant , although they may have had a slight effect ; however , any such effect could be a consequence of the infants of mothers given oxytocics being less mature than those whom mothers did not receive oxytocics . The duration of labour and the mother 's age also had no effect on risk of jaundice . Thus , neonatal jaundice after induced and stimulated labour seems to be primarily associated with fetal maturity ; the pharmacological side-effect , if any , of oxytocics is of no importance The induction of labour with prostagl and in E2 ( PGE2 ) tablets in two dosage regimens , and with desamino-oxy-tocin , has been studied in association with amniotomy . In multiparas at or near term and with a high Bishop score . PGE2 appears superior with regard to the induction-to-delivery interval and the duration of labour , but both preparations are highly effective in this respect . In nulliparas with a low Bishop score , however , intravenous oxytocin after amniotomy is the method of choice A double blind study was undertaken to determine the effectiveness or oral prostagl and in E2 as a means of improving the pelvic score prior to induction of labour . 48 patients who were greater than 37 weeks gestation and who had Bishop scores of less than 6 entered the study . Ten tablets were given on an hourly regime . Of 25 patients in the prostagl and in group , 17 were considered successes ( 68.0 % ) , whereas of 23 patients who received a placebo , 9 were successes ( 39.1 % ) . No adverse effects were recorded . Prostagl and in E2 is therefore considered a safe and effective method for priming the unfavourable cervix prior to induction of labour We report the results of a pilot study conducted to compare the efficacy of oral prostagl and in E2 versus intravenous oxytocin in inducing labour after lower amniotomy in 20 primigravid patients at term . The results suggest no significant differences in the performance of each group for the induction to delivery interval , the mode of delivery , the Apgar score at five minutes or for third stage abnormalities . However , the use of oral PGE2 allows the patient unrestricted mobility and avoids the discomfort of i.v . infusions Sixty‐nine patients ( 48 primigravidae and 21 multigravidae ) with 12 hours of spontaneous premature rupture of membranes ( PROM ) after 36 weeks gestation were r and omly allocated to receive either prostagl and in E2 ( PGE2 ) oral tablets or intravenous oxytocin to stimulate labor Prostagl and in E2-tablets were compared to intravenous oxytocin for the stimulation of labor in 201 patients at or near term , with premature spontaneous rupture of the membranes without labor activity for 6 hours after the escape of fluid . The patients were r and omly allocated ; 99 were treated with PGE2-tablets ( 0.5 - 1.5 mg/hr ) and 102 with intravenous oxytocin ( 7.5 - 45 mIU/min ) . The treatment was ineffective in the PGE2 group in 3 cases ; these were treated successfully with intravenous oxytocin . In the oxytocin group , 3 patients were delivered by cesarean section for reasons not associated with the drug . A significant difference was found in the stimulation-delivery time , in favor of intravenous oxytocin . Although PGE2 tablets are a safe and convenient alternative to intravenous oxytocin , the investigation showed that intravenous oxytocin is preferable in cases of premature rupture of the membranes with more than 6 hours without labor activity Abstract . Oral prostagl and in in hourly doses of 0.5 mg PGE2 was given to 58 patients with an initial Bishop score of five or less , for two 12‐hour periods in order to prime the cervix . After priming , the patients were induced with oral PGE2 ; 90 % of these patients were delivered . In a control group comprising 59 patients induced with oxytocin , the delivery rate was only 51 % Summary A prospect i ve survey was carried out on 187 parous patients , in whom labour was induced by amniotomy and either intravenous oxytocin or oral prostagl and in E2 , (PGE2).The results show no significant difference in the performance of each group for the induction to delivery interval , the mode of delivery , the Apgar score at 5 minutes or for third stage anomalies . The use of oral PGE2offers advantages to the patient who is spared the discomfort , restriction and minor risks associated with an intravenous infusion ; and to the midwife who does not have to make frequent checks on the flow rate if an infusion pump is not available . The method also permits the ancillary equipment , which may well be in limited supply , to be reserved for more ‘ at risk ’ cases Fifty pregnant women at term , with a cervix unfavorable for induction , were electively induced with intravenous oxytocin after priming with either oral prostagl and in E2 or a placebo . Oral PGE2 was effective in increasing the Bishop score and in inducing labor prior to the induction , but did not increase the incidence of successful inductions A clinical trial involving 60 patients was conducted to assess the relative efficacy of intravenous oxytocin and oral prostagl and in E2 in ripening the unfavourable cervix , when given as a priming dose on the day before induction of labour . There was significant improvement in the Bishop score , and the subsequent induction‐delivery interval following priming with prostagl and in . This improvement appeared to be dose‐related Objective : The appropriate date of delivery in twin pregnancies is supposed to be earlier than that in singleton pregnancy . The aim of this study was to compare two strategies for managing twin pregnancies ( i.e. , immediate induction and expectant management ) . Methods : Seventeen patients underwent immediately induced labor by administration of oral prostagl and in E2 at 37 weeks , while 19 patients underwent expectant management . Results : The average gestational age at delivery in the induction group was 37.5 ± 0.4 weeks , significantly earlier than that in the expectant management group ( 39.0 ± 1.1 weeks ) . However , there were no significant differences in the average birth weight between the two groups ( 2,700 ± 330 g in the induction group vs. 2,672 ± 392 g in the expectant management group ) . The cesarean delivery rate in the induction group was 18 % , not significantly different from that in the expectant management group ( 32 % ) . The most common indication for cesarean section in the expectant management group was maternal infection , while there was no maternal infection in the induction group ( p = 0.08 ) . Conclusion : It may be acceptable do intervene in twin pregnancies earlier than in singleton pregnancies during term In 100 clinical ly-normal women , labor was induced at term by low amniotomy and PGE2 . The drug was administered by either the oral or the oromucosal route , the same incremental dose scheme ( initial dose of 0.5 mg ; hourly increment of 0.5 mg until adequate uterine stimulation or a maximum single dose of 3.0 mg ) being applied . Both routes of administration had comparable efficacy and were equally safe . The incidence of abnormal monitoring findings ( uterine hypertonus , transient bradycardia and dips II during the first stage ; late decelerations , progressive and transient bradycardia during the second stage of labor ) and of low Apgar scores were similar . Acid-base and lactate-pyruvate equilibria in mother and fetus were not influenced by the route of drug administration in parous women . In nulliparae treated with PGE2 by the oromucosal route , higher values were found for the fetal-maternal difference in excess lactate than in those given oral PGE2 ; however , this is probably of little clinical importance Oral prostagl and in E2 was used for inducing labour in 37 patients without initial rupture of membranes . Two dosage regimens were used : in the one 0.5 mg of oral PGE2 was given hourly , and in the other the dose of oral PGE2 was doubled hourly , starting with a dose of 0,5 mg and increasing to a maximum single dose of 2,0 mg . The incremental dosage regimen was found to be more successful in inducing labour than the constant dosage regimen . The success rate was 94,95 % . Side-effects were found to occur rarely and to be dose-related . Fetal distress did not occur in this study A double-blind study was undertaken to determine the effectiveness of prostagl and in E2 as a means for improving the prelabor pelvic conditions preparatory to induction of labor at term in 30 patients with unfavorable Bishop scores of less than 6 . An interval of priming was followed after 8 to 12 hours by induction with oxytocin infusion . No meaningful differences were found in index cases as compared with controls to verify that PGE2 has any priming or enhancing effect under the conditions of the investigation A carefully controlled , prospect i ve study was undertaken in 100 patients to compare orally administered prostagl and in E2 capsules with intravenous oxytocin in the induction of labour at term . Orally administered prostagl and in E2 induced labour in slightly more patients than did intravenous oxytocin ( 48 out of 50 v. 45 out of 50 ) and a larger trail is in progress to evaluate this observation further . Mild gastro-intestinal symptoms occurred in 28 % of the patients when oral prostagl and in was given . However , the oral route is more convenient and more comfortable for the patient and the administration requires less adjustment by the nursing staff A double-blind study evaluating two dose schedules of oral prostagl and in E2 ( PGE2 ) was conducted in 56 normal “ unripe ” multiparas at term . The effect of PGE2 was evaluated by comparing the change in Bishop score of the cervix and patient 's response to oxytocin induction of labor after the prostagl and in priming . In the two study groups ( one group on a fixed PGE2 dosage and the other on a variable drug regimen ) an average change of more than three points in the Bishop score was observed . In the control group no significant change in cervical ripeness was observed . Nine of the 32 patients ( 28 % ) receiving prostagl and in delivered during the priming phase of the study , whereas only 1 control patient ( 4.2 % ) delivered during priming . Six of 24 control patients ( 25 % ) failed to deliver , whereas only 3 of 32 study patients ( 9 % ) failed . In the successfully induced patients , the response to oxytocin , as expressed by the time to active phase , total time of labor , and mean dose of oxytocin required , did not vary significantly when control and study groups were compared . It is concluded that PGE2 at either dosage schedule is effective in changing the Bishop score of the cervix and that it is not feasible to titrate the PGE2 dose in order to effectively ripen the cervix without a very high incidence of induction of labor . In those cases where priming was completed , without accidental deliver ) ' , the induction phase was successful more than 90 % of the time . No adverse effect to mother or baby was observed during this study A r and omised controlled trial was carried out in 50 primigravidae and 50 multigravidae to compare the effectiveness in induction of labour after low amniotomy of prostagl and in E2 , given as an oral solution , and oxytocin , given as buccal tablets . The results showed that in dosages recommended by the manufacturers , both oxytocic preparations were almost equally effective . With oral oxytocin , once labour had been established and dosage was left to the discretion of the staff , there appeared to be a potentially dangerous tendency to continue giving large doses despite adequate uterine contractions . The authors comment that this was probably the reason why oxytocin-treated multigravidae having normal deliveries within 24 hours had labours significantly shorter on average than those of other successfully induced patients The efficacy and safety of oral PGE2 or intravenous infusion of oxytocin , in both cases combined with early amniotomy , for induction of labor on medical grounds , were compared in a r and omized study of 200 women . After an initial dose of 0.5 mg , 1.0 mg of PGE2 was given at hourly intervals for up to 24 hours . Oxytocin was administered as an intravenous pump infusion , the dose being increased step wise up to 20 mIU/min . The two methods were equally effective . All patients went into labor and were delivered within approximately 24 hours . Of the total of 200 patients included in the study , 92 per cent were delivered vaginally and 8 per cent with Caesarean section . In 26 per cent the delivery was completed by vacuum extraction . The frequency of instrumental delivery was significantly lower in multiparous than in primiparous patients . If the patient was a multiparous woman and the modified Bishop score was 6 or more , the combined frequency of Caesarean section and instrumental delivery was for PGE2 2.5 per cent and for oxytocin 3.1 per cent Abstract . A r and omized comparative study of 387 consecutive patients admitted for induction of labor was carried out using two orally administered oxytocics ( prostagl and in E2 tablets ( ProstinR ) or Demoxytocin resoriblets for buccal administration ( S and opartR ) ) , the results of which are reported here A double‐blind , placebo‐controlled study was undertaken to evaluate the priming effect on the cervix and also the effect on the subsequent induction of labor . 0.5 mg oral PGEj or placebo was given hourly for two 12‐h periods . A total of 191 women with risk pregnancies and Bishop score < 5 were studied . The induction of labor was carried out with oxytocin or oral PGE2 in a r and omized manner . Labor was induced in 39 % of the women during the PGEj priming . The best result , 71 % vaginal deliveries , was achieved with the combination of PGE2 priming and induction of labor with oxytocin A comparative study of the efficacy of oral prostagl and in E2 and buccal tablets of demoxytocin for induction of labor in overdue pregnancies was made in groups of r and omly selected patients . Labor was successfully induced in 95.7 % of the women in the prostagl and in group and 92.1 % of the women in the demoxytocin group . Although the operative delivery rate was low in both groups , it was significantly higher for the demoxytocin group . A low rate of perinatal distress was recorded and there were no serious side effects in either group . The time from start of induction until delivery , as well as the time from amniotomy until delivery , were compared for primiparae and multiparae separately . No significant differences were found . The blood loss during the third stage of labor was lower in the prostagl and in group . We find oral induction of labor in overdue pregnancies effective , safe and convenient |
10,540 | 30,038,723 | Circulating IL-6 levels appear to be an independent prognostic biomarker in patients with GI cancer , with high IL-6 levels associated with short overall survival ( OS ) .
The results for colorectal cancer were too ambiguous to give conclusive results .
IL-6 seemed to be a marker for some of the clinical characteristics of GI cancer , and may have a role in the diagnostic workup in general practice .
In conclusion , high circulating IL-6 was associated with short OS in most studies in GI cancer patients .
Whether inhibition of IL-6 would decrease GI cancer symptoms and increase quality of life is unknown | Gastrointestinal cancer ( GI ) is a major health problem .
Patients with gastric , pancreatic , colorectal , bile duct and gall bladder cancer often have advanced disease at the time of diagnosis and are generally difficult to cure , result ing in a dismal prognosis for most patients .
Inflammation plays an important role in the development and growth of cancer , which has led to a growing interest in the pro-inflammatory cytokine interleukin 6 ( IL-6 ) .
The aim of the present review was to evaluate the clinical use of IL-6 as a biomarker or therapeutic target in patients with GI cancer . | BACKGROUND AND STUDY AIM While colonoscopy screening is widely used in several European countries and the United States , there are no r and omized trials to quantify its benefits . The Nordic-European Initiative on Colorectal Cancer ( NordICC ) is a multinational , r and omized controlled trial aim ing at investigating the effect of colonoscopy screening on colorectal cancer ( CRC ) incidence and mortality . This paper describes the rationale and design of the NordICC trial . STUDY DESIGN Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and r and omly assigned to either once-only colonoscopy screening with removal of all detected lesions , or no screening ( st and ard of care in the trial regions ) . All individuals are followed for 15 years after inclusion using dedicated national registries . The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up . POWER ANALYSIS : We hypothesize a 50 % CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50 % compliance , yielding a 25 % mortality reduction among those invited to screening . For 90 % power and a two-sided alpha level of 0.05 , using a 2:1 r and omization , 45 600 individuals will be r and omized to control , and 22 800 individuals to the colonoscopy group . Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up . CONCLUSIONS The aim of the NordICC trial is to quantify the effectiveness of population -based colonoscopy screening . This will allow development of evidence -based guidelines for CRC screening in the general population Because interleukin-6 ( IL-6 ) is considered important in the proliferation of early multiple myeloma ( MM ) , we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab to the bortezomib-melphalan-prednisone ( VMP ) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM . One hundred and six patients were r and omized to receive 9 cycles of VMP or VMP plus siltuximab ( 11 mg/kg every 3 weeks ) followed by siltuximab maintenance . Baseline characteristics were well balanced except for immunoglobulin A subtype and 17p deletions . With a complete response ( CR ) rate of 27 % on siltuximab plus VMP ( S+VMP ) and 22 % on VMP , the study did not confirm its hypothesis that the addition of siltuximab would increase the CR rate by at least 10 % . Overall response rate was 88 % on S+VMP and 80 % on VMP , and at least very good partial response rates were 71 % and 51 % ( P = .0382 ) , respectively . Median progression-free survival ( 17 months ) and 1-year overall survival ( 88 % ) were identical in the 2 arms . Grade ≥3 adverse-event incidence was 92 % on S+VMP and 81 % on VMP ( P = .09 ) , with trends toward more hematologic events and infections on S+VMP . Maintenance therapy with siltuximab was well tolerated . In conclusion , the addition of siltuximab to VMP did not improve the CR rate or long-term outcomes . This study was registered at http:// clinical trials.gov as # NCT00911859 Despite years of research and hundreds of reports on tumour markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons that multiple studies of the same marker lead to differing conclusions . A variety of method ological problems have been cited to explain these discrepancies . Unfortunately , many tumour marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of the study results . The development of guidelines for the reporting of tumour marker studies was a major recommendation of the US National Cancer Institute and the European Organisation for Research and Treatment of Cancer ( NCI-EORTC ) First International Meeting on Cancer Diagnostics in 2000 . Similar to the successful CONSORT initiative for r and omised trials and the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines suggest helpful presentations of data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply Cytokines have been found to be elevated in cancer patients and have been associated with worse prognosis in single tumour entities . We investigated the association of eight different cytokines with venous thromboembolism ( VTE ) and prognosis in cancer patients . The Vienna Cancer and Thrombosis Study ( CATS ) , a prospect i ve study , includes patients with newly diagnosed tumour or disease progression . Patients with an overt infection are excluded . Study end‐points are VTE , death , loss to follow‐up or study completion . Interleukin ( IL ) serum levels were measured using the xMAP technology developed by Luminex . Among 726 included patients , no associations between IL levels and VTE were found , with the exception of a trend for IL‐1β and IL‐6 in pancreatic cancer . Elevated levels of IL‐6 [ as continuous variable per double increase hazard ratio ( HR ) = 1·07 , 95 % confidence interval ( CI ) = 1·027–1·114 , P = 0·001 , IL‐8 ( HR = 1·12 , 95 % CI = 1·062–1·170 , P < 0·001 ) and IL‐11 ( HR = 1·37 , 95 % CI = 1·103–1·709 , P = 0·005 ] were associated with worse survival . In subgroup analyses based on tumour type , colon carcinoma patients , who had higher IL‐6 levels , showed a shorter survival ( HR = 2·405 , 95 % CI = 1·252–4·618 , P = 0·008 ) . A significant association of elevated IL‐10 levels with a decrease in survival ( HR = 1·824 , 95 % CI = 1·098–3·031 , P = 0·020 ) was seen among patients with lung cancer . No correlation between VTE and IL levels was found , but higher IL‐6 , IL‐8 and IL‐11 levels were associated with worse survival in cancer patients . Further , elevated IL‐6 levels might be a prognostic marker in colorectal cancer and elevated IL‐10 levels in lung cancer patients Considering that the prognosis of patients with advanced biliary tract cancer ( BTC ) remains very poor , with a median survival of less than 1 year , new therapeutic approaches need to be developed . In the present study , a phase II clinical trial of personalized peptide vaccination ( PPV ) was conducted in advanced BTC patients to evaluate the feasibility of this treatment and to identify potential biomarkers . A maximum of 4 human leukocyte antigen-matched peptides , which were selected based on the pre-existing host immunity prior to vaccination , were subcutaneously administered ( weekly for 6 consecutive weeks and bi-weekly thereafter ) to 25 advanced BTC patients without severe adverse events . Humoral and /or T cell responses specific to the vaccine antigens were substantially induced in a subset of the vaccinated patients . As shown by multivariate Cox regression analysis , lower interleukin-6 ( IL-6 ) and higher albumin levels prior to vaccination and greater numbers of selected vaccine peptides were significantly favorable factors for overall survival [ hazard ratio (HR)=1.123 , 95 % confidence interval ( CI ) 1.008 - 1.252 , P=0.035 ; HR=0.158 , 95 % CI 0.029 - 0.860 , P=0.033 ; HR=0.258 , 95 % CI 0.098 - 0.682 , P=0.006 ; respectively ] . Based on the safety profile and substantial immune responses to vaccine antigens , PPV could be a promising approach for refractory BTC , although its clinical efficacy remains to be investigated in larger-scale prospect i ve studies . The identified biomarkers are potentially useful for selecting BTC patients who would benefit from PPV Background : Inflammation contributes to the pathogenesis of colorectal cancer ( CRC ) , and cytokine levels are altered during colorectal carcinogenesis . Methods : The serum levels of 13 cytokines and their relation to clinical and pathological parameters , and systemic inflammatory response ( mGPS , CRP and neutrophil – lymphocyte ratio ) , were analysed from a prospect i ve series of 148 CRC patients and 86 healthy age- and sex-matched controls . Results : CRC patients had higher serum platelet-derived growth factor , interleukin (IL)-6 , IL-7 , and IL-8 levels and lower monocyte chemotactic protein-1 ( MCP-1 ) levels than the controls . A logistic regression model for discriminating the patients from the controls – including the five most predictive cytokines ( high IL-8 , high IL-6 , low MCP-1 , low IL-1ra , and low IP-10 ) – yielded an area under curve value of 0.890 in receiver operating characteristics analysis . Serum cytokines showed distinct correlation with other markers of systemic inflammatory response , and advanced CRCs were associated with higher levels of IL-8 , IL-1ra , and IL-6 . A metastasised disease was accompanied by an orientation towards Th2 cytokine milieu . Conclusion : CRC is associated with extensive alterations in serum cytokine environment , highlighting the importance of study ing relative cytokine level alterations . Serum cytokine profile shows promise in separating CRC patients from healthy controls but its clinical value is yet to be confirmed Purpose We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival . Patients and Methods In all , 559 patients with pancreatic cancer from prospect i ve biomarker studies from Denmark ( n = 448 ) and Germany ( n = 111 ) were studied . Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay . Results Odds ratios ( ORs ) for prediction of pancreatic cancer were significant for all biomarkers , with CA 19.9 having the highest AUC ( CA 19.9 : OR = 2.28 , 95 % CI 1.97 to 2.68 , p<0.0001 , AUC = 0.94 ; YKL-40 : OR = 4.50 , 3.99 to 5.08 , p<0.0001 , AUC = 0.87 ; IL-6 : OR = 3.68 , 3.08 to 4.44 , p<0.0001 , AUC = 0.87 ) . Multivariate Cox analysis ( YKL-40 , IL-6 , CA 19.9 , age , stage , gender ) in patients operated on showed that high preoperative IL-6 and CA 19.9 ( dichotomized according to normal values ) were independently associated with short overall survival ( CA 19.9 : HR = 2.51 , 1.22–5.15 , p = 0.013 ; IL-6 : HR = 2.03 , 1.11 to 3.70 , p = 0.021 ) . Multivariate Cox analysis of non-operable patients ( Stage IIB-IV ) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival ( YKL-40 : HR = 1.30 , 1.03 to 1.64 , p = 0.029 ; IL-6 : HR = 1.71 , 1.33 to 2.20 , p<0.0001 ; CA 19.9 : HR = 1.54 , 1.06 to 2.24 , p = 0.022 ) . Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival ( p<0.005 ) compared to patients with normal levels of both biomarkers ( 45 % vs. 92 % alive after 12 months ) . Conclusions Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9 . Combination of pretreatment YKL-40 , IL-6 , and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis OBJECTIVES : Difficult diagnoses and a lack of effective therapy complicate biliary tract malignancies . Interleukin-6 ( IL-6 ) is a human bile duct epithelium growth factor correlated with tumor burden . We evaluated the usefulness of serum IL-6 in the diagnosis of primary BDC and measured changes in serum IL-6 levels following photodynamic therapy ( PDT ) . METHODS : We prospect ively measured serum IL-6 levels in patients with BDC ( N = 26 : 14 patients treated with PDT , 12 with biliary drainage alone ) , hepatocelluar carcinoma ( HCC , N = 26 ) , and healthy adults ( N = 23 ) . Serum IL-6 levels were measured by an enzyme-linked immunosorbent assay . Patients with clinical conditions known to increase IL-6 levels were excluded . RESULTS : IL-6 was detected in all patients with BDC and HCC , and in 6 of 23 healthy adults . Median and mean levels of IL-6 were higher in patients with BDC than in both other groups ( P < 0.001 ) . Using a 25.8 pg/mL cutoff , IL-6 provided a diagnostic sensitivity of 73 % and a specificity of 92 % ; positive and negative predictive values were 83 % and 87 % , respectively . Serum levels of IL-6 were correlated with tumor burden in BDC patients . One month after treatment of BDC with PDT , the mean IL-6 level decreased significantly from 282.1 ± 121.8 to 38.2 ± 9.9 pg/mL ( P = 0.008 ) . CONCLUSIONS : Serum IL-6 concentration is a useful addition to the available tests for the differential diagnosis of BDC , and serves as a marker for monitoring the response to treatment of BDC with PDT Objectives High serum level of interleukin 6 ( IL-6 ) is associated with high degree of tumor progression and systemic weakness . Anti – IL-6 therapy possibly improves the deterioration of clinical characteristics in patients with high IL-6 level . However , IL-6–related factors in patients with treatment-naive advanced pancreatic cancer ( PC ) have not been established . The goal of this study was to identify IL-6–related factors in patients with advanced PC who were scheduled to undergo first-line chemotherapy . Methods Patients with treatment-naive advanced PC were eligible for inclusion in this study . Patients who did not receive first-line chemotherapy were excluded . Serum IL-6 levels and clinical parameters were prospect ively recorded . Analyses were performed to identify risk factors for high IL-6 levels . Results Eighty patients were analyzed . IL-6–related factors were advanced age ( P < 0.01 ) , the presence of liver metastasis ( P < 0.01 ) , the large volume of liver metastasis ( P < 0.01 ) , severe fatigue ( P = 0.02 ) , high carcinoembryonic antigen levels ( P = 0.02 ) , anemia ( P < 0.01 ) , and high C-reactive protein levels ( P = 0.02 ) in multivariate analyses . Decreased skeletal muscle mass tended to be associated with high IL-6 levels . Conclusions High serum IL-6 was related to advanced age , the presence of hepatic metastasis , large tumor burden in liver , severe fatigue , high carcinoembryonic antigen , high C-reactive protein , and anemia in patients with treatment-naive advanced PC BACKGROUND Pancreatic cancer is a rapidly progressive disease which is often only amenable to palliative treatment . Few patients respond to palliative chemotherapy , so surrogate markers indicating which patients are likely to respond to treatment are required . There is a well-established link between pro-inflammatory circulating cytokines and growth factors ( CAF ) , and the development of neoplasia . Agents that may modulate these factors are of interest in developing potential novel therapeutic applications . METHODS As part of a single-arm phase II trial in patients with advanced pancreatic cancer ( APC ) treated with gemcitabine and intravenous ( i.v . ) omega-3 rich lipid emulsion ( n-3FA ) , serum sample s were analysed for 14 CAF using a multiplex cytokine array . Baseline serum concentrations were correlated with overall ( OS ) and progression-free survival ( PFS ) , and changes in concentration correlated with time and outcomes for CAF responders were analysed . RESULTS Platelet-derived growth factor ( PDGF ) and fibroblast growth factor ( FGF ) concentrations reduced significantly with treatment over time . Low baseline interleukin (IL)-6 and -8 were correlated with improved OS . PDGF responders showed a tendency towards improved OS and FGF responders a significantly improved PFS . DISCUSSION Treatment with gemcitabine plus i.v . n-3FA may reduce concentrations of CAF which may be associated with an improved outcome . Baseline IL-6 and -8 may be surrogate markers for outcome in patients with APC treated with this regimen BACKGROUND The aim of this study was to measure several parameters in patients with early-stage colorectal cancer ( CRC ) and to evaluate them for their utility in routine clinical practice . PATIENTS AND METHODS Pre-operative serum levels of the following parameters were measured in 174 patients with CRC ( clinical stage I-III ) : carcinoembryonic antigen ( CEA ) , carbohydrate antigen CA 19 - 9 , proliferative marker thymidine kinase ( TK ) , tissue polypeptide antigen ( TPA ) , tissue polypeptide-specific antigen ( TPS ) , interleukin-6 ( IL-6 ) , interleukin-10 ( IL-10 ) , matrix metalloproteinase-9 ( MMP-9 ) , tissue inhibitor of metalloproteinase-1 ( TIMP-1 ) , intercellular adhesion molecule-1 ( ICAM-1 ) , vascular cell adhesion molecule-1 ( VCAM-1 ) , vascular endothelial growth factor ( VEGF ) , C-peptide , insulin , adiponectin and leptin . The control group consisted of 50 patients who were undergoing a complete preventive medical examination and in these patients at the time of blood collection there was no evidence of any cancer disease . RESULTS Significant increase of the following parameters was found in patients with CRC : CEA , CA 19 - 9 , TPA , IL-6 , IL-10 , TIMP-1 , C-peptide , insulin and adiponectin . Only two of these , CA 19 - 9 and adiponectin , represent highly unfavorable prognostic factors . If elevated , they affect both progression-free interval and overall survival . CONCLUSION Based on our results , we can conclude that none of the measured parameters fulfills the criteria for use for screening nor for primary diagnosis of CRC . Some of the parameters are important for prognosis estimate : Elevated CA 19 - 9 is related to an unfavorable prognosis , in terms of cancer recurrence and mortality rate . Angiogenetic factor VEGF represents a prognostic factor important for OS . CEA represents a parameter which is related to disease progression . Interleukins seem to be prospect i ve complementary tumor markers . Adiponectin may be used for estimation of advanced stage of cancer and for estimate of risk of cancer recurrence BACKGROUND The immune system is important in epithelial ovarian cancer ( EOC ) . Interleukin-6 is associated with chemoresistance and an immune-suppressive tumor microenvironment . We investigated whether a combination of chemotherapeutics , blockade of interleukin 6 ( IL-6 ) receptor ( IL-6R ; tocilizumab ) , and immune enhancer interferon-α ( Peg-Intron ) is feasible , safe , and able to enhance immunity in patients with recurrent EOC . PATIENTS AND METHODS In this dose-escalation study , patients received tocilizumab 1 , 2 , 4 , or 8 mg/kg i.v . , q4 weeks during the first three cycles of carboplatin ( AUC5 ) plus doxorubicin [ pegylated liposomal doxorubicin ( PLD ) 30 mg/m(2 ) or doxorubicin 50 mg/m(2 ) i.v . , day 1 , q4 weeks , for six cycles ] . At the highest tocilizumab dose ( 8 mg/kg ) , Peg-Intron ( 1 µg/kg s.c . ) was added . Peripheral blood mononuclear cells were collected for immunomonitoring at baseline , after three and six cycles . Dose-limiting toxicity ( DLT ) , CA-125 , and radiologic response were evaluated . RESULTS In the 23 patients enrolled , no DLT was established . The most frequent grade 3/4 adverse events ( CTCAE v4.03 ) were neutropenia ( 23 % ) , febrile neutropenia ( 19 % ) , and ileus ( 19 % ) . No treatment-related deaths occurred . Using CT evaluation , 11 of 21 assessable patients responded , 6 had stable disease and 3 progressive disease . Patients receiving highest dose tocilizumab showed a functional blockade of IL-6R with increased levels of serum IL-6 ( P = 0.02 ) and soluble IL-6R ( P = 0.008 ) . Consequently , immune cells displayed decreased levels of pSTAT3 , myeloid cells produced more IL-12 and IL-1β while T cells were more activated and secreted higher amounts of effector cytokines interferon-γ and tumor necrosis factor-α . An increase in sIL-6R was potentially associated with a survival benefit ( P = 0.03 ) . CONCLUSIONS Functional IL-6R blocking is feasible and safe in EOC patients treated with carboplatin/(pegylated liposomal)doxorubicin , using 8 mg/kg tocilizumab . This combination is recommended for phase II evaluation based on immune parameters . CLINICAL TRIAL REGISTER NCT01637532 We compared the safety and efficacy of siltuximab ( S ) , an anti‐interleukin‐6 chimeric monoclonal antibody , plus bortezomib ( B ) with placebo ( plc ) + B in patients with relapsed/refractory multiple myeloma in a r and omized phase 2 study . Siltuximab was given by 6 mg/kg IV every 2 weeks . On progression , B was discontinued and high‐dose dexamethasone could be added to S/plc . Response and progression‐free survival ( PFS ) were analyzed pre‐dexamethasone by European Group for Blood and Marrow Transplantation ( EBMT ) criteria . For the 281 r and omized patients , median PFS for S + B and plc + B was 8.0 and 7.6 months ( HR 0.869 , P = 0.345 ) , overall response rate was 55 versus 47 % ( P = 0.213 ) , complete response rate was 11 versus 7 % , and median overall survival ( OS ) was 30.8 versus 36.8 months ( HR 1.353 , P = 0.103 ) . Sustained suppression of C‐reactive protein , a marker reflective of inhibition of interleukin‐6 activity , was seen with S + B. Siltuximab did not affect B pharmacokinetics . Siltuximab/placebo discontinuation ( 75 versus 66 % ) , grade ≥3 neutropenia ( 49 versus 29 % ) , thrombocytopenia ( 48 versus 34 % ) , and all‐ grade infections ( 62 versus 49 % ) occurred more frequently with S + B. The addition of siltuximab to bortezomib did not appear to improve PFS or OS despite a numerical increase in response rate in patients with relapsed or refractory multiple myeloma . © 2014 Wiley Periodicals , Inc. Am . J. Hematol . 90:42–49 , 2015 . © 2014 Wiley Periodicals , AIM To investigate the association of plasma levels of interleukin (IL)-6 and -8 with Wilms ' tumor 1 (WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma ( PDA ) treated with dendritic cells ( DCs ) pulsed with three types of major histocompatibility complex class I and II-restricted WT1 peptides combined with chemotherapy . METHODS During the entire treatment period , plasma levels of IL-6 and -8 were analyzed by ELISA . The induction of WT1-specific immune responses was assessed using the WT1 peptide-specific delayed-type hypersensitivity ( DTH ) test . RESULTS Three of 7 patients displayed strong WT1-DTH reactions throughout long-term vaccination with significantly decreased levels of IL-6/-8 after vaccinations compared with the levels prior to treatment . Moreover , overall survival ( OS ) was significantly longer in PDA patients with low plasma IL-6 levels ( < 2 pg/mL ) after 5 vaccinations than in patients with high plasma IL-6 levels ( ≥ 2 pg/mL ) ( P = 0.025 ) . After disease progression , WT1-DTH reactions decreased severely and were ultimately negative at the terminal stage of cancer . The decreased levels of IL-6/-8 observed throughout long-term vaccination were associated with WT1-specific DTH reactions and long-term OS . CONCLUSION Prolonged low levels of plasma IL-6/-8 in PDA patients may be a prognostic marker for the clinical outcomes of chemoimmunotherapy Objectives The aim of this study was to investigate the role of several cytokines including IL-2 , IL-6 , IL-8 , IL-10 , and TNF-α in the diagnosis of HPB cancers . Material s and Methods The prospect i ve study was performed between October 2007 and September 2014 . The study included 226 patients who were divided into 5 groups depending on their postoperative and histopathologic diagnosis : Control group included 30 healthy volunteers . Hepatocellular cancer ( HCC ) group included 24 patients diagnosed with HCC . Gallbladder cancer ( GBC ) group included 36 patients diagnosed with GBC . Cholangiocellular carcinoma group included 64 patients diagnosed with cholangiocellular carcinoma . Pancreatic cancer group included 72 patients diagnosed with pancreatic cancer . Serum levels of IL-2 , IL-6 , IL-8 , IL-10 , and TNF-α were measured using an enzyme-linked immunosorbent assay kit in accordance with the guidelines of the producer . Results Serum TNF-α concentration was significantly higher in the cholangiocellular carcinoma and pancreatic cancer groups compared to other groups . IL-6 and IL-10 were significantly increased in both the HCC and GBC groups , IL-2 , IL-6 , IL-10 , and TNF-α in the cholangiocellular carcinoma group , and IL-2 , IL-6 , IL-8 , and TNF-α in the pancreatic cancer group . Conclusion We suggest that cytokines can be used as useful markers in the diagnosis of HPB cancers |
10,541 | 31,711,383 | Conclusions MRAs seem to be effective in AF prevention , especially regarding recurrent AF episodes | Background Mineralocorticoid receptor antagonists ( MRAs ) have emerged as potential atrial fibrillation ( AF ) preventive therapy , but inconsistent results have been reported .
We aim ed to examine the effects of MRAs on AF occurrence and explore factors that could influence the magnitude of the effect size . | BACKGROUND The mineralocorticoid receptor antagonist eplerenone improved clinical outcomes among patients with heart failure with reduced ejection faction ( HFrEF ) in the EMPHASIS-HF ( Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure ) study . However , similar efficacy and safety have not been established in Japanese patients . We evaluated the efficacy and safety of eplerenone in patients with HFrEF in a multicenter , r and omized , double-blind placebo-controlled outcome study ( Clinical Trials.gov Identifier : NCT01115855 ) . The aim of the study was to evaluate efficacy predefined as consistency of the primary endpoint with that of EMPHASIS-HF at a point estimate of < 1 for the hazard ratio . Methods and Results : HFrEF patients with NYHA functional class II-IV and an EF ≤35 % received eplerenone ( n=111 ) or placebo ( n=110 ) on top of st and ard therapy for at least 12 months . The primary endpoint was a composite of death from cardiovascular causes or hospitalization for HF . The primary endpoint occurred in 29.7 % of patients in the eplerenone group vs. 32.7 % in the placebo group [ hazard ratio=0.85 ( 95 % CI : 0.53 - 1.36 ) ] . Hospitalization for any cause and changes in plasma BNP and LVEF were favorable with eplerenone . A total of 17 patients ( 15.3 % ) in the eplerenone group and 10 patients ( 9.1 % ) in the placebo group died . Adverse events , including hyperkalemia , were similar between the groups . CONCLUSIONS Eplerenone was well-tolerated in Japanese patients with HFrEF and showed results consistent with those reported in the EMPHASIS-HF study BACKGROUND Atrial fibrillation ( AF ) is a common arrhythmia that frequently recurs after restoration of sinus rhythm ( SR ) . Identifying risk factors for recurrence may help define the best strategy for secondary prevention . METHODS The GISSI-AF trial enrolled 1,442 patients in SR with at least 2 documented AF episodes in the previous 6 months or after cardioversion in the last 2 weeks . Patients were r and omized to valsartan or placebo ; all other treatments for AF or underlying heart diseases were allowed . Primary end points were time to first recurrence of AF and proportion of patients with > 1 AF episode during 1-year follow-up . We evaluated clinical and electrocardiographic baseline characteristics of all patients to identify independent predictors for AF recurrence using a Cox multivariable model . RESULTS Risk factors for AF recurrence were a history of 2 or more AF episodes in the previous 6 months , independent of the modality of SR restoration , spontaneous ( HR 1.42 , 95 % CI 1.14 - 1.77 , P = .002 ) , or by cardioversion ( HR 1.19 , 95 % CI 1.01 - 1.40 , P = .038 ) , and a lower heart rate during SR ( HR 0.99 , 95 % CI 0.99 - 1.00 , P = .052 ) . The risk factors were the same for > 1 AF recurrence . Patients treated with amiodarone had a lower risk for both end points ( P < .0001 and P = .017 ) , whereas those on diuretics had a greater risk ( P = .009 and P = .003 ) . CONCLUSIONS In the GISSI-AF study population , AF history had significant prognostic value independent of the modality of SR restoration . Amiodarone and diuretic treatment affected the rate of AF recurrence AIM Supraventricular arrhythmia is a major public health problem because of its prevalence and clinical consequences . The first step of the treatment usually consists in restoring sinusal rhythm . The aim of this study is to evaluate results and predictive factors of success of electrical cardioversion . METHODS We studied a series of 143 consecutive electric cardioversion preformed in 131 French patients . RESULTS The rate of successful direct current cardioversion was 91.2 % . Negative predictive factors are the height body mass index and the age of arrhythmia . Atrial flutter is a predictive factor of success . These results agree with published results . Our study highlights the interest of some nonantiarrhythmic drugs received by the patient during the period before the direct current cardioversion . Thus , a spironolactone treatment appears to be a new predictive factor of the success of electrical cardioversion ( success in patients treated with spironolactone : 100 % vs 89 % without , P = 0.04 ) . CONCLUSIONS Our results agree with usual predictive factors of the success of cardioversion . Nevertheless , a new approach is that of the positive effect of spironolactone on cardioversion . A prospect i ve r and omized study is necessary to confirm this result 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 Patients with congestive heart failure ( CHF ) often have increased aldosterone activity that leads to hypomagnesemia . Hypomagnesemia can induce arrhythmias , an important cause of death in patients with CHF . We determined whether the aldosterone receptor antagonist spironolactone improved magnesium homeostasis and reduced arrhythmias in patients with CHF . METHODS AND RESULTS We r and omized 116 consecutive patients with CHF into placebo control group ( n = 58 ) and spironolactone group ( 20 mg daily , n = 58 ) in addition to conventional therapy . Plasma magnesium concentration ( PMC ) , erythrocyte magnesium concentration ( EMC ) , and erythrocyte magnesium efflux were not different between the 2 groups of patients before treatment . Compared with control patients , patients treated with spironolactone for 6 months had increased PMC and EMC and decreased erythrocyte magnesium efflux . Patients on spironolactone therapy also had a marked decrease of 24-hour mean heart rate , ventricular and atrial premature beats , and the risk of atrial fibrillation/flutter . Pooled data from the 116 patients showed that patients with a higher EMC or a lower sodium-dependent erythrocyte magnesium efflux had a slower heart rate , fewer ventricular premature beats , and a lower risk of atrial fibrillation/flutter . CONCLUSIONS Our results suggest that reducing cellular magnesium efflux and loss may contribute to the spironolactone-reduced arrhythmias in patients with CHF Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Introduction The aim of this study was to compare the effect of ramipril/canrenone versus ramipril/hydrochlorothiazide ( HCTZ ) combination on atrial fibrillation ( AF ) recurrence in type 2 diabetic hypertensives with and without cardiac autonomic neuropathy ( CAN ) . Material and methods A total of 289 hypertensive type 2 diabetic patients , 95 with CAN , in sinus rhythm but with at least two episodes of AF in the previous 6 months were r and omized to ramipril 5 mg plus canrenone 50 mg ( titrated to 10/100 mg ) or to ramipril 5 mg plus HCTZ 12.5 mg ( titrated to 10/25 mg ) or to amlodipine 5 mg ( titrated to 10 mg ) for 1 year . Clinic blood pressure ( BP ) and a 24-h ECG were evaluated monthly . Patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible . Serum procollagen type I carboxy-terminal peptide ( PIP ) and carboxy-terminal telopeptide of collagen type I ( CITP ) were evaluated before and after each treatment period . Results Blood pressure was similarly and significantly reduced by all treatments . A total of 51 % of patients with amlodipine had a recurrence of AF , as did 31 % of patients with ramipril/HCTZ ( p < 0.05 vs. amlodipine ) and 13 % of patients with ramipril/canrenone ( p < 0.01 vs. amlodipine and p < 0.05 vs. ramipril/HCTZ ) . A similar trend was found in diabetic patients with CAN . Both combinations reduced PIP and increased CITP , but the effects of ramipril/canrenone were significantly more marked . Conclusions These findings suggest that in type 2 diabetic hypertensives , ramipril/canrenone treatment was more effective than ramipril/HCTZ in reducing AF recurrence . This could be related to the greater improvement in cardiac fibrosis Objective : Postoperative atrial fibrillation ( POAF ) is associated with poor outcomes after coronary artery bypass graft ( CABG ) surgery . We aim ed to assess the additional value of preoperative plasma aldosterone levels , a biomarker promoting proarrhythmic and profibrotic pathways , for predicting POAF after CABG . Methods : We conducted a prospect i ve cohort study involving consecutive patients with left ventricular ejection fraction ( LVEF ) more than 50 % requiring elective CABG in our university hospital . Plasma aldosterone levels , two-dimensional echocardiography including left atrial strain analysis and galectin-3 ( Gal-3 ) examination were assessed before cardiac surgery . The primary endpoint was the occurrence of POAF within 30 days after surgery . Results : POAF occurred in 34 ( 24.8 % ) out of the 137 included patients . Compared with controls , patients experiencing POAF were significantly older ( 73 years old ± 8 vs 65 ± 11 , P < 0.001 ) and had higher preoperative plasma aldosterone levels [ 183 pmol/l ( interquartile range 138–300 ) vs 143 pmol/l ( interquartile range 96.5–216.5 ) , P < 0.01 ] . Age [ odds ratio ( OR ) , 1.088 ; 95 % confidence interval ( CI ) ( 1.038–1.140 ) ; P = 0.0004 ] and plasma aldosterone levels [ OR , 1.007 ; 95 % CI ( 1.003–1.012 ) ; P = 0.0013 ] were independently associated with POAF in multivariate analysis and could therefore be combined to predict the occurrence of POAF [ ‘ Aldoscore ’ , OR , 2.7 ; 95 % CI ( 1.7–4.3 ) ; P < 0.0001 ] . Reverse transcriptase PCR analysis performed on right atrial appendage and plasma examination revealed that Gal-3 was activated in POAF patients . Conclusion : We developed the preoperative ‘ Aldoscore ’ for POAF risk stratification among patients with preserved LVEF requiring elective CABG . This new tool may be helpful to identify good responders to interventions targeting the proarrhythmic and profibrotic pathways of aldosterone OBJECTIVES The aim of this report was to show that the rate of cardiovascular events is increased in patients with either subtype of primary aldosteronism ( PA ) . BACKGROUND Primary aldosteronism involves hypertension ( HTN ) , hypokalemia , and low plasma renin . The two major PA subtypes are unilateral aldosterone-producing adenoma ( APA ) and bilateral adrenal hyperplasia . METHODS During a three-year period , the diagnosis of PA was made in 124 of 5,500 patients referred for comprehensive evaluation and management . Adenomas were diagnosed in 65 patients and idiopathic hyperaldosteronism in 59 patients . During the same period , clinical characteristics and cardiovascular events of this group were compared with those of 465 patients with essential hypertension ( EHT ) r and omly matched for age , gender , and systolic and diastolic blood pressure . RESULTS A history of stroke was found in 12.9 % of patients with PA and 3.4 % of patients with EHT ( odds ratio [ OR ] = 4.2 ; 95 % confidence interval [ CI ] 2.0 to 8.6 ] ) . Non-fatal myocardial infa rct ion was diagnosed in 4.0 % of patients with PA and in 0.6 % of patients with EHT ( OR = 6.5 ; 95 % CI 1.5 to 27.4 ) . A history of atrial fibrillation was diagnosed in 7.3 % of patients with PA and 0.6 % of patients with EHT ( OR = 12.1 ; 95 % CI 3.2 to 45.2 ) . The occurrence of cardiovascular complications was comparable in both subtypes of PA . CONCLUSIONS Patients presenting with PA experienced more cardiovascular events than did EHT patients independent of blood pressure . The presence of PA should be detected , not only to determine the cause of HTN , but also to prevent such complications Background Mannitol therapy to treat cerebral edema induces osmotic diuresis and electrolyte loss . In neurocritical care patients , potassium is the electrolyte that most often needs replacement . Objective of this study was to evaluate the effects of adding potassium sparing diuretic ( canrenone ) to mannitol therapy on potassium urinary excretion , potassium plasma levels , and incidence of new cardiac arrhythmias in patients receiving neurocritical care for cerebral edema . Methods Fifty-six patients were prospect ively assigned to mannitol or mannitol plus i.v . canrenone . Potassium urinary excretion , potassium plasma levels , urinary volume , and the incidence of new cardiac arrhythmias were recorded during the first 8 days of therapy . Results In patients treated with mannitol the potassium urinary excretion was stable over the first 3 days and significantly increased , compared to baseline , on day 4th to 8th ( baseline 20.3 ± 10.6 mEq/l/die , day 8th 24.6 ± 10.6 mEq/l/die , P < 0.05 ) ; while potassium plasma levels significantly decreased . In patients receiving mannitol plus canrenone potassium urinary excretion decreased from day 3rd to 8th ( baseline 21.9 ± 11.6 mEq/l/die , day 8th 15.9 ± 10.9 mEq/l/die , P < 0.015 ) and potassium plasma levels increased but remained within normal values range . The incidence of new cardiac arrhythmias was higher in the mannitol group than the mannitol plus canrenone group ( 35.7 vs. 10.7 % ; P < 0.01 ) . Urinary volumes , potassium balance , and sodium plasma concentration were similar in the 2 study groups . Conclusion In patients receiving neurocritical care for cerebral edema , the adjunct of a potassium sparing diuretic ( canrenone ) to mannitol therapy reduces potassium urinary loss , prevents hypokalemia , and reduces the incidence of new cardiac arrhythmias Objective : This study tested the hypothesis that interruption of the renin – angiotensin system with either an angiotensin-converting enzyme inhibitor or a mineralocorticoid receptor antagonist will decrease the prevalence of atrial fibrillation after cardiac surgery . Design : R and omized double-blind placebo-controlled study . Setting : University-affiliated hospitals . Patients : Four hundred forty-five adult patients in normal sinus rhythm undergoing elective cardiac surgery . Interventions : One week to 4 days prior to surgery , patients were r and omized to treatment with placebo , ramipril ( 2.5 mg the first 3 days followed by 5mg/day , with the dose reduced to 2.5mg/day on the first postoperative day only ) , or spironolactone ( 25mg/day ) . Measurements : The primary endpoint was the occurrence of electrocardiographically confirmed postoperative atrial fibrillation . Secondary endpoints included acute renal failure , hyperkalemia , the prevalence of hypotension , length of hospital stay , stroke , and death . Main Results : The prevalence of atrial fibrillation was 27.2 % in the placebo group , 27.8 % in the ramipril group , and 25.9 % in the spironolactone group ( p = .95 ) . Patients in the ramipril ( 0.7 % ) or spironolactone ( 0.7 % ) group were less likely to develop acute renal failure than those r and omized to placebo ( 5.4 % , p = .006 ) . Patients in the placebo group tended to be hospitalized longer than those in the ramipril or spironolactone group ( 6.8±8.2 days vs. 5.7±3.2 days and 5.8±3.4 days , respectively , p = .08 for the comparison of placebo vs. the active treatment groups using log-rank test ) . Compared with patients in the placebo group , patients in the spironolactone group were extubated sooner after surgery ( 576.4±761.5 mins vs. 1091.3±3067.3 mins , p = .04 ) . Conclusions : Neither angiotensin-converting enzyme inhibition nor mineralocorticoid receptor blockade decreased the primary outcome of postoperative atrial fibrillation . Treatment with an angiotensin-converting enzyme inhibitor or mineralocorticoid receptor antagonist was associated with decreased acute renal failure . Spironolactone use was also associated with a shorter duration of mechanical ventilation after surgery BACKGROUND AND AIMS Recent clinical evidence demonstrates that chronic low-dose mineralocorticoid receptor antagonists ( MRA ) , when added to optimal treatment , result in reductions in cardiovascular mortality . However , continuation of MRAs before cardiac surgery in patients with CKD has never been evaluated and its potential benefit or harm in this specific clinical setting is largely unknown . MATERIAL S AND METHODS This is an observational study that included adult CKD patients undergoing cardiac surgery . Patients were divided into two groups according to preoperative use of spironolactone ( SPL ) . The studied outcomes were postoperative acute kidney injury ( AKI ) requiring dialysis , mortality , and major morbidities ( cardiovascular , neurologic , and infectious ) . RESULTS Data on 698 patients with preoperative CKD stage III and IV were analyzed : 99 received SPL preoperatively and 599 did not . At baseline , patients on SPL had higher EuroScore and had more complicated surgery . No significant differences in the incidence of postoperative AKI , myocardial infa rct ion ( MI ) , cardiovascular accident ( CVA ) , sepsis , and mortality were detected between groups in both univariate and multivariate analyses . However , incidence of postoperative low cardiac output state ( p < 0.008 ) was significantly higher in the SPL group . Propensity score matching analyses yielded similar results . CONCLUSIONS Although SPL is usually administered to significantly sicker patients , its use is not associated with increased major postoperative complications . However , the modulating effect of SPL in this clinical study remains to be eluci date d in a prospect i ve r and omized trial . Angiotensin II and aldosterone are key factors responsible for the structural and neurohormonal remodeling of the atria and ventricles in patients with atrial fibrillation ( AF ) . The aim of the present study was to evaluate the antiarrhythmic effects of spironolactone compared to angiotensin-converting enzyme inhibitors in patients with recurrent AF . A cohort of 164 consecutive patients ( mean age 66 years , 87 men ) , with an average 4-year history of recurrent AF episodes , was enrolled in a prospect i ve , r and omized , 12-month trial with 4 treatment arms : group A , spironolactone , enalapril , and a β blocker ; group B , spironolactone and a β blocker ; group C , enalapril plus a β blocker ; and group D , a β blocker alone . The primary end point of the trial was the presence of symptomatic AF episodes documented on the electrocardiogram . At 3- , 6- , 9- , and 12 months , a significant ( p < 0.001 ) reduction had occurred in the incidence of AF episodes in both spironolactone-treated groups ( group A , spironolactone , enalapril , and a β blocker ; and group B , spironolactone plus a β blocker ) compared to the incidence in patients treated with enalapril and a β blocker ( group C ) or a β blocker alone ( group D ) . No significant difference was seen in AF recurrences between patients taking spironolactone and a β blocker with ( group A ) and without ( group B ) enalapril . No significant differences were found in the systolic or diastolic blood pressure or heart rate among the groups before and after 1 year of follow-up . In conclusion , combined spironolactone plus β-blocker treatment might be a simple and valuable option in preventing AF episodes in patients with normal left ventricular function and a history of refractory paroxysmal AF OBJECTIVE The aim of the study was to evaluate the association between renin - angiotensin - aldosterone system blockers and risk of postoperative atrial fibrillation ( AF ) development in patients with mild and moderate left ventricular systolic dysfunction . METHODS The population of this prospect i ve and observational study consisted of 269 patients with an ejection fraction of < or = 50 % undergoing coronary artery bypass and /or valve surgery . Use of renin -angiotensin-aldosterone system blockers ( angiotensin converting enzyme inhibitors ( ACEI ) , angiotensin receptor blockers ( ARB ) and spironolactone ) and their association with postoperative AF ( AF episode lasting < or = 5 min ) were evaluated . In statistical analysis t test for independent sample s , Chi-square test and Mann Whitney U test were used for comparison of variables between groups . Predictors of postoperative AF were determined by multiple logistic regression analysis . RESULTS During follow-up , 50 patients ( 13 % ) developed postoperative AF . With multiple logistic regression analysis , risk factors for postoperative AF were determined : left atrial diameter ( OR- 1.09 ; 95%CI 1.01 - 1.16 , p=0.02 ) , age ( OR-1.04 ; 95%CI 1.002- 1.08 , p=0.04 ) , aortic cross-clamp duration ( OR- 1.03 , 95%CI -1.00 - 1.05 , p=0.01 ) , use of left internal mammarian artery ( OR-0.33 ; 95%CI 0.13 - 0.88 , p=0.03 ) , ACEIs treatment ( OR-0.27 ; 95%CI 0.12 - 0.62 , p=0.002 ) , and ARBs treatment ( OR - 0.21 , 95%CI 0.07 - 0.62 , p=0.005 ) . CONCLUSIONS Our results indicate that although treatments with ACEIs and ARBs are associated with low incidence of postoperative AF in patients with mild and moderate left ventricular systolic dysfunction , treatment with spironolactone is not OBJECTIVES This study assessed the relationship between atrial fibrillation ( AF ) and outcomes in the TOPCAT ( Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist ) trial , to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-r and omization AF . BACKGROUND AF is common in heart failure with preserved ejection fraction ( HFpEF ) and likely contributes to increased risk of adverse outcomes . METHODS A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups : no known AF , history of AF without AF at enrollment , and AF found on the electrocardiogram ( ECG ) at enrollment . We assessed outcomes and treatment response to spironolactone in all groups , and the association between post-r and omization AF and outcomes in patients free of AF at baseline . The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality , aborted cardiac arrest , or heart failure hospitalization . RESULTS A total of 760 patients ( 43 % ) had a history of AF ( 18 % ) or AF on ECG at enrollment ( 25 % ) . The highest adjusted risk was associated with AF at enrollment ( primary outcome , hazard ratio : 1.34 ; 95 % confidence interval : 1.09 to 1.65 ; p = 0.006 ; and an increased early risk of secondary outcomes ) . Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone . Post-r and omization AF , which occurred in 6.3 % of patients , was not influenced by spironolactone treatment , but was associated with an increased early risk of the primary outcome ( hazard ratio : 2.32 ; 95 % confidence interval : 1.59 to 3.40 ; p < 0.0001 ) and secondary outcomes . CONCLUSIONS AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study . Post-r and omization AF , which was associated with an increased risk of morbidity and mortality , was not influenced by spironolactone . ( Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [ TOPCAT ] ; NCT00094302 ) BACKGROUND Effectiveness , safety , and other factors associated with success of cardioversion ( CV ) of atrial fibrillation ( AF ) have not yet been evaluated in patients with reduced left ventricular ejection fraction . We studied 148 consecutive patients with left ventricular dysfunction ( ejection fraction < or = 45 % ) , who underwent electrical CV for AF in our department . The patients had New York Heart Association heart failure ranging from class II to IV . The overall CV success rate was 71 % . We relied on univariate and multivariate regression and sought variables influencing success rate . Conversion success did not correlate with New York Heart Association class . Instead , we found that the greatest predictor was the degree of heart failure treatment . Patients receiving beta-blockers , angiotensin-converting enzyme inhibitors or angiotension receptor blockers , plus mineralocorticoid receptor blockers had the greatest chance for conversion success . Success was more likely in patients with coronary artery disease ( 91 % ) than in patients with nonischemic cardiomyopathy . CONCLUSIONS Cardioversion is a safe and effective method for the restoration of sinus rhythm in patients with AF and reduced left ventricular ejection fraction . Our findings underscore the value of aggressive heart failure treatment before CV in patients with AF |
10,542 | 32,129,728 | Conclusion : The findings proposed that adherence to diets with high DII ® scores was associated with increased WC . | Background s : Central obesity , as a pivotal component of metabolic syndrome is associated with numerous co-morbidities .
Dietary factors influence central obesity by increased inflammatory status .
However , recent studies did n't evaluate the association between central obesity and dietary inflammation index ( DII ® ) that give score to dietary factors according to their inflammatory potential . | In 1998 , the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention . Among the strategies discussed was the measurement of markers of inflammation.1 The Conference concluded that “ many of these markers ( including inflammatory markers ) are not yet considered applicable for routine risk assessment because of : ( 1 ) lack of measurement st and ardization , ( 2 ) lack of consistency in epidemiological findings from prospect i ve studies with endpoints , and ( 3 ) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors . ” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using st and ard risk factors . Since these publications , a large number of peer- review ed scientific reports have been published relating inflammatory markers to cardiovascular disease ( CVD ) . Several commercial assays for inflammatory markers have become available . As a consequence of the exp and ing research base and availability of assays , the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly . Despite this , there has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice . On March 14 and 15 , 2002 , a workshop titled “ CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease : Applications to Clinical and Public Health Practice ” was convened in Atlanta , Ga , to address these issues . The goals of this workshop were to determine which of the currently available tests should be used ; what results should be used to define high risk ; which patients should be tested ; and the indications for which the tests would be most useful . These Background Diet is known to play a key role in atherogenesis and in the development of cardiovascular events . Dietary factors may mediate these processes acting as potential modulators of inflammation . Potential Links between inflammatory properties of diet and the occurrence of cardiovascular events have not been tested previously . Objective We aim ed to assess the association between the dietary inflammatory index ( DII ) , a method to assess the inflammatory potential of the diet , and incident cardiovascular disease . Methods In the prospect i ve , dynamic SUN cohort , 18,794 middle-aged , Spanish university graduates were followed up for 8.9 years ( median ) . A vali date d 136-item food-frequency question naire was used to calculate the DII . The DII is based on scientific evidence about the relationship between diet and inflammatory biomarkers ( C-reactive protein , IL-1β , IL-4 , IL-6 , IL-10 and TNF-α ) . Cox proportional hazard models were used to estimate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) for the association between the DII and incident cardiovascular disease ( myocardial infa rct ion , stroke or cardiovascular death ) . Results The risk for cardiovascular events progressively increased with each increasing quartile of DII ( ptrend = 0.017 ) . The multivariable-adjusted HR for participants in the highest ( most pro-inflammatory ) vs. the lowest quartile of the DII was 2.03 ( 95 % CI 1.06–3.88 ) . Conclusions A pro-inflammatory diet was associated with a significantly higher risk for developing cardiovascular events Inflammation plays a central role in pancreatic cancer etiology and can be modulated by diet . We aim ed to examine the association between the inflammatory potential of diet , assessed with the Dietary Inflammatory Index ( DII ® ) , and pancreatic cancer risk in the Prostate , Lung , Colorectal and Ovarian Cancer Screening Trial prospect i ve cohort . Our study included 101,449 participants aged 52 - 78 years at baseline who completed both baseline question naire and a diet history question naire . Energy-adjusted DII ( E-DII ) scores were computed based on food and supplement intake . Cox proportional hazards models and time dependent Cox models were used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) with participants in the lowest E-DII quintile ( most anti-inflammatory scores ) as referent . After a median 8.5 years of follow-up , 328 pancreatic cancer cases were identified . E-DII scores were not associated with pancreatic cancer risk in the multivariable model ( HRQ5vsQ1 = 0.94 ; 95 % CI = 0.66 - 1.35 ; p-trend = 0.43 ) . Time significantly modified the association ( p-interaction = 0.01 ) . During follow up < 4 years , there was suggestive evidence of an inverse association between E-DII and pancreatic cancer ( HRQ5vsQ1 = 0.60 ; 95 % CI = 0.35 - 1.02 ; p-trend = 0.20 ) while there was a significant positive trend in the follow up ≥4 years ( HRQ5vsQ1 = 1.31 ; 95 % CI = 0.83 - 2.08 ; p-trend = 0.03 ) . Similar results were observed for E-DII from food only . Our study does not support an association between inflammatory potential of diet and pancreatic cancer risk ; however , heterogeneous results were obtained with different follow-up times . These divergent associations may result from the influences of undetected disease in the short-term Previous studies have reported an association between a more pro-inflammatory diet profile and various chronic metabolic diseases . The Dietary Inflammatory Index ( DII ) was used to assess the inflammatory potential of nutrients and foods in the context of a dietary pattern . We prospect ively examined the association between the DII and the incidence of cardiovascular disease ( CVD : myocardial infa rct ion , stroke or cardiovascular death ) in the PREDIMED ( Prevención con Dieta Mediterránea ) study including 7216 high-risk participants . The DII was computed based on a vali date d 137-item food frequency question naire . Multivariate-adjusted hazard ratios ( HR ) and 95 % confidence intervals of CVD risk were computed across quartiles of the DII where the lowest ( most anti-inflammatory ) quartile is the referent . Risk increased across the quartiles ( i.e. , with increasing inflammatory potential ) : HRquartile2 = 1.42 ( 95%CI = 0.97–2.09 ) ; HRquartile3 = 1.85 ( 1.27–2.71 ) ; and HRquartile4 = 1.73 ( 1.15–2.60 ) . When fit as continuous the multiple-adjusted hazard ratio for each additional st and ard deviation of the DII was 1.22 ( 1.06–1.40 ) . Our results provide direct prospect i ve evidence that a pro-inflammatory diet is associated with a higher risk of cardiovascular clinical events The possible relationship between diet-related inflammation and the risk of prediabetes requires further investigation , especially in non-Western population s. We examined the ability of the dietary inflammatory index ( DII ) to predict the risk of prediabetes in a case-control study conducted at specialized centers in Esfahan , Iran . A total of 214 incident cases of prediabetes were selected with the nonr and om sampling procedure , and the 200 controls r and omly selected from the same clinics were frequency-matched on age ( ±5 years ) and sex . DII scores were computed based on dietary intake assessed using a vali date d and reproducible 168-item food-frequency question naire . Linear and logistic regression models were used to estimate multivariable beta estimates and odds ratios ( ORs ) . Subjects in tertile 3 versus tertile 1 ( T3VS1 ) of DII had significantly higher fasting plasma glucose ( DIIT3VS1 : b = 4.49 ; 95 % CI 1.89 , 7.09 ) , oral glucose tolerance ( DIIT3VS1 : b = 8.76 ; 95 % CI 1.78 , 15.73 ) , HbA1c ( DIIT3VS1 : b = 0.30 ; 95 % CI 0.17 , 0.42 ) , low-density lipoprotein ( DIIT3VS1 : b = 16.37 ; 95 % CI 11.04 , 21.69 ) , triglyceride ( DIIT3VS1 : b = 21.01 ; 95 % CI 8.61 , 33.42 ) and body fat ( DIIT3VS1 : b = 2.41 ; 95 % CI 0.56 , 4.26 ) and lower high-density lipoprotein ( DIIT3VS1 : b = -3.39 ; 95 % CI -5.94 , -0.84 ) and lean body mass ( DIIT3VS1 : b = -3.11 ; 95 % CI -4.83 , -1.39 ) . After multivariate adjustment , subjects in the most pro-inflammatory DII group had 19 times higher odds of developing prediabetes compared with subjects in tertile 1 ( DIIT3VS1 : OR = 18.88 ; 95 % CI 7.02 , 50.82 ) . Similar results were observed when DII was used as a continuous variable , ( DIIcontinuous : OR = 3.62 ; 95 % CI 2.50 , 5.22 ) . Subjects who consumed a more pro-inflammatory diet were at increased risk of prediabetes compared with those who consumed a more anti-inflammatory diet SCOPE Low- grade chronic inflammation is associated with several chronic conditions , and diet is known to play a role in chronic inflammation . We aim ed to evaluate the association between the inflammatory potential of the diet and mortality in the Spanish population from the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Spain ) . METHODS AND RESULTS The study included 41 199 participants ( 62 % female ) aged 29 - 69 years from five Spanish regions . During 18 years of follow-up 3316 deaths were identified . The dietary inflammatory potential was assessed by means of an inflammatory score of the diet ( ISD ) , calculated using 30 dietetic components and their corresponding inflammatory scores ( weights ) . The association between the ISD and mortality was analyzed by multivariate Cox regression models . There was a significant association between ISD and mortality : subjects classified in the fifth quintile of the ISD ( more proinflammatory diets ) had a hazard ratio of 1.42 ( 95%-confidence interval 1.25 - 1.60 ) as compared with those in the first quintile ; the corresponding figures were 1.89 ( 1.48 - 2.40 ) for cardiovascular diseases mortality and 1.44 ( 1.22 - 1.69 ) for death by cancer . CONCLUSION Consuming more proinflammatory diets , expressed by means of the ISD , is associated with higher mortality ; this effect seems to be stronger for deaths by cardiovascular diseases BACKGROUND Inflammation is known to be related to the leading causes of death including cardiovascular disease , several types of cancer , obesity , type 2 diabetes , depression-suicide and other chronic diseases . In the context of whole dietary patterns , the Dietary Inflammatory Index ( DII ® ) was developed to appraise the inflammatory potential of the diet . OBJECTIVE We prospect ively assessed the association between DII scores and all-cause mortality in two large Spanish cohorts and valuated the consistency of findings across these two cohorts and results published based on other cohorts . DESIGN We assessed 18,566 participants in the " Seguimiento Universidad de Navarra " ( SUN ) cohort followed-up during 188,891 person-years and 6790 participants in the " PREvencion con DIeta MEDiterránea " ( PREDIMED ) r and omized trial representing 30,233 person-years of follow-up . DII scores were calculated in both cohorts from vali date d FFQs . Higher DII scores corresponded to more proinflammatory diets . A total of 230 and 302 deaths occurred in SUN and PREDIMED , respectively . In a r and om-effect meta- analysis we included 12 prospect i ve studies ( SUN , PREDIMED and 10 additional studies ) that assessed the association between DII scores and all-cause mortality . RESULTS After adjusting for a wide array of potential confounders , the comparison between extreme quartiles of the DII showed a positive and significant association with all-cause mortality in both the SUN ( hazard ratio [ HR ] = 1.85 ; 95 % CI : 1.15 , 2.98 ; P-trend = 0.004 ) and the PREDIMED cohort ( HR = 1.42 ; 95 % CI : 1.00 , 2.02 ; P-trend = 0.009 ) . In the meta- analysis of 12 cohorts , the DII was significantly associated with an increase of 23 % in all-cause mortality ( 95 % CI : 16%-32 % , for the highest vs lowest category of DII ) . CONCLUSION Our results provide strong and consistent support for the hypothesis that a pro-inflammatory diet is associated with increased all-cause mortality . The SUN cohort and PREDIMED trial were registered at clinical trials.gov as NCT02669602 and at is rct n.com as IS RCT N35739639 , respectively BACKGROUND The Dietary Inflammatory Index ( DII ) is a comprehensive , literature -derived index for assessing the effect of dietary constituents on inflammatory biomarkers . Several studies have shown an association between DII score and mortality , but there are limited prospect i ve studies in Asian population s. OBJECTIVES The aim of this study was to investigate the association between DII score and risk of all-cause , total cardiovascular disease ( CVD ) , stroke , coronary heart disease ( CHD ) , total cancer , digestive cancer , and noncancer/non-CVD mortality in the Japanese population . METHODS A total of 58,782 Japanese participants aged 40 - 79 y who were enrolled in the Japan Collaborative Cohort Study during 1988 - 1990 were included in the analysis . DII scores were calculated based on a food-frequency question naire . HRs and 95 % CIs for mortality according to DII quintiles were estimated using Cox proportional hazards models . RESULTS During the median follow-up period of 19.3 y , a total of 11,693 participants died . The multivariable HR for all-cause mortality for the highest compared with the lowest DII quintiles was 1.13 ( 95 % CI : 1.05 , 1.21 ) . For CVD mortality , the highest multivariable HRs were 1.30 ( 95 % CI : 1.13 , 1.49 ) , 1.29 ( 95 % CI : 1.05 , 1.59 ) , and 1.30 ( 95 % CI : 0.96 , 1.76 ) for total CVD , stroke , and CHD , respectively . No significant associations were observed between DII and risk of total cancer , digestive cancer , and noncancer/non-CVD mortality . CONCLUSION Our findings suggest that a higher DII was associated with an increased risk of all-cause and CVD mortality among Japanese adults OBJECTIVE This study prospect ively assessed the association of the inflammatory potential of a diet using the dietary inflammatory index ( DII ) with average yearly weight changes and incident overweight/obesity . METHODS Seven thous and and twenty-seven university graduates with body mass index < 25 from the Seguimiento Universidad de Navarra ( SUN ) cohort were followed up during a median of 8.1 years . The DII , a vali date d tool based on scientific evidence to appraise the relationship between dietary parameters and inflammatory biomarkers , was used . A vali date d food-frequency question naire was used to assess intake of total energy , food , and nutrients , from which DII scores were calculated at baseline and after 10 years of follow-up . RESULTS After a median follow-up of 8.1 years , 1,433 incident cases of overweight or obesity were observed . Hazard ratios for overweight/obesity were calculated , including multivariable time-dependent Cox regression models with repeated measures of diet . The hazard ratio for subjects in the highest quartile ( most pro-inflammatory diet ) was 1.32 ( 95 % confidence interval 1.08 - 1.60 ) compared with participants in the lowest quartile ( most anti-inflammatory diet ) , with a significant linear dose-response relationship ( P = 0.004 ) . Consistently , increases in average yearly weight gains were significantly associated with proinflammatory diets . CONCLUSIONS A proinflammatory diet was significantly associated with a higher annual weight gain and higher risk of developing new-onset overweight or obesity |
10,543 | 23,207,739 | There were no significant differences in side effects between groups .
Levalbuterol was not superior to albuterol regarding efficacy and safety in subjects with acute asthma .
We suggest that levalbuterol should not be used over albuterol for acute asthma | BACKGROUND Conventional albuterol is a racemic mixture of (S)-albuterol and (R)-albuterol ( levalbuterol ) .
Levalbuterol is therapeutically active component of albuterol whereas (S)-albuterol is considered inert with some unwanted effects .
OBJECTIVES To evaluate efficacy and safety of levalbuterol versus albuterol in acute asthma . | STUDY OBJECTIVE An efficacy treatment study is conducted comparing levalbuterol to racemic albuterol for acute pediatric asthma in the emergency department ( ED ) . METHODS This was a prospect i ve , double-blind , r and omized , controlled study involving 129 children ( 2 to 14 years ) , presenting to a pediatric ED with an acute moderate or severe asthma exacerbation . Children were treated using a st and ard ED asthma pathway . Primary outcomes were changes from baseline in clinical asthma score and the percentage of predicted forced expiratory volume in 1 second after the first , third , and fifth treatment . Secondary outcomes included number of treatments , length of ED care , rate of hospitalization , and changes in pulse rate , respiratory rate , and oxygen saturation . Occurrence of adverse events was recorded . RESULTS Sixty-four children in the racemic albuterol and 65 children in the levalbuterol group completed the study . There were no differences between groups in primary outcomes , secondary outcomes , or adverse events . CONCLUSION There was no difference in clinical improvement in children with acute moderate to severe asthma exacerbations treated with either racemic albuterol or levalbuterol The (R)-enantiomer of racemic albuterol produces bronchodilation , whereas the (S)-enantiomer may increase airway reactivity . After oral or intravenous administration of racemic albuterol , the (R)- enantiomer is metabolized several times faster than the (S)-enantiomer ; however , enantiomer disposition after inhaling racemic albuterol with a metered-dose inhaler ( MDI ) is not known . Accordingly , 10 healthy subjects inhaled racemic albuterol with a MDI alone and with a MDI and holding chamber . We measured plasma levels of unchanged (R)- and (S)-albuterol before and up to 4 h after inhalation of racemic albuterol , and determined the unchanged R/S ratio in urine before and at 0.5 , 4 , 8 , and 24 h later . The disposition of albuterol 's enantiomers with a MDI and holding chamber was similar to that with a MDI alone . The area under the curve ( AUC ) of the plasma levels over time was significantly lower for the (S)- than for the (R)-enantiomer-395.5 + /- 141.0 ( SE ) versus 882.7 + /- 126.4 ng . ml(-)(1 ) . min ( p < 0.05)-indicating preferential retention of (S)-albuterol in the lung . The R/S ratio in urine at 0 . 5 h after albuterol was > 1 , reflecting the higher plasma level of the (R)-enantiomer . In conclusion , preferential retention of the (S)- compared with the (R)-enantiomer in the lung could lead to accumulation of the (S)-enantiomer after long-term use of racemic albuterol Objective To compare efficacy and tolerability of levosalbutamol ( Group 1 ) and racemic salbutamol ( Group 2 ) for the treatment of acute exacerbation of asthma in children age 5 to 18 yr . Methods A r and omized double blind clinical study involving 60 children was undertaken between October ’ 06 to December ’ 07 . Results The following baseline clinical characteristic were recorded initially and after giving 3 nebulizations at 20 min intervals in the Ist hour of presentation viz respiratory rate ( RR ) , heart rate ( HR ) , oxygen saturation in room air SPO2 , PEFR ( peak expiratory flow rate ) , serum K+ level and asthma score . In Group 1 patients ( levosalbutamol ) , there was significant increment in SPO2 and PEFR ( P<0.05 ) values with decrease in tachypnea and asthma score while no significant difference was found in pre and post treatment HR & Serum K+ levels . In Group 2 patients although there was clinical improvement in terms of SPO2 , PEFR , RR and asthma score , it result ed in significant tachycardia and decrease in K+ levels . Conclusion Levosalbutamol appears to be more efficacious than racemic salbutamol in terms of improvement in PEFR , SPO2 and asthma score while deleterious effects of tachycardia and fall in serum K+ were seen with racemic salbutamol Objective : To compare levalbuterol and racemic albuterol for the treatment of acute exacerbation of asthma in pediatric population . Design : Prospect i ve , double-blind , r and omized research trial in a pediatric emergency department of an urban tertiary care hospital . Participants : Children 5 to 21 years with a history of asthma presenting to the emergency department in acute exacerbation . Interventions : As per a computer-generated r and omization sequence , patients received either 1.25 mg of levalbuterol or albuterol 2.5 mg via nebulization along with ipratropium hydrochloride . Patients received 3 back-to-back treatments as needed every 20 minutes , maximum of 3 ; 2 mg/kg of oral prednisone was administered to the patients after the second treatment . Baseline respiratory parameters such as oxygen saturations , respiratory rates , and peak flow rates were measured and repeated after every treatment . The decision for further treatments and or hospitalization was made by the treating emergency department physician as per his/her clinical judgement of the respiratory parameters at the end of 3 treatments . Results : Seventy patients completed the study . Most of the patients were in moderate severity of asthma exacerbation . All patients in both groups showed improvement in oxygen saturations , respiratory rates , and peak flow rates . However , no statistically significant difference was observed in the 2 groups regarding the respiratory parameters ( P > 0.05 ) . Conclusion : Levalbuterol is not more efficacious than racemic albuterol in improving respiratory parameters in children presenting with acute exacerbation of asthma Objective . To compare racemic albuterol ( RAC ) with levalbuterol ( LEV ) in continuous form for the treatment of acute pediatric asthma exacerbations in the emergency department . Study design . Children between the ages of 6 and 17 inclusive were enrolled if they had a history of asthma , presented to the emergency department with an acute asthma exacerbation , and had an initial forced expiratory volume in 1 second ( FEV1 ) < 70 % predicted . Patients were then r and omized to receive either 7.5 mg of RAC or 3.75 mg of LEV over 1 hour , in addition to st and ard asthma therapies . Spirometry and asthma scoring were performed at the end of the first hour , and a second hour-long nebulization with the same drug was administered if deemed necessary . Spirometry and asthma scoring were again performed and the final disposition was recorded . As a second , optional part of the study , baseline serum albuterol levels were collected on some patients before treatment . Results . A total of 99 patients completed the study ( 44 RAC and 55 LEV ) . Baseline characteristics were similar except that the RAC group had a higher baseline asthma score . Children in the RAC group had a greater improvement in their FEV1 ( p = .043 ) as well as in their asthma scores ( p = .01 ) after 1 hour of continuous treatment compared to the LEV group . The greater improvement in asthma scores was maintained after the second hour of continuous therapy in the RAC group ( p = .008 ) but not for FEV1 measurements ( p = .57 ) . There were no differences between groups for changes in heart rate , respiratory rate , oxygen saturation , or rates of admission . Conclusions . At the doses used , RAC appears to be superior to LEV with respect to changes in FEV1 and asthma score . There was no significant difference between the drugs with respect to admission rates or side-effect profile Objectives of this study were to compare the pharmacokinetics , pharmacodynamics and safety of single cumulative doses of active (R)-salbutamol given either as the single enantiomer or racemic mixture by inhalation to subjects with mild to moderate asthma . This was a double-blind , crossover , cumulative-dose , r and omized study where all subjects received either four doses of 1.25 mg of (R)-salbutamol or 2.5 mg of racemic ( RS- ) salbutamol by nebulization . The pharmacokinetic parameters were determined by noncompartmental analysis and model-fitting . Changes in FEV(1 ) , plasma potassium , plasma glucose , heart rate , and QTc interval were measured . The potassium and glucose data were fitted to indirect response pharmacodynamic models . The heart rate and QTc data were evaluated using data descriptors . No significant differences in pharmacokinetics of (R)-salbutamol given as either (R)- or (RS)-salbutamol were found with AUC values of 11.90 + /- 4.37 and 11 . 47 + /- 2.88 ng.h/ml . The t(max)of about 2 h reflected serial dosing rather than delayed absorption . The t(1/2)averaged about 3.5 h. The (S)-salbutamol showed AUC of 48.46 + /- 12.11 ng.h/ml with a t(1/2)of about 5 h. The changes in FEV(1)reached a plateau after an initial increase and did not return to pre-drug values for 10 h. All pharmacodynamic parameters were similar whether (R)- or (RS)-salbutamol was given . The exposure to (R)-salbutamol was identical after inhalation of ( R ) - and (RS)-salbutamol by subjects with asthma . Several pharmacological responses including FEV(1)were also similar and there were no unique safety concerns with either treatment UNLABELLED This multicenter , r and omized , double-blind trial compared nebulized levalbuterol ( Lev ) and racemic albuterol ( Rac ) in the treatment of acute asthma . METHODS Adults with acute asthma exacerbations ( FEV(1 ) 20%-55 % predicted ) received prednisone and either Lev ( 1.25 mg , n = 315 ) or Rac ( 2.5 mg , n = 312 ) . Nebulized treatments were administered every 20 minutes in the first hour , then every 40 minutes for 3 additional doses , then as necessary for up to 24 hours . The primary end point was time to meet discharge criteria . Secondary end points included changes in lung function and hospitalization rates . A subset of 160 patients had plasma (S)-albuterol concentrations determined at study entry . RESULTS Time to meet discharge criteria did not differ between the 2 treatments . FEV(1 ) improvement was greater following Lev compared with Rac , both after dose 1 and cumulatively over the entire treatment period ( dose 1 in intent to treat [ ITT ] group : Lev 0.50 + /- 0.43 L , Rac 0.43 + /- 0.37 L ; P = .02 ) , particularly among the 60 % of patients not on recent steroid therapy ( dose 1 : Lev 0.58 + /- 0.47 L , Rac 0.44 + /- 0.37 L ; P < .01 ) , and patients whose entry (S)-albuterol concentrations were in the highest quartile of those measured . A small and similar proportion of Lev-treated ( 7.0 % ) and Rac-treated ( 9.3 % ) patients required hospitalization ( P = .28 ) . Among patients not on steroids , fewer Lev- than Rac-treated patients required admission ( 3.8 % vs 9.3 % , P = .03 ) , as was also the case for patients with high plasma (S)-albuterol concentrations . Asthma relapses ( 5 % in 30 days ) were lower than in previous reports and did not differ between groups . CONCLUSIONS This study suggests that early , regular nebulized beta(2)-agonist and systemic corticosteroid therapy may reduce hospitalization and relapse rates in patients with acute severe asthma . Lev was well tolerated and compared favorably with Rac in improving airway function , particularly in those who were not on inhaled or oral corticosteroids and in those who had high plasma (S)-albuterol concentrations at presentation |
10,544 | 24,499,628 | In non-comparative longitudinal studies , the use of a single-dose of primaquine was shown to deter the transmission of malaria briefly .
Conclusion Evidence on the transmission blocking effect of artemisinin derivatives and primaquine is conclusive . | Background Among the currently used drugs in malaria case management , artemisinin derivatives and primaquine have an impact on the transmissible stages of Plasmodium falciparum .
Hence , they reduce the transmission of the parasite from the patient to the mosquitoes .
The present study aim ed to assess evidence for this hypothesis from controlled trials . | Abstract The prophylactic and sporontocidal efficacy of st and ard antimalarials was studied among non-immune adult male volunteers challenged by mosquitoes heavily infected with two strains of chloroquine resistant Plasmodium falciparum from Malaya . The Poo . strain from Trengganu broke through in 12 of 15 men receiving chloroquine 300 mg . ( base ) and primaquine 45 mg . ( base ) at weekly intervals , whereas 8 weeks of this treatment protected all 3 men challenged with the Tay . strain from Kota Tinggi , Johore State . The Poo . strain broke through in 5 men given amodiaquine base 300 mg . and DDS 300 mg . weekly . Proguanil 200 mg . ( 2·1–3·2 mg . per kg . body weight ) given daily for 8 weeks after challenge provided complete suppression of the Poo . strain in 4 men ( and probably a fifth ) , and also of the Tay . strain in 4 men , nor did parasitaemia develop after completion of the prophylactic course . Pyrimethamine 25 mg . given weekly failed to protect 2 of 3 men challenged with Poo . , and the Tay . strain also broke through in both men receiving this regimen . A single dose of 45 mg . ( base ) of primaquine was gametocytocidal for both strains and , in one case of Poo . infection studied , rendered gametocytes non-infective to an efficient vector mosquito fed on the patient 24 hours later Background Resistance of malaria parasites to chloroquine ( CQ ) and sulphadoxine-pyrimethamine ( SP ) is increasing in prevalence in Africa . Combination therapy can both improve treatment and provide important public health benefits if it curbs the spread of parasites harbouring resistance genes . Thus , drug combinations must be identified which minimise gametocyte emergence in treated cases , and so prevent selective transmission of parasites resistant to any of the partner drugs . Methods and Findings In a r and omised controlled trial , 497 children with uncomplicated falciparum malaria were treated with CQ and SP ( three doses and one dose respectively ; n = 91 ) , or six doses of artemether in fixed combination with lumefantrine ( co-artemether [ Coartem , Riamet ] ) ( n = 406 ) . Carriage rates of Plasmodium falciparum gametocytes and trophozoites were measured 7 , 14 , and 28 d after treatment . The infectiousness of venous blood from 29 children carrying P. falciparum gametocytes 7 d after treatment was tested by membrane-feeding of Anopheles mosquitoes . Children treated with co-artemether were significantly less likely to carry gametocytes within the 4 weeks following treatment than those receiving CQ/SP ( 30 of 378 [ 7.94 % ] versus 42 of 86 [ 48.8 % ] ; p < 0.0001 ) . Carriers in the co-artemether group harboured gametocytes at significantly lower densities , for shorter periods ( 0.3 d versus 4.2 d ; p < 0.0001 ) and were less infectious to mosquitoes at day 7 ( p < 0.001 ) than carriers who had received CQ/SP . Conclusions Co-artemether is highly effective at preventing post-treatment transmission of P. falciparum . Our results suggest that co-artemether has specific activity against immature sequestered gametocytes , and has the capacity to minimise transmission of drug-resistant parasites Background The combination of artesunate and mefloquine has been reported to be effective against multi-drug resistant Plasmodium falciparum malaria , which has been reported in Nigeria . The objective of this multi-centre study was to evaluate the efficacy , safety and tolerability of the co-packaged formulation of artesunate and mefloquine in the treatment of uncomplicated malaria in two weight groups : those between 15 – 29 kg and ≥ 30 kg respectively . Methods The trial was conducted in rural communities in the north-east , north- central , south-west and south-eastern parts of Nigeria . The WHO protocol for testing antimalarial drugs was followed . Out patients having amongst other criteria , parasite density of ≥1,000 μl were enrolled . The co-packaged drugs were administered for 3 days at a dosage of artesunate , 4 mg/kg body wt/day and mefloquine , 25 mg/kg/body wt total ) on days 0 , 1 and 2 . Patients were followed up for 28 days with the assessment of the parasitological parameters on days 1 , 2 , 3 , 7 , and 28 . Results Four hundred and forty-six ( 446 ) patients were enrolled and 431 completed the study . Cure rates in both treatment groups was > 90 % at day 28 . The mean parasite clearance times in treatment groups I and II were 40.1 and 42.4 hours respectively . The combination of artesunate and mefloquine showed good gametocidal activity , ( gametocyte clearance time of 42.0 & 45.6 hours in treatment groups I and II respectively ) . There were no serious adverse events . Other adverse events observed were headache , dizziness , vomiting and abdominal discomfort . There was no significant derangement in the haematological and biochemical parameters . Conclusion This co-packaged formulation of artesunate + mefloquine ( Artequin ™ ) is highly efficacious , safe and well-tolerated . It is recommended for the treatment of uncomplicated P. falciparum malaria in Nigeria ABSTRACT The activities of primaquine in combination with quinine or artesunate against asexual- and sexual-stage parasites were assessed in 176 adult Thai patients with uncomplicated Plasmodium falciparum malaria . Patients were r and omized to one of the six following 7-day oral treatment regimens : ( i ) quinine alone , ( ii ) quinine with tetracycline , ( iii ) quinine with primaquine at 15 mg/day , ( iv ) quinine with primaquine at 30 mg/day , ( v ) artesunate alone , or ( vi ) artesunate with primaquine . Clinical recovery occurred in all patients . There were no significant differences in fever clearance times , rates of P. falciparum reappearance , or recurrent vivax malaria between the six treatment groups . Patients treated with artesunate alone or in combination with primaquine had significantly shorter parasite clearance times ( mean ± st and ard deviation = 65± 18 versus 79 ± 21 h ) and lower gametocyte carriage rates ( 40 versus 62.7 % ) than those treated with quinine ( P ≤ 0.007 ) . Primaquine did not affect the therapeutic response ( P > 0.2 ) . Gametocytemia was detected in 98 patients ( 56 % [ 22 % before treatment and 34 % after treatment ] ) . Artesunate reduced the appearance of gametocytemia ( relative risk [ 95 % confidence interval ] = 0.34 [ 0.17 to 0.70 ] ) , whereas combinations containing primaquine result ed in shorter gametocyte clearance times ( medians of 66 versus 271 h for quinine groups and 73 versus 137 h for artesunate groups ; P≤ 0.038 ) . These results suggest that artesunate predominantly inhibits gametocyte development whereas primaquine accelerates gametocyte clearance in P. falciparum malaria Background Artesunate and amodiaquine ( AS&AQ ) is at present the world 's second most widely used artemisinin-based combination therapy ( ACT ) . It was necessary to evaluate the efficacy of ACT , recently adopted by the World Health Organization ( WHO ) and deployed over 80 countries , in order to make an evidence -based drug policy . Methods An individual patient data ( IPD ) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints . Results A total of 11,700 patients ( 75 % under 5 years old ) , from 33 different sites in 16 countries were followed for 28 days . Loss to follow-up was 4.9 % ( 575/11,700 ) . AS&AQ was given to 5,897 patients . Of these , 82 % ( 4,826/5,897 ) were included in r and omized comparative trials with polymerase chain reaction ( PCR ) genotyping results and compared to 5,413 patients ( half receiving an ACT).AS&AQ and other ACT comparators result ed in rapid clearance of fever and parasitaemia , superior to non-ACT . Using survival analysis on a modified intent-to-treat population , the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90 % ( the WHO cut-off ) in 11/16 countries . In r and omized comparative trials ( n = 22 ) , the crude efficacy of AS&AQ was 75.9 % ( 95 % CI 74.6–77.1 ) and the PCR-adjusted efficacy was 93.9 % ( 95 % CI 93.2–94.5 ) . The risk ( weighted by site ) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT , superior to dihydroartemisinin-piperaquine ( DP , in one Ug and an site ) , and not different from AS+SP or AL ( artemether-lumefantrine ) . The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ug and an site compared to AL and DP , and lower compared to non-ACT ( p = 0.001 , for all comparisons ) . Anaemia recovery was not different than comparator groups , except in one site in Rw and a where the patients in the DP group had a slower recovery . Conclusion AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many , but not all , the sub-Saharan African countries where it was studied . Efficacy varies between and within countries . An IPD analysis can inform general and local treatment policies . Ongoing monitoring evaluation is required Background The gametocyte sex ratio of Plasmodium falciparum , defined as the proportion of gametocytes that are male , may influence transmission but little is known of the effects of mefloquine or artesunate-mefloquine on gametocyte sex ratio and on the sex ratio of first appearing gametocytes . Methods 350 children with uncomplicated P. falciparum malaria were enrolled in prospect i ve treatment trial of mefloquine or artesunate-mefloquine between 2007 and 2008 . Gametocytaemia was quantified , and gametocytes were sexed by morphological appearance , before and following treatment . The area under curve of gametocyte density versus time ( AUCgm ) was calculated by linear trapezoidal method . Results 91 % and 96 % of all gametocytes appeared by day 7 and day 14 , respectively following treatment . The overall rate of gametocytaemia with both treatments was 31 % , and was significantly higher in mefloquine than in artesunate-mefloquine treated children if no gametocyte was present a day after treatment began ( 25.3 % v 12.8 % , P = 0.01 ) . Gametocyte clearance was significantly faster with artesunate-mefloquine ( 1.8 ± 0.22 [ sem ] v 5.6 ± 0.95 d ; P = 0.001 ) . AUCgm was significantly lower in the artesunate mefloquine group ( P = 0.008 ) . The pre-treatment sex ratio was male-biased , but post-treatment sex ratio or the sex ratio of first appearing gametocytes , was significantly lower and female-biased two or three days after beginning of treatment in children given artesunate-mefloquine . Conclusion Addition of artesunate to mefloquine significantly modified the emergence , clearance , and densities of gametocytes and has short-lived , but significant , sex ratio modifying effects in children from this endemic area Background Artemisinin-based combination therapy ( ACT ) is being widely promoted as a strategy to counteract the increase in Plasmodium falciparum antimalarial drug resistance . Methods A r and omized , double-blind , placebo-controlled , clinical trial of the efficacy , effect on gametocytes and safety of the addition of artesunate/placebo ( 4 mg/kg/day × 3 d ) to amodiaquine ( 10 mg/kg/day × 3 d ) was conducted in Choco department , a low intensity transmission area in northwest Colombia . Results From 2,137 screened subjects , 85 entered the study : 43 in the amodiaquine plus placebo and 42 in the amodiaquine plus artesunate groups . Potentially eligible cases failed to qualify mostly because they were not available for follow-up visits ( 73 % ) . Based on a per protocol analysis , the therapeutic response to both treatments was high : amodiaquine/placebo 35/36 , 97.2 % ( 95 % CI 85.5–99.9 ) , and amodiaquine/artesunate 32/32 , 100 % ( 89.1–100 ) after PCR genotyping . The Kaplan-Meier survival estimates based on all eligible patients enrolled ( amodiaquine/placebo : n = 42 ; amodiaquine/artesunate : n = 41 ) were similar in the two study groups ( P = 0.3 ) . The addition of artesunate significantly decreased gametocyte carriage on Day 4 ( OR = 0.1 95 % CI 0.02–0.6 ) , Day 7 ( OR = 0.2 95%CI 0.04–0.9 ) , Day 14 ( OR = 0.09 95 % CI 0–0.8 ) , and Day 21 ( OR95%CI 0–0.9 ) . Most subjects in both groups ( 81 % in amodiaquine/placebo and 75.6 % in amodiaquine/artesunate ) reported at least one drug related adverse event . Symptoms were generally mild and self-limiting and there was no serious adverse event . Two patients on amodiaquine/artesunate voluntarily withdrew from study because they could not tolerate the medication . Conclusion Both drug regimens were effective in this area of Colombia . The addition of artesunate reduced gametocyte carriage and did not adversely affect tolerability . In this set of patients , the rate of adverse events was higher than in other studies . Patients ' follow-up is problematic in areas with dispersed population and affects the conduct of clinical studies and monitoring of treatment effects . The results are discussed in the light of concurrent increase resistance to amodiaquine in other endemic areas in Colombia and the factors that may influence a change in the national antimalarial drug policy Background Dealing with heterogeneity in meta-analyses is often tricky , and there is only limited advice for authors on what to do . We investigated how authors addressed different degrees of heterogeneity , in particular whether they used a fixed effect model , which assumes that all the included studies are estimating the same true effect , or a r and om effects model where this is not assumed . Methods We sample d r and omly 60 Cochrane review s from 2008 , which presented a result in its first meta- analysis with substantial heterogeneity ( I2 greater than 50 % , i.e. more than 50 % of the variation is due to heterogeneity rather than chance ) . We extracted information on choice of statistical model , how the authors had h and led the heterogeneity , and assessed the method ological quality of the review s in relation to this . Results The distribution of heterogeneity was rather uniform in the whole I2 interval , 50 - 100 % . A fixed effect model was used in 33 review s ( 55 % ) , but there was no correlation between I2 and choice of model ( P = 0.79 ) . We considered that 20 review s ( 33 % ) , 16 of which had used a fixed effect model , had major problems . The most common problems were : use of a fixed effect model and lack of rationale for choice of that model , lack of comment on even severe heterogeneity and of reservations and explanations of its likely causes . The problematic review s had significantly fewer included trials than other review s ( 4.3 vs. 8.0 , P = 0.024 ) . The problems became less pronounced with time , as those review s that were most recently up date d more often used a r and om effects model . Conclusion One-third of Cochrane review s with substantial heterogeneity had major problems in relation to their h and ling of heterogeneity . More attention is needed to this issue , as the problems we identified can be essential for the conclusions of the review BACKGROUND Artemisinin-combination therapy ( ACT ) is recommended as first-line treatment of falciparum malaria throughout the world , and fixed-dose combinations are preferred by WHO ; whether a single gametocytocidal dose of primaquine should be added is unknown . We aim ed to compare effectiveness of four fixed-dose ACTs and a loose tablet combination of artesunate and mefloquine , and assess the addition of a single gametocytocidal dose of primaquine . METHODS In an open-label r and omised trial in clinics in Rakhine state , Kachin state , and Shan state in Myanmar ( Burma ) between Dec 30 , 2008 , and March 20 , 2009 , we compared the effectiveness of all four WHO-recommended fixed-dose ACTs ( artesunate-mefloquine , artesunate-amodiaquine , dihydroartemisinin-piperaquine , artemether-lumefantrine ) and loose artesunate-mefloquine in Burmese adults and children . Eligible patients were those who presented to the clinics with acute uncomplicated Plasmodium falciparum malaria or mixed infection , who were older than 6 months , and who weighed more than 5 kg . Treatments were r and omised in equal numbers within blocks of 50 and allocation was in sealed envelopes . All patients were also r and omly assigned to receive either a single dose of primaquine 0·75 mg base/kg or not . Patients were followed up for 63 days . Treatment groups were compared by analysis of variance and multiple logistic regression . The primary outcome was the 63 day recrudescence rate . This study is registered with clinical trials.gov , number NCT00902811 . FINDINGS 155 patients received artesunate-amodiaquine , 162 artemether-lumefantrine , 169 artesunate-mefloquine , 161 loose artesunate-mefloquine , and 161 dihydroartemisinin-piperaquine . By day 63 of follow-up , 14 patients ( 9·4 % ; 95 % CI 5·7 - 15·3 % ) on artesunate-amodiaquine had recrudescent P falciparum infections , a rate significantly higher than for artemether-lumefantrine ( two patients ; 1·4 % ; 0·3 - 5·3 ; p=0·0013 ) , fixed-dose artesunate-mefloquine ( 0 patients ; 0 - 2·3 ; p<0·0001 ) , loose artesunate-mefloquine ( two patients ; 1·3 % ; 0·3 - 5·3 ; p=0·0018 ) , and dihydroartemisinin-piperaquine ( two patients 1·3 % ; 0·3 - 5·2 % ; p=0·0012 ) . Hazard ratios for re-infection ( 95 % CI ) after artesunate-amodiaquine were 3·2 ( 1·3 - 8·0 ) compared with the two artesunate-mefloquine groups ( p=0·01 ) , 2·6 ( 1·0 - 6 - 0 ) compared with artemether-lumefantrine ( p=0·04 ) , and 2·3 ( 0·9 - 6·0 ) compared with dihydroartemisinin-piperaquine ( p=0·08 ) . Mixed falciparum and vivax infections were common : 129 ( 16 % ) had a mixed infection at presentation and 330 ( 41 % ) patients had one or more episodes of Plasmodium vivax infection during follow-up . The addition of a single dose of primaquine ( 0·75 mg/kg ) reduced P falciparum gametocyte carriage substantially : rate ratio 11·9 ( 95 % CI 7·4 - 20·5 ) . All regimens were well tolerated . Adverse events were reported by 599 patients , most commonly vomiting and dizziness . Other side-effects were less common and were not related to a specific treatment . INTERPRETATION Artesunate-amodiaquine should not be used in Myanmar , because the other ACTs are substantially more effective . Artesunate-mefloquine provided the greatest post-treatment suppression of malaria . Adding a single dose of primaquine would substantially reduce transmission potential . Vivax malaria , not recurrent falciparum malaria , is the main complication after treatment of P falciparum infections in this region . FUNDING Médecins sans Frontières ( Holl and ) and the Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme Background . Artemisinin-based combination therapy ( ACT ) reduces microscopically confirmed gametocytemia and mosquito infection . However , molecular techniques have recently revealed high prevalences of su bmi croscopic gametocytemia . Our objective here was to determine the effect of sulfadoxine-pyrimethamine ( SP ) monotherapy and treatment with SP plus amodiaquine ( AQ ) , SP plus artesunate ( AS ) , and artemether-lumefantrine ( AL ; Coartem ) on su bmi croscopic gametocytemia and infectiousness . Methods . Kenyan children ( n=528 ) 6 months-10 years of age were r and omized to 4 treatment arms . Gametocytemia was determined by both microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification ( Pfs25 QT-NASBA ) . Transmission was determined by membrane-feeding assays . Results . Gametocyte prevalence , as determined by Pfs25 QT-NASBA , was 89.4 % ( 219/245 ) at enrollment and decreased after treatment with SP plus AS , SP plus AQ , and AL . Membrane-feeding assays for a group of r and omly selected children revealed that the proportion of infectious children was as much as 4-fold higher than expected when based on microscopy . ACT did not significantly reduce the proportion of infectious children but did reduce the proportion of infected mosquitoes . Conclusions . Su bmi croscopic gametocytemia is common after treatment and contributes considerably to mosquito infection . Our findings should be interpreted in the context of transmission intensity , but the effect of ACT on malaria transmission appears to be moderate and restricted to the duration of gametocyte carriage and the proportion of mosquitoes that are infected by carriers Combination therapy that includes artemisinin derivatives cures most falciparum malaria infections . Lowering transmission by reducing gametocyte infectivity would be an additional benefit . To examine the effect of such therapy on transmission , Gambian children with Plasmodium falciparum malaria were treated with st and ard regimens of chloroquine or pyrimethamine-sulfadoxine alone or in combination with 1 or 3 doses of artesunate . The infectivity to mosquitoes of gametocytes in peripheral blood was determined 4 or 7 days after treatment . Infection of mosquitoes was observed in all treatment groups and was positively associated with gametocyte density . The probability of transmission was lowest in those who received pyrimethamine-sulfadoxine and 3 doses of artesunate , and it was 8-fold higher in the group that received pyrimethamine-sulfadoxine alone . Artesunate reduced posttreatment infectivity dramatically but did not abolish it completely . The study raises questions about any policy to use pyrimethamine-sulfadoxine alone as the first-line treatment for malaria BACKGROUND Artemisinin-based combination therapy ( ACT ) reduces the potential for malaria transmission , compared with non-ACTs . It is unclear whether this effect differs between ACTs . METHODS A total of 298 children ( age , 6 months to 10 years ) with uncomplicated falciparum malaria were r and omized to artemether-lumefantrine ( AL ; n = 153 ) or dihydroartemisinin-piperaquine ( DP ; n = 145 ) in Mbita , a community in western Kenya . Gametocyte carriage was determined by molecular methods on days 0 , 1 , 2 , 3 , 7 , 14 , 28 , and 42 after treatment initiation . The gametocyte infectiousness to mosquitoes was determined by mosquito-feeding assays on day 7 after beginning therapy . RESULTS The cumulative risk of recurrent parasitemia on day 42 after initiation of treatment , unadjusted by polymerase chain reaction findings , was 20.7 % ( 95 % confidence interval [ CI ] , 14.4 - 28.2 ) for AL , compared with 3.7 % ( 95 % CI , 1.2 - 8.5 ) for DP ( P < .001 ) . The mean duration of gametocyte carriage was 5.5 days ( 95 % CI , 3.6 - 8.5 ) for AL and 15.3 days ( 95 % CI , 9.7 - 24.2 ) for DP ( P = .001 ) . The proportion of mosquitoes that became infected after feeding on blood from AL-treated children was 1.88 % ( 43 of 2293 ) , compared with 3.50 % ( 83 of 2371 ) for those that fed on blood from DP-treated children ( P = .06 ) ; the oocyst burden among mosquitoes was lower among those that fed on blood from AL-treated children ( P = .005 ) CONCLUSIONS : While DP was associated with a longer prophylactic time after treatment , gametocyte carriage and malaria transmission to mosquitoes was lower after AL treatment . CLINICAL TRIALS REGISTRATION NCT00868465 BACKGROUND Artemisinin-based combination therapy is very effective in clearing asexual stages of malaria and reduces gametocytemia , but may not affect mature gametocytes . Primaquine is the only commercially available drug that eliminates mature gametocytes . METHODS We conducted a 2-arm , open-label , r and omized , controlled trial to evaluate the efficacy of single-dose primaquine ( 0.75 mg/kg ) following treatment with dihydroartemisinin-piperaquine ( DHP ) on Plasmodium falciparum gametocytemia , in Indonesia . Patients aged ≥5 years with uncomplicated falciparum malaria , normal glucose-6-phosphate dehydrogenase enzyme levels , and hemoglobin levels ≥8 g/dL were assigned by computerized-generating sequence to a st and ard 3-day course of DHP alone ( n = 178 ) or DHP combined with a single dose of primaquine on day 3 ( n = 171 ) . Patients were seen on days 1 , 2 , 3 , and 7 and then weekly for 42 days to assess the presence of gametocytes and asexual parasites by microscopy . Survival analysis was stratified by the presence of gametocytes on day 3 . RESULTS DHP prevented development of gametocytes in 277 patients without gametocytes on day 3 . In the gametocytemic patients ( n = 72 ) , primaquine was associated with faster gametocyte clearance ( hazard ratio = 2.42 [ 95 % confidence interval , 1.39 - 4.19 ] , P = .002 ) and reduced gametocyte densities ( P = .018 ) . The day 42 cure rate of asexual stages in the DHP + primaquine and DHP-only arms were : polymerase chain reaction ( PCR ) unadjusted , 98.7 % vs 99.4 % , respectively ; PCR adjusted , 100 % for both . Primaquine was well tolerated . CONCLUSIONS Addition of single-dose 0.75 mg/kg primaquine shortens the infectivity period of DHP-treated patients and should be considered in low-transmission regions that aim to control and ultimately eliminate falciparum malaria . Clinical Trials Registration . NCT01392014 Background The suppression of indoor malaria transmission requires additional interventions that complement the use of insecticide treated nets ( ITNs ) and indoor residual spraying ( IRS ) . Previous studies have examined the impact of house structure on malaria transmission in areas of low transmission . This study was conducted in a high transmission setting and presents further evidence about the association between specific house characteristics and the abundance of endophilic malaria vectors . Methods Mosquitoes were sample d using CDC light traps from 72 r and omly selected houses in two villages on a monthly basis from 2008 to 2011 in rural Southern Tanzania . Generalized linear models using Poisson distributions were used to analyze the association of house characteristics ( eave gaps , wall types , roof types , number of windows , rooms and doors , window screens , house size ) , number of occupants and ITN usage with mean catches of malaria vectors ( An.gambiae s.l . and An . funestus ) . Results A total of 36490 female An . gambiae s.l . were collected in Namwawala village and 21266 in Idete village . As for An . funestus females , 2268 were collected in Namwawala and 3398 in Idete . Individually , each house factor had a statistically significant impact ( p < 0.05 ) on the mean catches for An . gambiae s.l . but not An . funestus . A multivariate analysis indicated that the combined absence or presence of eaves , treated or untreated bed-nets , the number of house occupants , house size , netting over windows , and roof type were significantly related ( p < 0.05 ) to An.gambiae s.l . and An . funestus house entry in both villages . Conclusions Despite significant reductions in vector density and malaria transmission caused by high coverage of ITNs , high numbers of host-seeking malaria vectors are still found indoors due to house design s that favour mosquito entry . In addition to ITNs and IRS , significant efforts should focus on improving house design to prevent mosquito entry and eliminate indoor malaria transmission INTRODUCTION Antimalarial treatment effects on Plasmodium falciparum gametocytemia has been the focus of few studies in the Americas . OBJECTIVE Relationships are described that occur between falciparum gametocytemia and the treatment with amodiaquine-sulfadoxine-pyrimethamine , artesunate-sulfadoxine-pyrimethamine or amodiaquine-artesunate . MATERIAL S AND METHODS The experimental design consisted of a r and omized selection of patients not balanced or blinded . A total of 241 patients were evaluated , residents of Turbo , El Bagre and Zaragoza ( Antioquia , Colombia ) . The follow up occurred 21 - 28 days after antimalarial treatment . The World Health Organization ( 1998 ) protocol was used . RESULTS The therapeutic efficacy of amodiaquine-sulfadoxine-pyrimethamine , artesunate-sulfadoxine-pyrimethamine and amodiaquine-artesunate were equal at day 21 of the follow up . Four cases ( 1.7 % ) were therapeutic failures . Amodiaquine-sulfadoxine-pyrimethamine was less effective than the artesunate treatments in reducing the gametocyte load . On day 7 , none of the three treatments had eliminated completely the gametocytes . Most patients ( 56.0 % ) were observed not to have circulating gametocytes pre-treatment and did not develop them later . CONCLUSION The three treatment schemes were similar in their therapeutic efficacy and in their incapacity to eliminate gametocytes at day seven BACKGROUND On the western border of Thail and the efficacy of mefloquine in the treatment of falciparum malaria has declined while gametocyte carriage rates have increased , which suggests increased transmissibility of these resistant infections . We compared the following antimalarial drugs in relation to subsequent Plasmodium falciparum gametocyte carriage : mefloquine , halofantrine , quinine , and the artemisinin derivatives . METHODS Between 1990 and 1995 we assessed gametocytaemia in a series of prospect i ve studies of antimalarial drug treatment in 5193 adults and children with acute uncomplicated falciparum malaria in an area of malarious hill forest on the western border of Thail and . Weekly parasite counts from thick and thin blood films were done during the 4-week ( 1990 - 93 ) or 9-week ( 1993 - 95 ) follow-up period . Gametocyte positivity rates and person gametocyte week ( PGW ) rates were calculated to measure gametocyte carriage and transmission potential . FINDINGS In primary P falciparum infections the gametocyte carriage rate was significantly higher after treatment with mefloquine than after treatment with the artemisinin derivatives ( PGW 34.1 [ 95 % CI 25.2 - 42.9 ] vs 3.9 [ 1.9 - 5.9 ] per 1000 person weeks ; relative risk 8.0 [ 4.1 - 15.6 ] ; p<0.0001 ) . Recrudescent infections were associated with increased gametocyte carrier rates ( relative risk 2.2 [ 1.6 - 3.0 ] ; p<0.0001 ) , but retreatment with artemisinin derivatives reduced subsequent gametocyte carriage 18.5 fold [ 3.5 - 98 ] compared with mefloquine retreatment and 6.8 fold ( 3.1 - 15.1 ) compared with quinine retreatment ( p<0.001 ) . The introduction of the artemisinin derivatives in routine treatment at this study site in mid 1994 was associated with a reduction in the subsequent incidence of falciparum malaria of 47 (25 - 69)% INTERPRETATION Although environmental changes affect vector numbers , and hence malaria incidence , artemisinin derivatives were found to reduce the transmission potential of falciparum malaria . Widespread introduction of artemisinin derivatives in the treatment of falciparum malaria may prevent the spread of multidrug resistance ABSTRACT Artemisinin combination therapies eliminate immature Plasmodium falciparum gametocytes but not mature gametocytes , which may persist for up to 1 month posttreatment . A single dose of primaquine , which is inexpensive and effective against mature gametocytes , could be added to further reduce the potential for posttreatment parasite transmission . Currently , we have few data regarding the effectiveness or safety of doing so . We collected data from 21 therapeutic efficacy trials of the National Antimalarial Drug Resistance Monitoring System of India conducted during 2009 to 2010 , wherein 9 sites used single-dose primaquine ( 0.75 mg/kg of body weight ) administered on day 2 along with artesunate plus sulfadoxine-pyrimethamine ( AS+SP ) while 12 did not . We estimated the effect of primaquine on posttreatment gametocyte clearance and the total number of gametocyte-weeks as determined by microscopy . We compared the median area under the curve for gametocyte density and reported adverse events . One thous and three hundred thirty-five patients completed the antimalarial drug treatment . Adjusting for region , primaquine increased the rate of gametocyte clearance ( hazard ratio , 1.9 ; 95 % confidence interval [ CI ] , 1.1 to 3.3 ) , prevented 45 % ( 95 % CI , 19 to 62 ) of posttreatment gametocyte-weeks , and decreased the area under the gametocyte density curve over the 28-day follow-up compared to AS+SP alone ( P value = 0.01 ) . The results were robust to other adjustment sets , and the estimated effect of primaquine increased during sensitivity analysis on the measurement of exposure time . No serious adverse events were detected . In conclusion , the addition of primaquine to AS+SP was effective in reducing the posttreatment presence of P. falciparum gametocytes . Primaquine was well tolerated and could be administered along with an artemisinin combination therapy as the first-line therapy OBJECTIVES Combination therapy using existing anti-malarials together with artesunate ( AS ) has been advocated as a method to slow the spread of drug resistance . We assessed the effect on Plasmodium falciparum transmissibility of the addition of AS to chloroquine ( CQ ) in an area of The Gambia where resistance to CQ is increasing . METHODS Gambian children with acute uncomplicated P. falciparum malaria were treated with either CQ monotherapy ( n=120 ) or the combination of CQ plus three doses of AS ( CQ/AS ; n=352 ) . Post-treatment sexual-stage parasitaemia was assessed during a 4-week follow-up period . Experimental infections of Anopheles gambiae s.s . mosquitoes were performed with blood from patients who were carrying gametocytes 7 days after starting treatment ( n=69 ) . RESULTS The addition of AS significantly reduced post-treatment prevalence and mean density of gametocytes in the first 14 days ( day 7 : 43.7 % vs. 12.4 % , 62.4/microl vs. 6.2/microl ; day 14 : 32.9 % vs. 3.7 % ; 21.9/microl vs. 5.2/microl ; CQ vs. CQ/AS ) , although by day 28 the benefits of the combination were substantially less marked ( 40.5 % vs. 21.8 % ; 23.0/microl vs. 63.1/microl ; CQ vs. CQ/AS ) . The duration of gametocyte carriage over the study period was significantly lower in the CQ/AS group ( 5.2 days vs. 1.5 days ; CQ vs. CQ/AS ) . The estimated infectious proportion of children at day 7 was also lower in the combination group ( 19.2 % vs. 3.4 % ; CQ vs. CQ/AS ) , as were the proportion of mosquitoes infected and mean oocyst density ( 11.5 % vs. 0.9 % ; 0.3 vs. 0.01 ; CQ vs. CQ/AS ) . Treatment failure was associated with threefold and twofold higher gametocyte carriage rates during follow-up in CQ and CQ/AS groups , respectively ( P<0.001 in both cases ) , and 26-fold and 2.3-fold higher intensity of infection at day 7 among CQ- and CQ/AS-treated children , respectively ( P=0.002 and 0.30 , respectively ) . CONCLUSION The benefits of adding AS to CQ monotherapy in lowering gametocyte prevalence and density were transient , suggesting that the addition of AS delayed , but did not prevent , the emergence of gametocytes . This is consistent with our finding that treatment failure , and thus the presence of CQ-resistant parasites , was significantly associated with a higher gametocyte carriage rate in both treatment groups . At day 7 , CQ monotherapy significantly favoured transmission of resistant infections , which showed an 11-fold greater intensity of transmission compared with infections that were successfully treated . In contrast , the combination of CQ/AS did not significantly favour resistant infections at day 7 . We conclude that significant transmission-reduction is achieved by the combination but is not maintained because of the recrudescence of CQ-resistant parasites This study compared the efficacy against Plasmodium falciparum gametocytes of four regimens : amodiaquine-sulfadoxine/pyrimethamine ( AQ-SP ) and mefloquine-artesunate ( MQ-AS ) , with and without primaquine ( PQ ) administered with the second dose of the schizonticide ( AQ-SP ; AQ-SP-PQ ; MQ-AS ; MQ-AS-PQ ) . Efficacy was determined by thick smear on days 1 , 4 and 8 after the beginning of treatment . A total of 82 patients ( 19 - 23/group ) were recruited . After AQ-SP administration , gametocytemia steadily increased until day 8 . With AQ-SP-PQ , a marked decline in gametocytemia was detected on days 4 and 8 . MQ-AS treatment result ed in reduced gametocytemia on days 4 and 8 , and with MQ-AS-PQ it was reduced even further . None of the treatments cleared gametocytemia by day 8 . Currently , artemisinin-based combination therapies plus PQ are the recommended treatment option against falciparum malaria ; however , further studies are required to optimize the use of PQ . Issues to be addressed include the optimal time of administration , treatment duration , optimal daily and total dose , and day of evaluation of the gametocytocidal effect . In falciparum malaria , the WHO recommends a maximum of 4days of treatment ; consequently , an effective regimen must clear asexual parasites and symptoms within this time frame . The same criteria should be taken into account when evaluating the anti-gametocyte activity |
10,545 | 29,303,758 | The human histologic studies showed evidence of perpendicular insertion of human gingival fibroblasts into the treated abutment surface .
Laser-ablated , hydrophilic , and oxidized titanium surfaces result ed in this type of attachment .
Epithelial cells seem to slightly favor zirconia and polished titanium surfaces .
Improvements in the surface topography and macro design of dental abutments might improve biocompatibility and adherence to soft tissue ; however , manipulation of soft tissue and second-stage surgery could negate any advantages of the improved surfaces | Soft tissue integration in the transmucosal zone of dental abutments supports the peri-implant tissues , improves esthetics , ensures soft tissue seal against microorganisms , and preserves crestal bone level .
The aim of this literature review was to define the most favorable surface topography and macro design of the transmucosal zone of abutments to achieve optimal soft tissue seal . | OBJECTIVES To ( i ) investigate the influence of different extensions of a laser microgrooved abutment zone on connective tissue attachment and ( ii ) assess the impact of a repeated abutment dis-/reconnection on soft- and hard-tissue healing . MATERIAL S AND METHODS Titanium implants were inserted epicrestally in the lower jaws of six dogs . Healing abutments with either partially ( LP ) or completely ( LC ) laser microgrooved margins or machined surface margins ( M ) were r and omly allocated either to a single (1 × )/repeated ( 2 × ) dis-/reconnection at 4 and 6 weeks ( test ) , respectively , or left undisturbed ( control ) . At 6 and 8 weeks , histomorphometrical ( e.g. most coronal level of bone in contact with the implant [ CBI ] , subepithelial connective tissue attachment [ STC ] ) and immunohistochemical ( Collagen Type-I [ CI ] ) parameters were assessed . RESULTS At control sites , LP/LC groups revealed lower mean CBL ( 8 weeks , 0.95 ± 0.51 vs. 0.54 ± 0.63 vs. 1.66 ± 1.26 mm ) , higher mean STC ( 8 weeks , 82.58 ± 24.32 % vs. 96.37 ± 5.12 % vs. 54.17 ± 8.09 % ) , but comparable CI antigen reactivity . A repeated abutment manipulation was associated with increased mean CBL ( 8 weeks , 1.53 ± 1.09 vs. 0.94 ± 0.17 vs. 1.06 ± 0.34 mm ) , decreased STC ( 8 weeks , 57.34 ± 43.06 % vs. 13.26 ± 19.04 % vs. 37.76 ± 37.08 % ) and CI values . CONCLUSIONS It was concluded that ( i ) LC > LP abutments enhanced subepithelial connective tissue attachment and preserved crestal bone levels , ( ii ) repeated abutment dis-/reconnection during the initial healing phase ( 4 - 6 weeks ) may be associated with increased soft- and hard-tissue changes and ( iii ) LP and LC should be considered using a one abutment , one time approach Previous research has demonstrated the effectiveness of laser-ablated microgrooves placed on implant collars to support direct connective tissue attachments to altered implant surfaces . Such a direct connective tissue attachment serves as a physiologic barrier to the apical migration of the junctional epithelium and prevents crestal bone resorption . The current prospect i ve pre clinical trial sought to evaluate bone and soft tissue healing patterns when laser-ablated microgrooves were placed on the abutment . A canine model was selected for comparison to previous investigations that examined the negative bone and soft tissue sequelae of the implant-abutment microgap . The results demonstrate significant improvement in peri-implant hard and soft tissue healing compared to traditional machined abutment surfaces BACKGROUND : If an implant with a rough surface is exposed to the oral cavity , it may accumulate greater amounts of plaque than a smooth surface , which may lead to severe problems with mucositis and peri-implantitis . The purpose of the present paper was to investigate the early inflammatory response to mucosa-penetrating abutments prepared with varying surface roughness . METHODS : Nine patients had all five of their original abutments exchanged to test abutments for a 4-week period . The test abutments were prepared with five different roughnesses . The surface roughness was measured with an optical profilometer . At the end of the test period , clinical evaluation was performed ; the health of the surrounding mucosa , the amount of accumulated plaque and marginal bleeding were registered . One biopsy was taken from each test abutment . Qualitative and quantitative histological evaluations were performed . RESULTS : There was a statistically significant difference between patients regarding the amount of accumulated plaque on the abutment surfaces and inflammatory cells , but no difference between the surface modifications in relation to plaque accumulation or number of inflammatory cells . CONCLUSION : No relation was found between inflammatory response and abutment surface roughness after an evaluation time of 4 weeks in a human test model The roughness of intraoral hard surfaces plays an important role in bacterial adhesion and colonization . Earlier studies have shown that rough surfaces accumulate up to 25 times more subgingival plaque than do smooth sites . In the present study , the influence of surface smoothing was studied . In six partially edentulous patients waiting for a fixed prosthesis supported by endosseous titanium implants , four titanium abutments with different surface roughness were r and omly placed . After 1 month of intraoral exposure , subgingival plaque sample s from each abutment were compared within each patient by means of differential phase-contrast microscopy . After 3 months , supragingival and subgingival plaque sample s were taken from all abutments for differential phase-contrast microscopy and culturing . Probing depth , recession , and bleeding upon probing were scored at the same visit . Differential phase-contrast microscopy showed that subgingivally , only the two roughest abutments harbored spirochetes after 1 month . After 3 months , subgingivally , the composition of the flora showed little variation on the different abutment types , although spirochetes were only noticed around the roughest abutments . Anaerobic culturing result ed in comparable amounts of colony-forming units for all abutment types , both supragingivally and subgingivally . Subgingivally , the microbiologic composition did not show major interabutment differences . Clinical ly , small differences in probing depth were observed . The roughest abutment showed some attachment gain ( 0.2 mm ) during 3 months , whereas all other abutments had an attachment loss ranging from 0.8 to greater than 1 mm . The results indicate that a reduction in surface roughness ( less than a roughness of 0.2 micron ) had no major effect on the microbiologic composition , supragingivally or subgingivally . These observations indicate the existence of a threshold roughness below which no further impact on the bacterial adhesion and /or colonization should be expected . However , clinical evaluation seems to indicate that a certain surface roughness is necessary for increased resistance to clinical probing OBJECTIVES To histologically evaluate and compare the performance of healing abutments with either hydrophobic or hydrophilic surface properties in humans . MATERIAL S AND METHODS According to a parallel-group design , titanium implants placed in the posterior m and ible and maxilla of 30 patients were r and omly assigned to either ( 1 ) hydrophobic machined ( M ) , ( 2 ) chemically modified hydrophilic ( mod ) acid etched ( MA ) titanium ( Ti ) ( modMA1 ) or ( 3 ) modMA Ti- Zirconium alloy ( modMA2 ) healing abutments and left to heal in a transmucosal position . At 8 weeks , the abutments and a limited soft tissue biopsy were harvested according to a st and ardized procedure and processed for histological analysis ( primary outcomes : percentage epithelial- ( EC ) and subepithelial connective tissue contact ( CTC ) to the abutment surface ) . RESULTS The surgical procedure was associated with an incomplete mucosal coverage of the study abutments in nine patients , and an unintentional submerged healing procedure in three patients . Per protocol analysis ( 18 patients ) has pointed to an improved quantitative EC [ modMA2 ( 53.45 ± 28.25 ) > modMA1 ( 32.25 ± 24.3 ) > M ( 23.15 ± 16.09 ) ] and CTC [ modMA2 ( 75.12 ± 43.22 ) > modMA1 ( 69.41 ± 46.74 ) > M ( 47.63 ± 19.28 ) ] ( % ) to modMA surfaced abutments . CONCLUSIONS It was concluded that modMA surfaces may have the potential to enhance soft tissue adhesion at the transmucosal aspect of titanium dental implants |
10,546 | 28,396,643 | Meta-analytic synthesis showed that FIp improved service user functioning and reduced the likelihood of relapse by the end of treatment .
Psychotic symptoms were significantly reduced in the FIp group at follow up , but this was not evident at end of treatment .
In terms of FIp target mechanisms , carers receiving FIp were more likely to shift from high to low expressed emotion and less likely to report patient focused criticism or engage in conflict communication than carers r and omized to st and ard care .
Carer burden and well-being were improved by the end of treatment but gains were not sustained at follow up .
FIp had no impact on carer emotional over-involvement .
The findings indicate that FIp is an effective intervention for early psychosis service users and their relatives . | Family interventions for psychosis ( FIp ) are effective in reducing service user relapse and carer distress in people with schizophrenia-spectrum conditions .
Several treatment and best practice guidelines recommend FIp for all people with schizophrenia .
However , outcome findings in relation to early psychosis groups have been inconsistent .
The current paper reports a systematic review and meta-analyses of articles that evaluated FIp in early psychosis with a clearly defined comparison group . | A controlled longitudinal treatment study was carried out to investigate the effect of a behavioral family treatment on Expressed Emotion ( EE ) and to examine the correspondence between EE changes and relapse rates . Subjects were 52 patients with recent onset schizophrenia or related disorders and their parents . After completion of inpatient treatment they were r and omly allocated to individual treatment or individual treatment plus family treatment . The family treatment consisted of education and training in communication and problem-solving skills . Expressed Emotion was measured with the Five-Minute Speech Sample ( FMSS ) . The findings show that family treatment did not have a significant positive effect on EE level . The dichotomous FMSS/EE did not systematic ally change and these findings were comparable with the results of prior EE research . A scoring system that included all subscores of the FMSS was somewhat more sensitive to changes . In the individual treatment condition relapse rates tended to co-occur with a change in FMSS/EE level , irrespective of the direction of this change OBJECTIVE To compare outcomes in psychoeducational multiple-family group treatment vs psychoeducational single-family treatment . METHOD A total of 172 acutely psychotic patients , aged 18 to 45 years , with DSM-III-R schizophrenic disorders were r and omly assigned to single- or multiple-family psychoeducational treatment at six public hospitals in the state of New York . Psychotic relapse , symptom status , medication compliance , rehospitalization , and employment were assessed independently during 2 years of supervised treatment . RESULTS The multiple-family groups yielded significantly lower 2-year cumulative relapse rates than did the single-family modality ( 16 % vs 27 % ) and achieved markedly lower rates in patients whose conditions had not remitted at index hospital discharge ( 13 % vs 33 % ) . The relapse hazard ratio between treatments was 1:3 . The relapse rate for both modalities was less than half the expected rate ( 65 % to 80 % for 2 years ) for patients receiving individual treatment and medication . Rehospitalization rates and psychotic symptoms decreased significantly , and medication compliance was high , to an equal degree in both modalities . CONCLUSION Psychoeducational multiple-family groups were more effective than single-family treatment in extending remission , especially in patients at higher risk for relapse , with a cost-benefit ratio of up to 1:34 OBJECTIVE The present study aims to assess the efficacy of a structured psychoeducational group intervention for adolescents with early-onset psychosis and their families . The intervention was implemented in parallel in 2 separate groups by focusing specifically on problem-solving strategies and structured psychosis-related information to manage daily life difficulties associated with the disease , to mitigate crises , and to prevent relapses . METHOD We performed a 9-month , r and omized , rater-blinded clinical trial involving 55 adolescent patients with early-onset psychosis and either or both of their parents . A psychoeducational problem-solving group intervention ( n = 27 ) was compared with a nonstructured group intervention ( n = 28 ) . The primary outcomes were number of hospitalizations , days of hospitalization , and visits to the emergency department . The secondary outcome measures were clinical variables and family environment . RESULTS Assessment s were performed before and after the intervention . At the end of the group intervention , 15 % of patients in the psychoeducational group and 39 % patients in the nonstructured group had visited the emergency department ( χ² = 3.62 , df = 1 , p = .039 ) . The improvement in negative symptoms was more pronounced in the psychoeducational group ( 12.84 [ 7.87 ] ) than in the nonstructured group ( 15.81 [ 6.37 ] ) ( p = .039 ) . CONCLUSION A parallel psychoeducational group intervention providing written instructions in a structured manner could help adolescents with early-onset psychosis and their parents to manage crises by implementing problem-solving strategies within the family , thus reducing the number of visits to the emergency department . Negative symptoms improved in adolescents in the psychoeducational group . Clinical trial registration information -- Intervention Module AGES ( AGES-CM ) ; http:// clinical trials.gov/ ; NCT02101372 . [ corrected ] Duration of untreated psychosis ( DUP ) has emerged as a reliable predictor of outcome but continues to remain under scientific scrutiny . The present study examines the effect of differential periods of DUP on long-term outcome of first episode schizophrenia at Mumbai , India . This research was a prospect i ve , 10-year follow-up naturalistic study . Hospitalized patients of first episode schizophrenia were selected and followed up . Results showed that the mean DUP was higher for a group which showed clinical recovery on Clinical Global Impression Scale [ 14.0 months ( SD=8.0 ) in recovered and 10.8 months ( SD=5.7 ) in non-recovered group ( P=0.091 ) ] . DUP was not found to be significantly associated with any of the end point parameters of good clinical or social outcome . Thus , this study found that DUP alone does not determine outcome status confirming the role of psychopathological heterogeneity OBJECTIVE Longitudinal studies have begun to clarify the phenotypic characteristics of adolescents and young adults at clinical high risk for psychosis . This 8-site r and omized trial examined whether a 6-month program of family psychoeducation was effective in reducing the severity of attenuated positive and negative psychotic symptoms and enhancing functioning among individuals at high risk . METHOD Adolescents and young adults ( mean age 17.4 ± 4.1 years ) with attenuated positive psychotic symptoms , brief and intermittent psychosis , or genetic risk with functional deterioration were r and omly assigned to 18 sessions of family-focused therapy for individuals at clinical high risk ( FFT-CHR ) in 6 months or 3 sessions of family psychoeducation ( enhanced care [ EC ] ) . FFT-CHR included psychoeducation about early signs of psychosis , stress management , communication training , and problem-solving skills training , whereas EC focused on symptom prevention . Independent evaluators assessed participants at baseline and 6 months on positive and negative symptoms and social-role functioning . RESULTS Of 129 participants , 102 ( 79.1 % ) were followed up at 6 months . Participants in FFT-CHR showed greater improvements in attenuated positive symptoms over 6 months than participants in EC ( F1,97 = 5.49 , p = .02 ) . Negative symptoms improved independently of psychosocial treatments . Changes in psychosocial functioning depended on age : participants more than 19 years of age showed more role improvement in FFT-CHR , whereas participants between 16 and 19 years of age showed more role improvement in EC . The results were independent of concurrent pharmacotherapy . CONCLUSION Interventions that focus on improving family relationships may have prophylactic efficacy in individuals at high risk for psychosis . Future studies should examine the specificity of effects of family intervention compared to individual therapy of the same duration and frequency . Clinical trial registration information-Prevention Trial of Family Focused Treatment in Youth at Risk for Psychosis ; http:// clinical trials.gov/ ; NCT01907282 Aims . Occupational functioning is severely impaired in people with psychosis . Social cognition has recently been found to be a stronger predictor of functioning than neurocognition . This study is the first to investigate if externalizing attributional biases that are typically associated with psychosis play a role in the vocational pathways of people with early psychosis . Methods . A cross-sectional design was used . Fifty participants with early psychosis were recruited from a cohort of 144 participants of the Lambeth Early Onset r and omized control trial at 18-month follow-up . Information on occupational functioning was obtained using case notes and interview . Severity of symptoms was assessed and participants completed measures on attributional style and executive functioning . Results . Although executive functioning and positive symptoms were associated with poor occupational functioning , an externalizing attributional style for failures and reduced engagement in occupational activities during the previous 18 months emerged as the only predictors of poor occupational functioning at 18-month follow-up . Conclusions . An externalizing attributional bias is associated with poor occupational functioning . Further research is needed to investigate the direction of this relationship and whether attributional biases mediate the impact of symptoms and cognitive impairment on functioning The effect of in-patient and individual orientated psychosocial intervention ( IPI ) and in-patient and individual and family orientated intervention ( IPFI ) across levels of expressed emotion ( EE ) on relapse was compared in a group of patients with recent onset schizophrenic disorders . Patients were r and omly assigned to an individual orientated psychosocial intervention programme or to an identical psychosocial programme plus a behavioural family intervention . Seventy-six patients were studied during a 12 month out-patient treatment period after an in-patient treatment programme in which parents followed a psychoeducational programme . Overall relapse rates during the out-patient interventions were low ( 16 % ) . Adding family intervention to the psychosocial intervention did not affect the relapse rate . Patients in low EE families relapsed slightly more often during the psychosocial plus family intervention . In-patient treatment with psychoeducation for parents , followed by an out-patient psychosocial intervention programme , has a favourable impact on relapse . Additional family intervention may increase stress in low EE families , thus affecting relapse in their children At the time of discharge from their first stay in psychiatric hospital , 78 male schizophrenic patients were r and omly assigned to a family intervention ( experimental ) group or a ' st and ard care ' control group and were followed for the next 18 months . The family intervention consisted of both group and individual counselling sessions every 1 - 3 months that focused on education about the illness and on methods of dealing with the patient . There was a significantly lower rate of hospital readmission in the family intervention group than in the control group ( 15.4 % versus 53.8 % , chi 2 = 12.75 , P < 0.01 ) , and the mean hospital-free period for those who were readmitted was significantly longer in the experimental group than in the control group ( 245 days versus 130 days , t = 2.91 , P < 0.01 ) . Moreover , the clinical status and overall level of functioning in patients who were not readmitted were significantly better in experimental subjects than in control subjects . Stratified analysis showed that family intervention and regular use of medication had independent and additive effects on the outcome . During the 18 months after the index discharge patients who did not take medication regularly and who did not receive family intervention were 7.9 times as likely to be readmitted to hospital as patients who took medication regularly and received family intervention BACKGROUND Empirical evidence of the efficacy and effectiveness of psychosocial family intervention and of the specificity of its effects on the course of schizophrenia is limited . The aim was to study the efficacy and effectiveness of psychosocial family intervention with regard to clinical and social functioning and family burden after controlling for compliance and several prognostic factors . METHOD A 2-year r and omized controlled trial with blind assessment s. Fifty patients with DSM-IV schizophrenia and persistent positive symptoms and /or previous clinical relapse were allocated to psychosocial family intervention , individual counselling and st and ard treatment versus individual counselling and st and ard treatment . RESULTS Family intervention was associated with fewer clinical relapses , hospitalizations and major incidents , and an improvement in positive and negative symptoms , social role performance , social relations , employment and family burden . The reduction in hospitalizations in the family intervention group was significantly greater than that observed in the group of patients who refused to participate but this was not the case for the control group . The effects of family intervention were independent of compliance and prognostic factors . CONCLUSIONS Family intervention is effective in severe schizophrenia independently of compliance and prognostic factors BACKGROUND It is unclear if the impact of psychoeducational family intervention for patients with schizophrenia can be sustained over 10 years . In this study , we explored the 14-year effect of psychoeducational family intervention for patients with schizophrenia in a Chinese rural area . METHOD The data from a cluster r and omized control trial ( C RCT ) study of psychoeducational family intervention in a 14-year follow-up was analyzed . All patients with schizophrenia ( n = 326 ) who participated in the C RCT drawn from six townships in Xinjin County of Chengdu in 1994 , of whom 238 ( 73.0 % ) who were still alive , and their informants were followed up in 2008 . The Patients Follow-up Scale , the Positive and Negative Syndrome Scale ( PANSS ) and the Global Assessment of Functioning were used in the follow-up study . RESULTS There were no significant differences of marital status , mean scores of PANSS positive symptoms , negative symptoms , general mental health , and total scores among the psychoeducational family intervention , medication , and control groups in 2008 . The psychoeducational family intervention group had a significantly higher rate of antipsychotic medication and a higher level of work ability than other two groups . The control group had a significantly higher rate of never-treated ( 26.0 % ) than psychoeducational family intervention group ( 6.5 % ) . CONCLUSION Psychoeducational family intervention might be still effective in the 14-year follow-up , especially in patients ' treatment adherence/compliance and social functioning . Psychoeducational family intervention might be more effective in places where family members frequently participated in patients ' care and had a lower level of knowledge on mental illness . Family intervention should be considered when making mental health policy and planning mental health services PURPOSE Evidence for the recommendation to deliver Cognitive Behavioural Therapy ( CBT ) and Family Interventions ( FI ) to under-18s with psychosis derives from adult research , and no previous study has focused exclusively on an adolescent population . We evaluated adaptations of these therapies for adolescent in patients with psychosis ( CBTpA and FIpA ) , delivered as an adjunct to inpatient st and ard care ( SC ) . SUBJECTS AND METHODS Thirty adolescent in patients with psychotic symptoms on admission were sequentially allocated to receive CBTpA+SC ( n=10 ) ; FIpA+SC ( n=10 ) or SC alone ( n=10 ) . Psychotic symptoms and functioning were measured at admission and discharge . RESULTS Group comparisons did not reach conventional significance , but effect sizes in this pilot study showed a promising impact of CBTpA compared to SC alone , in reducing symptoms ( ES : d=0.6 ) , with smaller effect sizes for functioning ( d=0.2 ) and for FIpA ( symptoms , d=0.1 and functioning , d=0.4 ) . There was no advantage of either additional treatment in reducing length of stay , but self-report satisfaction ratings were higher for both psychological therapies . DISCUSSION AND CONCLUSIONS The study is the first to focus on an exclusively adolescent population , using appropriately adapted therapy protocol s. Findings suggest that the interventions are feasible , acceptable and helpful for adolescents with psychosis . Larger r and omised controlled trials are now needed Family interventions for first-episode psychosis ( FEP ) are an integral component of treatment , with positive effects mainly on patients ’ mental state and relapse rate . However , comparatively little attention has been paid to the effects of family interventions on caregivers ’ stress coping and well-being , especially in non-Western countries . We aim ed to test the effects of a 5-month clinician-supported problem-solving bibliotherapy ( CSPSB ) for Chinese family caregivers of people with FEP in improving family burden and carers ’ problem-solving and caregiving experience , and in reducing psychotic symptoms and duration of re-hospitalizations , compared with those only received usual outpatient family support ( UOFS ) . A r and omized controlled trial was conducted across 2 early psychosis clinics in Hong Kong , where there might be inadequate usual family support services for FEP patients . A total of 116 caregivers were r and omly selected , and after baseline measurement , r and omly assigned to the CSPSB or UOFS . They were also assessed at 1-week and 6- and 12-month post-intervention . Intention-to-treat analyses were applied and indicated that the CSPSB group reported significantly greater improvements in family burden and caregiving experience , and reductions in severity of psychotic symptoms and duration of re-hospitalizations , than the UOFS group at 6- and 12-month follow-up . CSPSB produces moderate long-term benefits to caregivers and FEP patients , and is a low-cost adjunct to UOFS " Expressed emotion " ( EE ) is considered a marker of dysfunctional family interaction in patients with schizophrenia . An alternative hypothesis , however , is that at least some of the different elements of EE really represent attempts on the part of carers to cope with and care for a relative with a psychiatric disorder . EE ( criticism and emotional overinvolvement ) was measured in relatives ( n = 31 ) of patients with psychotic illness using the Five-Minute Speech Sample ( FMSS ) . Level of EE was examined in relation to ( 1 ) patient-reported family involvement in care over the previous 2 years as indicated by medication monitoring , involvement in treatment decisions , and providing a substitute for institutional care ; and ( 2 ) symptom severity and number of psychotic episodes . Presence of EE in the relative was strongly associated with the degree of family involvement in care ( odds ratio [ OR ] over three levels : 3.2 ; 95 % confidence interval [ CI ] , 1.1 to 9.0 ) . In addition , presence of high EE was associated with number of psychotic episodes in the previous 5 years in the prob and ( OR over 0 , 1 , or 2 episodes : 6.2 ; 95 % CI , 1.2 to 31.9 ) . The association with family involvement was confined to emotional overinvolvement ( OR = 9.1 ; 95 % CI , 2.0 to 42.2 ) , whereas the association with previous psychotic episodes was confined to criticism ( OR = 20.6 ; 95 % CI , 2.8 to 149.3 ) . Emotional overinvolvement may be a state marker for attempts on the part of relatives to be partners in the care for patients with psychotic illness . High level of criticism may be a trait marker in relatives associated with poor prognosis , but could also develop in reaction to a frequently relapsing illness OBJECTIVE This study investigated whether family focused therapy ( FFT-CHR ) , an 18-session intervention that consisted of psychoeducation and training in communication and problem solving , brought about greater improvements in family communication than enhanced care ( EC ) , a 3-session psychoeducational intervention , among individuals at clinical high risk for developing psychosis . METHOD This study was conducted within a r and omized controlled trial across 8 sites . We examined 10-min problem-solving discussion s at baseline and 6-month re assessment among 66 adolescents and young adults and their parents . Trained coders who were blind to treatment and time of assessment achieved high levels of interrater reliability when evaluating family discussion s on categories of calm-constructive and critical-conflictual behavior . RESULTS Individuals at high risk and their family members who participated in FFT-CHR demonstrated greater improvement from baseline to 6-month re assessment in constructive communication and decreases in conflictual behaviors during family interactions than those in EC . Participants in FFT-CHR showed greater increases from baseline to 6 months in active listening and calm communication and greater decreases in irritability and anger , complaints and criticism , and off-task comments compared to participants in EC . These changes occurred equally in high-risk participants and their family members . CONCLUSIONS A 6-month family skills training treatment can bring about significant improvement in family communication among individuals at high risk for psychosis and their parents . Future studies should examine the association between enhancements in family communication and reduced risk for the onset of psychosis among individuals at high risk OBJECTIVE To test whether the statistically significant results of a r and omized clinical trial of an inpatient family intervention were clinical ly significant for hospital practice , the authors reanalyzed outcome data using a measure of clinical significance based on the extent to which patients had recovered during the course of the intervention . METHODS A total of 169 hospitalized subjects and their families were r and omly assigned to a psychoeducational inpatient family intervention or to a comparison group . Patient and family outcome measures were assessed at admission , discharge , and six and 18 months after admission . Analyses of statistically significant differences in outcome suggested that inpatient family intervention was effective for certain patient subgroups identified by gender and diagnosis . Global Assessment Scale scores two or more st and ard deviations above the pretreatment ( admission ) mean were used as indicators for clinical ly significant improvement . RESULTS The re analysis confirmed that inpatient family intervention was associated with clinical ly significant improvement at discharge , especially for female patients and patients with chronic schizophrenia and bipolar disorder . These effects were maintained six months after admission before attenuating at 18 months . CONCLUSIONS Inpatient family intervention results in clinical ly meaningful outcomes for certain subgroups of patients and their families OBJECTIVE To investigate whether the beneficial effects of a structured , psychoeducational , parallel-group program for adolescents with early-onset psychosis and their families observed immediately after the intervention were maintained 2 years later . METHOD The present study examines the longitudinal efficacy of a r and omized controlled trial based on a psychoeducational , problem-solving , structured group intervention for adolescents with early-onset psychosis and their families ( PE ) and compares it with that of a nonstructured group intervention ( NS ) after a 2-year follow-up . We analyzed whether the differences between PE and NS found after the intervention persisted 2 years later . Intergroup differences in number and duration of hospitalizations , symptoms , and functioning were also assessed . RESULTS After 2 years of follow-up , we were able to reassess 89 % of patients . In the PE group , 13 % of patients had visited the emergency department , compared with 50 % in the NS group ( p = .019 ) . However , no statistically significant differences were found between the groups for negative symptoms or number and duration of hospitalizations . A significant improvement in Positive and Negative Syndrome Scale ( PANSS ) general symptoms was observed in the PE group . CONCLUSION Our psychoeducational group intervention showed sustained effects by diminishing the number of visits to emergency departments 2 years after the intervention . Our findings indicate that this psychoeducational intervention could provide patients with long-lasting re sources to manage crises more effectively . Clinical trial registration information-Intervention Module AGES ( AGES-CM ) ; http:// clinical trials.gov/ ; NCT02101372 BACKGROUND Carers ' satisfaction with psychiatric services related to information and advice is generally poor . This may be particularly true for services trying to meet the needs of ethnically diverse communities . It is important that services attempt to ameliorate carers ' concerns as early as possible . The authors aim ed to assess the impact of a brief educational and advice support service on carers of patients with a first episode of psychotic illness . METHOD Carers of all patients identified with a first episode of psychosis in a defined psychiatric catchment area of North London were invited to participate . Following consent from patients and relatives , relatives were r and omly allocated to receive ( in addition to usual services ) a brief intervention comprising education and advice about the disorder from a support team or to usual care from community psychiatric services . RESULTS One hundred and six carers were recruited to the study . Take-up of the intervention was less than expected and the intervention had little impact . The authors found no differences over time between the r and omized arms for relatives ' satisfaction ( F = 23 , p = 0 .4 , df = 1 ) or number of days spent by patients in hospital over nine months from entry to the trial ( F= 1.7 , p= 0.18 , df = 1 ) . CONCLUSIONS It was found that the support and advice intervention for families had little impact on their satisfaction or on patients ' outcomes . However , failure to take up the intervention threatens the conclusions as the power to show an effect was reduced . Although family interventions , in general , are considered an important adjunct to the treatment of patients with chronic psychosis , there may be difficulties in providing an educational and support intervention shortly after first onset . How and when psychiatric services provide information and advice to carers of people newly diagnosed with a psychosis requires further study A ‘ short family therapy in schizophrenia , according to a specific systemic model ( the ‘ Elementary Pragmatic Model ’ or EPM ) with a strong paradoxical structure is presented . A total of 38 schizophrenic patients , r and omly allocated , were treated according to the EPM model combined with psychotropic drugs ( 19 cases , each of whom underwent 10 weekly sessions of family therapy ) or a traditional clinical ‐pharmacological approach ( 19 cases ) . With regard to all measures ( number of drop‐outs , symptoms according to the Brief Psychiatric Rating Scale , social activity according to the Strauss‐Carpenter Outcome Scale and an interactive test ) the EPM group showed better results . It is suggested that the systemic approach could be used not only as an effective therapy model in schizophrenia but also as an intervention in addition to or integrated into an ongoing psychoeducational family therapy BACKGROUND Positive effects on the relapse from illness and compliance with medication by patients have been observed from family intervention for schizophrenia . However , little attention has been paid to the effects on family members , particularly those in non-Western countries . Inconsistent and inconclusive findings were found on the family-related outcomes and longer-term effects of family intervention . OBJECTIVE This study tested the effects of a nine-month family-led mutual support group for Chinese people with schizophrenia , compared with a psycho-education group and st and ard psychiatric care over a 24-month follow-up . DESIGN A r and omised controlled trial [ registered with Clinical Trials.gov ( NCT00940394 ) ] with repeated- measures , three-group design . SETTING S Two regional psychiatric outpatient clinics in Hong Kong . PARTICIPANTS One hundred and thirty-five Chinese family caregivers and their patients with schizophrenia were r and omly recruited , of whom 45 family dyads received family-led mutual support group , a psycho-education group , or st and ard care . METHODS After completing the pre-test question naire , the participants were r and omly assigned into one of the three study groups . The mutual support and psycho-education groups comprised 14 two-hour group sessions , with patients participating in at least 5 sessions . Those in st and ard care ( and two treatment groups ) received routine psychiatric care . Multiple patient and family-related psychosocial outcomes were compared at recruitment and at one week , 12 months , and 24 months following interventions . RESULTS One hundred and twenty-six of 135 family dyads completed the three post-tests and 43 ( 95.6 % ) attended at least nine group sessions ( 60 % ) of the mutual support group programme . Mean ages of the family caregivers in the study ranged from 41.2 ( SD=7.0 ) to 42.7 ( SD=7.6 ) years . About two-thirds of the caregivers were male and patients ' parent or spouse . The results of multivariate analysis of variance followed by Helmert contrasts tests indicated that the participants in the mutual support group indicated significantly greater improvement in family and patient functioning [ F(2 , 132)=5.40 , p=0.005 and F(2 , 132)=6.88 , p=0.001 , respectively ] and social support for families [ F(2 , 131)=5.01 , p=0.005 ] , and in reducing patients ' symptom severity [ F(2 , 132)=4.65 , p=0.01 ] and length of re-hospitalisations [ F(2 , 132)=4.78 , p=0.01 ] at 12- and 24-month follow-ups . CONCLUSIONS Family-led mutual support group for schizophrenia produces longer-term benefits to both the patients ' and families ' functioning and relapse prevention for patients , compared with psycho-education and st and ard care . This group programme can be an effective family intervention for Chinese people with schizophrenia After a brief inpatient hospitalization , 104 acute , young schizophrenics , stratified by premorbid adjustment , were r and omly assigned to one of four aftercare conditions for a six-week controlled trial . Conditions involved one of two dose levels of fluphenazine enanthate ( 1 ml or 0.25 ml ) and presence or absence of crisis-oriented family therapy . Relapses during the six-week period and at six-month follow-up were least in patients who received both high-dose and family therapy ( 0 % ) and greatest ( 48 % ) in the low-dose-no therapy group . Brief Psychiatric Rating Scale symptom ratings disclosed a significant family therapy effect at six weeks that was sustained at six months only for therapy patients originally receiving the high drug dose . Numerous interactions were found between premorbid adjustment status and response to the two treatment conditions BACKGROUND Family intervention for psychotic disorders is an integral part of psychiatric treatment with positive effects on patients ' mental state and relapse rate . However , the effect of such family-based intervention on caregivers ' psychological distress and well-being , especially in non-Western countries , has received comparatively much less attention . OBJECTIVES To test the effects of guided problem-solving-based manual-guided self-learning programme for family caregivers of adults with recent-onset psychosis over a 6-month period of follow-up , when compared with those in usual family support service . DESIGN A single-centre r and omised controlled trial , which was registered at Clinical Trials.gov ( NCT02391649 ) , with a repeated- measures , two-arm ( parallel-group ) design . SETTING S One main psychiatric outpatient clinic in the New Territories of Hong Kong . PARTICIPANTS A r and om sample of 116 family caregiverss of adult out patients with recent-onset psychosis . METHODS Following pre-test measurement , caregivers were assigned r and omly to one of two study groups : a 5-month self-help , problem-solving-based manual-guided self-learning ( or bibliotherapy ) programme ( in addition to usual care ) , or usual family support service only . Varieties of patient and caregiver health outcomes were assessed and compared at baseline and at 1-week and 6-month post-intervention . RESULTS One hundred and eleven ( 96 % ) caregivers completed the 6-month follow-up ( two post-tests ) ; 55 of them ( 95 % ) completed ≥4 modules and attended ≥2 review sessions ( i.e. , 75 % of the intervention ) . The family participants ' mean age was about 38 years and over 64 % of them were female and patient 's parent or spouse . Multivariate analyses of variance indicated that the manual-guided self-learning group reported significantly greater improvements than the usual care group in family burden [ F(1,110)=6.21 , p=0.006 ] and caregiving experience [ F(1,110)=6.88 , p=0.0004 ] , and patients ' psychotic symptoms [ F(1,110)=6.25 , p=0.0003 ] , functioning [ F(1,110)=7.01 , p=0.0005 ] and number of hospitalisations [ F(1,110)=5.71 , p=0.005 ] over 6-month follow-up . CONCLUSIONS Problem-solving-based , manual-guided self-learning programme for family caregivers of adults with recent-onset psychosis can be an effective self-help programme and provide medium-term benefits to patients ' and caregivers ' mental health and duration of patients ' re-hospitalisations Caring for young people with first-episode psychosis ( FEP ) is challenging and can adversely affect carer well-being , with limited evidence -based support material s available . We aim ed to examine whether completion of a self-directed problem-solving bibliotherapy among carers of young people with FEP led to a better experience of caring , less distress and expressed emotion , and better general health than carers who only received treatment as usual ( TAU ) . A r and omized controlled trial was conducted across two early-intervention psychosis services in Melbourne , Australia . A total of 124 carers were r and omized to problem-solving bibliotherapy intervention ( PSBI ) or TAU and assessed at baseline , 6-week and 16-week follow-up . Intent-to-treat analyses were carried out and indicated that recipients of PSBI had a more favorable experience of caring than those receiving TAU , and these effects were sustained at both follow-up time points . Across the other measures , both groups demonstrated improvements by week 16 , although the PBSI group tended to improve earlier . The PSBI group experienced a greater reduction in negative emotional evaluations of the need to provide additional support to young people with FEP than the TAU group by week 6 , while the level of psychological distress decreased at a greater rate from baseline to 6 weeks in the PSBI compared with the TAU group . These findings support the use of problem-solving bibliotherapy for first-time carers , particularly as a cost-effective adjunct to TAU |
10,547 | 28,431,202 | There was no evidence of any differences in short-term mortality in any of the comparisons ( very low- quality evidence ) .
AUTHORS ' CONCLUSIONS Very low- quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis .
However , the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions .
We did not find consistent clinical benefits with any intervention . | BACKGROUND In people with acute pancreatitis , it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure .
OBJECTIVES To assess the effects of different pharmacological interventions in people with acute pancreatitis . | BACKGROUND Oxidative stress ( OS ) in acute pancreatitis ( AP ) has been pathologically linked with the systemic inflammatory response and antioxidant supplementation may have a clinical benefit . METHODS In this prospect i ve , r and omised open label , controlled pilot study , patients admitted within 72 hours of onset of pain were r and omised to receive either placebo ( only st and ard medical treatment ; SMT ) or antioxidants ( vitamin C 500 mg , N-acetyl cysteine 200 mg 8 hourly and antoxyl forte 1 capsule hourly with st and ard medical treatment ; SMT + AO ) daily , following informed consent . Patients with co-morbid illness and pregnancy were excluded . Primary efficacy measures were length of hospital stay and complications whilst secondary measures were biochemical markers of oxidative stress ( thiobarbituric acid reactive substances [ TBARS ] and superoxide dismutase [ SOD ] and total antioxidant capacity [ TAC ] and vitamin C ) at Days 1 , 3 and 7 . RESULTS Of 53 patients , 30 patients were r and omised to SMT and 23 patients to SMT + AO . The mean duration of hospital stay in the SMT group ( 10.3 + /- 7 days ) was more compared to SMT + AOT ( 7.2 + /- 5 days ) , but was not statistically significant ( p=0.07 ) , complications were similar in the 2 groups . At Day 7 , OS was significantly lower in the SMT + AO group when compared with the SMT group ( TBARS , p=0.05 ; SOD , p=0.03 ) with a significant increase in FRAP and vitamin C ( p=0.01 ) . CONCLUSIONS Antioxidant supplementation may decrease the length of hospital stay and complication rate in patients with AP , but a larger clinical trial is needed to support this hypothesis . Further , it decreased the OS and improved the antioxidant status in patients with AP OBJECTIVE To investigate the effects of continuous early enteral nutrition ( EEN ) supplemented with glutamine and arginine on gut barrier function in patients with severe acute pancreatitis ( SAP ) . METHODS Thirty two patients with a diagnosis of acute pancreatitis predicted to develop severe disease were r and omized into 2 groups : EEN group ( n = 18 ) and EEN + glutamine and arginine group ( enteral immunonutrition group , n = 14 ) . EEN was initiated when homeostasis was achieved within 72 hours after attack , and both group received isocaloric isonitrogenous nutrition . Glutamine and arginine were administered into jejunum in the enteral immunonutrition group . Serum amylase , plasma diamine oxidase ( DAO ) , C-reactive protein ( CRP ) , plasma endotoxin , urinary excretion of lactulose ( L ) , and mannitol ( M ) were measured , and APACHE-II scores were recorded on days 1 , 7 , and 14 . Complications , and length and cost of hospitalization were recorded as well . RESULTS EEN and enteral immunonutrition were both tolerated well . There was no difference in APACHE-IIscore between the two groups ( P > 0.05 ) . The DAO , CRP , plasma endotoxin , and urinary L/M levels decreased with the course of SAP . However , the plasma endotoxin and urinary L/M on day 7 of the enteral immunonutrition group were ( 10.0 + /- 3.8 ) EU/ml and 0.29 + /- 0.15 respectively , both significantly higher than those of the EEN group [ ( 7.9 + /- 2.8 ) EU/ml and 0.16 + /- 0.08 respectively , both P < 0.05 ] . The length of hospital stay and cost showed no differences between the two groups . CONCLUSION EEN is safe and feasible in treatment of SAP . Enteral immunonutrition containing glutamine and arginine improves the gut barrier function by reducing the gut permeability and decreasing plasma endotoxin level in the early stage of SAP In acute pancreatitis ( AP ) tumor necrosis factor-α mediates multi-organ failure ; in animal models its blockade with pentoxifylline ameliorates AP . The efficacy of pentoxifylline in predicted severe AP ( pSAP ) was tested in a double-blinded , r and omized , control trial . Twenty-eight patients with pSAP were r and omized within 72 hours of diagnosis to pentoxifylline or placebo . Baseline characteristics were similar in both groups . The pentoxifylline group had fewer intensive care unit admissions and shorter intensive care unit and hospital stays of longer than 4 days ( all P < .05 ) . Patients receiving pentoxifylline had no adverse effects . Pentoxifylline within 72 hours of pSAP is safe ; a larger study of pentoxifylline in AP is needed to confirm efficacy . Clinical Trials.gov number : NCT01292005 Thirty patients with acute pancreatitis were allocated to indomethacin suppositories , 50 mg twice daily , or identical-looking placebo suppositories for 7 days in a controlled double-blind trial . The groups of patients were not different with regard to age , sex , etiology , or number of Ranson criteria . The number of days with pain and number of opiate injections were significantly less in patients treated with indomethacin . The median values of serum amylase and serum calcium were not different before or at any day during treatment . Bleeding from the gastrointestinal tract was not seen BACKGROUND / AIMS Experimental and clinical studies demonstrated that probiotics containing lactobacilli significantly improve the outcome of acute pancreatitis . In a prospect i ve , r and omized , double-blinded study the role of " Synbiotic 2000 " , a new synbiotic composition with high colony forming unit ( CFU ) was evaluated in the treatment of severe acute pancreatitis . METHODOLOGY Patients with severe acute pancreatitis were r and omized into two groups . Nasojejunal feeding was commenced within 24 hours after admission in both groups and continued for at least seven days . The first group of patients received four different lactobacilli preparations with 1010 CFU , respectively , and prebiotics containing four bioactive fibers ( inulin , beta-glucan , resistant starch and pectin ) in addition . Patients in the second ( control ) group received only prebiotics . RESULTS 62 patients with severe acute pancreatitis completed the study . Altogether 8 patients died . Lower incidence of multiorgan failure ( MOF ) , septic complications and mortality were detected in the first group compared to the control , but the differences were not significant statistically . The total incidence of systemic inflammatory response syndrome ( SIRS ) and MOF were significantly different between the two groups ( 8 vs. 14 ; p < 0.05 ) . Furthermore , the number patients recovering with complications were significantly less in the first group receiving modern synbiotic therapy compared to the control ( p < 0.05 ) . Finally , lower rate of late ( over 48 hours ) organ failure was detected in the first versus the control group ( 3.0 % vs. 17.2 % ) . CONCLUSIONS The results suggest that early nasojejunal feeding with synbiotics may prevent organ dysfunctions in the late phase of severe acute pancreatitis . In addition , the data also indicate that the infection of pancreatic necrosis may be associated with early phase organ failure Pancreatic infection is the main indication for surgery and the principal determinant of prognosis in acute necrotizing pancreatitis . Previous studies on the effects of antibiotics have not , however , uniformly demonstrated any reduction in the need for surgery or any decrease in mortality among these patients , although the incidence of pancreatic infections was significantly reduced . This single-center r and omized study was design ed to compare early vs. delayed imipenem treatment for acute necrotizing pancreatitis . Ninety patients with acute necrotizing pancreatitis ( C-reactive protein > 150 mg/L , necrosis on CT ) were r and omized within 48 hours either to a group receiving imipenem ( 1.0 g plus cilastatin intravenously 3 times a day ) or a control group . Not included were those who had been started on antibiotics at the referring clinic , those who were taken directly to the intensive care unit for multiorgan failure , and those who refused antibiotics or might have had adverse reactions . Thirty-two patients were excluded because they were over 70 years of age ( not potentionally operable ) or for any study violation . There were 25 patients in the imipenem group and 33 patients in the control group . The main end point was the indication for necrosectomy due to infection ( i.e. , after the initial increase and decrease , there was a second continuous increase in temperature , white blood cell count [ > 30 % ] and C-reactive protein [ > 30 % ] , with other infections ruled out , or bacteria were found on Gram stain of the pancreatic fine-needle aspirate ) . In the control group , imipenem was started when the operative indication was fulfilled . Conservative treatment was continued for at least 5 days before necrosectomy . The study groups did not differ from each other with regard to sex distribution , patient age , etiology , C-reactive protein concentration , and extent of pancreatic necrosis on CT . Two ( 8 % ) of 25 patients in the imipenem group compared to 14 ( 42 % ) of 33 in the control group fulfilled the operative indications ( P = 0.003 ) . Nine patients in the control group responded to delayed antibiotics but five had to undergo surgery . Of those receiving antibiotics , 2 ( 8 % ) of 25 in the early antibiotic ( imipenem ) group needed surgery compared to 5 ( 36 % ) of 14 in the delayed antibiotic ( control ) group ( P = 0.04 ) . Two ( 8 % ) of 25 patients in the imipenem group and 5(15 % ) of 13 patients in the control group died ( P = NS [ no significant difference ] ) . Seven ( 28 % ) of 25 in the imipenem group and 25 ( 76 % ) of 33 in the control group had major organ complications ( P = 0.0003 ) . Based on the preceding criteria , early imipenem-cilastatin therapy appears to significantly reduce the need for surgery and the overall number of major organ complications in acute necrotizing pancreatitis , and reduces by half the mortality rate ; this is not , however , statistically significant in a series of this size BACKGROUND The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis . AIM To investigate the efficacy of octreotide in acute pancreatitis in a r and omised , placebo controlled trial . METHODS 302 patients from 32 hospitals , fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms , were r and omly assigned to one of three treatment groups : group P ( n=103 ) received placebo , while groups O1 ( n=98 ) and O2 ( n=101 ) received 100 and 200 μg of octreotide , respectively , by subcutaneous injection three times daily for seven days . The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis . RESULTS The three groups were well matched with respect to pretreatment characteristics . An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality ( P : 16 % ; O1 : 15 % ; O2 : 12 % ) , the rate of newly developed complications , the duration of pain , surgical interventions , or the length of the hospital stay . A valid for efficacy analysis ( 251 patients ) also revealed no significant differences . CONCLUSIONS This trial shows no benefit of octreotide in the treatment of acute pancreatitis AIM To compare the beneficial effects of early enteral nutrition ( EN ) with prebiotic fiber supplementation in patients with severe acute pancreatitis ( AP ) . METHODS Thirty consecutive patients with severe AP , who required stoppage of oral feeding for 48 h , were r and omly assigned to nasojejunal EN with or without prebiotics . APACHE II score , Balthazar 's CT score and CRP were assessed daily during the study period . RESULTS The median duration of hospital stay was shorter in the study group [ 10 + /- 4 ( 8 - 14 ) d vs 15 + /- 6 ( 7 - 26 ) d ] ( P < 0.05 ) . The median value of days in intensive care unit was also similar in both groups [ 6 + /- 2 ( 5 - 8 ) d vs 6 + /- 2 ( 5 - 7 ) d ] . The median duration of EN was 8 + /- 4 ( 6 - 12 ) d vs 10 + /- 4 ( 6 - 13 ) d in the study and control groups , respectively ( P > 0.05 ) . Deaths occurred in 6 patients ( 20 % ) , 2 in the study group and 4 in the control group . The mean duration of APACHE II normalization ( APACHE II score < 8) was shorter in the study group than in the control group ( 4 + /- 2 d vs 6.5 + /- 3 d , P < 0.05 ) . The mean duration of CRP normalization was also shorter in the study group than in the control group ( 7 + /- 2 d vs 10 + /- 3 d , P < 0.05 ) . CONCLUSION Nasojejunal EN with prebiotic fiber supplementation in severe AP improves hospital stay , duration nutrition therapy , acute phase response and overall complications compared to st and ard EN therapy OBJECTIVES : Antibiotic prophylaxis improves the outcome of acute pancreatitis . Since bacterial translocation from the gut occurs in the first h of disease , early therapy is likely to achieve the maximal effect . The study compares early antibiotic treatment with treatment started after the demonstration of pancreatic necrosis . METHODS : Two hundred fifteen patients with pancreatitis were r and omized to either group A ( N = 108 ) , who started antibiotic therapy ( meropenem 500 mg t.i.d . ) at admission , or group B ( N = 107 ) , who received antibiotics after the demonstration of necrosis at computed tomography ( CT ) . CT was performed in both groups after at least 48 hr of hospitalization . The clinical course of disease was compared in the two groups . RESULTS : Thirty patients in group A and 29 in B showed necrosis on CT . The two groups were similar in demographics and characteristics of disease . Antibiotic treatment was started after 4.56 ± 1.2 days from hospitalization in group B and after 1.07 ± 0.6 days in A. Pancreatic infection occurred in four patients in group A ( 13.3 % ) and in nine in B ( 31 % ) ( p = 0.1 ) . Extrapancreatic infection occurred in 16.6 % of patients in group A and in 44.8 % in B ( p < 0.05 ) . Need for surgery and length of hospitalization were also higher in group B. Mortality rates were similar in the two groups , but , 3 of 4 patients with infected necrosis in group A and only 2 of 9 in group B died . CONCLUSIONS : Early antibiotic treatment is associated with a significant improvement in the prognosis of necrotizing acute pancreatitis ( AP ) , because of a reduction in the occurrence of septic complications Microbial infection of the pancreatic tissue in patients with severe acute pancreatitis increases the morbidity and mortality rates . Colonization of the lower gastrointestinal tract and oropharynx with Gram‐negative , but sometimes also Gram‐positive , bacteria precedes contamination of the pancreas . The aim of this study was to determine whether lactic acid bacteria such as Lactobacillus plantarum 299 could prevent colonization of the gut by potential pathogens and thus reduce the endotoxaemia associated with acute pancreatitis OBJECTIVE To investigate the effects of ω-3 fish oil lipid emulsion via vein on the inflammatory response , immune and organ function in patients with severe acute pancreatitis . METHODS A total of 53 patients with severe acute pancreatitis were r and omized into conventional therapy plus fish oil group ( FO group ) and conventional therapy group ( CON group ) . The patients in FO group were treat with ω-3 fish oil lipid emulsion ( 0.2 g × kg(-1) × d(-1 ) , 10 % ) based on conventional therapy for 14 days . The level of C-reactive protein ( CRP ) , TG and TC were detected before treatment and at day 7 and day 14 after treatment . CD(4)(+ ) , CD(4)(+)/CD(8)(+ ) and C(3 ) , C(4 ) were also detected at day 1 and day 14 after treatment . At the same time , acute physiology and chronic health evaluation II score ( APACHEII score ) , intra-abdominal pressure , negative fluid balance time , enteral nutrition start-time and ICU stay time were observed and recorded . RESULTS Forty-five out of 53 patients were finally recruited into results statistics . The level of CD(4)(+ ) , CD(4)(+)/CD(8)(+ ) and C(3 ) at day 14 after treatment in FO groups improved significantly than that in the CON group ( P < 0.05 ) . The levels of CRP , intra-abdominal pressure and APACHE II score at day 7 and day 14 in FO group descended more obviously than that in the CON group ( P < 0.05 ) . The negative liquid balance time in FO group ( 3.55 ± 0.86)days was obvious shorter than that in CON group ( 4.61 ± 1.12 ) days , while enteral nutrition start-time ( 3.86 ± 1.17 ) days was significantly earlier compared with CON group ( 5.30 ± 1.61 ) days ( P < 0.05 ) , however ICU stay time and 28 days mortality rate had no significant difference between the two groups . CONCLUSIONS ω-3 fish oil lipid emulsion can decrease the inflammatory response and the negative liquid balance time , improve the immune function and restore bowel function in severe acute pancreatitis patients . Therefore , it maybe provide a new and effective means for severe acute pancreatitis BACKGROUND Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retro grade cholangiopancreatography ( ERCP ) . METHODS In this multicenter , r and omized , placebo-controlled , double-blind clinical trial , we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP . Patients were determined to be at high risk on the basis of vali date d patient- and procedure-related risk factors . The primary outcome was post-ERCP pancreatitis , which was defined as new upper abdominal pain , an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure , and hospitalization for at least 2 nights . RESULTS A total of 602 patients were enrolled and completed follow-up . The majority of patients ( 82 % ) had a clinical suspicion of sphincter of Oddi dysfunction . Post-ERCP pancreatitis developed in 27 of 295 patients ( 9.2 % ) in the indomethacin group and in 52 of 307 patients ( 16.9 % ) in the placebo group ( P=0.005 ) . Moderate-to-severe pancreatitis developed in 13 patients ( 4.4 % ) in the indomethacin group and in 27 patients ( 8.8 % ) in the placebo group ( P=0.03 ) . CONCLUSIONS Among patients at high risk for post-ERCP pancreatitis , rectal indomethacin significantly reduced the incidence of the condition . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT00820612 . ) BACKGROUND & AIMS Antibiotic prophylaxis in necrotizing pancreatitis remains controversial . Until now , there have been no double-blind studies dealing with this topic . METHODS A total sample size of 200 patients was calculated to demonstrate with a power of 90 % that antibiotic prophylaxis reduces the proportion of patients with infected pancreatic necrosis from 40 % placebo ( PLA ) to 20 % ciprofloxacin/metronidazole ( CIP/MET ) . One hundred fourteen patients with acute pancreatitis in combination with a serum C-reactive protein exceeding 150 mg/L and /or necrosis on contrast-enhanced CT scan were enrolled and received either intravenous CIP ( 2 x 400 mg/day ) + MET ( 2 x 500 mg/day ) or PLA . Study medication was discontinued and switched to open antibiotic treatment when infectious complications , multiple organ failure sepsis , or systemic inflammatory response syndrome ( SIRS ) occurred . After half of the planned sample size was recruited , an adaptive interim analysis was performed , and recruitment was stopped . RESULTS Fifty-eight patients received CIP/MET and 56 patients PLA . Twenty-eight percent in the CIP/MET group required open antibiotic treatment vs. 46 % with PLA . Twelve percent of the CIP/MET group developed infected pancreatic necrosis compared with 9 % of the PLA group ( P = 0.585 ) . Mortality was 5 % in the CIP/MET and 7 % in the PLA group . In 76 patients with pancreatic necrosis on contrast-enhanced CT scan , no differences in the rate of infected pancreatic necrosis , systemic complications , or mortality were observed . CONCLUSIONS This study detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis 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 explore the clinical efficacy and safety of ulinastatin plus octreotide for patients with severe acute pancreatitis ( SAP ) . METHODS During January 2011 to January 2014 at our hospital , 120 SAP patients were r and omly divided into control and observation groups ( n = 60 each ) . The control group received an injection of octreotide injection while the observation group had a combination of ulinastatin and octreotide . After treatment , clinical efficiency , serum indicators and their improvements and complications were compared for two groups . RESULTS The overall efficiency of observation group was significantly higher than that of control group ( 83.3 % vs 65.0 % , P < 0.05 ) . And abdominal pain relief time , decompression time , surgical intervention rate , length of stay and mortality rate of observation group ( 1.9 ± 0.9 d , 6.3 ± 2.2 d , 1.7 % , 11.8 ± 0.5 d , 5 % ) were significantly lower than those of control group ( 3.6 ± 0.7 d , 10.4 ± 3.1 d , 8.3 % , 23.7 ± 2.1 d , 15.0 % ) ( P < 0.05 ) . After treatment , the levels of blood amylase , white blood cell ( WBC ) , C-reactive protein ( CRP ) and interleukin 6 ( IL-6 ) of observation group ( 107.2 ± 9.1 U/L , 6.2 ± 1.0 × 10(9)/L , 7.3 ± 3.4 mg/L , 28.3 ± 4.3 pg/ml ) were significantly lower than those of control group ( 430.8 ± 20.2 ) U/L , ( 11.2 ± 1.2 ) × 10(9)/L , ( 16.3 ± 5.2 ) mg/L , ( 45.3 ± 5.9 ) ng/L , ( P < 0.05 ) . And the incidences of such complications as acute respiratory distress syndrome ( ARDS ) , acute renal failure and shock of observation group ( 10.0 % , 5.0 % , 13.3 % ) were significantly lower than those of control group ( 36.7 % , 21.7 % , 33.3 % ) ( P < 0.05 ) . CONCLUSION Ulinastatin plus octreotide can significantly improve the serum and clinical parameters and reduce the incidence of complications in SAP patients . And it is worthy of wider popularization Background / Aim : Oxidative stress plays a major role in the pathogenesis of pancreatitis . Antioxidant therapy in the form of high-dose vitamin has been used for the treatment of severe acute pancreatitis with equivocal results . We wished to evaluate the efficacy and safety of antioxidant ( vitamin A , vitamin C , vitamin E ) therapy in patients with severe acute pancreatitis . Setting and design : This was a single-center , prospect i ve , r and omized , open-label with blinded endpoint assessment study of antioxidant therapy , conducted in the emergency department attached to our hospital . Material s and Methods : Thirty-nine patients with severe acute pancreatitis were r and omly assigned to antioxidant treatment group ( n=19 ) or a control group ( n=20 ) within 96 hours of developing symptoms . Patients in the antioxidant group received antioxidants ( vitamin A , vitamin E , vitamin C ) in addition to the st and ard treatment provided to both the groups for a period of 14 days . The primary outcome variable was presence of organ dysfunction at day 7 . The secondary outcome variables were length of hospital stay , multiorgan dysfunction ( MODS ) at day 7 , recovery at the end of 4 weeks , complications , and mortality . The change in markers of oxidative stress from baseline was also measured . Results : We demonstrated no significant difference in organ dysfunction ( P=1.0 ) , MODS ( P=0.8 ) , and length of hospital stay ( P=0.29 ) between the two groups . All the patients survived in the antioxidant-treated group , whereas two patients died in the control group . The change in the levels of malondialdehyde , superoxide dismutase , and reduced glutathione were not significantly different in the two groups at day 7 . Univariate analysis showed marginal benefit with antioxidant treatment ( P=0.034 ) in patients with severe acute pancreatitis . Conclusions : This r and omized study demonstrates that there is no significant benefit from antioxidant therapy in patients with established severe acute pancreatitis In a r and omized double-blind study the effect of CaNa2EDTA , a phospholipase A2 inhibitor , was tested as a treatment for acute pancreatitis . CaNa2EDTA was infused intravenously during the first 2 days after admission to hospital , in addition to normal conservative treatment . CaNa2EDTA decreased the serum phospholipase A2 activity and appeared to promote recovery from the illness . To what extent the inhibition of serum phospholipase activity may prevent the progress of severe haemorrhagic pancreatitis or diminish mortality and morbidity in acute pancreatitis should be investigated in further studies BACKGROUND In acute pancreatitis ( AP ) administration of n-3 polyunsaturated fatty acids ( PUFAs ) might change the course of the disease through modulation of eicosanoid synthesis . PATIENTS AND METHODS In a prospect i ve , r and omized clinical trial from 28 patients with moderate-severe AP , 14 received n-3 PUFAs ( fish oil ) enterally ( 3.3g/day for 5 - 7 days ) . Measurement of erythrocyte superoxide-dysmutase ( SOD ) activity , serum total antioxidant status ( TAS ) , vitamin A and E , fatty acids , C-reactive protein , transthyretin concentrations were performed at admission , day 3 , 7 and 14 . RESULTS The n-3 to n-6 LCPUFA ratios increased significantly in serum lipids of the patients receiving n-3 PUFA supplementation , whereas remained unchanged in the controls . Supplementation result ed in significant decrease in length of hospitalization ( 13.07+/-6.70 vs. 19.28+/-7.18 days , P<0.05 ) and jejunal feeding ( 10.57+/-6.70 vs. 17.57+/-10.52 , P<0.05 ) . Complications developed in 6/14 ( 42 % ) of treated and 9/14 ( 64 % ) of control patients . The SOD activity was significantly higher at day 3 in the supplemented group ( P<0.05 ) , but there were no significant differences between the two groups in other antioxidants and acute phase reactants . CONCLUSION The use of enteral formula enriched with n-3 PUFAs in the treatment of AP seems to have clinical benefits based upon the shortened time of jejunal feeding and hospital stay Introduction Previous human studies have shown low activity of protein C ( APC ) in severe acute pancreatitis ( SAP ) . This , together with the findings in animal models , suggests that activated protein C ( APC ) may protect against pancreatic injury and ameliorate the disease . We , therefore , evaluated its effect on multiple organ dysfunction ( MOD ) measured by the SOFA ( Sequential Organ Failure Assessment ) and on organ-failure-free days , and the safety of APC in SAP . Methods A prospect i ve double blind r and omized pilot study was use . The study occurred in one university hospital tertiary intensive care unit ( ICU ) with eight beds . The patients were chosen according to the following inclusion criteria : 1 ) Those admitted to the hospital < 96 h from the onset of pain , 2 ) Those who had a three-fold increase in serum amylase over normal upper range or/ and in whom computed tomography ( CT ) verification of SAP was noted , 3 ) Those who had one or more organ dysfunction ( OD ) , and 4 ) Those in whom less than 48 hours had passed since their first OD . Of a total of 215 adult patients with SAP screened between June 2003 and August 2007 , 158 fulfilled the study inclusion criteria . After exclusions 32 patients were r and omized to the study . The intervention consisted of APC ( N = 16 ) administered intravenously for 96 hours with a dose of 24 μg/kg/hour or placebo ( N = 16 ) with a similar infusion rate . The sample size for the study was calculated according to the primary end-point : the change in SOFA during study drug infusion ( Days 0 and 5 ) . Comparisons between the study groups were performed using patient-related changes and calculation of difference in means ( DIM , 95 % CIs ) and regarding categorical variables with Fisher 's exact test . For all comparisons P < 0.05 was considered significant . Results No serious bleeding was detected clinical ly or by CT scans in either group . No significant difference in SOFA score change between the APC and placebo groups was found ( difference in means ( DIM ) + 2.3 , 95 % CI -0.7 to + 5.3 ) . Treatment with APC was associated with an increase in serum levels of both total and conjugated bilirubin . No differences in ventilator-free days , in renal replacement therapy-free days , in vasopressor-free days , or in days alive outside the hospital were detected . Conclusions No serious bleeding or differences in the evolution of MOD were detected between APC and the placebo . Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP.Trial registration Clinical Trials.gov NCT01017107 Summary A prospect i ve , controlled , and r and omized clinical study was carried out with the purpose of evaluating the influence of somatostatin in the evolution of acute pancreatitis . One hundred patients were r and omly divided into two groups , a control group ( n = 50 patients ) and a somatostatin group ( n = 50 patients to whom a dosage of 250 μg/h was administered for 48 h following a bolus of 250 μg at the beginning of therapy ) . The two groups were homogenous in age , sex , etiology , and severity of clinical picture ( on admission ) . The following parameters were compared in the two groups OBJECTIVE To observe the therapeutic effect of Dachaihu Decoction ( DCHD ) on acute mild pancreatitis of Gan-qi stagnant syndrome type . METHODS Thirty-six acute pancreatitis patients were r and omized into three groups ( Group A , B and C ) equally , and they were treated with conventional Western medicine ( WM ) , WM plus placebo and WM plus DCHD , respectively for 7 days . The time for pain relieving , fasting and total hospitalization were observed , and serum amylopsin and C-reactive protein ( CRP ) levels were measured before treatment and at various time points after treatment . RESULTS After treatment , amylopsin and CRP level significantly decreased in the 3 groups , comparing with those before treatment ( P < 0.05 , P < 0.01 ) . In Group C , amylopsin level was obviously higher on dl , d3 and d5 , CRP level was higher on dl , d3 , d5 and d7 , and the remission time of abdominal pain , the fasting time , as well as the hospitalization time were all significantly shorter than those in Group A and B ( P < 0.05 , P < 0.01 ) . CONCLUSION The accessory use of DCHD upon conventional Western medical treatment can strikingly shorten the course of disease and enhance the therapeutic effect on mild acute pancreatitis patients Thirty-one patients suffering severe acute pancreatitis entered a protocol design ed to evaluate the therapeutic value of synthetic salmon calcitonin . All 31 patients were su bmi tted to st and ardized treatment and , in addition , 14 received daily 300 MRCU of calcitonin for 15 days . The parameters evaluated were : mortality rate , effectiveness of conservative treatment , pleural effusion , date of return to oral feeding , days of hospitalization , pain , abdominal distention , peristalsis , fever , pulse rate , serum and urinary amylase , serum calcium , hematocrit level , and leukocyte count . Significant differences were not found between the 2 groups . Therefore , the conclusion is that synthetic salmon calcitonin is of no benefit in the treatment of severe acute pancreatitis . RésuméTrente et un malades atteints de pancréatite aiguë sévère ont été soumis à une étude destinée à évaluer la valeur thérapeutique de la calcitonine synthétique . Quatorze parmi eux furent traités suivant les méthodes classiques et reçurent en supplément 300 MRCU de calcitonine par 24 heures . Les critères suivants furent pris en compte : mortalité , action du traitement conservateur , épanchement pleural , date du retour à l'alimentation entérale , nombre de jours d'hospitalisation , douleur , distension abdominale , péristaltisme , fièvre , fréquence du pouls , amylase sanguine et urinaire , calcémie , hématocrite , nombre de leucocytes . Aucune différence significative ne fut observée entre les deux groupes . En fonction de cette étude comparative , il est possible d'affirmer que la calcitonine n'est d'aucune utilité pour traiter la pancréatite aiguë grave . ResumenTreinta y uno pacientes con pancreatitis aguda severa fueron ingresados a un protocol o destinado a evaluar el valor terapéutico de la calcitonina de salmon sintética . Catorce pacientes recibieron el tratamiento corriente y , además , les fueron administradas 300 MRCU ( Medical Research Council Units ) de calcitonina . Los otros 17 solo recibieron el tratamiento corriente y sirvieron como control . Los parámetros de evaluación fueron : mortalidad , efectividad del tratamiento conservador , efusión pleural , fecha del retorno a alimentación oral , días de hospitalización , dolor , distensión abdominal , peristalsis , fiebre , frecuencia del pulso , amilasa sérica y urinaria , calcemia , hematócrito y recuento leucocitario . No se encontraron diferencias significativas entre los dos grupos . Por consiguiente , la conclusión es que la calcitonina de salmón no tiene utilidad en el tratamiento de la pancreatitis aguda severa Integrated traditional Chinese medicine ( ITCM ) is known to improve health in patients with acute pancreatitis ( AP ) ; however , the molecular mechanisms underlying this effect are unknown . AP is associated with the expression of PRSS1 and SPINK1 . Thus , the present study aim ed to investigate whether ITCM was able to ameliorate AP by regulating the expression levels of protein , serine 1 ( PRSS1 ) and serine peptidase inhibitor , Kazal type 1 ( SPINK1 ) . A total of 100 AP patients were divided at r and om into two groups . The treatment group were treated externally with a herbal ITCM preparation , while the control group received a routine placebo treatment . The mRNA and protein expression levels of PRSS1 and SPINK1 were subsequently compared between the two groups . The results revealed that the health of the patients who had received ITCM improved significantly when compared with the control group patients ( P<0.05 ) . In addition , the expression levels of PRSS1 and SPINK1 were found to be lower in the treatment group when compared with the control group ( P<0.05 ) . Therefore , ITCM exhibited a significant therapeutic effect on AP and produced no side effects since the treatment was applied externally . ITCM may ameliorate AP by downregulating the expression of PRSS1 and SPINK1 ; thus , should be considered as a potential therapy for the development of drugs against AP Despite improvements in surgical treatment and intensive care , mortality from severe acute pancreatitis remains high . We have carried out a r and omised study of 60 consecutive patients with alcohol-induced necrotising pancreatitis to find out whether early antibiotic treatment can improve outcome . 30 patients were assigned cefuroxime ( 4.5 g/day intravenously ) from admission . In the second group , no antibiotic treatment was given until clinical or microbiologically verified infection or after a secondary rise in C-reactive protein . The inclusion criteria were C-reactive protein concentration above 120 mg/L within 48 h of admission and low enhancement ( < 30 Hounsfield units ) on contrast-enhanced computed tomography . There were more infectious complications in the non-antibiotic than in the antibiotic group ( mean per patient 1.8 vs 1.0 , p = 0.01 ) . The most common cause of sepsis was Staphylococcus epidermidis ; positive cultures were obtained from pancreatic necrosis or the central venous line in 14 of 18 patients with suspected but blood-culture-negative sepsis . Mortality was higher in the non-antibiotic group ( seven vs one in the antibiotic group ; p = 0.03 ) . Four of the eight patients who died had cultures from pancreatic necrosis positive for Staph epidermidis . We conclude that cefuroxime given early in necrotising pancreatitis is beneficial and may reduce mortality , probably by decreasing the frequency of sepsis Recent evidence of pancreatic penetration of several antibiotics active against the usual flora found in pancreatic sepsis , at therapeutic minimal inhibitory concentration , prompted the authors to perform a r and omized , multicenter , clinical trial on imipenem prophylaxis in acute pancreatitis . Seventy-four patients with computed tomographic ( CT ) scans demonstrating necrotizing pancreatitis within 72 hours of onset were r and omly assigned to two groups receiving no antibiotic treatment or 0.5 gram of prophylactic imipenem administered intravenously every eight hours for two weeks . Pancreatic sepsis was always detected by means of cultures ( percutaneous CT or ultrasound-guided needle aspiration and intraoperative sample s ) . The incidence of pancreatic sepsis was much less in treated patients ( 12.2 versus 30.3 percent , p < 0.01 ) . Therefore , the authors recommend prophylactic use of imipenem in patients with acute necrotizing pancreatitis BACKGROUND Experimental and clinical studies on the effect of octreotide in the treatment of patients with acute pancreatitis have presented controversial results . Since January 1992 , we have been conducting a prospect i ve r and omized study on the clinical effect of octreotide in severe acute pancreatitis , at three hospitals in Israel . STUDY DESIGN The entering criteria included three or more of the Ranson 's prognostic signs and computed tomographic findings of severe pancreatitis . Patients were r and omly assigned to conservative treatment either with or without octreotide ( 0.1 mg injected subcutaneously three times a day ) . The end points of the study included : complication rate ( adult respiratory distress syndrome [ ARDS ] , sepsis , renal failure , pseudocyst , fistula , and abscess ) , length of hospital stay , and mortality . RESULTS During the first two years ( from January 1992 to December 1993 ) , 51 patients entered the study . After evaluation , 13 patients were excluded due to failure to meet the entering criteria , incomplete data , or incorrect diagnosis . Of the remaining 38 patients , 19 were assigned to octreotide ( treatment group ) and 19 to conservative treatment alone ( control group ) . The two groups were matched with regard to age , sex , etiology , and severity of disease . The complication rate was lower in the treatment group compared with the control group with regard to sepsis ( 26 compared with 74 percent , p = 0.004 ) and ARDS ( 37 compared with 63 percent , p = 0.1 ) . The hospital stay was shorter in the treatment group compared with the control group ( 17.9 compared with 34.1 days , p = 0.02 ) . Death occurred in two patients in the treatment group and six patients in the control group . CONCLUSIONS Although some of the parameters did not reach statistical significance , these preliminary results suggest that octreotide may have a beneficial effect in the treatment of patients with severe acute pancreatitis . This study is scheduled to continue for two more years In two prospect i ve studies the effect of proteinase inhibiting agents and glucagon in acute pancreatitis have been studied by a r and omised series . Moreover the effect of the basic therapy was examined in additional 103 patients . Symptoms , clinical and laboratory chemical findings correspond to each other in all collectives . The results seem to be the best ones in those patients having been treated by basic therapy only Sixty-two cases of acute pancreatitis , evaluated for severity according to uniform st and ards , were treated identically except that patients in one group received glucagon hydrochloride ( group A ) and those in the other oxyphenonium bromomethylate ( group B ) . Each of the two homologous series comprise 31 patients , and mortality was the same for both groups ( 3/31 , 10 % ) . Statistical comparison of both series showed no significant differences in frequency of expected complications nor in fall of serum amylase levels . During treatment , serum calcium levels were significantly reduced in group A ( P less than .005 ) , and the duration of the abdominal pain was shortened ( P less than .05 ) . The volume of gastric aspirate was smaller in group B ( P less than .005 ) , and vesical catheterization proved necessary more frequently ( P less than .005 ) . Thus , similar results are obtained when glucagon or anticholinergics are employed in the treatment of acute pancreatitis , although secondary effects differ AIM To observe the therapeutic efficacy of high-dose Vitamin C ( Vit . C ) on acute pancreatitis ( AP ) , and to explore its potential mechanisms . METHODS Eighty-four AP patients were divided into treatment group and control group , 40 healthy subjects were taken as a normal group . In the treatment group , Vit . C ( 10 g/day ) was given intravenously for 5 days , whereas in the control group , Vit . C ( 1 g/day ) was given intravenously for 5 days . Symptoms , physical signs , duration of hospitalization , complications and mortality rate were monitored . Meanwhile , serum amylase , urine amylase and leukocyte counts were also determined . The concentration of plasma vitamin C ( P-VC ) , plasma lipid peroxide ( P-LPO ) , plasma vitamin E ( P-VE ) , plasma beta-carotene ( P-beta-CAR ) , whole blood glutathione ( WB-GSH ) and the activity of erythrocyte surperoxide dimutase ( E-SOD ) and erythrocyte catalase ( E-CAT ) as well as T lymphocyte phenotype were measured by spectrophotometry in the normal group and before and after treatment with Vit . C in the treatment and the control group . RESULTS Compared with the normal group , the average values of P-VC , P-VE , P-beta-CAR , WB-GSH and the activity of E-SOD and E-CAT in AP patients were significantly decreased and the average value of P-LPO was significantly increased , especially in severe acute pancreatitis ( SAP ) patients ( P<0.05 . P-VC , P=0.045 ; P-VE , P=0.038 ; P=0.041 ; P-beta-CAR , P=0.046 ; WB-GSH , P=0.039 ; E-SOD , P=0.019 ; E-CAT , P=0.020 ; P-LPO , P=0.038 ) . Compared with the normal group , CD3 and CD4 positive cells in AP patients were significantly decreased . The ratio of CD4/CD8 and CD4 positive cells were decreased , especially in SAP patients ( P<0.05 . CD4/CD8 , P=0.041 ; CD4 , P = 0.019 ) . Fever and vomiting disappeared , and leukocyte counts and amylase in urine and blood become normal quicker in the treatment group than in the control group . Moreover , patients in treatment group also had a higher cure rate , a lower complication rate and a shorter in-ward days compared with those in he control group . After treatment , the average value of P-VC was significantly higher and the values of SIL-2R , TNF-alpha , IL-6 and IL-8 were significantly lower in the treatment group than in the control group ( P<0.05 P-VC , P=0.045 ; SIL-2R , P=0.012 ; TNF-alpha , P=0.030 ; IL-6 , P=0.015 ; and IL-8 , P=0.043 ) . In addition , the ratio of CD4/CD8 and CD4 positive cells in the patients of treatment group were significantly higher than that of the control group after treatment ( P<0.05 . CD4/CD8 , P=0.039 ; CD4 , P=0.024 ) . CONCLUSION High-dose vitamin C has therapeutic efficacy on acute pancreatitis . The potential mechanisms include promotion of anti-oxidizing ability of AP patients , blocking of lipid peroxidation in the plasma and improvement of cellular immune function Abstract Background : Experience with administration of synbiotics ( prebiotics/probiotics ) in patients with severe acute pancreatitis ( SAP ) has demonstrated immunomodulatory capacity . The aim of this trial was evaluation of the feasibility and perspective of early clinical application of oral synbiotic/prebiotic supplements in patients with SAP . Methods : 90 SAP patients were enrolled during the period from 2005–2008 . Patients were stratified according to the feeding mode . CONTROL ( n = 32 ) group received st and ard whole protein feeding formula . SYNBIO ( n = 30 ) and FIBRE groups ( n = 28 ) received early ( within first 24–48 hours ) synbiotic or prebiotic supplements . Oral administration of synbiotics or prebiotics was commenced when patients were able to sip water . Results : Daily provided average volume and calories of synbiotic/prebiotic blends were smaller compared to the CONTROL , p = 0.001 . Oral administration of synbiotic/prebiotic supplements was associated with lower infection rate ( pancreatic and peripancreatic necrosis ) compared to the CONTROL , ( p = 0.03 ; p = 0.001 ) , lower rate of surgical interventions , p = 0.005 , shorter ICU ( p = 0.05 ) and hospital stay ( p = 0.03 ) . Synbiotic supplemented enteral stimulation of the gut result ed in reduced mortality rate compared to the CONTROL , p = 0.02 . Conclusion : Early low volume oral synbiotic/prebiotic supplemented enteral stimulation of the gut seems to be a potentially valuable complement to the routine treatment protocol of SAP A prospect i ve study was carried out to evaluate the efficacy of somatostatin in the treatment of acute pancreatitis . Seventy one patients were r and omised to control ( h = 36 ) , or to the somatostatin group ( h = 35 ) who received somatostatin 100 micrograms/h after a 250 microgram bolus for the first two days . The following were compared in the two groups on admission and two days later : laboratory tests of prognostic significance , severity of pancreatitis , and also morbidity and mortality . Of the nine laboratory tests compared , the white blood cell count , lactate dehydrogenase , and urea concentrations were significantly lower in the somatostatin group two days after admission . Severity of pancreatitis after hospitalisation increased in fewer patients given somatostatin ( NS ) . There was a trend toward fewer complications , especially local , in the somatostatin group . Mortality in both groups was low . Somatostatin appeared to reduce the local complications of acute pancreatitis . A larger trial is necessary to show its beneficial effect conclusively The aims of the study were to determine whether the platelet‐activating factor antagonist Lexipafant could alter the clinical course and suppress the inflammatory response of human acute pancreatitis . In a double‐blind , placebo‐controlled study 83 patients were r and omized to receive Lexipafant 60 mg intravenously for 3 days , or placebo . Clinical progression was assessed by daily Acute Physiology And Chronic Health Evaluation ( APACHE ) II score and organ failure score ( OFS ) . The magnitude of the inflammatory response on days 1‐5 was assessed by serial measurement of interleukin ( IL ) 8 , IL‐6 , E‐selectin , polymorphonuclear elastase‐alpha1‐antitrypsin ( PMNE‐α1‐AT ) , and C‐reactive protein ( CRP ) . At entry , patients receiving Lexipafant ( n = 42 ) or placebo ( n = 41 ) were matched for age and sex , aetiology , APACHE II score and OFS . The disease was classified as severe in 29 patients ( APACHE II score eight or more ) . There was a significant reduction in the incidence of organ failure ( P = 0±041 ) and in total OFS ( P=0±048 ) at the end of medication ( 72 h ) . During this time seven of 12 patients with severe acute pancreatitis who had Lexipafant recovered from an organ failure ; only two of 11 with severe acute pancreatitis who had placebo recovered from an organ failure and two others developed new organ failure . Lexipafant treatment significantly reduced serum IL‐8 ( P = 0±038 ) , and IL‐6 declined on day 1 . Plasma PMNE‐α1‐AT complexes peaked on day 1 ; the gradual fall to baseline over 5 days observed in controls did not occur in patients given Lexipafant . No effect was observed on serum CRP . This study provides a rationale for further clinical trials with the potent PAF antagonist Lexipafant in human acute pancreatitis The results of a double-blind trial of glucagon in 69 patients with acute pancreatitis are reported . In a subgroup of 59 patients statistical analysis showed no significant differences between the glucagon-treated ( n = 29 ; 2 X 5 mg protamine-zinc glucagon intramuscularly per day ) and the placebo-treated ( n = 30 ) subjects for the following data : duration of pain left spontaneously and induced by palpation , amounts of analgesics and antispasmodics required by the patients , duration of hospital stay , amylase activities in serum and 24 hour urine collection s. Mortality rates did not differ significantly between the glucagon-treated and the placebo-treated subjects in the total group of 69 patients and in the two subgroups of patients who were treated conservatively ( n = 59 ) and those who underwent laparotomy because of severe peritonitis ( n = 10 ) . From the results of this study it is concluded that favourable effects of glucagon upon the course of acute pancreatitis -- if they do exist -- are not significant Summary The authors report the results of a r and omized , double-blind multicenter clinical trial on the use of gabexate mesilate vs aprotinin in the therapy of acute pancreatitis . The size of the study sample and the end points chosen for evaluation of the early systemic complications of the pancreatitis — carefully selected targets for reliable assessment of the efficacy of any protease inhibitor — lead to the conclusion that gabexate mesilate is more efficacious than aprotinin in reducing the early complications of necrotizing acute pancreatitis , if administered within 72 h of onset of symptoms . Its good tolerability means that it can be used safely even at the dose of 3 g/24 OBJECTIVE To observe the efficacy of combined therapy with S and ostatin ( SDS ) and Yiyan Mixture ( YYM ) in treating severe acute pancreatitis ( SAP ) . METHODS Thirty-six patients with SAP were assigned to two groups equally , the treated group treated with the combined therapy and the control group treated by SDS alone . Biochemical indexes , including lactate dehydrogenase ( LDH ) , aspartate aminotransferase ( AST ) , amylase ( AMY ) , endotoxin ( ET ) , C-reactive protein ( CRP ) , and APACHE II score were determined before and after treatment . And the incidence of complication and mortality were assessed . RESULTS The time of abdominal pain , tenderness and distention disappearance , air charge recovering , and average hospitalization days in the treated group were significantly shorter than those in the control group respectively ( P < 0.05 ) . Levels of LDH , AST , AMY , serum ET , CRP and APACHE II scores were lowered after treatment in both groups , but the decrement was more significant in the treated group than that in the control group respectively ( P < 0.05 ) . The difference in incidence of local complications and mortality between the two groups showed no statistical significance ( P > 0.05 ) . CONCLUSION Combined therapy of S and ostatin and YYM is a recommended recipe for treatment of SAP , it could obviously improve the condition of patients and enhance the efficacy of treatment BACKGROUND Ulinastatin is reported to inhibit pro-inflammatory markers and also inhibits coagulation and fibrinolysis . The drug is available in East Asia for the treatment of acute pancreatitis . AIM To study the effect of addition of ulinastatin to st and ard care on mortality and morbidity in Indian subjects with acute pancreatitis . DESIGN R and omized , double-blind , placebo-controlled , multi-centre trial across 15 centres in India . METHODS Subjects , aged 18 to 70 years , with acute pancreatitis and elevated serum C-reactive protein ( CRP ) levels , were eligible for enrolment . Acute pancreatitis was diagnosed if the patient had at least two of the following criteria : suggestive abdominal pain , serum amylase and /or lipase > 3 times upper limit of normal , and imaging findings of acute pancreatitis . Subjects were classified as having mild or severe acute pancreatitis on the basis of the APACHE II score ( < 8 mild , > or = 8 severe ) . St and ard care was given to all subjects as per the treating physician 's protocol . Eligible subjects were r and omized to receive intravenous infusion of 200,000 IU ulinastatin or placebo in 100 mL of 0.9 % saline given over one hour every 12 hours for 5 days . RESULTS Of 135 r and omized subjects , 129 completed the study ( mild 62 , severe 67 ) . Pancreatitis was due to alcohol intake in a majority ( 81 % ) of subjects . Baseline characteristics were similar between the ulinastatin and placebo groups . Efficacy was evaluated in subjects who had received at least 3 days ( 6 doses ) of ulinastatin/placebo . One subject with severe pancreatitis in the ulinastatin group versus six in the placebo group died ( p = 0.048 ) . New organ dysfunction developed in 5 ulinastatin vs 4 placebo group subjects ( p = 0.744 ) with mild pancreatitis and 12 ulinastatin vs 29 placebo group subjects ( p = 0.0026 ) with severe pancreatitis . Adverse events were significantly lower in subjects with severe pancreatitis in the ulinastatin group as compared to the placebo group ( p = 0.00001 ) . Reduction in serum CRP was not different between the groups . Median hospitalization was shorter by one day in the ulinastatin group ; the difference was not significant . There was no infusion-related adverse event . CONCLUSIONS Ulinastatin prevents new organ dysfunction and reduces mortality in subjects with severe pancreatitis Summary Fifty-five patients with severe acute pancreatitis were treated with peritoneal lavage at the Dept . of Surgery at Malmö General Hospital . In a r and omized study 26 of the 55 patients received in addition 500,000 KIU aprotinin in the lavage fluid every 2 h. There were no significant differences between the aprotinin- and non-aprotinin-treated groups as to mortality and clinical results . The initial concentration ofα1-antitrypsin in plasma was mainly within normal range with increasing values during the treatment . No differences were seen between the two groups . The initial mean level ofα2-macroglobulin in plasma was slightly decreased , but 17 patients showed values below normal range . Theα2-macroglobulin level during the lavage showed a similar course in the two groups.α1-Antitrypsin and α2-macroglobulin in the lavage fluids showed signs of complexation but in plasma these inhibitors did not show any signs of complexation . On admission to the hospital the mean levels of C3 and kininogen in the plasma were slightly below normal . During the lavage treatment no differences were seen between the two groups . Degradation products of C3 and kininogen were seen in both serum and peritoneal fluids . The electrophoretic patterns of C3 and kininogen normalized in serum as well as in lavage fluids during the lavage treatment without any significant differences in the two groups . High levels of immunoreactive trypsin , pancreatic elastase , PSTI , and leukocyte elastase in serum were seen equally in both groups of patients BACKGROUND AND AIMS This study addresses whether antibiotic prophylaxis is beneficial for acute necrotizing pancreatitis . METHODS This r and omized , controlled trial enrolled 276 patients with severe acute pancreatitis . There were 56 patients with 30 % or more necrosis proved by contrast-enhanced computerized tomography who were eligible for r and omization : 29 in the study group and 27 in the control group , who received i.v . imipenem-cilastatin ( 3 x 500 mg/day ) within 72 h of the onset of symptoms for 7 - 14 days , and no antibiotic prophylaxis , respectively . The primary end-point was the incidence of infectious complication . The secondary end-points were mortality , the incidence of necrosectomy for infected necrosis , the incidence of organ complication and hospital courses . RESULTS Characteristics of baseline data were similar in the two groups . No significant differences were found in the incidence of infected pancreatic necrosis ( 37 % vs 27.6 % ) , mortality ( 10.3 % vs 14.8 % ) and the incidence of operative necrosectomy ( 29.6 % vs 34.6 % ) between the study group and the control group ( P > 0.05 ) . The incidence of extrapancreatic infections , organ complications and hospital courses between the groups were also not significantly different . However , a significantly increased incidence of fungal infection was observed in the study group versus the control group ( 36.1 % vs 14.2 % , P < 0.05 ) . CONCLUSION There was no benefit in the outcomes when antibiotic prophylaxis was routinely used in patients with acute necrotizing pancreatitis BACKGROUND Infectious complications and associated mortality are a major concern in acute pancreatitis . Enteral administration of probiotics could prevent infectious complications , but convincing evidence is scarce . Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis . METHODS In this multicentre r and omised , double-blind , placebo-controlled trial , 298 patients with predicted severe acute pancreatitis ( Acute Physiology and Chronic Health Evaluation [ APACHE II ] score > or = 8 , Imrie score > or =3 , or C-reactive protein > 150 mg/L ) were r and omly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation ( n=153 ) or placebo ( n=145 ) , administered enterally twice daily for 28 days . The primary endpoint was the composite of infectious complications -- ie , infected pancreatic necrosis , bacteraemia , pneumonia , urosepsis , or infected ascites -- during admission and 90-day follow-up . Analyses were by intention to treat . This study is registered , number IS RCT N38327949 . FINDINGS One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis ; thus , 152 individuals in the probiotics group and 144 in the placebo group were analysed . Groups were much the same at baseline in terms of patients ' characteristics and disease severity . Infectious complications occurred in 46 ( 30 % ) patients in the probiotics group and 41 ( 28 % ) of those in the placebo group ( relative risk 1.06 , 95 % CI 0.75 - 1.51 ) . 24 ( 16 % ) patients in the probiotics group died , compared with nine ( 6 % ) in the placebo group ( relative risk 2.53 , 95 % CI 1.22 - 5.25 ) . Nine patients in the probiotics group developed bowel ischaemia ( eight with fatal outcome ) , compared with none in the placebo group ( p=0.004 ) . INTERPRETATION In patients with predicted severe acute pancreatitis , probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality . Probiotic prophylaxis should therefore not be administered in this category of patients Background : Based on equivocal clinical data , intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis . To date there is no r and omised comparison of this therapy in severe acute pancreatitis . Methods : We conducted a r and omised , double blind , placebo controlled trial of intravenous antioxidant ( n-acetylcysteine , selenium , vitamin C ) therapy in patients with predicted severe acute pancreatitis . Forty-three patients were enrolled from three hospitals in the Manchester ( UK ) area over the period June 2001 to November 2004 . R and omisation stratified for APACHE-II score and hospital site , and delivered groups that were similar at baseline . Results : Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial . However , at 7 days , there was no statistically significant difference in the primary end point , organ dysfunction ( antioxidant vs placebo : 32 % vs 17 % , p = 0.33 ) or any secondary end point of organ dysfunction or patient outcome . Conclusions : This study provides no evidence to justify continued use of n-acetylcysteine , selenium , vitamin C based antioxidant therapy in severe acute pancreatitis . In the context of any future trial design , careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study Twenty-one patients with a medium severe form of acute pancreatitis were divided into two groups . Eleven were treated with octreotide , 200 micrograms s.c . every 8 hours , combined with st and ard conservative treatment , 10 patients had the same treatment but without octreotide . In the octreotide-treated group the level of free oxygen radicals and important antioxidants -- vitamins A , E and C -- was assessed . In the octreotide-treated group the authors found after five days normal levels of originally elevated free oxygen radicals and a significant increase of the vitamin C level . As compared with the control group , in the octreotide group the period of hospitalization was significantly shorter ( 9.8 + /- 3.2 vs. 13.7 + /- 4.7 ) . The number of complications was not affected Objectives : A r and omized controlled trial was conducted to clarify whether continuous regional arterial infusion ( CRAI ) of protease inhibitor and antibiotic could reduce mortality rate of severe acute pancreatitis ( SAP ) . Methods : Seventy-eight patients with SAP were included in the study . Thirty-nine patients were treated with CRAI , 31 patients completed the study ; and another group of 39 patients was treated without CRAI therapy . Groups were well matched in clinical characteristics . The CRAI patients were treated continuously with nafamostat mesylate 240 mg/d and imipenem 1 g/d for 5 days via one of the arteries perfusing the pancreas . Later , imipenem was given intravenously ( 0.5 g every 8 hours ) for 9 days . The non-CRAI patients received imipenem ( 0.5 g every 8 hours ) intravenously for 14 days . Statistical analysis of the intention-to-treat ( ITT ) group was performed . Results : Lack of septic complications was observed in 23 patients with CRAI therapy and 20 non-CRAI patients ( not significant ) . The additional antibiotics were applied in 8 of CRAI patients and in 18 non-CRAI ( ITT , P = 0.02 ) . Mortality rate was 5.1 % in CRAI and 23.1 % in non-CRAI group ( ITT , P = 0.02 ) . Urgent surgical intervention was necessary in 10.3 % CRAI patients and in 33.3 % non-CRAI ( ITT , P = 0.01 ) . Conclusions : The results show that CRAI of protease inhibitor and antibiotic is effective in preventing complications and in reducing mortality rate in SAP Conclusions Trasylol in the dosage used in this trial was of no value in the treatment of acute pancreatitis . There is some evidence , both experimental and clinical , to suggest that a further double-blind trial of Trasylol using very much larger doses would be valuable . In the meanwhile , and until we have further knowledge on the matter , it would appear that if Trasylol is given for acute pancreatitis at least 200,000 U. per day should be administered . Obviously with this dosage a close watch must be kept for toxic effects Abstract Objectives : Activated protein C ( APC ) , an endogenous anticoagulant , has antithrombotic , fibrinolytic and anti-inflammatory properties . We recently conducted a controlled study ( APCAP , activated protein C in severe acute pancreatitis ) of APC treatment of patients with severe acute pancreatitis ( SAP ) . Here we studied the effect of APC on the pivotal coagulation parameters of the surviving patients in the APCAP study . Methods : The study consisted of 20 patients of whom 10 patients had received APC and 10 patients had received placebo . Coagulation parameters , physiological anticoagulants , thrombograms and circulating levels of IL-6 and CRP were determined on admission and at days 1 , 3–4 and 6–7 . Results : During follow-up , the temporal levels of prothrombin time ( PT ) decreased and the temporal levels of thromboplastin time ( TT ) increased in placebo group ( p < 0.001 for both ) , but not in APC group . The temporal levels of antithrombin ( AT ) increased less in APC group than in placebo group ( p = 0.011 ) . The shapes of the SAP patients ’ thrombograms were strongly deranged and were marginally affected by APC treatment . Conclusions : Coagulopathy in SAP , a complex phenomenon , is not alleviated by APC treatment . Rather , the patients receiving APC are heading toward normal homeostasis of coagulation slower than patients receiving placebo OBJECTIVE To observe the changes in serum interleukin-8 ( IL-8 ) and tumor necrosis factor-alpha ( TNF-alpha ) after intravenous administration of alanyl-glutamine ( Gln ) in patients with severe pancreatitis . METHODS Fifty patients with severe pancreatitis were r and omized equally into 2 groups and received st and ard total parenteral nutrition ( TPN ) with intravenous infusion of Gln or normal saline ( control ) for 1 week . The plasma glutamine level was measured with high-performance liquid chromatography ( HPLC ) in these patients one day before and on day 7 of Gln administration , and the serum IL-8 , TNF-alpha and heat shock protein 70 ( Hsp70 ) were detected with enzyme-linked immunosorbent assay . RESULTS On day of Gln administration , the plasma glutamine level in patients of Gln group increased significantly ( P<0.01 ) , and serum IL-8 and TNF-alpha levels decreased significantly ( P>0.05 ) in comparison with those of the control group . The patients receiving Gln supplementation had significantly higher serum albumin level and greater body fat content with shorter hospital stay than those in the control group ( P<0.05 ) , and the mortality rate in Gln group was also significantly lower ( P<0.05 ) . CONCLUSION Gln-enriched TPN may improve the clinical outcomes of patients with severe pancreatitis probably by decreasing serum IL-8 and TNF-alpha levels Objectives Prophylactic antibiotics are helpful in decreasing the incidence of septic complications in acute pancreatitis . The aim of this study was to compare the efficacy of meropenem , a new carbapenem antibiotic , with that of imipenem , which is the st and ard prophylactic treatment in patients with severe acute pancreatitis . Methods One hundred seventy-six patients with necrotizing pancreatitis were prospect ively r and omized to prophylactic treatment with 0.5 g meropenem t.i.d . intravenously or 0.5 g imipenem q.i.d . intravenously . The occurrence of infection of pancreatic necrosis , rate of extrapancreatic infections , systemic and local complications , need for surgery , mortality rate , and length of hospitalization were recorded for each group . When a septic complication of pancreatic necrosis was suspected , fine needle aspiration with cultures of the sample was performed . Surgery was performed in cases of verified infected necrosis . Conclusion No difference was observed between patients treated with meropenem and those treated with imipenem in terms of incidence of pancreatic infection ( 11.4 % versus 13.6 % ) and extrapancreatic infections ( 21.6 % versus 23.9 % ) and clinical outcome . Meropenem is as effective as imipenem in preventing septic complications of patients with severe acute pancreatitis Objective A r and omized , controlled , multicenter trial was undertaken in 102 patients with objective evidence of severe acute pancreatitis to evaluate whether selective decontamination reduces mortality . Summary Background Data Secondary pancreatic infection is the major cause of death in patients with acute necrotizing pancreatitis . Controlled clinical trials to study the effect of selective decontamination in such patients are not available . Methods Between April 22 , 1990 and April 19 , 1993 , 102 patients with severe acute pancreatitis were admitted to 16 participating hospitals . Patients were entered into the study if severe acute pancreatitis was indicated , on admission , by multiple laboratory criteria ( Imrie score ≥ 3 ) and /or computed tomography criteria ( Balthazar grade D or E ) . Patents were r and omly assigned to receive st and ard treatment ( control group ) or st and ard treatment plus selective decontamination ( norfloxacin , colistin , amphotericin ; selective decontamination group ) . All patients received full supportive treatment , and surveillance cultures were taken in both groups . Results Fifty patients were assigned to the selective decontamination group and 52 were assigned to the control group . There were 18 deaths in the control group ( 35 % ) , compared with 11 deaths ( 22 % ) in the selective decontamination group . ( adjusted for Imrie score and Balthazar grade : p = 0.048 ) . This difference was mainly caused by a reduction of late mortality ( > 2 weeks ) due to significant reduction of gram-negative pancreatic infection ( p = 0.003 ) . The average number of laparotomies per patient was reduced in patients treated with selective decontamination ( p < 0.05 ) . Failure of selective decontamination to prevent secondary gram-negative pancreatic infection with subsequent death was seen in only three patients ( 6 % ) and transient gram-negative pancreatic infection was seen in one ( 2 % ) . In both groups of patients , all gram-negative aerobic pancreatic infection was preceded by colonization of the digestive tract by the same bacteria We investigated the effect of a new synthetic protease- and phospholipase A2-inhibitor gabexate mesilate ( FOY ) in a multicenter ( 6 hospitals in Hannover and vicinity ) double-blind study on the clinical course of acute pancreatitis . 50 patients were r and omized into two subgroups . One group was treated with 3 X 300 mgs of gabexate mesilate per day for 9 days as a continuous intravenous infusion , the control group received placebo . There was no difference in these two groups regarding age and sex , but there was a discrepancy concerning the severity ( stage I-IV ) of the acute pancreatitis at the onset of treatment . More of the patients in the gabexate mesilate-group had severe disease on admission to hospital . Of the 7 patients ( 14 % ) who died , 5 were in the gabexate mesilate-group whereas only 2 were in the placebo group . This difference in the mortality rate is not significant . There was , however , a significant difference at the 5 % level between the verum-group and the control group concerning the decline in alpha-amylase activity in serum and the number of complications . The difference was greatest in alcohol induced acute pancreatitis . A non-parametric test showed a significant reduction in hospitalisation time in the gabexate mesilate-group . Due to the small number of patients and the inhomogeneous clinical course of the acute pancreatitis a definite conclusion concerning the effect of gabexate mesilate on the clinical course of acute pancreatitis is not possible . Further studies with a much greater number of patients and more homogeneous groups with respect to the severity of the acute pancreatitis at the onset of the therapy with gabexate mesilate or placebo are necessary To evaluate the therapeutic efficacy of high-dose octreotide in patients with predicted severe acute pancreatitis ( SAP ) or SAP , two hundred and thirty-six patients with predicted SAP and 136 patients with SAP were r and omized into control , high-dose octreotide ( High-O ) and low-dose octreotide ( Low-O ) groups . In addition to the conventional managements administrated in control group , High-O group received an intravenous infusion of octreotide at 50 μg/h × 3d + 25 μg/h × 4d , and Low-O group received octreotide at 25 μg/h × 7d . The major primary outcomes included the numbers of predicted SAP patients which developed SAP after intervention and the number of patients with SAP amelioration . Secondary outcomes included APACHE II , SIRS scores , plasma levels of somatostatin ( SST ) , tumor necrosis factor-α ( TNF-α ) , and interleukin-6 ( IL-6 ) . There were no significant differences between the control and Low-O groups in terms of prevention and treatment for SAP . The incidence of SAP in patients with predicted SAP who received High-O was significantly lower than the Low-O group : 37.5 % vs. 59.8 % , p=0.005 . Compared with Low-O group , the number of SAP patients in the SAP arm in the High-O group was reduced by 29.8 % . Plasma levels of SST in both predicted SAP and the SAP patients were efficiently recovered ( from 132.71±31.40 pg/ml to 180.00±23.50 pg/ml , p<0.05 ) after high-dose octreotide supplementation , which concomitantly reduced TNF-α and IL-6 levels . High-dose octreotide administration within 48h after AP onset may efficiently reduce the risk of SAP developing and partly attenuate SAP through raising plasma SST to a normal level and decreasing IL-6 and TNF-α Despite controversial experimental and clinical findings , the use of Aprotinin ( A ) in the treatment of acute pancreatitis ( AP ) is still widespread in our country . Compared to A , Gabexate Mesilate ( FOY ) should have the following advantages : lack of antigenicity , low molecular weight with better cellular penetrance , wide inhibitory spectrum ( against phospholipase A2 too ) and good tolerability . In order to verify the efficacy of FOY versus , we decided to carry out a prospect i ve multicenter ( 34 centers ) r and omized double blind trial in moderate-severe AP with FOY 3g/day versus A 1,500,000 U.I.K./day infused for 7 days with central venous line . Based on st and ard clinical , biochemical and radiological data , 199 patients suffering from AP were enrolled to the study from January 1989 to December 1990 . The main admission criteria were : onset of the disease from no more than 72 hours , at least 2 Ranson positive criteria and C.T. evidence of acute pancreatic damage . Seventeen no protocol patients were excluded . The Etiology in the 182 analyzed patients ( 106 male , 76 female ; mean age 57.6 years , range 21 - 91 ) were : biliary 102 ( 56 % ) , alcohol 47 ( 25.8 % ) , post-operative 13 ( 7.1 % ) , unknown causes 13 ( 7.1 % ) and others 7 ( 3.8 % ) . Median Ranson 's Score was 3 . CT examination showed 66 AP with edema , while 116 cases ( 63.7 % ) were recognized as severe forms with pancreatic necrotic involvement of 30 % of the gl and in 71 ( 61.2 % ) , 50 % in 31 ( 26.7 % ) , and more than 50 % in 14 ( 12.1 % ) . Out of 182 patients , 91 were treated with A and 91 with FOY . The two groups were comparable regarding the main prognostic factors . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this prospect i ve , double-blinded pilot trial study was to evaluate the effects of Thymosin alpha 1 use in the early phase on immunomodulation and clinical outcomes in patients with severe acute pancreatitis ( SAP ) . A total of 24 patients with SAP were r and omized to receive either conventional therapy for SAP or immunomodulatory therapy ( TA1 group ) . The patients in the thymosin group were injected with Talpha1 3.2 mg twice per day for 7 days . The serum level of HLA-DR and CD4/CD8 ratio and other immune parameters were measured on admission , the 8th day and the 28th day . There was a low expression of monocyte HLA-DR in both groups on admission , and more rapid alterations in the HLA-DR were found in the TA1 group . The positive rates of blood and abdominal drainage culture were statistically significant during the 28th follow-up period . The duration of ICU stay was shorter after TA1 treatment . Improves cell-induced immunity and reduces infection rate in severe acute pancreatitis patients & NA ; Infectious complications currently account for 80 % of deaths from acute pancreatitis . The aim of this study was to evaluate the necessity for prophylactic antibiotics in patients with severe acute pancreatitis . Twenty‐three consecutive patients suffering from acute alcoholic pancreatitis with computed tomography demonstrating two or more fluid collection s were r and omly assigned to one of two groups receiving either nonantibiotic treatment or prophylactic antibiotics ( ceftazidime , amikacine , and metronidazole for 10 days ) . Sepsis was always diagnosed by positive cultures . Seven episodes of severe sepsis occurred ( pancreatic infection and septic shock ) in the nonantibiotic group , and no infection occurred in the prophylactic antibiotic group ( p < 0.03 ) . In conclusion , the use of prophylactic antibiotics in severe alcoholic acute pancreatitis significantly reduces the incidence of severe infection INTRODUCTION Severe acute pancreatitis ( SAP ) is still one of the great challenges in gastro-intestinal surgery . According to recent studies , intravenously administered glutamine with total parenteral nutrition may be beneficial in the prevention of infectious complications and may reduce mortality rate . However , it has not been investigated yet , whether i.v . glutamine is able to achieve the same effect with early enteral nutrition as well . OBJECTIVES The objective of our prospect i ve r and omized double-blind study was to explore the effects of intravenously administered glutamine with early nasojejunal nutrition in severe acute pancreatitis . PATIENTS AND METHODS Forty-five patients with severe acute pancreatitis ( with a Glasgow score at least 3 and /or a CRP level above 150 mg/ml on admission ) were r and omized into two groups . Group Glutamine ( n = 24 ) was given 0.5 g/kg/die glutamine intravenously , while the control group ( n = 21 ) received normal amino acid solution in the same quantity for 7 days . Nasojejunal nutrition was introduced 48 hours after admission in case of all patients , and their management was the same in every other aspect , too . The primary end-points of the study were the rate of pancreas-specific infectious complications and organ failure , and the secondary end-points were the necessity for radiological and surgical interventions , length of hospital stay and mortality rate . RESULTS In group Glutamine , infected acute peripancreatic fluid collection s ( APFC ) were detected in 4 patients , 2 patients had post-necrotic pancreatic/peripancreatic fluid collection s ( PNPFC ) , 2 patients had infected pseudocysts and 2 patients had walled-off pancreatic necrosis ( WOPN ) . Ten patients were cured by ultrasound assisted puncture or drainage successfully . No surgical intervention was necessary . In the control group , 4 patients had infected APFC , 2 patients had infected PNPFC , infected pseudocysts and infected WOPN were diagnosed in 3 cases . Radiological intervention was effective in 9 cases , but 3 patients needed surgery . Three patients died of multi-organ failure , thus the mortality rate of the control group was 14 % , while the mortality rate of the Glutamine group was zero . The mean hospital stay of the Glutamine group was 10.6 days , which is significantly shorter than the mean hospital stay of the control group , which was 15.9 days ( p = 0.00104 ) . DISCUSSION The results of the Glutamine group are better in every end-points , however , statistically significant difference was detected in one parameter only , the length of hospital stay OBJECTIVE : Somatostatin regulates immune inflammatory response via apoptosis and adhesion of leukocytes in many diseases . This article reported a study that aim ed to observe the mechanism and effect of somatostatin on the immune inflammatory response through apoptosis and adhesion of leukocytes in severe acute pancreatitis Summary A double-blind comparison of cimetidine and placebo has been carried-out in 60 patients with acute pancreatitis . No clear-cut benefit from cimetidine was observed , either in the whole group , or in alcohol or gallstone-associated pancreatitis Background : The aim of this study was to evaluate the efficacy of somatostatin , ulinastatin and Salvia miltiorrhiza for treatment of severe acute pancreatitis . Methods : Three hundred six patients with severe acute pancreatitis were divided r and omly into 5 groups : basic treatment , somatostatin , somatostatin + ulinastatin , somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza . Amount of time for resolution of abdominal pain/distention , recovery to normal heart and respiratory rates , amylase and blood glucose levels , Acute Physiology and Chronic Health Evaluation II scores , and levels of tumor necrosis factor-&agr ; , interleukin (IL)-6 , and IL-10 were analyzed and recorded for all 5 subgroups . Results : Tumor necrosis factor-&agr ; and IL-6 levels on the fourth and seventh days , and Acute Physiology and Chronic Health Evaluation II scores on the seventh day after treatment showed significant decrease in the somatostatin , somatostatin + ulinastatin , somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza subgroups compared with the basic treatment subgroup . IL-10 levels on the fourth and seventh days were significantly improved in the somatostatin + ulinastatin , somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza subgroups compared with the basic treatment subgroup . The incidences of pancreatic sepsis , multiple organ dysfunction syndrome and mortality were lower in the somatostatin , somatostatin + ulinastatin , somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza subgroups compared with the basic treatment subgroup . Conclusions : Somatostatin is effective for the treatment of acute pancreatitis and both ulinastatin and S miltiorrhiza demonstrate improvement in therapeutic benefits A multicenter r and omized double-blind trial on the use of synthetic salmon calcitonin ( SCT ) was carried out in 94 patients with acute pancreatitis . In addition to strict st and ard treatment -- without aprotinin , atropine , or antacids--50 patients received daily 3 x 20 micrograms = 300 MRCU SCT intravenously and 44 patients received placebo for 6 days . Mortality rate was not influenced , overall mortality being 5.3 % . The number of patients without pain and with normalized serum amylase on a given day was significantly higher in the group treated with SCT . Other parameters such as doses of analgesics , leukocyte count , and normalization of seven defined clinical and laboratory criteria within 6 days showed a positive trend without reaching significance A prospect i ve r and omized clinical trial was carried out to evaluate the efficacy of atropine in the treatment of acute pancreatitis . Fifty-one patients with elevated amylase levels , and with the clinical signs and symptoms of acute pancreatitis , were included in the study . All were treated with fluids intravenously and analgesics , and a nasogastric tube if needed . In addition , on a r and om basis , 19 were given atropine intramuscularly and 32 were not . The clinical courses of the two groups of patients did not differ significantly CONTEXT Current best evidence is in favour of early institution of enteral feeding in acute severe pancreatitis with promising results from trials in immunonutrition on other patient groups . OBJECTIVE To identify which groups of patients and products are associated with benefit , we investigated immunonutrition in patients with predicted acute severe pancreatitis . DESIGN A r and omised trial of a study feed containing glutamine , arginine , tributyrin and antioxidants versus an isocaloric isonitrogenous control feed was undertaken . PATIENTS Thirty-one patients with a diagnosis of acute pancreatitis predicted to develop severe disease : 15 study feeds and 16 control feeds . INTERVENTIONS Enteral feeding via nasojejunal tube for 3 days . If patients required further feeding the study was continued up to 15 days . MAIN OUTCOME MEASURES Reduction in C-reactive protein ( CRP ) by 40 mg/L after 3 days of enteral feeding was the primary endpoint . Carboxypeptidase B activation peptide ( CAPAP ) levels were taken at regular intervals . RESULTS After 3 days of feeding , in the study group 2/15 ( 13 % ) of patients had reduced their CRP by 40 mg/L or more . In the control group 6/16 ( 38 % ) of patients had reduced their CRP by this amount . This difference was found to be near the statistical significant limit ( P=0.220 ) . CONCLUSIONS The cause of the unexpectedly higher CRP values in the study group is unclear . The rise in CRP was without a commensurate rise in CAPAP or outcome measures so there was no evidence that this represented pancreatic necrosis . The contrast between the CRP and CAPAP results is of interest and we believe that specific pancreatic indices such as CAPAP should be considered in larger future studies BACKGROUND The objective of this study was to investigate whether altering the fatty acid ( FA ) profile by omega-3 FA supplementation affects inflammatory response and systemic disease sequelae in severe acute pancreatitis . METHODS Forty severe acute pancreatitis patients were enrolled and r and omly assigned to receive parenteral nutrition ( PN ) for 5 days in a double-blind manner . Patients received PN with identical amounts of amino acids ( 1.25 g/kg/d ) , glucose ( 3 g/kg/d ) , and fat ( 1 g/kg/d ) but different lipid compositions : the control group received a soybean oil ( SO ; Lipovenos 20 % ; Fresenius , Germany)-based fat solution and the omega-3 FA group was supplemented with 0.15 - 0.2 g/kg/d fish oil ( FO ; Omegaven 10 % ; Fresenius , Germany ) . Serum concentrations of eicosapentaenoic acid ( EPA ) , interleukin-6 , C-reactive protein ( CRP ) , white blood cell count , and routine respiratory and renal parameters were measured before PN , and again on day 6 after starting PN . Outcomes such as infection morbidity , mortality , intensive care unit time , and length of hospital stay were recorded . RESULTS Patients treated with FO had a significantly higher EPA concentration ( P < .01 ) , lower CRP level ( P < .05 ) , and better oxygenation index ( P < .05 ) after 5 days of PN . Moreover , the number of days of continuous renal replacement therapy ( CRRT ) in the omega-3 FAs group was significantly less than that in the control group ( P < .05 ) . CONCLUSIONS PN supplemented with omega-3 FAs diminishes the hyperinflammatory response by the EPA increase and the proinflammatory cytokine decrease in severe acute pancreatitis . This , together with improved respiratory function and shortened CRRT time , suggests that the systemic response to pancreatic and organ injury is attenuated Nineteen consecutive patients with acute pancreatitis were sequentially allocated to treatment with high-dose octreotide ( N=9 ) or to act as controls ( N=10 ) . All other aspects of treatment were similar and were according to a strict treatment protocol . There was no significant difference between the two groups on admission with regard to recognized criteria of poor prognosis . The octreotide-treated group required significantly less analgesia and after 48 hr developed significantly fewer poor prognostic indicators , including falls in hematocrit of > 10 % , in serum albumin to < 32 g/liter , and in serum calcium to < 2.00 mmol/liter . Falls in arterial PO2 to < 10 kPa , in serum albumin of > 20 % , and in hemoglobin of > 2 g/dl were also significantly less frequent . There was a trend towards improvement in the octreotide-treated group in every other physiological and radiological indicator of disease severity . High-dose octreotide may reduce the severity of acute pancreatitis BACKGROUND / AIMS Exaggerated production of various proteases may account for the late presence of organ dysfunction in acute pancreatitis . This study examined the effects of early administration of gabexate mesilate on the condition of patients with severe acute pancreatitis and organ dysfunctions . METHODOLOGY Fifty-two patients with acute pancreatitis and organ dysfunction were enrolled . The treatment group included 26 patients receiving intravenous gabexate mesilate infusion at a dose of 100 mg/hr for 7 days . APACHE-II score , clinical and biochemical parameters were monitored intensively . RESULTS Coagulopathy ileus , and abdominal pain was significantly improved with gabexate mesilate . Gabexate mesilate reduced the necessity for surgical intervention and peritoneal lavage . The 7-day-mortality and 90-day-mortality rates were also significantly reduced with gabexate mesilate therapy . CONCLUSIONS There are strong indications from this study that early intravenous gabexate mesilate infusion results in improved survival in acute pancreatitis with organ dysfunctions Background Many patients with severe acute pancreatitis develop organ system failure during the first few days of illness , and this accounts for the majority of early deaths . No specific therapy is available and treatment remains supportive The treatment of acute pancreatitis in most instances is nonoperative [ ll , 131 . The medical management has become st and ardized and includes intravenous fluids , nasogastric suction , pain medication , often anticholinergics , and usually parenteral antibiotics [ 6 ] . Uncomplicated acute pancreatitis is a sterile inflammatory process and the need for or benefit from antibiotic therapy in such cases has not been demonstrated [ 3 , 91 . Secondary infection with the development of a pancreatic abscess is not common , but when it occurs it carries a high mortality [ 5 ] . In an effort to prevent such septic complications most clinicians use antibiotics prophylactically in acute pancreatitis [ 2 , 12 , 191 . In order to evaluate the efficacy of antibiotic administration in the treatment of acute pancreatitis , a prospect i ve r and omized study was performed at The Johns Hopkins Hospital comparing the incidence of septic complications in patients treated with ampicillin to those receiving no antibiotic therapy To evaluate the effect of somatostatin in the treatment of acute pancreatitis , 63 patients were r and omly allocated to continuous intravenous infusion for three days of 250 micrograms of somatostatin ( Dura Scan , Odense , Denmark ) per hour ( n = 33 ) , or placebo ( n = 30 ) . Patients with a first attack of pancreatitis , serum amylase level of more than 450 units per liter and symptoms for less than 24 hours were eligible for participation in the study . Apart from a slightly significant faster decrease in serum amylase concentrations , we were unable to demonstrate any significant benefit from somatostatin with regard to para clinical values and clinical course This study involves a multicenter trial aim ed at evaluating the comparative beneficial therapy of somatostatin and traditional symptomatic therapy in the management of acute pancreatitis . According to our final data somatostatin has not proved to be any better than traditional medical treatment . Nevertheless , in our opinion , the advantage of a single and expeditious therapy makes somatostatin administration preferable to the combined employment of several therapeutic measures usually applied in these circumstances BACKGROUND / AIMS Controversial results are present in clinical studies on the effect of octreotide in the treatment of patients with acute pancreatitis . The aim of this study was to analyze the effect of octreotide in biochemical , physiological and radiological prognostic criteria of acute pancreatitis at the end of 48 hours . METHODOLOGY Between January 1995 and August 1997 , we conducted a prospect i ve controlled clinical study . Forty-three patients with a diagnosis of acute pancreatitis ( acute abdominal pain and a serum amylase > 1000 IU/liter ) were sequentially allocated to treatment with high dose octreotide ( N=22 ) , 0.5 microg/kg/hr by continued i.v . infusion , or design ated as controls ( N=21 ) . The other aspects of the treatment protocol were similar in both groups . RESULTS There was no significant difference between the two groups on admission with regard to Ranson criteria ( P=0.13 ) . A significant difference was not observed in fasting blood glucose , albumin , calcium , hemoglobin , hematocrit , white blood cell count , LDH , AST , urea , systolic and diastolic pressure , heart rate and pyrexial changes between the two groups at admission and at the end of 48 hours ( p>0.05 ) , but serum amylase changes were significantly different ( p=0.000 ) . Pleural effusion at the end of 48 hours was more frequent in the octreotide treated group ( 22.7 % vs. 9.5 % , p>0.05 ) , but pancreatic edema ( 52.4 % vs. 13.6 % , p=0.022 ) , ascites ( 19.5 % vs. 4.5 % , p>0.05 ) and retroperitoneal edema ( 4.76 % vs. 4.5 % , p>0.05 ) were observed more frequently in the control group . One death occurred in each group . Patients treated with octreotide tolerated oral intake sooner than the control group ( 3.76 vs. 4.9 days , p=0.041 ) . CONCLUSIONS Although biochemical and physiologic changes between the two groups were not significantly different , a more pronounced decrease in serum amylase levels , improvements in pancreatic edema and earlier return to oral intake in the high dose-octreotide group suggest that octreotide may have a beneficial role in the management of acute pancreatitis OBJECTIVE To investigate the prognostic effects of integrated traditional Chinese and Western medicine therapy without antibiotics in treatment of patients with severe acute pancreatitis ( SAP ) . METHODS SAP patients were r and omly divided into treatment group ( 26 cases included ) and control group ( 28 cases included ) . In addition to the same protocol of integrated traditional Chinese and Western medicine treatment for both groups , intravenous drip infusion of 0.5 g imipenem-cilastatin was administered to the patients in the control group every eight hours for ten days . The 48-hour Ranson score , 24-hour acute physiology and chronic heath evaluation II score , and incidence rates of complications were observed . The concentrations of serum C-reactive protein ( CRP ) on days 1 , 3 , 7 and 10 were measured , and strains of infection were detected with smear and culture examination for bacteria and fungi . RESULTS There were no statistical differences in demographic information , baseline data and incidence rates of complications between the two groups ( P>0.05 ) , but fungal infection rate in the control group was higher than that in the treatment group ( P<0.05 ) . There were no statistical differences in infection rates of G- and G+ germs between the two groups ; blood and some organs including lung , pancreas , intestine , and urethra were infected with bacteria and fungi . There were also no significant differences in the serum CRP concentrations on days 1 , 3 , 7 and 10 between the two groups ( P>0.05 ) , but the serum CRP concentrations on days 1 , 3 , 7 and 10 in infected patients were higher than those in non-infected patients ( P<0.05 , P<0.01 ) . CONCLUSION The study can not confirm that the incidence rates of secondary infection and mortality in SAP patients treated with integrated traditional Chinese and Western medicine are reduced by prophylaxis with imipenem-cilastatin Goals To study the role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis ( AP ) . Background Bacterial translocation has been implicated in infective complications in AP , which has been shown to be prevented by probiotics . Study A double-blind , r and omized placebo-controlled trial was conducted . Consecutive patients with AP presenting within 72 hours after the onset of abdominal pain or who had been nil orally at the time of presentation for up to 5 days were included in the study . The probiotic group received 4 sachets of Probiotics ( 2.5 billion bacteria per sachet ) whereas the placebo group received 4 sachets of placebo for 7 days . Primary outcome measures were effect on gut permeability [ assessed by lactulose/mannitol ( L/M ) excretion in urine ] and endotoxemia assessed by endotoxin-core antibody types IgG and IgM ( EndoCab IgG and IgM ) . Secondary outcome measures were mortality , total hospital/intensive care unit stay , abdominal discomfort , organ failure , C-reactive protein , and prealbumin levels . The study was prematurely stopped after the publication of probiotic prophylaxis in patients with predicted severe acute pancreatitis trial . Results From March 2007 to May 2008 , 50 patients with AP were included in the study ( 26 in placebo group and 24 in probiotic group ) . There was no difference after intervention in gut permeability , whereas values of C-reactive protein and immunoglobulins decreased significantly [ IgG : 140 ( 20–920 ) to 90 ( 20–600 ) GGU/mL and IgM : 65 ( 13–230 ) to 51 ( 9–240 ) GMU/mL ] in the probiotic group . No difference was observed in prealbumin values , duration of hospital/intensive care unit stay , and mortality in both the groups . Conclusions No significant trend was identified for an effect of probiotics on gut permeability or endotoxemia in AP . However , the study was underpowered owing to premature study termination Background & Aims : In patients with severe , necrotizing pancreatitis , it is common to administer early , broad-spectrum antibiotics , often a carbapenem , in the hope of reducing the incidence of pancreatic and peripancreatic infections , although the benefits of doing so have not been proved . Methods : A multicenter , prospect i ve , double-blind , placebo-controlled r and omized study set in 32 centers within North America and Europe . Participants : One hundred patients with clinical ly severe , confirmed necrotizing pancreatitis : 50 received meropenem and 50 received placebo . Interventions : Meropenem ( 1 g intravenously every 8 hours ) or placebo within 5 days of the onset of symptoms for 7 to 21 days . Main Outcome Measures : Primary endpoint : development of pancreatic or peripancreatic infection within 42 days following r and omization . Other endpoints : time between onset of pancreatitis and the development of pancreatic or peripancreatic infection ; all-cause mortality ; requirement for surgical intervention ; development of nonpancreatic infections within 42 days following r and omization . Results : Pancreatic or peripancreatic infections developed in 18 % ( 9 of 50 ) of patients in the meropenem group compared with 12 % ( 6 of 50 ) in the placebo group ( P = 0.401 ) . Overall mortality rate was 20 % ( 10 of 50 ) in the meropenem group and 18 % ( 9 of 50 ) in the placebo group ( P = 0.799 ) . Surgical intervention was required in 26 % ( 13 of 50 ) and 20 % ( 10 of 50 ) of the meropenem and placebo groups , respectively ( P = 0.476 ) . Conclusions : This study demonstrated no statistically significant difference between the treatment groups for pancreatic or peripancreatic infection , mortality , or requirement for surgical intervention , and did not support early prophylactic antimicrobial use in patients with severe acute necrotizing pancreatitis A multi-center double-blind trial was performed on 48 patients with severe acute pancreatitis . All patients were treated with intraperitoneal lavage . One group ( n=22 ) was also treated with high doses of the protease inhibitor , aprotinin ( Trasylol ; Bayer AG , Leverkusen , Germany ) administered intraperitoneally . Eight patients died , giving a total mortality of 16.6 % . No difference was observed between the two groups . Altogether , 12 patients were operated on , corresponding to 25 % . In the group not treated with aprotinin , 6 patients were operated on because of pancreatic necrosis , compared with none in the treated group . The difference was statistically significant . There were no significant differences between the two groups with regard to organ failure or other complications . It was concluded that aprotinin counteracts the development of pancreatic necrosis when given intraperitoneally in high doses to patients with severe acute pancreatitis , thus reducing the need for surgical intervention in these patients Objective : The objective of this study is to evaluate the efficacy of somatostatin , ulinastatin and gabexate for the treatment of severe acute pancreatitis . Material s and Methods : A total of 492 patients with severe acute pancreatitis were assigned r and omly into the following 4 groups : ( 1 ) somatostatin ; ( 2 ) somatostatin + ulinastatin ; ( 3 ) somatostatin + gabexate and ( 4 ) somatostatin + ulinastatin + gabexate . Acute physiology and chronic health evaluation II scores ; clinical parameters including time of abdominal pain and distention extinct ; recovering to normality of heart rate and respiration rate ; amylase and blood glucose ; ratios of efficacy ; multiple organ dysfunction syndrome ( MODS ) ; mortality ; complication ; levels of endotoxin ; tumor necrosis factor alpha ; interleukin‐6 ( IL‐6 ) , IL‐8 and IL‐10 and side effects were analyzed . Results : Acute physiology and chronic health evaluation II scores , time of abdominal pain extinct and distention extinct , time of recovering to normality of heart rate , time of recovering to normality of respiration rate and time of recovering to normality of amylase and blood glucose were significantly decreased in the somatostatin + ulinastatin , the somatostatin + gabexate and the somatostatin + ulinastatin + gabexate subgroups compared with the somatostatin subgroup . Ratios of efficacy were significantly improved , whereas ratios of MODS , mortality and complication were significantly decreased in the somatostatin + ulinastatin and the somatostatin + ulinastatin + gabexate subgroups compared with the somatostatin subgroup . Tumor necrosis factor alpha , IL‐6 and IL‐8 levels on the fourth day after treatment showed significant decrease in the somatostatin + ulinastatin , the somatostatin + gabexate and the somatostatin + ulinastatin + gabexate subgroups compared with the somatostatin subgroup . The IL‐10 levels on the fourth day were significantly improved in the somatostatin + ulinastatin , the somatostatin + gabexate and the somatostatin + ulinastatin + gabexate subgroups compared with the somatostatin subgroup . Conclusions : Somatostatin is effective for the treatment of acute pancreatitis , ulinastatin demonstrates improvement in therapeutic benefits and gabexate can relieve the clinical symptoms and shorten the course of disease but can not improve the effective ratio or decrease MODS , mortality and complication Background The use of prophylactic antibiotics in acute severe necrotizing pancreatitis is controversial . Methods Prospect i ve , r and omized , placebo-controlled , double-blind study was carried out at Bellvitge Hospital , in Barcelona , Spain . Among 229 diagnosed with severe acute pancreatitis , 80 had evidence of necrotizing pancreatitis ( 34/80 patients were excluded of the protocol ) . Forty-six patients without previous antibiotic treatment with pancreatic necrosis in a contrast-enhanced CT scan were r and omly assigned to receive either intravenous ciprofloxacin or placebo . Five patients were secondarily excluded , and the remaining 41 patients were finally included in the study ( 22 patients received intravenous ciprofloxacin and 19 patients placebo ) . Results Comparing the 22 with intravenous ciprofloxacin and 19 with placebo , infected pancreatic necrosis was detected in 36 % and 42 % respectively ( p = 0.7 ) . The mortality rate was 18 % and 11 % , respectively ( p = 0.6 ) . No significant differences between both treatment groups were observed with respect to variables such as : non-pancreatic infections , surgical treatment , timing and the re-operation rate , organ failure , length of hospital and ICU stays . Conclusion The prophylactic use of ciprofloxacin in patients with severe necrotizing pancreatitis did not significantly reduce the risk of developing pancreatic infection or decrease the mortality rate . The small number of patients included in this study should be considered Purpose To prospect ively determine the quality of life and functional outcome at 3 , 6 and 12 months following acute necrotising pancreatitis . Methods Thirty-one consecutive patients with acute necrotising pancreatitis requiring intensive care in our hospital were identified . Survivors were assessed at 3 , 6 and 12 months following hospital discharge by an investigator blinded to their previous treatment . Health-related quality of life was assessed by the Short Form 36 ( SF-36 ) question naire and functional outcome by the six minute walk test . Results Twenty-one patients ( 68 % ) survived to leave hospital . The median score for the physical function domain increased from 32 at 3 months to 38 and 12 months ( P = 0.013 ) , but remained lower than the score in the normal population of 88 ( P < 0.001 ) . The median physical component summary score increased from 33 at 3 months to 40 at 12 months ( P = 0.030 ) , but remained lower than the score in the normal population of 50 ( P = 0.009 ) . Between 3 and 12 months the median distance walked in 6-min increased from 358 to 424 m ( P = 0.021 ) , but remained lower than the predicted distance of 503 m ( P = 0.014 ) . Conclusions In the first year after acute necrotising pancreatitis patients showed improvement in their physical components of quality of life and in their physical function , but their outcome at 12 months was still poor compared to the general population . This patient group in particular may benefit from a structured rehabilitation programme continuing after hospital discharge Summary Conclusion Although high-dose aprotinin given intraperitoneally to patients with severe acute pancreatitis seems to inhibit activated trypsin in the peritoneal cavity , the treatment has little effect on the balance between proteases and antiproteases . Plasma levels of leukocyte proteases were high in all the patients , indicating leukocyte activation to be an important feature of the pathophysiology of severe acute pancreatitis . A surprise finding was that the patients had higher peritoneal levels of pancreatic secretory trypsin inhibitor ( PSTI ) after the lavage procedure . Background Although most studies have shown protease inhibitor therapy to have little or no effect on acute pancreatitis , in an earlier study we found that very high doses of the protease inhibitor aprotinin given intraperitoneally to patients with severe acute pancreatitis seemed to reduce the need of surgical treatment for pancreatic necrosis . In the present study we have further analyzed plasma and peritoneal sample s from the same patients to ascertain whether the aprotinin treatment affects the balance between proteases and endogenous antiproteases . Methods In a prospect i ve double-blind r and omized multicenter trial , 48 patients with severe acute pancreatitis were treated with intraperitoneal lavage . One group ( aprotinin group , n=22 ) was also treated with high doses ( 20 million KIU given over 30 h ) of aprotinin intraperitoneally . The remaining 26 patients made up the control group . The protease-antiprotease balance was studied by measuring immunoreactive anionic trypsin ( irAT ) , cationic trypsin ( i rCT ) , complexes between cationic trypsin and alpha 1-protease inhibitor ( i rCT -α1PI ) , leukocyte elastase and neutrophil proteinase 4 ( NP4 ) , as well as the endogenous protease inhibitors , pancreatic secretory trypsin inhibitor ( PSTI ) , alpha 2-macroglobulin ( α 2 M ) , alpha 1-protease inhibitor ( α 1PI ) , antichymotrypsin ( ACHY ) , and secretory leukocyte protease inhibitor ( SLPI ) . Intraperitoneal levels were studied before and after the lavage procedure , and plasma levels were followed for 21 d. Results The control group had lower plasma levels of SLPI and analysis of peritoneal fluid showed the reduction of i rCT -α 1PI to be more pronounced in the aprotinin group . None of the other variables measured differed significantly between the two groups . All patients had very high levels of leukocyte elastase and NP4 both in peritoneal exu date and in plasma . Peritoneal levels of PSTI were higher after the lavage procedure in contrast to the other measured variables that all showed lower peritoneal levels after the lavage Forty-eight patients with severe acute pancreatitis were treated with intraperitoneal lavage in a double-blind r and omized multi-center trial . One group ( aprotinin group , n=22 ) was also treated intraperitoneally with high doses of the protease inhibitor aprotinin . In the group not treated with aprotinin ( control group ) , 6 patients were operated on because of pancreatic necrosis , compared with none in the treated group . Complement activation and the acute phase response were studied with measurements of anaphylatoxin C3a , C1 inhibitor ( C1 Inh ) , interleukin 6 ( IL-6 ) , and C-reactive protein ( CRP ) . The control group had higher plasma levels of C3a and lower levels of C1 Inh compared with the aprotinin group . The differences were statistically significant for C3a but not for C1 Inh . Both groups had high plasma levels of IL-6 and CRP . There were no differences between the groups in CRP levels , but the control group had higher IL-6 levels ( not statistically significant ) than the aprotinin group . This was caused by very high levels in the 6 patients operated on because of pancreatic necrosis , indicating that IL-6 could be a good plasma marker of pancreatic necrosis . The results also show that massive antiprotease treatment reduces complement activation , as illustrated by the lower C3a levels in the aprotinin group . The lower C1 Inh levels in the control group could have been caused by an increased consumption of the inhibitor The known suppressive actions of glucagon on the secretion of pancreatic enzymes and of gastric acid , and the reported effectiveness of glucagon in treating acute pancreatitis , prompted the authors to carry out a prospect i ve , r and omized , double-blind , controlled trial of this hormone . Sixty-six patients with acute pancreatitis admitted to the surgical service of the Vancouver General Hospital were r and omized into two groups of 33 , receiving either glucagon or placebo in addition to their conventional therapy . The two groups were comparable with respect to the cause of the pancreatitis and the severity of the disease . Glucagon did not reduce the patients ' analgesic requirements or the duration of abdominal signs , ileus , hyperamylasemia or hospital stay . Of the 66 patients , 4 died . Three of these were in the group receiving glucagon . The authors conclude that , contrary to theoretical expectations and the results of past uncontrolled trials , glucagon has no beneficial effect on the clinical course or outcome of acute pancreatitis , irrespective of the etiology or severity of the disease In order to evaluate the efficacy and safety of FOY injectable ( [ ethyl-4-(6-guanidinohexanoyloxy ) benzoate ] methane sulfonate ) on acute pancreatitis , a comparative clinical study was carried out using Trasylol as the control at 38 hospitals in Japan . Favourable results were obtained in 60 ( 71 % ) out of 84 patients in the FOY group and 29 ( 44 % ) out of 66 patients in the Trasylol group . The results showed that these both drugs were effective and the statistical analysis revealed considerable difference ( X2 = 10.464 , p less than 0.005 ) between the two groups in this condition of clinical trial . In addition , a double blind trial was carried out at 4 hospitals using FOY-305 ( [ n.n-dimethylcarbamoylmethy 4-(4-guanidinobenzoyloxy)-phenylacetate ] methane sulfonate ) oral capsule and inactive placebo . Favourable results were obtained in 18 ( 69 % ) out of 26 patients in the FOY-305 group and 8 ( 32 % ) out of 25 patients in the inactive placebo group , indicating a significant difference between the two groups ( X2 = 8.930 , p less than 0.01 ) . The results of the present study suggest that synthetic protease inhibitor , FOY or FOY-305 , is beneficial in the treatment of acute pancreatitis OBJECTIVE To evaluate the immuno-modulatory effect of short course administration of somatostatin ( stilamin ) continuously at early stage in patients with severe acute pancreatitis ( SAP ) . METHODS Thirty-nine patients with SAP ( 22 men , 17 women ; the middle age was 49 years)were r and omly allocated into control group ( 20 patients treated with non-surgical integrated traditional Chinese and Western medicine ) and treatment group ( 19 patients treated with somatostatin administered intravenously at a dosage of 250 mug/h for consecutive 72 hours as well as the treatment for the control group ) . Laboratory parameters , including the expressions of CD(3 ) , CD(4 ) and CD(8 ) in lymphocytes ( tested by flow cytometry ) and C reactive protein ( CRP ) , and indexes of therapeutic effect , including the occurrence of organic dysfunction , local complication and mortality between the two groups were compared . Another group of 30 healthy volunteers ( 19 men , 11 women ; the middle age was 47 years ) were recruited for testing the normal levels of CD(3 ) , CD(4 ) and CD(8 ) . RESULTS ( 1 ) The levels of CD(3 ) , CD(4 ) and CD(4)/CD(8 ) in lymphocytes before treatment in both groups were significantly lower than those in the healthy subjects ( P<0.05 ) , but there were no statistical differences between the two groups . At the 4th day , CD(3 ) , CD(4 ) and CD(4)/CD(8 ) increased significantly in the treatment group ( P<0.05 ) while no changes in the control group ; the levels of CD(4 ) and CD(4)/CD(8 ) in the treatment group were also higher than those in the control group ( P<0.05 ) . ( 2 ) The CRP levels of the 2 groups showed no statistical difference before and 4 days after the treatment , but the CRP level in the treatment group was significantly lower than that in the control group at the 7th day ( P<0.05 ) . WBC count , serum levels of amylase , lipase , lactate dehydrogenase , aspartate aminotransferase , as well as the score of APACHE II in the treatment group recovered more quickly than those in the control group ( P<0.05 ) . ( 3 ) The occurrences of organic dysfunctions , local complications and mortality in both groups were not statistically different . CONCLUSION The short course administration of somatostatin continuously at early stage can reduce the inflammatory response , up-regulate the cell immune function and improve the conditions of the patients with SAP , but its effect on mortality and morbidity needs further study BACKGROUND Platelet activating factor ( PAF ) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome ( SIRS ) in acute pancreatitis , result ing in multiorgan dysfunction syndrome . We tested the hypothesis that a potent PAF antagonist , lexipafant , could dampen SIRS and reduce organ failure in severe acute pancreatitis . METHODS We conducted a r and omised , double blind , placebo controlled , multicentre trial of lexipafant ( 100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms ) involving 290 patients with an APACHE II score > 6 . Power calculations assumed that complications would be reduced from 40 % to 24 % . Secondary end points studied included severity of organ failure , markers of the inflammatory response , and mortality rate . FINDINGS Overall , 80/138 ( 58 % ) patients in the placebo group and 85/148 ( 57 % ) in the lexipafant group developed one or more organ failures . The primary hypothesis was invali date d by the unexpected finding that 44 % of patients had organ failure on entry into the study ; only 39 ( 14 % ) developed new organ failure . Organ failure scores were reduced in the lexipafant group only on day 3 : median change −1 ( range −4 to + 8) versus 0 ( −4 to + 10 ) in the placebo group ( p=0.04 ) . Systemic sepsis affected fewer patients in the lexipafant group ( 13/138v 4/148 ; p=0.023 ) . Local complications occurred in 41/138 ( 30 % ) patients in the placebo group and in 30/148 ( 20 % ) in the lexipafant group ( 20 % ; p=0.065 ) ; pseudocysts developed in 19 ( 14 % ) and eight ( 5 % ) patients , respectively ( p=0.025 ) . Deaths attributable to acute pancreatitis were not significantly different . Interleukin 8 , a marker of neutrophil activation , and E-selectin , a marker of endothelial damage , decreased more rapidly in the lexipafant group ( both p<0.05 ) ; however , absolute values were not different between the two groups . INTERPRETATION The high incidence of organ failure within 72 hours of the onset of symptoms undermined the primary hypothesis , and power calculations for future studies in severe acute pancreatitis will need to allow for this . Lexipafant had no effect on new organ failure during treatment . This adequately powered study has shown that antagonism of PAF activity on its own is not sufficient to ameliorate SIRS in severe acute Objectives : To determine the relation between intestinal barrier dysfunction , bacterial translocation , and clinical outcome in patients with predicted severe acute pancreatitis and the influence of probiotics on these processes . Summary of Background data : R and omized , placebo-controlled , multicenter trial on probiotic prophylaxis ( Ecologic 641 ) in patients with predicted severe acute pancreatitis ( PROPATRIA ) . Methods : Excretion of intestinal fatty acid binding protein ( IFABP , a parameter for enterocyte damage ) , recovery of polyethylene glycols ( PEGs , a parameter for intestinal permeability ) , and excretion of nitric oxide ( NOx , a parameter for bacterial translocation ) were assessed in urine of 141 patients collected 24 to 48 h after start of probiotic or placebo treatment and 7 days thereafter . Results : IFABP concentrations in the first 72 hours were higher in patients who developed bacteremia ( P = 0.03 ) , infected necrosis ( P = 0.01 ) , and organ failure ( P = 0.008 ) . PEG recovery was higher in patients who developed bacteremia ( PEG 4000 , P = 0.001 ) , organ failure ( PEG 4000 , P < 0.0001 ) , or died ( PEG 4000 , P = 0.009 ) . Probiotic prophylaxis was associated with an increase in IFABP ( median 362 vs. 199 pg/mL ; P = 0.02 ) , most evidently in patients with organ failure ( P = 0.001 ) , and did not influence intestinal permeability . Overall , probiotics decreased NOx ( P = 0.05 ) but , in patients with organ failure , increased NOx ( P = 0.001 ) . Conclusions : Bacteremia , infected necrosis , organ failure , and mortality were all associated with intestinal barrier dysfunction early in the course of acute pancreatitis . Overall , prophylaxis with this specific combination of probiotic strains reduced bacterial translocation , but was associated with increased bacterial translocation and enterocyte damage in patients with organ failure BACKGROUND & AIMS Antibiotic prophylaxis in severe pancreatitis has recently yielded promising clinical results , with imipenem significantly reducing the incidence of infected necrosis compared with an untreated control group . On the bases of pefloxacin 's spectrum of action and pancreatic penetration , we investigated whether such drugs represent a valid alternative to imipenem . METHODS In a multicenter study , 60 patients with severe acute pancreatitis with necrosis affecting at least 50 % of the pancreas were r and omly allocated to receive intravenous treatment for 2 weeks with pefloxacin , 400 mg twice daily ( 30 patients ) , or imipenem , 500 mg three times daily ( 30 patients ) , within 120 hours of onset of symptoms . Age , sex , body weight , Ranson and Apache II scores , C-reactive protein , etiology , and time from onset of symptoms to treatment were well matched in the two groups . RESULTS The incidences of infected necrosis and extrapancreatic infections were 34 % and 44 % , respectively , in the pefloxacin group and 10 % and 20 % in the imipenem group . Imipenem proved significantly more effective in prevention of pancreatic infections ( P < /= 0.05 ) . Mortality was not significantly different in the two groups . CONCLUSIONS Despite its theoretical potential , pefloxacin is inferior to imipenem in the prevention of infections associated with severe pancreatitis AIM To compare the efficacy of two different schedules of gabexate mesilate ( 900 mg/day , or 1,500 mg/day ) in the treatment of severe acute pancreatitis . SETTING Forty-two Italian medical and surgical centres took part in the study . STUDY DESIGN A multicentre , prospect i ve , open label , comparative , parallel-group , r and omized study . METHODS The patients enrolled in the study had acute pancreatitis as demonstrated by typical abdominal pain and baseline serum amylase concentrations more than twice the upper normal limit , findings compatible with acute pancreatitis at imaging techniques , and a Glasgow criteria score of > or =3 . Patients were r and omly assigned to one of the two schedules of treatment with gabexate mesilate being administered intravenously for at least 7 days . The minimum clinical ly relevant difference ( delta ) , between groups , in incidence of complications due to acute pancreatitis , during the first month of the study treatment , was predefined as equal to 10 % . RESULTS A total of 199 patients were assigned to gabexate mesilate 900 treatment and 189 to gabexate mesilate 1,500 . Complications developed in 88 patients within one month of beginning treatment 44/199 : patients ( 22.1 % ) in the gabexate mesilate 900 group and 44/189 patients ( 23.3 % ) in the gabexate mesilate 1,500 group ( difference 1.2 % ; 95 % confidence interval : -7.2 ; 9.5 % ) . CONCLUSIONS Gabexate mesilate 900 mg per day is as effective as gabexate mesilate 1,500 mg per day in reducing the complications due to acute pancreatitis This study is a double “ blind ” prospect i ve evaluation of the efficacy of antibiotics ( Ampicillin ) in the treatment of acute alcohol-induced and idiopathic pancreatitis . Fifty-eight patients with acute pancreatitis were r and omly divided into antibiotic and non-antibiotic treatment groups . The two groups were comparable clinical ly at the onset of the study and other than for antibiotics received identical therapy . The patients without antibiotics had a clinical course equal or slightly more favorable than the antibiotic treatment group in all parameters examined . These data indicate that prophylactic use of Ampicillin is not indicated in patients with routine acute alcohol-induced or idiopathic pancreatitis . The role of prophylactic antibiotics in patients with pancreatitis related to biliary calculi and those with more severe varieties of acute hemorrhagic or necrotizing pancreatitis remains to be more clearly defined OBJECTIVE To evaluate whether enteral prophylaxis with probiotics in patients with predicted severe acute pancreatitis prevents infectious complications . DESIGN Multicentre , r and omised , double-blind , placebo-controlled trial . METHOD A total of 296 patients with predicted severe acute pancreatitis ( APACHE II score > or = 8 , Imrie score > or = 3 or C-reactive protein concentration > 150 mg/l ) were included and r and omised to one of two groups . Within 72 hours after symptom onset , patients received a multispecies preparation of probiotics or placebo given twice daily via a jejunal catheter for 28 days . The primary endpoint was the occurrence of one of the following infections during admission and go-day follow-up : infected pancreatic necrosis , bacteraemia , pneumonia , urosepsis or infected ascites . Secondary endpoints were mortality and adverse reactions . The study registration number is IS RCT N38327949 . RESULTS Treatment groups were similar at baseline with regard to patient characteristics and disease severity . Infections occurred in 30 % of patients in the probiotics group ( 46 of 152 patients ) and 28 % of those in the placebo group ( 41 of 144 patients ; relative risk ( RR ) : 1.1 ; 95 % CI : 0.8 - 1.5 ) . The mortality rate was 16 % in the probiotics group ( 24 of 152 patients ) and 6 % ( 9 of 144 patients ) in the placebo group ( RR : 2.5 ; 95 % CI : 1.2 - 5.3 ) . In the probiotics group , 9 patients developed bowel ischaemia ( of whom 8 patients died ) , compared with none in the placebo group ( p = 0.004 ) . CONCLUSION In patients with predicted severe acute pancreatitis , use of this combination of probiotic strains did not reduce the risk of infections . Probiotic prophylaxis was associated with a more than two-fold increase in mortality and should therefore not be administered in this category of patients Summary Conclusion In this study , octreotide was not found to be of benefit in the treatment of acute pancreatitis . Background Somatostatin and its long-acting analog octreotide have both been proposed for the treatment of patients with acute pancreatitis , but neither agent has been adequately assessed in patients with severe attacks . Methods Fifty-eight patients with moderate or severe acute pancreatitis who were admitted to hospitals within the west of Scotl and over an 18-mo period were r and omized to receive octreotide , 40 μg/h , by continuous iv infusion for 5 d , or placebo in addition to st and ard supportive therapy . Results There was no significant difference in the incidence of complications ( 54 % octreotide group and 40 % placebo group ) or mortality ( octreotide group 18 % ; placebo group 20 % ) A double blind study testing the effect of long-acting zinc-protamine-glucagon ( 7.5 mg every 12 hours for 4 - -5 days ) was carried out in acute pancreatitis . There were 32 patients in ZP-glucagon- and 39 patients in the placebo group . The results show that glucagon had a slightly favourable effect on the general clinical course of the disease but they do not give enough evidence for routine use of glucagon in pancreatitis Objectives To evaluate the efficacy of octreotide in preventing severe acute pancreatitis ( SAP ) in obese patients . Methods A prospect i ve multi-center partly r and omized control trial was conducted in patients with mild acute pancreatitis ( AP ) . Nonobese patients received conventional management ( nonobese-C , n = 82 ) , whereas obese patients ( body mass index ≥25 kg/m2 ) were r and omized into 2 groups : obese-C ( n = 79 ) , who received conventional management , and obese-C+O ( n = 82 ) , who received conventional management plus intravenous infusion of octreotide , 50 & mgr;g/h for 72 hours . Results The risk ratio and relative risk reduction in the development of SAP in the obese-C+O group were 0.27 ( 95 % confidence interval , 0.10–0.69 ) and 0.73 ( 95 % confidence interval , 0.31–0.90 ) , respectively . The number of cases developing local complications in the obese-C+O group was significantly smaller than that in the obese-C group : 4.9 % vs 19 % , P = 0.006 . The plasma level of somatostatin in the obese-C+O group was significantly higher than that in the obese-C group : 165.5 ± 42.6 vs 112.1 ± 24.86 pg/mL , P < 0.05 . Supplement of octreotide also accompanied with reduction in plasma levels of tumor necrosis factor & agr ; and IL-6 . Conclusions Intravenous administration of octreotide ( 50 & mgr;g/h ) for 72 hours in the early stage of AP could prevent the development of SAP effectively in obese patients by raising plasma somatostatin to a normal level and reducing circulating cytokines Three hundred patients with acute pancreatitis have been studied . Pancreatitis was associated with alcoholism in 207 , biliary tract disease in 51 and other conditions in 42 . Twenty-two patients died , and an additional 34 patients required more than one week of treatment in the intensive care unit . Retrospective analysis of the first 100 patients identified 11 objective findings which correlated with the occurrence of serious illness or death . They were , on admission , age over 55 years , blood glucose level over 200 milligrams per cent , white blood count over 16,000 per cubic millimeter , serum lactic dehydrogenase level over 350 International units per liter and serum glutamic-oxalacetic transaminase level over 250 Sigma Frankel units per cent . During the initial 48 hours of therapy , the findings were hematocrit value decrease over 10 percentage points , serum calcium level below 8 milligrams per cent , base deficit over 4 milli-equivalents per liter , a blood urea nitrogen level increase over 5 milligrams per cent , estimated fluid sequestration over 6 liters and arterial oxygen tension less than 60 millimeters of mercury . Prospect i ve application of these signs in the latter 200 patients permitted the accurate early identification of those with severe pancreatitis . Only one of 162 patients with fewer than three of these early features was seriously ill or died , while 24 of 38 patients with three or more early positive findings were seriously ill or died . The objective early identification of patients with severe pancreatitis permits more vigorous management of this group and also provides a basis for the selection of patients for the evaluation of proposed improved therapies . Percutaneous peritoneal dialysis in severe pancreatitis was evaluated in ten patients , with three or more positive early signs , who were r and omly assigned to dialysis or continued conventional care . Morbidity was strikingly reduced in patients who underwent dialysis , and while death or more than nine days of intensive care occurred in two of five patients who did not receive dialysis , all five patients having dialysis recovered after fewer than nine days of intensive care treatment . Serious illness or death occurred in 31 of the first 100 patients but in only 26 of the more recent 200 patients . There has been a similar fall in mortality from 15.0 to 3.5 per cent . Factors which may contribute to this improvment include the objective early identification of patients with severe disease , the avoidance of early laparotomy whenever practical , the prolongation of nasogastric suction until all evidence of pancreatic inflammation has resolved , careful monitoring of respiratory function and early treatment of pulmonary complications and peritoneal dialysis in patients with severe disease Objective . The main causes of death in severe pancreatitis are multiorgan failure and septic complications . Prophylactic treatment with effective antibiotics is therefore a tempting therapeutic option . However , there could be side effects such as selection of resistant microbes and fungi . The aim of the present study was to compare the rate of infectious complications , interventions , days in the intensive care unit ( ICU ) , morbidity and mortality in patients with severe pancreatitis r and omized to prophylactic therapy with imipenem compared with those receiving no treatment at all . Material and methods . Seventy-three patients with severe pancreatitis were included in a prospect i ve , r and omized , clinical study in seven Norwegian hospitals . The number of patients was limited to 73 because of slow patient accrual . Severe pancreatitis was defined as a C-reactive protein ( CRP ) level of > 120 mg/l after 24 h or CRP > 200 48 h after the start of symptoms . The patients were r and omized to either early antibiotic treatment ( imipenem 0.5 g × 3 for 5–7 days ) ( imipenem group ) ( n=36 ) or no antibiotics ( control group ) ( n=37 ) . Results . The groups were similar in age , cause of pancreatitis , duration of symptoms and APACHE II score . Patients in the imipenem group experienced lower rates of complications ( 12 versus 22 patients ) ( p=0.035 ) and infections ( 5 versus16 patients ) ( p=0.009 ) than those in the control group . There was no difference in length of hospital stay ( 18 versus 22 days ) , need of intensive care ( 8 versus 7 patients ) , need of acute interventions ( 10 versus 13 ) , nor for surgery ( 3 versus 3 ) or 30-day mortality rates ( 3 versus 4 ) . Conclusions . The study , although underpowered , supports the use of early prophylactic treatment with imipenem in order to reduce the rate of septic complications in patients with severe pancreatitis The effects of glucagon versus placebo were evaluated in a double-blind trial including only patients with a first attack of severe acute pancreatitis not associated with biliary disease . All 22 patients had deterioriation of their clinical condition , elevated serum amylase and pulse rate above 100/min . or shock . An initial dose of 1 mg . glucagon was given as a bolus injection followed by infusion of 6 mg . in 1,500 ml . saline/24 hr . for three days . All were treated with nasogastric decompression , fluids , calcium and antibiotics . Severe complications developed in five of the 10 patients receiving glucagon and in eight of the 12 given a placebo . Three of the 10 ( glucagon ) and five of the 12 ( placebo ) died from these complications . Hemorrhagic pancreatitis was found in 11 patients at laparotomy or autopsy . Three of the five with hemorrhagic pancreatitis in the glucagon group and four of the six in the placebo group died . Pooling the data of the present and two other studies makes it probable that glucagon has no effect on mortality from acute severe pancreatitis One hundred and sixty‐one consecutive patients with primary acute pancreatitis were admitted to a double‐blind trial of intravenous Trasylol therapy as a supplement to a st and ard regimen of conservative management . The patients were subdivided into younger ( less than 60 years ) and older patients ( aged 60 years and over ) , and subjects in each group were r and omly allocated on a double‐blind basis either to Trasylol therapy ( starter 500 000 KIU and thereafter 200 000 q. i. d. for 5 days ) or to placebo . There were 14 deaths ( 8.7 per cent ) , 7 in the Trasylol and 7 in the placebo group , and no significant difference was found in either the mortality or the major complications rate , either overall or within either age group Although Trasylol has been available for the treatment of acute pancreatitis for 15 years a review of the literature reveals that its effectiveness has never been either proved or disproved . A prospect i ve double blind controlled trial was therefore started in 1967 . The results are now reported A multicenter , r and omized , double-blind trial was carried out to evaluate the efficacy of gabexate mesylate ( FOY ) in acute pancreatitis . One hundred unselected patients were r and omly allocated into two groups : 51 were assigned to receive FOY ( 12 mg/kg/day as continuous intravenous infusion for a minimum of 4 days and a maximum of 12 days ) , and 49 were allocated to placebo . The groups were comparable in demographic , clinical and biochemical parameters , etiology of pancreatitis , and disease severity , which was generally mild . Gallstones were the main etiological factor . All patients received fluid and electrolyte replacement , analgesia and nasogastric suction for at least 48 h after admission . Experimental therapy was initiated no later than 12 h after the beginning of symptoms . The results showed no statistically significant differences between the two groups with respect to the evolution of clinical and biochemical parameters , analgesic requirements , development of complications , hospitalization time or mortality at completion of the trial . In conclusion , early treatment with FOY does not appear to have any demonstrable beneficial effects in acute pancreatitis Acute necrotizing pancreatitis is still associated with high morbidity and mortality . In this prospect i ve clinical trial , we analyzed the effect of octreotide in patients with acute pancreatitis . Eight patients received either 3 x 100 , 3 x 200 or 3 x 500 micrograms octreotide subcutaneously per day over a period of 10 days . The complication rate was lower in the group of patients who received 3 x 200 or 3 x 500 micrograms octreotide than in the control group and the group of patients who received the dosis of 3 x 100 micrograms octreotide per day . The results of this study are promising and must be vali date d in a controlled clinical trial with octreotide in a larger patient population Summary The aim of this study was to explore the effects of parenteral supplementation with ω-3 fish oil emulsion ( Omegaven ® ) on systemic inflammatory response syndrome ( SIRS ) during the initial stage of severe acute pancreatitis ( SAP ) . In a prospect i ve , r and omized and controlled trial , 60 patients with SAP were r and omized either to treat with conventional therapy ( Con group , n=30 ) or conventional therapy plus intravenous supplementation with ω-3 fish oil emulsion 0.2 g/kg every day ( FO group , n=30 ) . The effects were analyzed by the SIRS-related indexes . The results showed that APACHE-II scores in FO group were significantly lower , and the gap increased much farther after the 4th day than those in Con group ( P<0.05 ) . Fluid equilibrium time became shorter markedly in FO group than in Con group ( 5.1±2.2 days vs 8.4±2.3 days ) . In FO group , SIRS scores were markedly decreased and the SIRS state vanished after the 4th day ; Plasma level of TNF-α was significantly reduced , while IL-10 decreased markedly , most prominently between the 4th and 7th day , and the ratio of IL-10/TNF-α raised as compared with Con group ( P<0.05 ) . During the initial stage of SAP , parenteral supplementation with ω-3 fish oil emulsion could efficiently lower the magnitude and persistence time of the SIRS , markedly retrieve the unbalance of the pro-/anti-inflammatory cytokines , improve severe condition of illness and may provide a new way to regulate the SIRS |
10,548 | 26,620,831 | Retrusion of the upper and lower lips were also verified , with less retraction of the lower lip in 2-premolar extraction groups .
When Class II division 1 malocclusion is treated with premolar extraction s , the NLA increases and the lips are retracted .
However , there is less retraction of the lower lip in the 2-maxillary premolar extraction protocol | BACKGROUND Concerns about the effects caused by premolar extraction s on the soft-tissue profile have motivated many investigations in different malocclusions .
OBJECTIVES To evaluate the cephalometric facial soft-tissue changes after orthodontic treatment with premolar extraction s of Class II division 1 malocclusion subjects . | OBJECTIVE To compare the treatment effects of maxillary anterior teeth retraction with mini-implant anchorage in young adults with Class II division 1 malocclusion undergoing extraction of the maxillary first premolars with similar patients treated by a fixed functional appliance . MATERIAL S AND METHODS Thirty-four young adult female patients ( mean age 16.5 ± 3.2 years , overjet ≥ 6 mm ) with a Class II division 1 malocclusion were divided into two groups : group 1 ( G1 ) , in which overjet correction was obtained with a fixed functional appliance ( FFA ) , and group 2 ( G2 ) , in which upper first premolars were extracted , followed by space closure with MIs as anchor units . Dentoskeletal and soft tissue changes were analyzed on lateral cephalograms taken before ( T1 ) and after ( T2 ) correction of the overjet . RESULTS Both methods were useful in improving the overjet and interincisal relationships . Extrusion and mesial movement of the lower molar , together with lower incisor proclination , were noted in G1 . G2 showed distalization and intrusion of the upper molar . The nasio-labial angle became more obtuse in G2 , while lower lip protrusion was seen for G1 . CONCLUSIONS The two treatment protocol s provided adequate dental compensation for the Class II malocclusion , but did not correct the skeletal discrepancy . There were significant differences in the dental and soft tissue treatment effects between the two treatment protocol INTRODUCTION The esthetic impact of the soft-tissue profile might play a major role in deciding on premolar extraction or non extraction treatment , particularly in borderline patients . The purpose of this study was to compare the esthetic impact of extraction and non extraction therapy on Korean patients . METHODS Panels of 50 dentists and 50 laypersons evaluated r and omly presented pretreatment and posttreatment soft-tissue profiles of 50 extraction and 50 non extraction patients . As subjects in this study , borderline patients were selected based on their initial diagnostic records . Two panels were asked to compare the pretreatment and posttreatment profile tracings and to quantify their perceptions of the esthetic impact of treatment change using a visual analog scale . RESULTS Premolar extraction patients showed greater improvement in facial profile compared with non extraction patients , regardless of the panel . Based on the results of regression analysis to determine the degree of lip protrusion at which the retraction that commonly follows premolar extraction would be needed , the intersection was about 3.0 mm behind the Ricketts ' E-line ; this is far behind the Korean norm . CONCLUSIONS The results indicate that premolar extraction is more beneficial than non extraction treatment in terms of facial profile improvement in Korean borderline patients BACKGROUND No r and omized controlled trial has tried to compare treatment outcomes between the sliding en-masse retraction of upper anterior teeth supported by mini-implants and the two-step sliding retraction technique employing conventional anchorage devices . OBJECTIVE To evaluate skeletal , dental , and soft tissue changes following anterior teeth retraction . DESIGN AND SETTING Parallel-groups r and omized controlled trial on patients with class II division 1 malocclusion treated at the University of Al-Baath Dental School in Hamah , Syria between July 2011 and May 2013 . PARTICIPANTS One hundred and thirty-three patients with an upper dentoalveolar protrusion were evaluated and 80 patients fulfilled the inclusion criteria . R and omization was performed using computer-generated tables ; allocation was concealed using sequentially numbered opaque and sealed envelopes . Fifty-six participants were analysed ( mean age 22.34 ± 4.56 years ) . They were r and omly distributed into two groups with 28 patients in each group ( 1:1 allocation ratio ) . INTERVENTION Following first premolar extraction , space closure was accomplished using either the en-masse technique with mini-implants or the two-step technique with transpalatal arches ( TPAs ) . MAIN OUTCOME MEASURE The antero-posterior displacements of upper incisal edges and upper first molars were measured on lateral cephalograms at three assessment times . Assessor blinding was employed . RESULTS A bodily retraction ( -4.42 mm ; P < 0.001 ) with a slight intrusion ( -1.53 mm ; P < 0.001 ) of the upper anterior teeth was achieved in the mini-implants group , whereas upper anterior teeth retraction was achieved by controlled palatal tipping in the TPA group . CONCLUSIONS When retracting anterior teeth in patients with moderate to severe protrusion , the en-masse retraction based on mini-implants anchorage gave superior results compared to the two-step retraction based on conventional anchorage in terms of speed , dental changes , anchorage loss , and aesthetic outcomes Objective : The objective of this study was to establish whether and how premolar extraction affects the soft tissue profile and incisor inclination in patients with Angle Class II , Division 1 malocclusion . Our primary intention was to identify differences between patients who had four premolars extracted and those who had only two upper premolars removed during camouflage treatment . Our control group consisted of patients with an Angle Class II , Division 1 treated without extraction s. Material s and Methods : These patients ’ lateral cephalograms were cephalometrically analyzed before and after treatment . Computer-assisted analysis of the data using Onyx Ceph ® was followed by a single-factor variance analysis ( one-way ANOVA ) . Results : Our results demonstrate that patients who have undergone camouflage treatment exhibit significantly more retruded upper central incisors than those with extraction s in both jaws , and that their upper incisors are highly significantly more retruded and their m and ibles significantly more retrognathic than those of patients who have not undergone extraction therapy . Conclusion : We did not observe that the patients ’ profiles did become worse after extraction therapy . ZusammenfassungZiel : Es soll dargestellt werden , ob und wie sich eine Prämolarenextraktion auf das Weichteilprofil und die Schneidezahnneigung bei Patienten mit Angle-Klasse II,1 auswirkt . Vor allem sollen Unterschiede zwischen Patienten , bei denen vier Prämolaren extrahiert wurden , und Patienten , denen i m Rahmen einer Camouflage-Beh and lung nur zwei Prämolaren i m Oberkiefer entfernt wurden , ermittelt werden . Als Vergleichsgruppe dienen Patienten mit einer Angle-Klasse II,1 , die ohne Extraktionen beh and elt wurden . Material und Method ik : Die Fernröntgenseitenbilder dieser Patienten wurden vor und nach der Beh and lung kephalometrisch ausgewertet . I m Anschluss an die computergestützte Auswertung der Date n mit Onyx Ceph ® erfolgte eine einfaktorielle Varianzanalyse ( Oneway ANOVA).Ergebnisse : Die Ergebnisse zeigen , dass Patienten mit Camouflage-Beh and lung nach Therapie signifikant retrudierter stehende obere mittlere Schneidezähne als Patienten mit Extraktionen in beiden Kiefern haben und dass sie höchst signifikant retrudierter stehende obere Schneidezähne sowie signifikant retrognather liegende Unterkiefer als Patienten ohne Extraktionstherapie aufweisen . Schlussfolgerung : Eine Profilverschlechterung nach Extraktionstherapie konnte nicht nachgewiesen werden Soft-tissue profiles were examined in 160 orthodontic patients treated with removal of four first premolars . Records of 10- to 30-year-old patients were selected at r and om from five sources : patients treated by Charles H. Tweed on file at the Tweed Foundation , patients treated with the Begg technique by the Kesling-Rocke group , patients from two practice s with pretorqued , preangulated edgewise appliances , and patients with premolars enucleated at an early age . The mean changes for the total sample included an increase of 5.2 degrees in the nasolabial angle , and retraction of the upper and lower lips 3.4 and 3.6 mm to the E line , respectively . For different measurements , between 5 % and 25 % of the sample had values indicating more protrusive lips after treatment . In comparisons among groups , the Tweed patients generally exhibited the greatest lower lip retraction . When profile changes were compared to values representing normal ( or " ideal " ) facial esthetics , it was evident that extraction of four first premolars generally did not result in a " dished-in " profile . Approximately 10 % to 15 % of cases could be defined as excessively flat after treatment . Eighty percent to 90 % of patients treated by extraction of four first premolars had soft-tissue measurements that suggested the profile was improved by treatment or remained satisfactory throughout treatment INTRODUCTION A prospect i ve r and omized study was design ed to compare the skeletal , dental , and soft-tissue profile changes in Class I borderline patients treated with extraction and non extraction by means of the air-rotor stripping ( ARS ) technique and to compare the treatment times . METHODS Twenty-six borderline patients with balanced and orthognathic facial profiles were r and omly divided into 2 groups . In the first group , 13 subjects with a mean age of 18.1 + /- 3.7 years and mean maxillary and m and ibular crowding of 5.7 + /- 1.5 and 5.9 + /- 1.4 mm , respectively , were treated by removal of 4 premolars with minimum anchorage . In the second group , 13 subjects with a mean age of 17.8 + /- 2.4 years and mean maxillary and m and ibular crowding of 5.0 + /- 1.3 and 5.9 + /- 1.3 mm , respectively , were treated with ARS . Lateral cephalometric radiographs and dental models taken before and after treatment were evaluated . RESULTS The initial skeletal , dental , and profile characteristics of both groups were similar . In the first group , the maxillary and m and ibular incisors were slightly retracted , whereas lip positions did not change . In the non extraction group , maintenance of maxillary incisor position , slight protrusion of the m and ibular incisors and the upper and lower lips were observed at the end of treatment . The nasolabial angle decreased significantly . Because of postpubertal growth of the nose and the chin , the lips appeared slightly retrusive after extraction therapy , whereas lip protrusion was compensated in the non extraction group . The main soft-tissue profile differences between the 2 groups were 1 to 1.5 mm more retruded upper and lower lip positions in the extraction patients , but both groups had well-balanced and desirable facial esthetics with all profile measurements within normal limits . Non extraction therapy with ARS reduced treatment time by 8 months . CONCLUSIONS Both extraction and ARS combined with non extraction therapies are effective treatment alternatives for Class I borderline patients with good facial profile and moderate dental crowding This investigation was design ed to compare the esthetic effects of extraction and non extraction treatments . Panels of 58 laypersons and 42 dentists evaluated r and omly presented pre- and posttreatment profiles of 70 extraction and 50 non extraction Class I and II Caucasian patients . The sample s were similar at the outset ; however , at the end of treatment , the extraction patients ' faces were , on average , 1.8 mm " flatter " than the faces of non extraction subjects . The flatter faces were preferred by both panels , dentists more so than laypersons . In general , non extraction treatment was seen as having little effect on the profile , whereas the perceived effect of extraction treatment was a statistically significant function of initial soft tissue protrusion-the greater the initial protrusion , the greater the benefit . The point at which a reduction in protrusion produces a perceived improvement was explored by way of regression analysis . Both panels saw extraction as being potentially beneficial when the lips were more protrusive than 2 to 3 mm behind Ricketts ' E-plane . It is concluded that extraction treatment can produce improved facial esthetics for many patients who present with some combination of crowding and protrusion Aim : It was the aim of this clinical study to compare the skeletal and dentoalveolar effects as well as those on the profile of three different treatment approaches in Class II patients ( camouflage orthodontics , dentofacial orthopedics , and combined orthodontic and surgical treatment ) . Patients and Method : Our study cohort consisted of 60 young adults presenting a skeletal Class II , Division 1 malocclusion : 20 patients whose overjet was reduced by camouflage following premolar extraction , 20 patients whose occlusions were corrected by placement of a fixed functional orthopedic appliance , and 20 who underwent orthognathic surgery ( bilateral sagittal split osteotomy of the m and ible without genioplasty ) . We documented the therapeutic progress using cephalometry . Results : Each patient group achieved a reduction in overjet via their respective treatment . While no treatment-related changes in the maxillary area were assessable , the effects on the m and ible differed . We observed advancement of the bony chin and an increase in m and ibular length in the sagittal-diagonal dimension in the surgical and functional orthopedic groups . However , the extent of the treatment-related changes was significant only in the group of patients that had undergone orthognathic surgery . Only the surgical group presented changes in vertical relationships . Incisor repositioning as an outcome of the respective treatments differed fundamentally , with those in the surgical group revealing significant protrusion of the upper incisors . The maxillary incisors were retruded and m and ibular incisors proclined in the functional orthopedic group , whereas the upper and lower incisors both retruded significantly in the extraction group . Softtissue remodeling bore no linear relationship to treatment-induced skeletal and dental effects . Still , orthognathic surgery led to the most marked profile changes . Treatment using fixed functional orthopedic appliances reduced the convexity of the soft-tissue profile at least moderately . Camouflage orthodontics , on the other h and , result ed in an increase in the nasolabial angle . Conclusions : In young adults fixed functional appliances are a treatment alternative to extraction therapy but to a lesser extent to orthognathic surgery . Because of their limited skeletal effects and minor changes in the profile they are indicated only in patients with a moderately severe Class II malocclusion . Pre-treatment proclined m and ibular incisors limit the scope of indications for fixed functional appliances , as they can cause an increase in lower incisor proclination . Significant reductions in profile convexity are achievable only by combined orthodontic and surgical treatment of the malocclusion . When performing camouflage orthodontics in conjunction with maxillary premolar extraction s in adults , an increase in the nasolabial angle , which is often esthetically undesirable , has to be discussed as a potential side effect and has to be taken into account when considering the different therapeutic approaches . ZusammenfassungZiel : Ziel einer klinischen Studie war es , skelettale und dentoalveoläre Effekte sowie Auswirkungen auf das Profil bei drei unterschiedlichen Beh and lungen von Distalbisslagen ( Camouflage-Orthodontie , dentofaziale Orthopädie , Kombinationsbeh and lung Orthodontie und Dysgnathiechirurgie ) zu vergleichen . Patienten und Method e : Das Prob and engut umfasste 60 junge Adulte mit einer skelettalen Klasse-II/1-Anomalie : 20 Patienten , bei denen nach Prämolarenextraktionen durch Camouflage-Orthodontie die sagittale Frontzahnstufe verringert wurde , 20 Patienten , bei denen ein festsitzendes funktionskieferorthopädisches Gerät zur Korrektur der Bisslagen eingegliedert wurde , sowie 20 Dysgnathiechirurgiefälle ( bilaterale sagittale Spaltosteotomie der M and ibula ohne Genioplastik ) . Die Beh and lungsverläufe wurden kephalometrisch dokumentiert . Ergebnisse : Bei allen Patientengruppen konnte infolge der jeweiligen Beh and lung eine Reduktion der sagittalen Frontzahnstufe erreicht werden . Während keine therapiebedingten Veränderungen i m maxillären Bereich evaluiert werden konnten , differierten die Effekte auf die M and ibula : Vorverlagerungen des knöchernen Kinns und Längenzunahmen der M and ibula in sagittal-diagonaler Richtung waren bei den Patienten der Chirurgie- und der Funktionskieferorthopädie-(FKO-)Gruppe nachweisbar , jedoch war das Ausmaß der therapeutischen Veränderung nur in der Gruppe der dysgnathiechirurgisch beh and elten Patienten signifikant . Veränderungen der vertikalen Relation f and en lediglich in der Chirurgiegruppe statt . Die infolge der jeweiligen Beh and lung result ierenden Positionsveränderungen der Schneidezähne unterschieden sich grundlegend : Eine signifikante Protrusion der oberen Schneidezähne konnte bei den Patienten der Chirurgiegruppe festgestellt werden . In der FKO-Gruppe wurden die oberen Inzisivi retrahiert und die unteren Schneidezähne nach labial gekippt . In der Extraktionsgruppe hingegen wurden beide Schneidezahnpartien signifikant retrahiert . Die Weichgewebeadaptationen st and en in keinem linearen Zusammenhang zu den therapeutisch erzielten skelettalen und dentalen Effekten . Dennoch result ierten infolge der Dysgnathiechirurgie die ausgeprägtesten Veränderungen des Profils . Durch eine Beh and lung mit festsitzenden funktionskieferorthopädischen Geräten erfuhr auch das Weichteilprofil eine zumindest moderate Konvexitätsreduzierung . Eine Camouflage-Orthodontie hingegen führte insbesondere zu einer Vergrößerung des Nasolabialwinkels . Schlussfolgerungen : Aufgrund der nur eingeschränkten skelettalen Wirkungen und der geringen Auswirkungen auf das Profil sind festsitzende funktionskieferorthopädische Geräte bei jungen Adulten eine therapeutische Alternative zur Extraktionstherapie , weniger zur Dysgnathiechirurgie und nur bei Patienten mit einer moderat ausgeprägten Klasse-II-Anomalie indiziert . Eine bereits prätherapeutisch vorh and ene Protrusion der Unterkieferfront stellt aufgrund einer therapiebedingten Progredienz eine Indikationseinschränkung für festsitzende funktionskieferorthopädische Geräte dar . Eine signifikante Reduktion der Profilkonvexität kann nur infolge einer kombiniert orthodontisch-dysgnathiechirurgischen Beh and lung erzielt werden . Bei Durchführung einer Camouflage-Orthodontie mit Extraktion von Prämolaren des Oberkiefers muss bei Erwachsenen eine ästhetisch oft unerwünschte Vergrößerung des Nasolabialwinkels als mögliche Nebenwirkung diskutiert und bei differentialtherapeutischen Überlegungen beachtet werden High- quality research should form the basis of all clinical practice . R and omized controlled trials currently provide the gold st and ard for investigating the effectiveness of treatment interventions and these are increasingly being used in orthodontics . Here we discuss the reasons why this form of investigation provides the most useful evidence for assessing treatment outcome . The methods available to achieve true r and omization , a fundamental component in the design of these trials , are also discussed . In addition , we focus on how to minimize bias in clinical research , not only during the design and management of a trial , but also when disseminating results . We focus on the importance of using control groups correctly and describe methods that are available to adequately power a trial . Finally , we emphasise the importance of accurate and transparent reporting , which facilitates correct communication and assessment of the evidence OBJECTIVE To develop models for predicting changes in lip position of Class I extraction patients . MATERIAL S AND METHODS Pretreatment and posttreatment lateral cephalograms of 46 white female adults and 109 white female adolescents were examined . Mean pretreatment ages for the adolescent and adult groups were 12.2 + /- 1.2 years and 23.0 + /- 8.5 years , respectively . Subjects were treated with conventional edgewise mechanics . Multivariate prediction models were derived from a r and omly selected sample of 119 subjects and vali date d on the remaining 36 subjects . RESULTS Adolescents demonstrated significant vertical and horizontal skeletal growth and treatment changes , while adults showed only small increases in anterior face height . While significant retraction of the upper and lower incisors occurred in both groups , the amounts were greater in adults than in adolescents . Ratios for horizontal hard tissue to soft tissue movements ranged from 1.4:1 to 1.1:1 and 1.3:1 to 1:1 for the upper ( Ls ) and lower ( Li ) lips , respectively . There were moderate relationships between horizontal lip and underlying hard tissue movements ( correlations ranged from .57 to .78 for Ls and from .58 to .86 for Li ) . Multiple regressions to predict lip movements showed moderately strong relationships for the upper lip ( R = .79 to .81 ) and strong relationships for the lower lip ( R = .89 to .90 ) . Two to three variables were necessary to predict vertical lip movements ( R = .82 to .87 ) . The validation sample showed no systematic biases and similar levels of accuracy . CONCLUSIONS Upper and lower lip retraction in four first premolar extraction cases can be predicted with moderately high levels of accuracy in white female adolescents and adults |
10,549 | 27,682,208 | Racial/ethnic differences in experimental pain sensitivity were more pronounced with suprathreshold than with threshold stimuli , which is important in clinical pain treatment . | Abstract Our objective was to describe the racial and ethnic differences in experimental pain sensitivity . | OBJECTIVE Studies have shown that perceived racial discrimination is a significant predictor of clinical pain severity among African Americans . It remains unknown whether perceived racial discrimination also alters the nociceptive processing of painful stimuli , which , in turn , could influence clinical pain severity . This study examined associations between perceived racial discrimination and responses to noxious thermal stimuli among African Americans and non-Hispanic Whites . Mistrust of medical research ers was also assessed given its potential to affect responses to the noxious stimuli . METHOD One-hundred and 30 ( 52 % African American , 48 % non-Hispanic White ) community-dwelling older adults with symptomatic knee osteoarthritis completed two study sessions . In session one , individuals provided demographic , socioeconomic , physical and mental health information . They completed question naires related to perceived lifetime frequency of racial discrimination and mistrust of medical research ers . In session two , individuals underwent a series of controlled thermal stimulation procedures to assess heat pain sensitivity , particularly heat pain tolerance . RESULTS African Americans were more sensitive to heat pain and reported greater perceived racial discrimination as well as greater mistrust of medical research ers compared with non-Hispanic Whites . Greater perceived racial discrimination significantly predicted lower heat pain tolerance for African Americans but not non-Hispanic Whites . Mistrust of medical research ers did not significantly predict heat pain tolerance for either racial group . CONCLUSION These results lend support to the idea that perceived racial discrimination may influence the clinical pain severity of African Americans via the nociceptive processing of painful stimuli In Malaysia , it is a common belief among health care workers that females and Indians have lower pain threshold . This experience , although based on anecdotal experience in the healthcare setting , does not allow differentiation between pain tolerance , and pain expression . To determine whether there is a difference in the tolerance to pain between the three main ethnic groups , namely the Malays , Chinese and Indians as well as between males and females . This was a prospect i ve study , using a laboratory pain model ( ischaemic pain tolerance ) to determine the pain tolerance of 152 IMU medical students . The mean age of the students was 21.8 years ( range 18 - 29 years ) . All of them were unmarried . The median of ischaemic pain tolerance for Malays , Chinese and Indians were 639s , 695s and 613s respectively ( p = 0.779 ) . However , statistically significant difference in ischaemic pain tolerance for males and females Indian students were observed . Possible ethnic difference in pain tolerance in casual observation is not verified by this laboratory pain model . Difference in pain tolerance between genders is shown only for Indians Abstract The aim of this study was to examine experimental pain sensitivity in three ethnic groups , African Americans , Hispanic Americans and non‐Hispanic White Americans , and to determine whether ethnic identity is differentially associated with pain sensitivity across ethnic groups . Participants included sixty‐three African American , sixty‐one Hispanic and eighty‐two non‐Hispanic white participants who were assessed using three experimental pain measures : thermal , cold‐pressor and ischemic . Participants ’ ethnic identity was assessed using the Multi‐group Ethnic Identity Measure ( MEIM ) . Ethnic group differences in pain responses were observed , with African American and Hispanic subjects showing lower cold and heat pain tolerances than non‐Hispanic White Americans . In addition , pain range ( i.e. tolerance‐threshold ) was computed for heat , cold and ischemic pain , and the two minority groups again had lower values compared to non‐Hispanic White Americans . Ethnic identity was associated with pain range only for African American and Hispanic groups . Statistically controlling for ethnic identity rendered some of the group differences in pain range non‐significant . These findings indicate that ethnic identity is associated with pain sensitivity in ethnic minority groups , and may partially mediate group differences in pain perception . The results of the present investigation provide evidence of ethnic group differences in responses to experimental pain across multiple noxious stimuli , with both minority groups exhibiting greater sensitivity to laboratory evoked pain compared to non‐Hispanic White Americans & NA ; Ethnic differences in the experience of pain , pain‐related health care utilization and pain‐reducing activities have been reported . Thus , evaluating of such variations is important in clinical and experimental pain . Since clinical pain is greatly influenced by disease‐specific factors ( severity , duration , type and treatment ) , evaluating ethnic differences in experimental pain models may not only provide some information about underlying mechanisms but also may predict or explain group differences in clinical pain . Migraine prevalence within ethnic population s is varied . Capsaicin injection to the forehead of healthy volunteers induces the state of an experimental trigeminal sensitization , which is one of the proposed mechanisms of migraine . The aim of the present study was to investigate ethnic differences between Caucasians and South Indians in this model of trigeminal sensitization . Thirty‐two healthy male volunteers ( 16 South Indians and 16 Danish Caucasians ) were included . Capsaicin ( 100 μg/0.1 ml ) was injected intradermally to the right forehead skin . Pain sensitivity , secondary hyperalgesic area , and pressure pain threshold were assessed . Overall , the model showed significant greater pain responses in South Indians ( 8.75±1.25 cm pain intensity and 9.33±2.32 cm2 hyperalgesic area ) compared to Caucasians ( 6.25±1.95 cm pain intensity and 6.25±1.41 cm2 hyperalgesic area ) . The model may provide important information for further clinical research , e.g. migraine or differences in mechanisms underlying trigeminal sensitization OBJECTIVE A growing body of literature suggests ethnic differences in experimental pain . However , these studies largely focus on adults and the comparison between Caucasians and African Americans . The primary aim of this study is to determine ethnic differences in laboratory-induced pain in a multiethnic child sample . METHOD Participants were 214 healthy children ( mean age = 12.7 , SD = 3.0 years ) . Ninety-eight Caucasian , 58 Hispanic , 34 African American , and 24 Asian children were exposed to four trials of pressure and radiant heat pain stimuli . Pain responses were assessed with self-report measures ( i.e. , pain intensity and unpleasantness ) and behavioral observation ( i.e. , pain tolerance ) . RESULTS Asians demonstrated more pain sensitivity than Caucasians , who evidence d more pain sensitivity than African Americans and Hispanics . The results hold even after controlling for age , sex , SES , and experimenter 's ethnicity . Asians also showed higher anticipatory anxiety compared with other ethnic groups . Anticipatory anxiety accounted for some ethnic differences in pain between Asians , Hispanics , and African Americans . CONCLUSIONS By examining response to laboratory pain stimuli in children representing multiple ethnicities , an understudied sample , the study reveals unique findings compared to the existing literature . These findings have implication s for clinicians who manage acute pain in children from diverse ethnic background s. Future investigations should examine mechanisms that account for ethnic differences in pain during various developmental stages OBJECTIVE Although numerous studies have reported ethnic differences in the prevalence and severity of clinical pain , little is known about how these differences affect the perception of experimental pain . The present experiment examined the effects of ethnicity ( African American vs. white ) on thermal pain responses in a healthy undergraduate population . METHODS Thirty white subjects ( 16 women and 14 men ) and 18 African Americans ( 10 women and 8 men ) participated in the study . Thermal testing included evaluation of the following : warmth thresholds , thermal pain thresholds , thermal pain tolerances , and magnitude estimates of both the intensity and unpleasantness of thermal pain ( at 46 degrees , 47 degrees , 48 degrees , and 49 degrees C ) . RESULTS Although no group differences emerged for warmth thresholds , thermal pain thresholds , or pain intensity ratings , African Americans demonstrated lower thermal pain tolerances than whites . In addition , African Americans had smaller slopes and larger intercepts than whites for ratings of pain unpleasantness . Additional analyses suggested that these findings were a consequence of group differences in thermal pain unpleasantness ratings at the lowest temperatures assessed ( 46 degrees and 47 degrees C ) ; at these temperatures , African Americans rated the stimuli as more unpleasant than whites . Finally , group differences in thermal pain tolerance and thermal pain unpleasantness ratings seemed to partially account for greater self-reported daily pain symptoms among African Americans . CONCLUSIONS Collectively , these findings seem to suggest ethnic differences in the perception of the affective-motivational dimension of thermal pain |
10,550 | 31,413,762 | NG has been proven to reduce tumours with an acceptable toxicity profile in metastatic pancreatic cancer .
This analysis further demonstrates the efficacy and safety of NG for treating LAPC | To evaluate the effectiveness of nab-paclitaxel plus gemcitabine ( NG ) as a first-line treatment for advanced pancreatic cancer .
A meta- analysis was performed to assess the impact on the objective response rate ( ORR ) , survival rate and grade 3/4 adverse events . | Purpose The primary objective of this study was to evaluate the dose-limiting toxicities ( DLTs ) and identify the maximum-tolerated dose ( MTD ) and recommended dose of nab-paclitaxel plus gemcitabine as a first-line treatment in Chinese patients with advanced pancreatic ductal adenocarcinoma ( PDA ) . Methods Patients with previously untreated advanced PDA were treated with nab-paclitaxel followed by gemcitabine ( 1,000 mg/m2 ) administered intravenously for 30 min on days 1 and 8 and repeated every 21 days . Results Patients received nab-paclitaxel at the following dose levels : 80 mg/m2 ( n = 3 ) , 100 mg/m2 ( n = 6 ) , and 120 mg/m2 ( n = 12 ) . The DLTs evaluated were elevated alanine aminotransferase and febrile neutropenia . However , there had no two out of three to six patients experienced DLTs , the MTD was not met . A total of 93 cycles were administered . The most common grade 3/4 toxicities were neutropenia ( 9.52 % ) , thrombocytopenia ( 4.76 % ) , and sensory neuropathy ( 4.76 % ) . For 12 patients receiving 120 mg/m2 , the overall response rate and disease control rate were 41.67 and 83.33 % , respectively , and the median progression-free survival and overall survival were 5.23 and 12.17 months , respectively . Conclusions Treatment with albumin-bound nab-paclitaxel ( 120 mg/m2 ) plus gemcitabine has a favorable safety profile with an encouraging antitumor effect in Chinese patients BACKGROUND Pancreas adenocarcinoma is the sixth cause of cancer-related death worldwide with an increasing mortality in the Western countries . Recently , the association between nab-paclitaxel ( nab-P ) and gemcitabine ( GEM ) has significantly improved progression-free and overall survival . PATIENTS AND METHODS Patients affected by metastatic pancreas adenocarcinoma were treated at the Department of Abdominal Oncology of the National Cancer Institute of Naples from July 2015 to July 2016 with nab-P at 125 mg per square meter of body-surface area followed by GEM at 1,000 mg per square meter on days 1 , 8 and 15 every 4 weeks . Computed tomography ( CT ) was performed every three months of therapy . Toxicity was grade d with National Cancer Institute-Common Toxicity Criteria ( NCI-CTC ) v4.0 . Objective responses were evaluated with Response Evaluation Criteria in Solid Tumors ( RECIST ) . Analysis of time-to-progression is only descriptive . Pain was evaluated with a visual analogue scale ( VAS ) . RESULTS Twenty-three patients were treated . Median age was 67 years ( range=45 - 81 ) ; 8 patients were ≥70 years old . Performance status ( PS ) Eastern Cooperative Oncology Group ( ECOG ) was 2 in 8 patients , 1 in 10 and 0 in 5 . Twelve patients presented with diffuse hepatic metastases , 4 with carcinosis , 7 with more than one organ involvement . Nab-P was reduced at 100 mg per square meter in all patients . The most common G3/G4 adverse events were neutropenia ( 13.0 % G4 , 8.6 % G3 ; none was febrile ) , neuropathy ( 30.4 % G3 ) and asthenia ( G3 17.3 % ) . The disease control rate was 43.4 % ( partial response+stable disease ( PR+SD ) 10/23 ) . The median time-to-progression was 7.9 months ( 95 % confidence interval (CI)=5.8 - 11.2 ) . After three months of therapy the PS improved in 14 patients , as well as pain in 18 patients . CONCLUSION We present an experience with nab-P and GEM association in a series with poor PS and highly metastatic disease relatively to a previous r and omized study . The schedule is feasible , with nab-P at 100 mg per square meter achieving a good disease control rate , as well as a clinical benefit Background The LAP07 r and omized trial calls into question the role of radiation therapy ( RT ) in the modern treatment of locally advanced pancreatic cancer ( LAPC ) . However , advances in chemotherapy and RT limit application of the LAP07 results to current clinical practice . Here we utilize the National Cancer Data base ( NCDB ) to evaluate the effects of RT in patients receiving chemotherapy for LAPC . Methods Using the NCDB , patients with American Joint Committee on Cancer ( AJCC ) clinical stage T2–4 , N0–1 , M0 adenocarcinoma of the pancreas from 2004 to 2014 were analyzed . Patients were stratified into chemotherapy only ( CT ) and chemoradiation ( CRT ) cohorts . Patients undergoing definitive RT , defined as at least 20 fractions or ≥ 5 Gy per fraction [ i.e. , stereotactic body radiation therapy ( SBRT ) ] were included in the CRT cohort . Propensity-score matching ( PSM ) and l and mark analysis were used to address selection bias and lead-time bias , respectively . Results 13,004 patients met inclusion criteria , of whom 7034 ( 54 % ) received CT and 5970 ( 46 % ) received CRT . After PSM , 5215 patients remained in each cohort . The CRT cohort demonstrated better overall survival ( OS ) compared with CT alone , with median and 1-year OS of 12 versus 10 months , and 50 % and 41 % , respectively ( p < 0.001 ) . On multivariable analysis , CRT was associated with superior OS with hazard ratio of 0.79 ( 95 % confidence interval 0.76–0.83 ) compared with CT alone . Conclusions In our series , addition of definitive radiotherapy to CT was associated with better OS when compared with CT alone in LAPC . Definitive radiotherapy should remain a treatment option for LAPC , but optimal selection criteria remain unclear Purpose For unresectable locally advanced ( UR-LA ) pancreatic cancer , chemoradiotherapy has been recommended by the NCCN guidelines . We design ed a chemoradiotherapy protocol using nab-paclitaxel combined with gemcitabine ( GnP ) for patients with UR-LA pancreatic cancer . The purpose of this phase I study was to determine a recommended dose ( RD ) for this novel regimen . Methods Patients with UR-LA pancreatic cancer were eligible . The frequency of dose-limiting toxicities ( DLTs ) was evaluated , and the RD was determined . Patients were classified according to the design ated dose levels of chemoradiotherapy using the GnP regimen . After additional 6 cycles of the GnP regimen were administered , surgery was considered if the patients had stable disease and tumor marker levels had normalized . Results DLT ( grade 4 thrombocytopenia ) was observed only in 1 of 12 patients , and the RD was set at level 3 . Grade 3–4 leukopenia was observed in 9 ( 75.0 % ) patients , and neutropenia in 7 ( 58.3 % ) . The response rate was 41.7 % , and the disease control rate was 100 % . Conversion surgery was performed in 6 ( 50 % ) patients , and curative resection ( R0 ) was performed in all 6 patients ( 100 % ) . Stratification according to the Evans classification system demonstrated one patient with grade 1b , one with grade 2 , two with grade 3 , and two with grade 4 disease . Conclusion The RD for weekly administration was 800 mg/m2 for gemcitabine and 100 mg/m2 for nab-paclitaxel with a 50.4 Gy radiation . The GnP regimen at this dosage was promising with 6 of 12 patients proceeding to conversion surgery , and should be evaluated further in a phase II trial BACKGROUND In a phase 1 - 2 trial of albumin-bound paclitaxel ( nab-paclitaxel ) plus gemcitabine , substantial clinical activity was noted in patients with advanced pancreatic cancer . We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer . METHODS We r and omly assigned patients with a Karnofsky performance-status score of 70 or more ( on a scale from 0 to 100 , with higher scores indicating better performance status ) to nab-paclitaxel ( 125 mg per square meter of body-surface area ) followed by gemcitabine ( 1000 mg per square meter ) on days 1 , 8 , and 15 every 4 weeks or gemcitabine monotherapy ( 1000 mg per square meter ) weekly for 7 of 8 weeks ( cycle 1 ) and then on days 1 , 8 , and 15 every 4 weeks ( cycle 2 and subsequent cycles ) . Patients received the study treatment until disease progression . The primary end point was overall survival ; secondary end points were progression-free survival and overall response rate . RESULTS A total of 861 patients were r and omly assigned to nab-paclitaxel plus gemcitabine ( 431 patients ) or gemcitabine ( 430 ) . The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group ( hazard ratio for death , 0.72 ; 95 % confidence interval [ CI ] , 0.62 to 0.83 ; P<0.001 ) . The survival rate was 35 % in the nab-paclitaxel-gemcitabine group versus 22 % in the gemcitabine group at 1 year , and 9 % versus 4 % at 2 years . The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group , as compared with 3.7 months in the gemcitabine group ( hazard ratio for disease progression or death , 0.69 ; 95 % CI , 0.58 to 0.82 ; P<0.001 ) ; the response rate according to independent review was 23 % versus 7 % in the two groups ( P<0.001 ) . The most common adverse events of grade 3 or higher were neutropenia ( 38 % in the nab-paclitaxel-gemcitabine group vs. 27 % in the gemcitabine group ) , fatigue ( 17 % vs. 7 % ) , and neuropathy ( 17 % vs. 1 % ) . Febrile neutropenia occurred in 3 % versus 1 % of the patients in the two groups . In the nab-paclitaxel-gemcitabine group , neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days . CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma , nab-paclitaxel plus gemcitabine significantly improved overall survival , progression-free survival , and response rate , but rates of peripheral neuropathy and myelosuppression were increased . ( Funded by Celgene ; Clinical Trials.gov number , NCT00844649 . ) PURPOSE To provide evidence -based recommendations to oncologists and others for treatment of patients with locally advanced , unresectable pancreatic cancer . METHODS American Society of Clinical Oncology convened an Expert Panel of medical oncology , radiation oncology , surgical oncology , gastroenterology , palliative care , and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015 . Outcomes included overall survival , disease-free survival , progression-free survival , and adverse events . RESULTS Twenty-six r and omized controlled trials met the systematic review criteria . RECOMMENDATIONS A multiphase computed tomography scan of the chest , abdomen , and pelvis should be performed . Baseline performance status and comorbidity profile should be evaluated . The goals of care , patient preferences , psychological status , support systems , and symptoms should guide decisions for treatments . A palliative care referral should occur at first visit . Initial systemic chemotherapy ( 6 months ) with a combination regimen is recommended for most patients ( for some patients radiation therapy may be offered up front ) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile . There is no clear evidence to support one regimen over another . The gemcitabine-based combinations and treatments recommended in the metastatic setting ( eg , fluorouracil , leucovorin , irinotecan , and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel ) have not been evaluated in r and omized controlled trials involving locally advanced , unresectable pancreatic cancer . If there is local disease progression after induction chemotherapy , without metastasis , then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile . If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities , radiation therapy may be offered as an alternative . Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline . Follow-up visits every 3 to 4 months are recommended . Additional information is available at www.asco.org/ guidelines /LAPC and www.asco.org/ guidelines /MetPC and www.asco.org/ guidelines wiki LBA4003 Background : CRT in patients with LAPC controlled after induction CT could be superior to continuing CT ( Huguet , JCO 2007 ) . The role of erlotinib is unknown . We aim ed to define the role of 1 ) CRT after disease control with gemcitabine , 2 ) erlotinib in LAPC . METHODS LAPC PS 0 - 2 patients were first r and omized to gemcitabine alone or plus erlotinib 100 mg/d for 4 months ( R1 , stratification : center , PS ) . Patients with controlled disease were then r and omized to 2 additional months of CT ( Arm 1 ) or CRT ( Arm 2 ) 54 Gy and capecitabine 1600 mg/m2/d ( R2 , stratification : center , initial arm ) . Patients receiving erlotinib at R1 had maintenance with this drug after protocol completion . Quality control for radiotherapy included dummy runs and assessment of treated patients . PRIMARY OBJECTIVE overall survival ( OS ) in R2 patients . Secondary objectives : role of erlotinib on OS ( R1 ) , tolerance , predictive markers , and circulating tumor cells . Taking into account a 30 % progression rate between R1 and R2 , and 5 % lost to follow-up , 722 patients were required to observe 392 deaths to show a median OS increase from 9 to 12 m ( HR=0.75 ) in the CRT arm ( 2 sided α=5 % and β=20 % ) with planned interim analyses using alpha spending function and O'Brien Fleming boundaries ( to reject H0 or H1 ) . Kaplan-Meier , log rank and univariate Cox tests were used . RESULTS From 442 pts included for R1 , 269 pts reached R2 ( arm1:136 ; arm 2:133 ) . Main baseline characteristics in arms 1/2 : female 44%/56 % , mean age 63/62 , head tumor 65%/62 % , PS 0 56%/48 % . After a median follow-up of 36 m , 221 deaths had occurred allowing the planned interim analysis ( information fraction 56.4 % ) . OS in R2 pts was 16.5 m [ 15.5 - 18.5 ] and 15.3 m [ 13.9 - 17.3 ] in arms 1 and 2 , respectively ( HR=1.03 [ 0.79 - 1.34 ] , p=0.83 ) . IDMC has confirmed that the futility boundary for the hypothesis of CRT superiority was crossed and considered this as the final analysis of the study . CONCLUSIONS Administering CRT is not superior to continuing CT in patients with controlled LAPC after 4 months of CT . CLINICAL TRIAL INFORMATION NCT00634725 Background Both FOLFIRINOX and gemcitabine/nab-paclitaxel ( G-nP ) are used increasingly in the neoadjuvant treatment ( NAT ) of pancreatic ductal adenocarcinoma ( PDA ) . This study aim ed to compare neoadjuvant FOLFIRINOX and G-nP in the treatment of resectable ( R ) and borderline resectable ( BR ) head PDA . Methods A single-institution retrospective review of R and BR patients undergoing pancreaticoduodenectomy after NAT with FOLFIRINOX or G-nP was performed . Comparative analysis was performed using inverse-probability-weighted ( IPW ) estimators . The end points of the study were overall survival ( OS ) and an 80 % reduction in CA19 - 9 with NAT . Results In this study , 193 patients were analyzed , with 73 patients receiving FOLFIRINOX and 120 patients receiving G-nP. The median OS was 38.7 months for FOLFIRINOX versus 28.6 months for G-nP ( p = 0.214 ) . The patients who received FOLFIRINOX were younger and had fewer comorbidities , more BR disease , and larger tumors than those treated with G-nP ( all p < 0.05 ) . The two regimens were equally effective in achieving an 80 % decline in CA19 - 9 ( p = 0.8 ) . The R0 resection rates were similar ( 80 % ) , but FOLFIRINOX was associated with a reduction in pN1 disease ( 56 % vs. 72 % ; p = 0.028 ) . The receipt of adjuvant therapy was similar ( 74 vs. 75 % ; p = 0.79 ) . In the Cox regression analysis with adjustment for baseline and treatment-related variables ( FOLFIRINOX vs. G-nP , age , gender , computed tomography ( CT ) tumor size , BR vs. R , pre-NAT CA19 - 9 ) , regimen type was not associated with a survival benefit . In the IPW analysis of 166 patients , however , the average treatment effect of FOLFIRINOX was to increase OS by 4.9 months compared with G-nP ( p = 0.012 ) . Conclusions Both FOLFIRINOX and G-nP are viable options for neoadjuvant treatment of PDA . In this study , neoadjuvant FOLFIRINOX was associated with a 4.9-month improvement in survival compared with G-nP after adjustment for covariates |
10,551 | 28,756,617 | Adverse effects were not reported but there was possible increased risk of skin rashes in the multivitamin group .
Adverse effects were not consistently reported in these eye studies , but there is evidence from other large studies that beta-carotene increases the risk of lung cancer in people who smoke or who have been exposed to asbestos .
None of the studies reported quality of life or re source use and costs .
AUTHORS ' CONCLUSIONS Taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD .
There is no evidence with respect to other antioxidant supplements , such as lutein and zeaxanthin .
Although generally regarded as safe , vitamin supplements may have harmful effects , and clear evidence of benefit is needed before they can be recommended . | BACKGROUND There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins ( carotenoids , vitamins C , and E ) or minerals ( selenium and zinc ) may be less likely to develop age-related macular degeneration ( AMD ) .
OBJECTIVES To determine whether or not taking antioxidant vitamin or mineral supplements , or both , prevent the development of AMD . | In the Physicians ' Health Study , a r and omized , placebo-controlled , double-blind trial of aspirin in the reduction of cardiovascular mortality and beta-carotene in decreasing cancer incidence , 33,223 subjects were eligible and willing to enter the trial . Instead of r and omizing this group immediately , all participants received identical calendar packs that contained active aspirin and beta-carotene placebo . Following an 18-week run-in , only 22,071 subjects who remained eligible and willing and had taken at least 2/3 of their pills were r and omized . We estimated the effect of the run-in as follows : pill taking compliance increased 20 - 41 per cent ; sample size decreased 34 per cent ; duration of follow-up decreased 7 per cent which result ed in a 7 per cent decrease in the expected event rate for the placebo group . To estimate these changes , we made assumptions about compliance and outcome risk for those excluded by the run-in . Our conclusion , however , about the net effect of the run-in on the power of the study remains constant across variations in a number of those assumptions . The power with the run-in , with 22,071 good compliers was typically higher , and never more than negligibly lower , than the power without the run-in , with 33,223 good and poor compliers . In addition , savings from enrolling 11,152 fewer subjects in the trial result ed from the use of the run-in Abstract Nine VA Medical Centers are participating in a 2-year double-blind placebo controlled study of antioxidant treatment for tardive dyskinesia ( TD ) conducted by the Department of Veteran Affairs Cooperative Studies Program . One of the principal outcome measures of this study is the score derived from the instrumental assessment of upper extremity dyskinesia . Dyskinetic h and movements are quantified by assessing the variability associated with steady-state isometric force generated by the patient . In the present report , we describe the training procedures and results of a multi-center reliability assessment of this procedure . Data from nine study centers comprising 45 individual patients with six trials each ( three from left h and and three from right h and ) were reanalyzed by an independent investigator and the results were subjected to reliability assessment . For the statistic of interest ( average coefficient of variation over trials 2 and 3 for each h and , then take the larger of these two values ) , we found very high intraclass correlation coefficients for reliability over all patients across sites ( ICC = 0.995 ) . We also calculated the reliability of the measures across trials within patient for each combination of h and ( right , left , dominant ) , rater group ( site , control ) , and trials set ( all three , trials 2 and 3 ) . For a given h and and trial set , the reliability of the site raters was similar to that of the control . This study demonstrates that instrumental measures for the assessment of dyskinesia are reliable and can be implemented in multi-center studies with minimal training BACKGROUND Even though dietary fiber has been hypothesized to reduce the risk of coronary heart disease , few large epidemiological studies have examined this relation with good methodology . METHODS AND RESULTS The Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study was a r and omized , double-blind , placebo-controlled trial with daily supplementation of alpha-tocopherol and /or beta-carotene . Of the participants , 21930 smoking men aged 50 to 69 years who were free of diagnosed cardiovascular disease and had completed a vali date d dietary question naire at baseline were followed for 6.1 years . We monitored the incidence of major coronary events ( a combination of first nonfatal myocardial infa rct ion and coronary heart disease death ; n = 1399 ) and mortality from coronary heart disease ( n = 635 ) . Both entities had a significant inverse association with dietary fiber , but the association was stronger for coronary death . For men in the highest quintile of total dietary fiber intake ( median , 34.8 g/d ) , the relative risk for coronary death was 0.69 ( 95 % confidence interval , 0.54 to 0.88 ; P < .001 for trend ) compared with men in the lowest quintile of intake ( median , 16.1 g/d ) . With an adjustment for known cardiovascular risk factors , intake of saturated fatty acids , beta-carotene , vitamin C , and vitamin E did not material ly change the result . Water-soluble fiber was slightly more strongly associated with reduced coronary death than water-insoluble fiber , and cereal fiber also had a stronger association than vegetable or fruit fiber . CONCLUSIONS These findings suggest that independent of other risk factors , greater intake of foods rich in fiber can substantially reduce the risk of coronary heart disease , and particularly coronary death , in middle-aged , smoking men Although administration of zinc to human subjects has been reported to interfere with lymphocyte function , this single report has never been confirmed or refuted . We have developed zinc as a lifelong therapy for patients with Wilson 's disease . Interference with lymphocyte function occurring as a side effect of zinc therapy could produce serious problems in our patients . We evaluated lymphocyte mitogenic response and natural killer cell activity in patients with Wilson 's disease treated for 5 years or longer with zinc , in comparison with normal controls , and found no differences . In a second study , we evaluated these same parameters in patients with Wilson 's disease before and after 1 year of zinc therapy , and again found no significant differences . We have seen no indications of immune suppression or increased susceptibility to infections in our patients , who have now been treated with zinc for up to 15 years . We conclude that any side effects from compromised lymphocyte function caused by administration of zinc are not of concern to patients with Wilson 's disease The purpose of this study was to evaluate the effect of selenium ( Se ) in the prevention of human primary liver cancer . Three intervention trials were conducted among the residents at high risk to primary liver cancer ( PLC ) in Qidong county , Jiang-su province , the People ’s Republic of China . This area has the second highest rate of PLC in China . One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite ( Se-salt ) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt . The second trial was undertaken among hepatitis B virus surface antigen carriers ( HBVsAg+ ) receiving supplement of 200 μg Se in form of selenized , yeast ( Se-yeast ) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast ( 200 μg of Se daily ) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly Purpose The high concentration of carotenoids in the macula , plus evidence linking oxidative stress to age-related macular degeneration ( AMD ) and carotenoids to antioxidation , generated the hypothesis that higher antioxidant intakes can prevent AMD . The aim of this study was to determine whether nutritional supplementation with a targeted nutritional supplement improves visual acuity and visual function in AMD . Methods In this multicenter , prospect i ve open-label r and omized study , 145 patients were r and omly assigned to 2 different treatment groups . Interventions were lutein ( 10 mg ) , zeaxanthin ( 1 mg ) , astaxanthin ( 4 mg ; AZYR SIFI , Catania , Italy ) , and antioxidants/vitamins supplementation formula or no dietary supplementation for 2 years . Primary outcome was mean changes in visual acuity ( VA ) at 12 and 24 months . Other measures included contrast sensitivity ( CS ) and National Eye Institute visual function question naire ( NEI VFQ-25 ) scores at 12 and 24 months . Results Patients in the treated group showed stabilization of VA with significantly ( p=0.003 ) better VA scores ( 81.4±7.2 ) compared to the nontreated group ( 76.8±8.9 ) at 24-month follow-up . An improvement in CS ( p=0.001 ) and final mean NEI VFQ-25 composite scores at 12 and 24 months higher in treated group compared to nontreated group were also shown ( p<0.001 ) . Conclusions Patients treated with lutein/zeaxanthin and astaxanthin together with other nutrients were more likely to report clinical ly meaningful stabilization/improvements in VA , CS , and visual function through 24 months compared with nontreated subjects . Further studies are needed with more patients and for longer periods of time Ageing is associated with impaired immune responses and increased infection-related morbidity . This study assessed the effect of physiological amounts of vitamins and trace elements on immunocompetence and occurrence of infection-related illness . 96 independently living , healthy elderly individuals were r and omly assigned to receive nutrient supplementation or placebo . Nutrient status and immunological variables were assessed at baseline and at 12 months , and the frequency of illness due to infection was ascertained . Subjects in the supplement group had higher numbers of certain T-cell subsets and natural killer cells , enhanced proliferation response to mitogen , increased interleukin-2 production , and higher antibody response and natural killer cell activity . These subjects were less likely than those in the placebo group to have illness due to infections ( mean [ SD ] 23 [ 5 ] vs 48 [ 7 ] days per year , p = 0.002 ) . Supplementation with a modest physiological amount of micronutrients improves immunity and decreases the risk of infection in old age OBJECTIVE To determine whether supplements of vitamin A or vitamin E alone or in combination affect the course of retinitis pigmentosa . DESIGN R and omized , controlled , double-masked trial with 2 x 2 factorial design and duration of 4 to 6 years . Electroretinograms , visual field area , and visual acuity were measured annually . SETTING Clinical research facility . PATIENTS 601 patients aged 18 through 49 years with retinitis pigmentosa meeting preset eligibility criteria . Ninety-five percent of the patients completed the study . There were no adverse reactions . INTERVENTION Patients were assigned to one of four treatment groups receiving 15,000 IU/d of vitamin A , 15,000 IU/d of vitamin A plus 400 IU/d of vitamin E , trace amounts of both vitamins , or 400 IU/d of vitamin E. MAIN OUTCOME MEASURE Cone electroretinogram amplitude . RESULTS The two groups receiving 15,000 IU/d of vitamin A had on average a slower rate of decline of retinal function than the two groups not receiving this dosage ( P = .01 ) . Among 354 patients with higher initial amplitudes , the two groups receiving 15,000 IU/d of vitamin A were 32 % less likely to have a decline in amplitude of 50 % or more from baseline in a given year than those not receiving this dosage ( P = .01 ) , while the two groups receiving 400 IU/d of vitamin E were 42 % more likely to have a decline in amplitude of 50 % or more from baseline than those not receiving this dosage ( P = .03 ) . While not statistically significant , similar trends were observed for rates of decline of visual field area . Visual acuity declined about 1 letter per year in all groups . CONCLUSIONS These results support a beneficial effect of 15,000 IU/d of vitamin A and suggest an adverse effect of 400 IU/d of vitamin E on the course of retinitis pigmentosa BACKGROUND Among apparently healthy men , elevated levels of C-reactive protein ( CRP ) , a marker for systemic inflammation , predict risk of myocardial infa rct ion and thromboembolic stroke . Whether increased levels of CRP are also associated with the development of symptomatic peripheral arterial disease ( PAD ) is unknown . METHODS AND RESULTS Using a prospect i ve , nested , case-control design , we measured baseline levels of CRP in 144 apparently healthy men participating in the Physicians ' Health Study who subsequently developed symptomatic PAD ( intermittent claudication or need for revascularization ) and in an equal number of control subjects matched on the basis of age and smoking habit who remained free of vascular disease during a follow-up period of 60 months . Median CRP levels at baseline were significantly higher among those who subsequently developed PAD ( 1.34 versus 0.99 mg/L ; P=.04 ) . Furthermore , the risks of developing PAD increased significantly with each increasing quartile of baseline CRP concentration such that relative risks of PAD from lowest ( referent ) to highest quartile of CRP were 1.0 , 1.3 , 2.0 , and 2.1 ( Ptrend=.02 ) . Compared with those with no clinical evidence of disease , the subgroup of case patients who required revascularization had the highest baseline CRP levels ( median= 1.75 mg/L ; P= .04 ) ; relative risks from lowest to highest quartile of CRP for this end point were 1.0 , 1.8 , 3.8 , and 4.1 ( Ptrend=.02 ) . Risk estimates were similar after additional control for body mass index , hypercholesterolemia , hypertension , diabetes , and a family history of premature atherosclerosis . CONCLUSIONS These prospect i ve data indicate that among apparently healthy men , baseline levels of CRP predict future risk of developing symptomatic PAD and thus provide further support for the hypothesis that chronic inflammation is important in the pathogenesis of atherothrombosis Associations between antioxidants and zinc and the 5-year incidence of early , age-related maculopathy ( ARM ) were investigated in a population -based cohort of middle-aged and older adults participating in the Beaver Dam Eye Study in Beaver Dam , Wisconsin . A food-frequency question naire was administered at baseline ( 1988 - 1990 ) to collect dietary information for that time period and a period of time 10 years earlier ( 1978 - 1980 ) from a 50 percent r and om sample of persons participating in this study . The incidence of the specific lesions of larger drusen ( > 125 microns ) and pigmentary abnormalities and the incidence of any ARM were assessed by masked grading of stereoscopic color fundus photographs in 1,709 persons who participated in 5-year follow-up eye examinations . Significant , but modest , inverse associations ( p < 0.05 ) were observed between intakes of pro-vitamin A carotenoids and dietary vitamin E and the incidence of large drusen and between zinc and the incidence of pigmentary abnormalities . No significant inverse associations were found between antioxidant or zinc intake and the incidence of overall early ARM . If ARM , which is characterized by a broad spectrum of lesions , involves a number of different underlying pathophysiologic processes , then associations between specific antioxidants and the incidence of distinct macular lesions may be biologically important . However , because there were too few incident late ARM cases in this cohort , the authors were unable to assess whether antioxidant intake is associated with the progression of early ARM to late-stage macular degeneration . Clinical trials and longer-term prospect i ve studies are needed to eluci date further the impact of antioxidants and zinc on the development and progression of ARM Seventeen months ' supplementation of the diet with vitamin C in elderly residents in an old persons ' home failed to show any changes in sublingual lesions , which on histological examination proved to be aneurysmal dilatations of the venules . Nine months ' supplementation of 40 to 80 mg . daily of vitamin C was necessary before the white-cell vitamin levels reached that found in younger people . There was a marked individual variation in response CONTEXT Multivitamin preparations are the most common dietary supplement , taken by at least one-third of all US adults . Observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality . OBJECTIVE To determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men . DESIGN , SETTING , AND PARTICIPANTS A large-scale , r and omized , double-blind , placebo controlled trial ( Physicians " Health Study II ) of 14 641 male US physicians initially aged 50 years or older ( mean [ SD ] age , 64.3 [ 9.2 ] years ) , including 1312 men with a history of cancer at r and omization , enrolled in a common multivitamin study that began in 1997 with treatment and follow-up through June 1 , 2011 . INTERVENTION Daily multivitamin or placebo . MAIN OUTCOME MEASURES Total cancer ( excluding nonmelanoma skin cancer ) , with prostate , colorectal , and other site-specific cancers among the secondary end points . RESULTS During a median ( interquartile range ) follow-up of 11.2 ( 10.7 - 13.3 ) years , there were 2669 men with confirmed cancer , including 1373 cases of prostate cancer and 210 cases of colorectal cancer . Compared with placebo , men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer ( multivitamin and placebo groups , 17.0 and 18.3 events , respectively , per 1000 person-years ; hazard ratio [ HR ] , 0.92 ; 95 % CI , 0.86 - 0.998 ; P=.04 ) . There was no significant effect of a daily multivitamin on prostate cancer ( multivitamin and placebo groups , 9.1 and 9.2 events , respectively , per 1000 person-years ; HR , 0.98 ; 95 % CI , 0.88 - 1.09 ; P=.76 ) , colorectal cancer ( multivitamin and placebo groups , 1.2 and 1.4 events , respectively , per 1000 person-years ; HR , 0.89 ; 95 % CI , 0.68 - 1.17 ; P=.39 ) , or other site-specific cancers . There was no significant difference in the risk of cancer mortality ( multivitamin and placebo groups , 4.9 and 5.6 events , respectively , per 1000 person-years ; HR , 0.88 ; 95 % CI , 0.77 - 1.01 ; P=.07 ) . Daily multivitamin use was associated with a reduction in total cancer among 1312 men with a baseline history of cancer ( HR , 0.73 ; 95 % CI , 0.56 - 0.96 ; P=.02 ) , but this did not differ significantly from that among 13 329 men initially without cancer ( HR , 0.94 ; 95 % CI , 0.87 - 1.02 ; P=.15 ; P for interaction=.07 ) . Conclusion In this large prevention trial of male physicians , daily multivitamin supplementation modestly but significantly reduced the risk of total cancer . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00270647 We showed previously that natural killer ( NK ) cell activity is significantly greater in elderly men supplemented with beta-carotene than in those taking placebo . In an attempt to determine the mechanism of beta-carotene 's effect , we analyzed the production of NK cell-enhancing cytokines ( interferon alpha , interferon gamma , and interleukin 12 ) . Boston-area participants in the Physicians ' Health Study ( men aged 65 - 88 y ; mean age , 73 y ) who had been supplemented with beta-carotene ( 50 mg on alternate days ) for an average of 12 y were enrolled in a r and omized , placebo-controlled , double-blind study . Elderly subjects taking beta-carotene supplements had significantly greater plasma beta-carotene concentrations than those taking placebo . Beta-carotene-supplemented elderly men had significantly greater NK cell activity than did elderly men receiving placebo . Percentages of NK cells ( CD16+CD56 + ) were not significantly different between the beta-carotene and placebo groups . Production of interleukin 12 , interferon alpha , or concanavalin A-stimulated interferon gamma by cultured peripheral blood mononuclear cells was not significantly different between beta-carotene-supplemented elderly and those taking placebo . Our results indicate that beta-carotene-induced enhancement of NK cell activity is not mediated by changes in percentages of CD16+CD56 + NK cells nor through up-regulation of interleukin 12 or interferon alpha We describe a r and omized clinical trial of oral beta-carotene ( 50 mg/day ) for preventing nonmelanoma skin cancer . It is a multicenter study conducted at sites in California , Minnesota , and New Hampshire . This report describes the design of the study , baseline characteristics of the 1805 r and omized patients , changes in their plasma beta-carotene and retinol levels after 1 year of treatment , and plans for statistical analyses . Important features of this study are ( 1 ) a high proportion of potential subjects were found to be ineligible or chose not to enter the study , ( 2 ) the study agent is readily available over the counter and in common foods , and ( 3 ) nonmelanoma skin cancer is a relatively minor health concern for most patients . These considerations necessitated intensive efforts to encourage compliance with the study regimen . There are also some unusual statistical features of the study . One is that the study outcome is routinely assessed only at annual examinations , so the precise time of failure can not be identified . Also , a secondary goal of the study is to determine whether beta-carotene decreases the average number of new skin cancers per patient per year , and there are no established statistical methods for analysis of data in this situation . Alternative approaches to the analysis are discussed Antioxidants may have a role in the prevention of atherosclerosis . In the present trial , we investigated the antioxidant properties of Palm Vitee , a γ-tocotrienol- , and α-tocopherol enriched fraction of palm oil , in patients with carotid atherosclerosis . Serum lipids , fatty acid peroxides , platelet aggregation , and carotid artery stenosis were measured over an 18-month period in fifty patients with cerebrovascular disease . Change in stenosis was measured with duplex ultrasonography . Ultrasound scans were done at six months , twelve months , and yearly thereafter . Bilateral duplex ultrasonography revealed apparent carotid atherosclerotic regression in seven and progression in two of the 25 tocotrienol patients , while none of the control group exhibited regression and ten of 25 showed progression ( P<0.002 ) . Serum thiobarbituric acid reactive substances , anex vivo indicator of maximal platelet peroxidation , decreased in the treatment group from 1.08±0.70 to 0.80±0.55 μM/L ( P<0.05 ) after 12 mon , and in the placebo group , they increased nonsignificantly from 0.99±0.80 to 1.26±0.54 μM/L. Both tocotrienol and placebo groups displayed significantly attenuated collagen-induced platelet aggregation responses ( P<0.05 ) as compared with entry values . Serum total cholesterol , low density lipoprotein cholesterol , and triglyceride values remained unchanged in both groups , as did the plasma high density lipoprotein cholesterol values . These findings suggest that antioxidants , such as tocotrienols , may influence the course of carotid atherosclerosis Supplementation of healthy elderly persons with beta-carotene has been considered a way to enhance immune responses . In study 1 the short-term effect of beta-carotene ( 90 mg/d for 3 wk ) on immunity was assessed in a r and omized , double-blind , placebo-controlled longitudinal comparison of healthy elderly women . In study 2 the long-term effect of beta-carotene ( 50 mg every other day for 10 - 12 y ) on immunity was assessed in a r and omized , double-blind , placebo-controlled longitudinal comparison of men enrolled in the Physicians ' Health Study . Subjects from both studies taking active supplements had significantly greater plasma beta-carotene concentrations than did subjects taking placebo . The pre- to postintervention change in delayed-type hypersensitivity skin test responses between beta-carotene and placebo groups in the short-term study was not significantly different , nor was the response between treatment groups in the long-term study . There were no significant effects due to beta-carotene supplementation on in vitro lymphocyte proliferation , production of interleukin 2 , or production of prostagl and in E2 as a result of short- or long-term beta-carotene supplementation . In addition , there were no differences in the profiles of lymphocyte subsets [ total T cells ( CD3 + ) , T helper cells ( CD4 + ) , T cytotoxic-suppressor cells ( CD8 + ) , and B cells ( CD19 + ) ] due to short- or long-term beta-carotene supplementation , nor were there differences in percentages of CD16 + natural killer cells or activated lymphocytes ( cells expressing interleukin 2 transferrin receptor ) due to long-term beta-carotene supplementation . Consistent results from these two trials show that beta-carotene supplementation did not have an enhancing or suppressive effect on T cell-mediated immunity of healthy elderly To determine the effects of long-term beta-carotene supplementation on concentrations of carotenoids and tocopherols in plasma and in blood cells , fasting blood was collected from 73 r and omly selected physicians from the Boston area who are participating in the Physicians Health Study ( PHS ) . The PHS is a r and omized , placebo-controlled , double-blind study . In 1982 , 22,071 male physicians were assigned to one of four treatments ( 325 mg aspirin alone , 50 mg beta-carotene alone , both , or neither ) every other day . Plasma , peripheral blood mononuclear cells ( P BMC s ) , and red blood cells ( RBCs ) from physicians who have participated in the study for approximately 12 y were analyzed for carotenoids and tocopherols . Compared with the placebo group , the supplemented group had higher beta-carotene concentrations in plasma ( 1.73+/-0.16 compared with 0.54+/-0.06 micromol/L0 , RBCs ( 91.5+/-9.7 compared with 31.2+/-4.2 pmol/g hemoglobin ) , and P BMC s ( 61.6+/-10.3 compared with 15.5+/-2.5 pmol/10(7 ) cells ) . There were no differences in other carotenoids or tocopherols in plasma , RBCs , and P BMC s between these two groups . The beta-carotene concentrations . Plasma cryptoxanthin correlated with both RBC and P BMC cryptoxanthin concentrations but plasma lycopene correlated only with P BMC lycopene concentrations . These data suggest that plasma may not be the best indicator of carotenoid status . Furthermore , long-term beta-carotene supplementation in men results in higher beta-carotene concentrations in plasma , RBCs and P BMC s without lowering concentrations of other carotenoids or tocopherols The effect of beta-carotene supplementation on major serum carotenoid fractions ( lutein/zeaxanthin , beta-cryptoxanthin , lycopene , alpha-carotene , and beta-carotene ) was investigated in 224 people with colorectal adenomas ( 139 men , 85 women ) recruited for the Australian Polyp Prevention Project ( APPP ) . Each subject was r and omly assigned to take either 20 mg beta-carotene/d or placebo over 24 mo . Besides the expected increase in serum concentration of beta-carotene ( 1073 % in men , 839 % in women ) , lycopene ( 176 % in men ) and alpha-carotene ( 211 % in men and 166 % in women ) concentrations were also increased after body mass index , baseline concentration , change in respective carotenoid intake , and other confounding factors were adjusted for . The increase in serum concentrations of these carotenoids after beta-carotene supplementation suggests that beta-carotene may interact biologically with other carotenoids and such interaction would need to be taken into consideration when the protective effect of beta-carotene supplementation for cancer or other diseases is examined High doses of beta-carotene , a lipid-soluble nutrient , may affect the plasma concentrations of other lipid-soluble nutrients . The purpose of this study was to assess the effects of long-term daily supplementation with beta-carotene ( 50 mg/d ) on circulating concentrations of other carotenoids , retinol , and alpha-tocopherol over time . Data were available from 259 men and women participating in the Carotene Prevention Trial , a 2-center chemoprevention trial design ed to determine whether supplemental beta-carotene can prevent second malignant tumors in patients cured of an early stage cancer of the oral cavity , pharynx , or larynx . Up to 2 blood sample s were obtained before the intervention ( before and after a 1-mo placebo run-in ) , with postr and omization sample s obtained at 3 , 12 , 24 , 36 , 48 , and 60 mo . Supplementation with beta-carotene produced a persistent 9- to 10-fold increase in median plasma beta-carotene concentrations ( 225 nmol/L at baseline to 2255 nmol/L at 3 mo ) and a persistent 2-fold increase in median plasma alpha-carotene concentrations ( 45 nmol/L at baseline to 95 nmol/L at 3 mo ) . Concentrations of retinol , alpha-tocopherol , lycopene , and lutein/zeaxanthin were not affected by supplemental beta-carotene . Up to 5 y of daily supplementation with beta-carotene increased circulating concentrations of alpha- and beta-carotene , but did not alter concentrations of lycopene , lutein/zeaxanthin , retinol , or alpha-tocopherol Results from a pilot study to assess the feasibility of conducting a full-scale lung-cancer-prevention trial using pharmacologic beta-carotene are reported . Participants in the study were r and omized in a double-blind fashion to receive either 15 mg orally of beta-carotene or placebo daily . Findings for the first 300 men to complete 1 y on study are presented . After 10 mo of treatment , serum levels in the placebo group showed essentially no change whereas levels in the treated group increased almost 10-fold after 4 mo of treatment . The relationship between change in serum levels are evaluated in regard to body mass index , alcohol consumption , amount of smoking , lipids , and other variables . The results to date clearly indicate that substantial serum response can be achieved with only 15 mg/d and that with this dosage no skin discoloration or other toxicities are observed We determined whether serum carotenoid or retinol concentrations were altered by beta-carotene supplementation in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study and whether such effects were modified by alcohol consumption or cigarette use . Participants in this sub study were 491 r and omly selected men aged 58 - 76 y from the metropolitan Helsinki study center [ 237 receiving supplemental beta-carotene ( 20 mg/d ) and 254 not receiving such supplementation ] . Dietary carotenoids , retinol , and alcohol , and serum beta-carotene , alpha-tocopherol , retinol , and cholesterol were assessed at baseline . After an average of 6.7 y of supplementation , serum was collected and carotenoid , retinol , and alpha-tocopherol concentrations were determined by HPLC . Serum carotenoid fractions were highly correlated with each other ( P < or = 0.0001 ) . Compared with the unsupplemented group , the beta-carotene group had significantly higher serum concentrations of beta-carotene ( 1483 % ) , alpha-carotene ( 145 % ) , and beta-cryptoxanthin ( 67 % ) ( P < or = 0.0001 ) . Retinol concentrations were 6 % higher ( P = 0.03 ) and lutein was 11 % lower ( P = 0.02 ) in the supplemented group . Serum lycopene , zeaxanthin , and alpha-tocopherol did not differ according to beta-carotene-supplementation status . Although these beta-carotene-group differences were not significantly altered by amount of alcohol consumption , higher consumption ( > 12.9 g/d , median ) was related to lower ( 10 - 38 % ) concentrations of carotenoids , particularly beta-carotene , alpha-carotene , and beta-cryptoxanthin , in both the supplemented and unsupplemented groups . Smoking status did not significantly influence the supplementation-related differences in serum carotenoid and retinol values but concentrations of carotenoids were generally highest in participants who quit smoking while in the study and lowest in current smokers of > or = 20 cigarettes/d . This study showed that serum concentrations of non-beta-carotene carotenoids are altered by long-term beta-carotene supplementation and confirms the adverse effects of alcohol and cigarette smoking on serum carotenoids Natural killer ( NK ) cell activity has been postulated to be an immunologic link between beta-carotene and cancer prevention . In a cross-sectional , placebo-controlled , double-blind study we examined the effect of 10 - 12 y of beta-carotene supplementation ( 50 mg on alternate days ) on NK cell activity in 59 ( 38 middle-aged men , 51 - 64 y ; 21 elderly men , 65 - 86 y ) Boston area participants in the Physicians ' Health Study . No significant difference was seen in NK cell activity due to beta-carotene supplementation in the middle-aged group . The elderly men had significantly lower NK cell activity than the middle-aged men ; however , there was no age-associated difference in NK cell activity in men supplemented with beta-carotene . beta-carotene-supplemented elderly men had significantly greater NK cell activity than elderly men receiving placebo . The reason for this is unknown ; however , it was not due to an increase in the percentage of NK cells , nor to an increase in interleukin 2 ( IL-2 ) receptor expression , nor to IL-2 production . beta-carotene may be acting directly on one or more of the lytic stages of NK cell cytotoxicity , or on NK cell activity-enhancing cytokines other than IL-2 , such as IL-12 . Our results show that long-term beta-carotene supplementation enhances NK cell activity in elderly men , which may be beneficial for viral and tumoral surveillance Sixty-one patients admitted with acute myocardial infa rct ion , and a symptom 's duration of less than 6 hr were r and omized into two groups . Immediately after hospitalisation , members of the verum group ( n = 32 ) received 500 mcg of selenium ( as sodium selenite ) . Thereafter they received a daily dosage of 100 mg coenzyme Q10 ( Bio-Quinone ) and 100 mcg selenium ( Bio-Selenium in the form of 1-seleno-methionine ) for a period of one year . The control group ( n = 29 ) were given matching placebo preparations . The groups were comparable as with respect to age , sex and medical treatment . Biochemical parameters showed a reduced concentration of CPK- and ASAT-level in the verum group during the acute phase ( although not statistically significant ) . None of the patients in the verum group ( i.e. on antioxidative treatment ) showed prolongation of the frequency corrected QT-interval . In the control group , 40 % revealed a prolongation of the QT-interval by more than 440 msec ( p < 0.001 ) . There were no significant differences , with respect to early complications . During the one-year follow-up period after myocardial infa rct ion , six patients ( 20 % ) from the control group died from re-infa rct ion whereas one patient from the verum group suffered a non-cardiac death Several studies have reported elevated circulating homocyst(e)ine levels in subjects with cerebral atherosclerosis . We assessed prospect ively whether high plasma levels of homocyst(e)ine affect risk of ischemic stroke and evaluated whether high blood pressure modifies any such effect . Methods The study sample was drawn from the Physicians′ Health Study , a r and omized , double-blind , placebo-controlled trial of aspirin and beta-carotene in 22 071 US male physicians . A total of 14 916 subjects 40 to 84 years old with no prior history of stroke , transient ischemic attack , or myocardial infa rct ion provided blood sample s at baseline and were followed for 5 years , with 99.7 % morbidity and 100 % mortality follow-up . Using a nested case-control design , we assayed homocyst(e)ine in sample s from 109 subjects who subsequently developed ischemic stroke and 427 control subjects . Results The mean plasma concentration of homocyst(e)ine was slightly higher in subjects with stroke ( 11.1±4.0 [ ±SD ] nmol/mL ) than in control subjects ( 10.6±3.4 nmol/mL ) , but the difference was not statistically significant ( P=.12 ) . The crude odds ratio of ischemic stroke for subjects in the upper 20 % ( > 12.7 nmol/mL ) compared with those in the bottom 80 % of homocyst(e)ine levels was 1.4 ( 95 % confidence inter-val , 0.8 to 2.2 ) . The odds ratio was 1.2 ( 95 % confidence interval , 0.7 to 2.0 ) after controlling for several risk factors and other potential confounders . In subgroup analyses , elevated homocyst(e)ine levels appeared to be more strongly predictive of ischemic stroke in normotensive subjects and in men 60 years or younger . Although not statistically significant , in these subgroups increases in risks of 100 % and 70 % , respectively , were observed for men in the upper 20 % of homocyst(e)ine values . Conclusions In this study , the data were compatible with a small but nonsignificant association between elevated plasma homocyst(e)ine and risk of ischemic stroke . However , since the sample size is small and the confidence intervals are wide , either no association or a moderate increase in risk can not be excluded , particularly in subgroups otherwise at low risk , eg , younger men and those with normal blood pressure The Physicians ' Health Study is a r and omized , double-blind , placebo-controlled trial using a 2 x 2 factorial design to test the effects of low-dose aspirin on risk of cardiovascular disease and beta-carotene supplementation on the incidence of cancer . To evaluate self-reported compliance with assigned treatment , we measured serum thromboxane B2 , which is decreased after aspirin use , and plasma beta-carotene in sample s of study participants drawn from three geographic locations in three different time periods . Thromboxane B2 levels were markedly lower in those assigned to aspirin ( median = 63.5 pg/mL ) than in those given aspirin placebo ( median = 3,600 pg/mL , P less than .0001 ) . Similarly , those assigned to beta-carotene had significantly higher levels ( median = 1,176 ng/mL ) than those given placebo ( median = 306 ng/mL , P less than .0001 ) . In addition , there was a highly significant positive correlation between levels of these biochemical markers and the self-reports of compliance ( r = 0.65 for thromboxane B2 and r = 0.69 for beta-carotene , P less than .0001 ) . These findings support the validity of the self-reported compliance in the Physicians ' Health Study OBJECTIVES The purpose of this study was to examine prospect ively the association between reported use of vitamin supplements and risk of cataract and cataract extraction . METHODS The study population consisted of 17,744 participants in the Physicians ' Health Study , a r and omized trial of aspirin therapy and beta-carotene among US male physicians 40 to 84 years of age in 1982 who did not report cataract at baseline and provided complete information about vitamin supplementation and other risk factors for cataract . Self-reports of cataract and cataract extraction were confirmed by medical record review . RESULTS During 60 months of follow-up , there were 370 incident cataracts and 109 cataract extraction s. In comparison with physicians who did not use any supplements , those who took only multivitamins had a relative risk of cataract of 0.73 after adjustment for other risk factors . For cataract extraction , the corresponding relative risk was 0.79 . Use of vitamin C and /or E supplements alone was not associated with a reduced risk of cataract , but the size of this subgroup was small . CONCLUSIONS These data suggest that men who took multivitamin supplements tended to experience a decreased risk of cataract and support the need for rigorous testing of this hypothesis in large-scale r and omized trials in men and women EUROSCAN ( EUROpean Study on Chemoprevention with vitamin A and N-acetylcysteine ) is a study which has the aim to demonstrate the efficacy of vitamin A and N-acetylcysteine in the prevention of second primary tumours in patients treated for lung , larynx and oral cancer . In this study are involved more than 50 medical centres in all Europe , co-ordinated by European Organization for research and Treatment of Cancer ( EORTC ) . In December 1993 almost 2300 patients have been r and omized ; at the present day , in our department , we follow 29 patients curatively treated for oral cancer ( pTNM : pT1N0M0 , pT2N0M0 , pT2N1M0 ) and , for this reason , at high risk to develop local recurrences or second primary tumours . These patients are allocated to four different arms according to the drugs they take : vitamin A as retinol palmitate ( 300,000 UI a day for the first year and 150,000 UI for the second year ) , N-acetylcysteine ( 600 mg a day for two years ) , both these drugs , no drugs ( control group ) . During follow-up all the patients have clinical examinations and blood tests ( in patients taking vitamin A ) every 3 - 6 months . The r and omization is expected to stop around September 1994 , when , probably , the number of 2600 patients will be reached . The first analysis allowing a conclusion on chemopreventive efficacy of retinol and N-acetylcysteine will be performed not before September 1996 with a median follow-up time of more than 3 years . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables , as well as high serum levels of vitamin E ( alpha-tocopherol ) and beta carotene , are associated with a reduced risk of lung cancer . METHODS We performed a r and omized , double-blind , placebo-controlled primary -prevention trial to determine whether daily supplementation with alpha-tocopherol , beta carotene , or both would reduce the incidence of lung cancer and other cancers . A total of 29,133 male smokers 50 to 69 years of age from southwestern Finl and were r and omly assigned to one of four regimens : alpha-tocopherol ( 50 mg per day ) alone , beta carotene ( 20 mg per day ) alone , both alpha-tocopherol and beta carotene , or placebo . Follow-up continued for five to eight years . RESULTS Among the 876 new cases of lung cancer diagnosed during the trial , no reduction in incidence was observed among the men who received alpha-tocopherol ( change in incidence as compared with those who did not , -2 percent ; 95 percent confidence interval , -14 to 12 percent ) . Unexpectedly , we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not ( change in incidence , 18 percent ; 95 percent confidence interval , 3 to 36 percent ) . We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer . Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not . Beta carotene had little or no effect on the incidence of cancer other than lung cancer . Alpha-tocopherol had no apparent effect on total mortality , although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not . Total mortality was 8 percent higher ( 95 percent confidence interval , 1 to 16 percent ) among the participants who received beta carotene than among those who did not , primarily because there were more deaths from lung cancer and ischemic heart disease . CONCLUSIONS We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene . In fact , this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects This pilot study evaluated the feasibility and effectiveness of conducting a double-blind clinical trial for the prevention of lung cancer with selenium ( Se ) in Yunnan Tin Corporation , the People 's Republic of China , where the incidence rates of lung cancer are extraordinarily high among the miners . Forty healthy miners were r and omized to either 300 μg of Se in high Se malt cakes or an identical placebo of malt cakes daily for one year . Subjects consumed their usual daily diet . The low Se concentrations in plasma ( 0.05±0.008 μg/mL ) and hair ( 0.442±0.085 μg/g ) reflected their low dietary Se intake in the control subjects . In Se-supplemented group , the Se status was increased by 178 % for serum and 194.8 % for hair . The serum GSHpx activity was increased by 155.7 % , whereas the lipid peroxide level was reduced by 74.5 % compared to the placebo . The results of UDS assay indicated that the lymphocyte DNA damage induced by ultraviolet irradiation and carcinogen 3,4-benzpyrene could be protected by Se supplementation . Se-supplementation did not affect the liver function test ( SGPT ) , as well as the concentrations of hemoglobin , albumin , and cholesterol . Thus , daily intake of 300 μg Se in form of Se-malt as a chemopreventive measure is safe and effective to humans with low Se status Conflicting reports of the effects of beta-carotene supplementation on serum alpha-tocopherol concentration led us to evaluated serum alpha-tocopherol in subjects with and without beta-carotene ( 30 mg/day ) supplementation for up to 2 years duration in an ongoing chemoprevention trial . No adverse effect has been observed at any of the time periods examined Much of our knowledge about the relationship between micronutrients and cancer comes from studies in which plasma ( serum ) micronutrient levels have been correlated with cancer incidence ; however , the relationship between the concentrations of micronutrients in the plasma and in the target tissues has not been established . Ninety-three subjects ( 62 males and 31 females ages 42 - 86 , median age 69 ) with actinic keratoses were recruited for investigation of this relationship . The subjects were r and omly assigned and received placebo or retinol ( 25,000 IU/day ) intervention for 48 to 65 months as part of a skin cancer chemoprevention trial . Shortly before the end of the trial , three fasting plasma sample s and one skin biopsy were obtained from each subject . The concentrations of lutein , zeaxanthin , beta-cryptoxanthin , lycopene , alpha-carotene , beta-carotene , cis-beta-carotene , retinol , retinyl palmitate , alpha-tocopherol and gamma-tocopherol in the plasma and skin were simultaneously measured using HPLC . The profiles of the eleven micronutrients in the plasma and skin were similar . Lycopene , beta-carotene and alpha-tocopherol were the predominant micronutrients in both plasma and skin , but the ratio of retinyl palmitate to retinol was much greater in the skin than plasma . The three fasting plasma concentrations from the same subject during a one-month period were very consistent ; however , the between-person variations were very large . The retinol supplementation caused a significant increase in the plasma concentrations of retinol , retinyl palmitate , lutein and alpha-tocopherol , especially retinyl palmitate as well as the skin concentrations of retinol and retinyl palmitate . ( ABSTRACT TRUNCATED AT 250 WORDS The association between prostate cancer and baseline vitamin E and selenium was evaluated in the trial-based cohort of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study ( n = 29,133 ) . During up to 9 years of follow-up , 317 men developed incident prostate cancer . Multivariate Cox proportional hazards models that adjusted for intervention group , benign prostatic hyperplasia , age , smoking , and urban residence were used to evaluate associations between prostate cancer and exposures of interest . There were no significant associations between baseline serum alpha-tocopherol , dietary vitamin E , or selenium and prostate cancer overall . The associations between prostate cancer and vitamin E and some of the baseline dietary tocopherols differed significantly by alpha-tocopherol intervention status , with the suggestion of a protective effect for total vitamin E among those who received the alpha-tocopherol intervention ( relative risk was 1.00 , 0.68 , 0.80 , and 0.52 for increasing quartiles ; P = 0.07 ) Background An inverse association between height and risk of coronary heart disease ( CHD ) has been reported in several case-control and cohort studies , but the reasons for the association remain uncertain . We evaluated this association among 22071 male physicians , a population homogeneous for high educational attainment and socioeconomic status in adulthood . Methods and Results The study population was comprised of participants in the Physicians ' Health Study , a r and omized , double-blind , placebo-controlled trial of low-dose aspirin and β-carotene in the primary prevention of cardiovascular disease and cancer among US male physicians , aged 40 to 84 years , in 1982 . Participants were classified into five height categories at study entry , from shortest to tallest , and were followed an average of 60.2 months to determine the incidence of myocardial infa rct ion ( MI ) , stroke , and death from cardiovascular disease . Men in the tallest ( ≥73 in . or 185.4 cm ) compared with the shortest ( ≤67 in . or 170.2 cm ) height category had a 35 % lower risk of MI ( relative risk , 0.65 ; 95 % confidence interval , 0.44 to 0.99 ; P=.04 ) , after adjusting for known cardiovascular risk factors . Further , a marginally significant inverse trend ( P trend=.05 ) across the height categories was observed . Although the relationship was not strictly linear , for every inch of added height , there was an approximate 2 % to 3 % decline in risk of MI . In contrast , men in the tallest compared with the shortest height category had only small and nonsignificant decreases in risk of stroke and cardiovascular death . While no significant trend in risks of these end points across the height categories was observed , the numbers of events for these end points were far less than for MI , and thus the confidence intervals were wide . Conclusions These data indicate that height is inversely associated with subsequent risk of MI . At this time , a few mechanisms are plausible , but none are convincing . Other epidemiological and basic research efforts are needed to explore a variety of physiological correlates of height that may be responsible for mediating the height-MI association . In the meantime , while height is not modifiable , it is easy to measure and may be useful to evaluate CHD disease risk profiles and target lifestyle interventions Objective : To determine whether vitamin E supplementation influences the incidence or rate of progression of age related maculopathy ( AMD ) . Design : Prospect i ve r and omised placebo controlled clinical trial . Setting : An urban study centre in a residential area supervised by university research staff . Participants : 1193 healthy volunteers aged between 55 and 80 years ; 73 % completed the trial on full protocol . Interventions : Vitamin E 500 IU or placebo daily for four years . Main outcome measures : Primary outcome : development of early age related macular degeneration in retinal photographs . Other measures included alternative definitions of age related macular degeneration , progression , changes in component features , visual acuity , and visual function Results : The incidence of early age related macular degeneration ( early AMD 3 ) was 8.6 % in those receiving vitamin E versus 8.1 % in those on placebo ( relative risk 1.05 , 95 % confidence interval 0.69 to 1.61 ) . For late disease the incidence was 0.8 % versus 0.6 % ( 1.36 , 0.67 to 2.77 ) . Further analysis showed no consistent differences in secondary outcomes . Conclusion : Daily supplement with vitamin E supplement does not prevent the development or progression of early or later stages of age related macular degeneration CONTEXT Basic research and observational studies suggest vitamin E or vitamin C may reduce the risk of cardiovascular disease . However , few long-term trials have evaluated men at initially low risk of cardiovascular disease , and no previous trial in men has examined vitamin C alone in the prevention of cardiovascular disease . OBJECTIVE To evaluate whether long-term vitamin E or vitamin C supplementation decreases the risk of major cardiovascular events among men . DESIGN , SETTING , AND PARTICIPANTS The Physicians ' Health Study II was a r and omized , double-blind , placebo-controlled factorial trial of vitamin E and vitamin C that began in 1997 and continued until its scheduled completion on August 31 , 2007 . There were 14,641 US male physicians enrolled , who were initially aged 50 years or older , including 754 men ( 5.1 % ) with prevalent cardiovascular disease at r and omization . INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily . MAIN OUTCOME MEASURES A composite end point of major cardiovascular events ( nonfatal myocardial infa rct ion , nonfatal stroke , and cardiovascular disease death ) . RESULTS During a mean follow-up of 8 years , there were 1245 confirmed major cardiovascular events . Compared with placebo , vitamin E had no effect on the incidence of major cardiovascular events ( both active and placebo vitamin E groups , 10.9 events per 1000 person-years ; hazard ratio [ HR ] , 1.01 [ 95 % confidence interval { CI } , 0.90 - 1.13 ] ; P = .86 ) , as well as total myocardial infa rct ion ( HR , 0.90 [ 95 % CI , 0.75 - 1.07 ] ; P = .22 ) , total stroke ( HR , 1.07 [ 95 % CI , 0.89 - 1.29 ] ; P = .45 ) , and cardiovascular mortality ( HR , 1.07 [ 95 % CI , 0.90 - 1.28 ] ; P = .43 ) . There also was no significant effect of vitamin C on major cardiovascular events ( active and placebo vitamin E groups , 10.8 and 10.9 events per 1000 person-years , respectively ; HR , 0.99 [ 95 % CI , 0.89 - 1.11 ] ; P = .91 ) , as well as total myocardial infa rct ion ( HR , 1.04 [ 95 % CI , 0.87 - 1.24 ] ; P = .65 ) , total stroke ( HR , 0.89 [ 95 % CI , 0.74 - 1.07 ] ; P = .21 ) , and cardiovascular mortality ( HR , 1.02 [ 95 % CI , 0.85 - 1.21 ] ; P = .86 ) . Neither vitamin E ( HR , 1.07 [ 95 % CI , 0.97 - 1.18 ] ; P = .15 ) nor vitamin C ( HR , 1.07 [ 95 % CI , 0.97 - 1.18 ] ; P = .16 ) had a significant effect on total mortality but vitamin E was associated with an increased risk of hemorrhagic stroke ( HR , 1.74 [ 95 % CI , 1.04 - 2.91 ] ; P = .04 ) . CONCLUSIONS In this large , long-term trial of male physicians , neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events . These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00270647 CONTEXT Secondary analyses of 2 r and omized controlled trials and supportive epidemiologic and pre clinical data indicated the potential of selenium and vitamin E for preventing prostate cancer . OBJECTIVE To determine whether selenium , vitamin E , or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men . DESIGN , SETTING , AND PARTICIPANTS A r and omized , placebo-controlled trial ( Selenium and Vitamin E Cancer Prevention Trial [ SELECT ] ) of 35,533 men from 427 participating sites in the United States , Canada , and Puerto Rico r and omly assigned to 4 groups ( selenium , vitamin E , selenium + vitamin E , and placebo ) in a double-blind fashion between August 22 , 2001 , and June 24 , 2004 . Baseline eligibility included age 50 years or older ( African American men ) or 55 years or older ( all other men ) , a serum prostate-specific antigen level of 4 ng/mL or less , and a digital rectal examination not suspicious for prostate cancer . INTERVENTIONS Oral selenium ( 200 microg/d from L-selenomethionine ) and matched vitamin E placebo , vitamin E ( 400 IU/d of all rac-alpha-tocopheryl acetate ) and matched selenium placebo , selenium + vitamin E , or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years . MAIN OUTCOME MEASURES Prostate cancer and prespecified secondary outcomes , including lung , colorectal , and overall primary cancer . RESULTS As of October 23 , 2008 , median overall follow-up was 5.46 years ( range , 4.17 - 7.33 years ) . Hazard ratios ( 99 % confidence intervals [ CIs ] ) for prostate cancer were 1.13 ( 99 % CI , 0.95 - 1.35 ; n = 473 ) for vitamin E , 1.04 ( 99 % CI , 0.87 - 1.24 ; n = 432 ) for selenium , and 1.05 ( 99 % CI , 0.88 - 1.25 ; n = 437 ) for selenium + vitamin E vs 1.00 ( n = 416 ) for placebo . There were no significant differences ( all P>.15 ) in any other prespecified cancer end points . There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group ( P = .06 ) and type 2 diabetes mellitus in the selenium group ( relative risk , 1.07 ; 99 % CI , 0.94 - 1.22 ; P = .16 ) but not in the selenium + vitamin E group . CONCLUSION Selenium or vitamin E , alone or in combination at the doses and formulations used , did not prevent prostate cancer in this population of relatively healthy men . TRIAL REGISTRATION clinical trials.gov identifier : NCT00006392 In a prospect i ve cohort study , the authors examined whether self- selection for antioxidant vitamin supplement use affects the incidence of age-related maculopathy . The study population consisted of 21,120 US male physician participants in the Physicians ' Health Study I who did not have a diagnosis of age-related maculopathy at baseline ( 1982 ) . During an average of 12.5 person-years of follow-up , a total of 279 incident cases of age-related maculopathy with vision loss to 20/30 or worse were confirmed by medical record review . In multivariate analysis , as compared with nonusers of supplements , persons who used vitamin E supplements had a possible but nonsignificant 13 % reduced risk of age-related maculopathy ( relative risk = 0.87 , 95 percent confidence interval ( CI ) 0.53 - 1.43 ) , while users of multivitamins had a possible but nonsignificant 10 % reduced risk ( relative risk = 0.90 , 95 % CI 0.68 - 1.19 ) . Users of vitamin C supplements had a relative risk of 1.03 ( 95 % CI 0.71 - 1.50 ) . These observational data suggest that among persons who self-select for supplemental use of antioxidant vitamin C or E or multivitamins , large reductions in the risk of age-related maculopathy are unlikely . R and omized trial data are accumulating to enable reliable detection of the existence of more plausible small-to-moderate benefits of these agents alone and in combination on age-related maculopathy BACKGROUND Experimental and epidemiologic investigations suggest that alpha-tocopherol ( the most prevalent chemical form of vitamin E found in vegetable oils , seeds , grains , nuts , and other foods ) and beta-carotene ( a plant pigment and major precursor of vitamin A found in many yellow , orange , and dark-green , leafy vegetables and some fruit ) might reduce the risk of cancer , particularly lung cancer . The initial findings of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study ( ATBC Study ) indicated , however , that lung cancer incidence was increased among participants who received beta-carotene as a supplement . Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial ( CARET ) , which tested a combination of beta-carotene and vitamin A. PURPOSE We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics ( e.g. , age , number of cigarettes smoked , dietary or serum vitamin status , and alcohol consumption ) , by study compliance , and in relation to clinical factors , such as disease stage and histologic type . Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other population s. METHODS A total of 29,133 men aged 50 - 69 years who smoked five or more cigarettes daily were r and omly assigned to receive alpha-tocopherol ( 50 mg ) , beta-carotene ( 20 mg ) , alpha-tocopherol and beta-carotene , or a placebo daily for 5 - 8 years ( median , 6.1 years ) . Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry , along with measurements of serum levels of alpha-tocopherol and beta-carotene . Incident cases of lung cancer ( n = 894 ) were identified through the Finnish Cancer Registry and death certificates . Each lung cancer diagnosis was independently confirmed , and histology or cytology was available for 94 % of the cases . Intervention effects were evaluated by use of survival analysis and proportional hazards models . All P values were derived from two-sided statistical tests . RESULTS No overall effect was observed for lung cancer from alpha-tocopherol supplementation ( relative risk [ RR ] = 0.99 ; 95 % confidence interval [ CI ] = 0.87 - 1.13 ; P = .86 , logrank test ) . beta-Carotene supplementation was associated with increased lung cancer risk ( RR = 1.16 ; 95 % CI = 1.02 - 1.33 ; P = .02 , logrank test ) . The beta-carotene effect appeared stronger , but not substantially different , in participants who smoked at least 20 cigarettes daily ( RR = 1.25 ; 95 % CI = 1.07 - 1.46 ) compared with those who smoked five to 19 cigarettes daily ( RR = 0.97 ; 95 % CI = 0.76 - 1.23 ) and in those with a higher alcohol intake ( > or = 11 g of ethanol/day [ just under one drink per day ] ; RR = 1.35 ; 95 % CI = 1.01 - 1.81 ) compared with those with a lower intake ( RR = 1.03 ; 95 % CI = 0.85 - 1.24 ) . CONCLUSIONS Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke . beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers , and this effect may be associated with heavier smoking and higher alcohol intake . IMPLICATION S While the most direct way to reduce lung cancer risk is not to smoke tobacco , smokers should avoid high-dose beta-carotene supplementation Dietary supplementation with n‐3 fatty acids from fish oil alleviates inflammation in various chronic inflammatory disease states . Reductions in the production of pro‐inflammatory cytokines interleukin 1β ( IL‐1β ) , tumour necrosis factor alpha ( TNF‐α ) , and interleukin 6 ( IL‐6 ) have been seen in humans after short‐term n‐3 fatty acid supplementation . We investigated long‐term effects of dietary n‐3 fatty acids on circulating cytokine concentrations and on ex vivo stimulated whole‐blood production of IL‐1β , TNF‐α and interleukin 1 receptor antagonist ( IL‐1Ra ) , the naturally occurring antagonist of IL‐1 . A total of 58 monks with a mean age of 56 years were r and omized into four groups and their diets were supplemented with 0 , 3 , 6 , or 9 g of fish oil , providing 0 , 1.06 , 2.13 or 3.19 g of n‐3 fatty acids per day . Subjects received equal amounts of saturated fatty acids , vitamin E and cholesterol . Compliance was excellent and erythrocyte fatty acid profiles closely reflected the amounts of n‐3 fatty acids ingested . In the group receiving 9 g of fish oil per day , no influence of n‐3 fatty acids on circulating cytokine concentrations was observed relative to placebo . Endotoxin‐stimulated whole‐blood cytokine production was measured at 26 and 52 weeks after the start and at 4 , 8 and 26 weeks after cessation of supplementation . In all groups , the production of IL‐1β and IL‐1Ra was higher during supplementation than afterwards . However , no differences in cytokine production were noted between the placebo group and the various treatment groups at any point in time . Our results suggest that long‐term supplementation of fish oil does not affect ex vivo cytokine production in man OBJECTIVE To examine the effect of supplementation with vitamin E ( alpha tocopherol ) , beta carotene , or both on the incidence of angina pectoris in men without known previous coronary heart disease . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING AND PARTICIPANTS Participants in the Alpha Tocopherol , Beta Carotene Cancer Prevention Study ( N=29133 ) were male smokers aged 50 through 69 years who were living in southern and western Finl and . Of these men , 22269 were considered free of coronary heart disease at baseline and were followed up for the incidence of angina pectoris . INTERVENTION Participants were r and omized to receive 50 mg/d of alpha tocopherol , 20 mg/d of beta carotene , both , or placebo in a 2x2 design . OUTCOME MEASURES An incident case was defined as the first occurrence of typical angina pectoris identified in administering the annually repeated World Health Organization ( Rose ) Chest Pain Question naire . RESULTS During a median follow-up time of 4.7 years ( 96427 person-years ) , 1983 new cases of angina pectoris were detected . Comparing alpha tocopherol-supplemented subjects with non-alpha tocopherol-supplemented subjects showed a relative risk ( RR ) of angina pectoris incidence of 0.91 ( 95 % confidence interval[CI ] , 0.83 to 0.99 ; P=.04 ) . The RR for incidence of angina pectoris for the beta carotene- supplemented subjects compared with those not receiving beta carotene was 1.06 ( 95 % CI , 0.97 to 1.16 ; P=.19 ) . Compared with those receiving placebo , the RRs for incidence of angina pectoris were 0.97 ( 95 % CI , 0.85 to 1.10 ) and 0.96 ( 95 % CI , 0.85 to 1.09 ) in the alpha tocopherol and alpha tocopherol plus beta carotene groups , respectively , and 1.13 ( 95 % CI , 1.00 to 1.27 ) in the beta carotene group ( P=.06 ) . Baseline dietary intakes and serum levels of alpha tocopherol and beta carotene did not predict incidence of angina pectoris . CONCLUSIONS Supplementation with alpha tocopherol was associated with only a minor decrease in the incidence of angina pectoris . Beta carotene had no preventive effect and was associated with a slight increase of angina Objective To evaluate the effects of α tocopherol and β carotene supplements on recurrence and progression of angina symptoms , and incidence of major coronary events in men with angina pectoris . Design Placebo controlled clinical trial . Setting The Finnish α tocopherol β carotene cancer prevention study primarily undertaken to examine the effects of α tocopherol and β carotene on cancer . Subjects Male smokers aged 50–69 years who had angina pectoris in the Rose chest pain question naire at baseline ( n = 1795 ) . Interventions α tocopherol ( vitamin E ) 50 mg/day , β carotene 20 mg/day or both , or placebo in 2 × 2 factorial design . Main outcome measures Recurrence of angina pectoris at annual follow up visits when the question naire was readministered ; progression from mild to severe angina ; incidence of major coronary events ( non-fatal myocardial infa rct ion and fatal coronary heart disease ) . Results There were 2513 recurrences of angina pectoris during follow up ( median 4 years ) . Compared to placebo , the odds ratios for recurrence in the active treatment groups were : α tocopherol only 1.06 ( 95 % confidence interval ( CI ) 0.85 to 1.33 ) , α tocopherol and β carotene 1.02 ( 0.82 to 1.27 ) , β carotene only 1.06 ( 0.84 to 1.33 ) . There were no significant differences in progression to severe angina among the groups given supplements or placebo . Altogether 314 major coronary events were observed during follow up ( median 5.5 years ) and the risk for them did not differ significantly among the groups given supplements or placebo . Conclusions There was no evidence of beneficial effects for α tocopherol or β carotene supplements in male smokers with angina pectoris , indicating no basis for therapeutic or preventive use of these agents in such patients CONTEXT Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer , and vitamins E and C are among the most common individual supplements . A large-scale r and omized trial suggested that vitamin E may reduce risk of prostate cancer ; however , few trials have been powered to address this relationship . No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer . OBJECTIVE To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men . DESIGN , SETTING , AND PARTICIPANTS The Physicians ' Health Study II is a r and omized , double-blind , placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31 , 2007 . A total of 14,641 male physicians in the United States initially aged 50 years or older , including 1307 men with a history of prior cancer at r and omization , were enrolled . INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily . MAIN OUTCOME MEASURES Prostate and total cancer . RESULTS During a mean follow-up of 8.0 years , there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers . Compared with placebo , vitamin E had no effect on the incidence of prostate cancer ( active and placebo vitamin E groups , 9.1 and 9.5 events per 1000 person-years ; hazard ratio [ HR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.85 - 1.09 ; P = .58 ) or total cancer ( active and placebo vitamin E groups , 17.8 and 17.3 cases per 1000 person-years ; HR , 1.04 ; 95 % CI , 0.95 - 1.13 ; P = .41 ) . There was also no significant effect of vitamin C on total cancer ( active and placebo vitamin C groups , 17.6 and 17.5 events per 1000 person-years ; HR , 1.01 ; 95 % CI , 0.92 - 1.10 ; P = .86 ) or prostate cancer ( active and placebo vitamin C groups , 9.4 and 9.2 cases per 1000 person-years ; HR , 1.02 ; 95 % CI , 0.90 - 1.15 ; P = .80 ) . Neither vitamin E nor vitamin C had a significant effect on colorectal , lung , or other site-specific cancers . Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results . Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk . CONCLUSIONS In this large , long-term trial of male physicians , neither vitamin E nor C supplementation reduced the risk of prostate or total cancer . These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00270647 Atherosclerotic cardiovascular disease remains a major cause of mortality and morbidity in most developed countries . Experimental and clinical evidence suggests that angiotensin-converting enzyme inhibitors and vitamin E therapy may retard the atherosclerotic process ; however , definitive proof in humans is lacking . The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E ( SECURE ) is design ed to assess the effects of ramipril -- an angiotensin-converting enzyme inhibitor , at 2 doses : 2.5 mg daily ( which has little effect on lowering blood pressure ) and 10 mg daily-- and the antioxidant vitamin E , 400 IU daily , on atherosclerosis progression in 732 patients using a factorial 3 x 2 study design . High-risk patients with a documented history of significant cardiovascular disease or with diabetes and additional risk factors were enrolled and will be followed for 4 years . The extent and progression of atherosclerosis are assessed noninvasively by B-mode carotid ultrasonography . The SECURE trial is a sub study of the larger Heart Outcomes Prevention Evaluation ( HOPE ) study of 9,541 high-risk patients evaluating the effects of ramipril and vitamin E on major cardiovascular events ( cardiovascular death , myocardial infa rct ion , and stroke ) . The 2 studies are complementary . Whereas HOPE is expected to provide information on major clinical outcomes , SECURE will shed light on the mechanisms by which these effects may be mediated In recent years , increasing attention has focused on the need for more research to be conducted in women on health issues directly relevant to women . No one would disagree that the need for such studies is both crucial and timely . However , while the need for more research in women is urgent , the planning and conduct of such studies must always be driven by good science . Specifically , investigations in women may have unique and important scientific and logistic problems which must be recognized and addressed . However , if the trials are well design ed and conducted , they will provide a sound and reliable body of data upon which to base rational clinical decision making and public health recommendations for women from women . These general issues are discussed in the context of a particular trial , the Women 's Health Study , a r and omized trial of the risks and benefits of low-dose aspirin , beta-carotene and vitamin E in the primary prevention of cardiovascular disease and cancer among healthy women One gram of ascorbic acid ( Vitamin C ) administered r and omly to a group of healthy young people ( aged 29 ± 5 years ) produced a significant mean fall in serum cholesterol of 16 per cent within two months . A similar supplement to a group of healthy older people ( aged 58 ± 3 years ) produced a significant mean fall in serum cholesterol of 14 per cent but required six to 12 months ' administration . Serial observations on a mixed age group of healthy people ( aged 38 ± 12 years ) over one calendar year revealed a seasonal fluctuation in serum cholesterol , the lowest levels being in summer ( June 5.5 ± 0.7 mmols/l ) and the highest levels in winter ( January 6.4 ± 0.8 mmols/l ) , a significant rise of 16 per cent . These changes showed an inverse relationship with the leucocyte and serum ascorbic acid levels which also revealed a seasonal fluctuation , the months April/September being higher than the months October/March . The administration of 1 g of ascorbic acid per day throughout the year abolished the winter rise in serum cholesterol levels . These results are discussed in the light of the relationship between cholesterol and vascular disease and the observations by Sir Richard Doll that lowering the cholesterol level , whether achieved by drugs or diet , results in a reduction in morbidity from myocardial infa rct ion Vitamin A therapy has been cl aim ed in isolated reports to be of benefit to patients with Crohn 's disease . To investigate this further , 86 patients were entered into a long-term double-blind study of vitamin A , 50,000 U twice daily , as compared with placebo . After a mean of 14.1 mo of treatment there was no significant difference between the groups as measured by a variety of activity indices ( including the National Cooperative Crohn 's Disease Activity Index ) , the number of acute attacks , and the surgical rate . No toxic effects of vitamin A were observed during the study . In this study vitamin A has not been shown to be of benefit to patients with Crohn 's disease who are in remission We have initiated a population ‐based , double‐blind , r and omized controlled trial to examine the effects of supplementation of beta‐carotene and vitamin C on the incidence of gastric cancer . The subjects were participants in an annual health screening program conducted by four municipalities in Akita prefecture , one of the regions with the highest mortality from gastric cancer in Japan . We measured their serum levels of pepsinogens ( PGs ) I and II , and asked persons diagnosed with chronic atrophic gastritis ( defined as PGI < 70 ng/ml and PGI/PGII ratio < 3.0 ) to take diet supplements containing 0 or 15 mg/day beta‐carotene and 50 or 500 mg/day vitamin C for 5 years . During the first year of recruitment conducted in one village from June through September , 1995 , 52 % ( 635/1214 ) of screening participants had chronic atrophic gastritis and 73 % ( 439/602 ) of eligible persons responded . However , in response to a National Cancer Institute press report released on January 18 , 1996 , indicating that two beta‐carotene trials had shown no benefit and potential harm from the supplement , we discontinued the beta‐carotene and continued with the trial using only vitamin C. Of 397 participants remaining at this point , 77 % ( 305 ) consented to stay in the study . The results indicate that a r and omized controlled trial for cancer prevention is feasible in the Japanese asymptomatic population PURPOSE To investigate the safety and preliminary efficacy of OT-551 , a disubstituted hydroxylamine with antioxidant properties , for the treatment of geographic atrophy ( GA ) , the advanced atrophic form of age-related macular degeneration ( AMD ) . METHODS The study was a single-center , open-label phase II trial , enrolling 10 participants with bilateral GA . Topical 0.45 % OT-551 was administered in one r and omly assigned eye three times daily for 2 years . Safety measures were assessed by complete ophthalmic examination , fundus photography , and review of symptoms . The primary efficacy outcome measure was the change in best corrected visual acuity at 24 months . Secondary efficacy measures included changes in area of GA , contrast sensitivity , microperimetry measurements , and total drusen area from baseline . RESULTS Study drug was well tolerated and was associated with few adverse events . The mean change in BCVA at 2 years was + 0.2 ± 13.3 letters in the study eyes and -11.3 ± 7.6 letters in fellow eyes ( P = 0.0259 ) . However , no statistically significant differences were found between the study and fellow eyes for all other secondary outcome measures . CONCLUSIONS OT-551 was well tolerated by study participants and was not associated with any serious adverse effects . Efficacy measurements in this small study indicate a possible effect in maintaining visual acuity . However , the absence of significant effects on other outcomes measures in this study suggests that OT-551 , in the current concentration and mode of delivery , may have limited or no benefit as a treatment for GA ( Clinical Trials.gov number , NCT00306488 ) BACKGROUND The D/I polymorphism of the ACE gene has been studied in relation to a variety of cardiovascular disorders , including stroke . A number of small studies have been conducted , with inconsistent results . We investigated the association between ACE genotype and the incidence of stroke in a large , prospect i ve , matched case-control sample from the Physicians ' Health Study . METHODS AND RESULTS In the Physicians ' Health Study , 348 subjects who had been apparently healthy at enrollment suffered a stroke during 12 years of follow-up , as determined from medical records and autopsy . A total of 348 cases were matched by age , time of r and omization , and smoking habit to an equal number of controls ( who had remained free of stroke ) . The D/I polymorphism was determined by polymerase chain reaction . Data were analyzed for the entire nested case-control sample , and also among a subgroup without a history of hypertension or diabetes mellitus , considered to be at low conventional risk ( 207 cases and 280 controls ) . All observed genotype frequencies were in Hardy-Weinberg equilibrium . The relative risk associated with the D allele was 1.11 ( 95 % CI , 0.90 to 1.37 ; P=0.35 ) , assuming an additive model in the matched analysis . Additional analyses assuming dominant or recessive effects of the D allele , as well as the analysis after stratification for low-risk status , showed no material as a statistically significant association . CONCLUSIONS The results of this large , prospect i ve study indicate that the ACE D/I gene polymorphism is not associated with subsequent risk of stroke BACKGROUND Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease , and earlier basic research suggested plausible mechanisms . Because large r and omized trials of long duration were necessary to test this hypothesis directly , we conducted a trial of beta carotene supplementation . METHODS In a r and omized , double-blind , placebo-controlled trial of beta carotene ( 50 mg on alternate days ) , we enrolled 22,071 male physicians , 40 to 84 years of age , in the United States ; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982 . By December 31 , 1995 , the scheduled end of the study , fewer than 1 percent had been lost to follow-up , and compliance was 78 percent in the group that received beta carotene . RESULTS Among 11,036 physicians r and omly assigned to receive beta carotene and 11,035 assigned to receive placebo , there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease , or in overall mortality . In the beta carotene group , 1273 men had any malignant neoplasm ( except nonmelanoma skin cancer ) , as compared with 1293 in the placebo group ( relative risk , 0.98 ; 95 percent confidence interval , 0.91 to 1.06 ) . There were also no significant differences in the number of cases of lung cancer ( 82 in the beta carotene group vs. 88 in the placebo group ) ; the number of deaths from cancer ( 386 vs. 380 ) , deaths from any cause ( 979 vs. 968 ) , or deaths from cardiovascular disease ( 338 vs. 313 ) ; the number of men with myocardial infa rct ion ( 468 vs. 489 ) ; the number with stroke ( 367 vs. 382 ) ; or the number with any one of the previous three end points ( 967 vs. 972 ) . Among current and former smokers , there were also no significant early or late differences in any of these end points . CONCLUSIONS In this trial among healthy men , 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms , cardiovascular disease , or death from all causes Folate derivatives are important in experimental colorectal carcinogenesis ; low folate intake , particularly with substantial alcohol intake , is associated with increased risk . The enzyme 5,10-methylenetetrahydrofolate reductase ( MTHFR ) catalyzes the conversion of 5,10-methylenetetrahydrofolate , required for purine and thymidine syntheses , to 5-methyltetrahydrofolate , the primary circulatory form of folate necessary for methionine synthesis . A common mutation ( 677C-->T ) in MTHFR reduces enzyme activity , leading to lower levels of 5-methyltetrahydrofolate . To evaluate the role of folate metabolism in human carcinogenesis , we examined the associations of MTHFR mutation , plasma folate levels , and their interaction with risk of colon cancer . We also examined the interaction between genotype and alcohol intake . We used a nested case-control design within the Physicians ' Health Study . Participants were ages 40 - 84 at baseline when alcohol intake was ascertained and blood sample s were drawn . During 12 years of follow-up , we identified 202 colorectal cancer cases and matched them to 326 cancer-free controls by age and smoking status . We genotyped for the MTHFR polymorphism and measured plasma folate levels . Men with the homozygous mutation ( 15 % in controls ) had half the risk of colorectal cancer [ odds ratio ( OR ) , 0.49 ; 95 % confidence interval ( CI ) , 0.27 - 0.87 ] compared with the homozygous normal or heterozygous genotypes . Overall , we observed a marginal significant increased risk of colorectal cancer ( OR , 1.78 ; 95 % CI , 0.93 - 3.42 ) among those whose plasma folate levels indicated deficiency ( <3 ng/ml ) compared with men with adequate folate levels . Among men with adequate folate levels , we observed a 3-fold decrease in risk ( OR , 0.32 ; 95 % CI , 0.15 - 0.68 ) among men with the homozygous mutation compared with those with the homozygous normal or heterozygous genotypes . However , the protection due to the mutation was absent in men with folate deficiency . In men with the homozygous normal genotype who drank little or no alcohol as reference , those with the homozygous mutation who drank little or no alcohol had an 8-fold decrease in risk ( OR , 0.12 ; 95 % CI , 0.03 - 0.57 ) , and for moderate drinkers , a 2-fold decrease in risk ( OR , 0.42 ; 95 % CI , 0.15 - 1.20 ) ; no decrease in risk was seen in those drinking 1 or more drinks/day . Our findings provide support for an important role of folate metabolism in colon carcinogenesis . In particular , these results suggest that the 677C-->IT mutation in MTHFR reduces colon cancer risk , perhaps by increasing 5,10-methylenetetrahydrofolate levels for DNA synthesis , but that low folate intake or high alcohol consumption may negate some of the protective effect PURPOSE To describe the methodology of eye examination and the baseline eye characteristics of the Vitamin E , Cataract and Age-Related Maculopathy ( VECAT ) study participants . METHODS A sample of volunteers from an urban area of Melbourne , Australia , were recruited to participate in a r and omized , controlled trial investigating the effect of vitamin E on the development of cataract and age-related maculopathy St and ardized eye examinations involved clinical assessment , which included Wilmer grading of the lens , digital photography of the lens with Nidek EAS-1000 lens camera and stereo photography of the macular area with the Nidek 3-DX fundus camera . All cases of ophthalmic findings were determined on the basis of pathology in the worse eye . RESULTS Most eyes were free from abnormalities . The most frequent findings were cataract and age-related macular changes . Nuclear cataract ( nuclear opacity grade > 2 ) was present in 4.5 % , cortical cataract ( cortical opacity grade > 2 ) in 14.3 % and posterior subcapsular cataract in 3.0 % of participants ; in addition , coronary cataract was observed in 13.6 % . Soft drusen larger than 125 pm were found in 11.4 % , retinal pigment epithelium changes in 9.5 % , epiretinal membrane in 6.6 % and age-related macular degeneration in 0.5 % of participants . SUMMARY Due to the selection criteria , the majority of participants had clear or minor lens changes and /or minor retinal age-related changes . Precise instrumental documentation will allow an accurate assessment of the incidence and dynamics of these changes throughout 4 years of observation The Roche European-American Anticataract Trial ( REACT ) will assess the effect of antioxidants on progression of cataract in humans . This report evaluates the methods used in REACT . Seventy three subjects ( 139 eyes ) with cortical ( C ) , posterior subcapsular ( P ) , nuclear ( N ) or mixed cataract were seen twice within two weeks for eye examinations , assessment s of visual function , lens photographs and CCD images . The degree of cataract and nuclear color ( NC ) were assessed with subjective ( LOCS III ) and objective ( computerized , CASE 2000 CCD ) methods . Repeat visit values were used to calculate intraclass correlation coefficients ( r1 ) and 95 % tolerance limits ( TL ) . A clinical ly significant change ( CSC ) was defined as one step in LOCS III . The relative power of each method to detect cataract change and sample sizes needed to achieve statistically significant results were calculated . The r1 values for visual function tests ranged from 0.76 to 0.88 ; if these tests of visual function were used to detect a clinical ly significant change in cataract severity , sample sizes of 840 to 2707 per group would be needed . The r1 values for LOCS III were 0.88 to 0.97 , and sample sizes ranged from 50 to 135 per group . The r1 values for the CCD were 0.93 to 0.98 , and sample sizes ranged from 1 to 42 with poorer values relating to measurement of P. We conclude that the methods used in REACT are reproducible . The analytical algorithms in the image analysis programs did not permit differentiation between C and P opacification ; therefore , P cataract is best measured with LOCS III . REACT sample sizes are adequate to detect a difference of 0.2 LOCS III units/year between the mean rates of cataract progression in two groups PURPOSE A national cooperative group trial was conducted in patients with early-stage cutaneous malignant melanoma to determine if oral vitamin A can increase disease-free survival or survival . PATIENTS AND METHODS Two hundred forty-eight patients with completely resected melanoma of Breslow 's thickness greater than 0.75 mm and clinical ly negative lymph nodes were r and omized to oral vitamin A ( 100,000 IU/d ) for 18 months or to observation . Patients were stratified by Breslow 's thickness of primary lesion ( 0.76 to 1.50 mm , 1.51 to 3.00 mm , or > 3.00 mm ) , sex , and type of therapy ( excision , excision plus node dissection , excision plus perfusion , or excision plus both ) . The median duration of follow-up observation of living patients is greater than 8 years . The relative risk ( RR ) in disease-free survival and overall survival in the treatment compared with the observation group was calculated using Cox proportional hazards models . RESULTS Overall , there was no difference in disease-free survival or overall survival between the two groups . Examination of treatment by stratification interactions and subset analysis did not show any treatment-effect differences based on sex or type of therapy . There was also no difference between groups in disease-free survival based on Breslow 's thickness of the primary lesion . Overall , 12 % of patients who received vitamin A experienced grade 3 or 4 toxicities . CONCLUSION Based on the lack of overall survival benefit , further evaluation of vitamin A as adjuvant therapy for melanoma does not appear warranted OBJECTIVE To determine the cost-effectiveness of vitamin therapy ( antioxidants plus zinc ) for all indicated patients diagnosed with age-related macular degeneration ( AMD ) . DESIGN We compared the impacts of vitamin therapy with those of no vitamin therapy using a computerized , stochastic , agent-based model . The model simulated the natural history of AMD and patterns of ophthalmic service use in the United States in a cohort from age 50 years until 100 or death . PARTICIPANTS AND /OR CONTROLS The model created 20 million simulated individuals . These individuals each received both the intervention ( vitamin therapy after diagnosis ) and the control ( no vitamin therapy ) . Expected outcomes generated when vitamins were taken after diagnosis were compared with the expected outcomes generated when they were not . METHODS The model created individuals representative of patients in the U.S. Incidence of early AMD was based on published studies , as was vision loss and response to choroidal neovascularization therapies . Post-incident disease progression was governed by previously unpublished data drawn from the Age-Related Eye Disease Study . MAIN OUTCOME MEASURES Extent of disease progression , years and severity of visual impairment , cost of ophthalmic care and nursing home services , and quality -adjusted life years ( QALYs ) . Costs and benefits were considered from the health care perspective and discounted using a 3 % rate . The analysis was run for 50 years starting in 2003 . RESULTS Compared with no therapy , vitamin therapy yielded a cost-effectiveness ratio of $ 21,387 per QALY gained and lowered the percentage of patients with AMD who ever developed visual impairment in the better-seeing eye from 7.0 % to 5.6 % . CONCLUSIONS Our model demonstrates that vitamin therapy for AMD improves quality of life at a reasonable cost PURPOSE The Age-Related Eye Disease Study ( AREDS ) has shown that supplementation of antioxidants slows the progression of age-related macular degeneration ( AMD ) . The mechanism underlying this therapeutic effect may be related to a reduction of reactive oxygen species ( ROS ) . The authors have recently introduced a model showing that the response of retinal blood flow ( RBF ) to hyperoxia is diminished by administration of lipopolysaccharide ( LPS ) . In the present study , the hypothesis was that this response can be restored by the AREDS medication . METHODS Twenty-one healthy volunteers were included in this r and omized , double-masked , placebo-controlled , parallel group study . On each study day , RBF and the reactivity of RBF to hyperoxia were investigated before and after infusion of 2 ng/kg LPS . Between the two study days , subjects took either the AREDS medication or placebo for 14 days . RESULTS After administration of LPS reduced retinal arterial vasoconstriction during hyperoxia ( AREDS group : 12.5 % + /- 4.8 % pre-LPS vs. 9.4 % + /- 4.6 % post-LPS ; placebo group : 9.2 % + /- 3.3 % pre-LPS vs. 7.1 % + /- 3.5 % post-LPS ) and a reduced reactivity of RBF during hyperoxia ( AREDS : 50.4 % + /- 8.9 % vs. 44.9 % + /- 11.6 % , placebo : 54.2 % + /- 8.6 % vs. 46.0 % + /- 6.9 % ) was found . The reduced responses were normalized after 2 weeks of AREDS antioxidants but not after placebo ( vasoconstriction : 13.1 % + /- 4.5 % vs. 13.1 % + /- 5.0 % AREDS , 11.2 % + /- 4.2 vs. 7.4 % + /- 4.2 % placebo ; RBF : 52.8 % + /- 10.5 % vs. 52.4 % + /- 10.5 % AREDS , 52.4 % + /- 9.3 % vs. 44.2 % + /- 6.3 % placebo ) . CONCLUSIONS The sustained retinal vascular reaction to hyperoxia after LPS in the AREDS group indicates that antioxidants reduce oxidative stress-induced endothelial dysfunction , possibly by eliminating ROS . The model may be an attractive approach to study ing the antioxidative capacity of dietary supplements for the treatment of AMD ( Clinical Trials.gov number , NCT00431691 ) OBJECTIVE To test whether beta carotene supplementation affects the incidence of age-related maculopathy ( ARM ) in a large-scale r and omized trial . DESIGN R and omized , double-masked , placebo-controlled trial among 22 071 apparently healthy US male physicians aged 40 to 84 years . Participants were r and omly assigned to receive beta carotene ( 50 mg every other day ) or placebo . Main Outcome Measure Incident ARM responsible for a reduction in best-corrected visual acuity to 20/30 or worse . RESULTS After 12 years of treatment and follow-up , there were 162 cases of ARM in the beta carotene group vs 170 cases in the placebo group ( relative risk [ RR ] , 0.96 ; 95 % confidence interval [ CI ] , 0.78 - 1.20 ) . The results were similar for the secondary end points of ARM with or without vision loss ( 275 vs 274 cases ; RR , 1.01 ; 95 % CI , 0.86 - 1.20 ) and advanced ARM ( 63 vs 66 cases ; RR , 0.97 ; 95 % CI , 0.69 - 1.37 ) . CONCLUSIONS These r and omized data relative to 12 years of treatment among a large population of apparently healthy men indicate that beta carotene supplementation has no beneficial or harmful effect on the incidence of ARM . Long-term supplemental use of beta carotene neither decreases nor increases the risk of ARM OBJECTIVE To examine whether body mass index is an independent predictor of cataract . ( Body mass index is a st and ardized measure defined as weight in kilograms divided by the square of the height in meters . ) DESIGN Prospect i ve cohort study , with 5 years of follow-up . PARTICIPANTS A total of 17,764 US male physicians participating in the Physicians ' Health Study , aged 40 to 84 years , who were free of cataract , myocardial infa rct ion , stroke , and cancer at baseline and reported complete information about body mass index and other cataract risk factors . MAIN OUTCOME MEASURE Incident cataract , defined as a self-report , confirmed by medical record review , first diagnosed after r and omization , age-related in origin , and responsible for a decrease in best corrected visual acuity to 20/30 or worse . RESULTS Incident cataract occurred during follow-up in 370 participants . In proportional hazards models that adjusted for potential confounding variables , body mass index had a strong , grade d relationship with risk of cataract . Relative to those with body mass index less than 22 , relative risks ( 95 % confidence intervals ) associated with body mass index of 22 to less than 25 , 25 to less than 27.8 , and 27.8 or more were 1.54 ( 1.04 to 2.27 ) , 1.46 ( 0.98 to 2.20 ) , and 2.10 ( 1.35 to 3.25 ) , respectively . Relative to any given level of body mass index , a 2-unit higher level predicted a 12 % increase in risk of cataract ( 95 % confidence interval , 5 % to 19 % ) . Higher body mass index was especially strongly related to risk of posterior subcapsular and nuclear sclerotic cataracts and was also significantly related to risk of cataract extraction . CONCLUSIONS In a prospect i ve cohort study of apparently healthy men , higher body mass index , a potentially modifiable risk factor , was a determinant of cataract . The leanest men had the lowest rates , consistent with experimental evidence that restriction of energy intake slows development of cataract . Although precise mechanisms are unclear , the effect of body mass index on cataractogenesis is apparently independent of other risk factors , including age , smoking , and diagnosed diabetes OBJECTIVE To examine the association between cigarette smoking and the incidence of age-related macular degeneration ( AMD ) in men . DESIGN Prospect i ve cohort study with average person-years of follow-up for AMD of 12.2 years . PARTICIPANTS A total of 21 157 US male physicians participating in the Physicians ' Health Study who did not have a diagnosis of AMD at baseline , were followed for at least 7 years , and had known levels of baseline smoking . Based on information reported at baseline , 11 % were current smokers , 39 % were past smokers , and 50 % were never smokers . MAIN OUTCOME MEASURE Incident AMD , defined as a self-report that was confirmed by medical record , review , first diagnosed after r and omization , and responsible for vision loss to 20/30 or worse . RESULTS A total of 268 incident cases of AMD with vision loss were confirmed . In multivariate analysis , current smokers of 20 or more cigarettes per day , compared with never smokers , had an increased risk of AMD ( relative risk [ RR ] , 2.46 ; 95 % confidence interval [ CI ] , 1.60 - 3.79 ) . Past smokers had a modest elevation in risk of AMD ( RR , 1.30 ; 95 % CI , 0.99 - 1.70 ) . For current smokers of fewer than 20 cigarettes per day , there was a nonsignificant 26 % increased risk of AMD ( RR , 1.26 ; 95 % CI , 0.61 - 2.59 ) . CONCLUSIONS These prospect i ve data provide support for the hypothesis that cigarette smoking increases the risk of developing AMD BACKGROUND There is evidence that medications or vitamins that increase the levels of brain catecholamines and protect against oxidative damage may reduce the neuronal damage and slow the progression of Alzheimer 's disease . METHODS We conducted a double-blind , placebo-controlled , r and omized , multicenter trial in patients with Alzheimer 's disease of moderate severity . A total of 341 patients received the selective monoamine oxidase inhibitor selegiline ( 10 mg a day ) , alpha-tocopherol ( vitamin E , 2000 IU a day ) , both selegiline and alpha-tocopherol , or placebo for two years . The primary outcome was the time to the occurrence of any of the following : death , institutionalization , loss of the ability to perform basic activities of daily living , or severe dementia ( defined as a Clinical Dementia Rating of 3 ) . RESULTS Despite r and om assignment , the baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups , and this variable was highly predictive of the primary outcome ( P<0.001 ) . In the unadjusted analyses , there was no statistically significant difference in the outcomes among the four groups . In analyses that included the base-line score on the Mini-Mental State Examination as a covariate , there were significant delays in the time to the primary outcome for the patients treated with selegiline ( median time , 655 days ; P=0.012 ) , alpha-tocopherol ( 670 days , P=0.001 ) or combination therapy ( 585 days , P=0.049 ) , as compared with the placebo group ( 440 days ) . CONCLUSIONS In patients with moderately severe impairment from Alzheimer 's disease , treatment with selegiline or alpha-tocopherol slows the progression of disease OBJECTIVE To evaluate , in a prospect i ve design , whether migraine is an independent risk factor for subsequent stroke . DESIGN Evaluated as part of the Physicians ' Health Study , a r and omized , double-blind , placebo-controlled trial of aspirin and beta-carotene in the primary prevention of cardiovascular disease and cancer begun in 1982 . The aspirin component of the study was terminated in 1988 , with average follow-up of 60.2 months . SETTING Conducted by mail among male physicians throughout the United States . PARTICIPANTS A total of 22,071 US male physicians aged 40 to 84 years in 1982 with no prior history of cancer or cardiovascular diseases who were enrolled in the Physicians ' Health Study . INTERVENTIONS Participants were r and omized to receive 325 mg of aspirin or aspirin placebo every other day and to receive 50 mg of beta-carotene or placebo on alternate days . MAIN OUTCOME MEASURES The primary outcomes of the Physicians ' Health Study were cardiovascular disease and cancer . Because stroke was a main outcome , this provided the opportunity to evaluate the association between migraine headaches and stroke . RESULTS Physicians reporting migraine ( n = 1479 ) had significantly increased risks of subsequent total stroke and ischemic stroke compared with those not reporting migraine . After adjustment for age , aspirin and beta-carotene treatment assignment , and a number of cardiovascular risk factors , the relative risks were 1.84 ( 95 % confidence interval , 1.06 to 3.20 ) for total stroke and 2.00 ( 95 % confidence interval , 1.10 to 3.64 ) for ischemic stroke . There were too few hemorrhagic strokes in the study to evaluate this end point . No associations were seen between ordinary nonmigraine headache and subsequent stroke or between migraine and subsequent myocardial infa rct ion or cardiovascular death . CONCLUSION These data raise the possibility that vascular events associated with migraine may also have causative importance in stroke but require confirmation in other studies specifically design ed to evaluate this question Because supplements of vitamins C and E had been associated with reduction of fecal mutagen levels , a double-blind r and omized trial was design ed to examine the effects of these vitamins on the rate of recurrence of colorectal polyps , presumed precursors for colorectal cancer . Two hundred patients believed to be free of polyps after removal of at least one colorectal polyp were r and omized to receive a supplement of 400 mg each of ascorbic acid and alpha-tocopherol , or a placebo . Fifteen patients had to be excluded because a review of pathology indicated that their polyps were not adenomatous . A second colonoscopic examination was planned after 2 yr of supplementation . One hundred thirty-seven people ( 75 % of eligible subjects ) completed the study ; polyps were observed in the second colonoscopy in 41.4 % of 70 subjects on vitamin supplements and in 50.7 % of 67 subjects on placebos . After adjustment for differences between groups in demographic and dietary factors before study entry , the relative risk of polyp occurrence was 0.86 , with 95 % confidence limits from 0.51 to 1.45 , in an analysis of 129 subjects with complete information on demographic and dietary factors who had completed the trial . Of the 48 patients who had not completed the study , 7 had died , 33 had not returned to their physician for an examination , and 8 had had a follow-up colonoscopy or sigmoidoscopy . Inclusion of the three polyps found in these eight examinations led to an estimate of relative risk of 0.86 ( 95 % confidence limits , 0.51 to 1.43 ) . The findings of this investigation suggest that any reduction in the rate of polyp recurrence associated with vitamin supplementation is small , and a larger study would be required to ensure that an effect of this size was not a chance finding Ninety seven geriatric patients from two Danish homes for old people accepted to participate in a blinded experiment design ed to counteract ageing phenomena . The subjects were split into two groups , i.e. , the verum and the placebo group . The verum group received daily for one year an antioxidative cocktail consisting of : 300 μg selenium asl-selenomethionine , 45 mg zinc , 270 mg vitamin C , 2.7 mg vitamin A , 6 mg vitamin B-6 , and 465 mg vitamin E ( d-alfatocopherol ) . Furthermore , in order to enhance exchange in polyenoic acids , each subject received daily 250 mg gamma-linolenic acid . The placebo groups received similar looking pills and capsules without the active components . During one year in the verum group , the whole blood selenium , the hydrogen-dependent glutathione peroxidase ( GSH-Px ) of erythrocytes , and the vitamin E level in serum was found increased compared to the pretreatment values and to the placebo group . No change could be traced in thet-butylhydroperoxide dependent GSH-Px , an enzyme that also assays the glutathione-s-transferase . During the same period of time , the fasting levels of serum fatty acid and the content of lipofuscin in erythrocytes were estimated . Compared to the pretreatment values , the lipofuscin level declined significantly and the level of w-3 penta- and hexaenoic acids increased in the verum , but not in the placebo group . During the study period , slight , but significant improvements in psychological scores could be traced . Furthermore , the assays of bloodflow in different areas of the brain surface ( i.e. , the ISI values ) revealed a general trend to improvement in all areas , when the ISI values were compared during treatment with the pretreatment values and the values in the placebo group PURPOSE To analyze brightness , contrast , and color balance of digital versus film retinal images in a multicenter clinical trial , to propose a model image from exemplars , and to optimize both image types for evaluation of age-related macular degeneration ( AMD ) . METHODS The Age-Related Eye Disease Study 2 ( AREDS2 ) is enrolling subjects from 90 clinics , with three quarters of them using digital and one quarter using film cameras . Image brightness ( B ) , contrast ( C ) , and color balance ( CB ) were measured with three-color luminance histograms . First , the exemplars ( film and digital ) from expert groups were analyzed , and an AMD-oriented model was constructed . Second , the impact of B/C/CB on the appearance of typical AMD abnormalities was analyzed . Third , B/C/CB in AREDS2 images were compared between film ( 156 eyes ) and digital ( 605 eyes ) , and against the model . Fourth , suboptimal images were enhanced by adjusting B/C/CB to bring them into accord with model parameters . RESULTS Exemplar images had similar brightness , contrast , and color balance , supporting an image model . Varying a specimen image through a wide range of B/C/CB revealed greatest contrast of drusen and pigment abnormalities against normal retinal pigment epithelium with the model parameters . AREDS2 digital images were more variable than film , with lower correspondence to our model . Ten percent of digital were too dim and 19 % too bright ( oversaturated ) , versus 1 % and 4 % of film , respectively . On average , digital had lower green channel contrast ( giving less retinal detail ) than film . Overly red color balance ( weaker green ) was observed in 23 % of digital versus 8 % of film . About half of digital ( but fewer film ) images required enhancement before AMD grading . After optimization of both image types , AREDS2 image quality was judged as good as that in AREDS ( all film ) . CONCLUSIONS A histogram-based model , derived from exemplars , provides a pragmatic guide for image analysis and enhancement . In AREDS2 , the best digital images matched the best film . Overall , however , digital provided lower contrast of retinal detail . Digital images taken with higher G-to-R ratio showed better brightness and contrast management . Optimization of images in the multicenter study helps st and ardize documentation of AMD ( Clinical Trials.gov NCT00345176 ) We investigated the association between self-reported alcohol ingestion and colorectal cancer in a cohort of male smokers in Finl and . Among 27,109 men aged 50 to 69 years , 87 colon and 53 rectal cases were diagnosed during the five to eight years of follow-up . Among drinkers , colorectal cancer risk increased with the amount of alcohol consumed ( P trend = 0.01 ) with risk increasing by 17 percent for each drink consumed . Both beer and spirits contributed to this increased risk . Further analyses revealed that the positive association with alcohol was primarily for colon cancer ( P trend = 0.01 ) . Interestingly , risk of colorectal cancer associated with drinking ( cf self-reported abstinence ) changed with follow-up time , suggesting an inverse association for alcohol early in follow-up , and a positive association after about three- and -a-half years of follow-up . Follow-up time did not modify the positive association with amount of alcohol among drinkers , however . Results also indicated that β-carotene supplementation may attenuate the effect of alcohol on colorectal cancer risk among drinkers . In conclusion , this study supports a role for alcohol in colon carcinogenesis and suggests that similar studies should evaluate carefully the effects of lifetime drinking habits and recent abstinence PURPOSE To examine whether low-dose aspirin ( 325 mg on alternate days ) reduces the risk of age-related cataract and subtypes . This report extends previous findings , including both subtypes and additional newly identified incident cases since the earlier report . METHODS All 20,979 participants in the Physicians ' Health Study , a r and omized trial of aspirin and beta-carotene among U.S. male physicians age 40 - 84 in 1982 , who did not report cataract at baseline were included . Average follow-up was five years . The main outcome measure was incident , age-related cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse , based on self-report confirmed by medical record review . RESULTS 501 age-related cataracts were diagnosed during follow-up , including 416 with nuclear sclerosis and 212 with a posterior subcapsular component ; 318 cataracts progressed to surgical extraction . Overall , there were 245 cataracts in the aspirin group and 256 in the placebo group ( relative risk [ RR ] , 0.94 ; 95 % confidence interval [ CI ] , 0.79 to 1.13 ; P = 0.52 ) . Cataract extraction s were 19 % less frequent in the aspirin than in the placebo group ( RR , 0.81 ; 95 % CI , 0.65 to 1.01 ; P = 0.06 ) . In subgroup analyses of subtypes , aspirin takers had a lower risk of posterior subcapsular cataract ( RR , 0.74 ; 95 % CI , 0.57 to 0.98 ; P = 0.03 ) but not nuclear sclerosis ( RR , 0.96 ; 95 % CI , 0.79 to 1.16 ; P = 0.65 ) cataract . CONCLUSIONS Overall , these r and omized trial data tend to exclude a large benefit of five years of low-dose aspirin therapy on cataract development and extraction . The data are compatible with a modest benefit on cataract extraction for this duration of aspirin therapy . Subgroup analyses raise the possibility of a modest , but potentially important , protective effect of aspirin on posterior subcapsular cataract , a particularly disabling subtype To examine whether vitamin/mineral supplementation may lower mortality and incidence from human cancer and mortality from other diseases as well as to provide the scientific basis and feasible approach for human cancer prevention and control , between 1982 - 1991 scientists from China and USA conducted two r and omized , double-blind , and placebo-controlled nutrition intervention trials in Linxian , China , where the esophageal/gastric cardia cancer mortality rates are among the highest in the world and there is suspicion that the population 's chronic deficiencies of multiple nutrients are etiologically involved . In the first trial , the Dysplasia Trial , 3,318 individuals with a cytologic diagnosis of esophageal dysplasia received daily 26 vitamin/mineral supplements or placebos for 6 years ; The second trial , the General Population Trial , involved 29,584 individuals and used an one-half replicate of a 2(4 ) fractional factorial design which r and omized to 8 groups for testing the effects of daily supplementation of 4 different vitamin/mineral combinations and placebo for a period of 5 1/4 years . Compliance assessed by monthly pill counts and quarterly monitoring of biochemical assays indicated that the participant compliance was excellent . As endpoints of the trials , incident cancers and deaths were identified through all medical facilities in local areas , supplemented by special endoscopy and cytology examinations , and confirmed by 3-level review groups . A total of 323 deaths occurred during 6 year period among participants in the dysplasia trial , and 2,127 deaths from the general population trial during 5 1/4 years . Besides , an eye examination , which included detailed lens evaluations , was included in the extensive re-examination protocol to ascertain whether use of the supplements had affected the risk of developing age-related cataracts among participants in the two trials . Results from Dysplasia Trial indicated that after 6 years of daily supplementation with multiple vitamins and minerals , total mortality among those in the active treatment group was slightly ( 9 % ) lower than in the placebo group ; and deaths of esophageal cancer also declined by 17 % , as well as a sizeable reduction in cerebrovascular disease mortality ( near 40 % ) was seen , though none was statistically significant . However , intervention had decreased prevalence of eye nuclear cataract ( 43 % ) ( P < 0.01 ) . The findings from the General Population Trial provide support for the hypothesis that intake of specific micronutrients may inhibit cancer development . Significant reduction of total mortality ( 9 % ) , cancer mortality ( 13 % ) , gastric cancer mortality ( 20 % ) , and mortality of the other cancers ( 19 % ) occurred among those receiving beta-carotene/vitamin E/selenium supplementation ( P < 0.05 ) . Patterns of cancer incidence , based on 1307 cases , generally resembled those for cancer mortality . ( ABSTRACT TRUNCATED AT 400 WORDS Purpose : To test the hypothesis that daily use of zinc-monocysteine ( ZMC ) supplement will be well tolerated and result in improved macular function in persons with dry age-related macular degeneration ( AMD ) . Methods : Eligible , consenting subjects were r and omized to either ZMC 25 mg or placebo twice daily for 6 months . Both ZMC and placebo groups enrolled 40 participants , with best corrected visual acuity 20/25 to 20/70 , macular drusen , and pigment changes . Masked personnel determined baseline , 3- and 6-month best-corrected visual acuity , contrast sensitivity , and light flash recovery time . Differences between ZMC and placebo were analyzed by a one-sided unpaired t-test of the paired differences between baseline and 3- and 6-month timepoints for right and left eyes separately . Results : By 6 months the ZMC group showed improved visual acuity ( p < 0.0001 ) and contrast sensitivity ( p < 0.0001 ) . Macular light flash recovery time shortened in the ZMC group at 3 months by 2.1 sec ( left eye , p = 0.0001 ) to 3.6 sec ( right eye , p < 0.0001 ) , and at 6 months by 7.2 sec ( left eye , p < 0.0001 ) to 7.4 sec ( right eye , p < 0.0001 ) . This variable had no improvement in the placebo group . ZMC had a gastrointestinal irritation rate of under 2 % . Conclusion : ZMC 25 mg twice daily was well tolerated and was associated with improved macular function in comparison to a placebo in persons with dry AMD The objective of this study was to determine the effects of a year of Zn supplementation on Zn concentrations in circulating cells and on cellular immune functions in the elderly . Subjects , aged 60 - 89 , were given a placebo , 15 mg Zn , or 100 mg Zn daily for 12 months . All subjects also received a multivitamin/mineral supplement that contained no additional Zn . Blood sample s were drawn and immune functions assessed prior to and at 3 , 6 , 12 , and 16 months after beginning Zn supplementation . Subject diets were also assessed at each visit . Dietary folate , pyridoxine , alpha-tocopherol , copper , zinc , and magnesium were consistently below recommended intakes . Although plasma Zn increased significantly in the 100 mg Zn treatment group , concentrations of Zn in erythrocytes , mononuclear cells , polymorphonuclear leukocytes , and platelets were not significantly increased by zinc supplementation . Natural killer cell activity was transiently enhanced by the 100 mg/day dose of Zn . There was a progressive improvement in delayed dermal hypersensitivity ( DDH ) and in lymphocyte proliferative responses to two mitogens ; this may have been due to one or more components of the multivitamin/mineral supplement administered to all study subjects . The enhancement of DDH was significantly greater in the placebo group than in either zinc treatment group . Thus , zinc had a beneficial effect on one measure of cellular immune function while simultaneously having an adverse effect on another measure of cellular immunity PURPOSE Animal research and observational studies in man suggest a protective effect of antioxidant vitamins in the development of age-related maculopathy ( ARM ) . METHODS The ATBC study , a population -based , controlled clinical trial of alpha-tocopherol and beta carotene to prevent lung cancer , took place in Finl and between 1984 and 1993 . Over 29,000 smoking males aged 50 to 69 years were r and omly assigned to alpha-tocopherol ( AT ; 50 mg/day ) , beta-carotene ( BC ; 20 mg/day ) , both of these , or placebo . We performed an end-of-trial ophthalmological examination on a r and om sample of 941 participants aged 65 years or more from two of the fourteen study areas , to discover if the five to eight-year intervention with alpha-tocopherol and /or beta-carotene had been associated with a difference in ARM prevalence . Age-related maculopathy was assessed using colour photographs of the macula . RESULTS Altogether , 269 cases of ARM were found ; there were more cases in the AT group ( 32 % ; 75/237 ) , BC group ( 29 % ; 68/234 ) , and combined antioxidant group ( 28 % ; 73/257 ) than in the placebo group ( 25 % ; 53/213 ) . However , neither substance was significantly associated with the risk of ARM in a logistic regression analysis controlling for possible risk factors . CONCLUSIONS No beneficial effect of long-term supplementation with alpha-tocopherol or beta-carotene on the occurrence of ARM was detected among smoking males Colonic adenomas represent the natural precursor lesions of most colorectal cancers . The treatment of choice is endoscopic polypectomy . However , after endoscopic removal , polyps recur in a large fraction of cases . Thus , we evaluated the effect of antioxidant vitamins or lactulose on the recurrence rate of adenomatous polyps . After polypectomy , 255 individuals were r and omized into three groups . Group 1 was given vitamin A ( 30,000 IU/ day ) , vitamin C ( 1 g/day ) , and vitamin E ( 70 mg/day ) ; Group 2 was given lactulose ( 20 g/day ) ; Group 3 received no treatment . Forty-six subjects had to be excluded because the histologic diagnosis was not consistent with adenoma . The remaining 209 individuals were included in the analysis according to the “ intention to treat ” criterion , though 34 did not adhere to the scheduled treatment or were lost during the follow-up . Subjects were followed at regular intervals for an average of 18 months . Polyps recurring before one year from index colonoscopy were considered missed by the endoscopist . In the 209 evaluable subjects , the percentages of recurrence of adenomas were 5.7 percent , 14.7 percent , and 35.9 percent in the vitamins , lactulose , and untreated groups , respectively . The fraction of subjects remaining free of adenomas , estimated by Kaplan-Meier survival curves , was significantly different among the three groups ( log-rank chisquared = 17.138;P < 0.001 ) . Using Cox 's regression analysis , treatment was the only variable that significantly contributed to the model ( regression coefficient=0.905;P<0.001 ) . In conclusion , either antioxidant vitamins or , to a lesser extent , lactulose lower the recurrence rate of adenomas of the large bowel and can be proposed as chemopreventive agents , at least in high-risk individuals The Physicians ' Health Study is a r and omized , double-blind , placebo-controlled trial of primary prevention design ed to assess the effects of low-dose aspirin on cardiovascular disease and of beta-carotene on risks of cancer . A total of 22,071 U.S. male physicians 40 to 84 years of age were r and omized to one of four treatment groups : active aspirin and active beta-carotene , active aspirin and beta-carotene placebo , aspirin placebo and active beta-carotene , or both placebos . Whereas the beta-carotene component of the trial is ongoing , the blinded aspirin component was terminated early primarily because of a statistically extreme benefit of aspirin on first myocardial infa rct ion . We obtained data relating to a large number of variables , including demographics , personal medical history , family history , health habits , and diet before r and omization and compared them among the four treatment groups . As expected in a r and omized trial of this sample size , the distribution of baseline characteristics was virtually identical among the treatment groups . This comparison indicates certainly no confounding by the baseline variables that were collected and suggests that other unmeasured or unknown potential confounders are also likely to be distributed evenly between the treatment groups . Thus , any observed differences in outcome between these groups likely result from the effects of the treatments themselves The role of alcohol as a determinant of age-related cataract is largely unexplored , although a possible influence has been suggested by previous retrospective and cross-sectional studies . We used the prospect i ve data base of the Physicians ' Health Study to examine the association between alcohol consumption and incidence of cataract as well as cataract extraction among U.S. male physicians . Participants in the Physicians ' Health Study , a r and omized trial of aspirin and beta-carotene among 22,071 male physicians 40 - 84 years of age at entry in 1982 , were included in these analyses if they did not report cataract at baseline and if they provided information about alcohol consumption and other cataract risk factors . A total of 17,824 physicians satisfied these criteria . An incident cataract was defined as a self-report confirmed by medical record review , first diagnosed after r and omization , with an age-related cause , and responsible for a reduction in best corrected visual acuity to 20/30 or worse . During 88,565 person-years of follow-up , 371 participants had a confirmed incident cataract and 110 underwent cataract extraction . Compared to physicians consuming alcohol less than once per month , daily consumers of alcohol had an age-adjusted relative risk ( RR ) of cataract of 1.31 ( 95 % confidence interval [ CI ] = 0.95 , 1.81 ) . For posterior subcapsular ( PSC ) cataract , the most disabling subtype in terms of vision loss , the RR was 1.38 ( 95 % CI = 0.84 , 2.27 ) ; for PSC cataract extraction , the RR was 1.43 ( 95 % CI = 0.71 , 2.88 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Epidemiological evidence suggests that antioxidants protect against the development of atherosclerosis . To determine the effectiveness of antioxidant therapy in patients with lower limb atherosclerosis , a r and omized placebo-controlled trial was performed in 120 men and women with intermittent claudication and an ankle/brachial pressure index ( ABPI ) ≤0.9 . The study was analysed on an intention-to-treat basis . After 2 years , there were no significant differences between antioxidant and placebo groups in plasma cholesterol , lipoproteins , haemostatic or rheological factors . However , after 6 months , low density lipoprotein cholesterol was significantly lower in those taking antioxidant ( 108.0 mg/dl compared with 120.1 mg/dl , p < 0.05 ) . There were no differences in the ABPI or walking distance , although both groups improved slightly with time . The incidence of cardiovascular events and death was nonsignificantly lower in the antioxidant compared with the placebo group : event rates per year were 5.5 % ( 95 % Cl 2.4–8.6 ) in the first year and 9.6 % ( 95 % Cl 6.8–12.4 ) in the second year for those on antioxidants ; and 7.7 % ( 95 % Cl 5.1–10.3 ) and 13.3 % ( 95 % Cl 8.9–17.7 ) respectively for those on placebo . Significantly fewer serious adverse events occurred in the antioxidant than the placebo group : 21.8 % ( 95 % Cl 16.2–27.4 ) compared with 40.0 % ( 95 % Cl 33.9–46.1 ) . This study therefore suggests that although antioxidants may prevent cardiovascular events in patients with peripheral atherosclerosis , they do not improve lower limb function On the basis of epidemiologic and experimental evidence of an anticancer activity of vitamin A , a r and omized clinical trial was activated in Milan with the aim of evaluating if retinol palmitate administration ( per os , 300,000 I.U. daily ) after complete resection of stage Ia non small-cell lung cancer could reduce the occurrence of cancer relapses ( within 3 years ) and /or the occurrence of new primary tumors ( beyond 3 years ) . By September 1987 , 181 patients had entered the trial : 87 in the treatment arm and 94 in the control arm . After a median follow-up of 14 months , the interim analysis was focused on the evaluation of toxicity , compliance , and early recurrences . Although the large majority of patients were affected by skin and mucous membrane desquamation and dryness during treatment , these symptoms were generally mild and well tolerated , and never induced the patient to stop the treatment . Other side effects like headache , hair loss , itching , or dyspepsia were detected at a much lower frequency . Only in 3 patients the treatment was interrupted , because of signs or symptoms potentially related to vitamin A administration . At the time of the analysis , a total of 42 ( 23 % ) patients had relapsed ; 16 ( 18 % ) in the treated arm , and 26 ( 28 % ) in the control arm . The largest difference between treated patients and controls was observed for bone metastases ( 2 vs. 7 ) and brain metastases ( 3 vs. 6 ) , and for squamous histology ( 6 vs. 11 ) . Only 2 cases of new primary cancer were detected , both in the control arm . These results are promising both in terms of tolerance and efficacy of treatment , but given the short median follow-up they must be very cautiously interpreted . A longer follow-up is necessary to establish whether a significant proportion of early recurrences could be prevented , or only delayed , by vitamin A administration PURPOSE To examine if long-term supplementation with alpha-tocopherol ( AT ) or beta-carotene ( BC ) was associated with the prevalence of vascular changes in retinal arterioles . METHODS An end-of-trial sub sample from a double-blind , placebo-controlled clinical trial design ed to study the effects of alpha-tocopherol and beta-carotene on lung cancer incidence ( ATBC Study ) . SETTING Source population of Helsinki and the surrounding province . PARTICIPANTS 1072 men 50 - 69 years old and smoking at least 5 cigarettes per day at study entry . INTERVENTIONS R and om allocation to one of four supplementation regimens : 50 mg per day alpha-tocopherol , 20 mg per day beta-carotene , both alpha-tocopherol and beta-carotene , or placebo . Median follow-up time was 6.6 years ( range 5.2 - 8.0 years ) . MAIN OUTCOME MEASURE Presence of vascular changes in retinal arterioles as determined from end-of-trial retinal color photographs . RESULTS Retinal vascular changes were most prevalent in the AT ( 161 men , 62 % ) , and in the BC ( 163 men , 62 % ) groups . The prevalence rate was lowest in the AT plus BC group ( 161 men , 55 % ) , and slightly higher in the placebo group ( 145 men , 57 % ) . There was no statistically significant association of either AT ( OR 0.9 , 95 % CI 0.7 - 1.2 ) or BC ( OR 1.0 , 95 % CI 0.8 - 1.3 ) supplementation with the prevalence of retinal vascular changes after adjusting for major risk factors . CONCLUSIONS Supplementation with alpha-tocopherol or beta-carotene for a median of 6.6 years does not protect against retinal vascular changes among smoking males BACKGROUND AND PURPOSE The evaluation of cerebrovascular end points in prospect i ve studies is often based exclusively on medical record examination and may be made by more than one observer over time . To address the issues of adequacy of medical record information and consistency in diagnosis over time , we evaluated interobserver agreement for the main items of the stroke classification system used in the Physicians ' Health Study . This trial included 22,071 physicians r and omly assigned in 1982 to receive either aspirin or placebo to assess the subsequent risk of cardiovascular events , including stroke . METHODS Stroke subtype , stroke severity , and certainty of diagnosis were first classified from medical records from the years 1982 through 1988 . The 216 stroke events reported in this period were independently reclassified in 1994 and compared with the initial classification using kappa statistics . RESULTS Overall agreement in major stroke types ( hemorrhagic , ischemic , undetermined stroke ) as well as in hemorrhagic stroke subtypes was excellent ( kappa = 0.81 and kappa = 0.95 , respectively ) . A wide range of values for the ischemic stroke subtypes ( kappa = 0.13 to kappa = 0.96 ) was obtained . Agreement was substantial in assessment of stroke severity ( kappa = 0.71 ) , and it was fair ( kappa = 0.33 ) for certainty of diagnosis . CONCLUSIONS Interobserver agreement is high for major stroke types as well as for categories of hemorrhagic stroke on the basis of review of medical records and results of imaging data . The classification of ischemic stroke subtypes , however , is subject to substantial interobserver disagreement . Periodic reclassification of r and om sample s of end points might be considered in long-term prospect i ve studies to assess potential misclassification of events by different observers PURPOSE To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of the diagnosis of age-related macular degeneration ( AMD ) in a large-scale r and omized trial of male physicians . DESIGN R and omized , double-masked , placebo-controlled trial . PARTICIPANTS We included 14 236 apparently healthy United States male physicians aged ≥50 years who did not report a diagnosis of AMD at baseline . METHODS Participants were r and omly assigned to receive 400 international units ( IU ) of vitamin E or placebo on alternate days , and 500 mg of vitamin C or placebo daily . Participants reported new diagnoses of AMD on annual question naires and medical record data were collected to confirm the reports . MAIN OUTCOME MEASURES Incident diagnosis of AMD responsible for a reduction in best-corrected visual acuity to ≤20/30 . RESULTS After 8 years of treatment and follow-up , a total of 193 incident cases of visually significant AMD were documented . There were 96 cases in the vitamin E group and 97 in the placebo group ( hazard ratio [ HR ] , 1.03 ; 95 % confidence interval [ CI ] , 0.78 - 1.37 ) . For vitamin C , there were 97 cases in the active group and 96 in the placebo group ( HR , 0.99 ; 95 % CI , 0.75 - 1.31 ) . CONCLUSIONS In a large-scale , r and omized trial of United States male physicians , alternate-day use of 400 IU of vitamin E and /or daily use of 500 mg of vitamin C for 8 years had no appreciable beneficial or harmful effect on risk of incident diagnosis of AMD OBJECTIVES This study evaluated whether increased intake of fish oils ( eicosapentaenoic and docosahexaenoic acids ) might reduce the risk of coronary heart disease . BACKGROUND Observational and clinical studies have suggested that increased intake of fish oils , as reflected in plasma levels of fish oils , may reduce the risk of myocardial infa rct ion . METHODS A nested case-control study was conducted among the 14,916 participants in the Physicians ' Health Study with a sample of plasma before r and omization . Each participant with myocardial infa rct ion occurring during the first 5 years of follow-up was matched by smoking status and age with a r and omly chosen control participant who had not developed coronary heart disease . RESULTS Mean levels of fish oils ( with 95 % confidence interval [ CI ] for paired differences and p values ) in case and control participants , expressed as percent of total fatty acids , were , for eicosapentaenoic acid , 0.26 versus 0.25 ( 95 % CI -0.03 to 0.05 , p = 0.70 ) in cholesterol esters and 0.56 versus 0.54 ( 95 % CI -0.04 to 0.09 , p = 0.44 ) in phospholipids , and for docosahexaenoic acid , 0.23 versus 0.24 ( 95 % CI -0.07 to 0.04 , p = 0.64 ) in cholesterol esters and 2.22 versus 2.14 ( 95 % CI -0.10 to 0.27 , p = 0.36 ) in phospholipids . Results adjusted for major cardiovascular risk factors showed a very similar lack of association between fish oil levels and the incidence of myocardial infa rct ion . CONCLUSIONS These results indicate no beneficial effect of increased fish oil consumption on the incidence of a first myocardial infa rct ion . However , the effect of very high levels of fish oils could not be evaluated Alpha-tocopherol ( vitamin E ) may play a role in the treatment of arterial thromboembolic disease , possibly by inhibiting platelet aggregation . Thus far , no clinical evidence exists for this effect . The objective of this study was to assess the effect of alpha-tocopherol supplementation on gingival bleeding either in combination with acetylsalicylic acid ( ASA ) or without it . This study was an end-point examination of a r and om sample of male smokers who had participated in a controlled clinical trial , the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study ( ATBC Study ) for 5 - 7 years . The study included 409 men aged 55 - 74 years of whom 191 received alpha-tocopherol supplementation ( 50 mg/day ) ; 56 used ASA , 30 received both and 132 received neither . Gingival bleeding was examined by probing with a WHO probe and reported as a percentage of bleeding sites adjusted by the logistic regression model . Gingival bleeding was more common in those who received alpha-tocopherol compared with nonreceivers among subjects with a high prevalence of dental plaque ( P < 0.05 ) . ASA alone increased bleeding only slightly . The highest risk of gingival bleeding was among those who took both alpha-tocopherol and ASA ( 33.4 % of probed sites bleeding vs 25.8 % among subjects taking neither alpha-tocopherol nor ASA , P < 0.001 ) . In the ATBC Study , more deaths from haemorrhagic stroke and fewer from ischaemic heart disease were observed among those participants who received alpha-tocopherol compared with those who did not . Based on the results of the present study and the ATBC Study , we conclude that alpha-tocopherol supplementation may increase the risk of clinical ly important bleedings , particularly when combined with ASA The objective of this study was to examine the effect of retinol and isotretinoin on the incidence of nonmelanoma skin cancer in high-risk subjects . A total of 525 participants with a history of at least four basal cell carcinomas ( BCCs ) and /or cutaneous squamous cell carcinomas ( SCCs ) were entered into a r and omized , double-blind , placebo-controlled trial , performed in free-st and ing study clinics . Participants were r and omly assigned to receive oral retinol ( 25,000 units ) , isotretinoin ( 5 - 10 mg ) , or placebo supplementation daily for 3 years . The time to first new occurrence of BCC or cutaneous SCC was used as the outcome measure . During the study period , 319 BCCs and 125 cutaneous SCCs were diagnosed clinical ly and pathologically . There were no differences between those who received retinol , isotretinoin , or the placebo , with regard to the time to first occurrence or to the total number of tumors noted . No beneficial effects were noted with regard to the prevention of nonmelanoma skin cancer with either retinol or isotretinoin In cancer chemoprevention trials , biomarkers as intermediate end points have gained importance . A variety of biomarkers have been proposed as intermediate end points for upper aerodigestive tract cancers . This study was aim ed at study ing the frequency of micronucleated cells and carcinogen DNA adducts as indicators of DNA damage and intervention end points in chemoprevention trials . Reverse smokers of chutta ( rolled tobacco ) from four villages numbering 298 in total were selected . Out of these , 150 were supplemented with four nutrients ( vitamin A , riboflavin , zinc and selenium ) and 148 controls received placebo , one capsule twice a week for 1 year . Slides of buccal smears were prepared and stained with Fuelgen reaction and counterstained with Fast Green and examined microscopically for the presence of micronucleated cells . Oral cell washings were collected and centrifuged . The DNA adducts were evaluated by the 32P post-labelling assay method . Protein and RNA free DNA ( adducted ) isolated from the cells was digested with MN/SPD and the DNA adducts isolated by the butanol enrichment procedure . The DNA adducts were identified and quantitated by multidimensional chromatography on PEI-TLC sheets by screen enhanced autoradiography and presented as RAL ( relative adduct labelling ) values . Both the micronuclei and DNA adducts were significantly elevated in subjects with lesions . At the end of 1 year the frequency of micronuclei decreased significantly ( P < 0.001 ) in the supplemented subjects with or without lesions . The DNA adducts in the supplement group at the end of 1 year also reduced significantly . The adducts decreased by 95 % in subjects with all categories of lesions and by 72 % in subjects without lesions . No such effects were noted in the placebo group . The two biomarkers investigated in the case study appear to be modifiable by the administration of micronutrient supplements . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE Zinc is a common dietary supplement that is widely believed to have beneficial health effects . To assess the impact of high dose supplemental zinc on genitourinary diseases we analyzed a recent r and omized trial comparing zinc , antioxidants and their combination to placebo for complications related to the genitourinary tract . MATERIAL S AND METHODS In a further analysis of the recent Age-related Eye Disease Study we examined the data pool for primary International Classification of Diseases , 9th revision codes given for hospital admissions related to urological problems . The Age-Related Eye Disease Study r and omized 3,640 patients with age related macular degeneration to 1 of 4 study arms , including placebo , antioxidants ( 500 mg vitamin C , 400 IU vitamin E and 15 mg beta-carotene ) , 80 mg zinc and antioxidant plus zinc . Statistical analyses using Fisher 's exact test were performed . RESULTS We found a significant increase in hospital admissions due to genitourinary causes in patients on zinc vs nonzinc formulations ( 11.1 % vs 7.6 % , p = 0.0003 ) . The risk was greatest in male patients ( RR 1.26 , 95 % CI 1.07 - 1.50 , p = 0.008 ) . In the study group of 343 patients requiring hospital admission the most common primary International Classification of Diseases , 9th revision codes included benign prostatic hyperplasia/urinary retention ( benign prostatic hyperplasia ) , urinary tract infection , urinary lithiasis and renal failure . When comparing zinc to placebo , significant increases in urinary tract infections were found ( p = 0.004 ) , especially in females ( 2.3 % vs 0.4 % , RR 5.77 , 95 % CI 1.30 - 25.66 , p = 0.013 ) . Admissions for urinary lithiasis approached significance in men on zinc compared to placebo ( 2.0 % vs 0.5 % , RR = 4.08 , 95 % CI 0.87 - 19.10 ) . There was no increase in prostate or other cancers with zinc supplementation . A significant decrease in prostate cancer diagnoses was seen in patients receiving antioxidants vs placebo ( RR = 0.6 , 95 % CI 0.49 - 0.86 , p = 0.049 ) . Subgroup analysis revealed that this finding was significant in men who smoked but not in nonsmokers . CONCLUSIONS Zinc supplementation at high levels results in increased hospitalizations for urinary complications compared to placebo . These data support the hypothesis that high dose zinc supplementation has a negative effect on select aspects of urinary physiology BACKGROUND Beta carotene has been associated with a decreased risk of human cancer in many studies employing dietary question naires or blood measurements , and it has had protective effects in some animal models of carcinogenesis . METHODS We tested the possible cancer-preventing effects of beta carotene by r and omly assigning 1805 patients who had had a recent nonmelanoma skin cancer to receive either 50 mg of beta carotene or placebo per day and by conducting annual skin examinations to determine the occurrence of new nonmelanoma skin cancer . RESULTS Adherence to the prescribed treatment was good , and after one year the actively treated group 's median plasma beta carotene level ( 3021 nmol per liter ) was much higher than that of the control group ( 354 nmol per liter ) . After five years of follow-up , however , there was no difference between the groups in the rate of occurrence of the first new nonmelanoma skin cancer ( relative rate , 1.05 ; 95 percent confidence interval , 0.91 to 1.22 ) . In subgroup analyses , active treatment showed no efficacy either in the patients whose initial plasma beta carotene level was in the lowest quartile or in those who currently smoked . There was also no significant difference between treated and control groups in the mean number of new nonmelanoma skin cancers per patient-year . CONCLUSIONS In persons with a previous nonmelanoma skin cancer , treatment with beta carotene does not reduce the occurrence of new skin cancers over a five-year period of treatment and observation Epidemiological evidence suggests that airway obstruction is an independent risk factor for lung cancer and that this can not be explained by active or passive smoking alone . Chlamydia pneumoniae infection has been associated with chronic bronchitis and its exacerbates . Our aim was to evaluate the association between chronic C. pneumoniae infection and risk of lung cancer among male smokers . Smoking males with lung cancer ( n = 230 ) and their age- and locality-matched controls were selected among participants of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study . The presence of C. pneumoniae infection was assessed by analyzing specific antibodies and immune complexes in 2 serum sample s collected with a 3-year interval before the lung cancer diagnosis . The diagnosis of chronic infection was based on stable levels of positive specific IgA antibody ( titer > or = 16 ) and immune complex ( titer > or = 4 ) . Relative risks were estimated by odds ratios ( OR ) adjusted for age , locality and smoking history by a conditional logistic regression model . Markers suggesting chronic C. pneumoniae infection were present in 52 % of cases and 45 % of controls and hence were positively associated with the incidence of lung cancer ( OR 1.6 ; 95 % confidence interval [ CI ] 1.0 - 2.3 ) . The incidence was especially increased in men younger than 60 years ( OR 2.9 ; 95 % CI 1.5 - 5.4 ) but not in the older age group ( OR 0.9 ; 95 % CI 0.5 - 1.6 ) . Before concluding that C. pneumoniae infection is a new independent risk factor for lung cancer , corroboration from other studies with larger number of cases and longer follow-up is needed 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 ) OBJECTIVE : To examine the effect of alpha tocopherol and beta carotene supplementation on the incidence of age related cataract extraction . SETTING : The Alpha-tocopherol Beta-carotene ( ATBC ) Study was a r and omised , double blind , placebo controlled , 2 x 2 factorial trial conducted in south western Finl and . The cataract surgery study population of 28,934 male smokers 50 - 69 years of age at the start . INTERVENTION : R and om assignment to one of four regimens : alpha tocopherol 50 mg per day , beta carotene 20 mg per day , both alpha tocopherol and beta carotene , or placebo . Follow up continued for five to eight years ( median 5.7 years ) with a total of 159,199 person years . OUTCOME MEASURE : Cataract extraction , ascertained from the National Hospital Discharge Registry . RESULTS : 425 men had cataract surgery because of senile or presenile cataract during the follow up . Of these , 112 men were in the alpha tocopherol alone group , 112 men in the beta carotene alone group , 96 men in the alpha tocopherol and beta carotene group , and 105 men in the placebo group . When supplementation with alpha tocopherol and with beta carotene were introduced to a Cox proportional hazards model with baseline characteristics ( age , education , history of diabetes , body mass index , alcohol consumption , number of cigarettes smoked daily , smoking duration , visual acuity , and total cholesterol ) , neither alpha tocopherol ( relative risk , RR , 0.91 , 95 % confidence intervals , CI , 0.74 , 1.11 ) nor beta carotene ( RR 0.97 , 95 % CI 0.79 , 1.19 ) supplementation affected the incidence of cataract surgery . CONCLUSION : Supplementation with alpha tocopherol or beta carotene does not affect the incidence of cataract extraction s among male smokers A r and omized , double-blind , placebo-controlled clinical trial was conducted to determine the effects of a low-dose ( < 2 times the Recommended Dietary Allowance ) micronutrient supplement containing trace minerals ( zinc and selenium ) and /or vitamins/provitamins ( vitamin C , alpha-tocopherol , and beta-carotene ) on the incidence of respiratory and urogenital infections in institutionalized elderly . After 2 years , there was a significant decrease in the mean number of infections in elders given trace elements ( p < 0.01 ) but not vitamins A double-blind , placebo-controlled trial is being conducted in a population at high risk for gastric cancer in Venezuela . The main aim of the trial is to assess the effect of antioxidant vitamins ( beta-carotene , vitamin C and vitamin E ) in blocking the progression of precancerous lesions of the stomach . Within the framework of a screening programme for stomach cancer , 2200 subjects of 35 - 69 years of age have been recruited . At study entry , a dietary question naire was completed , and gastroscopy with the collection of seven gastric biopsies was performed . After baseline examinations , the study participants were r and omized to receive antioxidant treatment or placebo for three years . The treatment phase will be completed in mid-1998 . At the end of the treatment phase , the investigations performed at study entry will be repeated . Before the initiation of the trial , various pilot studies were carried out that showed an extremely high prevalence of Helicobacter pylori infection ( over 90 % ) . Two eradication trials using anti-H. pylori treatments that give good results in Europe and North America gave very poor results in our study population . The low eradication rates achieved ( 5 - 20 % ) suggest a high prevalence of antibiotic-resistant H. pylori strains or high reinfection rates . These disappointing results led to deletion of an anti-H. pylori treatment phase of the main trial OBJECTIVE To assess the effect of alpha-tocopherol and beta-carotene supplementation on the prevalence of oral mucosal lesions in smokers . DESIGN An end-point examination of a r and om sample of participants in a controlled trial for 5 - 7 years ( Alpha-Tocopherol Beta-Carotene Cancer Prevention Study ) in Helsinki , Finl and . SUBJECTS A total of 409 white male cigarette smokers , aged 55 - 74 years who received either alpha-tocopherol ( 50 mg per day ) or beta-carotene ( 20 mg per day ) supplementation , both of these or placebo capsules . METHODS Clinical examination of oral mucosae , histological examination of lesions showing leukoplakia and cytological examination of buccal epithelium . Statistical analysis using Fisher 's exact test . RESULTS No statistically significant differences were found between the study groups either in the prevalence of oral mucosal lesions or in the cells of unkeratinized epithelium . Leukoplakia was present in 24 ( 5.9 % ) of the subjects . Seven lesions showed dysplasia . CONCLUSION The present study on oral health does not support the hypothesis that alpha-tocopherol or beta-carotene supplementation plays an essential role in preventing oral mucosal changes in smokers The possibility of pharmacological control of large bowel adenomas has been suggested by effectiveness of antioxidants in experimental tumor models and by the results of a limited clinical study using ascorbic acid . Over a two year period we tested this hypothesis in a r and omized , double‐blind study of 49 patients with polyposis coli . Of 36 patients who were evaluable at completion , 19 had received ascorbic acid , 3g/day , and 17 had received a placebo . We found a reduction in polyp area in the ascorbic acid‐treated group at nine months of follow‐up ( P < 0.03 ) and trends toward reduction in both number and area of rectal polyps during the middle of the trial . A labeling study of rectal epithelium with tritiated thymidine also hinted at a treatment effect . Our data suggest that ascorbic acid temporarily influenced polyp growth or turnover . Although these results have no current therapeutic value , our findings support continued studies of chemoprevention in this and other high risk setting BACKGROUND Lung cancer and cardiovascular disease are major causes of death in the United States . It has been proposed that carotenoids and retinoids are agents that may prevent these disorders . METHODS We conducted a multicenter , r and omized , double-blind , placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers , former smokers , and workers exposed to asbestos . The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol ( vitamin A ) in the form of retinyl palmitate per day on the primary end point , the incidence of lung cancer , were compared with those of placebo . RESULTS A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up ( mean length of follow-up , 4.0 years ) . The active-treatment group had a relative risk of lung cancer of 1.28 ( 95 percent confidence interval , 1.04 to 1.57 ; P=0.02 ) , as compared with the placebo group . There were no statistically significant differences in the risks of other types of cancer . In the active-treatment group , the relative risk of death from any cause was 1.17 ( 95 percent confidence interval , 1.03 to 1.33 ) ; of death from lung cancer , 1.46 ( 95 percent confidence interval , 1.07 to 2.00 ) ; and of death from cardiovascular disease , 1.26 ( 95 percent confidence interval , 0.99 to 1.61 ) . On the basis of these findings , the r and omized trial was stopped 21 months earlier than planned ; follow-up will continue for another 5 years . CONCLUSIONS After an average of four years of supplementation , the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer , cardiovascular disease , and any cause in smokers and workers exposed to asbestos BACKGROUND The intercellular adhesion molecule ICAM-1 mediates adhesion and transmigration of leucocytes to the vascular endothelial wall , a step proposed to be critical in the initiation and progression of atherosclerosis . Whether concentrations of soluble ICAM-1 ( sICAM-1 ) are raised in apparently healthy individuals who later suffer acute myocardial infa rct ion is unknown . METHODS We obtained baseline plasma sample s from a prospect i ve cohort of 14,916 healthy men enrolled in the Physicians ' Health Study . With a nested case-control design , we measured sICAM-1 concentrations for 474 participants who developed a first myocardial infa rct ion , and 474 controls ( participants who remained healthy throughout the 9-year follow-up ) . Cases were matched to controls according to age and smoking status at the time of myocardial infa rct ion . FINDINGS We found a significant association between increasing concentration of sICAM-1 and risk of future myocardial infa rct ion ( p = 0.003 ) , especially among participants with baseline sICAM-1 concentrations in the highest quartile ( > 260 ng/mL ; relative risk 1.6 [ 95 % Cl 1.1 - 2.4 ] , p = 0.02 ) . This association was present overall as well as among non-smokers , and persisted after control for lipid and non-lipid risk factors . In multivariate analyses , the risk of future myocardial infa rct ion was 80 % higher for participants with baseline sICAM-1 concentrations in the highest quartile ( relative risk 1.8 [ 1.1 - 2.8 ] , p = 0.02 ) . Similar risk estimates were seen among non-smokers . We found slight but significant correlations between sICAM-1 and fibrinogen , high-density-lipoprotein cholesterol , homocysteine , triglycerides , tissue-type plasminogen-activator antigen , and C-relative protein , but adjustment for these altered the risk little . The risk of myocardial infa rct ion associated with raised concentrations of sICAM-1 seemed to increase with length of follow-up . INTERPRETATION Our data support the hypothesis that cellular mediators of inflammation have a role in atherogenesis and provide a clinical basis to consider antiadhesion therapies as a novel means of cardiovascular disease prevention We undertook a prospect i ve study in senile cataract patients using systemic aspirin and systemic vitamin E. Vitamin E treated eyes did show less progression of PSC opacities extent and less new nuclear opacities during the follow-up , but overall vitamin E treated eyes did no better than the control group eyes . More eyes in systemic aspirin treated group maintained the initial vision and loss of vision in the aspirin group was also less marked . Aspirin also caused a significant less mean increase in cortical opacity extent , nuclear/opacity and density and PSC opacity extent and density as well as in ophthalmoscopically grade d opacity extent and density . We suggest that aspirin is a potential drug which should be further evaluated in large double blind photodocumentated studies . The present data does not justify the recommendation that aspirin be prescribed for slowing down cataract progression . This must await large studies and confirmation This intervention trial carried out in Uzbekistan ( former USSR ) in an area with a high incidence of oral and esophageal cancer involved r and om allocation of 532 men , 50 to 69 years old , with oral leukoplakia and /or chronic esophagitis to one of four arms in a double-blind , two-by-two factorial design , with active arms defined by the administration of ( a ) riboflavin ; ( b ) a combination of retinol , beta-carotene , and vitamin E ; or ( c ) both . Weekly doses were 100,000 IU of retinol , 80 mg of vitamin E , and 80 mg of riboflavin . The dose of beta-carotene was 40 mg/d . Men in the trial were followed for 20 months after r and omization . The aim of the trial was to determine whether treatment with these vitamins or their combination could affect the prevalence of oral leukoplakia and /or protect against progression of oral leukoplakia and esophagitis , conditions considered to be precursors of cancer of the mouth and esophagus . A significant decrease in the prevalence odds ratio ( OR ) of oral leukoplakia was observed after 6 months of treatment in men receiving retinol , beta-carotene , and vitamin E ( OR = 0.62 ; 95 % confidence interval ( CI ) : 0.39 to 0.98 ) . After 20 months of treatment , no effect of vitamin supplementation was seen when the changes in chronic esophagitis were compared in the four different treatment groups , although the risk of progression of chronic esophagitis was lower in the subjects allocated to receive retinol , beta-carotene and vitamin E ( OR = 0.65 ; 95 % CI : 0.29 to 1.48 ) A secondary analysis not based on the r and omized design revealed a decrease in the prevalence of oral leukoplakia in men with medium ( OR = 0.45 ; 95 % CI : 0.21 to 0.96 ) and high ( OR = 0.59 ; 95 % CI : 0.29 to 1.20 ) blood concentrations of beta-carotene after 20 months of treatment . Risk of progression of chronic esophagitis was also lower in men with a high blood concentration of beta-carotene , odds ratios being 0.30 ( 95 % CI : 0.10 to 0.89 ) and 0.49 ( 95 % CI : 0.15 to 1.58 ) for medium and high levels , respectively . A decrease in risk , also statistically not significant , was observed for high vitamin E levels ( OR = 0.39 ; 95 % CI : 0.14 to 1.10 ) . These results were based on levels of vitamins in blood drawn after 20 months of treatment Cataract is the leading cause of blindness in the world today , while age-related macular degeneration is responsible for the majority of new cases of visual impairment in the Western world . There is a growing body of evidence suggesting a role for antioxidant therapy to prevent the progression of these conditions . A 4-year prospect i ve , r and omised , controlled trial of an antioxidant versus placebo in a population of healthy volunteers aged 55 - 80 years at enrolment is described . This paper outlines the primary aims of the Vitamin E , Cataract and Age-related Macular Degeneration ( VECAT ) Study , the methodology , and the recruitment rates . Additional data on the toxicity and non-ocular effects of vitamin E will also be collected . St and ardised clinical grading of macular and lens features , and comparison of serial macular photographs and digital lens photographs will form the basis for assessment of primary study outcomes . Information collected in this study will assist in the assessment of the potential value of antioxidants in preventing the enormous burden imposed on developed communities by age-related eye disease . In addition , important data on prevalence and progression rates of cataract and macular degeneration will be collected In the fall of 1995 , 3411 subjects in 13 rural villages in Linqu County , Sh and ong Province , China , began participating in a blinded , r and omized 23 factorial trial to determine whether interventions can reduce the prevalence of dysplasia and other precancerous gastric lesions . One intervention is treatment for infection by Helicobacter pylori with amoxicillin and omeprazole . A second is dietary supplementation with capsules containing vitamin C , vitamin E , and selenium . A third is dietary supplementation with capsules containing steam-distilled garlic oil and Kyolic aged garlic extract . Investigators will evaluate histopathologic endpoints after gastroscopies with biopsies from seven st and ard sites in 1999 . Initial data from pill counts and sample d blood levels of vitamin E , vitamin C , and S-allylcysteine indicate excellent compliance . Subjects have tolerated all interventions well , although 3.1 % of those assigned to amoxicillin and omeprazole developed rashes , compared to 0.3 % to those in the control group . Preliminary breath tests demonstrate substantial reductions in gastric urease activity , an indication of infection by Helicobacter pylori , among those assigned to amoxicillin and omeprazole The U.S. Physicians ' Health Study , a primary prevention trial of low-dose aspirin in the reduction of cardiovascular disease and of beta-carotene in lowering cancer risk , implemented a number of design strategies to decrease costs and increase efficiency . These included the choice of physicians as the study population , use of a factorial design , implementation of a pre-r and omization run-in phase , and the collection of pre-r and omization blood specimens . The use of these strategies enabled us to enroll 22,071 subjects and maintain high compliance and long-term follow-up at a fraction of the usual cost of large-scale trials of primary prevention OBJECTIVE To evaluate the efficacy of low-dose aspirin in the primary prevention of myocardial infa rct ion among patients with chronic stable angina . DESIGN A r and omized , double-blind , trial . PATIENTS The study included 333 men with baseline chronic stable angina but with no previous history of myocardial infa rct ion , stroke , or transient ischemic attack who were enrolled in the Physicians ' Health Study , a trial of aspirin among 22,071 male physicians . INTERVENTION Patients were r and omly assigned to receive alternate-day aspirin therapy ( 325 mg ) or placebo and were followed for an average of 60.2 months for the occurrence of myocardial infa rct ion , stroke , or cardiovascular death . RESULTS During follow-up , 27 patients had confirmed myocardial infa rct ions ; 7 were among the 178 patients with chronic stable angina who received aspirin therapy and 20 were among the 155 patients who received placebo ( relative risk , 0.30 ; 95 % CI , 0.14 to 0.63 ; P = 0.003 ) . While simultaneously controlling for other cardiovascular risk factors in a proportional hazards model , an overall 87 % risk reduction was calculated ( relative risk , 0.13 ; CI , 0.04 to 0.42 ; P less than 0.001 ) . For the subgroup of patients with chronic stable angina but no previous coronary bypass surgery or coronary angioplasty , an almost identical reduction in the risk for myocardial infa rct ion was found ( relative risk , 0.14 ; CI , 0.04 to 0.56 ; P = 0.006 ) . Of 13 strokes , 11 occurred in the aspirin group and 2 in the placebo group ( relative risk , 5.4 ; CI , 1.3 to 22.1 ; P = 0.02 ) . No stroke was fatal , but 4 produced some long-term impairment of function . One stroke , in the aspirin group , was hemorrhagic . CONCLUSION Our data indicated that alternate-day aspirin therapy greatly reduced the risk for first myocardial infa rct ion among patients with chronic stable angina , a group of patients at high risk for cardiovascular death ( P less than 0.001 ) . Although our results for stroke were based on small numbers , they suggested an apparent increase in frequency of stroke with aspirin therapy ; this finding requires confirmation in r and omized trials of adequate sample size Over a 4-year period in a chemoprevention trial on large bowel neoplasia , 58 patients with familial adenomatous polyposis were treated with 4 g of ascorbic acid ( vitamin C)/day plus 400 mg of alpha-tocopherol ( vitamin E)/day alone or with a grain fiber supplement ( 22.5 g/day ) . In this r and omized , double-blind , placebo-controlled study , we determined the effects of these supplements on rectal polyps in these patients . Analysis by intent to treat suggested that the high-fiber supplement had a limited effect . Analysis adjusted for patient compliance showed a stronger benefit from the high-fiber supplement during the middle 2 years of the trial . The results provide evidence for inhibition of benign large bowel neoplasia by grain fiber supplements in excess of 11 g/day in this study population . The findings are consistent with the hypothesis that dietary grain fiber and total dietary fat act as competing variables in the genesis of large bowel neoplasia BACKGROUND People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel . Antioxidant vitamins , which are present in vegetables and fruits , have been associated with a diminished risk of cancers at various anatomical sites . We conducted a r and omized , controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma , a precursor of invasive cancer . METHODS We r and omly assigned 864 patients , using a two-by-two factorial design , to four treatment groups , which received placebo ; beta carotene ( 25 mg daily ) ; vitamin C ( 1 g daily ) and vitamin E ( 400 mg daily ) ; or the beta carotene plus vitamins C and E. In order to identify new adenomas , we performed complete colonoscopic examinations in the patients one year and four years after they entered the study . The primary end points for analyses were new adenomas identified after the first of these two follow-up examinations . RESULTS Patients adhered well to the prescribed regimen , and 751 completed the four-year clinical trial . There was no evidence that either beta carotene or vitamins C and E reduced the incidence of adenomas ; the relative risk for beta carotene was 1.01 ( 95 percent confidence interval , 0.85 to 1.20 ) ; for vitamins C and E , it was 1.08 ( 95 percent confidence interval , 0.91 to 1.29 ) . Neither treatment appeared to be effective in any subgroup of patients or in the prevention of any subtype of polyp defined by size or location . CONCLUSIONS The lack of efficacy of these vitamins argues against the use of supplemental beta carotene and vitamins C and E to prevent colorectal cancer . Although our data do not prove definitively that these antioxidants have no anticancer effect , other dietary factors may make more important contributions to the reduction in the risk of cancer associated with a diet high in vegetables and fruits OBJECTIVE To examine the association between cigarette smoking and the incidence of cataract . DESIGN , SETTING , AND PARTICIPANTS The design was a prospect i ve cohort study using data from the Physicians ' Health Study , a r and omized trial of aspirin and beta carotene among 22,071 US male physicians aged 40 to 84 years that began in 1982 . This analysis includes the 17,824 physicians who did not report cataract at baseline and did provide complete risk factor information . Based on information reported at baseline , 10 % were current smokers , 39 % were past smokers , and 51 % were never smokers . MAIN OUTCOME MEASURE An incident cataract was defined as a self-report confirmed by medical record review to have been first diagnosed after r and omization , age-related in origin , and responsible for a decrease in best corrected visual acuity to 20/30 or worse . MAIN RESULTS During 60 months of follow-up , 557 incident cataracts among 371 participants were confirmed . Compared with never smokers , current smokers of 20 or more cigarettes per day had a statistically significant increase in the risk of cataract ( relative risk [ RR ] , 2.16 ; 95 % confidence interval [ Cl ] , 1.46 to 3.20 ; P less than .001 ) . Similar results were obtained after simultaneously controlling for other potential cataract risk factors in a logistic regression model ( RR , 2.05 ; 95 % Cl , 1.38 to 3.05 ; P less than .001 ) . Among the 557 eyes with cataract , nuclear sclerotic changes were present in 442 while posterior subcapsular changes were present in 204 . After controlling for other potential cataract risk factors , current smokers of 20 or more cigarettes per day had statistically significant increases in nuclear sclerosis ( RR , 2.24 ; 95 % Cl , 1.47 to 3.41 ; P less than .001 ) and posterior subcapsular ( RR , 3.17 ; 95 % Cl , 1.81 to 5.53 ; P less than .001 ) cataract . Past smokers had an elevated risk of posterior subcapsular ( RR , 1.44 ; 95 % Cl , 0.97 to 2.13 ; P = .07 ) but not nuclear sclerosis cataract . For current smokers of fewer than 20 cigarettes per day , no increased risks were observed of total , nuclear sclerosis , or posterior subcapsular cataract . CONCLUSIONS These data provide support for the hypothesis that cigarette smoking increases the risk of developing both nuclear sclerosis and posterior subcapsular cataract Background Previous studies have demonstrated an increase in macular pigment optical density ( MPOD ) with lutein (L)-based supplementation in healthy eyes . However , not all studies have assessed whether this increase in MPOD is associated with changes to other measures of retinal function such as the multifocal ERG ( mfERG ) . Some studies also fail to report dietary levels of L and zeaxanthin ( Z ) . Because of the associations between increased levels of L and Z , and reduced risk of AMD , this study was design ed to assess the effects of L-based supplementation on mfERG amplitudes and latencies in healthy eyes . Methods Multifocal ERG amplitudes , visual acuity , contrast sensitivity , MPOD and dietary levels of L and Z were assessed in this longitudinal , r and omized clinical trial . Fifty-two healthy eyes from 52 participants were r and omly allocated to receive a L-based supplement ( treated group ) , or no supplement ( non-treated group ) . Results There were 25 subjects aged 18–77 ( mean age ± SD ; 48 ± 17 ) in the treated group and 27 subjects aged 21–69 ( mean age ± SD ; 43 ± 16 ) in the non-treated group . All participants attended for three visits : visit one at baseline , visit two at 20 weeks and visit three at 40 weeks . A statistically significant increase in MPOD ( F = 17.0 , p ≤ 0.001 ) and shortening of mfERG ring 2 P1 latency ( F = 3.69 , p = 0.04 ) was seen in the treated group . Conclusions Although the results were not clinical ly significant , the reported trend for improvement in MPOD and mfERG outcomes warrants further investigation The evidence for a potential benefit of antioxidant vitamins in the prevention and therapy of atherosclerotic disease is derived from laboratory , clinical , and observational epidemiologic studies but remains inconclusive . Data from r and omized clinical trials are sparse , particularly for women . Therefore , it is both timely and important to conduct large-scale primary and secondary prevention trials of antioxidants and cardiovascular disease ( CVD ) . The Women 's Antioxidant and Cardiovascular Study ( WACS ) is a r and omized , double-blind , placebo-controlled secondary prevention trial of the balance of benefits and risks of antioxidant vitamins ( vitamins E and C , and beta-carotene ) among 8000 women with preexisting CVD . This secondary prevention trial will be conducted as a companion to the recently started Women 's Health Study , a primary prevention trial of vitamin E and beta-carotene , as well as aspirin . In the WACS , US female health professionals aged 40 years and older with a history of myocardial infa rct ion , angina pectoris , coronary revascularization , stroke , transient cerebral ischemia , carotid endarterectomy , or peripheral artery surgery will be r and omly assigned , utilizing a 2 x 2 x 2 factorial design , to receive vitamin E , vitamin C , beta-carotene , and /or placebo . Cardiovascular end points include nonfatal myocardial infa rct ion , nonfatal stroke , coronary revascularization procedures , and total CVD mortality . The present article describes the rationale , design , and methods of the trial The possibility that the taking of vitamin supplements may influence cognitive functioning was explored . One hundred and twenty-seven young healthy adults took either ten times the recommended daily dose of nine vitamins , or a placebo , under a double-blind procedure , for a year . After 12 months better performance on two measures of attention was found in females who had taken the vitamin supplement , even though the blood status of nine vitamins reached a plateau after 3 months . The use of regression equations demonstrated the association between improved thiamin status and improved performance on a range of measures of cognitive functioning in females rather than males . Although it was not possible to establish the reason for a beneficial response in females rather than males , the evidence that females respond differently to dietary factors was discussed The authors examined the association between dietary intake of fish and omega 3 fatty acids from seafood and the risk of cardiovascular disease in a prospect i ve cohort study of 21,185 US male physicians who are participants in the Physicians ' Health Study . In 4 years of follow-up , there were 281 incident cases of total ( fatal and nonfatal ) myocardial infa rct ion , 173 cases of stroke , and 121 cardiovascular deaths . There was no evidence for association between dietary intake of fish and any cardiovascular endpoint , including myocardial infa rct ion , stroke , and cardiovascular death . The relative risks of total myocardial infa rct ion , adjusted for age and r and omized treatment assignment , for categories of fish intake were : 1.0 for < 1 meal/week ( referent ) , 1.6 ( 95 % confidence interval ( Cl ) 1.1 - 2.3 ) for 1 fish meal/week ; 1.4 ( 95 % Cl 1.0 - 2.0 ) for 2 - 4 fish meals/week ; and 1.2 ( 95 % Cl 0.6 - 2.2 ) for > or = 5 fish meals/week ; chi 2 for trend = 0.9 , p = 0.34 . The relative risks were similar for omega 3 fatty acid intake and for specific types of fish , and did not change after adjustment for history of hypertension , hypercholesterolemia , diabetes mellitus , or angina pectoris , parental history of myocardial infa rct ion before age 60 years , obesity , exercise , smoking , alcohol use , saturated fat intake , and vitamin supplement use . These data do not support the hypothesis that moderate fish consumption lowers the risk of cardiovascular disease BACKGROUND Eighty-one elderly hospitalized subjects ( > 65 years ) were recruited for a double-blind placebo-controlled study to examine low dose supplementation of antioxidant vitamins and minerals on biological and functional parameters of free radical metabolism . Subjects were r and omly assigned to one of the four treatment groups , daily receiving for 2 years : placebo group ; mineral group : 20 mg zinc , 100 micrograms selenium ; vitamin group : 120 mg vitamin C ( Vit C ) , 6 mg beta-carotene ( beta CA ) , 15 mg vitamin E ( Vit E ) ; mineral and vitamin group : Zn 20 mg , Se 100 micrograms , Vit C 120 mg , beta CA 6 mg , Vit E 15 mg . RESULTS Fifty-seven subjects completed the study . A large frequency of Vit C , Zn and Se deficiencies were observed at baseline . As early as 6 months of treatment , a significant increase in vitamin and mineral serum levels was observed in the corresponding groups . The increases ranged from 1.1 - 4.0 fold depending on the nutrient . Antioxidant defense , studied in vitro with a test using red blood cells in presence of 2,2'-azo-bis ( 2-amidinopropane ) by hydrochloride , showed an increase of cell resistance in patients receiving vitamins ( p = 0.002 ) ; it was positively correlated with serum Vit C ( p < 0.0001 ) , alpha-tocopherol/cholesterol ( p = 0.06 ) , beta CA ( p = 0.0014 ) , serum Cu and Se ( p < 0.05 ) . Moreover , red blood cell antioxidant defense was reduced in elderly compared with young control subjects ( 50 % hemolysis time : 69 + /- 14 mn and 109 + /- 12 mn , respectively ) . Erythrocyte glutathione peroxidase activity was enhanced in groups receiving minerals , whereas no significant change was observed for other indicators of oxidative stress ( erythrocyte superoxide dismutase activity , thiobarbituric acid-reactive substances , total glutathione , reduced and oxidized forms ) . DISCUSSION Our results provide experimental evidence that a low dose supplementation with vitamins and minerals was able to normalize biological nutrient status as early as 6 months of treatment . In addition , our data indicate that antioxidant defense in elderly subjects was improved with low doses of vit C , vit E and beta CA as studied by means of a functional test utilizing red blood cells challenged in vitro with free radicals Former blue asbestos workers known to be at high risk of asbestos‐related diseases , particularly malignant mesothelioma and lung cancer , were enrolled in a chemo‐prevention program using vitamin A. Our aims were to compare rates of disease and death in subjects r and omly assigned to β‐carotene or retinol . Subjects were assigned r and omly to take 30 mg/day β‐carotene ( 512 subjects ) or 25,000 IU/day retinol ( 512 subjects ) and followed up through death and cancer registries from the start of the study in June 1990 till May 1995 . Comparison between groups was by Cox regression in both intention‐to‐treat analyses and efficacy analyses based on treatment actually taken . Median follow‐up time was 232 weeks . Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects r and omised to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects r and omised to β‐carotene . The relative rate of mesothelioma ( the most common single cause of death in our study ) for those on retinol compared with those on β‐carotene was 0.24 ( 95 % CI 0.07–0.86 ) . In the retinol group , there was also a significantly lower rate for death from all causes but a higher rate of ischaemic heart disease mortality . Similar results were found with efficacy analyses . Our results confirm other findings of a lack of any benefit from administration of large doses of synthetic β‐carotene . The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation . Int . J. Cancer 75:362–367 , 1998 . © 1998 Wiley‐Liss , To evaluate the clinical antioxidant effects of vitamin E , 161 healthy volunteers aged 39 to 56 years , were given 100 or 3 mg of d-α-tocopheryl acetate orally daily for 6 years using a r and omized , double-blind design . Among the 147 volunteers who qualified for the analysis , seven of the 73 volunteers receiving 3 mg d-α-tocopheryl acetate daily and none of the 74 volunteers receiving 100 mg had coronary disorders including myocardial damage ( P < 0.02 ) . ST or T wave abnormalities on electrocardiograms were considered to indicate coronary disorders ( four volunteers ) . The mean serum total tocopherol ( TOC ) concentration in the 100-mg group was significantly higher than that in the 3-mg group 6 months after the start of the study , and this raised value was maintained throughout the study ; the level in the 3-mg group did not change significantly from the baseline value . The low-density lipoprotein cholesterol/total TOC ratio , a parameter of the inhibition of peroxidation of low-density lipoprotein cholesterol , was the only serum lipid parameter that was significantly different , at baseline , in the volunteers with coronary disorders compared with the others . These findings indicate that long-term supplementation with 100 mg tocopheryl acetate daily may prevent the early stages of coronary atherosclerosis by decreasing peroxidation of low-density lipoprotein cholesterol We conducted a study to determine the effect of different doses of a lutein supplement on serum lutein concentration and macular pigment optical density ( MPOD ) . Lutein is one of the major components of human macular pigment . Eighty-seven subjects received daily doses of 5 , 10 , or 20 mg of lutein , or a placebo , over a 140 day period . Serum lutein concentration was determined by HPLC and MPOD by heterochromatic flicker photometry ( HFP ) . Serum lutein responded positively , except in the placebo group , reaching a plateau that , averaged for each dosage group , was linearly dependent on dose . Likewise MPOD , on average , increased at a rate that varied linearly with dose . For subjects deemed more proficient at HFP , approximately 29 % of the variability in MPOD response could be attributed to a linear dependence on the fractional change in serum lutein concentration . We did not detect any significant influence of age on serum lutein uptake or MPOD response OBJECTIVE To determine whether the vitamin/mineral supplements used in two cancer intervention trials affected the risk of developing age-related cataracts . DESIGN Two r and omized , double-masked trials with a duration of 5 to 6 years and end-of-trial eye examinations . SETTING Rural communes in Linxian , China . PARTICIPANTS In trial 1 , 2141 participants aged 45 to 74 years , and , in trial 2 , 3249 participants aged 45 to 74 years . INTERVENTIONS Multivitamin/mineral supplement or matching placebo in trial 1 ; factorial design to test the effect of four different vitamin/mineral combinations in trial 2 ( retinol/zinc , riboflavin/niacin , ascorbic acid/molybdenum , and selenium/alpha-tocopherol/beta carotene ) . MAIN OUTCOME MEASURES Prevalence of nuclear , cortical , and posterior subcapsular cataracts in treatment groups at end of trials . RESULTS In the first trial , there was a statistically significant 36 % reduction in the prevalence of nuclear cataract for persons aged 65 to 74 years who received the supplements . In the second trial , the prevalence of nuclear cataract was significantly lower in persons receiving riboflavin/niacin compared with persons not receiving these vitamins . Again , persons in the oldest group , 65 to 74 years , benefited the most ( 44 % reduction in prevalence ) . No treatment effect was noted for cortical cataract in either trial . Although the number of posterior subcapsular cataracts was very small , there was a statistically significant deleterious effect of treatment with riboflavin/niacin . CONCLUSIONS Findings from the two trials suggest that vitamin/mineral supplements may decrease the risk of nuclear cataract . Additional research is needed in less nutritionally deprived population s before these findings can be translated into general nutritional recommendations BACKGROUND Oxidized low-density lipoprotein is involved in the pathogenesis of atherosclerosis . In epidemiological studies antioxidants have been inversely related with coronary heart disease . Findings from controlled trials are inconclusive . METHODS We studied the primary preventive effect of vitamin E ( alpha tocopherol ) and beta carotene supplementation on major coronary events in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study , a controlled trial undertaken primarily to examine the effects of these agents on cancer . A total of 27 271 Finnish male smokers aged 50 to 69 years with no history of myocardial infa rct ion were r and omly assigned to receive vitamin E ( 50 mg ) , beta carotene ( 20 mg ) , both agents , or placebo daily for 5 to 8 years ( median , 6.1 years ) . The end point was the first major coronary event , either nonfatal myocardial infa rct ion ( surviving at least 28 days ; n = 1204 ) or fatal coronary heart disease ( n = 907 ) . RESULTS The incidence of primary major coronary events decreased 4 % ( 95 % confidence interval , -12 % to 4 % ) among recipients of vitamin E and increased 1 % ( 95 % confidence interval , -7 % to 10 % ) among recipients of beta carotene compared with the respective nonrecipients . Neither agent affected the incidence of nonfatal myocardial infa rct ion . Supplementation with vitamin E decreased the incidence of fatal coronary heart disease by 8 % ( 95 % confidence interval , -19 % to 5 % ) , but beta carotene had no effect on this end point . CONCLUSIONS Supplementation with a small dose of vitamin E has only marginal effect on the incidence of fatal coronary heart disease in male smokers with no history of myocardial infa rct ion , but no influence on nonfatal myocardial infa rct ion . Supplementation with beta carotene has no primary preventive effect on major coronary events In association with a study of actinic skin disease , we undertook a comprehensive survey of ocular disease in a population sample of the town of Nambour , Queensl and , Australia . Particular emphasis was placed on those diseases with a putative relationship to exposure to solar radiation . In addition to collecting prevalence data , a r and omized controlled trial was commenced to determine , among other things , if daily ingestion of 30 mg of beta-carotene supplements reduces the incidence or progression of ocular diseases possibly related to solar radiation exposure . The study design , population and methodology of the study are described in detail as a background to the future reporting of the results . The study should provide unique epidemiological information about eye disease in an Australian community setting due to the representative nature of the subjects and the comprehensive examination performed PURPOSE To evaluate the functional effect of short-term supplementation of saffron , a spice containing the antioxidant carotenoids crocin and crocetin , in early age-related macular degeneration ( AMD ) . METHODS Twenty-five patients with AMD were r and omly assigned to oral saffron 20 mg/d or placebo supplementation over a 3-month period and then reverted to placebo or saffron for a further 3 months . Focal electroretinograms ( fERGs ) and clinical findings were recorded at baseline and after 3 months of saffron or placebo supplementation . fERGs were recorded in response to a sinusoidally modulated ( 41 Hz ) , uniform field presented to the macular region ( 18 ° ) at different modulations between 16.5 % and 93.5 % . Main outcome measures were fERG amplitude ( in microvolts ) , phase ( in degrees ) , and modulation thresholds . RESULTS After saffron , patients ' fERGs were increased in amplitude , compared with either baseline or values found after placebo supplementation ( mean change after saffron , 0.25 log μV ; mean change after placebo , -0.003 log μV ; P < 0.01 ) . fERG thresholds were decreased after saffron supplementation but not placebo , compared with baseline ( mean change after saffron , -0.26 log units ; mean change after placebo , 0.0003 log units ) . CONCLUSIONS The results indicate that short-term saffron supplementation improves retinal flicker sensitivity in early AMD . Although the results must be further replicated and the clinical significance is yet to be evaluated , they provide important clues that nutritional carotenoids may affect AMD in novel and unexpected ways , possibly beyond their antioxidant properties . ( Clinical Trials.gov number , NCT00951288 . ) PURPOSE To study if long-term supplementation with alpha-tocopherol or beta-carotene is associated with cataract prevalence and severity . METHODS An end-of-trial r and om sample of 1828 participants from the r and omized , double-blind , placebo-controlled clinical trial the alpha-tocopherol , beta-carotene cancer prevention study . The alpha-tocopherol , beta-carotene cancer prevention study was originally design ed to examine whether supplementation with alpha-tocopherol or beta-carotene would reduce the incidence of lung cancer in male smokers . The participants for this study lived in Helsinki City or Uusimaa province and were at entry to the alpha-tocopherol , beta-carotene cancer prevention study 50 to 69 years old and smoked at least 5 cigarettes per day . They received alpha-tocopherol 50 mg/day , beta-carotene 20 mg/day , a combination of the two , or placebo supplements for 5 to 8 years ( median 6.6 years ) . Outcome measures were : cortical , nuclear , and posterior subcapsular cataract , differentiated and quantified with lens opacity classification system ( LOCS II ) . Lens opacity meter provided a continuous measure of cataract density . RESULTS Supplementation with alpha-tocopherol or beta-carotene was not associated with the end-of-trial prevalence of nuclear ( odds ratio 1.1 and 1.2 , respectively ) , cortical ( odds ratio 1.0 and 1.3 , respectively ) , or posterior subcapsular cataract ( odds ratio 1.1 and 1.0 , respectively ) when adjusted for possible confounders in logistic model . Neither did the median lens opacity meter values differ between the supplementation groups , indicating no effect of alpha-tocopherol or beta-carotene on cataract severity . CONCLUSION Supplementation with alpha-tocopherol or beta-carotene for 5 to 8 years does not influence the cataract prevalence among middle-aged , smoking men The U.S. National Cancer Institute and the Finnish National Public Institute jointly sponsored a large double-blind , placebo-controlled primary -prevention trial to examine the effects of vitamin E and beta-carotene supplementation on reducing the incidence of lung cancers in male smokers , ages 50 - 69 years . Supplementation did not result in a significant reduction in lung cancer , and a higher incidence of lung cancer was observed in the group receiving beta-carotene . These results should be examined within the context of the population studied before they are cited as definitive Although cigarette smoking is a risk factor for stroke , results conflict on the strength of the association [ 1 - 13 ] . Estimates of relative risks among current male smokers in cohort studies have ranged from 0.90 [ 14 ] to 4.2 [ 8 ] . Of 25 prospect i ve studies including men , 12 reported no association [ 14 - 25 ] . One prospect i ve study [ 3 ] found a dose-response relation with the number of cigarettes smoked , although 2 others did not [ 6 , 23 ] . Various reference groups have been used in these studies : Some investigations have compared the risk for stroke in current smokers with the risk in never-smokers , and others have compared this risk with the risk in current nonsmokers . Nine of these studies also included women [ 3 - 5 , 8 , 12 - 14 , 17 , 23 ] , generally finding slightly higher relative risks in women . The risk for stroke in female former smokers largely returns to the level of never-smokers within 2 to 4 years after quitting [ 26 ] . Increased alcohol consumption is linked with cigarette smoking [ 27 ] and with stroke [ 28 , 29 ] . However , only five prospect i ve studies in men have controlled for alcohol consumption [ 1 , 4 , 6 , 7 , 16 ] , and none has evaluated the potential modification of the effect of smoking by the level of alcohol intake . The largest of these five studies followed 7895 men [ 7 ] . In this study , we examined the relation of cigarette smoking with stroke in a cohort of 22 071 male physicians participating in the Physician 's Health Study . Methods Study Population The Physicians ' Health Study [ 30 , 31 ] is a r and omized , double-blind , placebo-controlled trial examining the effect of low-dose aspirin on cardiovascular disease and the effect of -carotene on cancer and cardiovascular disease . Briefly , 22 071 U.S. male physicians ( 40 to 84 years of age at entry in 1982 ) were r and omly assigned to aspirin alone , -carotene alone , aspirin and -carotene , or placebo alone , using a 2 2 factorial design . All participants enrolled in the trial were free from self-reported previous myocardial infa rct ion , stroke , and transient ischemic attack . The participants completed a mailed baseline question naire that included information about cigarette smoking status ( never , past only , or current ) and included the number of cigarettes smoked per day if they were currently smoking . Other information collected at baseline included age , history of angina pectoris , history of coronary revascularization procedures ( coronary artery bypass grafting or percutaneous transluminal coronary angioplasty ) , history of diabetes mellitus , history of hypertension , history of high cholesterol levels , height , weight , history of alcohol use , and frequency of vigorous exercise . Every 6 months during the first year and then annually , participants completed brief question naires inquiring about their compliance with the assigned treatment and about the occurrence of any relevant events , including stroke . On 15 January 1988 , the aspirin component of the study was terminated , mainly because of a statistically extreme 44 % decrease in the risk for a first myocardial infa rct ion among participants in the aspirin group . By that date , participants had been followed for an average of 60.2 months . This report includes all available data as of 14 October 1992 . By this date , participants had been followed for an average of 9.7 years ( range , 8.5 to 11.1 years ) . The completeness of follow-up for stroke-associated morbidity and mortality was 100 % . Ascertainment and Definition of Stroke End Points Nonfatal strokes were reported on the semiannual or annual question naires . Deaths were usually reported by the families or postal authorities , and persistent nonresponders to the question naires were telephoned . Strokes were considered confirmed only after medical records and all available information were review ed by the End Points Committee ( which consisted of two internists , a cardiologist , and a neurologist , who did not have knowledge of treatment assignment ) . Unconfirmed events were not used in any of our analyses . A definite case of nonfatal stroke was defined as a typical neurologic deficit that was sudden or rapid in onset , lasted more than 24 hours , and was attributable to a cerebrovascular event . Strokes were classified according to the probable cause ( ischemic or hemorrhagic ) on the basis of medical records , computed tomographic scanning , and the judgment of the neurologist . Computed tomographic scans were available for more than 95 % of all confirmed cases of stroke . Every case of hemorrhagic stroke was confirmed by either a computed tomographic scan or by lumbar puncture . Unknown strokes were those without an imaging study or other clear documentation of stroke subtype . Definite cases of fatal stroke were documented by convincing evidence of a cerebrovascular mechanism from all available sources , including death certificates , hospital records , and for death outside the hospitalobservers ' impressions . Only first cases of stroke were counted . Statistical Analyses Smoking status was defined as never smoked , formerly smoked , currently smoking less than 20 cigarettes per day , or currently smoking 20 or more cigarettes per day . Follow-up began with question naire completion in 1982 to 1983 and ended with the diagnosis of nonfatal or fatal stroke , or other fatal event , or 14 October 1992 , whichever came first . Five participants contributed no follow-up time to the analyses because , after r and omization , they reported strokes that occurred before r and omization . To compute relative risks adjusted for age and other factors , we used the SAS PHREG procedure [ 32 ] to do proportional-hazards regression [ 33 ] . The proportional-hazards assumption was confirmed using log-log plots [ 34 ] . Initial analyses to rule out effect modification by age were done using interaction terms . We then adjusted for age and treatment assignment and then further adjusted for all other covariates , including self-reported hypertension , angina , history of coronary revascularization , diabetes mellitus , high cholesterol level , alcohol consumption , vigorous exercise frequency , and baseline obesity status . These covariates are independent risk indicators for stroke , and all have some association with smoking ( except treatment assignment ) . Adjustment for treatment assignment has been routine in all analyses for the Physicians ' Health Study . Analyses restricted to specific levels of alcohol intake were done to assess the interactive effects of alcohol and smoking . To determine the independent effect of alcohol , we did analyses restricted to never-smokers ( 49.5 % of the cohort ) . Using interaction terms , we also tested for a treatment-assignment interaction for smoking with aspirin ( the -carotene component of the trial is still ongoing and is blinded ) and an interaction for smoking with hypertension . We tested for linear trend in relative risk across smoking categories using an ordinal smoking variable , with values ranging from 0 ( never smoking ) to 3 ( currently smoking 20 or more cigarettes per day ) . We calculated 95 % CIs for each relative risk , and all P values are two-tailed [ 35 ] , with those less than 0.05 declared statistically significant . The population attributable risk percentage for current cigarette smoking in relation to total stroke was calculated as the difference between the stroke incidence rate in the total population and the rate in current nonsmokers divided by the incidence rate in the total population ( x 100 % ) [ 36 ] . Results Baseline Distribution of Smoking and Other Exposure Variables In 1982 , 11.0 % of the physicians in this cohort were current smokers ( 7.1 % of the participants currently smoked 20 or more cigarettes per day and 3.9 % currently smoked less than 20 cigarettes per day ) , 39.3 % formerly smoked , and 49.5 % had never smoked . Information on cigarette smoking habit was missing for 67 ( 0.3 % ) physicians . With the exception of alcohol consumption ( 17.6 % of never-smokers reported daily drinking compared with 37.5 % of current heavy smokers ) , age and most of the other variables had similar distributions among the four groups ( Appendix Table 1 ) . Appendix Table 1 . Comparison of Baseline Characteristics of the Physicians according to Cigarette Smoking Status Total Stroke and Subtypes During 207 579 person-years of follow-up , 312 nonfatal and 28 fatal strokes occurred ( 275 ischemic , 56 hemorrhagic , and 9 of unknown cause ) . Physicians currently smoking 20 or more cigarettes per day had relative risks ( adjusted for age and treatment assignment ) for total nonfatal and fatal stroke of 2.52 and 1.24 , respectively , and in multivariate analyses controlling for other risk factors , these relative risks were 2.71 and 1.46 , respectively ( Table 1 ) . Ischemic stroke was more strongly related to current smoking than was hemorrhagic stroke . For total nonfatal stroke and ischemic stroke , we found linear increases in risk across the four cigarette smoking categories ( P for trend , < 0.0001 ) . Table 1 . Relative Risks for Total , Ischemic , and Hemorrhagic Stroke among U.S. Male Physicians according to Category of Cigarette Smoking Exposure Aspirin treatment assignment was associated with an increased risk for hemorrhagic stroke . In multivariate models , the relative risks associated with aspirin assignment were as follows : total stroke , 1.10 ( 95 % CI , 0.88 to 1.39 ) ; ischemic stroke , 0.99 ( CI , 0.76 to 1.27 ) ; and hemorrhagic stroke , 1.91 ( CI , 1.08 to 3.38 ) . Testing for Interaction We did not find any significant statistical interaction between aspirin treatment and smoking or between hypertensive history and smoking . Data on the effect of smoking within categories of alcohol consumption ( Figure 1 ) were too sparse to permit firm conclusions . In multivariate analyses restricted to never-smokers , we found that the relative risks for total stroke associated with consuming alcohol rarely or never , monthly , weekly , and daily were 1.00 ( referent ) ; 0.95 ( CI , 0.56 to 1.61 ) ; 0.75 ( CI , 0.47 to 1.22 ) ; and 1.14 ( CI , 0.63 to 2.05 ) . Analyses excluding 333 physicians The Physicians ' Health Study is a r and omized , double-blind , placebo-controlled prevention trial of 22,071 US physicians , using a factorial design to evaluate the role of aspirin in the prevention of cardiovascular mortality and beta carotene in the reduction of cancer incidence . After approximately 5 years of follow-up , the aspirin component was terminated , 3 years ahead of schedule . Several factors were considered in the decision to terminate , including a cardiovascular mortality rate markedly lower than expected in both aspirin and placebo subjects , precluding the evaluation of the primary aspirin hypothesis , and a highly significant ( P < .00001 ) and impressive ( 44 % ) reduction in the risk of first myocardial infa rct ion in the aspirin group . Issues in the decision to terminate are described in this report BACKGROUND Observational and experimental data suggest that antioxidant and /or zinc supplements may delay progression of age-related macular degeneration ( AMD ) and vision loss . OBJECTIVE To evaluate the effect of high-dose vitamins C and E , beta carotene , and zinc supplements on AMD progression and visual acuity . DESIGN The Age-Related Eye Disease Study , an 11-center double-masked clinical trial , enrolled participants in an AMD trial if they had extensive small drusen , intermediate drusen , large drusen , non central geographic atrophy , or pigment abnormalities in 1 or both eyes , or advanced AMD or vision loss due to AMD in 1 eye . At least 1 eye had best-corrected visual acuity of 20/32 or better . Participants were r and omly assigned to receive daily oral tablets containing : ( 1 ) antioxidants ( vitamin C , 500 mg ; vitamin E , 400 IU ; and beta carotene , 15 mg ) ; ( 2 ) zinc , 80 mg , as zinc oxide and copper , 2 mg , as cupric oxide ; ( 3 ) antioxidants plus zinc ; or ( 4 ) placebo . MAIN OUTCOME MEASURES ( 1 ) Photographic assessment of progression to or treatment for advanced AMD and ( 2 ) at least moderate visual acuity loss from baseline ( > or = 15 letters ) . Primary analyses used repeated- measures logistic regression with a significance level of.01 , unadjusted for covariates . Serum level measurements , medical histories , and mortality rates were used for safety monitoring . RESULTS Average follow-up of the 3640 enrolled study participants , aged 55 - 80 years , was 6.3 years , with 2.4 % lost to follow-up . Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc ( odds ratio [ OR ] , 0.72 ; 99 % confidence interval [ CI ] , 0.52 - 0.98 ) . The ORs for zinc alone and antioxidants alone are 0.75 ( 99 % CI , 0.55 - 1.03 ) and 0.80 ( 99 % CI , 0.59 - 1.09 ) , respectively . Participants with extensive small drusen , nonextensive intermediate size drusen , or pigment abnormalities had only a 1.3 % 5-year probability of progression to advanced AMD . Odds reduction estimates increased when these 1063 participants were excluded ( antioxidants plus zinc : OR , 0.66 ; 99 % CI , 0.47 - 0.91 ; zinc : OR , 0.71 ; 99 % CI , 0.52 - 0.99 ; antioxidants : OR , 0.76 ; 99 % CI , 0.55 - 1.05 ) . Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group . The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc ( OR , 0.73 ; 99 % CI , 0.54 - 0.99 ) . No statistically significant serious adverse effect was associated with any of the formulations . CONCLUSIONS Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD . Those with extensive intermediate size drusen , at least 1 large druse , non central geographic atrophy in 1 or both eyes , or advanced AMD or vision loss due to AMD in 1 eye , and without contraindications such as smoking , should consider taking a supplement of antioxidants plus zinc such as that used in this study Chemoprevention with retinoids is currently an experimental approach to prevent local relapses and second primaries in treated head and neck cancer patients . We evaluated the effectiveness of vitamin A in preventing the above events in a r and omised trial involving 106 head and neck cancer patients who had achieved complete regression of their disease with radiotherapy and /or surgery . They were r and omised to receive retinyl palmitate ( 200,000 IU per week for 1 year ) or placebo . 50 subjects on vitamin A and 43 on placebo completed 1 year supplementation ; 49 in the former group and 42 in the latter could be evaluated over a 3 year period from the initiation of the study . One fifth ( 11/56 ) of patients in the vitamin A group and one tenth ( 5/50 ) in the placebo group had loco-regional recurrence . The frequency of recurrences in stage I patients in the vitamin A group was higher compared to the placebo group , although it was not statistically significant . No second primaries were observed in the vitamin A group ; 2 patients in the placebo group had second primaries . No clinical ly obvious side effects were observed with vitamin A. The higher frequency of recurrences in the vitamin A group is of concern although it may be a chance finding given the small size of the trial . The effect on second primaries is consistent with other observations reported in literature One hundred patients with transient ischemic attacks , minor strokes , or residual ischemic neurologic deficits were enrolled in a double-blind , r and omized study comparing the effects of aspirin plus vitamin E [ 0.4 g ( 400 IU)/d ; n = 52 ] with aspirin alone ( 325 mg ; n = 48 ) . The patients received study medication for 2 y or until they reached a termination point . Preliminary results show a significant reduction in the incidence of ischemic events in patients in the vitamin E plus aspirin group compared with patients taking only aspirin . There was no significant difference in the incidence of hemorrhagic stroke although both patients who developed it were taking vitamin E. Platelet adhesion was also measured in a r and omized subgroup of both study population s by using collagen III as the adhesive surface . There was a highly significant reduction in platelet adhesiveness in patients who were taking vitamin E plus aspirin compared with those taking aspirin only . Measurement of alpha-tocopherol concentrations confirmed compliance of the patients with the medication schedule , showing a near doubling of serum concentrations of alpha-tocopherol . We concluded that the combination of vitamin E and a platelet antiaggregating agent ( eg , aspirin ) significantly enhances the efficacy of the preventive treatment regimen in patients with transient ischemic attacks and other ischemic cerebrovascular problems BACKGROUND Moderate alcohol consumption decreases the risk of coronary heart disease , but its relation to peripheral arterial disease ( PAD ) is uncertain . METHODS AND RESULTS In the Physicians ' Health Study , a r and omized trial of the use of aspirin and beta-carotene in 22071 apparently healthy men , we documented 433 incident cases of PAD during 11 years of follow-up . After we controlled for age and treatment assignment , daily drinkers ( > or = 7 drinks per week ) had a relative risk ( RR ) of PAD of 0.92 ( 95 % confidence interval , 0.72 to 1.17 ) compared with the reference group ( < 1 drink per week ) . After additional control for smoking , however , the RR was 0.68 ( 0.52 to 0.89 ) . Further control for exercise , diabetes mellitus , and parental history of myocardial infa rct ion revealed an RR of 0.74 ( 0.57 to 0.97 ) . CONCLUSIONS Moderate alcohol consumption appears to decrease the risk of PAD in apparently healthy men BACKGROUND Both yellow-blue ( YB ) discrimination thresholds and macular pigment optical density ( MPOD ) measurements in the eye exhibit large variability in the normal population . Although it is well established that selective absorption of blue light by the macular pigment ( MP ) can significantly affect trichromatic colour matches , the extent to which the MP affects colour discrimination ( CD ) sensitivity remains controversial . OBJECTIVE In this study , we assess whether the variability in YB thresholds is attributable to differences in MPOD , both at the fovea and in the para central visual field . We also investigated whether higher levels of MP offer any advantage in other visual functions such as red-green ( RG ) CD sensitivity . DESIGN CD thresholds and spatial MPOD profiles were measured in 24 normal trichromats supplemented with zeaxanthin ( OPTISHARP ) and /or lutein . Novel stimulus conditions that isolate YB and RG chromatic mechanisms were employed and MPOD profiles were measured up to an eccentricity of 8 degrees . RESULTS The data reveal an increase in MPOD in the supplemented subjects that was almost uniform within a centre region around the fovea subtending + /-4 degrees . RG sensitivity was high in all subjects with thresholds well within the normal range . Unexpectedly , YB thresholds were also normal and showed no correlation with MPOD . A model for threshold CD based on appropriate combinations of cone contrast signals was developed to explain the experimental findings . CONCLUSIONS YB thresholds remain unaffected by supplementation with lutein and /or zeaxanthin rather , at increased MPOD levels , RG vision tends to be improved . The model accounts for the absence of correlation between MPOD and YB thresholds and predicts a marginal improvement in RG discrimination when MPOD is high BACKGROUND The objective of this study was to examine whether definite hypertension and borderline isolated systolic hypertension predict subsequent cardiovascular disease and mortality . METHODS AND RESULTS This was a prospect i ve cohort study with a mean follow-up of 11.7 years . The subjects were a group of 18,682 apparently healthy US men , aged 40 to 84 years , participating in the Physicians ' Health Study , a r and omized trial of low-dose aspirin and beta-carotene . The main outcome measures were total cardiovascular disease , myocardial infa rct ion , stroke , cardiovascular death , and all-cause mortality . Hypertension was associated with substantially increased risks of total cardiovascular disease ( relative risk [ RR ] 1.92 ; 95 % confidence interval [ CI ] , 1.70 to 2.18 ) , myocardial infa rct ion ( RR,1.78 ; 95 % CI , 1.49 to 2.13 ) , stroke ( RR , 2.19 ; 95 % CI , 1.78 to 2.69 ) , and cardiovascular death ( RR , 2.10 ; 95 % CI , 1.68 to 2.63 ) . Borderline isolated systolic hypertension was associated with significantly increased risks of cardiovascular disease ( RR , 1.32 ; 95 % CI , 1.09 to 1.59 ) , stroke ( RR , 1.42 ; 95 % CI , 1.04 to 1.93 ) , and cardiovascular death ( RR , 1.56 ; 95 % CI , 1.13 to 2.15 ) , as well as a possible but non-significant increased risk of myocardial infa rct ion ( RR , 1.26 ; 95 % CI , 0.95 to 1.67 ) . Hypertension and borderline isolated systolic hypertension were associated with significantly increased risks of 41 % and 22 % , respectively , for all-cause mortality . CONCLUSIONS Hypertension as well as borderline isolated systolic hypertension are associated with elevated risks of cardiovascular diseases , especially stroke and cardiovascular death . Hypertension is associated with an increased risk of myocardial infa rct ion , and borderline isolated systolic hypertension predicts a possible but more modest increase in risk . These data add to the existing evidence that hypertension is a major cardiovascular risk factor and extend the findings to borderline isolated systolic hypertension A r and omised double-blind intervention trial was carried out in Huixian , Henan Province , People 's Republic of China , to determine whether combined treatment with retinol , riboflavine , and zinc could lower the prevalence of precancerous lesions of the oesophagus . 610 subjects in the age group 35 - 64 were r and omised to receive once a week the active treatment ( 15 mg [ 50 000 IU ] retinol , 200 mg riboflavine , and 50 mg zinc ) or placebo . Both at entry to the study and at the end of the treatment , 13.5 months later , the subjects were examined , with an emphasis on signs of vitamin A and riboflavine deficiences , and riboflavine , retinol , beta-carotene , and zinc levels were measured . Compliance was excellent . The final examination , on 567 ( 93 % ) subjects , included oesophagoscopy and at least two biopsies . The intervention did not affect the prevalence of oesophageal lesions : after one year , the prevalence of oesophagitis with or without atrophy or dysplasia was 45.3 % in the placebo group and 48.9 % in the vitamin/zinc treated group BACKGROUND Laboratory , clinical , and epidemiologic studies have recently suggested that regular use of aspirin can reduce colorectal cancer incidence or mortality . However , observational epidemiologic analyses have had limited opportunity to control for confounding bias or to specify aspirin doses used . PURPOSE Our purpose was to examine the relationship between regular use of low-dose aspirin and incidence of invasive and noninvasive colorectal tumors by utilizing data from the Physicians ' Health Study , a r and omized , double-blinded , placebo-controlled trial of aspirin and beta carotene . We also attempted to determine whether invasive cancers among aspirin users were associated with rectal bleeding and early stage at diagnosis . METHODS The Physicians ' Health Study includes 22071 U.S. male physicians . The aspirin arm was terminated in 1988 after a mean follow-up of 5 years . Stage at diagnosis and signs and /or symptoms during presentation were abstract ed from medical records . Cox proportional hazards models were used to estimate relative risk ( RR ) , 95 % confidence intervals ( CIs ) , and the association between aspirin and bleeding . Differences between aspirin and placebo groups in tumor risk over time were visualized with Kaplan-Meier curves . We assessed the association between aspirin and stage at diagnosis with a Mann-Whitney rank sum statistic for non-parametric comparison of two ordinal distributions . RESULTS The RR of developing colorectal cancer for aspirin compared with placebo was 1.15 ( 95 % CI = 0.80 - 1.65 ) . For in situ cancers and polyps , the RR was 0.86 ( 95 % CI = 0.68 - 1.10 ) . There was no significant trend for decreasing RR by year of follow-up for invasive cancers ( P = .09 ) or noninvasive tumors ( P = .96 ) . Aspirin and placebo groups did not differ in stage or prevalence of rectal bleeding at diagnosis . CONCLUSIONS Regular aspirin use , at a dose adequate for preventing myocardial infa rct ion , was not associated with a substantial reduction in the incidence of colorectal cancer during 5 years of r and omized treatment and follow-up . A small decrease in polyps in the aspirin group could not be reliably distinguished from a chance association . Our results suggest that among low-dose aspirin users , ( a ) colorectal cancer mortality is not likely to be reduced by earlier detection and ( b ) incidence is not likely to be increased due to aspirin-induced gastrointestinal bleeding . IMPLICATION S The potential for a benefit from higher doses of aspirin or longer duration of use should be addressed by more detailed observational epidemiologic studies and prevention trials with longer follow-up of r and omized participants BACKGROUND Vitamin E ( alpha-tocopherol ) is thought to have a role in prevention of atherosclerosis , through inhibition of oxidation of low-density lipoprotein . Some epidemiological studies have shown an association between high dietary intake or high serum concentrations of alpha-tocopherol and lower rates of ischaemic heart disease . We tested the hypothesis that treatment with a high dose of alpha-tocopherol would reduce subsequent risk of myocardial infa rct ion ( MI ) and cardiovascular death in patients with established ischaemic heart disease . METHODS In this double-blind , placebo-controlled study with stratified r and omisation , 2002 patients with angiographically proven coronary atherosclerosis were enrolled and followed up for a median of 510 days ( range 3 - 981 ) . 1035 patients were assigned alpha-tocopherol ( capsules containing 800 IU daily for first 546 patients ; 400 IU daily for remainder ) ; 967 received identical placebo capsules . The primary endpoints were a combination of cardiovascular death and non-fatal MI as well as non-fatal MI alone . FINDINGS Plasma alpha-tocopherol concentrations ( measured in subsets of patients ) rose in the actively treated group ( from baseline mean 34.2 micromol/L to 51.1 micromol/L with 400 IU daily and 64.5 micromol/L with 800 IU daily ) but did not change in the placebo group . Alpha-tocopherol treatment significantly reduced the risk of the primary trial endpoint of cardiovascular death and non-fatal MI ( 41 vs 64 events ; relative risk 0.53 [ 95 % Cl 0.34 - 0.83 ; p=0.005 ) . The beneficial effects on this composite endpoint were due to a significant reduction in the risk of non-fatal MI ( 14 vs 41 ; 0.23 [ 0.11 - 0.47 ] ; p=0.005 ) ; however , there was a non-significant excess of cardiovascular deaths in the alpha-tocopherol group ( 27 vs 23 ; 1.18 [ 0.62 - 2.27 ] ; p=0.61 ) . All-cause mortality was 36 of 1035 alpha-tocopherol-treated patients and 27 of 967 placebo recipients . INTERPRETATION We conclude that in patients with angiographically proven symptomatic coronary atherosclerosis , alpha-tocopherol treatment substantially reduces the rate of non-fatal MI , with beneficial effects apparent after 1 year of treatment . The effect of alpha-tocopherol treatment on cardiovascular deaths requires further study The Alpha-Tocopherol Beta-Carotene ( ATBC ) Cancer Prevention Study was a placebo-controlled , r and omized intervention trial testing the hypothesis that beta-carotene and alpha-tocopherol ( vitamin E ) supplements prevent lung and other cancers . The study is predicated on a substantial body of evidence supporting a role in cancer prevention for these micronutrients . Based on the 2 x 2 factorial study design , 29,133 eligible male cigarette smokers aged 50 - 69 y were r and omly assigned to receive beta-carotene ( 20 mg ) , alpha-tocopherol ( 50 mg ) , beta-carotene and alpha-tocopherol , or placebo daily for 5 - 8 y. Capsule compliance was high ( median = 99 % ) . beta-Carotene treatment did not result in a decrease in cancer at any of the major sites but rather in an increase at several sites , most notably lung , prostate , and stomach ( number of cases 474 compared with 402 , 138 compared with 112 , and 70 compared with 56 , respectively ) . The vitamin E group had fewer incident cancers of the prostate and colorectum compared with the group not receiving vitamin E ( number of cases 99 compared with 151 and 68 compared with 81 , respectively ) , but more cancers of the stomach ( 70 compared with 56 ) . In contrast to these intervention-based findings for beta-carotene and vitamin E supplements , we observed lower lung cancer rates in men with higher amounts of both serum and dietary beta-carotene and vitamin E at baseline OBJECTIVE To test whether alternate day vitamin E affects the incidence of age-related macular degeneration ( AMD ) in a large-scale r and omized trial of women . DESIGN R and omized , double-masked , placebo-controlled trial . PARTICIPANTS Thirty-nine thous and eight hundred seventy-six apparently healthy female health professionals aged 45 years or older . INTERVENTION Participants were assigned r and omly to receive either 600 IU of natural- source vitamin E on alternate days or placebo . MAIN OUTCOME MEASURES Incident AMD responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review . RESULTS After 10 years of treatment and follow-up , there were 117 cases of AMD in the vitamin E group and 128 cases in the placebo group ( relative risk , 0.93 ; 95 % confidence interval , 0.72 - 1.19 ) . CONCLUSIONS In a large-scale r and omized trial of female health professionals , long-term alternate-day use of 600 IU of natural- source vitamin E had no large beneficial or harmful effect on risk of AMD |
10,552 | 19,160,199 | New information for remedication shows that the combination extended the duration of analgesia by about one hour compared to treatment with the same dose of paracetamol alone . | BACKGROUND This is an up date d version of the Cochrane review published in Issue 4 , 1998 .
Combining drugs from different classes with different modes of action may offer opportunity to optimise efficacy and tolerability , using lower doses of each drug to achieve the same degree of pain relief .
Previously we concluded that addition of codeine to paracetamol provided additional pain relief , but at expense of additional adverse events .
New studies have been published since .
This review sought to evaluate efficacy and safety of paracetamol plus codeine using current data , and compare findings with other analgesics evaluated similarly .
OBJECTIVES Assess efficacy of single dose oral paracetamol plus codeine in acute postoperative pain , increase in efficacy due to the codeine component , and associated adverse events . | & NA ; Tramadol hydrochloride is a synthetic & mgr;‐opioid agonist with additional monoaminergic activity . Tramadol 's analgesic effect has been equated with that of pethidine , with a more favourable side‐effect profile . Tramadol has been the most‐selling prescription analgesic in Germany for several years , and it is now available in many other European countries , but still there is a lack of adequately controlled clinical studies of its analgesic properties . The purpose of this study was to compare the analgesic efficacy of 50 and 100 mg oral tramadol with our st and ard analgesic for postoperative pain treatment , 1000 mg paracetamol + 60 mg codeine , and placebo . A single‐dose , parallel group , double‐blind design was used . One hundred forty‐four patients were enrolled the day after total hip replacement if they had a pain intensity of 60 mm or more on a 0–100 mm visual analogue scale . Treatments were compared on the basis of pain intensity and derived variables ( pain intensity difference , and summed pain intensity differences ) , the need of rescue medication , and a global evaluation . Serum concentrations confirmed rapid and good absorption comparable with the reported in healthy volunteers . The active drug control , paracetamol + codeine , was significantly superior to placebo for all efficacy variables ( P = 0.0002–0.004 ) , confirming good assay sensitivity . Paracetamol + codeine was also significantly superior to both 50 mg tramadol ( P = 0.002–0.03 ) and 100 mg tramadol ( P = 0.002–0.02 ) . There was no difference between placebo and 50 and 100 mg tramadol for any of the efficacy variables . Adverse events were more common with tramadol than with the active control ( P < 0.02 ) , with significantly more emetic episodes after 50 and 100 mg tramadol ( P < 0.05 ) . Thus , this double‐blind , placebo‐ and active drug‐controlled study after orthopaedic surgery shows that 50 and 100 mg oral tramadol is well absorbed but has no significant analgesic effect in doses that are tolerable as single doses by mouth . We emphasize the importance of proper study design with documented assay sensitivity and sufficiently high initial pain intensity for differentiation between analgesics of different potencies A single-blind , parallel-group study was carried out to evaluate the efficacy and safety of an analgesic combining 650 mg of acetaminophen and 25 mg of pentazocine in 129 patients with moderate postoperative pain . Comparisons were made with a combination containing acetaminophen ( 300 mg ) and codeine ( 30 mg ) , a combination containing acetaminophen ( 650 mg ) and propoxyphene napsylate ( 100 mg ) , and a placebo . A nurse observer queried patients at regular intervals over a six-hour period concerning the intensity of pain and the degree of pain relief . The scores obtained were used in the calculation of st and ard measures of analgesic efficacy . Acetaminophen/pentazocine proved to be significantly superior to placebo and equivalent to the other active analgesic combinations . No side effects were reported with acetaminophen/pentazocine , acetaminophen/propoxyphene napsylate , or placebo . One mild side effect was question ably associated with acetaminophen/codeine . This study demonstrates that the combination of acetaminophen and pentazocine is as safe and effective in controlling postoperative pain of moderate severity as other commonly used analgesics 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 In a double‐blind , r and omized , single‐dose trial the analgesic contribution of acetaminophen , 1000 mg , and codeine , 60 mg , was determined . The study was a 2 × 2 factorial experiment in which 120 patients suffering from pain as a result of oral surgery rated their pain intensity and pain relief for up to 5 hours after a single dose of one of : 1000 mg acetaminophen , 60 mg codeine , 1000 mg acetaminophen plus 60 mg codeine , or placebo . The factorial analysis showed that both 1000 mg acetaminophen and 60 mg codeine made a statistically significant ( P < 0.05 ) contribution to the analgesic effectiveness of the combination on all measures of efficacy ( sum of pain intensity differences , largest pain intensity difference , total pain relief , largest pain relief , and time to remedication ) . The incidence of adverse effects did not appear to differ among the treatments , including placebo One hundred sixty-one patients with postoperative pain were treated at a single center in a double-blind , r and omized , parallel study design ed to compare the efficacy and safety of single oral doses of ketoprofen ( 50 and 150 mg ) , an acetaminophen ( 650 mg ) plus codeine ( 60 mg ) combination , and placebo . From 1 through 4 hours after administration of the study drugs , the mean summed pain intensity difference ( SPID ) and time-weighted total pain relief ( TOPAR ) scores for the three active treatments generally were significantly ( P less than 0.05 ) higher than those for placebo but not significantly different from each other . At the 6-hour evaluation , the ketoprofen groups , but not the acetaminophen-codeine group , had higher ( P less than 0.05 ) mean SPID and TOPAR scores than the placebo group , as a result of a shorter duration of pain relief in the acetaminophen-codeine group . The 6-hour TOPAR scores were significantly ( P less than 0.05 ) higher for both ketoprofen groups than for the acetaminophen-codeine group ; the ketoprofen 150 mg group also had significantly ( P less than 0.05 ) higher mean 6-hour SPID and global subjective assessment scores . As a result of a higher frequency of somnolence , there was a significantly ( P less than 0.05 ) greater incidence of central nervous system adverse drug reactions among patients treated with acetaminophen plus codeine than among those treated with 150 mg of ketoprofen . These results indicate that the analgesic efficacy of both 50 and 150 mg doses of ketoprofen equals that of acetaminophen 650 mg plus codeine 60 mg and the duration of the analgesic effect of ketoprofen is significantly longer Background : A r and omized , double‐blind , placebo‐controlled single oral dose study was done in order to examine whether codeine has an additive analgesic effect to that of paracetamol for moderate and strong postoperative pain after abdominal surgery . The maximum recommended single dose of paracetamol 1000 mg ( Paracet ® ) was compared with a combination of a submnximal dose of paracetamol 800 mg plus codeine 60 mg ( Paralgin forte ® ) and placebo for pain relief after Caesarean section in 125 patients & NA ; The objective was to investigate the relationship between pain relief scores produced by placebo and by active interventions in r and omised controlled trials ( RCTs ) . Individual patient categorical pain relief scores from 5 placebo‐controlled single‐dose parallel‐group RCTs in acute postoperative pain were used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) for the different treatments . One hundred and thirty of the 525 patients in the 5 trials had a placebo . Individual patients ' scores with placebo varied from 0 to 100 % of the maximum possible pain relief . The proportion who obtained more than 50 % of the maximum possible pain relief with placebo varied from 7 % to 37 % across the trials ; with the active drugs the variation was from 5 to 63 % . Mean placebo scores were related to the mean score for the active treatments in each study ; the higher the mean active score , the higher the mean placebo score . This relationship disappeared when median values were used . Medical folklore has it that the amount of relief obtained with placebo is one‐third of the maximum possible ( and does not vary ) , and that one‐third of patients respond to placebo . The results show that the amount of relief obtained with placebo varies considerably between patients , that 38 % of patients obtained more than 10 % of the maximum possible relief , and 16 % obtained greater than 50 % . In double‐blind , r and omised parallel‐group studies of high quality placebo scores should not vary . Despite these conditions being met the placebo scores did vary . The previous explanation , of a relationship between the mean placebo scores and the mean scores for the active treatments was not supported The efficacy of diclofenac sodium ( Voltarol ) with and without paracetamol in the control of post-surgical dental & NA ; Ibuprofen , 400 mg , was compared with 300 mg acetaminophen plus 30 mg of codeine and placebo in 120 post‐orthopedic surgery patients with moderate to severe pain . The study was design ed as a double‐blind , single‐dose , parallel‐group analgesic efficacy assay . Estimates of analgesia were obtained up to 6 h using categorical and visual analog measures of pain intensity and pain relief . Estimates of selected elements of mood and of sensory and affective components of pain were obtained at 0 and 2 h using contrasting mood word/phrase pairs and a portion of the McGill Pain Question naire , respectively . Drugs were distinguishable from placebo in total analgesic effect and ibuprofen was more effective than acetaminophen plus codeine , especially in terms of duration . While peak effects were comparable , they occurred 1 h later following ibuprofen . Differences among treatments were more discernible using visual analog measures . Side effects were minimal . Ibuprofen provided greater improvement in selected elements of mood than acetaminophen plus codeine at comparable levels of pain relief . While decreases in the sensory component of pain were most highly associated with pain relief provided by ibuprofen , decreases in the affective component were most highly associated with pain relief following acetaminophen plus codeine . These latter results indicate that mood assessment and the discrimination between sensory and effective components of pain could be particularly useful within analgesic drug assays , especially when comparing analge‐sics of differing pharmacologic class when comparing the result of such assays in pain syndromes characterised by differing pain quality Summary Acetylsalicylic acid(ASA ) was compared with paracetamol(P ) in a double-blind crossover study , in which essentially the same operation was performed on two separate occasions in 32 healthy patients , who required surgical removal of bilateral “ identically ” impacted wisdom teeth . Sixteen patients were given the drugsboth before and after(b & a-group ) the operations ( 0.5 g on the pre-operative evening , followed by 0.5 g × 4 for 3 days ) ; the other 16 patients did not start treatment until 2 hoursafter(a-group ) the operations . A number of objective and subjective factors were assessed , including swelling , bleeding , pain and preference , and were used to make comparisons of the pre- , per- and post-operative courses . About 50 % greater post-operative swelling was associated withASA compared toP , either if medication was begun prior to surgery or if the drugs were given only after operation . In theb & a-group , interference with platelet function and prolonged pre-operative bleeding time were produced byASA ( 8.9 vs 6.5 min ) , but the per-operative blood loss was not significantly increased ( 7.8 vs 7.4 ml ) . In both groupsASA tended to increase post-operative bleeding and the formation of haematomas and ecchymoses . There was no noticeable difference betweenASA and P with respect to pain score , but the preference scores showed a tendency to favourP in both groups . It appears that in circumstances with acute tissue injuries , P should be preferred toASA , if post-traumatic swelling and bleeding are to be prevented or reduced Purpose Following ambulatory surgery , long-acting analgesics may provide advantages over short-acting analgesics . This study compared controlled-release codeine ( CC ) and acetaminophen plus codeine ( A/C ; 300 mg/30 mg ) for pain control in the 48-hr period following laparoscopic cholecystectomy Methods Eligible patients were r and omized to CC or A/C in a double-blind , double-dummy parallel group study . Unrelieved pain in hospital was treated with fentanyliv bolus . Rain [ 100 mm visual analogue scale ( VAS ) ] was assessed before the first dose of medication ; at 0.5 , one , two , three , and four hours post-dose ; at discharge ; and three times a day for 48 hr . Adverse events were recorded and measures of patient satisfaction were assessed at the end of the study . Results Eighty-four patients were enrolled in the study ; 42 patients in each group . There were no statistically significant differences between CC and A/C treatment . Mean VAS baseline pain was similar in both groups ( P = 0.49 ) and there was no significant difference in the time to onset of analgesia ( P = 0.17 ) . At 0.5 hr , the mean VAS pain score was significantly reduced from baseline in both groups ( P = 0.0001 ) . The VAS pain scores at discharge were reduced 59 % and 56 % from baseline , respectively ( P = 0.61 ) . There was no difference between treatments in the incidence of adverse events and patients reported similar levels of satisfaction . Conclusions Controlled-release codeine provides an equivalent onset of analgesia , reduction in postoperative pain , and level of patient satisfaction , to acetaminophen plus codeine , over 48 hr following cholecystectomy , with the advantage of less frequent dosing . RésuméObjectifEn chirurgie ambulatoire , les analgésiques postopératoires d’action prolongée peuvent avoir des avantages sur les analgésiques d’action brève . Nous comparons la codéine à libération contrôlée ( CC ) et une combinaison d’acétaminophène et de codéine ( A/C ; 300 mg/30 mg ) comme analgésique pendant 48 h après une cholécystectomie laparoscopique . MéthodeDes patients admissibles à l’expérimentation ont reçu de la CC ou de l’A/C lors d’une étude à double insu , à double placebo en contrôle parallèle . A l’hôpital , la douleur tenace a été traitée avec des bolus iv de fentanyl . La douleur [ échelle visuelle analogique ( EVA ) de 100 mm ] a été évaluée avant la première dose de médicament ; à 0,5 , une , deux , trois et quatre heures après la dose ; au moment du départ et trois fois par pur pendant 48 h. Les événements indésirables ont été notés et des mesures de la satisfaction du patient ont été faites à la fin de l’étude . RésultatsLétude a été réalisée auprès de 84 patients : 42 dans chaque groupe . Il n’y a pas eu de différence statistiquement significative entre les traitements à la CC ou à l’A/C. La douleur initiale moyenne a été similaire dans les deux groupes ( P = 0,49 ) et il n’y a pas eu de différence significative de temps précédant le début de l’analgésie ( P = 0,17 ) . À 0,5 h , le score de douleur moyen à l’EVA était significativement réduit dans les deux groupes ( P = 0,0001 ) . Les scores à l’EVA au départ de l’hôpital ont été respectivement réduits de 59 % et de 56 % par rapport aux mesures initiales de la douleur ( P = 0,61 ) . Aucune différence intergroupe dans l’incidence d’événements indésirables n’a été notée et la satisfaction des patients était comparable d’un groupe à l’autre . Conclusion La codéine à libération contrôlée offre un délai d’installation de l’analgésie , une réduction de la douleur postopératoire et un niveau de satisfaction équivalents à une combinaison d’acétaminophène et de codéine pendant 48 h après une cholécystectomie , et ce , avec l’avantage d’un dosage moins fréquent A double blind trial to study the effects of analgetics was carried out in patients suffering from pain after third molar osteotomy . 204 patients were evaluated after r and om allocation to treatment with paracetamol 500 mg and paracetamol 500 mg plus codeine 30 mg . Statistical evaluation revealed a tendency for better analgesia using the combination of paracetamol and codeine . For further studies an exact stratification for sex and age is necessary . Sample sizes of 150 patients are necessary for each parameter BACKGROUND In recent studies of acute pain and primary dysmenorrhea , rofecoxib , a nonsteroidal anti-inflammatory drug that selectively targets the cyclooxygenase-2 enzyme , was found to be similar in efficacy to ibuprofen and naproxen sodium . OBJECTIVE The purpose of this study was to determine the analgesic efficacy of a single oral dose of rofecoxib 50 mg compared with the combination of codeine 60 mg/acetaminophen 600 mg in a model of postsurgical dental pain . METHODS In this double-blind , placebo- and active comparator-controlled , parallel-group study , patients experiencing moderate or severe pain after the surgical extraction of > or = 2 third molars , at least 1 of which was a m and ibular impaction , were r and omized to receive placebo , rofecoxib 50 mg , or codeine 60 mg/acetaminophen 600 mg . Patient evaluations of pain intensity , pain relief , and global assessment s were recorded throughout the 24-hour period after dosing . The 2-stopwatch method was used to determine time to confirmed perceptible pain relief . The primary end point assessing overall analgesic effect was total pain relief over 6 hours ( TOPAR6 ) . Secondary end points were patient global assessment of response to therapy ( PGART ) at 6 hours , onset of analgesia , peak analgesic effect , and duration of analgesia . RESULTS A total of 393 patients were enrolled ; 182 received rofecoxib , 180 received codeine/acetaminophen , and 31 received placebo . The overall analgesic effect of rofecoxib 50 mg was greater than that of codeine 60 mg/acetaminophen 600 mg for TOPAR6 ( 12.4 vs 7.0 ; P < 0.001 ) and PGART at 6 hours ( P < 0.001 ) . The onset of analgesic effect was similar for rofecoxib and codeine/acetaminophen . Peak analgesic effect as measured by peak pain relief scores during the first 6 hours was significantly greater in the rofecoxib group compared with the codeine/acetaminophen group ( P < 0.001 ) , as was the duration of analgesic effect measured by the time to rescue analgesia ( 9.6 hours vs 2.3 hours , P < 0.001 ) . Adverse events were reported in 33.0 % , 46.1 % , and 32.3 % of patients treated with rofecoxib , codeine/acetaminophen , and placebo , respectively . The most common adverse events were nausea ( 6.0 % , 25.0 % , and 9.7 % , respectively ) and vomiting ( 3.8 % , 18.3 % , and 6.5 % , respectively ) . Significantly more patients in the codeine/acetaminophen group than in the rofecoxib group experienced adverse events overall ( P < 0.050 ) and nausea in particular ( P < 0.001 ) . CONCLUSION In this study of moderate to severe postoperative dental pain , the analgesic efficacy of rofecoxib 50 mg was greater than that of codeine/acetaminophen , with a lower incidence of adverse events and nausea 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 We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials BACKGROUND Pain from episiotomy or tearing of perineal tissues during childbirth is often poorly treated and may be severe . This r and omized double-blind controlled trial was performed to compare the effectiveness , side effects and cost of , and patient preference for , 2 analgesics for the management of postpartum perineal pain . METHODS A total of 237 women who gave birth vaginally with episiotomy or a third- or fourth-degree tear between August 1995 and November 1996 at a tertiary-level teaching and referral centre for obstetric care in Vancouver were r and omly assigned to receive either ibuprofen ( 400 mg ) ( n = 127 ) or acetaminophen ( 600 mg ) with codeine ( 60 mg ) and caffeine ( 15 mg ) ( Tylenol No. 3 ) ( n = 110 ) , both given orally every 4 hours as necessary . Pain ratings were recorded before the first dose and at 1 , 2 , 3 , 4 , 12 and 24 hours after the first dose on a 10-cm visual analogue scale . Side effects and overall opinion were assessed at 24 hours . RESULTS Ibuprofen and acetaminophen with codeine had similar analgesic properties in the first 24 hours post partum ( mean pain rating 3.4 and 3.3 , mean number of doses in 24 hours 3.4 and 3.3 , and proportion of treatment failures 13.8 % [ 16/116 ] and 16.0 % [ 16/100 ] respectively ) . Significantly fewer subjects in the ibuprofen group than in the acetaminophen with codeine group experienced side effects ( 52.4 % v. 71.7 % ) ( p = 0.006 ) . There were no significant differences in overall patient satisfaction between the 2 groups . The major determinant of pain intensity was forceps-assisted delivery . Overall , 78 % of the treatment failures were in women with forceps-assisted deliveries . INTERPRETATION Since the 2 analgesics were rated similarly , ibuprofen may be the preferred choice because it is less expensive and requires less nursing time to dispense . Further studies need to address improved analgesia for women with forceps-assisted deliveries Two-hundred six out patients with postoperative pain after the surgical removal of impacted third molars were r and omly assigned on a double-blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg , ibuprofen 400 mg , acetaminophen 600 mg , a combination of acetaminophen 600 mg plus codeine 60 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 6 hours after medicating . All active medications were significantly superior to placebo . Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg ; however , these treatments were superior to acetaminophen alone and the acetaminophen-codeine combination . The analgesic effect of each active medication was significant by hour 1 and persisted for 5 - 6 hours . The data suggest a plateau in ketorolac 's analgesic efficacy at the 10-mg level . Repeat-dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg ; ketorolac 20 mg was also superior to acetaminophen-codeine . Differences among active medications were not significant when data for the entire postoperative period ( days 0 - 6 ) were evaluated . The frequency of adverse effects was similar for the active medications This study was conducted to compare the analgesic action of Lysine Clonixinate ( LC ) vs Paracetamol/Codeine association ( PC ) in the treatment of postepisiotomy pain in primiparae women : 131 primiparous patients with moderate-to-severe postepisiotomy pain were enrolled in a double blind dummy design study and r and omly allocated to either treatment with fixed doses of LC 125 mg or Paracetamol 500 mg+Codeine 30 mg 6 qh during 24 hours . Intensity of spontaneous pain and pain on walking was assessed according to a visual analog scale ( VAS ) and patient 's assessment before receiving treatment and after 1 , 2 , 6 and 24 hours . Intensity of spontaneous pain was reduced in 24 hours from 4.28 + /- 2.11 to 1.73 + /- 1.46 ( P < 0.0001 ) in the LC group and from 4.78 + /- 2.08 to 1.90 + /- 1.72 in the PC-treated group ( p < 0.0001 ) ; with no significant differences between treatments . 54 % of the patients treated with LC and 55 % of those receiving PC showed onset of analgesic action 30 minutes following dose administration . Patient 's final global assessment revealed that 95 % of LC-treated patients and 96 % of the PC group showed total or partial pain relief during the first treatment day . No sleep disturbances were seen during the night in 75 % of patients . Only one patient receiving LC showed nausea not requiring treatment discontinuation . It is concluded that both treatments are equally effective to relieve moderate-to-severe postepisiotomy pain Objective : To compare the overall analgesic effect , including time to onset , peak and duration of effect for etoricoxib 120 mg , a new COX-2 selective inhibitor , in patients with acute pain to that of placebo . Naproxen sodium 550 mg and acetaminophen/codeine 600/60 mg were the active comparators . Methods : A total of 201 patients with moderate to severe pain following surgical extraction of ≥2 third molars , of which at least the m and ibular tooth was impacted , were r and omly allocated to receive single oral doses of placebo ( n = 50 ) , etoricoxib 120 mg ( n = 50 ) , naproxen sodium 550 mg ( n = 51 ) , or acetaminophen/codeine 600/60 mg ( n = 50 ) . The endpoints included total pain relief over 8 hours ( TOPAR8 , primary end point ) , sum of pain intensity difference over 8 hours , patient ’s global evaluation , onset , peak , and duration of analgesia . Results : Etoricoxib 120 mg had a significantly greater least squares ( LS ) mean TOPAR8 score than placebo ( 20.9 vs 5.4 ; P < 0.001 ) and acetaminophen/codeine 600/60 mg ( 20.9 vs 11.5 ; P < 0.001 ) , and a similar LS mean TOPAR8 score to naproxen sodium 550 mg ( 20.9 vs 21.3 ) . All three active treatments had rapid onset of analgesia , median time ~30 minutes . The duration of analgesic effect , defined as median time to rescue medication use , was > 24 hours for etoricoxib , 20.8 hours for naproxen sodium , 3.6 hours for acetaminophen/codeine , and 1.6 hours for placebo . Discussion : Etoricoxib is a new COX-2 selective inhibitor under development for treatment of osteoarthritis , rheumatoid arthritis , and acute pain . In this study , etoricoxib 120 mg provided rapid and long-lasting pain relief to patients with moderate-to-severe postdental surgery pain . Etoricoxib was generally well tolerated A double-blind , r and omized , single-dose study was performed to compare the efficacy and safety of two commonly prescribed combination analgesic products to placebo . The combinations were acetaminophen 300 mg/codeine 30 mg(† ) , and aspirin 325 mg/butalbital 50 mg/caffeine 40 mg/codeine 30 mg(†† ) . One hundred twenty-three ( 123 ) oral surgery out patients took study medications when their pain became moderate to severe and recorded the levels of pain intensity , pain relief , anxiety and relaxation at 30 minutes and hourly for 6 hours after dosing . Remedication was permitted if study medications did not provide adequate pain relief . Time to remedication , and the number of observations with 50 % or better relief , were noted as were any side effects . An overall evaluation was obtained from each patient . Results of the study showed that the aspirin/butalbital/caffeine/codeine combination was significantly more effective than placebo for total pain relief , peak relief and global evaluation . While the acetaminophen/codeine combination was numerically superior to placebo , it achieved statistical significance only for global evaluation . The aspirin/butalbital/caffeine/codeine combination was numerically superior to acetaminophen/codeine for every measure of analgesic efficacy but the differences did not achieve statistical significance . Both active treatment groups experienced significantly less total anxiety than did the placebo group . Only 11 patients reported mild , transient adverse effects ; the most common was drowsiness . The adverse effects occurred equally among the three treatment groups . In this study , the aspirin/butalbital/caffeine/codeine combination was significantly superior to placebo and somewhat better than acetaminophen/codeine & 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 Patients who experienced pain after surgery were administered a single dose of 1 of 3 treatments : acetaminophen 1000 mg , codeine phosphate 60 mg , or a combination of these . Patients rated their pain intensity on ordinal and visual analog scales just prior to medication and at intervals thereafter for up to 5 hours . They also rated pain relief , pain half gone , and any adverse effects . Sum of pain intensity difference and total pain relief scores were analyzed using Dunnett 's procedure . The drug combination was statistically superior to codeine as measured by SPID , TOTPAR , pain half gone , and time to remedication . The combination achieved better mean scores than acetaminophen on all efficacy measures , but was ( marginally ) statistically superior only in pain half gone . No appreciable differences in adverse effects were noted among the treatments . The difficulty of showing the analgesic efficacy of codeine in a single dose trial is discussed Summary A double-blind , multicentre analgesic trial was carried out in patients suffering from pain after removal of an impacted lower wisdom tooth . 266 patients were evaluated after r and om allocation to treatment with paracetamol 500 mg , paracetamol 500 mg plus codeine 20 mg , paracetamol 500 mg plus codeine 30 mg , or paracetamol 500 mg plus codeine 40 mg . On the day of surgery the patients assessed their own pain intensity hourly on a visual analogue scale . The analysis of the results was carried out according to a method which considered repeated dose intake . A statistically significant dose-response relationship was obtained between the supplementary doses of codeine and analgesic efficacy . In the comparison of side effects , their frequency increased with increasing amounts of codeine . In clinical practice codeine 30 mg appeared to be the optimal supplement for paracetamol 500 mg The analgesic efficacy of single 500- and 1,000-mg doses of diflunisal ( Dolobid ) , a new nonsteroidal anti-inflammatory analgesic , was compared in a double-blind study with that of acetaminophen , 600 mg , the combination of acetaminophen , 600 mg , with codeine phosphate , 60 mg , and placebo in 159 oral surgery out patients . Using a self-rating record , patients rated their pain and its relief hourly for 12 hours after medication . Both doses of diflunisal were significantly more effective than acetaminophen alone and produced peak analgesia comparable to that of the acetaminophen-codeine combination . Diflunisal proved to have an unusually long duration of analgesic action . Acetaminophen and the combination were significantly superior to placebo through hours 2 and 5 , respectively ; both doses of diflunisal were significantly superior through the end of the 12-hour observation period . None of the active treatments produced more side effects than the placebo Summary A double-blind r and omized trial was carried out in 90 male patients suffering from pain after meniscectomy . The patients received a single dose of paracetamol 1 000 mg plus codeine 60 mg , paracetamol 1 000 mg , codeine 60 mg , or placebo . The tablets were taken when needed after surgery and the postoperative pain was recorded on a visual analogue scale . Over a period of 4 h the efficacy of the drugs was calculated in terms of pain intensity , pain intensity difference and percentage pain reduction . The greatest effect was obtained in patients taking the paracetamol plus codeine combination . Statistical analysis was carried out by use both of parametric and non-parametric procedures . The results suggest that pain reduction is a valuable measurement of analgesic efficacy and that non-parametric assumptions are preferable in the statistical analysis of analgesic activity The purpose of this double-blind , r and omized , parallel , multiple-dose study was to compare the efficacy and safety of flurbiprofen with acetaminophen with codeine phosphate in the 96-hr postoperative period following foot surgery . Analysis of mean pain intensity and mean pain relief for the patients not requiring rescue medication did not reveal any significant differences between treatment groups . There were also no significant differences between treatment groups with respect to patient and investigator global evaluations of therapy . The incidence of termination of the study because of side effects was higher for the acetaminophen with codeine group Tramadol/acetaminophen ( APAP ) combination tablets were shown effective and safe for postsurgical orthopedic pain in a 6-day , multicenter , r and omized , double-blind , active- and placebo-controlled study . Of 305 intent-to-treat ( ITT ) postsurgical patients , 153 patients undergoing arthroscopy who had at least moderate pain were r and omized to receive either tramadol 37.5 mg/APAP 325 mg ( mean , 4.3 tablets ) , or codeine 30 mg/APAP 300 mg ( mean , 4.6 tablets ) , or placebo . Tramadol/APAP was superior to placebo for the following outcome variables : total pain relief ( TOTPAR , P = .013 ) , sum of pain intensity differences ( SPID , P = .049 ) , sum of total pain relief and sum of pain intensity differences ( SPRID , P = .018 ) , and average daily pain relief ( P = .031 ) . Similar incidence of adverse events for tramadol/APAP and codeine/APAP was found , except for constipation ( 0 % vs 10.9 % ) and vomiting ( 8.2 % vs 16.4 % ) BACKGROUND This multicenter , r and omized , double-blind , active- and placebo-controlled trial evaluated tramadol plus acetaminophen ( APAP ) for orthopedic ( n = 153 ) and abdominal ( n = 152 ) postsurgical pain . METHODS Patients with moderate pain or greater were r and omized to an initial two tablets of 37.5 mg tramadol plus 325 mg APAP ( n = 98 ) , codeine 30 mg plus APAP 300 mg ( n = 109 ) , or placebo ( n = 98 ) ; thereafter , they received 1 to 2 tablets every 4 to 6 hours as needed for pain for 6 days . Outcome measures were pain relief and pain intensity , total pain relief , sum of pain intensity differences , and sum of pain relief and pain intensity differences during 4 hours and the daily averages . RESULTS Tramadol plus APAP was superior to placebo for total pain relief , sum of pain intensity differences , and sum of pain relief and pain intensity differences ( P < or = 0.015 ) ; tramadol plus APAP and codeine plus APAP did not separate ( P > or=0.281 ) . For average daily pain relief , average daily pain intensity , and overall medication assessment , tramadol plus APAP was superior to placebo ( P < or = 0.038 ) ; codeine plus APAP did not separate from placebo ( P > or = 0.125 ) . Discontinuation because of adverse events occurred in 8.2 % of tramadol plus APAP , 10.1 % of codeine plus APAP , and 3.0 % of placebo patients . Except for constipation ( 4.1 % tramadol plus APAP vs 10.1 % codeine plus APAP ) and vomiting ( 9.2 % vs 14.7 % , respectively ) , adverse events were similar for active treatments . CONCLUSIONS Tramadol plus APAP ( mean dose 4.4 tablets ) was effective and well tolerated for postsurgical pain and showed better tolerability than did codeine plus APAP A double-blind clinical study of analgesic drugs was conducted involving 47 healthy adults requiring removal of 90 bony impacted m and ibular third molars . The analgesic effect of paracetamol plus codeine ( P + C ) 350 + 20 mg was compared to that of acetylsalicylic acid ( ASA ) 500 mg and placebo . A st and ardized surgical procedure under local anesthesia was used . Insufficient analgesic effect was noted in 16 % of the ASA group and in 69 % of the placebo group but in none in the P+C group . On the first postoperative day , patients given P+C suffered less pain compared with those given ASA ( P less than 0.01 ) . No relationship could be demonstrated between the type of impaction and intensity of pain . Trismus , however , was found to be associated with difficulty of extirpation . Drowsiness and an increased sleeping tendency were the main side effects found in the P+C group . The incidence of secondary hemorrhage was high in the ASA group , compared with the P+C group a significance of 0.01 less than P less than 0.05 was found on various postoperative days . Registration of swelling revealed less postoperative edema in the P+C group than in the ASA group ( 0.01less thanPless than0.05 ) . The main conclusion from this study is that the analgesic effect of P+C orally administered after a specific oral surgical procedure is superior to ASA and placebo . P+C also appears to have a more marked antiphologistic effect than ASA PURPOSE The analgesic efficacy of 50 and 100 mg flurbiprofen was compared with acetaminophen 650 mg , acetaminophen 650 mg plus codeine 60 mg , and placebo . PATIENTS AND METHODS Subjects undergoing the surgical removal of impacted third molars were r and omly administered one of the five treatments after the onset of moderate to severe postoperative pain . Pain intensity , pain relief , and side effects were evaluated for 6 hours after drug administration . RESULTS Both doses of flurbiprofen result ed in significant analgesia in comparison with placebo , acetaminophen , and acetaminophen plus codeine as measured by pain intensity difference , pain relief , and global evaluation . The greatest incidence of side effects occurred in the group receiving acetaminophen plus codeine , and the fewest side effects were reported by subjects administered flurbiprofen . CONCLUSION The results of this study indicate that flurbiprofen is more effective and causes fewer effects than acetaminophen and codeine when used for post-operative dental pain , in ambulatory patients Enadoline , a selective agonist of the kappa-opioid receptor , was studied for its analgesic efficacy in patients with pain after obstetric or gynecologic surgery . An initial study involving a comparison of enadoline ( 2 , 5 , 15 micrograms ) , an acetaminophen-codeine ( ACET/COD ) combination , and placebo showed all treatments to be ineffective analgesics . Therefore , a second study with the same design but using higher doses of enadoline ( 15 and 25 micrograms ) and replacing ACET/COD with morphine 10 mg i.m . was conducted . Enadoline 25 micrograms produced similar pain relief to that of morphine , although of shorter duration , and better than enadoline 15 micrograms or placebo . However , enadoline was associated with dose-limiting neuropsychiatric adverse events , which led to early termination of the study & 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 In a r and omized double‐blind study , 120 patients with moderate to strong pain after surgical removal of wisdom teeth were given the following in single oral doses : 100‐mg enteric‐coated diclofenac tablets ; 1 g acetaminophen ( INN , paracetamol ) ; 1 g acetaminophen plus 60 mg codeine ; 100‐mg enteric‐coated diclofenac tablets plus 1 g acetaminophen ; or 100‐mg enteric‐coated diclofenac tablets plus 1 g acetaminophen plus 60 mg codeine . Patients recorded pain intensity and pain relief for 8 hours . Upside assay sensitivity was confirmed because acetaminophen plus codeine was superior to acetaminophen . Diclofenac plus acetaminophen with and without codeine had superior analgesic effect compared with diclofenac , acetaminophen , or acetaminophen plus codeine . Addition of 60 mg codeine increased the degree of side effects . These results support the clinical practice of combining diclofenac with acetaminophen for acute pain . Of clinical importance are superior and prolonged analgesia and fewer side effects after enteric‐coated diclofenac tablets plus acetaminophen compared with acetaminophen plus codeine BACKGROUND Codeine is frequently added to paracetamol to treat post-operative dento-alveolar pain ; studies have shown effectiveness in relief of post-operative pain at high doses but at the expense of central nervous and gastrointestinal side effects . There has been no trial to compare the efficacy and safety of paracetamol 1000 mg with paracetamol 1000 mg combined with codeine 30 mg . METHOD A r and omized , single centre , double-blind prospect i ve parallel group trial was performed to compare paracetamol 1000 mg with paracetamol 1000 mg with codeine 30 mg for the relief of pain following surgical removal of impacted third molars , and analysed on an intention-to-treat ( ITT ) basis . Eighty-two patients were assigned r and omly to receive either drug for a maximum of three doses . Patients recorded their pain intensity one hour after surgery and hourly thereafter for 12 hours . RESULTS The average increase in pain intensity over 12 hours was significantly less in patients receiving paracetamol plus codeine than in those receiving paracetamol alone ( p=0.03 ) -1.81 cm/h compared with 0.45 cm/h - a difference of 1.13 cm/h ( 95 per cent CI : 0.18 to 2.08 ) . Of the patients who received the paracetamol codeine combination , 62 per cent used escape medication compared with 75 per cent of those on paracetamol alone ( p=0.20 ) . There was no significant difference between the two groups in the proportion of patients experiencing adverse events ( p=0.5 ) . CONCLUSION A combination of 1000 mg paracetamol and 30 mg codeine was significantly more effective in controlling pain for 12 hours following third molar removal , with no significant difference of side effects during the 12 hour period studied In a single-dose , parallel group , r and omized block treatment allocation study , the relative analgesic efficacy of flurbiprofen , a nonsteroidal antiinflammatory drug , was compared to acetaminophen 650 mg with codeine 60 mg , zomepirac sodium 100 mg , and placebo . A total of 226 post-surgical dental patients ( 146 females and 80 males ) participated in the study . Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination . The results of this study support previous work on flurbiprofen Codeine , a relatively weak oral narcotic agent , is the most frequently prescribed oral opiate drug . It is also frequently utilized as a control drug in comparative analgesic efficacy studies . These studies are often single dose analysis of pain relief following surgery or childbirth . We conducted a single dose , post-operative analysis of 116 patients who were r and omly assigned to receive codeine 60 mg , acetaminophen 600 mg , the combination of codeine and acetaminophen at these doses , or a placebo . Only the combination agent was uniformly superior to placebo . Codeine 60 mg was not consistently superior to placebo in this post-operative single dose analysis . A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic , in acceptable oral doses , in the single dose setting . Previous reports , however , suggest that the multiple doses of codeine may afford adequate analgesia . Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult A double-blind r and omized analgesic trial was carried out in patients suffering from pain after removal of a third molar tooth . In a two-dose regimen , 108 patients received either 60 mg codeine , 500 mg acetaminophen , or 1000 mg acetaminophen . On the day of surgery , the patients assessed their pain intensity hourly on a visual analog scale . The evaluation was carried out during the 10-hour period after first medication . The best pain reducing effects were achieved with 1000 mg acetaminophen . Both the category and position of each tooth were examined in relation to pain intensity ; however , the statistical analysis did not reveal any significant correlation . In all treatment groups , the efficacy of the second dose was superior to that of the first , and the most pronounced difference was obtained in patients taking codeine , who increased their pain reduction from 20 to 60 per cent . Clinical comparisons including codeine may therefore be better carried out in a repeated-dose regimen Pain after episiotomy and /or perineal/vaginal rupture in childbirth is severe in many patients and in most cases it can be treated with oral analgesics . In this trial the efficacy and side-effect profile of two combination analgesics , paracetamol/codeine and paracetamol/dextropropoxyphene hydrochloride , were compared in post-partum pain after episiotomy and /or rupture of the perineum . Eighty-five patients were analysed for efficacy and 96 were included in an analysis of side-effects . Paracetamol/codeine was shown to give faster and more efficient pain relief while not causing constipation or other troublesome side-effects he combination of oral codeine and acetamino-phen is often used for postdischarge pain controlafter ambulatory surgery . However , frequentlyreported side effects include sedation , constipation , and nausea ( 1 ) . Furthermore , drugs containing co-deine may be abused ( 2 ) and may result in serious sideeffects when combined with alcohol or benzodiaz-epines . Nonsteroidal antiinflammatory drugs are anonprescription alternative to these drugs . The aim of this study was to compare ibuprofenwith codeine/acetaminophen for pain control duringthe first 72 h after ambulatory surgery The analgesic efficacy of a hydrocodone-acetaminophen combination , a codeine-acetaminophen combination , a codeine-APC ( aspirin , phenacetin , and caffeine ) combination , and a placebo was evaluated in out patients who had moderate or severe pain after the surgical removal of impacted third molars . Each of the active medications had a significant effect on essentially all measures of total and peak analgesia ; they did not differ significantly on any measure of analgesia . Adverse effects were transitory and , in general , appear to have been related to the central ly acting component of each combination analgesic PURPOSE The purpose of this double-blind , r and omized study was to compare the efficacy and safety of a single dose of the following medications : 2 tablets of Vicoprofen ( ibuprofen 200 mg/hydrocodone 7.5 mg ; Knoll Pharmaceutical Co , Mount Olive , NJ ) , 2 tablets ofp6 acetaminophen with codeine phosphate ( acetaminophen 300 mg/codeine 30 mg ) , and 2 tablets of placebo in the management of moderate to severe postoperative dental pain after surgical extraction of at least one impacted m and ibular third molar . PATIENTS AND METHODS One hundred twenty-five patients ( 75 women , 50 men ) participated in the study . The time of first perceptible pain relief and meaningful pain relief were measured using a stopwatch technique . Pain intensity and pain relief scores were recorded using st and ard verbal descriptors at 0.5 , 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 7 , and 8 hours after dosing . At the conclusion of the study , patients completed a global evaluation for the effectiveness of the study medication . RESULTS Both active treatments were superior to placebo for all analgesic measures . Pain relief scores were significantly better for Vicoprofen than placebo throughout the study and significantly better than for acetaminophen with codeine from 2 through 8 hours after dosing . The duration of analgesia ( time to remedication ) was significantly longer for Vicoprofen ( median , 5.50 hours ) compared with acetaminophen with codeine ( median , 3.03 hours ) and placebo ( median , 1.00 hours ) . Mean global evaluation for Vicoprofen was significantly better than for placebo and acetaminophen with codeine . Overall , there were no significant differences in the adverse event profile among the 3 treatment groups . CONCLUSIONS Vicoprofen was found to be an effective postoperative analgesic medication in the management of acute postoperative dental pain . Its total analgesic effect , duration of analgesia , and global evaluation were superior to acetaminophen with codeine and placebo in this study model STUDY OBJECTIVE To determine the relative analgesic potency and adverse effect liability of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg , codeine phosphate 30 mg with acetaminophen 300 mg , and placebo in the treatment of pain following oral surgery . DESIGN R and omized , double-blind , single-dose , placebo-controlled , parallel-group study with self-ratings at 30 minutes and then at hourly intervals from hour 1 to hour 6 . SETTING Private , oral surgery practice sites . PATIENTS Three hundred twenty-four out patients with moderate or severe pain after the surgical removal of impacted third molars were selected . One was lost to follow-up and 32 did not need an analgesic ; 232 patients had valid efficacy data . INTERVENTIONS Patients were treated with a single oral dose of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg , codeine phosphate 30 mg with acetaminophen 300 mg , or placebo when they experienced steady , moderate or severe pain that , in their opinion , required an analgesic . Using a self-rating record , subjects rated their pain and its relief for 6 hours after medicating ; estimates of peak and total analgesia were derived from these subjective reports . MEASUREMENTS AND MAIN RESULTS This study was a valid analgesic assay . Both active treatments were significantly superior to placebo for all measures of analgesic efficacy . The hydrocodone-acetaminophen combination was significantly superior to the codeine-acetaminophen combination for total pain relief and the number of evaluations with 50 % relief . Both active treatments manifested an analgesic effect within 30 minutes ; the effect persisted for 5 hours for the codeine combination and 6 hours for the hydrocodone combination . Adverse effects were transient , consistent with the pharmacologic profiles of opioids , and none required treatment . CONCLUSIONS A slight advantage in analgesic efficacy was demonstrated in this single-dose study for the hydrocodone-acetaminophen combination . Repeat-dose studies , however , should be conducted to determine the clinical significance of the difference in analgesic effect of these opioid combinations OBJECTIVE To determine analgesic efficacy of a single oral dose of rofecoxib 50 mg compared with acetaminophen/codeine 600/60 mg , we conducted a double-blind , r and omized , placebo- and active-comparator-controlled , parallel-group study . STUDY DESIGN Patients ( N = 390 ) experiencing moderate or severe pain post extraction of 2 or more third molars , with at least 1 m and ibular impaction , were r and omized to placebo ( n = 30 ) , rofecoxib ( n = 180 ) , or codeine/acetaminophen 60/600 mg ( n = 180 ) . Time to confirmed perceptible pain relief , and patient evaluations of pain intensity , pain relief , and global assessment s were recorded . RESULTS For total pain relief over 6 hours ( primary end point ) , rofecoxib was superior to codeine/acetaminophen ( 15.5 vs 10.7 ; P < .001 ) . Rofecoxib was statistically significantly superior to codeine/acetaminophen with respect to TOPAR4 , patient global assessment , peak pain relief , and duration of analgesic effect . Median onset of analgesia was similar for both drugs . The codeine/acetaminophen group had more patients with 1 or more adverse events . CONCLUSION Rofecoxib provided superior analgesic efficacy compared with codeine/acetaminophen with fewer gastrointestinal and nervous system adverse events One-hundred twenty-eight out patients with postoperative pain after the surgical removal of impacted third molars were r and omly assigned , on a double-blind basis , to receive oral doses of ketorolac tromethamine 10 mg , aspirin 650 mg , a combination of acetaminophen 600 mg plus codeine 60 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 6 hours after medicating . All active medications were significantly superior to placebo . The acetaminophen-codeine combination was significantly superior to aspirin for peak analgesia . Ketorolac was significantly superior to aspirin for every measure of total and peak analgesia , and significantly superior to acetaminophen-codeine for measures of total effect . The analgesic effect of ketorolac was significant by hour 1 and persisted for 6 hours . Repeat-dose data also suggested that ketorolac 10 mg was superior to aspirin 650 mg and acetaminophen-codeine on the day of surgery . Differences among the active medications were trivial for the postoperative days 1 - 6 analyses . The frequency of adverse effects was over 4 times greater for acetaminophen-codeine than for ketorolac or aspirin 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 The efficacy of an aspirin-caffeine-codeine-butalbital combination was compared to an acetaminophen-codeine combination and placebo in out patients who had moderate or severe pain after the surgical removal of impacted third molars . Using a self-rating record , patients rated their pain , relief , anxiety and relaxation hourly for up to 6 hours after medicating . Each active medication was significantly superior to placebo for measures of analgesia and relaxation . Although the butalbital-containing combination provided consistently greater analgesia , the differences between active medications were not statistically significant . The acetaminophen-codeine combination significantly reduced anxiety ; however , the butalbital containing combination did not . The results of this study suggest that female patients may have greater efficacy than male patients . All adverse effects were transitory and consistent with the known pharmacologic profiles of the study medications or the backup analgesic In a r and omized , double-blind , multiple-dose , parallel study of 107 patients , the safety and analgesic efficacy of single and multiple doses of orally administered ketorolac tromethamine ( 10–40 mg/day ) were compared with orally administered paracetamol ( 1000–4000 mg/day)/codeine ( 60–240 mg/day ) for treating moderate to severe pain after gynaecological surgery . Both drugs effectively reduced pain intensity . After the first dose of medication , over 90 % of the patients in each treatment group reported pain reduction of at least 50 % . The mean time until additional medication was requested was over 6 h for both groups . No statistically significant differences in analgesic efficacy were observed in the two treatment groups . Ketorolac tromethamine-treated patients reported a total of 62 adverse events ( 17 considered drug-related ) and the paracetamol/codeine-treated patients reported 65 ( 20 considered drug-related ) ; the adverse event profiles of the two treatment regimens were similar . Thus , both the single and the multiple doses of ketorolac tromethamine ( 10 mg ) alleviated moderate to severe pain after gynaecological surgery as safely and efficaciously as paracetamol ( 1000 mg)/codeine ( 60 mg ) This prospect i ve study compared the effectiveness of nine medications and a placebo in controlling pain following obturation . A total of 588 patients who required root canal obturation were included . After obturation of root canals , each patient took one of the medications , salicylic acid ( 2 x 250 mg ) , acetaminophen ( 2 x 250 mg ) , ibuprofen ( 2 x 250 mg ) , ketoprofen ( 2 x 250 mg ) , acetaminophen ( 2 x 250 mg ) plus codeine ( 2 x 250 mg ) , penicillin ( 2 x 250 mg ) , erythromycin base ( 2 x 250 mg ) , penicillin plus ibuprofen ( 2 x 250 mg ) , methylprednisolone ( 2 x 250 mg ) plus penicillin ( 2 x 250 mg ) , or a placebo , every 6 h for 72 h. All medications were encapsulated in identical capsules . The patients registered their degree of discomfort on a visual analogue scale of 0 to 9 . Statistical analysis of the data showed that the incidence of postoperative pain after obturation is lower than that following complete cleaning and shaping ( 5.83 % versus 21.76 % ) . In addition , there was no significant difference between the effectiveness of the various medications and placebo tablets in controlling postoperative pain following obturation Eighty-eight out patients with postoperative pain after the surgical removal of impacted third molars were r and omly assigned , on a double-blind basis , to receive a single , oral dose of flurbiprofen 100 mg , acetaminophen 600 mg , a combination of acetaminophen 600 mg with codeine 60 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 12 hours after medicating . Estimates of sum of pain intensity differences , peak pain intensity differences , total relief , peak relief , and hours of 50 % relief were derived from these subjective reports . Flurbiprofen and the acetaminophen-codeine combination were significantly superior to placebo for every measure of total and peak analgesia and significantly superior to acetaminophen alone for most measures of efficacy . Based on the 12-hour data , acetaminophen alone did not differ significantly from placebo ; however , it was superior to placebo for measures of total effect based on the 4-hour data . Flurbiprofen was significantly superior to the acetaminophen codeine combination with respect to the number of hours until remedication . All medications had manifested an effect by hour 1 ; analgesia persisted for 12 hours for flurbiprofen , 6 hours for acetaminophen-codeine , and 3 hours for acetaminophen alone . The frequency of adverse effects was similar for the active medications The relative analgesic efficacy and safety of single oral doses of 50 and 100 mg of flurbiprofen ( Ansaid , Upjohn ) were compared with 100 mg of zomepirac sodium , 650 mg of acetaminophen plus 60 mg of codeine , 650 mg of acetaminophen alone , and placebo in a r and omized , double-blind , parallel-group study . A total of 182 patients entered the study with moderate pain from a third molar extraction and were evaluated for six hours . For many efficacy variables , all active treatments were significantly ( p less than or equal to 0.05 ) more effective than placebo . The two doses of flurbiprofen gave approximately similar results , suggesting a plateau effect above 50 mg . With the exception of relief at one hour , there were no significant differences between zomepirac and either dose of flurbiprofen . However , the mean response with zomepirac was greater than with either 50 or 100 mg of flurbiprofen during the first four hours and lower during the last two hours . The analgesic effects of acetaminophen alone were not significantly different from acetaminophen in combination with codeine . At the first hour , acetaminophen plus codeine led to significantly better pain relief than did 100 mg of flurbiprofen . After the first hour , flurbiprofen result ed in greater mean scores than acetaminophen alone or acetaminophen plus codeine , and these differences were significant at the fifth and sixth hours . Five patients had adverse reactions while receiving acetaminophen , acetaminophen plus codeine , or placebo . There were no adverse effects with flurbiprofen or zomepirac |
10,553 | 20,858,956 | In conclusion , it appears that general anesthesia , compared to others , may increase the risk of developing POCD ; however this has not been shown for POD . | Post-operative cognitive complications such as delirium have been consistently associated with poor short and long term outcomes , and the role of anesthesia , particularly the role of general versus regional anesthesia , remains unclear .
The objective of this systematic review with meta- analysis was to compare the influence of general , regional , or a combination of anesthesia on the development of Post-Operative Cognitive Dysfunction ( POCD ) and Post-Operative Delirium ( POD ) . | St and ardized behavioural observations were used to establish the influence of the type of anaesthesia on the mental function and the subjective physical well-being in 60 patients , all men , following urological surgery . The patients were r and omized to two groups , receiving spinal or general anaesthesia . For evaluation of the influence of pre-operative physical condition on post-operative mental function , a supplementary group of 34 patients with pre-existing cardiovascular and /or pulmonary disorders was included in the study . These patients all received spinal anaesthesia . The patients were observed from the day before surgery until 4 weeks after . In all patients a short-lasting temporary decline in mental function was observed . The outcome was not influenced by the type of anaesthesia . In the two groups receiving spinal anaesthesia the decline in post-operative mental function and subjective sense of well-being was most pronounced in patients with a compromised physical condition pre-operatively . Four weeks after surgery , no signs of mental deterioration were present ; however , the subjective sense of physical well-being had not fully returned This study compared the effects of general and regional anesthesia on cognitive and psychosocial functioning in elderly persons . Sixty-four patients between 60 and 86 yr of age undergoing knee arthroplasty were r and omly assigned to receive either general or regional anesthesia . A battery of psychometric tests , including the Satz-Mogel form of the Wechsler Adult Intelligence Scale-Revised , the Wechsler Memory Scale-Revised and the Sickness Impact Profile , and various neuropsychological measures were administered by a blinded observer just before surgery and again 3 months later . Analyses of covariance revealed improvements in most measures that were equivalent between groups . The results indicated that there were no cognitive or psychosocial effects of general or regional anesthesia after 3 months in elderly persons undergoing knee arthroplasty . In this patient population , general anesthesia poses no more risk to long-term mental function than regional anesthesia Background and objectives : Postoperative confusion and delirium is a common complication in the elderly with a poorly understood pathophysiology . The aim of this study was to examine whether the type of anaesthesia ( general or regional ) plays a role in the development of cognitive impairment in elderly patients during the immediate postoperative period . Methods : Forty‐seven patients > 60 yr of age and undergoing major surgery were r and omly allocated to receive either regional or general anaesthesia . The mental status of the patients was assessed preoperatively and during the first three postoperative days with the Mini Mental State Examination . The incidence of delirium was also examined during the same period with the use of DSM III criteria . Results : Overall , during the first three postoperative days , the mean Mini Mental State Examination score decreased significantly ( P < 0.001 ) . However , this decline was very significant only in patients assigned to receive general anaesthesia ( P < 0.001 ) compared to regional anaesthesia . Nine patients developed delirium but the type of anaesthesia did not affect its incidence . The only important factor for the development of delirium was pre‐existing cardiovascular disease irrespective of anaesthesia type ( P < 0.025 ) . Conclusions : Elderly patients subjected to general anaesthesia displayed more frequent cognitive impairment during the immediate postoperative period in comparison to those who received a regional technique Background : Postoperative cognitive dysfunction ( POCD ) is a common complication after cardiac and major non‐cardiac surgery with general anaesthesia in the elderly . We hypothesized that the incidence of POCD would be less with regional anaesthesia rather than general OBJECTIVE --To determine the influence of general or regional anaesthesia on long term mental function in elderly patients . DESIGN -- Prospect i ve study of patients r and omly allocated to receive general or regional anaesthesia . SETTING --The patients ' homes and a large teaching hospital in Cardiff . SUBJECTS--146 Patients aged 60 and over scheduled for elective hip or knee replacement . MAIN OUTCOME MEASURES --Scores achieved in tests of cognitive function and functional competence . RESULTS --72 Patients were allocated to receive general anaesthesia and 74 regional anaesthesia . Anaesthetic technique did not influence the duration of the operation , time to mobilisation postoperatively , requirements for analgesia after the operation , or duration of stay in hospital . Three months after the operation there was an improvement in the score for the recognition component ( 76 ms , 95 % confidence interval 9 to 144 ) and the response component ( 82 ms , 5 to 158 ) of the choice reaction time in the group receiving general anaesthesia compared with the group receiving regional anaesthesia . This was the only significant difference between the two groups in the assessment s of cognitive and functional competence . Eleven patients receiving regional anaesthesia and 12 receiving general anaesthesia reported that their memory and concentration were worse than before the operation , but this was not confirmed by testing . CONCLUSION --Cognitive and functional competence in elderly patients was not detectably impaired after either general or regional anaesthesia when attention was paid to the known perioperative influences on mental function To evaluate whether there is a difference in mental function after general anaesthesia and epidural analgesia , a homogeneous group of 40 elderly men ( age between 60 and 80 ) undergoing transurethral prostatectomy was studied . The study was prospect i ve , r and omised and double blind . Patients with all types of complications believed to impair mental function were excluded . Long‐term , short‐term , verbal and visual memory were tested preoperatively , and 4 days , and 3 weeks postoperatively . In conclusion , we found a significant and equal decline in test performance on the fourth postoperative day . Three weeks postoperatively , however , both groups had returned to or exceeded preoperative levels of performance One hundred and one patients were r and omly allocated to have their peripheral vascular surgery performed under general anaesthesia ( 51 patients ) or spinal anaesthesia ( 50 patients ) . Intraoperative haemodynamic changes were markedly different between the two groups with a higher incidence of hypotension in the spinal group ( 72 % vs 31 % ) and a higher incidence of hypertension in the general anaesthesia group ( 22 % vs 0 % ) . Blood loss was significantly less in the spinal group ( 560 , SD 340 , ml vs 792 , SD 440 , ml ) . Postoperatively three patients from the general anaesthesia group died from causes unrelated to the anaesthesia , and one had a myocardial infa rct . Two patients in the spinal group had myocardial infa rcts , both had been treated for bradycardia and hypotension intraoperatively , and one died . There was a significantly higher incidence of postoperative chest infection in the general anaesthesia group ( 33 % vs 16 % ) . There was no significant difference between the groups in the incidence of postoperative confusion , or lower limb amputation rate or need for further surgery prior to hospital discharge Forty elderly patients ( mean age 78.9 years ) undergoing acute surgery for hip fracture were given at r and om either spinal analgesia with bupivacaine 0.75 % or general anaesthesia with diazepam , fentanly and N2O/O2 . Mental function was studied pre‐operatively with an abbreviated mental test and 1 week and 3 months postoperatively in both groups . Mortality and number of complications was similar in the two groups , but a shorter time of ambulation was seen in the spinal group compared to the general anaesthetic group . No persistent impairment in mental function was found after acute hip surgery under spinal or general anaesthesia and the only advantage of regional technique was a shorter time of ambulation One hundred and sixty‐nine patients ( aged 65–98 years ) were r and omised to receive either local or general anaesthesia for cataract surgery . Cognitive function was assessed using a battery of psychometric tests performed pre‐operatively , and at 24 h , 2 weeks and 3 months postoperatively . Oxygen saturation , blood pressure and heart rate were monitored and the results recorded throughout the anaesthetic and immediate recovery period . In the general anaesthetic group , 19 % of patients experienced at least one episode of oxygen desaturation during the procedure compared with none in the local anaesthetic group . Pulse rate and blood pressure were stable in the local anaesthetic group compared with the general anaesthetic group where marked fluctuations were noted ; 61 % of patients in the general anaesthetic group experienced falls in systolic blood pressure greater than 30 % of the pre‐induction value . No evidence of long‐term postoperative cognitive dysfunction was detected and there was no significant difference between the performances of the two groups The psychological effects of halothane , methoxyflurane , combined analgesic-relaxant anaesthesia , and epidural anaesthesia were assessed before one , and seven days after anaesthesia in 72 patients having operations for varicose veins . Subjective anxiety evaluation ( Hamilton Anxiety Rating Scale ) and personality tests of self- appraisal ( Minnesota Multiphasic Personality Inventory ) as well as of superficial ( Wartegg 's test ) and profound ( Rorschach 's test ) projection showed no significant differences among these methods of anaesthesia . Performance tests measuring memory for design s ( modified Graham-Kendall memory for design s ) , short-term memory ( digit span of Wechsler Adult Intelligence Scale ) , learning ( nonsense word series ) , perception ( symmetry-drawing ) , speed of observation ( Bourdon-Wiersma ) and visualization also revealed no significant psychological changes compared to the control ( epidural anaesthesia ) group . The methods of anaesthesia used therefore showed no harmful psychological effects and are in this respect safe in clinical use This study compared the postoperative mental function in 44 elderly patients following general anaesthesia ( GA ) or spinal anaesthesia ( SA ) with sedation for transurethral resection of prostate . The Mini-Mental State ( MMS ) was done preoperatively and postoperatively at six hours , one day , three days , five days and one month . The geriatric mental status examination was performed preoperatively and one month after the anaesthetic . There was no significant intergroup difference in the MMS score in the preoperative , six hours , one day , three days , five days and 30 days postoperative scores between the GA and SA with sedation groups . A significant intragroup difference between preoperative and postoperative MMS score was detected in the GA group ( P < 0.02 ) and in the SA group with sedation ( P < 0.03 ) . In the GA group , the significant decrease in MMS score occurred at 6 h postoperatively ( P < 0.002 ) whereas in the SA group with sedation , MMS score also decreased significantly at 6 h ( P < 0.005 ) . In conclusion , there was no significant difference in perioperative mental function between the general and spinal anaesthetic groups when supplemental IV sedation was given . In both groups , perioperative mental function decreased significantly at 6 h postoperatively . RésuméDans ce travail , nous comparons les fonctions mentales de 44 patients agés , après une résection trans-urétrale de la prostate sous anesthésie soit générale ( AG ) soil rachidienne avec sédation ( ARS ) . Nous avons fait un examen mental gériatrique ( GEMS ) avant et un mois après l’opération ainsi qu’un examen plus sommaire , le Mini-Mental State ( MMS ) juste avant et 6 , 24 , 72 , et 120 heures de même qu ’ un mois après l’intervention . Avec le MMS , nous n’avons pas identifié de différence significative entre les deux groupes à quelque moment que ce soit . A l’intérieur de chacun des deux groupes cependant , on a noté une baisse des résultats au MMS entre le préet le post-opératoire ( P < 0.02 pour AG et P < 0.03 pour ARS ) qui était détectable six heures après l’intervention ( P < 0.002 pour AG et P < 0.005 pour ARS ) . L’état mental post-opératoire des patients n’était done pas dépendant du type d’anesthésie , qu’elle soil générale ou rachidienne avec sédatifs par vote intraveineuse OBJECTIVE To develop and vali date a clinical prediction rule for postoperative delirium using data available to clinicians preoperatively . DESIGN Prospect i ve cohort study . SETTING General surgery , orthopedic surgery , and gynecology services at Brigham and Women 's Hospital , Boston , Mass. PATIENTS Consenting patients older than 50 years admitted for major elective noncardiac surgery between November 1 , 1990 , and March 15 , 1992 ( N = 1341 ) . MEASUREMENTS All patients underwent preoperative evaluations , including a medical history , physical examination , laboratory tests , and assessment s of physical and cognitive function using the Specific Activity Scale and the Telephone Interview for Cognitive Status . Postoperative delirium was diagnosed using the Confusion Assessment Method or using data from the medical record and the hospital 's nursing intensity index . Patients were followed up for the duration of hospitalization to determine major complication rates , length of stay , and discharge disposition . RESULTS Postoperative delirium occurred in 117 ( 9 % ) of the 1341 patients studied . Independent correlates included age 70 years or older ; self-reported alcohol abuse ; poor cognitive status ; poor functional status ; markedly abnormal preoperative serum sodium , potassium , or glucose level ; noncardiac thoracic surgery ; and aortic aneurysm surgery . Using these seven preoperative factors , a simple predictive rule was developed . In an independent population , the rule stratified patients into groups with low ( 2 % ) , medium ( 8 % , 13 % ) , and high ( 50 % ) rates of postoperative delirium . Patients who developed delirium had higher rates of major complications , longer lengths of stay , and higher rates of discharge to long-term care or rehabilitative facilities . CONCLUSIONS Using data available preoperatively , clinicians can stratify patients into risk groups for the development of delirium . Since delirium is associated with a variety of adverse outcomes , patients with substantial risk for this complication could be c and i date s for interventions to reduce the incidence of postoperative delirium and potentially improve overall surgical outcomes Background and Objectives . Outcome studies comparing general anesthesia combined with epidural anesthesia ( GEN‐EPI ) to general anesthesia ( GEN ) for major abdominal surgery have been equivocal . However , many believe that patients anesthetized with GEN‐EPI fair better than GEN . This study tests the hypothesis that there are favorable recovery characteristics associated with GEN‐EPI as compared with GEN following abdominal surgery . Methods . A prospect i ve r and omized double‐blind trial , consisting of 30 patients ages 18‐74 undergoing abdominal surgery was undertaken . Patients received either GEN‐EPI or GEN by st and ardized protocol . At the end of surgery the epidural catheter was removed and psychological testing was performed over 24 hours to determine recovery characteristics . These included the modified Slater test , the Self‐ Assessment Manikin , the Kendrick Digital Copying Test , the Hospital Anxiety and Depression Scale , as well as visual analog scales for pain and appearance . Results . Patients receiving GEN‐EPI emerged from anesthesia faster ( P < .03 ) with less pain on awakening ( P < .04 at rest ; P < .01 on coughing ) , had better psychomotor function at 2 hours ( P < .04 ) , and were less drowsy at 4 hours ( P < .04 ) , than patients with GEN . There was no difference in pain intensity after the initial assessment , morphine usage , mood , anxiety , and depression at any other measurement period . Conclusion . Transient quantifiable differences in recovery characteristics exist between patients receiving GEN‐EPI and GEN Background and objective : This prospect i ve , r and omized study was conducted to compare unilateral spinal block using small doses of hyperbaric bupivacaine and single-agent anaesthesia with sevoflurane in elderly patients undergoing hip surgery . Methods : Thirty patients ( > 65 yr ) undergoing hip fracture repair were r and omly allocated to receive unilateral spinal anaesthesia with hyperbaric bupivacaine 7.5 mg 0.5 % ( Group Spinal , n = 15 ) or volatile induction and maintenance anaesthesia with sevoflurane ( Group SEVO , n = 15 ) . General anaesthesia was induced by increasing the inspired concentration to 5 % . A laryngeal mask airway was placed without muscle relaxants , and the end-tidal concentrations of sevoflurane were adjusted to maintain cardiovascular stability . Hypotension ( decrease in systolic arterial pressure > 20 % from baseline ) , hypertension or bradycardia ( heart rate < 50 beats min−1 ) requiring treatment , and the length of stay in the postanaesthesia care unit was recorded . Cognitive functions were evaluated the previous day , and 1 and 7 days after surgery with the Mini Mental State Examination test . Results : Hypotension occurred in seven patients of Group Spinal ( 46 % ) and in 12 patients of Group SEVO ( 80 % ) ( P = 0.05 ) . Phenylephrine was required to control hypotension in three spinal patients ( 21 % ) and four SEVO patients ( 26 % ) ( n.s . ) . SEVO patients had lower heart rates than spinal patients from 15 to 60 min after anaesthesia induction ( P = 0.01 ) . Bradycardia was observed in three SEVO patients ( 22 % ) . Discharge from the postanaesthesia care unit required 15 ( range 5 - 30 ) min in Group Spinal and 55 ( 15 - 80 ) min in Group SEVO ( P = 0.0005 ) . Eight patients in Group Spinal ( 53 % ) and nine patients in Group SEVO ( 60 % ) showed cognitive decline ( Mini Mental State Examination test decreased ⩾ 2 points from baseline ) 24 h after surgery ( n.s . ) . Seven days after surgery , confusion was still present in one patient of Group Spinal ( 6 % ) and in three patients of Group SEVO ( 20 % ) ( n.s . ) . Conclusions : In elderly patients undergoing hemiarthroplasty of the hip , induction and maintenance with sevoflurane provide a rapid emergence from anaesthesia without more depression of postoperative cognitive function compared with unilateral spinal anaesthesia . This technique represents an attractive option when patient refusal , lack of adequate co-operation or concomitant anticoagulant therapy contraindicate the use of spinal anaesthesia Sixty-four patients aged over 60 about to undergo elective surgery of the lower limbs were allocated at r and om to two groups , one with general anaesthesia , the other with local/regional anaesthesia , in order to compare the effects of these two types of anaesthesia on superior brain functions . The two groups were similar in age , disease , treatment and risk from anaesthesia . Superior brain functions were evaluated by means of a score 24 hours before , then 24 hours and 7 days after the operation . The mean preoperative score was 26.3 + /- 3.4 for the local/regional anaesthesia group and 27.3 + /- 2.6 for the general anaesthesia group , and it remained the same throughout the investigation in both groups . The score decreased to pathological values ( less than or equal to 20 ) in 4 patients from the local/regional anaesthesia group , and this fall was associated with trans- and postoperative incidents ( haemorrhage , cardiorespiratory arrest , confusion after receiving pethidine , cardiac decompensation ) . This study shows that alterations of the superior brain functions are probably related to trans and postoperative incidents rather than to the type of anaesthesia administered OBJECTIVE To compare the effect of epidural vs general anesthesia on the incidence of long-term cognitive dysfunction after total knee replacement surgery in older adults . DESIGN R and omized controlled clinical trial . SETTING Orthopedic specialty academic hospital . PATIENTS A total of 262 patients undergoing elective primary total knee replacement with a median age of 69 years ; 70 % women . INTERVENTION R and om assignment to either epidural or general anesthesia . MAIN OUTCOME MEASURES A thorough neuropsychological assessment was performed preoperatively and repeated at 1 week and 6 months postoperatively . Cognitive outcome was assessed by within-patient change on 10 tests of memory , psychomotor , and language skills . Prospect i ve st and ardized surveillance for cardiovascular complications was performed to allow simultaneous assessment of anesthetic effects on cognitive and cardiovascular outcomes . RESULTS The two groups were similar at baseline in terms of age , sex , comorbidity , and cognitive function . There were no significant differences between the epidural and general anesthesia groups in within-subject change from baseline on any of the 10 cognitive test results at either 1 week or 6 months . Overall , 5 % of patients showed a long-term clinical ly significant deterioration in cognitive function . There was no difference between the anesthesia groups in the incidence of major cardiovascular complications ( 3 % overall ) . CONCLUSIONS The type of anesthesia , general or epidural , does not affect the magnitude or pattern of postoperative cognitive dysfunction or the incidence of major cardiovascular complications in older adults undergoing elective total knee replacement . This is the largest trial of the effects of general vs regional anesthesia on cerebral function reported to date , with more than 99 % power to detect a clinical ly significant difference on any of the neuropsychological tests Cognitive functions in 53 elderly men who underwent a transurethral prostatectomy were assessed pre-operatively and 4 days and 3 months post-operatively . Thirteen patients had a preference for one particular type of anesthesia , and the remaining 40 were r and omly allocated to receive either spinal or general anesthesia . Cognitive function was not different between the groups receiving different types of anesthesia at either time point and did not decrease post-operatively . No pre- or perioperative variable could distinguish the subgroup of patients who had a post-operative decrease of 2 points or more on the Mini-Mental State Examination . No difference in post-operative performance was found in the patient groups with pre-operative Mini-Mental State Examination scores above or under their age-specific norm . It is concluded that neither hospitalization nor the two forms of anesthesia investigated cause a decrease in cognitive function in elderly men OBJECTIVE To determine if different methods of anesthesia and analgesia will influence the incidence of early postoperative cognitive dysfunction ( POCD ) after non-cardiac surgery in the elderly . METHODS One hundred and three elderly patients undergoing elective abdominal surgery were r and omly allocated to receive either general anesthesia followed with postoperative intravenous analgesia ( general anesthesia group , 53 cases ) or combined general-epidural anesthesia followed with postoperative epidural analgesia ( combined general-epidural anesthesia group , 50 cases ) . Cognitive function was assessed preoperatively and 7 days postoperatively using a battery of nine neuropsychological tests . A postoperative deficit in any test was defined when decline by more than or equal to 20 % of the preoperative value of that test occurred . Any patient showing deficit in 2 or more tests was defined as having postoperative cognitive dysfunction . RESULTS Ninety-two patients completed both preoperative and postoperative neuropsychological tests . On day 7 , POCD occurred in 20/45 patients ( 44.4 % ) in the general anesthesia group and in 23/47 patients ( 48.9 % ) in the combined general-epidural anesthesia group . No significant difference was found between the two groups . Logistic regression analysis showed that short duration of education and operation of general surgery were independent risk factors of the occurrence of early POCD . CONCLUSION Early POCD occurred in 46.7 % of the elderly patients undergoing abdominal surgery . However , there was no significant difference between the effects of two different methods of anesthesia and postoperative analgesia on the incidence of POCD . Short duration of education and operation of general surgery were risk factors of early POCD OBJECTIVE The aim of the present study was to show the influence of cerebral oxygenation ( regional cerebral oxygen saturation rSO(2 ) by near infrared spectroscopy ) and of the nocturnal arterial oxygen saturation ( SatO(2 ) by pulse oximetry ) on the restitution of cognitive functions in patients aged between 40 and 85 years scheduled for elective hip arthroplasty . METHODS A total of 40 patients ( ASA II ) were r and omized to be operated either in general anaesthesia or regional anaesthesia . The patients were additionally classified by age ( 40 - 64 years and 65 - 85 years ) . Cognitive functions were tested 14 - 16 h pre-operatively ( t0 ) , 1.5 h post-operatively ( t1 ) and at the first and third postoperative days ( t2 and t3 ) . During testing , as well as during surgery and postoperatively until t1 , rSO(2 ) was continuously measured . SatO(2 ) was measured in the night before surgery ( N0 ) and for 3 nights after surgery ( N1 , N2 , N3 ) between 22.00 p.m. and 5.00 a.m. These measurements were divided into interval groups ( 80 - 83 % , 84 - 87 % , 88 - 91 % , 92 - 95 % , 96 - 100 % ) . RESULTS Almost all cognitive functions were significantly reduced at t1 in all groups compared to t0 , but recovered up to the third postoperative day ( t3 ) . RSO(2 ) in contrast was significantly reduced in all groups compared to t0 at the third postoperative day ( t3 ) . The relative proportion of the intervals compared to the total measurement time for SatO(2 ) shifted in both anaesthesia procedures : before surgery ( N0 ) the most frequented interval was 96 - 100 % , after surgery ( N1 , N2 ) it was 88 - 91 % . There was no correlation between rSO(2 ) , the restitution of the tested cognitive functions and SatO(2 ) . CONCLUSIONS Cognitive functions recovered completely during the first 3 postoperative days in patients scheduled for elective hip surgery under general or regional anaesthesia regardless of age and type of anaesthesia . This restitution of cognition occurred despite a significant decrease of cerebral oxygenation ( rSO(2 ) ) and despite an increase of nocturnal hypoxaemic intervals . Changes of the rsO(2 ) up to 3 % below the baseline values ( measured by NIRS ) do not predict cognitive restitution . A minimal limiting value of the rSO(2 ) could not be defined BACKGROUND Mental state changes after anesthesia seemed to be more frequent in older patients , but the results were still unclear . OBJECTIVE To compare the mental scores between adults and elderly patients after general and regional anesthesia . METHODS This was a stratified r and omized trial with factorial design . Sixty patients > or = 60 years old and sixty patients < 60 years old were r and omly assigned to receive general or regional anesthesia . Their mental states were assessed blind by investigators , using the Thai Mental State Examination score . RESULTS The two anesthetic groups showed no difference in the mental scores , but the two age groups showed significantly different scores . The components of mental states that were significantly different were orientation and recall . There were no significant differences in registration , attention , calculation and language . The model for predicting the score included age , education level and narcotics given within six hours before assessment . Sex , weight , intraoperative hypotension , blood loss and duration of anesthesia could not explain the change in the scores . CONCLUSION Age , but not anesthetic technique , affected the mental scores after anesthesia OBJECTIVE The aim of the present study was to show the influence of the parameters of gas exchange ( arterial oxygen pressure paO2 , arterial oxygen saturation SatO2 ) and haemodynamics ( arterial systolic and mean blood pressure RRs and MAP ) on the restitution of cognitive functions in geriatric patients scheduled for elective hip arthroplasty . METHODS A total of 30 patients ( 70 years , ASA II ) were r and omized to be operated either in regional anaesthesia ( n = 15 ) or general anaesthesia ( n = 15 ) . PaO2 ( by capillary blood gas analysis ) , RRs and MAP ( by oscillometry ) were measured 15 and 90 minutes after arrival in the recovery unit ( t1 and t2 ) , 24 and 72 hours postoperatively ( t3 and t4 ) , and cognitive functions were tested . Intraoperatively , throughout the day and the first night after surgery we measured satO2 by continuous pulse oximetry . We recorded MAP and RRs by oscillometry every 3 minutes during the operation and every 15 minutes for the rest of that day and night . RESULTS The parameters of gas exchange and haemodynamics did not differ among the groups . PaO2 was significantly reduced in both groups compared to baseline 24 hours postoperatively ( t3 ) and remained low until 72 hours postoperatively ( t4 ) . Nearly all cognitive functions were significantly reduced in both groups compared to baseline 15 and 90 minutes after arrival in the recovery unit ( t1 and t2 ) , but recovered on the first postoperative day ( t3 ) . Both groups kept deficits in verbal memory and reading capacity up to the third postoperative day ( t4 ) . There was no correlation between the physiological parameters and the restitution of the tested cognitive functions . CONCLUSION The restitution of cognitive functions during the first three postoperative days in geriatric patients scheduled for elective hip surgery does not depend on the anaesthetic technique . According to our results regional anaesthesia does not show any advantage for geriatric patients undergoing elective hip arthroplasty STUDY OBJECTIVE To compare propofol plus spinal anesthesia during spontaneous ventilation using the Laryngeal Mask Airway and propofol plus fentanyl anesthesia during mechanical ventilation with an endotracheal tube on quality of recovery after anesthesia . DESIGN Prospect i ve , r and omized study . SETTING Hirosaki National Hospital . PATIENTS 150 patients ( aged > 70 years ) undergoing total knee arthroplasty . INTERVENTIONS Patients were divided r and omly into two groups , to receive spontaneous ventilation with a Laryngeal Mask Airway during propofol-spinal anesthesia , or to receive propofol-fentanyl anesthesia with mechanical ventilation via endotracheal tube . MEASUREMENTS Quality of anesthesia recovery such as nausea , vomiting , headache , pain throat , hoarse voice , back pain , dizziness , feeling comfortable , dreaming , recovery times in recovery of anesthesia , recovery times , postoperative pain , confusion , was assessed . MAIN RESULTS The frequency of postoperative pain throat , hoarse voice , and nausea was significantly lower in the propofol-spinal anesthesia group than the propofol-fentanyl anesthesia group . The time to extubation , emergence , response to comm and s , and orientation were significantly faster ( p < 0.001 ) in the propofol-spinal anesthesia group than the propofol-fentanyl anesthesia group . The frequency of postoperative confusion occurring in the propofol-spinal anesthesia group during the first 24 hours was significantly lower than that of the propofol-fentanyl anesthesia group ( p = 0.03 ) . CONCLUSIONS Propofol-spinal anesthesia provided better and faster recovery than did propofol-fentanyl anesthesia for elderly patients undergoing total knee arthroplasty The postoperative course of mental performance during the first week and at 3 months after operation was studied in 30 patients above the age of 60 , undergoing total hip replacement arthroplasty . The patients were r and omly allocated to receive either general anesthesia , epidural analgesia , or general anesthesia plus epidural analgesia . The surgically induced increase in plasma cortisol and glucose was inhibited in the two groups receiving epidural analgesia . Mental performance was studied with psychological methods . An equal degree of postoperative impairment of mental performance of 3 - 4 days ' duration was found in all groups . Three months after surgery , mental function had improved slightly and to the same extent in all groups . We conclude that the after surgery , mental function had improved slightly and to the same extent in all groups . We conclude that the transient mental impairment occurring within the first postoperative week is caused by factors other than general anesthetic agents and the endocrine-metabolic response to surgery The behavior of 105 patients r and omly assigned to receive cither general or regional anesthesia and who underwent one of three types of surgery ( hysterectomy , prostatectomy , or joint replacement ) was assessed before , immediately after , and 3 mo after surgery . Psychologic status was assessed by the Sickness Impact Profile , the SCL-90-R , and a Metamemory Question naire . Cognitive functioning was measured by a battery of ten psychomotor , memory , and skilled performance tasks . Physical health was scored by the ASA classification of physical status , a health index , postoperative complications ratings , and a self-rated measure of the patient 's health . There were cognitive differences across surgery groups due to age and gender variability among the patients ; however , the type of anesthesia produced no difference in behavior . Both the physical and mental health indices showed improvement from the preoperativc to the postoperative periods . General anesthesia appears to pose no risk to mental function and recovery beyond that associated with regional anesthesia and surgery PURPOSE To examine the association of intraoperative factors , including route of anesthesia , hemodynamic complications , and blood loss , with the development of postoperative delirium . PATIENTS AND METHODS We studied 1,341 patients 50 years of age and older admitted for major elective noncardiac surgery at an academic medical center . Data on route of anesthesia , intraoperative hypotension , bradycardia and tachycardia , blood loss , number of blood transfusions , and lowest postoperative hematocrit were obtained from the medical record . Delirium was diagnosed by using daily interviews with the Confusion Assessment Method , as well as from the medical record and the hospital 's nursing intensity index . RESULTS Postoperative delirium occurred in 117 ( 9 % ) patients . Route of anesthesia and intraoperative hemodynamic complications were not associated with delirium . Delirium was associated with greater intraoperative blood loss , more postoperative blood transfusions , and postoperative hematocrit < 30 % . After adjusting for preoperative risk factors , postoperative hematocrit < 30 % was associated with an increased risk of delirium ( odds ratio = 1.7 , 95 % confidence interval 1.1 - 2.7 ) . CONCLUSIONS Further study is required to determine whether transfusion to keep postoperative hematocrit above 30 % can reduce the incidence of postoperative delirium Fifty-seven patients , all over the age of 64 , with femoral neck fracture were r and omized to receive epidural or halothane anesthesia to see if the anesthetic technique influenced the incidence of postoperative confusion . All patients were lucid on admission . Using the American Psychiatric Association 's Diagnostic and Statistical Manual of Mental Disorders ( DSM-III ) as criteria for confusion , we found that 44 % of the patients developed confusion that correlated closely to a history of mental depression ( P < 0.01 ) and to the use of drugs with anticholinergic effect ( P < 0.005 ) . There was no difference in the incidence of confusion between the two anesthetic groups . In patients given halothane , however , early postoperative hypoxemia was associated with confusion ( P < 0.05 ) . Patients with confusion had significantly more postoperative complications and almost four times longer hospitalization times . It is concluded that anticholinergic medication and a history of mental depression are predominant risk factors for development of postoperative confusion and in this respect are more important than the anesthetic technique We performed an open , prospect i ve , r and omized , controlled study of the incidence of major organ complications in 420 patients undergoing routine coronary artery bypass graft surgery with or without thoracic epidural anesthesia and analgesia ( TEA ) . All patients received a st and ardized general anesthetic . Group TEA received TEA for 96 h. Group GA ( gen- eral anesthesia ) received narcotic analgesia for 72 h. Both groups received supplementary oral analgesia . Twelve patients were excluded — eight in Group TEA and four in Group GA — because of incomplete data collection . New supraventricular arrhythmias occurred in 21 of 206 patients ( 10.2 % ) in Group TEA compared with 45 of 202 patients ( 22.3 % ) in Group GA ( P = 0.0012 ) . Pulmonary function ( maximal inspiratory lung volume ) was better in Group TEA in a subset of 93 patients ( P < 0.0001 ) . Extubation was achieved earlier ( P < 0.0001 ) and with significantly fewer lower respiratory tract infections in Group TEA ( TEA = 31 of 206 , GA = 59 of 202;P = 0.0007 ) . There were significantly fewer patients with acute confusion ( GA = 11 of 202 , TEA = 3 of 206;P = 0.031 ) and acute renal failure ( GA = 14 of 202 , TEA = 4 of 206;P = 0.016 ) in the TEA group . The incidence of stroke was insignificantly less in the TEA group ( GA = 6 of 202 , TEA = 2 of 206;P = 0.17 ) . There were no neurologic complications associated with the use of TEA . We conclude that continuous TEA significantly improves the quality of recovery after coronary artery bypass graft surgery compared with conventional narcotic analgesia BACKGROUND Opinions differ as to what is more appropriate anesthetic technique for elderly patients undergoing ambulatory surgery . The objective of this study is to compare the efficacy and safety of spinal anesthesia with small-dose lidocaine and those of propofol general anesthesia in elderly patients undergoing ambulatory prostate biopsy . METHODS Eighty ASA physical status I x II patients aged older than 65 year were r and omized to receive either spinal anesthesia with 1 % hyperbaric lidocaine 1 ml ( 10 mg ) ( group L ) or general anesthesia with 1.0 mg x kg(-1 ) of propofol injected at 180 mg x kg(-1 ) x hr(-1 ) followed by continuous infusion at 8 mg x kg(-1 ) x hr(-1 ) ( group P ) . RESULTS Significantly higher incidences of intraoperative hypotension and respiratory depression were found in the group P compared with the group L ( P < 0.05 ) . There were no major postoperative side effects , including transient neurologic symptoms and delirious sate , in either group . Both anesthetic techniques result ed in a high rate of patient satisfaction . Total perioperative costs were significantly lower in the group L compared with the group P ( P < 0.01 ) . CONCLUSIONS Spinal anesthesia with 10 mg of hyperbaric 1 % lidocaine may be more preferable to propofol anesthesia in elderly patiens undergoing ambulatory prostate biopsy , with respect to safety and costs |
10,554 | 15,637,130 | A more recently introduced predictive marker is HER-2 for selecting patients with advanced breast cancer for treatment with the therapeutic antibody trastuzumab ( Herceptin ) .
In adjuvant breast cancer , overproduction of HER-2 may also indicate an enhanced sensitivity to high-dose anthracycline-based regimens .
On the other h and , in both early and advanced breast cancer , high concentrations of HER-2 appear to correlate with a lower probability of response to hormone therapy .
Although many different anticancer drugs appear to mediate tumor regression by inducing apoptosis , there is currently no consistent evidence that any of the molecules implicated in this process can be used as predictive markers .
Currently , the only recommended predictive markers in oncology are ER and PR for selecting endocrine-sensitive breast cancers and HER-2 for identifying breast cancer patients with metastatic disease who may benefit from trastuzumab . | BACKGROUND Unpredictable efficacy and toxicity are hallmarks of most anticancer therapies .
Predictive markers are factors that are associated with response or resistance to a particular therapy . | PURPOSE Increased expression of the multidrug resistance gene ( MDR1 ) has been implicated in osteosarcoma prognosis . This study represents the first prospect i ve assessment of the prognostic value of MDR1 mRNA expression in patients with newly diagnosed extremity osteosarcoma . PATIENTS AND METHODS A series of patients with high- grade , nonmetastatic extremity osteosarcoma were enrolled from six tertiary care institutions and observed prospect ively for tumor recurrence ( median follow-up duration , 30 months ) . All patients were treated with (neo)adjuvant chemotherapy and surgery . Tumors from 123 patients were analyzed for MDR1 mRNA expression . The association of the level of MDR1 expression with the risk of systemic recurrence was examined using survival analyses with traditional and histologic markers as prognostic factors . RESULTS Using the highest MDR1 value for each patient , a dose-response relationship was not identified between the level of MDR1 expression and systemic relapse ( relative risk , 1.15 ; P = .44 ) . Analyses based on biopsy or resection values alone gave similar results ( P = .11 and .41 , respectively , log rank test ) . In multivariate analysis , large tumor size ( > 9 cm ) was the only significant independent predictor of systemic outcome ( relative risk , 2.8 ; P = .002 ) . CONCLUSION We did not identify any correlation between MDR1 mRNA expression and disease progression in patients with osteosarcoma . It is likely that alterations in other genes are involved in resistance to chemotherapy in osteosarcoma and that they play a more critical role than MDR1 in this disease PURPOSE A strong prognostic impact of urokinase-type plasminogen activator ( uPA ) and its inhibitor and plasminogen activator inhibitor type 1 ( PAI-1 ) as individual factors is well established in breast cancer . The improvement in clinical risk assessment gained by combining these factors is evaluated here . PATIENTS AND METHODS uPA and PAI-1 levels were prospect ively measured by enzyme-linked immunosorbent assay in tumor tissue extracts of 761 patients with primary breast cancer . RESULTS In the clinical ly important subgroup of node-negative patients without adjuvant systemic therapy ( n = 269 ; median follow-up , 60 months ) , the clinical value of testing both uPA and PAI-1 is demonstrated . The criterion either or both high identifies with high sensitivity the patients at high relapse risk while keeping more than half in the low-risk group . uPA/PAI-1 is the strongest predictor of disease-free survival and overall survival ; patients with high uPA/PAI-1 have an increased relapse risk ( P < .001 ; relative risk , 4.8 ; 95 % confidence interval [ CI ] , 2.5 to 9.1 ) , in particular for early relapse . Even within risk groups stratified by established criteria ( nodal or menopausal status , tumor size , grade , or steroid hormone receptors ) , uPA/PAI-1 provides significant risk group discrimination . In the whole collective , the significant interaction between uPA/PAI-1 and adjuvant systemic therapy suggests a benefit from adjuvant therapy in high-risk patients as defined by uPA/PAI-1 . CONCLUSION The clinical relevance of the two tumor-invasion factors uPA and PAI-1 is greatest when they are used in combination . The particular combination of uPA and PAI-1 ( both low v either or both high ) is superior to either factor alone and supports risk-adapted individualized therapy decisions |
10,555 | 21,852,412 | Processes of care improved for prescribing and monitoring mostly in hospital setting s , but the few studies measuring clinical outcomes showed small or no improvements .
CONCLUSIONS Almost half of MMIT interventions improved the process of care , but few studies measured clinical outcomes . | OBJECTIVE The US Agency for Healthcare Research and Quality funded an evidence report to address seven questions on multiple aspects of the effectiveness of medication management information technology ( MMIT ) and its components ( prescribing , order communication , dispensing , administering , and monitoring ) . | Background Interventions design ed to narrow the gap between research findings and clinical practice may be effective , but also costly . Economic evaluations are necessary to judge whether such interventions are worth the effort . We have evaluated the economic effects of a tailored intervention to support the implementation of guidelines for the use of antihypertensive and cholesterol-lowering drugs . The tailored intervention was evaluated in a r and omized trial , and was shown to significantly increase the use of thiazides for patients started on antihypertensive medication , but had little or no impact on other outcomes . The increased use of thiazides was not expected to have an impact on health outcomes . Methods and Findings We performed cost-minimization and cost-effectiveness analyses on data from a r and omized trial involving 146 general practice s from two geographical areas in Norway . Each practice was r and omized to either the tailored intervention ( 70 practice s ; 257 physicians ) or control group ( 69 practice s ; 244 physicians ) . Only patients that were being started on antihypertensive medication were included in the analyses . A multifaceted intervention was tailored to address identified barriers to change . Key components were an educational outreach visit with audit and feedback , and computerized reminders . Pharmacists conducted the visits . A cost-minimization framework was adopted , where the costs of intervention were set against the reduced treatment costs ( principally due to increased use of thiazides rather than more expensive medication ) . The cost-effectiveness of the intervention was estimated as the cost per additional patient being started on thiazides . The net annual cost ( cost minimization ) in our study population was US$ 53,395 , corresponding to US$ 763 per practice . The cost per additional patient started on thiazides ( cost-effectiveness ) was US$ 454 . The net annual savings in a national program was modeled to be US$ 761,998 , or US$ 540 per practice after 2 y. In this scenario the savings exceeded the costs in all but two of the sensitivity analyses we conducted , and the cost-effectiveness was estimated to be US$ 183 . Conclusions We found a significant shift in prescribing of antihypertensive drugs towards the use of thiazides in our trial . A major reason to promote the use of thiazides is their lower price compared to other drugs . The cost of the intervention was more than twice the savings within the time frame of our study . However , we predict modest savings over a 2-y period OBJECTIVE Direct physician order entry ( POE ) offers many potential benefits , but evidence suggests that POE requires substantially more time than traditional paper-based ordering methods . The Medical Gopher is a well-accepted system for direct POE that has been in use for more than 15 years . The authors hypothesized that physicians using the Gopher would not spend any more time writing orders than physicians using paper-based methods . DESIGN A r and omized controlled trial of POE using the Medical Gopher system in 11 primary care internal medicine practice s. MEASUREMENTS The authors collected detailed time use data using time motion studies of the physicians and surveyed their opinions about the POE system . RESULTS The authors found that physicians using the Gopher spent 2.2 min more per patient overall , but when duplicative and administrative tasks were taken into account , physicians were found to have spent only 0.43 min more per patient . With experience , the order entry time fell by 3.73 min per patient . The survey revealed that the physicians believed that the system improved their patient care and wanted the Gopher to continue to be available in their practice s. CONCLUSIONS Little extra time , if any , was required for physicians to use the POE system . With experience in its use , physicians may even save time while enjoying the many benefits of POE UNLABELLED What is already known about this subject . Computerized prompts and reminders have been shown to be effective in changing the behaviour of health professionals in a variety of setting s. There is little literature describing or evaluating electronic decision-support for pharmacists . What this study adds . An electronic prompt in dispensing software for a targeted clinical intervention has a significant effect on pharmacists ' behaviour . A markedly increased rate of recording and performing the targeted clinical intervention was found . The effect of the prompt reduces markedly once the prompt is deactivated . AIM To evaluate the effect of an electronic prompt in dispensing software on the frequency of clinical interventions recorded by community pharmacists . METHOD An electronic decision-support prompt identifying patients for a targeted proactive clinical intervention was developed and implemented . Each time an oral antidiabetic agent was dispensed , a prompt was displayed reminding pharmacists to discuss the suitability of aspirin therapy in eligible patients with diabetes . The prompt was r and omly assigned to 31 of 52 metropolitan pharmacies in Melbourne ( Australia ) for 6 weeks , with the remaining pharmacies as controls . RESULTS One hundred and fifty pharmacists in 52 pharmacies recorded a total of 2396 clinical interventions at an intervention rate of 0.92 interventions per 100 patients [ 95 % confidence interval ( CI ) 0.58 , 1.23 ] . Pharmacists recorded a total of 201 target interventions related to aspirin therapy in diabetes at an intervention rate of 2.55 interventions per 100 diabetic patients ( 95 % CI 0.85 , 4.24 ) . All of the targeted clinical interventions were recorded in the prompt arm ; no targeted interventions were recorded in the control group . The effect of the prompt decreased over the study period and was not maintained after prompt deactivation . CONCLUSION An electronic prompt significantly increased pharmacists ' recording of the targeted clinical intervention in diabetic patients . An electronic decision-support prompt has significant potential to promote community pharmacists ' contribution to the quality use of medicines BACKGROUND Adverse drug-related events are common in the elderly , and inappropriate prescribing is a preventable risk factor . Our objective was to determine whether inappropriate prescribing could be reduced when primary care physicians had computer-based access to information on all prescriptions dispensed and automated alerts for potential prescribing problems . METHODS We r and omly assigned 107 primary care physicians with at least 100 patients aged 66 years and older ( total 12 560 ) to a group receiving computerized decision-making support ( CDS ) or a control group . Physicians in the CDS group had access to information on current and past prescriptions through a dedicated computer link to the provincial seniors ' drug-insurance program . When any of 159 clinical ly relevant prescribing problems were identified by the CDS software , the physician received an alert that identified the nature of the problem , possible consequences and alternative therapy . The rate of initiation and discontinuation of potentially inappropriate prescriptions was assessed over a 13-month period . RESULTS In the 2 months before the study , 31.8 % of the patients in the CDS group and 33.3 % of those in the control group had at least 1 potentially inappropriate prescription . During the study the number of new potentially inappropriate prescriptions per 1000 visits was significantly lower ( 18 % ) in the CDS group than in the control group ( relative rate [ RR ] 0.82 , 95 % confidence interval [ CI ] 0.69 - 0.98 ) , but differences between the groups in the rate of discontinuation of potentially inappropriate prescriptions were significant only for therapeutic duplication by the study physician and another physician ( RR 1.66 , 95 % CI 0.99 - 2.79 ) and drug interactions caused by prescriptions written by the study physician ( RR 2.15 , 95 % CI 0.98 - 4.70 ) . INTERPRETATION Computer-based access to complete drug profiles and alerts about potential prescribing problems reduces the rate of initiation of potentially inappropriate prescriptions but has a more selective effect on the discontinuation of such prescriptions Background — Indirect evidence shows that alerting users with clinical decision support systems seems to change behavior more than requiring users to actively initiate the system . However , r and omized trials comparing these methods in a clinical setting are lacking . We studied the effect of both alerting and on-dem and decision support with respect to screening and treatment of dyslipidemia based on the guidelines of the Dutch College of General Practitioners . Methods and Results — In a clustered r and omized trial design , 38 Dutch general practice s ( 77 physicians ) and 87 886 of their patients ( 39 433 men 18 to 70 years of age and 48 453 women 18 to 75 years of age ) who used the ELIAS electronic health record participated . Each practice was assigned to receive alerts , on-dem and support , or no intervention . We measured the percentage of patients screened and treated after 12 months of follow-up . In the alerting group , 65 % of the patients requiring screening were screened ( relative risk versus control=1.76 ; 95 % confidence interval , 1.41 to 2.20 ) compared with 35 % of patients in the on-dem and group ( relative risk versus control=1.28 ; 95 % confidence interval , 0.98 to 1.68 ) and 25 % of patients in the control group . In the alerting group , 66 % of patients requiring treatment were treated ( relative risk versus control=1.40 ; 95 % confidence interval , 1.15 to 1.70 ) compared with 40 % of patients ( relative risk versus control=1.19 ; 95 % confidence interval , 0.94 to 1.50 ) in the on-dem and group and 36 % of patients in the control group . Conclusion — The alerting version of the clinical decision support systems significantly improved screening and treatment performance for dyslipidemia by general practitioners OBJECTIVE Many hospitals utilize antimicrobial management teams ( AMTs ) to improve patient care . However , most function with minimal computer support . We evaluated the effectiveness and cost-effectiveness of a computerized clinical decision support system for the management of antimicrobial utilization . DESIGN A r and omized controlled trial in adult in patients between May 10 and August 3 , 2004 . Antimicrobial utilization was managed by an existing AMT using the system in the intervention arm and without the system in the control arm . The system was developed to alert the AMT of potentially inadequate antimicrobial therapy . MEASUREMENTS Outcomes assessed were hospital antimicrobial expenditures , mortality , length of hospitalization , and time spent managing antimicrobial utilization . RESULTS The AMT intervened on 359 ( 16 % ) of 2,237 patients in the intervention arm and 180 ( 8 % ) of 2,270 in the control arm , while spending approximately one hour less each day on the intervention arm . Hospital antimicrobial expenditures were $ 285,812 in the intervention arm and $ 370,006 in the control arm , for a savings of $ 84,194 ( 23 % ) , or $ 37.64 per patient . No significant difference was observed in mortality ( 3.26 % vs. 2.95 % , p = 0.55 ) or length of hospitalization ( 3.84 vs. 3.99 days , p = 0.38 ) . CONCLUSION Use of the system facilitated the management of antimicrobial utilization by allowing the AMT to intervene on more patients receiving inadequate antimicrobial therapy and to achieve substantial time and cost savings for the hospital . This is the first study that demonstrates in a patient-r and omized controlled trial that computerized clinical decision support systems can improve existing antimicrobial management programs OBJECTIVE : Asthma continues to be 1 of the most common chronic diseases of childhood and affects ∼6 million US children . Although National Asthma Education Prevention Program guidelines exist and are widely accepted , previous studies have demonstrated poor clinician adherence across a variety of population s. We sought to determine if clinical decision support ( CDS ) embedded in an electronic health record ( EHR ) would improve clinician adherence to national asthma guidelines in the primary care setting . METHODS : We conducted a prospect i ve cluster-r and omized trial in 12 primary care sites over a 1-year period . Practice s were stratified for analysis according to whether the site was urban or suburban . Children aged 0 to 18 years with persistent asthma were identified by International Classification of Diseases , Ninth Revision codes for asthma . The 6 intervention- practice sites had CDS alerts imbedded in the EHR . Outcomes of interest were the proportion of children with at least 1 prescription for controller medication , an up-to- date asthma care plan , and the performance of office-based spirometry . RESULTS : Increases in the number of prescriptions for controller medications , over time , was 6 % greater ( P = .006 ) and 3 % greater for spirometry ( P = .04 ) in the intervention urban practice s. Filing an up-to- date asthma care plan improved 14 % ( P = .03 ) and spirometry improved 6 % ( P = .003 ) in the suburban practice s with the intervention . CONCLUSION : In our study , using a cluster-r and omized trial design , CDS in the EHR , at the point of care , improved clinician compliance with National Asthma Education Prevention Program guidelines Background : Recent clinical trials indicate that treatment with lipid modifying therapy improves outcomes in patients with ischemic heart disease ( IHD ) and low levels of high density lipoprotein ( HDL ) cholesterol . The results of these trials , however , have not been widely implemented in clinical practice . Objectives : To develop and test an intervention design ed to increase the rate of prescription of lipid modifying therapy and to determine the relative effectiveness of three different prompts ( progress notes , patient letters , or computer chart reminders ) . Methods : The study was conducted in 11 US Department of Veterans Affairs Medical Centers . The effect of the intervention on the proportion of eligible patients receiving lipid modifying therapy was compared between five intervention sites and six matched control sites using a controlled before and after study design . Additionally , 92 providers within the intervention clinics were r and omized to receive one of the three prompts . Data were analyzed using logistic regression modeling which incorporated terms to account for the clustered nature of the data . Results : At the intervention sites the prescription rate increased from 8.3 % during the pre-intervention period to 39.1 % during the intervention ( OR = 6.5 , 95 % CI 5.2 to 8.2 , p<0.0001 ) but remained unchanged at the control sites . The interaction between group ( control v intervention ) and time period was highly significant ( p<0.0001 ) . The adjusted odds of receiving a prescription during the intervention period was 3.1 times higher at the intervention sites than at the control sites ( 95 % CI 2.1 to 4.7 ) . Overall , there was no significant difference in prescription rates among the three prompt groups . However , there was a significant interaction between prompt group and site , indicating that the efficacy of the prompts differed by site . Conclusion : An intervention for primary care providers consisting of an educational workshop , opinion leader influence , and prompts substantially increased the prescription rate of lipid modifying therapy OBJECTIVE The aim of this study was to evaluate the impact of an integrated patient-specific electronic clinical reminder system on diabetes and coronary artery disease ( CAD ) care and to assess physician attitudes toward this reminder system . DESIGN We enrolled 194 primary care physicians caring for 4549 patients with diabetes and 2199 patients with CAD at 20 ambulatory clinics . Clinics were r and omized so that physicians received either evidence -based electronic reminders within their patients ' electronic medical record or usual care . There were five reminders for diabetes care and four reminders for CAD care . MEASUREMENTS The primary outcome was receipt of recommended care for diabetes and CAD . We created a summary outcome to assess the odds of increased compliance with overall diabetes care ( based on five measures ) and overall CAD care ( based on four measures ) . We surveyed physicians to assess attitudes toward the reminder system . RESULTS Baseline adherence rates to all quality measures were low . While electronic reminders increased the odds of recommended diabetes care ( odds ratio [ OR ] 1.30 , 95 % confidence interval [ CI ] 1.01 - 1.67 ) and CAD ( OR 1.25 , 95 % CI 1.01 - 1.55 ) , the impact of individual reminders was variable . A total of three of nine reminders effectively increased rates of recommended care for diabetes or CAD . The majority of physicians ( 76 % ) thought that reminders improved quality of care . CONCLUSION An integrated electronic reminder system result ed in variable improvement in care for diabetes and CAD . These improvements were often limited and quality gaps persist OBJECTIVES To determine whether a computerized tool that alerted pharmacists when patients aged 65 and older were newly prescribed potentially inappropriate medications was effective in decreasing the proportion of patients dispensed these medications . DESIGN Prospect i ve , r and omized trial . SETTING U.S. health maintenance organization . PARTICIPANTS All 59,680 health plan members aged 65 and older were r and omized to intervention ( n=29,840 ) or usual care ( n=29,840 ) . Pharmacists received alerts on all patients r and omized to intervention who were newly prescribed a targeted medication . INTERVENTION Prescription and age information were linked to alert pharmacists when a patient aged 65 and older was newly prescribed one of 11 medications that are potentially inappropriate in older people . MEASUREMENTS Physicians and pharmacists collaborated to develop the targeted medication list , indications for medication use for which an intervention should occur , intervention guidelines and scripts , and to implement the intervention . RESULTS Over the 1-year study , 543 ( 1.8 % ) intervention group patients aged 65 and older were newly dispensed prescriptions for targeted medications , compared with 644 ( 2.2 % ) usual care group patients ( P=.002 ) . For medication use indications in which an intervention should occur , dispensings of amitriptyline ( P<.001 ) and diazepam ( P=.02 ) were reduced . CONCLUSIONS This study demonstrated the effectiveness of a computerized pharmacy alert system plus collaboration between healthcare professionals in decreasing potentially inappropriate medication dispensings in elderly patients . Coupling data available from information systems with the knowledge and skills of physicians and pharmacists can improve prescribing safety in patients aged 65 and older OBJECTIVE To assess the effects on health care re source utilization of a network of microcomputer workstations for writing all inpatient orders . DESIGN R and omized controlled clinical trial . SETTING Inpatient internal medicine service of an urban public hospital . SUBJECTS A total of 5219 internal medicine patients and the 68 teams of house officers , medical students , and faculty internists who cared for them . INTERVENTION Microcomputer workstations , linked to a comprehensive electronic medical record system , for writing all inpatient orders . MAIN OUTCOME MEASURES Total inpatient charges for each admission and charges for specific categories of orders . A time-motion study of selected interns assessed the ordering system 's time consumption . RESULTS Intervention teams generated charges that were $ 887 ( 12.7 % ) lower per admission than did control teams ( P = .02 ) . Significant reductions ( P < .05 ) were demonstrated separately for bed charges , diagnostic test charges , and drug charges . Reductions of similar proportion and statistical significance were found for hospital costs . The mean length of stay was 0.89 day shorter for intervention resident teams ( P = .11 ) . Interns in the intervention group spent an average of 33 minutes longer ( 5.5 minutes per patient ) during a 10-hour observation period writing orders than did interns in the control group ( P < .0001 ) . CONCLUSIONS A network of microcomputer workstations for writing all inpatient orders significantly lowered patient charges and hospital costs . This would amount to savings of more than $ 3 million in charges annually for this hospital 's medicine service and potentially tens of billions of dollars nationwide . However , the system required more physician time than did the paper charts . Research at other sites and system advances to reduce time requirements are warranted OBJECTIVE Interruptive alerts within electronic applications can cause " alert fatigue " if they fire too frequently or are clinical ly reasonable only some of the time . We assessed the impact of non-interruptive , real-time medication laboratory alerts on provider lab test ordering . DESIGN We enrolled 22 outpatient practice s into a prospect i ve , r and omized , controlled trial . Clinics either used the existing system or received on-screen recommendations for baseline laboratory tests when prescribing new medications . Since the warnings were non-interruptive , providers did not have to act upon or acknowledge the notification to complete a medication request . MEASUREMENTS Data were collected each time providers performed suggested laboratory testing within 14 days of a new prescription order . Findings were adjusted for patient and provider characteristics as well as patient clustering within clinics . RESULTS Among 12 clinics with 191 providers in the control group and 10 clinics with 175 providers in the intervention group , there were 3673 total events where baseline lab tests would have been advised : 1988 events in the control group and 1685 in the intervention group . In the control group , baseline labs were requested for 771 ( 39 % ) of the medications . In the intervention group , baseline labs were ordered by clinicians in 689 ( 41 % ) of the cases . Overall , no significant association existed between the intervention and the rate of ordering appropriate baseline laboratory tests . CONCLUSION We found that non-interruptive medication laboratory monitoring alerts were not effective in improving receipt of recommended baseline laboratory test monitoring for medications . Further work is necessary to optimize compliance with non-critical recommendations BACKGROUND Medication errors are frequently related to failure to appropriately select medications or adjust for laboratory parameters . Differences between guideline recommendations and actual frequency of therapeutic laboratory monitoring are substantial . This study evaluated interventions to improve laboratory monitoring at initiation of medication therapy . METHODS This cluster-r and omized trial compared 3 interventions to usual care for 10 medications in 15 primary care clinics in a health maintenance organization with an electronic medical record system . Eligible patients , identified from electronic data bases , had not received recommended laboratory monitoring within 5 days after new dispensing of a study medication . Interventions were an electronic medical record reminder to the prescribing health care professional , an automated voice message to the patient , and a pharmacy team outreach to the patient . Primary outcome was completion of all recommended baseline laboratory monitoring . RESULTS A total of 961 patients participated in the study . At 25 days , 95 ( 48.5 % ) of 196 patients in the electronic medical record reminder group , 177 ( 66.3 % ) of 267 in the automated voice message group , 214 ( 82.0 % ) of 261 in the pharmacy team outreach group , and 53 ( 22.4 % ) of 237 in the usual care group had completed all recommended baseline laboratory monitoring ( P<.001 ) . After adjustments , the hazard ratios for completing laboratory monitoring compared with usual care were 2.5 ( 95 % confidence interval , 1.8 - 3.5 ) for electronic medical record reminder , 4.1 ( 95 % confidence interval , 3.0 - 5.6 ) for automated voice message , and 6.7 ( 95 % confidence interval , 4.9 - 9.0 ) for pharmacy team outreach . CONCLUSIONS All 3 interventions were effective in increasing laboratory monitoring when initiating new medications in primary care . Further work is necessary to determine if these interventions improve patient outcomes OBJECTIVE —To test Web-based care management of glycemic control using a shared electronic medical record with patients who have type 2 diabetes . RESEARCH DESIGN AND METHODS —We conducted a trial of 83 adults with type 2 diabetes r and omized to receive usual care plus Web-based care management or usual care alone between August 2002 and May 2004 . All patients had GHb ≥7.0 % , had Web access from home , and could use a computer with English language –based programs . Intervention patients received 12 months of Web-based care management . The Web-based program included patient access to electronic medical records , secure e-mail with providers , feedback on blood glucose readings , an educational Web site , and an interactive online diary for entering information about exercise , diet , and medication . The primary outcome was change in GHb . RESULTS —GHb levels declined by 0.7 % ( 95 % CI 0.2−1.3 ) on average among intervention patients compared with usual-care patients . Systolic blood pressure , diastolic blood pressure , total cholesterol levels , and use of in-person health care services did not differ between the two groups . CONCLUSIONS —Care management delivered through secure patient Web communications improved glycemic control in type 2 diabetes BACKGROUND Physicians frequently need to start antibiotic therapy before the results of bacterial cultures and antibiotic susceptibility tests are available . We developed and evaluated a computerized antibiotic consultant to assist physicians in the selection of appropriate empiric antibiotics . METHODS We used a two-stage r and om- selection study to compare antibiotics suggested by the antibiotic consultant with 482 associated antibiotic susceptibility results and the concurrent antibiotics ordered by physicians . The antibiotics ordered by r and omized physicians were then compared between crossover periods of antibiotic consultant use . RESULTS The antibiotic consultant suggested an antibiotic regimen to which all isolated pathogens were shown to be susceptible for 453 ( 94 % ) of 482 culture results , while physicians ordered an antibiotic regimen to which all isolated pathogens were susceptible for 369 culture results ( 77 % ) ( P < .001 ) . The physicians who prescribed antibiotics to which all pathogens were susceptible did so a mean of 21 hours after the culture specimens were collected . Physicians ordered appropriate antibiotics within 12 hours of the culture collection significantly more often when they had use of the antibiotic consultant than during the period before use ( P < .035 ) . Moreover , 88 % of the physicians stated they would recommend the program to other physicians , 85 % said the program improved their antibiotic selection , and 81 % said they felt use of the program improved patient care . CONCLUSIONS Information from computer-based medical records can be used to help improve physicians ' selection of empiric antibiotics for infections Guided dosing within a computerized provider order entry ( CPOE ) system is an effective method of individualizing therapy for patients . Physicians ' responses to guided dosing decision support have not been extensively studied . As part of a r and omized trial evaluating efficacy of dosing advice on reducing falls in the elderly , CPOE prompts to physicians for 88 drugs included tailored messages and guided dose lists with recommended initial doses and frequencies . The study captured all prescribing activity electronically . The primary outcome was the ratio between prescribed dose and recommended dose . Over 9 months , 778 providers entered 9111 study -related medication orders on 2981 patients . Physicians using guided orders chose recommended doses more often than controls(28.6 % vs. 24.1 % , p<0.001 ) . Selected doses were significantly lower in the intervention group ( median ratio of actual to recommended 2.5 , interquartile range [ 1.0,4.0 ] ) than the control group ( median 3.0 interquartile range [ 1.5,5.0 ] , p<0.001 ) . While physicians selected the recommended dose less than a third of the time , guided geriatric dosing modestly improved compliance with guidelines Introduction Medication errors in the intensive care unit ( ICU ) are frequent and lead to attributable patient morbidity and mortality , increased length of ICU stay and substantial extra costs . We investigated if the introduction of a computerized ICU system ( Centricity Critical Care Clinisoft , GE Healthcare ) reduced the incidence and severity of medication prescription errors ( MPEs ) . Methods A prospect i ve trial was conducted in a paper-based unit ( PB-U ) versus a computerized unit ( C-U ) in a 22-bed ICU of a tertiary university hospital . Every medication order and medication prescription error was vali date d by a clinical pharmacist . The registration of different classes of MPE was done according to the National Coordinating Council for Medication Error Reporting and Prevention guidelines . An independent panel evaluated the severity of MPEs . We identified three groups : minor MPEs ( no potential to cause harm ) ; intercepted MPEs ( potential to cause harm but intercepted on time ) ; and serious MPEs ( non-intercepted potential adverse drug events ( ADE ) or ADEs , being MPEs with potential to cause , or actually causing , patient harm ) . Results The C-U and the PB-U each contained 80 patient-days , and a total of 2,510 medication prescriptions were evaluated . The clinical pharmacist identified 375 MPEs . The incidence of MPEs was significantly lower in the C-U compared with the PB-U ( 44/1286 ( 3.4 % ) versus 331/1224 ( 27.0 % ) ; P < 0.001 ) . There were significantly less minor MPEs in the C-U than in the PB-U ( 9 versus 225 ; P < 0.001 ) . Intercepted MPEs were also lower in the C-U ( 12 versus 46 ; P < 0.001 ) , as well as the non-intercepted potential ADEs ( 21 versus 48 ; P < 0.001 ) . There was also a reduction of ADEs ( 2 in the C-U versus 12 in the PB-U ; P < 0.01 ) . No fatal errors occurred . The most frequent drug classes involved were cardiovascular medication and antibiotics in both groups . Patients with renal failure experienced less dosing errors in the C-U versus the PB-U ( 12 versus 35 serious MPEs ; P < 0.001 ) . Conclusion The ICU computerization , including the medication order entry , result ed in a significant decrease in the occurrence and severity of medication errors in the ICU Limited prospect i ve data exist that define advantages and disadvantages of text-based versus graphical user interfaces in Computerized Provider Order Entry ( CPOE ) . We created a single set of admission orders in both formats and , using a r and omized crossover design , assessed the usage and perceptions of the two interfaces by 51 physicians during the first six weeks ( 2 week blocks of one format , then the alternative , then free choice ) following implementation in a postsurgical unit OBJECTIVE To assess the impact of an automated intraoperative alert to redose prophylactic antibiotics in prolonged cardiac operations . DESIGN R and omized , controlled , evaluator-blinded trial . SETTING University-affiliated hospital . PATIENTS Patients undergoing cardiac surgery that lasted more than 4 hours after the preoperative administration of cefazolin , unless they were receiving therapeutic antibiotics at the time of surgery . INTERVENTION R and omization to an audible and visual reminder on the operating room computer console at 225 minutes after the administration of preoperative antibiotics ( reminder group , n = 137 ) or control ( n = 136 ) . After another 30 minutes , the circulating nurse was required to indicate whether a follow-up dose of antibiotics had been administered . RESULTS Intraoperative redosing was significantly more frequent in the reminder group ( 93 of 137 ; 68 % ) than in the control group ( 55 of 136 ; 40 % ) ( adjusted odds ratio , 3.31 ; 95 % confidence interval , 1.97 to 5.56 ; P < .0001 ) . The impact of the reminder was even greater when compared with the 6 months preceding the study period ( 129 of 480 ; 27 % ; P < .001 ) , suggesting some spillover effect on the control group . Redosing was formally declined for 19 of the 44 patients in the reminder group without redosing . The rate of surgical-site infection in the reminder group ( 5 of 137 ; 4 % ) was similar to that in the control group ( 8 of 136 ; 6 % ; P = .42 ) , but significantly lower than that in the pre- study period ( 48 of 480 ; 10 % ; P = .02 ) . CONCLUSION The use of an automatic reminder system in the operating room improved compliance with guidelines on perioperative antibiotic prophylaxis Abstract Objectives : To investigate the effect of a computer based clinical decision support system and a risk chart on absolute cardiovascular risk , blood pressure , and prescribing of cardiovascular drugs in hypertensive patients . Design : Cluster r and omised controlled trial . Setting : 27 general practice s in Avon . Participants : 614 patients aged between 60 and 79 years with high blood pressure . Interventions : Patients were r and omised to computer based clinical decision support system plus cardiovascular risk chart ; cardiovascular risk chart alone ; or usual care . Main outcome measures : Percentage of patients in each group with a five year cardiovascular risk≥10 % , systolic blood pressure , diastolic blood pressure , prescribing of cardiovascular drugs . Results : Patients in the computer based clinical decision support system and chart only groups were no more likely to have cardiovascular risk reduced to below 10 % than patients receiving usual care . Patients in the computer based clinical decision support group were more likely to have a cardiovascular risk≥10 % than chart only patients , odds ratio 2.3 ( 95 % confidence interval 1.1 to 4.8 ) . The chart only group had significantly lower systolic blood pressure compared with the usual care group ( difference in means−4.6 mm Hg ( 95 % confidence interval−8.4 to−0.8 ) . Reduction of diastolic blood pressure did not differ between the three groups . The chart only group were twice as likely to be prescribed two classes of cardiovascular drugs and over three times as likely to be prescribed three or more classes of drugs compared with the other groups . Conclusions : The computer based clinical decision support system did not confer any benefit in absolute risk reduction or blood pressure control and requires further development and evaluation before use in clinical care can be recommended . Use of chart guidelines are associated with a potentially important reduction in systolic blood pressure OBJECTIVE A research prototype Physician Workstation ( PWS ) incorporating a graphical user interface and a drug ordering module was compared with the existing hospital information system in an academic Veterans Administration General Medical Clinic . Physicians in the intervention group received recommendations for drug substitutions to reduce costs and were alerted to potential drug interactions . The objective was to evaluate the effect of the PWS on user satisfaction , on health-related outcomes , and on costs . DESIGN A one-year , two-period , r and omized controlled trial with 37 subjects . MEASUREMENTS Differences in the reliance on noncomputer sources of information , in user satisfaction , in the cost of prescribed medications , and in the rate of clinical ly relevant drug interactions were assessed . RESULTS The study subjects logged onto the workstation an average of 6.53 times per provider and used it to generate 2.8 % of prescriptions during the intervention period . On a five-point scale ( 5 = very satisfied , 1 = very dissatisfied ) , user satisfaction declined in the PWS group ( 3.44 to 2.98 p = 0.008 ) , and increased in the control group ( 3.23 to 3.72 , p < 0.0001 ) . CONCLUSION The intervention physicians did not use the PWS frequently enough to influence information-seeking behavior , health outcomes , or cost . The study design did not determine whether the poor usage result ed from satisfaction with the control system , problems using the PWS intervention , or the functions provided by the PWS intervention . Evaluative studies should include provisions to improve the chance of successful implementation as well as to yield maximum information if a negative study occurs OBJECTIVES To evaluate the effectiveness of computer-assisted decision support in reducing potentially inappropriate prescribing to older adults . DESIGN R and omized , controlled trial . SETTING An academic emergency department ( ED ) in Indianapolis , Indiana , where computerized physician order entry was used to write all medication prescriptions . PARTICIPANTS Sixty-three emergency physicians were r and omized to the intervention ( 32 physicians ) or control ( 31 physicians ) group . INTERVENTION Decision support that advised against use of nine potentially inappropriate medications and recommended safer substitute therapies . MEASUREMENTS The primary outcome was the proportion of ED visits by seniors that result ed in one or more prescriptions for an inappropriate medication . The main secondary outcomes were the proportions of medications prescribed that were inappropriate and intervention physicians ' reasons for rejecting the decision support . RESULTS The average age of the patients was 74 , two-thirds were female , and just over half were African American . Decision support was provided 114 times to intervention physicians , who accepted 49 ( 43 % ) of the recommendations . Intervention physicians prescribed one or more inappropriate medications during 2.6 % of ED visits by seniors , compared with 3.9 % of visits managed by control physicians ( P=.02 ; odds ratio=0.55 , 95 % confidence interval=0.34 - 0.89 ) . The proportion of all prescribed medications that were inappropriate significantly decreased from 5.4 % to 3.4 % . The most common reason for rejecting decision support was that the patient had no prior problems with the medication . CONCLUSION Computerized physician order entry with decision support significantly reduced prescribing of potentially inappropriate medications for seniors . This approach might be used in other efforts to improve ED care . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00297869 OBJECTIVE To evaluate whether an electronic reminder integrated into a routine computer system increases the use of antiplatelet drugs for diabetic patients among Italian general practitioners ( GPs ) . RESEARCH DESIGN AND METHODS A r and omized controlled trial was carried out among 300 GPs and their patients selected from the Health Search Data base . Among these , 150 GPs ( intervention group ) received instructions to activate an electronic reminder plus a letter summarizing the beneficial effects of antiplatelet drugs in diabetic patients with at least one additional cardiovascular risk factor ( " high risk " ) , whereas the other 150 GPs ( control group ) received only the letter . The electronic reminder , integrated into a st and ard software system for the management of the daily clinical practice , was displayed when every participating GP opened the medical record of diabetic patients aged > or = 30 years . Only high-risk diabetic patients were included in the analysis . Patients were considered under antiplatelet treatment if they received two or more prescriptions at baseline and during the follow-up . RESULTS We selected 15,343 high-risk diabetic patients , 7,313 belonging to GPs of the control group and 8,030 belonging to GPs of the intervention group . Overall , 1,672 patients ( 22.9 % ) of the control group and 1,886 ( 23.5 % ) patients of the intervention group received antiplatelet drugs at baseline ( P = N.S. ) . At the end of the follow-up , the number of treated patients was significantly increased in the intervention group ( odds ratio 1.99 , 95 % CI 1.79 - 2.22 ) versus the control group . The effect of the electronic reminder was more relevant among those patients with one or more cardiovascular risk factors but without previous cardiovascular diseases ( CVDs ) , compared with those with CVDs . CONCLUSIONS These findings provide evidence for the effect of an electronic reminder in affecting the prescriptive behavior of GPs Computers are steadily being incorporated in clinical practice . We conducted a nonr and omised , controlled , prospect i ve trial of electronic messages design ed to enhance adherence to clinical practice guidelines . We studied 126 physicians and nurse practitioners who used electronic medical records when caring for 349 patients with HIV infection in a primary care practice . We analysed the response times of clinicians to the situations that triggered alerts and reminders , the number of ambulatory visits , and hospitalisation . The median response times to 303 alerts in the intervention group and 388 alerts in the control group were 11 and 52 days ( p < 0.0001 ) , respectively . The median response time to 432 reminders in the intervention group was 114 days and that for 360 reminders in the control group was over 500 days ( p < 0.0001 ) . There was no effect on visits to the primary care practice . There was , however , a significant increase in the rate of visits outside the primary care practice ( p = 0.02 ) , which is explained by the increased frequency of visits to ophthalmologists . There were no differences in admission rates ( p = 0.47 ) , in admissions for pneumocystosis ( p = 0.09 ) , in visits to the emergency ward ( p = 0.24 ) , or in survival ( p = 0.19 ) . We conclude that the electronic medical record was effective in helping clinicians adhere to practice guidelines OBJECTIVE Authors evaluated whether displaying context sensitive links to infrequently accessed educational material s and patient information via the user interface of an inpatient computerized care provider order entry ( CPOE ) system would affect access rates to the material s. DESIGN The CPOE of V and erbilt University Hospital ( VUH ) included " baseline " clinical decision support advice for safety and quality . Authors augmented this with seven new primarily educational decision support features . A prospect i ve , r and omized , controlled trial compared clinicians ' utilization rates for the new material s via two interfaces . Control subjects could access study -related decision support from a menu in the st and ard CPOE interface . Intervention subjects received active notification when study -related decision support was available through context sensitive , visibly highlighted , selectable hyperlinks . MEASUREMENTS Rates of opportunities to access and utilization of study -related decision support material s from April 1999 through March 2000 on seven VUH Internal Medicine wards . RESULTS During 4,466 intervention subject-days , there were 240,504 ( 53.9/subject-day ) opportunities for study -related decision support , while during 3,397 control subject-days , there were 178,235 ( 52.5/subject-day ) opportunities for such decision support , respectively ( p = 0.11 ) . Individual intervention subjects accessed the decision support features at least once on 3.8 % of subject-days logged on ( 278 responses ) ; controls accessed it at least once on 0.6 % of subject-days ( 18 responses ) , with a response rate ratio adjusted for decision support frequency of 9.17 ( 95 % confidence interval 4.6 - 18 , p < 0.0005 ) . On average , intervention subjects accessed study -related decision support material s once every 16 days individually and once every 1.26 days in aggregate . CONCLUSION Highlighting availability of context -sensitive educational material s and patient information through visible hyperlinks significantly increased utilization rates for study -related decision support when compared to " st and ard " VUH CPOE methods , although absolute response rates were low BACKGROUND Although they are effective in outpatient setting s , computerized reminders have not been proved to increase preventive care in inpatient setting s. METHODS We conducted a r and omized , controlled trial to determine the effects of computerized reminders on the rates at which four preventive therapies were ordered for in patients . During an 18-month study period , a computerized system processed on-line information for all 6371 patients admitted to a general-medicine service ( for a total of 10,065 hospitalizations ) , generating preventive care reminders as appropriate . Physicians who were in the intervention group viewed these reminders when they were using a computerized order-entry system for in patients . RESULTS The reminder system identified 3416 patients ( 53.6 percent ) as eligible for preventive measures that had not been ordered by the admitting physician . For patients with at least one indication , computerized reminders result ed in higher adjusted ordering rates for pneumococcal vaccination ( 35.8 percent of the patients in the intervention group vs. 0.8 percent of those in the control group , P<0.001 ) , influenza vaccination ( 51.4 percent vs. 1.0 percent , P < 0.001 ) , prophylactic heparin ( 32.2 percent vs. 18.9 percent , P<0.001 ) , and prophylactic aspirin at discharge ( 36.4 percent vs. 27.6 percent , P<0.001 ) . CONCLUSIONS A majority of hospitalized patients in this study were eligible for preventive measures , and computerized reminders significantly increased the rate of delivery of such therapies CONTEXT Computerized systems to remind physicians to provide appropriate care have not been widely evaluated in large numbers of patients in multiple clinical setting s. OBJECTIVE To examine whether a computerized reminder system operating in multiple Veterans Affairs ( VA ) ambulatory care clinics improves resident physician compliance with st and ards of ambulatory care . DESIGN , SETTING , AND PARTICIPANTS A total of 275 resident physicians at 12 VA medical centers were r and omly assigned in firms or half-day clinic blocks to either a reminder group ( n = 132 ) or a control group ( n = 143 ) . During a 17-month study period ( January 31 , 1995-June 30 , 1996 ) , the residents cared for 12,989 unique patients for whom at least 1 of the studied st and ards of care ( SOC ) was applicable . MAIN OUTCOME MEASURES Compliance with 13 SOC , tracked using hospital data bases and encounter forms completed by residents , compared between residents in the reminder group vs those in the control group . RESULTS Measuring compliance as the proportion of patients in compliance with all applicable SOC by their last visit during the study period , the reminder group had statistically significantly higher rates of compliance than the control group for all st and ards combined ( 58.8 % vs 53.5 % ; odds ratio [ OR ] , 1.24 ; 95 % confidence interval [ CI ] , 1.08 - 1.42 ; P = .002 ) and for 5 of the 13 st and ards examined individually . Measuring compliance as the proportion of all visits for which care was indicated in which residents provided proper care , the reminder group also had statistically significantly higher rates of compliance than the control group for all st and ards combined ( 17.9 % vs 12.2 % ; OR , 1.57 ; 95 % CI , 1.45 - 1.71 ; P<.001 ) and for 9 of the 13 st and ards examined individually . The benefit of reminders , however , declined throughout the course of the study , even though the reminders remained active . CONCLUSIONS Our data indicate that reminder systems installed at multiple sites can improve residents ' compliance to multiple SOC . The benefits of such systems , however , appear to deteriorate over time . Future research needs to explore methods to better sustain the benefits of reminders . JAMA . 2000;284:1411 - 1416 A robust , h and -held , patient-oriented insulin regimen optimizer ( POIRO ) has been developed . Relevant information is entered by selecting appropriate items from choices displayed on a touch-sensitive screen rather than a conventional keyboard . All data items are recorded , together with their time and date of entry , and may be recalled at any time with glucose values displayed graphically to provide an overview of glycaemic control . When requested , an integral , hybrid , statistical and rule-based expert system program uses all available data to suggest an optimum insulin dose within physician determined , pre-set limits . POIRO has been formally evaluated in a r and omized crossover pilot trial , comparing two 3 week periods with and without decision support , in six patients with type 1 diabetes . Mean ( SE ) pre-pr and ial blood glucose levels were significantly lower during the period when decision support was available ( 7.5 ( 0.4 ) versus 8.9 ( 0.4 ) mmol/l , p = 0.015 ) with no increase in the frequency or severity of hypoglycaemia . The device , which was well received by the patients , may offer a relatively inexpensive method of providing expert diabetic advice at a distance . The persistence of improved glycaemic control , even after decision support was switched off , suggests the device could be used intermittently by patients and may have educational value Background It is possible to provide patients with secure access to their medical records using the Internet . Such access may assist patients in the self-management of chronic diseases such as heart failure . Objective To assess how a patient-accessible online medical record affects patient care and clinic operations . The SPPARO ( System Providing Access to Records Online ) software consisted of a web-based electronic medical record , an educational guide , and a messaging system enabling electronic communication between the patient and staff . Methods A r and omized controlled trial was conducted in a specialty practice for patients with heart failure . Surveys assessing doctor-patient communication , adherence , and health status were conducted at baseline , 6 months , and 1 year . Use of the system , message volume , utilization of clinical services , and mortality were monitored . Results One hundred and seven patients were enrolled ( 54 intervention and 53 controls ) . At 12 months , the intervention group was not found to be superior in self-efficacy ( KCCQ self-efficacy score 91 vs. 85 , p=0.08 ) , but was superior in general adherence ( MOS compliance score 85 vs. 78 , p=0.01 ) . A trend was observed for better satisfaction with doctor-patient communication . The intervention group had more emergency department visits ( 20 vs. 8 , p=0.03 ) , but these visits were not temporally related to use of the online medical record . There were no adverse effects from use of the system . Conclusions Providing patients with congestive heart failure access to an online medical record was feasible and improved adherence . An effect on health status could not be demonstrated in this pilot study OBJECTIVE To evaluate the implementation of clinical guidelines for hypertension in general practice by use of a computer-based clinical decision support system ( CDSS ) and a specific implementation strategy . Evaluation of patient outcome . DESIGN R and omised study with health centres as units . The intervention group had the CDSS installed and made ready for use , doctors and assistants were trained and received a user-manual , the doctors were offered telephone repetitions , a seminar in risk intervention and , at the same seminar , further demonstration of the CDSS . The doctors received baseline registration s with information of how they treated their own hypertensive patients , and use of the CDSS was checked repeatedly . SETTING General practice in Sør- and Nord-Trøndelag counties in Norway , 380,000 inhabitants . PARTICIPANTS Seventeen health centres with 24 doctors and 984 patients in the intervention group . Data from 879 patients used in the final analyses . Twelve health centres with 29 doctors and 1255 patients in the control group . Data from 1119 patients used in the final analyses . MAIN OUTCOME MEASURES After an intervention period of 18 months , group differences in level of systolic and diastolic blood pressure , serum cholesterol , body mass index , and risk score for myocardial infa rct ion were calculated , as well as group differences in fractions of smokers . RESULTS Significant group difference in favour of intervention group : diastolic blood pressure 1 mmHg ( 95 % CI -1.89 , -0.17 ) . However , a significant baseline difference in systolic blood pressure in favour of control group of 2.7 mmHg ( 95 % CI 1.0 , 4.5 ) had been reduced to 1.2 mmHg ( 95 % CI -0.6 , 3.0 ) after intervention . CONCLUSION Implementation of clinical guidelines in the treatment of hypertensive patients in general practice by means of a CDSS and several other procedures for implementation did not affect patient outcome in any clinical ly significant way Objectives : Having shown previously that an electronic prescription writer and decision support system improved pediatric prescribing behavior for otitis media in an academic clinic setting , we assessed whether point-of-care delivery of evidence could demonstrate similar effects for a wide range of other common pediatric conditions . Design : Cluster r and omized controlled trial . Setting : A teaching clinic/ clinical practice site and a primary care pediatric clinic serving a rural and semi-urban patient mix . Participants : A total of 36 providers at the teaching clinic/ practice site and eight providers at the private primary pediatric clinic . Intervention : An evidence -based message system that presented real-time evidence to providers based on prescribing practice s for acute otitis media , allergic rhinitis , sinusitis , constipation , pharyngitis , croup , urticaria , and bronchiolitis . Outcome measures : The proportion of prescriptions dispensed in accordance with evidence . Results : The proportion of prescriptions dispensed in accordance with evidence improved four percentage points , from 38 % at baseline to 42 % following the intervention . The control group improved by one percentage point , from 39 % at baseline to 40 % at trial 's conclusion . The adjusted difference between the intervention and control groups was 8 % ( 95 % confidence interval 1 % , 15 % ) . Intervention effectiveness did not decrease with time . Conclusion : For common pediatric outpatient conditions , a point-of-care evidence -based prescription writer and decision support system was associated with significant improvements in prescribing practice OBJECTIVE To test effects of a web-based decision support tool , the diabetes Disease Management Application ( DMA ) , developed to improve evidence -based management of type 2 diabetes . RESEARCH DESIGN AND METHODS We conducted a group r and omized controlled trial of 12 intervention and 14 control staff providers and 307 intervention and 291 control patients with type 2 diabetes in a hospital-based internal medicine clinic . Providers were r and omly assigned from May 1998 through April 1999 to have access to the DMA ( intervention ) or not to have access ( control ) . The DMA displays interactive patient-specific clinical data , treatment advice , and links to other web-based care re sources . We compared patients in the intervention and control groups for changes in processes and outcomes of care from the year preceding the study through the year of the study by intention-to-treat analysis . RESULTS The DMA was used for 42 % of scheduled patient visits . The number of HbA(1c ) tests obtained per year increased significantly in the intervention group ( + 0.3 tests/year ) compared with the control group ( -0.04 tests/year , P = 0.008 ) , as did the number of LDL cholesterol tests ( intervention , + 0.2 tests/year ; control , + 0.01 tests/year ; P = 0.02 ) and the proportions of patients undergoing at least one foot examination per year ( intervention , + 9.8 % ; control , -0.7 % ; P = 0.003 ) . Levels of HbA(1c ) decreased by 0.2 in the intervention group and increased by 0.1 in the control group ( P = 0.09 ) ; proportions of patients with LDL cholesterol levels < 130 mg/dl increased by 20.3 % in the intervention group and 10.5 % in the control group ( P = 0.5 ) . CONCLUSIONS Web-based patient-specific decision support has the potential to improve evidence -based parameters of diabetes care BACKGROUND AND OBJECTIVE Clinical guidelines discourage antibiotic prescribing for many acute respiratory infections ( ARIs ) , especially for non-antibiotic appropriate diagnoses . Electronic health record (EHR)-based clinical decision support has the potential to improve antibiotic prescribing for ARIs . METHODS We r and omly assigned 27 primary care clinics to receive an EHR-integrated , documentation-based clinical decision support system for the care of patients with ARIs - the ARI Smart Form - or to offer usual care . The primary outcome was the antibiotic prescribing rate for ARIs in an intent-to-intervene analysis based on administrative diagnoses . RESULTS During the intervention period , patients made 21 961 ARI visits to study clinics . Intervention clinicians used the ARI Smart Form in 6 % of 11 954 ARI visits . The antibiotic prescribing rate in the intervention clinics was 39 % versus 43 % in the control clinics ( odds ratio ( OR ) , 0.8 ; 95 % confidence interval ( CI ) , 0.6 - 1.2 , adjusted for clustering by clinic ) . For antibiotic appropriate ARI diagnoses , the antibiotic prescribing rate was 54 % in the intervention clinics and 59 % in the control clinics ( OR , 0.8 ; 95 % CI , 0.5 - 1.3 ) . For non-antibiotic appropriate diagnoses , the antibiotic prescribing rate was 32 % in the intervention clinics and 34 % in the control clinics ( OR , 0.9 ; 95 % CI , 0.6 - 1.4 ) . When the ARI Smart Form was used , based on diagnoses entered on the form , the antibiotic prescribing rate was 49 % overall , 88 % for antibiotic appropriate diagnoses and 27 % for non-antibiotic appropriate diagnoses . In an as-used analysis , the ARI Smart Form was associated with a lower antibiotic prescribing rate for acute bronchitis ( OR , 0.5 ; 95 % CI , 0.3 - 0.8 ) . CONCLUSIONS The ARI Smart Form neither reduced overall antibiotic prescribing nor significantly improved the appropriateness of antibiotic prescribing for ARIs , but it was not widely used . When used , the ARI Smart Form may improve diagnostic accuracy compared to administrative diagnoses and may reduce antibiotic prescribing for certain diagnoses BACKGROUND Physician adherence to National Cholesterol Education Program clinical practice guidelines has been poor . METHODS We recruited 68 primary care family and internal medicine practice s ; 66 were r and omly allocated to a study arm ; 5 practice s withdrew , result ing in 29 receiving the Third Adult Treatment Panel ( ATP III ) intervention and 32 receiving an alternative intervention focused on the Seventh Report of the Joint National Committee on the Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC-7 ) . The ATP III providers received a personal digital assistant providing the Framingham risk scores and ATP III-recommended treatment . All practice s received copies of each clinical practice guideline , an introductory lecture , 1 performance feedback report , and 4 visits for intervention-specific academic detailing . Data were abstract ed at 61 practice s from r and om sample s of medical records of patients treated from June 1 , 2001 , through May 31 , 2003 ( baseline ) , and from May 1 , 2004 , through April 30 , 2006 ( follow-up ) . The proportion screened with subsequent appropriate decision making ( primary outcome ) was calculated . Generalized estimating equations were used to compare results by arm , accounting for clustering of patients within practice s. RESULTS We examined 5057 baseline and 3821 follow-up medical records . The screening rate for lipid levels increased from 43.6 % to 49.0 % ( ATP III practice s ) and from 40.1 % to 50.8 % ( control practice s ) ( net difference , -5.3 % [ P = .22 ] ) . Appropriate management of lipid levels decreased slightly ( 73.4 % to 72.3 % ) in ATP III practice s and more markedly ( 79.7 % to 68.9 % ) in control practice s. The net change in appropriate management favored the intervention ( + 9.7 % ; 95 % confidence interval [ CI ] , 2.8%-16.6 % [ P < .01 ] ) . Appropriate drug prescription within 4 months decreased in both arms ( 38.8 % to 24.8 % in ATP III practice s and 45.3 % to 24.1 % in control practice s ; net change , + 7.2 % [ P = .37 ] ) Overtreatment declined from 6.6 % to 3.9 % in ATP III and rose from 4.2 % to 6.4 % in control practice s ( net change , -4.9 % [ P = .01 ] ) . CONCLUSIONS A multifactor intervention including personal digital assistant-based decision support may improve primary care physician adherence to the ATP III guidelines . Trial Registration clinical trials.gov Identifier : NCT00224848 BACKGROUND Medication reconciliation at transitions in care is a national patient safety goal , but its effects on important patient outcomes require further evaluation . We sought to measure the impact of an information technology-based medication reconciliation intervention on medication discrepancies with potential for harm ( potential adverse drug events [ PADEs ] ) . METHODS We performed a controlled trial , r and omized by medical team , on general medical inpatient units at 2 academic hospitals from May to June 2006 . We enrolled 322 patients admitted to 14 medical teams , for whom a medication history could be obtained before discharge . The intervention was a computerized medication reconciliation tool and process re design involving physicians , nurses , and pharmacists . The main outcome was unintentional discrepancies between preadmission medications and admission or discharge medications that had potential for harm ( PADEs ) . RESULTS Among 160 control patients , there were 230 PADEs ( 1.44 per patient ) , while among 162 intervention patients there were 170 PADEs ( 1.05 per patient ) ( adjusted relative risk [ ARR ] , 0.72 ; 95 % confidence interval [ CI ] , 0.52 - 0.99 ) . A significant benefit was found at hospital 1 ( ARR , 0.60 ; 95 % CI , 0.38 - 0.97 ) but not at hospital 2 ( ARR , 0.87 ; 95 % CI , 0.57 - 1.32 ) ( P = .32 for test of effect modification ) . Hospitals differed in the extent of integration of the medication reconciliation tool into computerized provider order entry applications at discharge . CONCLUSIONS A computerized medication reconciliation tool and process re design were associated with a decrease in unintentional medication discrepancies with potential for patient harm . Software integration issues are likely important for successful implementation of computerized medication reconciliation tools OBJECTIVE This study sought to determine whether a computerized tool that alerted pharmacists when pregnant patients were prescribed U.S. Food and Drug Administration pregnancy risk category D or X medications was effective in decreasing dispensings of these medications . DESIGN R and omized trial . Pharmacy , diagnostic , and laboratory data were linked to identify pregnant patients prescribed targeted medications . Women ( n = 11,100 ) were r and omized to intervention or usual care . Physicians and pharmacists collaborated on the intervention . MEASUREMENTS The primary outcome was the proportion of pregnant women dispensed a category D or X medication . The secondary outcome was the total number of first dispensings of targeted medications . RESULTS A total of 2.9 % of intervention ( n = 177 ) and 5.5 % of usual care ( n = 276 ) patients were dispensed targeted medications ( p < 0.001 ) : 1.8 % of intervention ( n = 108 ) and 3.9 % of usual care ( n = 198 ) patients were dispensed only category D medication(s ) ; 0.9 % of intervention ( n = 54 ) and 1.2 % of usual care ( n = 58 ) patients were dispensed only category X medication(s ) ; 0.2 % of intervention ( n = 15 ) and 0.4 % of usual care ( n = 20 ) patients were dispensed both category D and X medications ( p = 0.05 ) . This result ed in intervention patients receiving 238 dispensings of unique targeted medications and usual care patients receiving 361 dispensings of unique targeted medications ( p = 0.03 ) . The study was stopped primarily due to 2 false-positive alert types : Mis identification of medications as contraindicated in pregnancy by the pharmacy information system and mis identification of pregnancy related to delayed transfer of diagnosis information . CONCLUSION Coupling data from information systems with knowledge and skills of physicians and pharmacists result ed in improved prescribing safety . Systems limitations contributed to project discontinuation . Linking ambulatory clinical , laboratory , and pharmacy information to provide safety alerts is not sufficient to ensure project success and sustainability OBJECTIVE To measure the impact of a computerized guideline for glucose regulation in an ICU . DESIGN A r and omized , controlled trial with an off-on-off design . METHODS We implemented a glucose regulation guideline in an intensive care unit in paper form during the first study period . During the second period , the guideline was r and omly applied in either paper or computerized form . In the third period , the guideline was available only in paper form . MEASUREMENTS AND RESULTS We analyzed data for 484 patients . During the intervention period , the control group included 54 patients and the computerized intervention group included 66 patients . The two guideline -related outcome measures consisted of compliance with : ( a ) glucose measurement timing recommendations and ( b ) insulin dose advice . We measured clinical impact as the proportion of time that glucose levels fell within target range . In the first ( paper-based ) study period , 29.0 % of sample s occurred with optimal timing ; during the second period , this increased to 35.5 % for paper-based and to 40.2 % for computerized protocol s. The third study period timeliness scores reverted to the first period rates . Late ( suboptimal ) sampling occurred for 66 % of glucose measurements in the first study period , for 42 % of paper-based and 28 % of computer-based protocol sample s in the second period , and for 50.0 % of sample s in the third study period . In the first study period , insulin-dosing guideline compliance was 56.3 % ; in the second period , it was 64.2 % for paper-based and 77.3 % for computer-based protocol s , and it fell to 42.4 % in the third period . For the second study period , the time that a patient 's glucose values fell within target range improved for both the control ( 52.9 % ) and the computerized groups ( 54.2 % ) compared with the first study period ( 44.3 % ) and the third period ( 42.3 % ) . CONCLUSION Implementing a computerized version of a guideline significantly improved timeliness of measurements and glucose level regulation for critically ill patients compared with implementing a paper-based version of the guideline OBJECTIVE Errors of omission are a common cause of systems failures . Physicians often fail to order tests or treatments needed to monitor/ameliorate the effects of other tests or treatments . The authors hypothesized that automated , guideline -based reminders to physicians , provided as they wrote orders , could reduce these omissions . DESIGN The study was performed on the inpatient general medicine ward of a public teaching hospital . Faculty and housestaff from the Indiana University School of Medicine , who used computer workstations to write orders , were r and omized to intervention and control groups . As intervention physicians wrote orders for 1 of 87 selected tests or treatments , the computer suggested corollary orders needed to detect or ameliorate adverse reactions to the trigger orders . The physicians could accept or reject these suggestions . RESULTS During the 6-month trial , reminders about corollary orders were presented to 48 intervention physicians and withheld from 41 control physicians . Intervention physicians ordered the suggested corollary orders in 46.3 % of instances when they received a reminder , compared with 21.9 % compliance by control physicians ( p < 0.0001 ) . Physicians discriminated in their acceptance of suggested orders , readily accepting some while rejecting others . There were one third fewer interventions initiated by pharmacists with physicians in the intervention than control groups . CONCLUSION This study demonstrates that physician workstations , linked to a comprehensive electronic medical record , can be an efficient means for decreasing errors of omissions and improving adherence to practice guidelines CONTEXT Prescribing practice s for otitis media are not consistent with current evidence -based recommendations . OBJECTIVE To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written . DESIGN R and omized , controlled trial . SETTING Primary care pediatric clinic affiliated with university training program . Intervention . A point-of-care evidence -based message system presenting real time evidence to providers based on their prescribing practice for otitis media . MAIN OUTCOME MEASURES Proportion of prescriptions for otitis media that were for < 10 days and frequency with which antibiotics were prescribed . RESULTS Intervention providers had a 34 % greater reduction in the proportion of time they prescribed antibiotics for < 10 days . Intervention providers were less likely to prescribe antibiotics than were control providers . CONCLUSIONS A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition CONTEXT Computerized reminder systems increase influenza and pneumococcal vaccination rates , but computerized st and ing order systems have not been previously described or evaluated . OBJECTIVE To determine the effects of computerized physician st and ing orders compared with physician reminders on inpatient vaccination rates . DESIGN , SETTING , AND PATIENTS R and omized trial of 3777 general medicine patients discharged from 1 of 6 study wards during a 14-month period ( November 1 , 1998 , through December 31 , 1999 ) composed of 2 overlapping influenza seasons at an urban public teaching hospital . INTERVENTIONS The hospital 's computerized physician order entry system identified in patients eligible for influenza and pneumococcal vaccination . For patients with st and ing orders , the system automatically produced vaccine orders directed to nurses at the time of patient discharge . For patients with reminders , the computer system provided reminders to physicians that included vaccine orders during routine order entry sessions . MAIN OUTCOME MEASURE Vaccine administration . RESULTS During the approximately 6 months of the influenza season , 50 % of all hospitalized patients were identified as eligible for influenza vaccination . Twenty-two percent of patients hospitalized during the entire 14 months of the study were found eligible for pneumococcal vaccination . Patients with st and ing orders received an influenza vaccine significantly more often ( 42 % ) than those patients with reminders ( 30 % ) ( P < .001 ) . Patients with st and ing orders received a pneumococcal vaccine significantly more often ( 51 % ) than those with reminders ( 31 % ) ( P < .001 ) . CONCLUSIONS Computerized st and ing orders were more effective than computerized reminders for increasing both influenza and pneumococcal vaccine administration . Our findings suggest that computerized st and ing orders should be used more widely for this purpose Abstract Objective : To assess the effectiveness of tailored interventions to implement guidelines for urinary tract infections in women and sore throat Design : Unblinded , cluster r and omised pretest-post-test trial Setting : 142 general practice s in Norway Participants : 72 practice s received interventions to implement guidelines for urinary tract infection and 70 practice s received interventions to implement guidelines for sore throat , serving as controls for each other . 59 practice s in the urinary tract infection group and 61 practice s in the sore throat group completed the study . Outcomes were measured in 16 939 consultations for sore throat and 9887 consultations for urinary tract infection . Interventions : Interventions were developed to overcome identified barriers to implementing the guidelines . The main components of the tailored interventions were patient educational material , computer based decision support and reminders , an increase in the fee for telephone consultations , and interactive courses for general practitioners and practice assistants Main outcome measures : Changes in rates of use of antibiotics , laboratory tests , and telephone consultations Results : Patients in the sore throat group were 3 % less likely to receive antibiotics after the intervention . Women with symptoms of urinary tract infection in the intervention group were 5.1 % less likely to have a laboratory test ordered . No significant differences were found between the groups for the other outcomes . Large variation was found across the included practice sin the rates of antibiotic prescription , use of laboratory tests and telephone consultations , and in the extent of change for all three outcome measures Conclusions : Passively delivered , complex interventions targeted at identified barriers to change had little effect in changing BACKGROUND Appropriate antibiotic treatment decreases mortality , while superfluous treatment is associated with antibiotic resistance . We built a computerized decision support system for antibiotic treatment ( TREAT ) targeting these outcomes . METHODS Prospect i ve cohort study comparing TREAT 's advice to physician 's treatment followed by a cluster r and omized trial comparing wards using TREAT ( intervention ) versus antibiotic monitoring without TREAT ( control ) . We included patients suspected of harbouring bacterial infections in three hospitals ( Israel , Germany and Italy ) . The primary outcome , appropriate antibiotic treatment , was assessed among patients with microbiologically documented infections ( MDI ) . Length of hospital stay , adverse events , mortality ( interventional trial ) and antibiotic costs ( both studies ) , including costs related to future antibiotic resistance , were compared among all included patients . RESULTS Among 1203 patients included in the cohort study ( 350 with MDI ) , TREAT prescribed appropriate empirical antibiotic treatment significantly more frequently than physicians ( 70 % versus 57 % , P < 0.001 ) using less broad-spectrum antibiotics at half physicians ' antibiotic costs . The r and omized trial included 2326 patients , 570 with MDI . The rate of appropriate empirical antibiotic treatment was higher in intervention versus control wards [ 73 % versus 64 % , odds ratio ( OR ) : 1.48 , 95 % confidence interval ( CI ) : 0.95 - 2.29 , intention to treat , adjusted for location and clustering ] . For patients treated according to TREAT 's advice in intervention wards , the difference with controls was highly significant ( OR : 3.40 , 95 % CI : 2.25 - 5.14 ) . Length of hospital stay , costs related to future resistance and total antibiotic costs were lower in intervention versus control wards . CONCLUSIONS TREAT improved the rate of appropriate empirical antibiotic treatment while reducing antibiotic costs and the use of broad-spectrum antibiotic treatment OBJECTIVE To evaluate the effectiveness of a personal digital assistant (PDA)-based clinical decision support system ( CDSS ) on nonsteroidal anti-inflammatory drug ( NSAID ) prescribing safety in the outpatient setting . DESIGN The design was a r and omized , controlled trial conducted in a university-based resident clinic . Internal medicine residents received a PDA-based CDSS suite . For intervention residents , the CDSS included a prediction rule for NSAID-related gastrointestinal risk assessment and treatment recommendations . Unannounced st and ardized patients ( SPs ) trained to portray musculoskeletal symptoms presented to study physicians . Safety outcomes were assessed from the prescriptions given to the SPs . Each prescription was review ed by a committee of clinicians blinded to participant , intervention group assignment , and baseline or follow-up status . MEASUREMENTS Prescriptions were judged as safe or unsafe . The main outcome measure was the differential change in unsafe prescribing of NSAIDs for the intervention versus the control group . RESULTS At baseline , the mean proportion of cases per physician with unsafe prescriptions for the two groups was similar ( 0.27 vs. 0.29 , p > 0.05 ) . Controlling for baseline performance , intervention participants prescribed more safely than controls after receiving the CDSS ( 0.23 vs. 0.45 [ F = 4.24 , p < 0.05 ] ) . With the CDSS , intervention participants documented more complete assessment of patient gastrointestinal risk from NSAIDs . CONCLUSION PARTICIPANTS provided with a PDA-based CDSS for NSAID prescribing made fewer unsafe treatment decisions than participants without the CDSS We analyze the effect of a decision support tool design ed to help physicians detect and correct medical " missteps " . The data comes from a r and omized trial of the technology on a population of commercial HMO patients . The key findings are that the new information technology lowers average charges by 6 % relative to the control group . This reduction in re source utilization was the result of reduced in-patient charges ( and associated professional charges ) for the most costly patients . The rate at which identified issues were resolved was generally higher in the study group than in the control group , suggesting the possibility of improvements in care quality along measured dimensions and enhanced diffusion of new protocol s based on new clinical evidence BACKGROUND Dyslipidemia remains underdiagnosed and undertreated in patients with coronary artery disease . The Computer-based Clinical Decision Support System provides an opportunity t close these gaps . OBJECTIVES To study the impact of computerized intervention on secondary prevention of CAD . METHODS The CDSS was programmed to automatically detect patients with CAD and to evaluate the availability of an up date d lipoprotein profile and treatment with lipid-lowering drugs . The program produced automatic computer-generated monitoring and treatment recommendations . Adjusted primary clinics were r and omly assigned to intervention ( n=56 ) or st and ard care arms ( n=56 ) . Reminders were mailed to the primary medical teams in the intervention arm every 4 months updating them with current lipid levels and recommendations for further treatment . Compliance and lipid levels were monitored . The study group comprised all patients with CAD who were alive at least 3 months after hospitalization . RESULTS Follow-up was available for 7448 patients ( median 19.8 months , range 6 - 36 months ) . Overall , 51.7 % of patients were adequately screened , and 55.7 % of patients were compliant with treatment to lower lipid level . In patients with initial low density lipoprotein > 120 mg/dl , a significant decrease in LDL levels was observed in both arms , but was more pronounced in the intervention arm : 121.9 + /- 34.2 vs. 124.3 + /- 34.6 mg/dl ( P < 0.02 ) . A significantly lower rate of cardiac rehospitalizations was documented in patients who were adequately treated with lipid-lowering drugs , 37 % vs. 40.9 % ( P < 0.001 ) . CONCLUSIONS This initial assessment of our data represent a real-world snapshot where physicians and CAD patients often do not adhere to clinical guidelines , presenting a major obstacle to implementing effective secondary prevention . Our automatic computerized reminders system substantially facilitates adherence to guidelines and supports wide-range implementation OBJECTIVE Recommendations for routine laboratory monitoring to reduce the risk of adverse medication events are not consistently followed . We evaluated the impact of electronic reminders delivered to primary care physicians on rates of appropriate routine medication laboratory monitoring . DESIGN We enrolled 303 primary care physicians caring for 1,922 patients across 20 ambulatory clinics that had at least one overdue routine laboratory test for a given medication between January and June 2004 . Clinics were r and omized so that physicians received either usual care or electronic reminders at the time of office visits focused on potassium , creatinine , liver function , thyroid function , and therapeutic drug levels . MEASUREMENTS Primary outcomes were the receipt of recommended laboratory monitoring within 14 days following an outpatient clinic visit . The effect of the intervention was assessed for each reminder after adjusting for clustering within clinics , as well as patient and provider characteristics . RESULTS Medication-laboratory monitoring non-compliance ranged from 1.6 % ( potassium monitoring with potassium-supplement use ) to 6.3 % ( liver function monitoring with HMG CoA Reductase Inhibitor use ) . Rates of appropriate laboratory monitoring following an outpatient visit ranged from 14 % ( therapeutic drug levels ) to 64 % ( potassium monitoring with potassium-sparing diuretic use ) . Reminders for appropriate laboratory monitoring had no impact on rates of receiving appropriate testing for creatinine , potassium , liver function , renal function , or therapeutic drug level monitoring . CONCLUSION We identified high rates of appropriate laboratory monitoring , and electronic reminders did not significantly improve these monitoring rates . Future studies should focus on setting s with lower baseline adherence rates and alternate drug-laboratory combinations Context Prescription drug costs are a major component of health care expenditures , yet re sources to support evidence -based prescribing are not widely available . Objective To evaluate the effectiveness of computerized prescribing alerts , with or without physician-led group educational sessions , to reduce the prescribing of heavily marketed hypnotic medications . Design Cluster-r and omized controlled trial . Setting We r and omly allocated 14 internal medicine practice sites to receive usual care , computerized prescribing alerts alone , or alerts plus group educational sessions . Measurements Proportion of heavily marketed hypnotics prescribed before and after the implementation of computerized alerts and educational sessions . Main Results The activation of computerized alerts held the prescribing of heavily marketed hypnotic medications at pre-intervention levels in both the alert-only group ( adjusted risk ratio [ RR ] 0.97 ; 95 % CI 0.82–1.14 ) and the alert-plus-education group ( RR 0.98 ; 95 % CI 0.83–1.17 ) while the usual-care group experienced an increase in prescribing ( RR 1.31 ; 95 % CI 1.08–1.60 ) . Compared to the usual-care group , the relative risk of prescribing heavily marketed medications was less in both the alert-group ( Ratio of risk ratios [ RRR ] 0.74 ; 95 % CI 0.57–0.96 ) and the alert-plus-education group ( RRR 0.74 ; 95 % CI 0.58–0.97 ) . The prescribing of heavily marketed medications was similar in the alert-group and alert-plus-education group ( RRR 1.02 ; 95 % CI 0.80–1.29 ) . Most clinicians reported that the alerts provided useful prescribing information ( 88 % ) and did not interfere with daily workflow ( 70 % ) . Conclusions Computerized decision support is an effective tool to reduce the prescribing of heavily marketed hypnotic medications in ambulatory care setting s . Trial Registration clinical trials.gov Identifier : NCT00788346 OBJECTIVE To assess the effect of three computerized reminder systems on compliance with tetanus vaccination . DESIGN Prospect i ve r and omized controlled trial . SETTING Ottawa Civic Hospital Family Medicine Centre . PARTICIPANTS Of 8069 patients 20 years of age or more who were not in a hospital or institution 5589 were r and omly assigned , by family , to a control group , a physician reminder group , a telephone reminder group or a letter reminder group . The remaining 2480 patients were not included in the r and omized portion of the study but were monitored . Results are presented for the 5242 r and omized patients and the 2369 nonr and omized patients for whom there was no up-to- date record of tetanus vaccination at the start of the trial . INTERVENTIONS For the patients in the physician reminder group the physician was reminded at an office visit to assess the patient 's tetanus vaccination status and to recommend vaccination ; those in the other two reminder groups received a telephone call or letter enquiring about their tetanus vaccination status and recommending a booster dose . MAIN OUTCOME MEASURE Proportion of patients who received tetanus toxoid during the study year or who had a cl aim of vaccination in the previous 10 years . MAIN RESULTS The rate of recorded tetanus vaccination in the r and omized control group was 3.2 % . The difference between that rate and those for the three reminder groups was 19.6 % in the physician reminder group ( 95 % confidence interval [ CI ] 17.1 % to 22.2 % , p less than 0.00001 ) , 20.8 % in the telephone reminder group ( 95 % CI 18.3 % to 23.5 % , p less than 0.00001 ) and 27.4 % in the letter reminder group ( 95 % CI 24.8 % to 30.2 % , p less than 0.00001 ) ) . The letter reminders were more effective than either the telephone reminders ( p = 0.00013 ) or the physician reminders ( p less than 0.00001 ) in improving compliance . The cost to the practice per additional vaccination recorded was 43 for the physician reminders , $ 5.43 for the telephone reminders and $ 6.05 for the letter reminders . CONCLUSIONS Although all three reminder systems increased the rate of recorded tetanus vaccination they fell far short of achieving complete population coverage . More intensive interventions would be required to approach that goal . However , such interventions do not appear to be justified given the rarity of tetanus OBJECTIVE : Suboptimal treatment of hyperlipidemia in patients with coronary artery disease ( CAD ) is well documented . We report the impact of a computer-assisted physician-directed intervention to improve secondary prevention of hyperlipidemia . DESIGN AND SETTING : Two hundred thirty-five patients under the care of 14 primary care physicians in an academically affiliated practice with an electronic health record were enrolled in this proof-of-concept physician-blinded r and omized , controlled trial . Each patient with CAD or risk equivalent above National Cholesterol Education Program-recommended low-density lipoprotein ( LDL ) treatment goal for greater than 6 months was r and omized , stratified by physician and baseline LDL . Physicians received a single e-mail per intervention patient . E-mails were visit independent , provided decision support , and facilitated “ one-click ” order writing . MEASUREMENTS : The primary outcomes were changes in hyperlipidemia prescriptions , time to prescription change , and changes in LDL levels . The time spent using the system was assessed among intervention patients . RESULTS : A greater proportion of intervention patients had prescription changes at 1 month ( 15.3 % vs 2 % , P=.001 ) and 1 year ( 24.6 % vs 17.1 % , P=.14 ) . The median interval to first medication adjustment occurred earlier among intervention patients ( 0 vs 7.1 months , P=.005 ) . Among patients with baseline LDLs > 130 mg/dL , the first postintervention LDLs were substantially lower in the intervention group ( 119.0 vs 138.0 mg/dL , P=.04 ) . Physician processing time was under 60 seconds per e-mail . CONCLUSION : A visit-independent disease management tool result ed in significant improvement in secondary prevention of hyperlipidemia at 1-month postintervention and showed a trend toward improvement at 1 year A computer was used to prospect ively detect and suggest responses to simple , medication-related events as reflected in a computerized record in a prospect i ve , r and omized study of a diabetes clinic with primary -care responsibility . There were two categories of event/suggestions : when the last observation of a test required for medication control was too old , the computer suggested a repeat ; and when an abnormality with therapeutic implication s was detected , the computer suggested a specific change in therapeutics . Clinicians responded to 36 % of events in the first category with computer reminders and 11 % without ( P less than 0.0001 ) ; they responded to 28 % of events in the second category with computer assistance and 13 % without ( P less than 0.026 ) . For the most clinical ly significant of these second category events , the difference was even greater : 47 % with and 4 % without computer assistance ( P less than 0.0004 ) . I believe that computer detection and response ( in the form of reminders ) to simple clinical events will change clinician behavior Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists OBJECTIVE We developed AsthmaCritic , a non-inquisitive critiquing system integrated with the general practitioners ' electronic medical records . The system is based on the guidelines for asthma and chronic obstructive pulmonary disease ( COPD ) as issued by the Dutch College of General Practitioners . This paper assesses the effect of AsthmaCritic on monitoring and treatment of asthma and COPD by Dutch general practitioners in daily practice . METHODS A r and omized clinical trial in 32 practice s ( 40 Dutch general practitioners ) using electronic patient records . An intervention group was given the use of AsthmaCritic , a control group continued working in the usual manner . Both groups had the disposal of the asthma and COPD guidelines routinely distributed by the Dutch College of General Practitioners . We measured the average number of contacts , FEV 1 ( forced expiratory volume ) , and peak-flow measurements per asthma/ COPD patient per practice ; and , the average number of antihistamine , cromoglycate , deptropine , and oral bronchodilator prescriptions per asthma/ COPD patient per practice . RESULTS The number of contacts increased in the age group of 12 - 39 years . The number of FEV1 , peak-flow measurements , and the ratio of coded measurements increased , whereas the number of cromoglycate prescriptions decreased in the age group of 12 - 39 years . CONCLUSIONS Our study shows that the guideline -based critiquing system AsthmaCritic changed the manner in which the physicians monitored their patients and , to a lesser extent , their treatment behavior . In addition , the physicians changed their data -recording habits Background : Diabetes mellitus is a complex disease with serious complications . Electronic decision support , providing information that is shared and discussed by both patient and physician , encourages timely interventions and may improve the management of this chronic disease . However , it has rarely been tested in community-based primary care . Methods : In this pragmatic r and omized trial , we r and omly assigned adult primary care patients with type 2 diabetes to receive the intervention or usual care . The intervention involved shared access by the primary care provider and the patient to a Web-based , colour-coded diabetes tracker , which provided sequential monitoring values for 13 diabetes risk factors , their respective targets and brief , prioritized messages of advice . The primary outcome measure was a process composite score . Secondary outcomes included clinical composite scores , quality of life , continuity of care and usability . The outcome assessors were blinded to each patient ’s intervention status . Results : We recruited sequentially 46 primary care providers and then 511 of their patients ( mean age 60.7 [ st and ard deviation 12.5 ] years ) . Mean follow-up was 5.9 months . The process composite score was significantly better for patients in the intervention group than for control patients ( difference 1.27 , 95 % confidence interval [ CI ] 0.79–1.75 , p < 0.001 ) ; 61.7 % ( 156/253 ) of patients in the intervention group , compared with 42.6 % ( 110/258 ) of control patients , showed improvement ( difference 19.1 % , p < 0.001 ) . The clinical composite score also had significantly more variables with improvement for the intervention group ( 0.59 , 95 % CI 0.09–1.10 , p = 0.02 ) , including significantly greater declines in blood pressure ( −3.95 mm Hg systolic and −2.38 mm Hg diastolic ) and glycated hemoglobin ( −0.2 % ) . Patients in the intervention group reported greater satisfaction with their diabetes care . Interpretation : A shared electronic decision-support system to support the primary care of diabetes improved the process of care and some clinical markers of the quality of diabetes care . ( Clinical Trials.gov trial register no. NCT00813085 . OBJECTIVE It is difficult to control drug-prescribing behaviour in general practice , despite the development and distribution of guidelines . The purpose of this study was to assess the effect on drug-prescribing behaviour of implementing prescribing guidelines by means of a reactive computer reminder system ( CRS ) . DESIGN Cluster-r and omised controlled trial with an incomplete block design in the south of the Netherl and s : 25 GPs ( 7 GP practice s ) received reminders about antibiotics and asthma/ COPD prescriptions , 28 GPs ( 7 GP practice s ) received reminders about cholesterol prescriptions . Prescription guidelines were integrated into the computerised GP information system . MEASUREMENTS Both performance indicators and prescription volumes were calculated as the main outcome measures . Next to individual volume measure , sum scores were constructed on the volume measures per drug group ( antibiotics , asthma/ COPD and cholesterol ) . RESULTS Variation between GPs turned out to be larger and more skewed than expected . No differences between groups were found for indicators and volumes related to recommendations advocating certain drugs . Although there was a tendency towards clinical ly relevant results for prescription volumes that were supposed to drop , the difference in sum score between the groups was not significant . For antibiotic prescriptions that were supposed to drop , the sum score for the intervention group was 28.2 ( 95 % CI : 20.8 - 44.5 ) prescriptions per 1000 patients per GP , while this was 39.7 ( 95 % CI : 29.7 - 64.1 ) for the control group ( p 0.2 ) . For prescriptions asthma/ COPD that were supposed to drop , the sum score for the intervention group was 1.1 ( 95 % CI : 0.6 - 2.6 ) prescriptions per 1000 patients per GP , while this was 2.2 ( 95 % CI : 1.4 - 4.3 ) for the control group ( p 0.1 ) . On three specific recommendations ( on quinolones for cystitis , corticosteroids for CPOD , and antibiotics for acute sore throat ) significant differences were found . CONCLUSIONS This study turned out to be underpowered due to high inter doctor variation in prescribing behaviour . Nevertheless , computerised reminders sometimes have a favourable effect on restricting certain drugs that are not or no longer indicated in general practice BACKGROUND Translating guidelines into clinical practice has proved to be quite difficult , even when the guidelines are well accepted and noncontroversial . Both computerized reminders and academic detailing have been effective in changing physician prescribing behavior . In this study , we sought to use these methods , mediated by clinical pharmacists , to improve adherence to the secondary prevention guidelines in hospitalized patients with myocardial infa rct ion . METHODS A r and omized , prospect i ve study was performed in which computerized alerts identifying hospitalized patients with elevated troponin I levels were routed to clinical pharmacists . The pharmacists then conducted academic detailing for physicians caring for patients with acute myocardial infa rct ion who were r and omized to the intervention group . Patients in the control group received st and ard care . The main outcome measure was the proportion of patients discharged on a regimen of aspirin , beta-blockers , angiotensin-converting enzyme inhibitors , and statins . RESULTS The intervention had a significant impact on the proportion of patients discharged on a regimen of angiotensin-converting enzyme inhibitors ( 328/365 [ 89.9 % ] vs 409/488 [ 83.8 % ] , intervention vs control , respectively , P = .02 ) , and statins ( 344/365 [ 94.2 % ] vs 436/488 [ 89.3 % ] , P = .02 ) . There was no statistical impact on beta-blocker ( 350/365 [ 95.9 % ] vs 448/488 [ 91.8 % ] , P = .10 ) or aspirin use ( 352/365 [ 96.4 % ] vs 471/488 [ 96.5 % ] , P = .87 ) . When all 4 classes were considered together , 305 ( 83.6 % ) of 365 patients vs 343 ( 70.3 % ) of 488 patients were discharged on a regimen of all secondary prevention medications to which they did not have a contraindication ( P<.001 ) . CONCLUSION A computerized alert with pharmacist-mediated academic detailing is an effective means to increase adherence to secondary prevention guidelines for coronary heart disease UNLABELLED OBJECTIVE To determine whether a computerized clinical decision support system providing patient-specific recommendations in real-time improves the quality of prescribing for long-term care residents with renal insufficiency . DESIGN R and omized trial within the long-stay units of a large long-term care facility . R and omization was within blocks by unit type . Alerts related to medication prescribing for residents with renal insufficiency were displayed to prescribers in the intervention units and hidden but tracked in control units . Measurement The proportions of final drug orders that were appropriate were compared between intervention and control units within alert categories : ( 1 ) recommended medication doses ; ( 2 ) recommended administration frequencies ; ( 3 ) recommendations to avoid the drug ; ( 4 ) warnings of missing information . RESULTS The rates of alerts were nearly equal in the intervention and control units : 2.5 per 1,000 resident days in the intervention units and 2.4 in the control units . The proportions of dose alerts for which the final drug orders were appropriate were similar between the intervention and control units ( relative risk 0.95 , 95 % confidence interval 0.83 , 1.1 ) for the remaining alert categories significantly higher proportions of final drug orders were appropriate in the intervention units : relative risk 2.4 for maximum frequency ( 1.4 , 4.4 ) ; 2.6 for drugs that should be avoided ( 1.4 , 5.0 ) ; and 1.8 for alerts to acquire missing information ( 1.1 , 3.4 ) . Overall , final drug orders were appropriate significantly more often in the intervention units-relative risk 1.2 ( 1.0 , 1.4 ) . CONCLUSIONS Clinical decision support for physicians prescribing medications for long-term care residents with renal insufficiency can improve the quality of prescribing decisions . TRIAL REGISTRATION http:// clinical trials.gov Identifier : NCT00599209 OBJECTIVES To evaluate the efficacy of computerized provider order entry with clinical decision support for preventing adverse drug events in long-term care . DESIGN Cluster-r and omized controlled trial . SETTING Two large long-term care facilities . PATIENTS One thous and one hundred eighteen long-term care residents of 29 resident care units . INTERVENTION The 29 resident care units , each with computerized provider order entry , were r and omized to having a clinical decision support system ( intervention units ) or not ( control units ) . MEASUREMENTS The number of adverse drug events , severity of events , and whether the events were preventable . RESULTS Within intervention units , 411 adverse drug events occurred over 3,803 resident-months of observation time ; 152 ( 37.0 % ) were deemed preventable . Within control units , there were 340 adverse drug events over 3,257 resident-months of observation time ; 126 ( 37.1 % ) were characterized as preventable . There were 10.8 adverse drug events per 100 resident-months and 4.0 preventable events per 100 resident-months on intervention units . There were 10.4 adverse drug events per 100 resident-months and 3.9 preventable events per 100 resident-months on control units . Comparing intervention and control units , the adjusted rate ratios were 1.06 ( 95 % confidence interval (CI)=0.92 - 1.23 ) for all adverse drug events and 1.02 ( 95 % CI=0.81 - 1.30 ) for preventable adverse drug events . CONCLUSION Computerized provider order entry with decision support did not reduce the adverse drug event rate or preventable adverse drug event rate in the long-term care setting . Alert burden , limited scope of the alerts , and a need to more fully integrate clinical and laboratory information may have affected efficacy OBJECTIVE : To examine whether feedback and treatment advice for depression presented to primary care physicians ( PCPs ) via an electronic medical record ( EMR ) system can potentially improve clinical outcomes and care processes for patients with major depression . DESIGN : R and omized controlled trial . SETTING : Academically affiliated primary care practice in Pittsburgh , PA . PATIENTS : Two hundred primary care patients with major depression on the Primary Care Evaluation of Mental Disorders ( PRIME-MD ) and who met all protocol - eligibility criteria .INTERVENTION : PCPs were r and omly assigned to 1 of 3 levels of exposure to EMR feedback of guideline -based treatment advice for depression : “ active care ” ( AC ) , “ passive care ” ( PC ) , or “ usual care ” ( UC ) . MEASUREMENTS AND MAIN RESULTS : Patients ’ 3- and 6-month Hamilton Rating Scale for Depression ( HRS-D ) score and chart review of PCP reports of depression care in the 6 months following the depression diagnosis . Only 22 % of patients recovered from their depressive episode at 6 months ( HRS-D ≤7 ) . Patients ’ mean HRS-D score decreased regardless of their PCPs ’ guideline -exposure condition ( 20.4 to 14.2 from baseline to 6-month follow-up ; P<.001 ) . However , neither continuous ( HRS-D ≤7 : 22 % AC , 23 % PC , 22 % UC ; P=.8 ) nor categorical measures of recovery ( P=.2 ) differed by EMR exposure condition upon follow-up . Care processes for depression were also similar by PCP assignment despite exposure to repeated reminders of the depression diagnosis and treatment advice ( e.g. , depression mentioned in ≥3 contacts with usual PCP at 6 months : 31 % AC , 31 % PC , 18 % UC ; P=.09 and antidepressant medication suggested/prescribed or baseline regimen modified at 6 months : 59 % AC , 57 % PC , 52 % UC ; P=.3 ) . CONCLUSIONS : Screening for major depression , electronically informing PCPs of the diagnosis , and then exposing them to evidence -based treatment recommendations for depression via EMR has little differential impact on patients ’ 3- or 6-month clinical outcomes or on process measures consistent with high- quality depression care A computerized medical decision-making system was used to monitor signs and predisposing factors of digoxin intoxication in patients receiving digoxin . This process automatically review ed the patient 's data base nightly for drug interactions , laboratory data and electrocardiographic findings with known association with digoxin intoxication . These decisions were formated into a " digoxin alert report " and sent to line printers in the nursing division to be placed on the individual patients ' charts . To assess the effect of these reports on patient management , a r and omized double-blind study was undertaken . Patients were assigned to an alert or nonalert group . Alert reports were withheld from charts of patients in the nonalert group . A medical record review was subsequently carried out , wherein the physician 's orders were search ed to identify actions taken with possible relation to the digoxin alerts . The computer monitored 396 patients over a 3 month period . Of these , 211 ( 53 % ) were r and omized to the alert group and 185 ( 47 % ) to the nonalert group . Seventy-two percent of patients received at least one alert . The most frequently occurring alerts included : hypoxemia , hypokalemia , concurrent use of a beta-adrenergic blocking agent , renal insufficiency and ventricular arrhythmia . Results from the record review demonstrated a 22 % increase in physician actions for the alert group . Specifically , patients in the alert group were 2.7 times more likely to have a serum digoxin determination ordered and 2.8 times more likely to have digoxin withheld on the day of a digoxin alert than were patients in the nonalert group BACKGROUND One of the causes of postdischarge adverse events is poor discharge communication between hospital-based physicians , patients , and outpatient physicians . The value of hospital discharge software to improve communication and clinical ly relevant outcomes is unknown . OBJECTIVE To measure effects of a discharge software application of computerized physician order entry ( CPOE ) . DESIGN Cluster r and omized controlled trial . SETTING Tertiary care , teaching hospital in central Illinois . PATIENTS A total of 631 in patients discharged to home with high risk for readmission . INTERVENTION Seventy internal medicine hospital physicians were r and omly assigned ( allocation concealed ) to discharge software versus usual care , h and written discharge . MEASUREMENTS Blinded assessment of patient readmission , emergency department visit , and postdischarge adverse event . RESULTS A total of 590 ( 94 % ) patients provided 6-month follow-up data . Generalized estimating equations gave intervention variable coefficients with 95 % confidence interval ( CI ) . When comparing patients assigned to discharge software versus usual care , there was no difference in hospital readmission within 6 months ( 37.0 % versus 37.8 % ; coefficient -0.005 [ 95 % CI , -0.074 to 0.065 ] ; P = 0.894 ) , emergency department visit within 6 months ( 35.4 % versus 40.6 % ; coefficient -0.052 [ 95 % CI , -0.115 to 0.011 ] ; P = 0.108 ) , or adverse event within 1 month ( 7.3 % versus 7.3 % ; coefficient 0.003 [ 95 % CI ; -0.037 to 0.043 ] ; P = 0.884 ) . CONCLUSIONS Discharge software with CPOE did not affect readmissions , emergency department visits , or adverse events after discharge . Future studies should assess other endpoints such as patient perceptions or physician perceptions to see if discharge software has value BACKGROUND Identifying the appropriate long-term anti-thrombotic therapy following acute ischaemic stroke is a challenging area in which computer-based decision support may provide assistance . AIM To evaluate the influence on prescribing practice of a computer-based decision support system ( CDSS ) that provided patient-specific estimates of the expected ischaemic and haemorrhagic vascular event rates under each potential anti-thrombotic therapy . DESIGN Cluster-r and omized controlled trial . METHODS We recruited patients who presented for a first investigation of ischaemic stroke or TIA symptoms , excluding those with a poor prognosis or major contraindication to anticoagulation . After observation of routine prescribing practice ( 6 months ) in each hospital , centres were r and omized for 6 months to either control ( routine practice observed ) or intervention ( practice observed while the CDSS provided patient-specific information ) . We compared , between control and intervention centres , the risk reduction ( estimated by the CDSS ) in ischaemic and haemorrhagic vascular events achieved by long-term anti-thrombotic therapy , and the proportions of subjects prescribed the optimal therapy identified by the CDSS . RESULTS Sixteen hospitals recruited 1952 subjects . When the CDSS provided information , the mean relative risk reduction attained by prescribing increased by 2.7 percentage units ( 95%CI -0.3 to 5.7 ) and the odds ratio for the optimal therapy being prescribed was 1.32 ( 0.83 to 1.80 ) . Some 55 % ( 5/9 ) of clinicians believed the CDSS had influenced their prescribing . CONCLUSIONS Cluster-r and omized trials provide excellent frameworks for evaluating novel clinical management methods . Our CDSS was feasible to implement and acceptable to clinicians , but did not substantially influence prescribing practice for anti-thrombotic drugs after acute ischaemic stroke OBJECTIVES Osteoporosis treatment rates after a fracture are low . This study evaluated methods to increase guideline -recommended osteoporosis care postfracture . DESIGN Participants were r and omly assigned to usual care or one of two interventions . Analysis of primary outcomes used electronic data and linear regression . SETTING A Pacific Northwest nonprofit health maintenance organization . PARTICIPANTS Female patients aged 50 to 89 who suffered a fracture in 1999 and had not received bone mineral density ( BMD ) measurement or medication for osteoporosis ( n=311 ) and their primary care providers ( n=159 ) . INTERVENTION Patient-specific clinical guideline advice to the primary care provider delivered by electronic medical record ( EMR ) message or electronic reminder to the provider plus an educational letter mailed to the patient . MEASUREMENTS BMD measurement and osteoporosis medication . RESULTS At 6 months , provider reminder result ed in 51.5 % of patients receiving BMD measurement or osteoporosis medication , provider reminder plus patient education result ed in 43.1 % , and usual care result ed in 5.9 % ( P<.001 ) . The effect of provider advice combined with patient education was not significantly different from provider advice alone ( P=.88 ) . Patients aged 60 to 69 were 18 % ( 95 % confidence interval=3 - 34 ) more likely to receive BMD measurement or an osteoporosis medication than those aged 80 to 89 . CONCLUSION Patient-specific postfracture advice to the provider through an EMR message significantly increased BMD measurement and osteoporosis medication . As EMRs become more widespread , this intervention could improve osteoporosis management for many postfracture patients . Future research should identify barriers to and facilitators of care for older , high-risk patients OBJECTIVE To demonstrate the potential effect of deploying a sentinel system that scans administrative cl aims information and clinical data to detect and mitigate errors in care and deviations from best medical practice s. METHODS Members ( n = 39 462 ; age range , 12 - 64 years ) of a midwestern managed care plan were r and omly assigned to an intervention or a control group . The sentinel system was programmed with more than 1000 decision rules that were capable of generating clinical recommendations . Clinical recommendations triggered for subjects in the intervention group were relayed to treating physicians , and those for the control group were deferred to study end . RESULTS Nine hundred eight clinical recommendations were issued to the intervention group . Among those in both groups who triggered recommendations , there were 19 % fewer hospital admissions in the intervention group compared with the control group ( P < .001 ) . Charges among those whose recommendations were communicated were dollar 77.91 per member per month ( pmpm ) lower and paid cl aims were dollar 68.08 pmpm lower than among controls compared with the baseline values ( P = .003 for both ) . Paid cl aims for the entire intervention group ( with or without recommendations ) were dollar 8.07 pmpm lower than those for the entire control group . In contrast , the intervention cost dollar 1.00 pmpm , suggesting an 8-fold return on investment . CONCLUSION Ongoing use of a sentinel system to prompt clinical ly actionable , patient-specific alerts generated from administratively derived clinical data was associated with a reduction in hospitalization , medical costs , and morbidity Context Despite evidence showing that even mild elevation of blood pressure above 140/90 mm Hg puts patients at risk for cardiovascular complications , many patients who are treated for hypertension still have high blood pressure . Contribution The authors sought to improve the blood pressure of patients using a health systems approach . They r and omly assigned providers caring for hypertensive patients to receive a Web link to the Seventh Report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ; the Web link and a computer alert notifying them of the patient 's blood pressure ; or the Web link , computer alert , and a letter educating the patient about ways to control his or her blood pressure . Patients of providers r and omly assigned to the third group had greater decreases in blood pressure and were more likely to have a systolic blood pressure less than 140 mm Hg . Caution s The study took place in a Veterans Affairs setting , follow-up blood pressure measures were missing for many patients , and the study was not design ed to detect a mechanism for any observed changes . Implication s A health systems approach that gave providers feedback about their patients ' blood pressure and that gave patients information about ways to control it improved blood pressure control compared with provider education alone . The Editors Currently , more than 50 million persons in the United States have hypertension ( 1 ) . The Seventh Report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC 7 ) promotes blood pressure goals of less than 140/90 mm Hg ( 25 ) . Providers , however , often delay changes in therapy or use higher blood pressure thresholds for the treatment of hypertension ( 2 , 4 , 6 , 7 ) , which leads to a variance in guideline adherence that contributes to a quality gap in care . Despite widespread guideline promotion , 65 % of persons in the United States have poorly controlled hypertension ( 1 , 6 , 8 , 9 ) . Factors contributing to the achievement of hypertension goals include provider decision making and patient adherence to antihypertensive treatment . These factors can be influenced by other factors , such as patient interactions with clinicians , commercial influences , and patient participation in treatment decisions ( 6 , 1017 ) . A review of hypertension goal attainment in primary care ( 18 ) found that interventions with the largest positive change were complex , multifactorial , and involved 4 areas : activities directed at changing clinician behavior , changes to the organization , information enhancement , and educational programs directed at patients . Although these findings suggest opportunities to achieve effective intervention by directing a change at each component ( 2 , 17 , 1923 ) , the impact of each component is less well known . Our aim was 1 ) to improve the quality of care of patients with hypertension at our facility while examining the relative contribution of each aspect of a multifactorial intervention design ed to improve care and 2 ) to show the effects of physician-level clustering on quality assessment . We conducted a cluster r and omized , controlled study to evaluate common components of a multifactorial intervention in veterans with essential hypertension . Methods Study Design and Setting This project was a cluster r and omized , controlled trial design ed to examine the relative contribution of 3 quality improvement interventions of increasing intensity in improving blood pressure control in veterans . This study was the evaluation component of a Veterans Integrated Service Network campaign to improve blood pressure control in patients who are treated in the Tennessee Valley Healthcare System . The health care system comprises 2 teaching hospitals , 2 large community-based outpatient clinics , and 6 small community-based outpatient clinics . There were 523659 outpatient visits made by 69928 veterans during fiscal year 2004 . The institutional review board of V and erbilt University and the VA Tennessee Valley Healthcare System research and development committee for human subjects protection approved this study . Inclusion Criteria We first identified eligible patients and then r and omly assigned providers caring for at least 1 of those patients to receive study interventions . Patients were eligible for inclusion in the study if they were 21 to 90 years of age , filled their medications at Veterans Administration ( VA ) pharmacies , had at least 2 uncontrolled blood pressure measurements in the 6-month baseline period ( systolic blood pressure > 140 mm Hg or diastolic blood pressure 90 mm Hg ) , and were only taking 1 antihypertensive medication . We restricted our study sample to patients with uncontrolled hypertension who were only taking 1 antihypertensive medication because the JNC 7 guidelines propose that most patients with hypertension will require 2 or more medications to achieve their blood pressure goals ( 5 , 12 ) . Therefore , this sample includes patients for whom the quality of hypertension care could be improved . Eligible patients were identified between July and December 2003 by search ing data from the Mid-South Quality Improvement Data warehouse , which are downloaded monthly from Veterans Health Information System and Technology Architecture . The search initially identified 4648 patients with a primary care visit who had a diagnosis of hypertension indicated by International Classification of Diseases , Ninth Revision , Clinical Modification ( ICD-9-CM ) codes 401.1 or 401.9 and who were prescribed only 1 antihypertensive medication ( Figure ) . We excluded 2821 ( 60 % ) patients because they had at least 1 recorded blood pressure reading between July and December 2003 that was at goal ( systolic blood pressure 140 mm Hg and diastolic blood pressure < 90 mm Hg ) . We mailed an assent letter to the remaining 1827 patients in January 2004 asking permission to review their electronic medical record and indicating that their primary provider would potentially receive suggestions to improve their hypertension care . Another 486 patients were excluded after r and omization because they declined chart review ( n= 222 ) or were taking more than 1 antihypertensive medication at the time of chart review ( n= 264 ) . Figure . Study flow diagram . * Excluded providers who cared for patients who declined chart review or those who were taking more than 1 medication at the time of chart review after r and omization . Providers were eligible for r and omization if they provided care for at least 1 patient who fulfilled the eligibility criteria . Providers were classified as attending physicians , resident physicians , or nonphysician clinicians ( nurse practitioner or physician assistant ) and were stratified into providers with at least 30 eligible patients and those with less than 30 eligible patients to help balance the number of patients in each study group . One hundred eighty-two providers were r and omly assigned to study interventions ; after r and omization , 23 providers were additionally excluded because the patients they cared for declined chart review or were taking more than 1 antihypertensive medication at the time of chart review ( Figure ) . Interventions Providers were r and omly assigned to 1 of 3 study groups : provider education only ; provider education and alert ; or provider education , alert , and patient education . All interventions were performed during the week of 14 June through 18 June 2004 , and follow-up continued through 31 December 2004 . Provider Education All providers in the 3 study groups received an e-mail message that explained the planned intervention . Providers who received only the e-mail message were controls for those who received the other 2 more intensive interventions . The e-mail informed providers that they might receive electronic alerts in the computerized patient record requesting reevaluation of a patient 's antihypertensive regimen . It also reported that a letter was being sent to selected patients advocating medication adherence and lifestyle modification to lower blood pressure . The e-mail message included a Web link to the JNC 7 guidelines for the treatment of hypertension ( www.nhlbi.nih.gov/ guidelines /hypertension/jnc7full.pdf ) . The message was sent by the supervisory pharmacist at the VA Tennessee Valley Healthcare System and was signed by the medical director of the network . Provider Education and Alert In the second study group , an alert was added to provider education . The alert was a 1-time patient-specific electronic notification that was sent by the pharmacy to the prescribing provider through each eligible patient 's electronic medical record over a 1-week period in June 2004 . Each time providers signed on to a computer , any medical record that contained an alert was brought to their attention . The alert gave a brief outline of the JNC 7 recommendations ( 5 ) and reminded providers that goal blood pressure should be 140/90 mm Hg or less . It included date s and values of the patient 's last 3 recorded blood pressure measurements and offered the following options : addition of a thiazide or thiazide combination diuretic , addition of another antihypertensive medication , or continuation of current medications and dosages . The alert reminded providers of the available thiazides on the VA formulary and stated that thiazides were contraindicated in patients with renal insufficiency or allergies to sulfa medications . Provider Education , Alert , and Patient Education The third study group combined the provider education and alert described previously with a patient education component . We sent a personalized letter that contained educational information concerning hypertension to each eligible patient in this study group . The letter was labeled Notice : To Veterans with High Blood Pressure and was design ed at an eighth- grade reading level . The letter recommended the use of behavioral strategies , such as medication adherence , low-sodium diet , and exercise , We tested whether off-line data analysis , instead of event monitoring , was a viable method for initiating a clinical quality alert . A cohort of patients eligible for an alert was identified by off-line data analysis and a flag was set in their ambulatory Electronic Medical Records . One hundred clinicians were r and omly assigned either to a control group or to a group that received the alert when viewing the electronic medical record of eligible patients . Primarily due to actions of their clinicians , 315 of the 580 patients ( 54.3 % ) seen by alerted clinicians were no longer eligible for the alert at the end of the one month study , compared to 128 of the 496 patients ( 25.8 % ) seen by control clinicians ( p<.001 ) . When not alerted , Allied Health clinicians were less likely than physicians to prescribe aspirin , but they responded similarly to the alert . There were no differences in response by specialty or gender of the clinician . Off-line data analysis proved to be an effective method of initiating a clinical alert BACKGROUND Experience from other fields of internal medicine shows that Internet-based technology can be used to monitor various diseases . The new technology h and les complex calculation programs easily , and it is a unique way of communicating . These advantages might be used in optimizing the treatment for asthmatic subjects because undertreatment is a common problem found in European asthmatic subjects . OBJECTIVE We sought to investigate the outcome of monitoring and treatment using a physician-managed online interactive asthma monitoring tool and to assess whether the outcome differs from that of monitoring and treatment in an outpatient respiratory clinic or in primary care . METHODS Three hundred asthmatic subjects were r and omized to 3 parallel groups in a 6-month prospect i ve study : ( 1 ) Internet-based monitoring ( n = 100 ) ; ( 2 ) specialist monitoring ( n = 100 ) ; and ( 3 ) general practitioner ( GP ) monitoring ( n = 100 ) . All the patients were examined on entry into the study and after 6 months of treatment . RESULTS The treatment and monitoring with the Internet-based management tool lead to significantly better improvement in the Internet group than in the other 2 groups regarding asthma symptoms ( Internet vs specialist : odds ratio of 2.64 , P = .002 ; Internet vs GP : odds ratio of 3.26 ; P < .001 ) , quality of life ( Internet vs specialist : odds ratio of 2.21 , P = .03 ; Internet vs GP : odds ratio of 2.10 , P = .04 ) , lung function ( Internet vs specialist : odds ratio of 3.26 , P = .002 ; Internet vs GP : odds ratio of 4.86 , P < .001 ) , and airway responsiveness ( Internet vs GP : odds ratio of 3.06 , P = .02 ) . CONCLUSION When physicians and patients used an interactive Internet-based asthma monitoring tool , better asthma control was achieved BACKGROUND Web-based personal health records ( PHRs ) have been advocated as a means to improve type 2 diabetes mellitus ( DM ) care . However , few Web-based systems are linked directly to the electronic medical record ( EMR ) used by physicians . METHODS We r and omized 11 primary care practice s. Intervention practice s received access to a DM-specific PHR that imported clinical and medications data , provided patient-tailored decision support , and enabled the patient to author a " Diabetes Care Plan " for electronic su bmi ssion to their physician prior to upcoming appointments . Active control practice s received a PHR to up date and su bmi t family history and health maintenance information . All patients attending these practice s were encouraged to sign up for online access . RESULTS We enrolled 244 patients with DM ( 37 % of the eligible population with registered online access , 4 % of the overall population of patients with DM ) . Study participants were younger ( mean age , 56.1 years vs 60.3 years ; P < .001 ) and lived in higher-income neighborhoods ( median income , $ 53,784 vs $ 49,713 ; P < .001 ) but had similar baseline glycemic control compared with non participants . More patients in the intervention arm had their DM treatment regimens adjusted ( 53 % vs 15 % ; P < .001 ) compared with active controls . However , there were no significant differences in risk factor control between study arms after 1 year ( P = .53 ) . CONCLUSIONS Previsit use of online PHR linked to the EMR increased rates of DM-related medication adjustment . Low rates of online patient account registration and good baseline control among participants limited the intervention 's impact on overall risk factor control . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00251875 BACKGROUND Prophylaxis against deep-vein thrombosis in hospitalized patients remains underused . We hypothesized that the use of a computer-alert program to encourage prophylaxis might reduce the frequency of deep-vein thrombosis among high-risk hospitalized patients . METHODS We developed a computer program linked to the patient data base to identify consecutive hospitalized patients at risk for deep-vein thrombosis in the absence of prophylaxis . The program used medical-record numbers to r and omly assign 1255 eligible patients to an intervention group , in which the responsible physician was alerted to a patient 's risk of deep-vein thrombosis , and 1251 patients to a control group , in which no alert was issued . The physician was required to acknowledge the alert and could then withhold or order prophylaxis , including graduated compression stockings , pneumatic compression boots , unfractionated heparin , low-molecular-weight heparin , or warfarin . The primary end point was clinical ly diagnosed , objective ly confirmed deep-vein thrombosis or pulmonary embolism at 90 days . RESULTS More patients in the intervention group than in the control group received mechanical prophylaxis ( 10.0 percent vs. 1.5 percent , P<0.001 ) or pharmacologic prophylaxis ( 23.6 percent vs. 13.0 percent , P<0.001 ) . The primary end point occurred in 61 patients ( 4.9 percent ) in the intervention group , as compared with 103 ( 8.2 percent ) in the control group ; the Kaplan-Meier estimates of the likelihood of freedom from deep-vein thrombosis or pulmonary embolism at 90 days were 94.1 percent ( 95 percent confidence interval , 92.5 to 95.4 percent ) and 90.6 percent ( 95 percent confidence interval , 88.7 to 92.2 percent ) , respectively ( P<0.001 ) . The computer alert reduced the risk of deep-vein thrombosis or pulmonary embolism at 90 days by 41 percent ( hazard ratio , 0.59 ; 95 percent confidence interval , 0.43 to 0.81 ; P=0.001 ) . CONCLUSIONS The institution of a computer-alert program increased physicians ' use of prophylaxis and markedly reduced the rates of deep-vein thrombosis and pulmonary embolism among hospitalized patients at risk BACKGROUND : Electronic information systems have been proposed as one means to reduce medical errors of commission ( doing the wrong thing ) and omission ( not providing indicated care ) . OBJECTIVE : To assess the effects of computer-based cardiac care suggestions . DESIGN : A r and omized , controlled trial targeting primary care physicians and pharmacists . SUBJECTS : A total of 706 out patients with heart failure and /or ischemic heart disease . INTERVENTIONS : Evidence -based cardiac care suggestions , approved by a panel of local cardiologists and general internists , were displayed to physicians and pharmacists as they cared for enrolled patients . MEASUREMENTS : Adherence with the care suggestions , generic and condition-specific quality of life , acute exacerbations of their cardiac disease , medication compliance , health care costs , satisfaction with care , and physicians ’ attitudes toward guidelines . RESULTS : Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions . The intervention had no effect on physicians ’ adherence to the care suggestions ( 23 % for intervention patients vs 22 % for controls ) . There were no intervention-control differences in quality of life , medication compliance , health care utilization , costs , or satisfaction with care . Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients . CONCLUSIONS : Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease . Future studies must weigh the benefits and costs of different ( and perhaps more Draconian ) methods of affecting clinician behavior BACKGROUND Computerized decision support reduces medication errors in in patients , but limited evidence supports its effectiveness in reducing the coprescribing of interacting medications , especially in the outpatient setting . The usefulness of academic detailing to enhance the effectiveness of medication interaction alerts also is uncertain . METHODS This study used an interrupted time series design . In a health maintenance organization with an electronic medical record , we evaluated the effectiveness of electronic medical record alerts and group academic detailing to reduce the coprescribing of warfarin and interacting medications . Participants were 239 primary care providers at 15 primary care clinics and 9910 patients taking warfarin . All 15 clinics received electronic medical record alerts for the coprescription of warfarin and 5 interacting medications : acetaminophen , nonsteroidal anti-inflammatory medications , fluconazole , metronidazole , and sulfamethoxazole . Seven clinics were r and omly assigned to receive group academic detailing . The primary outcome , the interacting prescription rate ( ie , the number of coprescriptions of warfarin-interacting medications per 10 000 warfarin users per month ) , was analyzed with segmented regression models , controlling for preintervention trends . RESULTS At baseline , nearly a third of patients had an interacting prescription . Coinciding with the alerts , there was an immediate and continued reduction in the warfarin-interacting medication prescription rate ( from 3294.0 to 2804.2 ) , result ing in a 14.9 % relative reduction ( 95 % confidence interval , -19.5 to -10.2 ) at 12 months . Group academic detailing did not enhance alert effectiveness . CONCLUSIONS This study , using a strong and quasi-experimental design in ambulatory care , found that medication interaction alerts modestly reduced the frequency of coprescribing of interacting medications . Additional efforts will be required to further reduce rates of inappropriate prescribing of warfarin with interacting drugs BACKGROUND We conducted a cluster r and omized controlled trial to examine the effectiveness of computerized decision support ( CDS ) design ed to improve hypertension care and outcomes in a racially diverse sample of primary care patients . METHODS We r and omized 2,027 adult patients receiving hypertension care in 14 primary care practice s to either 18 months of their physicians receiving CDS for each hypertensive patient or to usual care without computerized support for the control group . We assessed prescribing of guideline -recommended drug therapy and levels of blood pressure control for patients in each group and examined if the effects of the intervention differed by patients ’ race/ethnicity using interaction terms . MEASUREMENTS AND MAIN RESULTS Rates of blood pressure control were 42 % at baseline and 46 % at the outcome visit with no significant differences between groups . After adjustment for patients ’ demographic and clinical characteristics , number of prior visits , and levels of baseline blood pressure control , there were no differences between intervention groups in the odds of outcome blood pressure control . The use of CDS to providers significantly improved Joint National Committee ( JNC ) guideline adherent medication prescribing compared to usual care ( 7 % versus 5 % , P < 0.001 ) ; the effects of the intervention remained after multivariable adjustment ( odds ratio [ OR ] 1.39 [ CI , 1.13–1.72 ] ) and the effects of the intervention did not differ by patients ’ race and ethnicity . CONCLUSIONS CDS improved appropriate medication prescribing with no improvement in disparities in care and overall blood pressure control . Future work focusing on improvement of these interventions and the study of other practical interventions to reduce disparities in hypertension-related outcomes is needed BACKGROUND Errors involving medication use are common . Computerized physician order entry ( CPOE ) can improve prescribing practice s. Few studies have examined the effect of CPOE in combination with decision support tools on prescribing practice s in the outpatient setting . Less is known about prescribers ' adherence to laboratory monitoring recommendations . OBJECTIVE To evaluate if reminders presented during CPOE for medications would increase physicians ' compliance with guidelines for laboratory monitoring at initiation of therapy . STUDY DESIGN R and omized prospect i ve intervention study . METHODS Two hundred seven primary care physicians in a group-model managed care organization were r and omized to receive or not receive drug laboratory monitoring alerts within the CPOE system . Adherence to laboratory monitoring recommendations for patients prescribed selected medications was compared between physician groups . RESULTS There was no significant difference between the control and intervention group physicians in the overall rate of compliance with ordering the recommended laboratory monitoring for patients prescribed study medications . Laboratory monitoring was performed as recommended 56.6 % of the time in the intervention group compared with 57.1 % of the time in the control group ( P = .31 ) . In cases in which a statistically significant difference was demonstrated , improved compliance favored the intervention group ( eg , 71.2 % vs 62.3 % [ P = .003 ] for gemfibrozil and 75.7 % vs 73.9 % [ P = .05 ] for statins ) . CONCLUSIONS As CPOE becomes more prevalent , additional research is needed to determine effective decision support tools . These findings then should be communicated to the developers and users of computerized medical record systems OBJECTIVE Translation of evidence -based guidelines into clinical practice has been inconsistent . We performed a r and omized , controlled trial of guideline -based care suggestions delivered to physicians when writing orders on computer workstations . STUDY SETTING Inner-city academic general internal medicine practice . STUDY DESIGN R and omized , controlled trial of 246 physicians ( 25 percent faculty general internists , 75 percent internal medicine residents ) and 20 outpatient pharmacists . We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease . Care suggestions concerning drugs and monitoring were delivered to a r and om half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations . A 2 x 2 factorial r and omization of practice sessions and pharmacists result ed in four groups of patients : physician intervention , pharmacist intervention , both interventions , and controls . DATA EXTRACTION / COLLECTION METHODS : Adherence to the guidelines and clinical activity was assessed using patients ' electronic medical records . Health-related quality of life , medication adherence , and satisfaction with care were assessed using telephone question naires . PRINCIPAL FINDINGS During their year in the study , patients made an average of five scheduled primary care visits . There were no differences between groups in adherence to the care suggestions , generic or condition-specific quality of life , satisfaction with physicians or pharmacists , medication compliance , emergency department visits , or hospitalizations . Physicians receiving the intervention had significantly higher total health care costs . Physician attitudes toward guidelines were mixed . CONCLUSIONS Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease BACKGROUND The importance of laboratory monitoring for drugs is reflected in product labeling and published guidelines , but monitoring recommendations are followed inconsistently . Opportunity exists to improve monitoring , with the potential to decrease therapy complications . METHODS The objective of this r and omized trial was to determine whether computerized alerts were effective at increasing the percentage of ambulatory patients with laboratory monitoring at initiation of drug therapy . Physicians and pharmacists teamed up to develop organization-specific guidelines for monitoring selected drugs . In collaboration with physicians , pharmacists were alerted to missing laboratory test results , ordered missing tests , reminded patients to obtain tests , assessed test completion , review ed test results , and managed abnormal results . Eligible individuals included patients with therapy initiated for any of 15 drugs among 400,000 health plan members . RESULTS In the intervention group , 79.1 % ( n = 4076 ; 95 % confidence interval [ CI ] , 78.0%-80.2 % ) of dispensings were monitored compared with 70.2 % ( n = 3522 ; 95 % CI , 68.9%-71.5 % ) in the usual-care group ( P < .001 ) . For example , 78.6 % of amiodarone ( 95 % CI , 73.1%-83.5 % ) dispensing was monitored in the intervention group vs 51.4 % ( 95 % CI , 44.4%-58.4 % ) in the group receiving usual care ( P < .001 ) . CONCLUSIONS This study demonstrates the effectiveness of a computerized tool plus collaboration among health care professionals at increasing the percentage of patients receiving laboratory monitoring at initiation of therapy . Coupling data available from information systems with the knowledge and skills of physicians and pharmacists can result in improved patient monitoring BACKGROUND Preventive care is an important role for general practitioners , yet opportunities for prevention are often missed . METHOD We provided an automatic electronic record preventive care reminder system for 12 preventive care activities for one 10 doctor practice . All patients who attended were r and omised by the terminal digit of their record number . RESULTS The control uptake of opportunistic prevention was low ; ranging from 1.5 % ( tetanus immunisation ) to 27 % ( influenza immunisation ) . The reminders increased this by significant but small amounts for four out of 12 activities ( immunisation for tetanus and pneumococcus and recording of allergies and weight ) , insignificant increases for four ( mumps , measles and rubella immunisation , recording of smoking , and taking of cervical smears and of blood pressure ) , and insignificantly decreased influenza immunisation , and screening for diabetes and hyperlipidaemia . DISCUSSION Opportunistic electronic reminders have the potential to increase preventive care in general practice OBJECTIVE : The goal was to assess the impact of influenza vaccine clinical alerts on missed opportunities for vaccination and on overall influenza immunization rates for children and adolescents with asthma . METHODS : A prospect i ve , cluster-r and omized trial of 20 primary care sites was conducted between October 1 , 2006 , and March 31 , 2007 . At intervention sites , electronic health record-based clinical alerts for influenza vaccine appeared at all office visits for children between 5 and 19 years of age with asthma who were due for vaccine . The proportion of captured immunization opportunities at visits and overall rates of complete vaccination for patients at intervention and control sites were compared with those for the previous year , after st and ardization for relevant covariates . The study had > 80 % power to detect an 8 % difference in the change in rates between the study and baseline years at intervention versus control practice s. RESULTS : A total of 23 418 visits and 11 919 children were included in the study year and 21 422 visits and 10 667 children in the previous year . The majority of children were male , 5 to 9 years of age , and privately insured . With st and ardization for selected covariates , captured vaccination opportunities increased from 14.4 % to 18.6 % at intervention sites and from 12.7 % to 16.3 % at control sites , a 0.6 % greater improvement . St and ardized influenza vaccination rates improved 3.4 % more at intervention sites than at control sites . The 4 practice s with the greatest increases in rates ( ≥11 % ) were all in the intervention group . Vaccine receipt was more common among children who had been vaccinated previously , with increasing numbers of visits , with care early in the season , and at preventive versus acute care visits . CONCLUSIONS : Clinical alerts were associated with only modest improvements in influenza vaccination rates BACKGROUND Physician-directed approaches have not eliminated the underuse of effective preventive therapies . METHODS In a cluster-r and omized design , 19 physicians caring for 334 eligible patients at least 40 years of age were r and omized . All clinicians received computerized reminders at office visits . Intervention physicians received e-mails asking whether aspirin was indicated for each patient . If so , patients received a mailing and nurse telephone call addressing aspirin . The primary outcome was self-reported regular aspirin use . RESULTS Outcome assessment telephone interviews were completed for 242 ( 72.5 % ) patients . At follow-up , aspirin use was reported by 60 ( 46 % ) of the 130 intervention patients and 44 ( 39 % ) of the 112 reminder-only patients , a nonsignificant 7.2 % difference ( 95 % confidence interval : -3.9 to 18 percentage points , p = .20 ) . In the subgroup reporting no aspirin use at baseline and no contraindications , 33 ( 43 % ) of the 76 intervention and 22 ( 30 % ) of the 74 reminder-only patients used aspirin , a 10 % difference accounting for clustering ( 95 % CI : 2.2 to 18 percentage points , p = .013 ) . DISCUSSION A patient-directed intervention modestly increased aspirin use among diabetes patients beyond that achieved using computerized clinician reminders for ideal c and i date s. Obstacles included difficulty contacting patients , real or perceived contraindications , and failure to follow the nurse 's advice STUDY OBJECTIVE To assess the effects of evidence -based treatment suggestions for hypertension made to physicians and pharmacists using a comprehensive electronic medical record system . DESIGN R and omized controlled trial with a 2 x 2 factorial design of physician and pharmacist interventions , which result ed in four groups of patients : physician intervention only , pharmacist intervention only , intervention by physician and pharmacist , and intervention by neither physician nor pharmacist ( control ) . SETTING Academic primary care internal medicine practice . SUBJECTS Seven hundred twelve patients with uncomplicated hypertension . MEASUREMENTS AND MAIN RESULTS Suggestions were displayed to physicians on computer workstations used to write outpatient orders and to pharmacists when filling prescriptions . The primary end point was generic health-related quality of life . Secondary end points were symptom profile and side effects from antihypertensive drugs , number of emergency department visits and hospitalizations , blood pressure measurements , patient satisfaction with physicians and pharmacists , drug therapy compliance , and health care charges . In the control group , implementation of care changes in accordance with treatment suggestions was observed in 26 % of patients . In the intervention groups , compliance with suggestions was poor , with treatment suggestions implemented in 25 % of patients for whom suggestions were displayed only to pharmacists , 29 % of those for whom suggestions were displayed only to physicians , and 35 % of the group for whom both physicians and pharmacists received suggestions ( p=0.13 ) . Intergroup differences were neither statistically significant nor clinical ly relevant for generic health-related quality of life , symptom and side-effect profiles , number of emergency department visits and hospitalizations , blood pressure measurements , charges , or drug therapy compliance . CONCLUSION Computer-based intervention using a sophisticated electronic physician order-entry system failed to improve compliance with treatment suggestions or outcomes of patients with uncomplicated hypertension Despite evidence from r and omized trials and national guidelines that recommend the use of aspirin , β-blockers , and cholesterol-lowering agents for patients with coronary artery disease , many patients are not treated appropriately.1,2,3 Several types of fixed-message physician reminder systems — including checklists , chart tags , and computer-generated reminders — have improved physician compliance with cancer screening guidelines , 4 but it is less clear whether they are effective at improving disease management . We examined whether the combination of a computer-generated and written reminder system provided during patient visits could increase patient receipt of aspirin , β-blockers , and cholesterol-lowering agents Background . Adherence with antihypertensive and lipid-lowering therapy is poor , result ing in an almost 2-fold increase in hospitalization . Treatment side effects , cost , and complexity are common reasons for nonadherence , and physicians are often unaware of these potentially modifiable problems . Objective . To determine if a cardiovascular medication tracking and nonadherence alert system , incorporated into a computerized health record system , would increase drug profile review by primary care physicians , increase the likelihood of therapy change , and improve adherence with antihypertensive and lipid-lowering drugs . Methods . There were 2293 primary care patients prescribed lipid-lowering or antihypertensive drugs who were r and omized to the adherence tracking and alert system or active medication list alone to determine if the intervention increased drug profile review , changes in cardiovascular drug treatment , and refill adherence in the first 6 months . An intention to treat analysis was conducted using generalized estimating equations to account for clustering within physician . Results . Overall , medication adherence was below 80 % for 36.3 % of patients using lipid-lowering drugs and 40.8 % of patients using antihypertensives at the start of the trial . There was a significant increase in drug profile review in the intervention compared to the control group ( 44.5 % v. 35.5 % ; P < 0.001 ) , a nonsignificant increase in drug discontinuations due to side effects ( 2.3 % v. 2.0 % ; P = 0.61 ) , and a reduction in therapy increases ( 28.5 % v. 29.1 % ; P = 0.86 ) . There was no significant change in refill adherence after 6 months of follow-up . Conclusion . An adherence tracking and alert system increases drug review but not therapy changes or adherence in prevalent users of cardiovascular drug treatment . Targeting incident users where adverse treatment effects are more common and combining adherence tracking and alert tools with motivational interventions provided by multidisciplinary primary care teams may improve the effectiveness of the intervention Electronic decision-support tools may help to improve management of hyperlipidemia and other chronic diseases . This study examined the impact of lipid management tools integrated into an electronic medical record ( EMR ) in primary care practice s. This r and omized controlled trial was conducted in a national network of physicians who use an outpatient EMR . Adult primary care physicians were r and omized by office to receive an electronic form that was embedded in the EMR . The form contained prompts regarding suboptimal care based on Adult Treatment Panel-III ( ATP-III ) guidelines , as well as reporting tools to identify patients outside of office visits whose lipid management was suboptimal . All active patients , ages 20 - 79 years , whose physicians participated in the study , were categorized as high , moderate , or low cardiovascular risk , and the proportion who were tested for hyperlipidemia , at lipid goal , and on lipid-lowering medications if not at goal were measured according to ATP-III guidelines . A total of 105 physicians from 25 offices and 64,150 patients were included in the study . Outcomes improved for most measures from before to 1 year after the intervention ( November 1 , 2005 to October 31 , 2006 ) . However , after controlling for confounding variables and for clustering in multilevel modeling , only up-to- date lipid testing for high-risk patients was statistically better in the intervention group as compared to the control group ( adjusted odds ratio 15.0 , P < 0.05 ) . This study showed few differences in quality of lipid management after implementing an EMR-based disease management intervention in primary care setting s. Future studies may need to examine more comprehensive interventions that include office staff in a team approach to care BACKGROUND Less than 63 % of individuals with diabetes meet professional guidelines target of hemoglobin A1c < 7.0 % , and only 7 % meet combined glycemic , lipid , and blood pressure goals . The primary study aim was to assess the impact on A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools . Secondary aims examined health care provider ( HCP ) adherence to prescribing guidelines and assessed HCPs ' adoption of the technology . METHODS Thirty patients with type 2 diabetes were recruited from three community physician practice s for a 3-month study and evenly r and omized . The intervention group received cell phone-based software design ed by endocrinologists and CDEs ( WellDoc Communications , Inc. , Baltimore , MD ) . The software provided real-time feedback on patients ' blood glucose levels , displayed patients ' medication regimens , incorporated hypo- and hyperglycemia treatment algorithms , and requested additional data needed to evaluate diabetes management . Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms . The system sent computer-generated logbooks ( with suggested treatment plans ) to intervention patients ' HCPs . RESULTS The average decrease in A1c for intervention patients was 2.03 % , compared to 0.68 % ( P < 0.02 , one-tailed ) for control patients . Of the intervention patients , 84 % had medications titrated or changed by their HCP compared to controls ( 23 % , P = 0.002 ) . Intervention patients ' HCPs reported the system facilitated treatment decisions , provided organized data , and reduced logbook review time . CONCLUSIONS Adults with type 2 diabetes using WellDoc 's software achieved statistically significant improvements in A1c . HCP and patient satisfaction with the system was clinical ly and statistically significant e-Prescribing systems with decision support do not routinely communicate an adequate amount of information regarding the prescribers ' decision to pharmacists . To address this communication gap in the e-prescribing process , we implemented a system called Show Your Work ( SYW ) that appends alerts and override comments to e-prescriptions generated by an e-prescribing system . To assess the quantitative impact of this system , we conducted a r and omized , double-blinded , controlled study to assess pharmacy callback rates and types , and to uncover any unintended consequences of the annotations . Each day , SYW output across the enterprise was turned " on " or " off " r and omly for all e-prescriptions . A convenience sample of three pharmacies , blinded to SYW status , su bmi tted callback logs each day . These logs were used to calculate the rate of and reason for callbacks . At the conclusion of the study , we surveyed the 50 most frequently used pharmacies in our area to assess the impact of SYW on satisfaction and communication . A total of 202 callbacks had occurred yielding a callback rate of 45 callbacks/1000 prescriptions for SYW " on " days and 40 callbacks/1000 prescriptions for " off " days ( p=0.4 ) . We received 38 surveys ( 76 % response rate ) with 33 respondents commenting about SYW . Most respondents agreed ( 69 % ) that SYW favorably impacted callbacks -- especially with pediatric prescriptions ( 82 % ) . Comments suggested that SYW increased callbacks where necessary and decreased them in other situations , but did not contribute to unnecessary callbacks . These findings support the continued and potentially exp and ed use of SYW by e-prescribing systems to enhance communication with pharmacists BACKGROUND Vancomycin-resistant enterococci represent an increasingly important cause of nosocomial infections . Minimizing vancomycin use represents a key strategy in preventing the spread of these infections . OBJECTIVE To determine whether a structured ordering intervention using computerized physician order entry that requires use of a guideline could reduce intravenous vancomycin use . DESIGN R and omized controlled trial assessing frequency and duration of vancomycin therapy by physicians . PARTICIPANTS AND SETTING Three hundred ninety-six physicians and 1,798 patients in a tertiary-care teaching hospital . INTERVENTION Computer screen displaying , at the time of physician order entry , an adaptation of the Centers for Disease Control and Prevention guidelines for appropriate vancomycin use . MAIN OUTCOME MEASURES The frequency of initiation and renewal of vancomycin therapy as well the duration of therapy prescribed on a per prescriber basis . RESULTS Compared with the control group , intervention physicians wrote 32 percent fewer orders ( 11.3 versus 16.7 orders per physician ; P = 0.04 ) and had 28 percent fewer patients for whom they either initiated or renewed an order for vancomycin ( 7.4 versus 10.3 orders per physician ; P = 0.02 ) . In addition , the duration of vancomycin therapy attributable to physicians in the intervention group was 36 percent lower than the duration of therapy prescribed by control physicians ( 26.5 versus 41.2 days ; P = 0.05 ) . Analysis of pharmacy data confirmed a decrease in the overall hospital use of intravenous vancomycin during the study period . CONCLUSION Implementation of a computerized guideline using physician order entry decreased vancomycin use . Computerized guidelines represent a promising tool for changing prescribing practice |
10,556 | 21,764,820 | Neonatal outcomes ( Apgar score , acid-base status ) and clinical quality variables ( patient satisfaction , surgical conditions ) showed non-significant differences between LD and CD .
This meta- analysis demonstrates that low-dose bupivacaine in spinal anaesthesia compromises anaesthetic efficacy ( risk of analgesic supplementation : high grade of evidence ) , despite the benefit of lower maternal side-effects ( hypotension , nausea/vomiting : moderate grade of evidence ) | Spinal anaesthesia is the preferred anaesthetic technique for elective Caesarean deliveries .
Hypotension is the most common side-effect and has both maternal and neonatal consequences .
Different strategies have been attempted to prevent spinal-induced hypotension , including the use of low-dose bupivacaine . | Background : The ideal intrathecal isobaric bupivacaine dose for cesarean delivery anesthesia is uncertain . While small doses ( 5–9 mg ) of bupivacaine may reduce side effects such as hypotension , they potentially increase spinal anesthetic failures . This study determined the ED50 and ED95 of intrathecal isobaric bupivacaine ( with adjuvant opioids ) for cesarean delivery . Methods : After institutional review board approval and written informed consent were obtained , 48 parturients undergoing elective cesarean delivery under combined spinal – epidural anesthesia were enrolled in this double-blind , r and omized , dose-ranging study . Patients received a 5- , 6- , 7- , 8- , 9- , 10- , 11- , or 12-mg intrathecal isobaric bupivacaine dose with 10 & mgr;g fentanyl and 200 & mgr;g morphine . Overall anesthetic success was recorded when no intraoperative epidural supplement was required during the cesarean delivery . ED50 and ED95 values for overall anesthetic success were determined using a logistic regression model . Results : ED50 and ED95 values for overall anesthetic success were 7.25 and 13.0 mg , respectively . No advantages for low doses could be demonstrated with regard to hypotension , nausea , vomiting , pruritus , or maternal satisfaction , although this study was underpowered to detect significant differences in secondary outcome variables . Conclusions : The ED50 and ED95 values ( 7.25 and 13.0 mg , respectively ) for intrathecal isobaric bupivacaine in this circumstance are similar to values the authors determined recently for hyperbaric bupivacaine using similar methodology . These ED50 and ED95 values are significantly higher than those advocated in previous reports in which success was cl aim ed using lower intrathecal bupivacaine doses . The current study used stricter criteria to define “ successful ” anesthesia and support the use of larger bupivacaine doses to ensure adequate patient comfort Amethocaine 1 % solution was mixed with equal volumes of water , 0.9 % saline or 10 % dextrose to prepare respectively , hypobaric , isobaric and hyperbaric solutions which were compared for intradural spinal anaesthesia in 60 patients . Thirty patients received 10 mg and 30 patients received 15 mg of amethocaine . Injections were made with the patients in the lateral recumbent position and the operating table was horizontal during and after injection . Equal numbers of patients and equal numbers of males and females received hypobaric , isobaric and hyperbaric solutions . The mean spread of analgesia after the hyperbaric solution was five dermatomes greater than after the other two solutions , but the extent of analgesia was not significantly different whether amethocaine 10 mg or 15 mg was injected . The mean duration of analgesia after the hyperbaric solution was 285 min compared with 332 min and 360 min after the isobaric and hypobaric solutions respectively . The mean duration of analgesia after amethocaine 15 mg was significantly greater than after 10 mg The safety of 0.5 % hyperbaric bupivacaine , as well as the incidence and severity of visceral pain , were evaluated in 36 women undergoing elective cesarean section under spinal anesthesia who , r and omly divided into two groups , received different dose ranges according to height , 7.5–10 mg in group A and 10–12.5 mg in group B. When sensory block to at least the fourth thoracic dermatome was established , surgery was begun and the occurrence and severity of visceral pain recorded ( visual analog scale ) by an observer unaware of patient data . The level of analgesia to pinprick was determined when and if there was onset of pain intraoperatively , and supplementary medication was administered as needed . Hypotension , the incidence of which was similar in both groups , was treated as necessary with ephedrine . No patients experienced pain until after delivery of the infant . Thereafter , moderate to severe pain , in association with peritoneal traction , occurred in 12 patients in group A ( 70.5 % ) but only in 6 patients in group B ( 31.6 % ) . In patients experiencing moderate to severe pain , the mean time between induction of anesthesia and onset of pain was similar in both groups , as was the amount of systemic narcotic given . Total time for regression of sensory analgesia to L5 was longer in patients in group B ( 243.9 versus 195.4 min ) , and the incidence of complete motor blockade was greater in group B. Increasing the amount of 0.5 % hyperbaric bupivacaine per spinal segment reduces the occurrence of moderate to severe visceral pain during elective cesarean section without jeopardizing mother or fetus Background Maternal hypotension occurs in 60–94 % of Cesarean deliveries with 10–15 mg spinal bupivacaine . Reduced doses of bupivacaine may decrease the incidence of hypotension , nausea , and vasopressor use . The primary objective of this study was to compare 4.5 mg and 12 mg doses of intrathecal bupivacaine on maternal hemodynamics . The secondary objective was to determine if anticipated reductions in side effects were reflected in increased patient satisfaction . Methods Following Research Ethics Board approval and informed consent 52 term parturients undergoing elective Cesarean delivery were r and omly assigned to isobaric bupivacaine 4.5 mg or hyperbaric bupivacaine 12 mg for spinal anesthesia . All patients received fentanyl 50 μg and morphine 200 μg intrathecally . Intravenous fluid and vasopressor administration were st and ardized . Maternal hemodynamics , and sensorimotor levels were recorded at regular intervals . Side effects and patient satisfaction were documented . Results Median cepahalad sensory block was C8 in both groups ( NS ) but the intensity of motor block was significantly less ( P < 0.001 ) and of shorter duration ( P < 0.001 ) with bupivacaine 4.5 mg . The proportion of patients requiring ephedrine ( > 70 % ) and the quantities of ephedrine used were similar in both groups ( NS ) . Use of supplemental analgesia , side effects , and measures of patient satisfaction were comparable in both groups . Discussion Intrathecal bupivacaine 4.5 and 12 mg yielded similar sensory block and side effects during Cesarean delivery . Patients receiving 4.5 mg did , however , experience significantly less motor blockade of shorter duration . Context eL’hypotension maternelle se rencontre dans 60’94 % des accouchements par césarienne avec 10’15 mg de bupivacaïne intrathécale . Des doses réduites de bupivacaïne pourraient réduire l’incidence d’hypotension et de nausées , ainsi que l’utilisation de vasopresseurs . L’objectif premier de cette étude était de comparer l’effet de doses intrathécales de bupivacaïne de 4,5 mg et 12 mg respectivement sur l’hémodynamie maternelle . Le deuxième objectif était de déterminer si les réductions anticipées d’effets secondaires se reflétaient par une satisfaction accrue des patientes . MéthodeLe Comité d’éthique de la recherche ayant donné son accord , cinquante-deux parturientes à terme devant subir un accouchement non urgent par césarienne ont été r and omisées en deux groupes pour la rachianesthésie : bupivacaïne isobare 4,5 mg ou bupivacaïne hyperbare 12 mg . Toutes les patientes ont reçu du fentanyl 50 μg et de la morphine 200 μg en intrathécal . L’administration de liquide intraveineux et de vasopresseurs a été st and ardisée . L’hémodynamie maternelle ainsi que les niveaux sensori-moteurs ont été enregistrés à intervalles réguliers . Les effets secondaires et la satisfaction des patientes ont été documentés . RésultatsLe bloc sensitif moyen en direction de la tête était situé à C8 dans les deux groupes ( NS ) , mais l’intensité du bloc moteur était significativement plus faible ( P < 0,001 ) et d’une durée moindre ( P < 0,001 ) avec la bupivacaïne 4,5 mg . La proportion de patientes nécessitant de l’éphédrine ( > 70 % ) et les quantités d’éphédrine administrées étaient similaires dans les deux groupes ( NS ) . L’utilisation d’analgésie supplémentaire , les effets secondaires et la satisfaction des patientes étaient comparables dans les deux groupes . Discussion Dans le cas d’accouchements par césarienne , les doses de 4,5 mget 12 mg de bupivacaïne intrathécale produisent un bloc sensitif et des effets secondaires similaires . Toutefois , les patientes ayant reçu 4,5 mg ont ressenti un bloc moteur plus faible et plus court , et cette différence était significative BACKGROUND Hypotension after spinal anesthesia for cesarean section is common and may result in serious complications despite the use of uterine displacement and volume preloading . Adequate amount of hyperbaric bupivacaine for Japanese parturients whose frames are generally smaller than those of Caucasian counterparts have not yet been examined . We compared the analgesic efficacy and the incidence of hypotension with 8 mg versus 10 mg hyperbaric bupivacaine during spinal anesthesia for cesarean section in Japanese parturients . METHODS Thirty six parturients were r and omly divided into two groups , one receiving 8 mg ( n = 19 ) and the other receiving 10 mg ( n = 17 ) hyperbaric bupivacaine . Sensory block level and the incidence of hypotension were evaluated from the time of injection to delivery . Hypotension was defined as a decrease in systolic blood pressure below 100 mmHg and to less than 80 % of the baseline value . RESULTS 15 minutes after spinal injection , the difference in sensory block level was not significant . Ten minutes after the spinal anesthesia , in 79 % of 8 mg group and in 88 % of 10 mg group , sensory block level reached T 4 . Hypotension occurred in 19 parturients ( 7 in 8 mg group and 12 in 10 mg group ) . The incidence of hypotension was significantly lower in 8 mg group ( 37 % ) than in 10 mg group ( 71 % ) . There were no significant differences either in neonatal Apgar scores or umbilical blood gas pH. CONCLUSIONS Injection of 8 mg hyperbaric bupivacaine is preferable than 10 mg in spinal anesthesia for cesarean section to obtain adequate analgesic efficacy and to avoid maternal hypotension INTRODUCTION Spinal anesthesia is the technique most often applied in cases of scheduled cesarean section . Many authors have tried decreasing the local anesthetic dose by adding opioids to achieve adequate analgesia with greater hemodynamic stability , although the ideal dose remains to be established . Our aim was to analyze hemodynamic stability and quality of analgesia with 2 different regimens for administering spinal hyperbaric bupivacaine . METHODS We design ed a controlled , double-blind trial comparing 2 doses of spinal hyperbaric bupivacaine with fentanyl in 42 patients undergoing elective cesarean section r and omized to 2 groups to receive either the low dose or the conventional one . One group received an 11 mg dose of bupivacaine and the other group received a 6.5 mg dose , combined with 20 microg of fentanyl in both cases . RESULTS The hemodynamic profile and the level of maximum sensory block obtained were similar in the two groups . The motor block was less intense in patients receiving the lower dose and it was necessary to convert 2 patients ( 10 % ) to general anesthesia in that group . CONCLUSIONS Spinal anesthesia with low doses of bupivacaine and fentanyl provides acceptable intraoperative conditions for a high percentage of patients undergoing cesarean section , with a similar incidence of hypotension . The low dose generates a less intense intraoperative motor blockade with similar spread of the sensory block . The low dose was not efficacious for 10 % of the patients who received it Purpose Spinal anesthesia for cesarean section is associated with a high incidence of maternal hypotension . The aim of this study was to assess the efficacy of low-dose bupivacaine with fentanyl to reduce the incidence of hypotension in spinal anesthesia for cesarean section . Methods Forty pregnant women undergoing elective cesarean section were r and omly allocated to two groups ; those receiving 10 mg bupivacaine to group B ( n = 20 ) and those receiving 4 mg bupivacaine plus 25 μg fentanyl to group BF ( n = 20 ) ; the agents were given intrathecally with patients in the sitting position , with a combined spinal-epidural technique . Results Sensory block was adequate for surgery in all patients . Hypotension occurred in all patients in group B ( 100 % ) and in 15 patients in group BF ( 75 % ) . The incidence of hypotension , number of ephedrine treatments , and need for ephedrine were significantly greater in group B than group BF . Three patients in group BF required i.v . fentanyl supplementation after delivery . In 1 of these patients , i.v . fentanyl was not adequate , and epidural supplementation of 1 % lidocaine was required . Conclusion The development of hypotension after spinal block in subjects undergoing cesarean section was not prevented despite low-dose ( 4 mg ) bupivacaine plus 25 μg fentanyl , but the severity of maternal hypotension , and the number of ephedrine treatments and the total dose of ephedrine were decreased UNLABELLED A variety of methods have been used to quantify aspects of recovery after anesthesia . Most are narrowly focused , are not patient-rated , and have not been vali date d. We therefore set out to develop a patient-rated quality of recovery score . We constructed a 61-item question naire that asked individuals ( patients and relatives , medical and nursing staff ; total n = 136 ) to rate various postoperative items describing features a patient may experience postoperatively . The most highly ranked items were included in a final nine-point index score , which we called the " QoR Score . " We then studied two cohorts of surgical patients ( n = 449 ) . There was good convergent validity between the QoR Score and the visual analog scale score ( rho = 0.55 , P < 0.0001 ) . Discriminant construct validity was supported by comparing result ant QoR Scores in patients undergoing day-stay , minor , and major surgery ( P = 0.008 ) , as well as a negative correlation with duration of hospital stay ( rho = -0.20 , P < 0.0001 ) , and , using multivariate regression , demonstrating a significant negative relationship between QoR Score and female gender ( P = 0.048 ) and older age ( P = 0.041 ) . There was also good interrater agreement ( rho = 0.55 , P < 0.0001 ) , test-retest reliability ( median rho = 0.61 , P < 0.0001 ) , and internal consistency ( alpha = 0.57 and 0.90 , P < 0.0001 ) . There was a significant difference between the groups of patients recovering from major and minor surgery ( P < 0.001 ) . This study demonstrates that the QoR Score has good validity , reliability , and clinical acceptability in patients undergoing many types of surgery . IMPLICATION S We set out to develop a patient-rated quality of recovery score ( QoR ) that could be used both as a measure of outcome in perioperative trials and for clinical audit . We first surveyed patients and staff to identify important aspects of recovery , then developed a nine-point QoR Score . This was then compared with other measures of postoperative outcome . We found that the QoR Score is a useful measure of recovery after anesthesia and surgery In a r and omized study , the incidence of visceral pain was evaluated in 46 patients undergoing elective caesarean section under spinal or epidural anaesthesia with 0.5 % bupivacaine . If the patient experienced pain during the operation , a st and ard visual analogue scale ranging from 0 to 10 was used to assess the degree of pain . Visceral pain occurred in 12/23 patients in the spinal group and in 13/23 patients in the epidural group . In neither group was a correlation found between the cephalad level of analgesia or the intensity of cutaneous analgesia in the sacral region , and the presence of visceral pain Background and Objectives : The hypotension following spinal anesthesia remains commonplace in cesarean delivery . Intrathecal opioids are synergistic with local anesthetics and intensify sensory block without increasing sympathetic block . The combination makes it possible to achieve spinal anesthesia with otherwise inadequate doses of local anesthetic . We hypothesized that this phenomenon could be used to provide spinal anesthesia for cesarean delivery while incurring less frequent hypotension . Methods : Thirty‐two women scheduled for cesarean delivery were divided into 2 groups of patients who received a spinal injection of either 10 mg of isobaric ( plain ) bupivacaine 0.5 % or 5 mg of isobaric bupivacaine with 25 μg fentanyl added . Each measurement of a systolic blood pressure less than 95 mm Hg or a decrease in systolic pressure of greater than 25 % from baseline was considered as hypotension and treated with a bolus of 5 to 10 mg of intravenous ephedrine . Results : Spinal block provided surgical anesthesia in all patients . Peak sensory level was higher ( T3 v T4.5 ) and motor block more intense in the plain bupivacaine group . The plain bupivacaine patients were more likely to require treatment for hypotension ( 94 % v 31 % ) and had more persistent hypotension ( 4.8 v 0.6 hypotensive measurements per patient ) than patients in the minidose bupivacaine‐fentanyl group . Mean ephedrine requirements were 23.8 mg and 2.8 mg , respectively , for the 2 groups . Patients in the plain bupivacaine group also complained of nausea more frequently than patients in the minidose bupivacaine‐fentanyl group ( 69 % v 31 % ) . Conclusions : Bupivacaine 5 mg + fentanyl 25 μg provided spinal anesthesia for cesarean delivery with less hypotension , vasopressor requirements , and nausea than spinal anesthesia with 10 mg bupivacaine BACKGROUND Spinal anaesthesia for caesarean section exposes to high incidence of arterial hypotension which can result in maternal and neonatal morbidity . We hypothesized that the reduction of this dose from 10 mg to 7.5 mg would minimize hypotension without altering pain relief . METHODS In this double-blind prospect i ve study , 80 ASA1 women scheduled for elective caesarean section were r and omized into two groups A and B receiving respectively 10 and 7.5 mg of isobaric bupivacaine both with 25 microg of fentanyl and 100 microg of morphine in spinal anaesthesia . Intravenous ephedrine was administered for each episode of hypotension . We recorded sensory and motor block , intraoperative pain , nausea and vomiting . In postanaesthesia care unit , sensory and motor recoveries were measured and maternal satisfaction rate was assessed . RESULTS In group A , a larger dose of ephedrine was needed ( 32 + /- 23 vs 19 + /- 16 mg ; p = 0.004 ) . Incidence of sensory block above T4 ( 52 vs 10 % ; p < 0.001 ) , nausea ( 52 vs 22 % ; p = 0.005 ) and vomiting ( 25 vs 8 % ; p = 0.03 ) were all higher than in group B. Arterial hypotension was less frequent in group B ( 68 vs 88 % ; p = 0.03 ) . The time required for recovery to T10 sensory level and motor regression were shorter than in group A ( p < 0.001 ) and the satisfaction rate was higher than in group A ( excellent and good in 90 % vs 67 % ; p = 0.03 ) . There was no difference in pain relief . CONCLUSION A dose of 7.5 mg of isobaric bupivacaine reduced incidence of hypotension , nausea and vomiting and improved patient satisfaction Background and Objectives : Visceral pain decreases in cesarean patients under spinal anesthesia when the dose of local anesthetic is increased . However , larger doses of local anesthetic are associated with higher sensory blocks . We hypothesized that the addition of fentanyl could reduce the dose of bupivacaine necessary to achieve adequate surgical anesthesia . Methods : Two double‐blinded , sequential , prospect i ve studies were performed on 120 patients . In the preliminary study , the patients received 8 , 10 , or 12 mg of 0.5 % hyperbaric bupivacaine intrathecally . In the second , main study , they received each bupivacaine dose with 10 μg of fentanyl . Each group consisted of 20 patients , and the groups were identified as B8 , B10 , B12 , BF8 , BF10 , and BF12 . Sensory and motor block , intraoperative pain defined by visual analogue scale ( VAS ) , muscle relaxation , and side effects were assessed . We also measured the sensory and motor recovery and the onset of pain in the postanesthesia care unit ( PACU ) . Results : Maximal block level and incidence of high block ( ≥T1 ) were higher in the 12‐mg groups . There was intraoperative pain in 35 % of the B8 patients and 20 % of the B10 patients , but none in the B12 patients and all fentanyl groups . Incidences of other side effects were not different . The addition of fentanyl to bupivacaine significantly delayed the onset of postoperative pain and sensory recovery , but motor recovery time did not change with additional fentanyl . Conclusions : The optimal dose of hyperbaric bupivacaine to produce surgical anesthesia was 12 mg , which was accompanied by high sensory block . With the addition of 10 μg of fentanyl , the dose of bupivacaine could be reduced to 8 mg in spinal anesthesia for cesarean delivery We conducted a double-blind comparison of three doses ( 7.5 mg , 8.75 mg and 10 mg ) of 0.5 % hyperbaric bupivacaine in women undergoing elective caesarean under spinal anaesthesia . Sixty women were r and omised into 3 groups of 20 . Group A received 7.5 mg , group B 8.75 mg and C 10 mg of study drug . The time to maximum sensory blockade did not differ among the groups ( P > 0.05 ) . Mean time to start of regression of sensory block was greater in group C than in groups A and B ( P < 0.001 and P < 0.05 respectively ) . Time required for complete regression of sensory block was longer in group C than in groups A and B ( P < 0.001 ) . Duration of motor block was greater in group C than in groups A and B ( P < 0.001 and < 0.05 respectively ) . Neonatal outcome was good in all the groups . None of the patients in any group experienced pain before delivery . After delivery of the baby , however , group C women had a lower incidence of visceral pain than did groups A and B ( P < 0.05 ) . The incidence of hypotension was greater in groups B and C than in group A ( P < 0.05 ) . Group C women had a greater incidence of bradycardia than did groups A and B ( P < 0.05 ) . The 7.5-mg dose of 0.5 % hyperbaric bupivacaine was observed to provide acceptable analgesia without any significant incidence of adverse effects such as maternal hypotension or bradycardia This prospect i ve study recorded levels of analgesia ( loss of sharp pin prick sensation ) and anaesthesia ( loss of touch sensation ) in 220 women during caesarean section under regional anaesthesia ( 70 epidurals , 150 spinals ) . At delivery the difference between analgesia and anaesthesia varied from 0 - 7 segments for epidurals and 0 - 9 segments for spinals . During surgery the level of anaesthesia at the time pain was experienced varied between T5 and T10 . No patient with a level of anaesthesia which remained above T5 experienced pain . These results indicate that assessing the adequacy of block by sharp pin prick may be misleading and that in the absence of spinal or epidural narcotics a level of anaesthesia up to and including T5 is required to prevent pain during caesarean section Background Successful cesarean delivery anesthesia has been reported with use of small doses ( 5–9 mg ) of intrathecal bupivacaine coadministered with opioids . This double-blind , r and omized , dose-ranging study determined the ED50 and ED95 of intrathecal bupivacaine ( with adjuvant opioids ) for cesarean delivery anesthesia . Methods Forty-two parturients undergoing elective cesarean delivery with use of combined spinal – epidural anesthesia received intrathecal hyperbaric bupivacaine in doses of 6 , 7 , 8 , 9 , 10 , 11 , or 12 mg in equal volumes with an added 10 & mgr;g intrathecal fentanyl and 200 & mgr;g intrathecal morphine . Sensory levels ( pinprick ) were evaluated every 2 min until a T6 level was achieved . The dose was a success(induction ) if a bilateral T6 block occurred in 10 min ; otherwise , it was a failure(induction ) . In addition to being a success(induction ) , the dose was a success(operation ) if no intraoperative epidural supplement was required ; otherwise , it was a failure(operation ) . ED50 and ED95 for both success(induction ) and success(operation ) were determined with use of a logistic regression model . Results ED50 for success(induction ) and success(operation ) were 6.7 and 7.6 mg , respectively , whereas the ED95 for success(induction ) and success(operation ) were 11.0 and 11.2 mg . Speed of onset correlated inversely with dose . Although no clear advantage for low doses could be demonstrated ( hypotension , nausea , vomiting , pruritus , or maternal satisfaction ) , this study was underpowered to detect significance in these variables . Conclusions The ED95 of intrathecal bupivacaine under the conditions of this study is considerably in excess of the low doses proposed for cesarean delivery in some recent publications . When doses of intrathecal bupivacaine less than the ED95 , particularly near the ED50 , are used , the doses should be administered as part of a catheter-based technique |
10,557 | 29,100,718 | The results show that intervention programs are effective to reduce the feeling of loneliness . | Loneliness is a problem that affects a very high percentage of older people , and can lead to physical and /or mental illness .
This article aims to present a systematic review of programs to combat loneliness directed towards the institutionalised elderly . | Loneliness is a prevalent and global problem for adult population s and has been linked to multiple chronic conditions in quantitative studies . This paper presents a systematic review of quantitative studies that examined the links between loneliness and common chronic conditions including : heart disease , hypertension , stroke , lung disease , and metabolic disorders . A comprehensive literature search process guided by the PRISMA statement led to the inclusion of 33 articles that measure loneliness in chronic illness population s. Loneliness is a significant biopsychosocial stressor that is prevalent in adults with heart disease , hypertension , stroke , and lung disease . The relationships among loneliness , obesity , and metabolic disorders are understudied but current research indicates that loneliness is associated with obesity and with psychological stress in obese persons . Limited interventions have demonstrated long-term effectiveness for reducing loneliness in adults with these same chronic conditions . Future longitudinal r and omized trials that enhance knowledge of how diminishing loneliness can lead to improved health outcomes in persons with common chronic conditions would continue to build evidence to support the translation of findings to recommendations for clinical care BACKGROUND Animal-assisted therapy ( AAT ) is cl aim ed to have a variety of benefits , but almost all published results are anecdotal . We characterized the resident population in long-term care facilities desiring AAT and determined whether AAT can objective ly improve loneliness . METHODS Of 62 residents , 45 met inclusion criteria for the study . These 45 residents were administered the Demographic and Pet History Question naire ( DPHQ ) and Version 3 of the UCLA Loneliness Scale ( UCLA-LS ) . They were then r and omized into three groups ( no AAT ; AAT once/week ; AAT three times/week ; n = 15/group ) and retested with the UCLA-LS near the end of the 6-week study . RESULTS Use of the DPHQ showed residents volunteering for the study had a strong life-history of emotional intimacy with pets and wished that they currently had a pet . AAT was shown by analysis of covariance followed by pairwise comparison to have significantly reduced loneliness scores in comparison with the no AAT group . CONCLUSIONS The desire for AAT strongly correlates with previous pet ownership . AAT reduces loneliness in residents of long-term care facilities This study examined the effects of indoor gardening on socialization , activities of daily living ( ADLs ) , and perceptions of loneliness in elderly nursing home residents . A total of 66 residents from two nursing homes participated in this two-phase study . In phase one , experimental group 1 participated once a week for 5 weeks in gardening activities while a control group received a 20-minute visit . While no significant differences were found between groups in socialization or perceptions of loneliness , there were significant pretest-posttest differences within groups on loneliness and guidance , reassurance of worth , social integration , and reliable alliance . The results also demonstrated gardening interventions had a significant effect on three ADLs ( transfer , eating , and toileting ) . Phase two examined differences in the effects of a 5-week versus a 2-week intervention program . Although no significant within-group differences were noted in socialization , loneliness , or ADLs , the 5-week program was more effective in increasing socialization and physical functioning OBJECTIVE The objective of this study was to examine the associations between objective and subjective social support and suicidal ideation in older adults receiving home healthcare services . METHOD Participants were r and omly selected from a sample of older adults newly starting skilled nursing care from a certified home health agency in Westchester County , NY . Research interviewers assessed 522 older adults aged 65 years and older who were receiving home care services . Subjective and objective components of social support were assessed using measures of social network , social interaction patterns , instrumental support , and perceptions of social support . Suicidal ideation was assessed using items from the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition and the Hamilton Depression Rating Scale . RESULTS In bivariate analyses , neither objective ly determined size of social network nor instrumental support was associated with suicidal ideation . However , lower social interaction patterns and lower perceived social support were significantly related to suicidal ideation . After adjusting for potential confounders , only lower perceived support remained significantly associated with suicidal ideation . In post hoc analyses of the perceptions of social support scale items , satisfaction with one 's relationships and feeling useful to family and friends were significantly associated with a lower likelihood of suicidal ideation in the final multivariate logistic regression model controlling for possible confounding variables . CONCLUSIONS Subjective social support is a potentially modifiable risk factor for suicide in later life . Findings suggest that the perception of social support is an important construct to examine in future longitudinal studies examining risk and protective factors for suicidal ideation and behaviors in older adults Pain is common in the aging population , particularly among older residents of nursing homes . It has been found that 50 % of older people living in the community have been experiencing chronic pain , and the number increased to 80 % for older residents of nursing homes . Exercise is an effective non-pharmacological intervention that can reduce pain and improve physical and psychological functions . A quasi-experimental study with a pretest-posttest control group design ed was conducted to evaluate the effects of a physical exercise program ( PEP ) on older residents of nursing homes who have chronic pain . Three-hundred-ninety-six older residents with chronic pain were recruited from 10 nursing homes run by non-governmental organizations in Hong Kong . The average age of the older residents was 85.44 ± 6.29 . Five nursing homes were r and omized to the experimental group with PEP ( n = 225 , age = 85.45 ± 6.25 ) ; the other five nursing homes were r and omized to the control group without the PEP ( n = 171 , age = 85.44 ± 6.35 ) . PEP was an eight-week training program given by a physiotherapist and nurses once a week . It consisted of warm-up exercises , muscle strengthening , stretching , balancing , and self-administered massage to acupressure points . At the end of each PEP session , pamphlets with pictures illustrating the " exercise of the day " were given to the older residents of nursing homes as a tool to enhance their self-management skills . The control group received no training during the eight weeks . Upon completion of the PEP , the experimental group experienced a significantly greater reduction in pain intensity from 4.19 ± 2.25 ( on an 11 point scale ) to 2.67 ± 2.08 , as compared to the control group ( p < .05 ) . In addition , the psychological well-being ( happiness , loneliness , life satisfaction , and depression ) of the experimental group was significantly improved ( p < .05 ) |
10,558 | 23,446,674 | In conclusion , skeletonized ITA appears to reduce the incidence of postoperative SWI in comparison with pedicled ITA after CABG , with this effect being modulated by the presence of diabetes | It is suggested that the internal thoracic artery ( ITA ) harvesting technique influences the incidence of sternal wound infection ( SWI ) after coronary artery bypass graft ( CABG ) .
To determine if there is any real difference between skeletonized vs pedicled ITA , we performed a meta- analysis to determine if there is any real difference between these two established techniques in terms of SWI . | Background — Observational studies suggest that skeletonization of the internal thoracic artery ( ITA ) can improve conduit flow and length and reduce deep sternal infections and postoperative pain . We performed a r and omized , double-blind , within-patient comparison of skeletonized and nonskeletonized ITAs in patients undergoing coronary surgery . Methods and Results — Patients ( n=48 ) undergoing bilateral ITA harvest were r and omized to receive 1 skeletonized and 1 nonskeletonized ITA . Intraoperatively , ITA flow was assessed directly and with a Doppler flow probe before and after topical application of papaverine . ITA harvest time and conduit length were recorded . A blinded assessment of pain ( visual analog scale ) and dysesthesia ( physical examination ) was performed at discharge , at 2 weeks , and at a 3-month follow-up . Sternal perfusion was assessed with nuclear imaging ( n=7 ) . Skeletonization required longer ITA harvest times ( 27±1 versus 24±1 minutes ; P=0.04 ) . There was a trend toward increased ITA length in the skeletonized group ( 18.2±0.3 versus 17.7±0.3 cm ; P=0.09 ) . In situ ITA flow was lower in skeletonized arteries ( 7.4±0.9 versus 10.1±1.0 mL/min ; P=0.01 ) and increased significantly after ITA division and papaverine application . Postanastomotic flows were similar between groups . Skeletonization was associated with decreased pain at the 3-month follow-up and a reduction in major sensory deficits at the 4-week and 3-month ( 17 % versus 50 % ; P=0.002 ) follow-ups . Baseline adjusted sternal perfusion was significantly greater by 17±6 % ( P=0.03 ) on the skeletonized side . Conclusions — Skeletonization results in reduced postoperative pain and dysesthesia and increased sternal perfusion at follow-up but does not produce increased conduit flow . ITA skeletonization may be a strategy for reducing morbidity after CABG OBJECTIVE Deep sternal wound infection is a dreaded complication of coronary artery bypass surgery , particularly in patients with diabetes . This study determines whether skeletonization of internal thoracic artery conduits compared with pedicled harvesting reduces the risk of deep sternal wound infection in patients with diabetes undergoing bilateral internal thoracic artery grafting . METHODS We review ed prospect ively gathered data on all patients who have undergone coronary artery bypass grafting and received bilateral internal thoracic artery grafts at our institution since 1990 . We compared patients with diabetes who received skeletonized ( n = 79 ) versus conventional pedicled ( n = 36 ) internal thoracic artery conduits . RESULTS The proportion of patients taking insulin ( 19.0 % vs 14.0 % for skeletonized vs conventional grafts , respectively , P = .6 ) or oral hypoglycemic agents ( 68.4 % vs 69.4 % , P = .9 ) , as well as the prevalence of type I diabetes ( 2.5 % vs 8.3 % , P = .18 ) , were similar in both groups . Patients who received skeletonized grafts were more likely to receive a free rather than an in situ right internal thoracic artery graft ( 93.7 % vs 30.6 % , P < .001 ) . The prevalence of deep sternal wound infection was significantly lower in patients who received skeletonized grafts compared with patients who received conventional grafts ( 1.3 % vs 11.1 % , P = .03 ) . Patients in the skeletonized group were also less likely to develop any ( superficial or deep ) sternal wound infection postoperatively ( 5.1 % vs 22.2 % , P = .03 ) . There was no significant difference in the prevalence of deep sternal wound infection between patients with diabetes who received skeletonized internal thoracic arteries and patients without diabetes who underwent conventional internal thoracic artery grafting ( n = 578 ) ( 1.2 % vs 1.6 % , respectively , P = .8 ) . CONCLUSIONS Skeletonization of internal thoracic artery conduits lowers the risk of deep sternal wound infection in patients with diabetes undergoing bilateral internal thoracic artery grafting . We no longer consider diabetes a contraindication to bilateral internal thoracic artery grafting , provided the internal thoracic arteries are skeletonized BACKGROUND The skeletonization of internal thoracic artery is postulated to improve graft length , early blood flow , sternal blood supply , and postoperative respiratory function . Concern exists that skeletonization may injure internal thoracic artery , precluding good results of surgery . Reports on endothelial function of skeletonized internal thoracic artery are lacking . METHODS A prospect i ve assessment of early clinical outcomes of 357 consecutive patients undergoing coronary artery bypass grafting was performed : 287 patients with nonskeletonized and 70 with skeletonized left internal thoracic artery ( LITA ) . The lengths of LITA and of its discarded distal segment , as well as free LITA blood flow , were measured . The dose-effect relationship for relaxation to acetylcholine was studied in the organ bath . RESULTS Apart from a higher incidence of breaching the pleura with nonskeletonized LITA the clinical outcomes were comparable . The length of skeletonized LITA was 17.8+/-1.14 cm versus 20.3+/-0.52 cm skeletonized ( p = 0.11 ) . The length of discarded LITA was shorter in nonskeletonized artery ( 0.8+/-0.28 cm versus 2.6+/-0.49 cm ; p = 0.022 ) . The free LITA blood flow was 66.3+/-7.42 mL/min in nonskeletonized vessel versus 100.3+/-14.84 mL/min in skeletonized ( p = 0.048 ) . The acetylcholine-induced relaxation was similar in both groups ( maximal relaxation , 80.7%+/-5.95 % in nonskeletonized versus 72.9%+/-9.11 % in skeletonized ; not significant ; negative logarithm of half-maximal effect , 7.43+/-0.18 versus 7.1+/-0.10 , respectively ; p = 0.063 ) . CONCLUSIONS Skeletonization does not damage the endothelial function of the LITA . Higher free blood flow and available LITA length should encourage the use of skeletonized LITA in clinical practice To minimize sternal ischemia , skeletonized internal mammary artery ( IMA ) harvesting has been performed in the last few years . The benefits of skeletonization in high risk patients , such as diabetic patients undergoing bilateral IMA grafting , are unknown . A total of 99 patients underwent isolated coronary artery bypass grafting ( CABG ) using a pedicled bilateral IMA between 6/1/1997 and 5/31/2000 ( group P ) , and 115 patients receiving a skeletonized IMA between 6/1/2001 and 3/31/2002 ( group S ) . An ultrasonic scalpel was used for skeletonization . The perioperative and early angiographic results of CABG using these two techniques were collected prospect ively and compared . There were two ( 1.7 % ) perioperative myocardial infa rct ions in group S and one ( 1.0 % ) in group P ( P = NS ) , none of which were related to the IMA graft . The incidence of mediastinitis was one ( 0.9 % ) in group S and three ( 3.0 % ) in group P , P = NS , however , minor chest wound complications were observed in four ( 3.5 % ) in group S , which was significantly less frequent than the 12 ( 12.1 % ) in group P ( P<0.05 ) . Angiographic control was obtained in 87 patients in group S and 36 in group P , revealing no IMA occlusions in either group . Bilateral skeletonized IMA grafting for diabetic patients is safe and may decrease wound complications OBJECTIVE The incidence of wound infection in coronary artery surgery is low , but there is an appreciable mortality associated with sternal infection . In other fields of surgery there is evidence that an all disposable paper gown and drape system has protective advantages over a fabric system . Using an established wound scoring system ( ASEPSIS ) , we investigated this in a prospect i ve , r and omised trial of patients undergoing cardiac surgery . METHODS 505 patients undergoing isolated coronary artery surgery in a single hospital over an 18 month period were r and omised to either a disposable , paper drape system or re-usable fabric drapes . Allocation was stratified according to whether or not the patient had had previous coronary artery surgery . Patients were followed for 3 months . Total infection scores for each wound were calculated from daily scores collected in hospital together with the scores at six weeks and three months . RESULTS The two r and omised groups were otherwise well matched . Full follow-up information was available for 464 ( 92 % ) patients . There was no evidence of any difference in rates of sternal or leg wound infection between the two groups ( P = 0.87 and 0.62 , respectively ) . Women were more likely to have infected sternal wounds ( P = 0.17 ) and significantly more likely to have infected leg wounds ( P = 0.04 ) . Patients with sternal wound infections had a significantly higher body mass index ( P = 0.001 ) . High Parsonnet scores and increased time on ventilation were significantly associated with leg wound but not sternal infections . For both wound sites , patients with infections had spent longer in the operating theatre . CONCLUSION In a r and omised controlled study of patients undergoing coronary artery surgery we found that the use of paper drapes and gowns conferred no benefit over a reusable fabric in terms of post-operative wound infection . Although females and diabetics are more likely to experience this complication , an important additional risk factor is an extended operating time OBJECTIVE The internal thoracic artery ( ITA ) is the ideal conduit for coronary artery bypass grafting ( CABG ) . The skeletonization technique of this arterial conduit has been proposed to reduce chest wall trauma , increase graft length and facilitate construction of sequential anastomoses . Nevertheless , some surgeons decline this technique because of potentially increased trauma to the ITA with impairment of flow . In this investigation we compared the free flow of skeletonized with that of pedicled ITA grafts . METHODS Two surgeons operated on 80 consecutive patients with coronary artery disease for elective CABG . In group I ( n = 40 ) , the left ITA was dissected using the skeletonization technique . In group II ( n = 40 ) , it was harvested as a pedicled graft . In 23 patients of group I both ITA 's were dissected in skeletonized fashion for complete arterial revascularization . Diluted papaverine was instilled into the lumen of the ITA after distal transection of the vessel in both groups . Free flow of the ITA was registered before and 15 min after intraluminal application of diluted papaverine . Mean arterial pressure was maintained at 70 mmHg . RESULTS Before the application of papaverine , free flow of skeletonized and pedicled ITA grafts was identical between the two groups . After treatment with papaverine maximum free flow was significantly higher in the skeletonized ITA 's ( group I 197.2 ( + /-66.6 ) ml/min ; group II 147.1 ( + /-70.5 ) ml/min ; P < 0.05 ) . There was no significant difference between free flow after dilatation of the left and right ITA in group I ( left 197.2 ( + /-66.6 ) ml/min ; right 198.9 ( + /-61.8 ) ml/min ) . CONCLUSIONS Preparation of the ITA with the skeletonization technique results in significantly , higher free flow capacity than in pedicled grafts . This may increase the safety of arterial revascularization by reducing the risk of ITA hypoperfusion syndrome OBJECTIVE To evaluate the role of intact pleurae regarding the postoperative respiratory functional status in patients undergoing coronary revascularization employing both internal mammary arteries ( IMAs ) , according to the pedunculated or skeletonized technique ( SKT ) with opened or intact pleurae . MATERIAL S AND METHODS Using both IMAs , 299 patients underwent elective coronary revascularization . They were r and omized and divided into group I ( n=82 , undergoing IMA harvesting according to the SKT without opening the pleurae ) ; group II ( n=186 , undergoing IMA harvesting according the pedunculated technique with open pleurae ) ; and group III ( n=31 , undergoing IMA harvesting according the SKT with incidentally opened pleurae ) . There were no differences regarding the preoperative patient characteristics and the anaesthetic and surgical management . RESULTS There were two deaths in group I versus seven in group II and one in group III ( P = ns ) . The number of total arterial myocardial revascularization and arterial composite grafts was significantly higher in groups I and III than in group II , ( P<0.001 and P<0.005 , respectively ) . The incidence of postoperative complications was similar between groups . Blood loss of > 1000 ml was significantly higher in group II than group I ( P<0.028 ) ; but the incidence of re-thoracotomy and blood transfusion was similar between groups . The mechanical ventilation time was significantly higher in groups II and III versus group I ( P<0.018 and P<0.02 , respectively ) . The incidence of prolonged ventilation ( > 24 h ) , pleural effusion , thoracocentesis and atelectasis , result ed in being significantly higher in group II than group I. The incidence of thoracocentesis was significantly higher in group III than group I. The pain score and analgesic requirements at 1 - 12 h after awakening were significantly higher in groups II and III versus group I , becoming similar after the chest tubes were removed . PaO(2 ) was significantly higher , and PaCO(2 ) and FiO(2 ) were significantly lower in group I than groups II and III at 1 and 4 h before extubation and at 1 and 4 h after extubation . PaO(2 ) and PaCO(2 ) became similar between groups at the 5th postoperative day . CONCLUSIONS According to our results , we may conclude that pleural integrity has beneficial effects on the respiratory functional status after coronary revascularization using both IMAs . A meticulous and more careful IMA harvesting approach significantly reduces the postoperative morbidity regarding the pulmonary functional status , and as a consequence , reduces the hospital costs OBJECTIVE To compare the free blood flow , caliber , and length of the left internal thoracic artery ( LITA ) , dissected in the pedicled ( P ) and skeletonized ( S ) manners , during surgery before and after topical vasodilator ( TV ) application . METHODS A r and omized , blind , clinical trial was carried out with 50 patients undergoing elective myocardial revascularization to assess the use of the LITA in situ in its pedicled or skeletonized form . The 25 patients in the pedicled group ( GP ) had NYHA class II or III angina , ejection fraction ( EF ) of 50.8+/-9.2 % , and 16 were of the male sex . The patients in the skeletonized group ( SG ) had NYHA class II angina , EF of 46.8+/-9.3 % , and 19 were of the male sex . The measurements were performed before extracorporeal circulation and divided into 2 phases : phase 1 ( before topical papaverine application ) and phase 2 ( 15 min after topical application of papaverine , 2.5 mg/mL , at 37 degrees C ) . During the measurements , mean blood pressure , central venous pressure , and heart rate were monitored . RESULTS The phase 1 and 2 results are as follows : 1 ) PG : blood flow , 46+/-16 and 77+/-28 mL/min ; caliber , 1.4+/-0.1 and 1.7+/-0.1 mm , respectively ; 2 ) SG : blood flow , 57+/-27 and 97+/-35 mL/min ; and caliber , 1.4+/-0.1 and 1.8+/-0.2 mm , respectively . No significant differences were observed in length . CONCLUSION The LITA in SG had a significant increase in blood flow and caliber after the use of TV compared with blood flow and caliber in PG ( P=0.03 and P=0.01 , respectively ) A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis BACKGROUND We examined the hypothesis that complete skeletonization of an internal thoracic artery ( ITA ) results in increased diameter of the graft for anastomosis and therefore improves graft flow in coronary artery bypass grafting . METHODS We studied 65 consecutive patients who underwent coronary artery bypass grafting , in which the left ITA was anastomosed to the left anterior descending artery . The first 20 consecutive ITA were harvested as a pedicle ( group P ) and later 45 consecutive ITAs were harvested as an ultrasonically skeletonized graft ( group S ) . Intraoperative ITA graft mean flows were obtained with a transit-time flowmeter . Three diameters of the ITA graft were measured quantitatively in postoperative angiograms performed 14 + /- 5 days after the coronary artery bypass grafting ; D1 , at the origin from the subclavian artery ; D2 , at the level of the second intercostal space ; and D3 , just proximal to the anastomosis . RESULTS Intraoperative mean flow was significantly greater in group S than in group P ( S : 42.6 + /- 29.1 mL/min versus P : 26.4 + /- 16.1 mL/min , p = 0.03 ) . Although the diameters D1 and D2 were not significantly different between groups , D3 was significantly larger in group S than in group p ( S : 1.77 + /- 0.28 mm versus P : 1.57 + /- 0.17 mm , p = 0.02 ) . CONCLUSIONS Compared with pedicle harvesting , complete skeletonization of ITA may make it possible to anastomose an ITA with a larger diameter in coronary artery bypass grafting , which leads to increased graft flow by decreasing vascular resistance OBJECTIVE In human patients the influence of skeletonized internal thoracic artery harvesting on the sternal microcirculation in the perioperative phase has not been well investigated . METHODS Twenty-four consecutive male patients who were scheduled for isolated coronary artery bypass grafting were prospect ively r and omized into 2 groups . The left internal thoracic artery was harvested by using the skeletonized technique in group 1 , and it was harvested with a pedicle in group 2 . Superficial ( 2 mm ) and deep ( 8 mm ) tissue oxygen saturation and blood flow were measured presternally and retrosternally in the upper , middle , and lower sternal parts with a novel laser Doppler flowmetric and remission spectroscopic system ( Oxygen-to-See ; LEA Medizintechnik , Giessen , Germany ) . RESULTS Presternal tissue oxygen saturation deteriorated at the upper and middle sternum , and presternal blood flow deteriorated at all measurement points after internal thoracic artery harvesting in both groups . Skeletonization had no advantage in maintaining presternal microcirculation . Retrosternal microcirculation also deteriorated at all measurement points after internal thoracic artery harvesting in both groups . However , the deterioration of the retrosternal microcirculation was significantly less in group 1 at the middle and lower sternum ; values of oxygen saturation to the baseline were 86 % + /- 3.8 % versus 60 % + /- 4.3 % ( P = .001 ) at 2-mm depth and 82 % + /- 4.2 % versus 61 % + /- 6.1 % ( P = .009 ) at 8-mm depth at the middle sternum and 95 % + /- 3.2 % versus 78 % + /- 1.3 % ( P = .001 ) at 2-mm depth and 94 % + /- 2.2 % versus 78 % + /- 4.6 % ( P = .004 ) at 8-mm depth at the lower sternum in groups 1 and 2 , respectively . CONCLUSION The damage of the tissue microcirculation in the middle and lower retrosternal area is significantly less after internal thoracic artery skeletonization compared with that after the pedicled internal thoracic artery harvesting technique OBJECTIVE A pain syndrome related to intercostal nerve injury during internal thoracic artery harvesting causes significant morbidity after coronary bypass surgery . We hypothesized that its incidence and severity might be reduced by using skeletonized internal thoracic artery harvesting rather than pedicled harvesting . METHODS In a prospect i ve double-blind clinical trial , 41 patients undergoing coronary bypass were r and omized to receive either unilateral pedicled or skeletonized internal thoracic artery harvesting . Patients were assessed 7 ( early ) and 21 ( late ) weeks postoperatively with reproducible sensory stimuli used to detect chest wall sensory deficits ( dysesthesia ) and with a pain question naire used to assess neuropathic pain . RESULTS At 7 weeks postoperatively , the area of harvest dysesthesia ( percentage of the chest ) in the skeletonized group ( n = 21 ) was less ( median , 0 % ; interquartile range , 0 - 0 ) than in the pedicled group ( n = 20 ) ( 2.8 % [ 0 - 13 ] , P = .005 ) . The incidence of harvest dysesthesia at 7 weeks was 14 % in the skeletonized group versus 50 % in the pedicled group ( P = .02 ) . These differences were not sustained at 21 weeks , as the median area of harvest dysesthesia in both groups was 0 % ( P = .89 ) and the incidence was 24 % and 25 % in the skeletonized and pedicled groups , respectively ( P = 1.0 ) . The incidence of neuropathic pain in the skeletonized group compared with the pedicled group was 5 % versus 10 % ( P = .6 ) at 7 weeks and 0 % versus 0 % ( P = 1.0 ) at 21 weeks . CONCLUSIONS Compared with pedicled harvesting , skeletonized harvesting of the internal thoracic artery provides a short-term reduction in the extent and incidence of chest wall dysesthesia after coronary bypass , consistent with reduced intercostal nerve injury and therefore the reduced potential for neuropathic chest pain Coronary artery bypass grafting ( CABG ) is one of the most frequently performed operations in the United States . The use of internal mammary artery ( IMA ) grafting has been identified as increasing the risk of sternal wound infections and mediastinitis . The purpose of our study was to prospect ively evaluate the effect of different techniques of left internal mammary artery ( LIMA ) harvesting on sternal vascularity . Thirty-three patients undergoing primary coronary artery bypass grafting were studied . The patients were divided into groups that received a skeletonized IMA ( group I , n = 11 ) , a pedicled IMA ( group II , n = 12 ) , or a semiskeletonized IMA ( group III , n = 10 ) graft . Each patient underwent a preoperative 99mTc-methylene diphosphonate bone scan using single photon emission computed tomography ( SPECT ) . The ratio of the mean counts/pixel for each side of the sternum was obtained . Post-operatively , all patients had a repeat bone SPECT . Ratios of unilateral sternal uptakes were compared to the preoperative study . A univariable analysis of post-operative to pre-operative ratios revealed statistically significant reduction in vascularity to the left side of the sternum post-operatively in group II compared with groups I and III ( 0.68 0.12 vs 0.99 0.24 and 0.93 0.09 ; P<0.01 ) . There was no difference between groups I and III ( P = 1 ) . Multivariable analysis revealed only the type of harvesting to be associated with post-operative reduction in left to right sternal activity ratio ( P<0.02 ) . Pairwise comparisons revealed that differences are due to pedicled type of harvesting ( group II vs group I , P = 0.03 ; II vs III , P = 0.001 ; and I vs III , P = 0.115 ) . A pedicled IMA graft causes acute post-operative sternal ischaemia . This does not occur when the IMA is skeletonized or semiskeletonized . Hence , it may be prudent to minimize dissection during mobilization of the IMA to decrease the likelihood of post-operative sternal complications BACKGROUND The preferential harvesting technique of the internal mammary artery has been periodically debated . This r and omized study evaluated the flow outcome of the skeletonized versus pedicled left internal mammary artery . METHODS Two hundred patients undergoing surgery for left anterior descending coronary artery revascularization were enrolled and r and omized to pedicled ( n=100 ) or skeletonized ( n=100 ) harvesting . Intraoperative baseline flow and post adenosine infusion into the left ventricle , hospital outcome , echocardiographic results , and troponin I leakage were analyzed . Noninvasive periodic evaluation of flow was carried out at rest and during intravenous adenosine infusion by transthoracic Doppler ultrasound , and was stratified according to the harvesting technique . Final angiographic evaluation was performed by 64-slice multidetector computed tomography . RESULTS Skeletonized left internal mammary arteries demonstrated better flow capacity at rest and during adenosine recruitment perioperatively and at all time points of follow-up . Troponin I leakage was significantly higher in the pedicled group ( 59 vs 42 , p=0.02 ) . Pedicled harvesting ( hazard ratio [ HR ] 3.6 , 95 % confidence interval [ CI ] 2.5 to 6.9 , p<0.001 ) ; indexed left ventricular mass greater than 150 g/m2 ( HR 4.6 , 95 % CI 3.1 to 7.5 , p<0.001 ) ; and baseline corrected thrombolysis in myocardial infa rct ion frame count greater than 30 ( HR 4.4 , 95 % CI , 3.8 to 7.2 , p<0.001 ) were the most powerful multivariable predictors of graft flow reserve less than 2.0 . Postoperative echocardiographic results and clinical and angiographic outcomes were comparable between the two groups . CONCLUSIONS Skeletonization of the left internal mammary artery , beyond traditional proven advantages , provided significantly higher flow capacity and better graft flow reserve |
10,559 | 25,308,694 | Not in all solid tumors the treatment-level association between PFS or TTP and OS has been investigated .
According to IQWiG 's framework , only PFS achieved acceptable evidence of surrogacy in metastatic colorectal and ovarian cancer treated with cytotoxic agents . | OBJECTIVES Licensing of , and coverage decisions on , new therapies should rely on evidence from patient-relevant endpoints such as overall survival ( OS ) .
Nevertheless , evidence from surrogate endpoints may also be useful , as it may not only expedite the regulatory approval of new therapies but also inform coverage decisions .
It is , therefore , essential that c and i date surrogate endpoints be properly vali date d. However , there is no consensus on statistical methods for such validation and on how the evidence thus derived should be applied by policy makers .
RESULTS A wide variety of statistical methods have been used to assess surrogacy . | PURPOSE To explore whether progression-free survival ( PFS ) or biochemical PFS can be used as a predictor of overall survival ( OS ) and to investigate the dependence between PFS and OS in men with castrate-resistant prostate cancer . PATIENTS AND METHODS Data from nine Cancer and Leukemia Group B trials that enrolled 1,296 men from 1991 to 2004 were pooled . Men were eligible if they had prostate cancer that had progressed during and rogen deprivation therapy and did not receive prior treatment with chemotherapy , immunotherapy , or other nonhormonal therapy . L and mark analyses of PFS at 3 and 6 months from r and omization/ registration were performed to minimize lead time bias . The proportional hazards model was used to assess the significance effect of PFS rate at 3 and at 6 months in predicting OS . In addition , biochemical progression using the definitions of Prostate-Specific Antigen Working Group ( PSAW ) Criteria PSAWG1 and PSAWG2 were analyzed as time-dependent covariates in predicting OS . RESULTS The median survival time among men who experienced progression at 3 months was 9.2 months ( 95 % CI , 8.0 to 10.0 months ) compared with 17.8 months in men who did not experience progression at 3 months ( 95 % CI , 16.2 to 20.4 months ; P < .0001 ) . Compared with men who did not progress at 3 and at 6 months , the adjusted hazard ratios for death were 2.0 ( 95 % CI , 1.7 to 2.4 ; P < .001 ) and 1.9 ( 95 % CI , 1.6 to 2.4 ; P < .001 ) for men who experienced progression at 3 and 6 months , respectively . In addition , biochemical progression at 3 months predicted OS . The association between PFS and OS was 0.30 ( 95 % confidence limits = 0.26 , 0.32 ) . CONCLUSION PFS at 3 and 6 months and biochemical progression at 3 months predict OS . These observations require prospect i ve validation Summary Progression-free survival ( PFS ) and time to progression ( TTP ) have been reported to correlate with overall survival ( OS ) in several types of cancers . To our knowledge , however , their use in the evaluation of new agents for AGC has not been investigated . We evaluated the potential of PFS and TTP to act as surrogates of OS in clinical trial setting s. R and omized trials of systemic chemotherapy for advanced gastric cancer were identified by comprehensive electronic and manual search . Correlations between PFS/TTP and OS were evaluated . Thirty-six trials with a total of 83 treatment arms and 10,484 patients were selected for analysis . The nonparametric Spearman rank correlation coefficient ( ρ ) between median PFS/TTP and OS was 0.70 ( 95 % CI , 0.59 to 0.82 ) and the correlation coefficient between hazard ratios in PFS/TTP and OS was 0.80 ( 95 % CI , 0.68 to 0.92 ) . Correlation tended to be higher in trials reporting PFS ( ρ = 0.85 ; 0.72–0.97 ) than in those reporting TTP ( ρ = 0.60 ; 0.24–0.97 ) , trials in Non-Asian countries ( ρ = 0.80 ; 0.61–0.99 ) than Asia ( ρ = 0.67 ; 0.39–0.94 ) , trials in patients with measurable lesions only ( ρ = 0.91 ; 0.77–1.00 ) than in those including non-measurable lesions ( ρ = 0.71 ; 0.50–0.93 ) , albeit that none of these differences was significant . Our results indicate that improvements in PFS/TTP in advanced gastric cancer strongly correlate with improvements in OS . Further research is needed to clarify the surrogacy of PFS/TTP for OS or the role of PFS as the true end point in future r and omized clinical trials of chemotherapy for AGC Background : The correlation between efficacy end points in r and omized controlled trials ( RCTs ) of systemic therapy for non-Hodgkin 's lymphoma ( NHL ) was investigated to identify an appropriate surrogate end point for overall survival ( OS ) . Methods : RCTs of previously untreated NHL published from 1990 to 2009 were identified . Associations between absolute differences in efficacy end points were determined using nonparametric Spearman 's rank correlation coefficients ( rs ) . Results : Thirty-eight RCTs representing 85 treatment arms for aggressive NHL and 20 RCTs representing 42 arms for indolent NHL were included . For aggressive NHL , differences in 3-year progression-free survival (PFS)/event-free survival ( EFS ) were high correlated with differences in 5-year OS { rs of 0.90 [ 95 % confidence interval ( CI ) 0.73–0.96 ] } and linear regression determined that a 10 % improvement in 3-year EFS or PFS would predict for a 7 % ± 1 % improvement in 5-year OS . For indolent histology disease , differences in complete response were strongly correlated with differences in 3-year EFS [ rs 0.86 ( 95 % CI 0.35–0.97 ) ] , but there was no correlation between 3-year time-to-event end points and 5-year OS . Conclusions : Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a c and i date surrogate end point . Definition of these relationships may inform future clinical trial design and interpretation of interim trial data We assessed six-month progression-free survival ( PFS ) as an alternative primary efficacy endpoint to overall survival in newly diagnosed glioblastoma multiforme ( GBM ) patients receiving temozolomide ( TMZ ) . A total of 183 patients with newly diagnosed GBM enrolled in 3 phase II protocol s at the University of California-San Francisco were included . Patients were treated with interventions based on the Stupp regimen , each with the added component of a second oral agent given concurrently with radiotherapy and TMZ , followed by its coadministration with adjuvant TMZ . We examined whether progression status at 2 , 4 , and 6 months predicted subsequent survival using the l and mark analysis . The hazard ratios of death as a function of progression status were estimated based on the Cox proportional hazards model after adjustment for putative prognostic factors . Progression status at 2 , 4 , and 6 months were all consistently found to be strong predictors of subsequent survival in all studies . The study -specific hazard ratios associated with progression status at 6 months ranged from 2.03 to 3.39 . The hazard ratios associated with the earlier time points ( 2- and 4-month progression ) all exceeded 2 in magnitude , ranging from 2.29 to 4.73 . P-values were statistically significant for all time points . In this report , we demonstrated a strong association between the endpoints of PFS at 2 , 4 , and 6 months and survival . Patients who showed the signs of early progression were at significantly higher risk of earlier death . Our analysis suggests that 6-month PFS may be an appropriate primary endpoint in the context of phase II upfront GBM trials in the TMZ era Background It is controversial for the use of survival surrogate end points including response rate ( RR ) , disease control rate ( DCR ) , time to progression , and progression-free survival ( PFS ) in trials of molecular targeted agents . Our aim was to determine the correlations of these surrogates with survival in the treatment of advanced non-small-cell lung cancer ( ANSCLC ) with epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR-TKIs ) , gefitinib and erlotinib . Methods Summary data of median survival time ( MST ) and surrogates from prospect i ve trials of EGFR-TKIs in ANSCLC were identified . Patient- or trial-related characteristics were introduced as covariates . Simple and multivariate linear regression models were fitted for MST and each surrogate , respectively . And the significance of each surrogate as a survival marker was compared by calculating the area under their receiver operating characteristic ( ROC ) curves . Results Sixty eligible trials ( 9,903 patients ) were enrolled . RR , DCR , and PFS were all strongly associated with MST . In their simple linear regression models , the coefficient of determination ( R2 ) was 0.83 ( p < 0.000001 ) , 0.58 ( p < 0.0001 ) , and 0.70 ( p < 0.0001 ) , respectively . And in their multivariate linear regression models , the st and ard coefficient was 0.71 ( p < 0.001 ) , 0.40 ( p < 0.001 ) , and 0.74 ( p < 0.001 ) , respectively , while RR and PFS were the preferred survival predictors in the ROC analysis . Conclusion RR or PFS may serve as an appropriate survival surrogate in the clinical trials of EGFR-TKIs for ANSCLC OBJECTIVES Our aim was to review the recommendations given by health technology assessment ( HTA ) institutions in their method ological guidelines concerning the use of surrogate outcomes in their assessment s. In a second step , we aim ed at quantifying the role surrogate parameters take in assessment reports . METHODS We analyzed method ological papers and guidelines from HTA agencies with International Network of Agencies for Health Technology Assessment membership as well as from institutions related to pharmaceutical regulation ( i.e. , reimbursement , pricing ) . We analyzed the use of surrogate outcomes in a sample of HTA reports r and omly drawn from the HTA data base . We checked methods , results ( including evidence tables ) , and conclusions sections and extracted the outcomes reported . We report descriptive statistics on the presence of surrogate outcomes in the reports . RESULTS We identified thirty-four method ological guidelines , twenty of them addressing the issue of outcome parameter choice and the problematic of surrogate outcomes . Overall HTA agencies call on caution regarding the reliance on surrogate outcomes . None of the agencies has provided a list or catalog of acceptable and vali date d surrogate outcomes . We extracted the outcome parameter of 140 HTA reports . Only around half of the reports determined the outcomes for the assessment prospect ively . Surrogate outcomes had been used in 62 percent of the reports . However , only 3.6 percent were based upon surrogate outcomes exclusively . All of them assessed diagnostic or screening technologies and the surrogate outcomes were predominantly test characteristics . CONCLUSIONS HTA institutions seem to agree on a cautious approach to the use of surrogate outcomes in technology assessment . Thorough assessment of health technologies should not rely exclusively on surrogate outcomes Progression-free survival ( PFS ) is an increasingly important end-point in cancer drug development . However , several concerns exist regarding the use of PFS as a basis to compare treatments . Unlike survival , the exact time of progression is unknown , so progression times might be over-estimated ( or under-estimated ) and , consequently , bias may be introduced when comparing treatments . In addition , the assessment of progression is subject to measurement variability which may introduce error or bias . Ideally trials with PFS as the primary end-point should be r and omised and , when feasible , double-blinded . All patients eligible for study should be evaluable for the primary end-point and thus , in general , have measurable disease at baseline . Appropriate definitions should be provided in the protocol and data collected on the case-report forms , if patients with only non-measurable disease are eligible and /or clinical , or symptomatic progression are to be considered progression events for analysis . Protocol defined assessment s of disease burden should be obtained at intervals that are symmetrical between arms . Independent review of imaging may be of value in r and omised phase II trials and phase III trials as an auditing tool to detect possible bias This paper is an overview of the new response evaluation criteria in solid tumours : revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents Common end points for phase II trials in patients with glioblastoma multiforme ( GBM ) are six-month progression-free survival ( PFS6 ) and 12-month overall survival ( OS12 ) . OS12 can be accurately measured but may be confounded with subsequent therapies upon progression , whereas the converse is true for PFS6 . Our goal was to assess the relationship between these end points separately for phase II trials in patients with newly diagnosed GBM and patients with recurrent GBM . Data were pooled from 11 North Central Cancer Treatment Group trials for patients with newly diagnosed GBM ( n = 1348 ) . All patients received radiotherapy and pharmaceutical therapy ( before , during , or after radiotherapy ) . Data were pooled from 16 trials that used various pharmaceuticals in treating patients for recurrent GBM ( n = 345 ) . All trial regimens were declared nonefficacious by predefined criteria . Overall per-patient concordance was estimated with a kappa statistic . The relationship between OS12 and PFS6 across study arms was assessed by weighted linear regression and Pearson 's correlation . Simulation was used to determine the agreement of study outcomes when using PFS6 versus OS12 end points . Cox models with progression status as a time-dependent variable and Kaplan-Meier estimators were used to ascertain the association between progression-free survival status and overall survival . At present , 97 % of the patients with newly diagnosed GBM and 95 % of those with recurrent GBM have died . The PFS6 and OS12 were 43 % and 41 % , respectively , for patients with newly diagnosed disease and 9 % and 14 % for patients with recurrent disease . There was only moderate concordance between the end points on both the patient level and the study level . For the simulation studies , we established phase II efficacy criteria for each end point by using the pooled estimates of OS12 ( PFS6 ) as historical controls . The study decisions made using PFS6 and OS12 were in agreement 88 % and 90 % of the time for the trials of newly diagnosed and recurrent disease , respectively . Finally , there was a strong association between progression-free survival status and overall survival . PFS6 seems to be a reasonable end point for phase II trials in patients with recurrent glioblastoma It can be difficult to identify endpoints that accurately reflect patient benefit in metastatic solid tumors . Overall survival ( OS ) is the gold st and ard although progression-free survival ( PFS ) is sometimes used as a surrogate for OS . Statistical modelling has suggested that the association between OS and PFS becomes weaker in diseases with longer survival post-progression ( SPP ) . To evaluate these statistical hypotheses we determined the relationship between PFS and OS in control and experimental arms of r and omised trials conducted in the last 10years , which have led to drug approval . Our data confirm that PFS is a poor surrogate for OS when SPP is long , but it is a better surrogate where SPP is short . In cancers with short SPP design ing trials to show OS benefit is feasible and , therefore , remains the preferred approach . In tumours with long SPP , PFS is not clinical ly meaningful unless it is also associated with improvement in patient reported outcomes such as quality of life . The oncology community should consider the further development and validation of composite endpoints including patient reported outcomes and PFS across different disease sites . Such endpoints have been successfully used in cancer trials in the past . With improvements in therapy and prolonged survival of patients with many cancers , and with increasing pressure from healthcare payers to prove that treatment leads to patient benefit , the choice of optimal endpoints for clinical trials is increasingly important . Composite measures comprising patient reported outcomes and intermediate endpoints such as PFS may be the solution and should be investigated further OBJECTIVES The aim of this study was to explore the use of surrogate outcomes --a substitute outcome that predicts final patient-related outcomes --in cost-effectiveness models ( CEM ) within health technology assessment ( HTA ) reports and provide guidance for their future use . METHODS Our sampling frame was all UK HTA Program monograph series reports published in 2005 and 2006 . Reports were included if they addressed a treatment effectiveness/efficacy question and included a CEM based on a surrogate outcome . The two authors independently applied inclusion and exclusion criteria , and the following data was extracted from included reports : source of surrogate outcome , level of evidence for validation of the surrogate outcomes , methods used in report to quantify link between surrogate outcome and final outcome , and consideration of the uncertainty associated with using surrogate outcomes in the results or conclusions of report . RESULTS Of 100 HTA reports , 35 complied with the inclusion criteria . Of these , four ( 11 percent ) reports included a CEM based on a surrogate outcome . All four reports source d treatment-related changes in surrogate outcome through a systematic review of the literature . One provided Level 1 surrogate evidence ( r and omized controlled trial data showing a strong association between the change in surrogate outcome and change final outcome ) ; two reported Level 2 evidence ( observational study data ) ; and one provided Level 3 evidence ( disease natural/ history data ) . The transparency of quantification and exploration of uncertainty of the surrogate and final outcome relationship varied considerably across all four reports . CONCLUSIONS Recommendations are made for the use of surrogate outcomes in future HTA reports Twenty-five years ago , in its first volume , the Journal of Clinical Oncology published our method ologic article , which highlighted an inappropriate analytic approach then in common use and suggested alternative unbiased techniques . Cited more than 380 times , this article and similar ones by other authors have had a large impact on how results from early-phase clinical trials are reported , almost completely eliminating so-called survival by tumor response analyses from the oncology literature . The success of treatments for patients with advanced cancers at diagnosis or recurrence is often assessed by computing overall response rates and survival from the start of treatment . Before 1983 , analysis of survival by tumor response category was commonly included as part of the reports of these treatments . Patients were characterized as responders or nonresponders , estimates of survival from the start of treatment were calculated for each responder category , and differences in survival by these tumor response categories were compared using a significance test appropriate for time-to-event data . These analyses had been used to bolster the cl aim of benefit for the treatment , often as a surrogate for a r and omized trial . Responders benefited from the therapy and thus constituted the treatment group . Nonresponders did not benefit , and thus their survival could be considered similar to that for untreated patients . Similarly , these analyses had also been used to argue that therapies that increase the response rate should necessarily result in increased survival . In March 1983 , Weiss et al reported the results of a review of articles published in Cancer or Cancer Treatment Reports and found 228 articles presenting data on responders and nonresponders , with 61 % containing formal statistical comparisons of survival by tumor response category . They identified problems in the interpretation of these comparisons . In November 1983 , our article in the Journal of Clinical Oncology , “ Analysis of Survival by Tumor Response , ” was published . We showed that the usual methods of comparing responders with nonresponders were wrong , leading to biased estimates of the survival distributions , invalid statistical tests , and misleading conclusions . This bias results in part from the fact that responders must live long enough for response to be observed ; there is no such requirement for nonresponders . We described several valid approaches to comparing survival by response category . One approach , the l and mark method , determines each patient ’s response at some fixed time point , with survival estimates calculated from that time point and associated statistical tests being conditional on patients ’ l and mark responses . Note that in this method , patients who die before the l and mark time point are excluded from the analysis . An alternative approach treats response status as a timedependent covariate , where all patients begin in the nonresponse state and patients move to the response state at the time of their response . Shortly thereafter , Simon and Makuch proposed a method of obtaining estimates of survival probabilities for responders and nonresponders , combining ideas from the l and mark and time-dependent covariate approaches . Even when these analyses were performed appropriately , we argued that longer survival for responders , as compared with nonresponders , could not be used to conclude that response caused longer survival . Response might act as a surrogate marker for prognostically favorable patients . Thus responders may survive longer than nonresponders , not because of an effect of response on survival , but because response identifies patients with pretreatment characteristics that favor longer survival . It is generally difficult to distinguish between cases where response prolongs survival and cases where it simply acts as a marker for favorable-prognosis patients . In 1985 , Cancer Treatment Reports indicated it would not publish comparisons of survival by tumor response . Notwithst and ing the reports by Weiss et al and us , And erson and Davis showed that between July 1984 and June 1985 , the Journal of Clinical Oncology published 18 articles that included analyses of survival by tumor response , 10 of which provided inappropriate statistical comparisons of survival of responders and nonresponders . They suggested that the Journal of Clinical Oncology follow the lead of Cancer Treatment Reports and no longer publish articles that include survival by tumor response . An editorial accompanying the letter by the then-editor of the Journal of Clinical Oncology , Joseph Bertino , MD , indicated that “ authors should not compare survival of responders and nonresponders without discussing the limitations of such a comparison ” . JOURNAL OF CLINICAL ONCOLOGY C E L E B R A T I N G 2 5 Y E A R S O F J C O VOLUME 26 NUMBER 24 AUGUST |
10,560 | 26,320,435 | CONCLUSIONS Gemcitabine combination therapy provides a modest improvement of survival , but is associated with more toxicity compared with gemcitabine monotherapy | BACKGROUND Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world .
Gemcitabine chemotherapy is the primary method of treatment of advanced pancreatic cancer , and in asco2014 , it is still first- line chemotherapy .
However gemcitabine+fluorouracil regimens are also licensed and widely used worldwide .
Clinical trials are the best way to evaluate drug efficacy .
In this study , we performed a systematic review and a meta- analysis of r and omized controlled trials ( RCTs ) to assess whether gemcitabine+fluoropyrimidine combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone . | This study was performed to determine the activity of adding continuous infusion ( CI ) of 5-fluorouracil ( 5-FU ) to gemcitabine ( GEM ) vs GEM alone in advanced pancreatic cancer ( APC ) . In all , 94 chemo-naïve patients with APC were r and omised to receive GEM alone ( arm A : 1000 mg m−2 per week for 7 weeks followed by a 2 week rest period , then weekly for 3 consecutive weeks out of every 4 weeks ) or in combination with CI 5-FU ( arm B : CI 5-FU 200 mg m−2 day−1 for 6 weeks followed by a 2 week rest period , then for 3 weeks every 4 weeks ) . Overall response rate ( RR ) was the primary end point and criteria for decision were planned according to the Simon 's optimal two-stage design . The overall RR was 8 % ( arm A ) and 11 % ( arm B ) ( 95 % confidence interval : 0.5–16 % and 2–22 % ) , respectively , and stable disease was 29 and 28 % . The median duration of RR was 34 weeks ( range 25–101 weeks ) for GEM and 26 weeks ( range 16–46 weeks ) for the combination . The median progression-free survival ( PFS ) was 14 weeks ( range 2–65 weeks ) and 18 weeks ( range 4–51 weeks ) , respectively . The median overall survival ( OS ) was 31 weeks ( range 1–101 weeks ) and 30 weeks ( 1–101 weeks ) . Toxicity was mild in both arms . This study does not show promising activity in terms of RR , PFS and OS for the double combination arm in APC PURPOSE This phase III trial compared the efficacy and safety of gemcitabine ( Gem ) plus capecitabine ( GemCap ) versus single-agent Gem in advanced/metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive GemCap ( oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks ) or Gem ( 1,000 mg/m2 by 30-minute infusion weekly for 7 weeks , followed by a 1-week break , and then weekly for 3 weeks every 4 weeks ) . Patients were stratified according to center , Karnofsky performance score ( KPS ) , presence of pain , and disease extent . RESULTS A total of 319 patients were enrolled between June 2001 and June 2004 . Median overall survival ( OS ) time , the primary end point , was 8.4 and 7.2 months in the GemCap and Gem arms , respectively ( P = .234 ) . Post hoc analysis in patients with good KPS ( score of 90 to 100 ) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm ( 10.1 v 7.4 months , respectively ; P = .014 ) . The overall frequency of grade 3 or 4 adverse events was similar in each arm . Neutropenia was the most frequent grade 3 or 4 adverse event in both arms . CONCLUSION GemCap failed to improve OS at a statistically significant level compared with st and ard Gem treatment . The safety of GemCap and Gem was similar . In the subgroup of patients with good performance status , median OS was improved significantly . GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status Purpose To evaluate the efficacy and safety of the combination of gemcitabine ( GEM ) and S-1 ( GS ) in comparison to GEM alone ( G ) for unresectable pancreatic cancer . Methods In this multicenter r and omized phase II study , we r and omly assigned unresectable pancreatic cancer patients to either the GS group or the G group . The GS group regimen consists of intravenous 1,000 mg/m2 GEM during 30 min on days 1 and 8 , combined with 80 mg/m2 oral S-1 twice daily on days 1–14 , repeated every 3 weeks . On the other h and , the G group regimen consists of intravenous 1,000 mg/m2 GEM on days 1 , 8 , and 15 , repeated every 4 weeks . The primary endpoint was objective response rate ( ORR ) . Secondary end points included treatment toxicity , clinical response benefit , progression-free survival ( PFS ) , and overall survival . Results We registered 117 patients from 16 institutions between June 2007 and August , 2010 . The ORR of the GS group was 28.3 % , whereas that of the G group was 6.8 % . This difference was statistically significant ( P = 0.005 ) . The disease control rate was 64.2 % in the GS group and 44.1 % in the G group . Median PFS was 6.15 months in the GS group and 3.78 month in the G group . This was also statistically significant ( P = 0.0007 ) . Moreover , the median overall survival ( OS ) of the GS group was significantly longer than that of the G group ( 13.7 months vs. 8.0 months ; P = 0.035 ) . The major grade 3–4 adverse events were neutropenia ( 54.7 % in the GS group and 22.0 % in the G group ) , thrombocytopenia ( 15.1 % in the GS group and 5.1 % in the G group ) , and skin rash ( 9.4 % in the GS group ) . Conclusions The GS group showed stronger anticancer activity than the G group , suggesting the need for a large r and omized phase III study to confirm GS advantages in a specific subset PURPOSE Our purpose in the study was to determine the maximum tolerated dose and dose-limiting toxicity and investigate the clinical pharmacology of S-1 , a combination of tegafur , 5-chloro-2,4-dihydroxypyridine ( CDHP ) , and potassium oxonate . EXPERIMENTAL DESIGN Eligible patients had advanced solid tumors , adequate organ function , and no anticancer therapy in the preceding 4 weeks . Dose level 1 was 30 mg/m(2)/dose , level 2 was 40 mg/m(2)/dose , and level 3 was 35 allmg/m(2)/dose , all of the levels comprising two daily doses . S-1 was administered as a single dose at each level , and its pharmacology was studied . The first course was begun 3 days later and consisted of 28 consecutive treatment days , followed by a 1-week rest . RESULTS Sixteen patients were enrolled ; toxicity could be assessed in all of the 16 and response in 15 . At dose level 1 , two of nine patients developed grade 3 hyperbilirubinemia or diarrhea . Dose-limiting toxicity ( diarrhea ) occurred in all three of the patients at dose level 2 . The protocol was , therefore , amended to include an intermediate dose level ( level 3 ) , which caused grade 3 or 4 diarrhea or hyperbilirubinemia in three of four patients . Dose level 1 was thus considered as the maximum tolerated dose . Other grade 3 or 4 toxic effects at dose level 2 or 3 were granulocytopenia , nausea , and vomiting . The pharmacology of tegafur , CDHP , potassium oxonate , and fluorouracil ( a metabolite of tegafur ) was characterized by rapid absorption and was consistent with first-order kinetics . One patient with colorectal cancer had a durable partial response . CONCLUSIONS The recommended S-1 dose for future studies is 30 mg/m(2 ) twice daily , and diarrhea is the most frequent toxic effect . Additional trials of S-1 in the treatment of patients with solid tumors are warranted Three hundred five patients with advanced pancreatic and gastric carcinoma were r and omly assigned to treatment with fluorouracil , fluorouracil plus doxorubicin ( Adriamycin ) ( FA ) , or fluorouracil plus doxorubicin plus mitomycin ( mitomycin C ) ( FAM ) . All regimens were equivalent with regard to patient survival . There is no reasonable likelihood that either the FA or FAM regimen could produce a meaningful survival advantage over fluorouracil alone . Interval to disease progression , objective response rates , and palliative effects ( improved performance , body weight , or symptoms ) were essentially equivalent among the three regimens . With regard to toxicity , the FAM regimen produced more anorexia , nausea , vomiting , leukopenia , thrombocytopenia , and cumulative bone marrow suppression . Fluorouracil alone produced more stomatitis and diarrhea . Because of a failure to produce improved survival or palliation , unrewarded toxicity , and excessive cost , neither the FA nor FAM regimen can be recommended for the treatment of advanced pancreatic or gastric cancer Background : This r and omised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer . Methods : Patients were r and omly assigned to 4-week treatment with gemcitabine alone ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 , 8 , and 15 ) or gemcitabine and S-1 combination therapy ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m−2 S-1 orally twice daily on days 1–15 ) . The primary end point was progression-free survival ( PFS ) . Results : Between July 2006 and February 2009 , 106 patients were enrolled . The PFS in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm ( 5.4 vs 3.6 months ) , with a hazard ratio of 0.64 ( P=0.036 ) . Overall survival ( OS ) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy ( 13.5 vs 8.8 months ) , with a hazard ratio of 0.72 ( P=0.104 ) . Overall , grade 3 or 4 adverse events were similar in both arms . Conclusion : Gemcitabine and S-1 combination therapy demonstrated longer PFS in advanced pancreatic cancer . Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy , though this was not statistically significant PURPOSE To compare clinical benefit response ( CBR ) and quality of life ( QOL ) in patients receiving gemcitabine ( Gem ) plus capecitabine ( Cap ) versus single-agent Gem for advanced/metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive GemCap ( oral Cap 650 mg/m(2 ) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2 ) in a 30-minute infusion on days 1 and 8 every 3 weeks ) or Gem ( 1,000 mg/m(2 ) in a 30-minute infusion weekly for 7 weeks , followed by a 1-week break , and then weekly for 3 weeks every 4 weeks ) for 24 weeks or until progression . CBR criteria and QOL indicators were assessed over this period . CBR was defined as improvement from baseline for > or= 4 consecutive weeks in pain ( pain intensity or analgesic consumption ) and Karnofsky performance status , stability in one but improvement in the other , or stability in pain and performance status but improvement in weight . RESULTS Of 319 patients , 19 % treated with GemCap and 20 % treated with Gem experienced a CBR , with a median duration of 9.5 and 6.5 weeks , respectively ( P < .02 ) ; 54 % of patients treated with GemCap and 60 % treated with Gem had no CBR ( remaining patients were not assessable ) . There was no treatment difference in QOL ( n = 311 ) . QOL indicators were improving under chemotherapy ( P < .05 ) . These changes differed by the time to failure , with a worsening 1 to 2 months before treatment failure ( all P < .05 ) . CONCLUSION There is no indication of a difference in CBR or QOL between GemCap and Gem . Regardless of their initial condition , some patients experience an improvement in QOL on chemotherapy , followed by a worsening before treatment failure Purpose The aim of this study was to evaluate efficacy and safety of gemcitabine plus S-1 ( GS ) combination chemotherapy in patients with unresectable pancreatic cancer . Methods Patients were r and omly assigned to receive GS ( oral S-1 60 mg/m2 daily on days 1–15 every 3 weeks and gemcitabine 1,000 mg/m2 on days 8 and 15 ) or gemcitabine ( 1,000 mg/m2 on days 1 , 8 , and 15 every 4 weeks ) . The primary endpoint was progression-free survival ( PFS ) . Results One hundred and one patients were r and omly assigned . PFS was significantly longer in the GS arm with an estimated hazard ratio ( HR ) of 0.65 ( 95 % CI 0.43–0.98 ; P = 0.039 ; median 5.3 vs 3.8 months ) . Objective response rate ( ORR ) was also better in the GS arm ( 21.6 vs 6 % , P = 0.048 ) . Median survival was 8.6 months for GS and 8.6 months for GEM ( HR 0.93 ; 95 % CI 0.61–1.41 ; P = 0.714 ) . Grade 3–4 neutropenia ( 44 vs 19.6 % , P = 0.011 ) and thrombocytopenia ( 26 vs 8.7 % , P = 0.051 ) were more frequent in the GS arm . Conclusions GS therapy improved PFS and ORR with acceptable toxicity profile in patients with unresectable pancreatic cancer PURPOSE Gemcitabine is generally considered to constitute first-line therapy for pancreatic cancer . To determine whether the addition of fluorouracil ( 5-FU ) improves on the results from single-agent gemcitabine , the Eastern Cooperative Oncology Group ( ECOG ) compared gemcitabine plus bolus 5-FU with gemcitabine alone for patients with advanced pancreatic carcinoma . PATIENTS AND METHODS This trial involved patients with biopsy-proven , advanced carcinoma of the pancreas not amenable to surgical resection . Patients were r and omized to receive either gemcitabine alone ( 1,000 mg/m(2)/wk ) weekly for 3 weeks of every 4 or to receive gemcitabine ( 1,000 mg/m(2)/wk ) followed by 5-FU ( 600 mg/m(2)/wk ) weekly on the same schedule . The primary end point of the trial was survival , with secondary end points of time to progression and response rate . RESULTS Of 327 patients enrolled over 18 months , 322 were eligible . Overall , the median survival was 5.4 months for gemcitabine alone and 6.7 months for gemcitabine plus 5-FU ( P = .09 ) . Progression-free survival for gemcitabine alone was 2.2 months , compared with 3.4 months for gemcitabine plus 5-FU ( P = .022 ) . Objective responses were uncommon and were observed in only 5.6 % of patients treated with gemcitabine and 6.9 % of patients treated with gemcitabine plus 5-FU . Most toxicities were hematologic or gastrointestinal ; no significant differences were noted between the two treatment arms . CONCLUSION 5-FU , administered in conjunction with gemcitabine , did not improve the median survival of patients with advanced pancreatic carcinoma compared with single-agent gemcitabine . Further studies with other combinations of gemcitabine and 5-FU are not compelling , and clinical trial re sources should address other combinations and novel agents BACKGROUND Chemotherapy is moderately efficient as a treatment for pancreatic adenocarcinoma , but patient survival and quality of life has improved with this modality in some trials . In a previous phase II trial , 5-fluorouracil ( 5-FU ) plus cisplatin ( FUP ) yielded a 26.5 % response rate and a 29 % survival rate at 1 year . The present study aim ed to compare FUP with 5-FU alone , which was the control arm in former Mayo Clinic trials . PATIENTS AND METHODS Patients with untreated cytologically or histologically proven metastatic or locally advanced adenocarcinoma of the pancreas were deemed measurable or evaluable . Chemotherapy regimens consisted of a control FU arm ( 5-FU 500 mg/m(2)/day for 5 days ) and the investigational FUP arm ( continuous 5-FU 1000 mg/m(2)/day for 5 days plus cisplatin 100 mg/m(2 ) on day 1 or day 2 ) . In both arms , chemotherapy was repeated at day 29 . RESULTS Two-hundred and seven patients from 18 centres were r and omised : 103 in the FU arm and 104 in FUP arm . Treatment arms were balanced with respect to performance status grade 0 - 1 ( 83 % versus 86 % , respectively ) and the presence of metastases ( 92 % versus 89 % , respectively ) . The median number of cycles administered was two in both arms ( range 0 - 14 ) . Five patients did not receive any chemotherapy and 45 received only one cycle . Toxicity ( WHO grade 3 - 4 ) was lower with FU than with FUP ( 20 % versus 48 % , P < 0.001 ) , as was neutropenia ( 6 % versus 23 % ) , vomiting ( 4 % versus 17 % ) and toxicity-related deaths ( one versus four early in the trial ) . The response rate was low in both arms , but superior in the FUP arm : 12 % versus 0 % ( intention-to-treat analysis , P < 0.01 ) . The survival rates at 6 months were 28 % and 38 % for the FU and FUP arms , respectively , and 1-year survival rates were 9 % and 17 % ( log-rank test , P = 0.10 ) . One-year progression-free survival was 0 % with FU versus 10 % with FUP ( log-rank test , P = 0.0001 ) . CONCLUSIONS In advanced pancreatic carcinomas with a poor prognosis , FUP was superior to FU in terms of response and progression-free survival , but not in terms of overall survival . The low response rate is partly related to the number of patients who received only one cycle of chemotherapy . A more effective , better tolerated version of this FUP combination is needed PURPOSE Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms . To date , no treatment has had a significant impact on the disease . In early studies with gemcitabine , patients with pancreas cancer experienced an improvement in disease-related symptoms . Based on those findings , a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer . PATIENTS AND METHODS One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were r and omized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest , then weekly x 3 every 4 weeks thereafter ( 63 patients ) , or to fluorouracil ( 5-FU ) 600 mg/m2 once weekly ( 63 patients ) . The primary efficacy measure was clinical benefit response , which was a composite of measurements of pain ( analgesic consumption and pain intensity ) , Karnofsky performance status , and weight . Clinical benefit required a sustained ( > or = 4 weeks ) improvement in at least one parameter without worsening in any others . Other measures of efficacy included response rate , time to progressive disease , and survival . RESULTS Clinical benefit response was experienced by 23.8 % of gemcitabine-treated patients compared with 4.8 % of 5-FU-treated patients ( P = .0022 ) . The median survival duration s were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients , respectively ( P = .0025 ) . The survival rate at 12 months was 18 % for gemcitabine patients and 2 % for 5-FU patients . Treatment was well tolerated . CONCLUSION This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced , symptomatic pancreas cancer . Gemcitabine also confers a modest survival advantage over treatment with 5-FU PURPOSE To investigate the side effects , determine the maximum-tolerated dose ( MTD ) , and study the pharmacokinetics of S-1 , an oral fluoropyrimidine-based antineoplastic agent consisting of the fluorouracil ( 5-FU ) prodrug tegafur combined with two modulators , 5-chloro-2,4-dihydroxypyridine and potassium oxonate . PATIENTS AND METHODS Patients with advanced solid tumors received S-1 bid for 28 days , followed by 1 week of rest . 5-FU pharmacokinetics were investigated after a single initial dose of S-1 during the first 24 hours and weekly thereafter . RESULTS Twenty-eight patients received S-1 at the four consecutive dose levels of 25 , 45 , 35 , and 40 mg/m(2 ) . The MTD was initially found at 45 mg/m(2 ) , with diarrhea as the dose-limiting toxicity ( DLT ) . Diarrhea was also the DLT at the dose of 40 mg/m(2 ) , which was the MTD for patients exposed to extensive prior chemotherapy . Other toxicities were generally mild . Two patients had a reduction of more than 50 % in tumor dimension . Plasma pharmacokinetics of 5-FU were linear ; at the highest S-1 dose level , 5-FU plasma peak concentrations reached 1 to 2 micromol/L , and the half-life of 5-FU was 3 to 4 hours . A statistically significant relationship was observed between the severity of diarrhea and pharmacokinetic parameters of 5-FU . CONCLUSION The recommended dose of S-1 in chemotherapy-naive or minimally chemotherapy-exposed patients is 40 mg/m(2 ) bid on 28 consecutive days , every 5 weeks . In heavily pretreated patients , the recommended dose is 35 mg/m(2 ) bid . Phase II trials are warranted in tumors known to be responsive to 5-FU treatment Purpose To confirm the efficacy and toxicity of gemcitabine and S-1 combination chemotherapy when used as a first-line therapy in patients with unresectable pancreatic cancer . Methods Patients with locally advanced or metastatic or recurrent pancreatic adenocarcinoma , which was histologically or cytologically proven , with at least one measurable lesion were eligible for the study . Gemcitabine at a dose of 1,000 mg/m2 was intravenously given over 30 min on days 1 and 8 , while S-1 at a dose of 40 mg/m2 was orally given twice daily from day 1 to 14 , and the cycle was repeated every 3 weeks . The objective response rate , which was assessed according to RECIST criteria , was the primary end point . Results A total of 38 patients were enrolled between June 2006 and June 2007 . The median number of treatment courses was 5.5 ( range 1–22 ) . Thirty-four patients were evaluable for response . Although no complete response was seen , partial responses were achieved in 11 patients , result ing in an overall response rate of 32 % [ 95 % confidence interval ( CI ) 17–48 % ] . The median response duration was 6.0 months ( 95 % CI 4.6–8.3 months ) , the median time-to-progression was 5.4 months ( 95 % CI 2.9–8.0 months ) , and the median overall survival was 8.4 months ( 95 % CI 5.7–11.1 months ) . The major grade 3/4 hematologic toxicities were neutropenia ( 39.5 % ) , leukopenia ( 15.8 % ) , thrombocytopenia ( 2.6 % ) , and anemia ( 7.9 % ) . The major grade 3/4 non-hematologic toxicities included anorexia ( 10.5 % ) , stomatitis ( 2.6 % ) , rash ( 7.9 % ) , fatigue ( 7.9 % ) and hyperbilirubinemia ( 5.3 % ) . Conclusions Gemcitabine and S-1 combination chemotherapy was effective and tolerable in patients with unresectable pancreatic cancer 4131 Background : GEM is a st and ard drug for chemotherapy in patients with APC . But they should be offered better therapy aim ed more effective response and prolonging survival . UFT is also available for treatment of APC . In order to evaluate the efficacy of GEM in combination with UFT , we performed following study . METHODS Eligibility : no pretreatment ( chemotherapy and irradiation ) , good performance status ( 50 - 100 in Karnofsky Performance Status ) and less than 75 years old in APC patients such as locally advanced or with distant metastasis . The study is r and omized trial comparing two arms , arm A in which patients are treated by GEM plus UFT ( day 1 , 8 , 15 : gemcitabine 1000 mg/m2 , d.i.v./30min ; everyday : UFT 300 mg/day , oral ; every 4 weeks as 1 course ) , arm B in which patients are treated by GEM alone ( day 1 , 8 , 15 : gemcitabine 1000 mg/m2 , div/30min ; every 4 weeks as 1 course ) . Primary endpoints are response rate ( RR ) and survival time ( MST ) . Time to progression ( TTP ) and Clinical benefit response ( CBR ) were also evaluated . RESULTS During July in 2001 to March in 2003 , 19 patients ( A : B=10 : 9 ) were r and omized from two centers.depends on document review Pretreatment characteristics were well balanced between the two groups ; A vs B as median age , 60.5 vs 58.4 , stage ( locally advanced : metastatic ) , 3:7 vs 2:7 , sex difference ( male : female ) , 7:3 vs 7:2 . RR ( 0/10 vs 3/9 ) and MST ( 5.0±0.6 months vs 7.6±2.1 ) were not significant ( NS ) . CBR ( 25 % vs 33.3 % ) was NS . But TTP ( 1.9±0.5 months vs 5.0±1.5 ) was significantly different ( p=0.0408 , Logrank ) . So , from a point of ethics , the study has already stopped . Toxicity ( NCI-CTC grade 3/4 ) ; leucocytes ( 20.0%:33.3 % ) , neutrophils ( 10.0%:11.1 % ) , platelets ( 10.0%:0 % ) , diarrhea ( 10.0%:0 % ) , anorexia ( 40.0%:11.1 % ) Conclusions : The chemotherapy by GEM plus UFT in this method may not be effective compared with GEM alone . No significant financial relationships to disclose Objective : The aim of this study was to determine the maximum-tolerated dose and dose-limiting toxicity ( DLT ) of combination therapy with gemcitabine and S-1 in patients with advanced pancreatic cancer . Methods : Chemotherapy-naive patients with histologically or cytologically proven unresectable or metastatic pancreatic cancer were enrolled . The patients received gemcitabine intravenously over 30 min on days 1 and 8 and S-1 orally twice daily from days 1 to 14 . Cycles were repeated every 21 days until disease progression . Patients were scheduled to receive gemcitabine ( mg/m2/week ) and S-1 ( mg/m2/day ) at four dose levels : 800/60 ( level 1 ) , 1,000/60 ( level 2 ) , 1,000/70 ( level 3 ) and 1,000/80 ( level 4 ) . Results : Eighteen patients were enrolled in this study . The maximum-tolerated dose was not reached even at the highest dose level ( level 4 ) because only 2 of the 6 patients at this level experienced DLT . The DLTs were neutropenia and rash . Six ( 33 % ) of the 18 patients achieved a partial response and median overall survival time was 7.6 months . Conclusions : Combination chemotherapy with gemcitabine and S-1 was well tolerated and showed good antitumor activity in the treatment of pancreatic cancer . We recommend a gemcitabine dose of 1,000 mg/m2/week and an S-1 dose of 80 mg/m2/day in further studies with this schedule BACKGROUND Advanced pancreatic carcinoma ( APC ) is a rapidly fatal disease and an active chemotherapy with palliative effects and impact on patient survival is needed . 5 fluorouracil ( 5-FU ) combined with cisplatin ( CDDP ) has a recognized synergistic activity , but its activity in APC has never been well established . METHODS Forty eligible patients ( pts ) with measurable APC were treated in a phase II trial with 5-FU 1000 mg/m2/day from day 1 to day 5 by continuous intravenous infusion and CDDP 100 mg/m2 on day 2 . Eighty percent of the pts ( 36/40 ) had metastatic disease , 32.5 % ( 13/40 ) were previously treated and 65 % ( 26/40 ) had performance states of 2 or 3 . RESULTS Of 38 evaluable pts , one had a complete response and 9 achieved partial responses ; the overall response rate ( RR ) was 26.5 % ( 95 % CI : 12 % to 40 % ) . The median duration of responses was 10 months ( range 4 - 18 ) . The RR in non-pretreated pts was 32 % A palliative effect was seen in 45 % of pts ( 17/38 ) . The median survival was 7 months and 12 pts ( 29 % ) were alive at 1 year . Leukopenia was the most important toxicity ; 11 pts ( 27 % ) had a grade 4 leukopenia and 3 had neutropenic fever . CONCLUSIONS The combination of CDDP and 5-FU in continuous infusion seems an active and well tolerated treatment in APC and will be compared to st and ard therapy in a multicentric r and omized trial |
10,561 | 10,796,167 | This benefit is due to the effect of induction of labour after 41 weeks .
Routine induction of labour had no effect on caesarean section .
REVIEW ER 'S CONCLUSIONS Routine early pregnancy ultrasound examination and subsequent adjustment of delivery date appear to reduce the incidence of post-term pregnancy .
Routine induction of labour after 41 weeks gestation appears to reduce perinatal mortality .
There is not enough evidence to evaluate the effects of breast and nipple stimulation , or tests of fetal wellbeing | BACKGROUND Perinatal mortality and morbidity is increased in pregnancies of more than 42 weeks that are otherwise low risk .
OBJECTIVES The objective of this review was to assess the effects of interventions aim ed at either reducing the incidence or improving the outcome of post-term pregnancy . | OBJECTIVE Management of the uncomplicated pregnancy prolonged beyond the estimated date of confinement is controversial , particularly when the cervix is unfavorable for induction . The benefit of reducing potential fetal risk with induction of labor must be balanced against the morbidity associated with this procedure . The objective of this study was to compare two strategies for managing postterm pregnancy ( i.e. , immediate induction and expectant management ) . STUDY DESIGN Four hundred forty patients with uncomplicated pregnancies at 41 weeks ' gestation were r and omized to either immediate induction of labor ( n = 265 ) or expectant management ( n = 175 ) . Patients with expectant management underwent nonstress testing and amniotic fluid volume assessment twice per week . Patients in the induction group underwent induction within 24 hours of r and omization . To evaluate the efficacy of intracervical prostagl and in E2 gel , patients in the induction group were r and omized in a 2:1 scheme to receive either 0.5 mg prostagl and in E2 gel or placebo gel intracervically 12 hours before induction of labor with oxytocin . RESULTS The incidence of adverse perinatal outcome ( neonatal seizures , intracranial hemorrhage , the need for mechanical ventilation , or nerve injury ) was 1.5 % in the induction group and 1 % in the expectant management group ( p > 0.05 ) . There were no fetal deaths in either group . There were no differences in mean birth weight or the frequency of macrosomia ( birth weight > or = 4000 gm ) between the two groups ( p > 0.05 ) . Regardless of parity , prostagl and in E2 intracervical gel was not more effective than placebo in ripening the cervix . The cesarean delivery rate was not significantly different in the expectant ( 18 % ) , prostagl and in E2 gel ( 23 % ) , or placebo gel ( 18 % ) groups . CONCLUSIONS Adverse perinatal outcome in otherwise uncomplicated pregnancies of > or = 41 weeks is very low with either of the management schemes described . Thus from the perspective of perinatal morbidity or mortality either management scheme is acceptable In 345 women with a favorable cervical score at due date , labor was either induced by means of intravaginal application of tablets containing 3 mg of prostagl and in E2 or spontaneous onset of labor was awaited until the 42nd week of pregnancy . Eighty percent of the nulliparae and 96.3 % of the multiparae of the induction group gave birth within 24 h of the administration of the first tablet . All pertinent delivery intervals were significantly shorter in this group compared to those women where spontaneous onset of labor was awaited . The rate of operative deliveries was lower in the induction group . With the exception of 1 fetal death 3 days after due date , fetal outcome was excellent in both groups . Elective induction was at least equivalent to awaiting the onset of spontaneous labor and was not associated with higher complication rates due to the method of induction A prospect i ve r and omized controlled trial design ed to investigate selective planned delivery is reported : 264 obstetrically normal women in the 38th week of pregnancy were admitted to this trial and 184 completed it . The infants of mothers in the planned delivery group had higher serum bilirubin levels on the fifth day post partum than control infants but no baby required treatment for hyperbilirubinaemia . Mothers in the planned delivery group required significantly greater amounts of pethidine while control mothers had a significantly higher incidence of meconium staining of the amniotic fluid . However , the infants in the two groups had similar Apgar scores at birth . There was one stillbirth in the control group ; this was due to unrecognized fetal hypoxia during labour induced at 42 weeks for postmaturity In a prospect i ve r and omized study , pregnancies with unfavorable cervix and well established gestational age of at least 42 weeks were selected for management by either antepartum fetal testing or prostagl and in gel induction of labor . Of the 108 pregnancies studied , 57 ( 53 % ) had labor induced and 51 ( 47 % ) continued without intervention . Comparison of the two groups showed no difference in meconium staining , fetal distress , length of first stage of labor , the need for intervention , or the mode of delivery . In terms of Apgar score the neonatal outcome was not significantly different but a greater proportion of the babies ( 7.8 % versus 1.8 % ) in the noninduced group required intubation . Our data show that there is no particular advantage in letting the pregnancy go beyond 42 completed weeks of gestation especially if prostagl and in is available for induction of labor Objecfive To determine the proper management of pregnancy in uncomplicated cases going beyond 42 weeks Objective To compare the impact on perinatal outcome of two different protocol s for antenatal fetal monitoring after 42 weeks gestation Abstract . In a prospect i ve r and omized study spontaneous and oxytocin induced labor “ for convenience ” have been compared with respect to uterine activity , duration of labor , the condition of the fetus and the newborn infant . The study consists of 84 normal patients , of whom 43 were induced at full term by amniotomy and oxytocin infusion using the Cardiff Infusion System Mark II ; 41 patients served as controls . No difference in maternal age , number of previous pregnancies and pelvic score one week before the day of delivery were found between the groups . The following parameters were calculated : duration of labor , uterine activity , amount of bleeding in the third stage of labor , number of early and late decelerations as well as number of episodes of bradycardia in the CTG‐recordings , birth weight , Apgar score one and five minutes post‐delivery and blood gases in mother and child 60 seconds after delivery . No significant differences between the two groups were found . It is concluded that there are no increased risks to mother or fetus compared to normal labor provided that there is cephalic presentation and normal pregnancy , careful selection with respect to the length of pregnancy and the condition of the cervix and that the Cardiff infusion system is used with intrauterine pressure recording and continuous fetal heart monitoring In a prospect i ve , r and omised trial , 111 obstetrically normal pregnant women , who had elective induction of labour performed between 39 and 40 weeks , were compared with 117 controls who were managed expectantly until 41 weeks . Compared with the controls , the patients who had elective induction of labour had significantly less meconium staining in labour and a smaller blood-loss after delivery . The mean length of labour , the amount of pethidine used , and the Apgar scores at 1 minute were similar in the two groups . In the electively induced group , the caesarean-section rate was lower and the use of epidural analgesia more common than in the controls , but the differences were mot statistically signficant . The hour of delivery was similar in the two groups , suggesting that convenience to medical and nursing staff would not be greatly changed by elective induction of labour . There was no evidence that the hazards to mother and child were increased by elective induction , and its use might improve perinatal mortality by reducing the number of unexplained mature stillbirths Nine hundred fifteen of 2171 pregnant patients had no indication for ultrasound at their first prenatal visit and were r and omly assigned to receive either a single routine screening ultrasound or usual prenatal care . The estimated date of confinement was altered in 24.9 % of routine-ultrasound patients and in 11.6 % of usual-care patients through ultrasound examinations obtained for a subsequent clinical indication . Of these , 8.3 % of routine-ultrasound and 5.2 % of usual-care patients had gestational age errors of 2 weeks or more . There were no differences between the groups in inductions for post- date s pregnancy ( 7.0 versus 7.5 % ; P=.87 ) , total inductions ( 22.6 versus 24.9 % ; P=.61 ) , or adverse perinatal outcomes ( 6.7 versus 8.3 % ; P=.63 ) . Both sets of twins were detected in the screened group . In the usual-care group , five of seven pairs of twins ( 71 % ) were diagnosed by 24 weeks'gestation . There was no benefit found from routine ultrasound as performed in this study A r and omized prospect i ve clinical trial of induction of labor at 42 completed weeks gestation versus expectant management in post date s pregnancies was performed . The primary screening test was the 24-hr urinary estriol creatinine ratio . The cesarean section rate was high in both groups and did not differ statistically . Intervention by delivery at 42 weeks decreased the development of small for gestational age infants , but costs slightly more . Twenty-four-hour urinary estriol creatinine ratio determinations predicted fetal distress in labor , but could not predict postmaturity syndrome or infants who were small for gestational age . As expectant management did not differ from induction of labor at 42 weeks from the st and point of maternal outcome , and as the cost difference was small , induction of labor at 42 weeks may be the preferred management as it improves infant outcome The influence of nipple stimulation ( NS ) at term on the duration of pregnancy was investigated among low-risk gravidas in a r and omized prospect i ve study . A significant inverse relationship was found between the duration of pregnancy and both gestational age at recruitment and cervical ( Bishop ) score , although the influence of cervical score was quantitatively small . Nipple stimulation did not influence either the duration of pregnancy or the probability of having a cesarean section or an instrumental delivery . Patient compliance was , however , poor , which may in part account for these findings , as there was an inverse trend between the daily average duration of NS and the duration of pregnancy Three hundred two low-risk obstetric patients with an unfavorable cervical examination and well-established gestational age of at least 287 days were r and omly selected for management by either antepartum fetal testing or prostagl and in gel cervical ripening followed by aggressive induction of labor and delivery . The patients managed by induction of labor had a lower incidence of meconium-stained amniotic fluid , meconium aspiration , low Apgar scores , postmaturity syndrome , fetal distress , and cesarean delivery than did patients managed with antepartum fetal testing . Our data suggest that prostagl and in gel cervical ripening and induction of labor and delivery by 42 weeks ' gestation may be the most appropriate management for patients with well-established gestational age and an unfavorable cervical examination In a prospect i ve r and omized study spontaneous and oxytocin induced labor have been compared with respect to duration of labor and the condition of the fetus and the newborn infant . The study consists of 166 normal patients at full term . No significant differences between the two groups were found , and the results of the study showed that induction of labor between the 40th and 41st week of pregnancy was safe for the fetus . It is concluded that there seems to be no increased risks to mother or fetus from induction of labor compared to normal labor provided that there is cephalic presentation and a normal pregnancy A non-aggressive approach to the management of post- date pregnancies was tested in a clinical trial involving 156 patients who had reached 294 days of amenorrhea and had a pelvic score of 4 or less . Date s had been established with certainty in each case . In half of the patients ( the study group ) no time limit was imposed on the pregnancy , but the women were checked at frequent intervals for any increase in pelvic score and for changes in any of the following : fetal movement count recorded daily by the mother , an oxytocin challenge test , and amnioscopy . The pregnancy ended either through spontaneous contractions or through surgical induction carried out because of a change in any one of the parameters or an increase above 4 in the pelvic score . In the 78 control patients labor was induced surgically on day 294 , even if the pelvic score was low . In the study group , labor started spontaneously in 52 patients ; labor was induced in 17 women after they showed an elevated pelvic score , in 7 because of a pathologic parameter and in one because a mild pre-eclampsia developed . There were 7 cesarean sections in the study group compared with 16 in the control group ( P less than 0.05 ) . The average duration of labor was 6.7 h in the study group , compared with 9.4 h in the control ( P less than 0.01 ) . There was no significant difference between the two groups with regard to meconium staining during labor , pathologic fetal heart rate , or the 5 min Apgar score . In the study group there was one neonatal death as a result of severe congenital heart disease , and in the control group one infant died due to asphyxia . It is concluded that conservative management of prolonged pregnancies , with close supervision , gives better results than routine induction of labor at 42 wk . The importance of the pelvic score as an indication for induction is stressed . A protocol has been developed which can be used in cases of uncertain date s as well OBJECTIVE To determine the cost-effectiveness of induction of labour versus serial fetal monitoring while awaiting spontaneous labour in postterm pregnancies . DESIGN Cost-effectiveness and cost-minimization analyses conducted as part of a Canadian multicentre r and omized clinical trial . SETTING Twenty-two Canadian hospitals , of which 19 were teaching hospitals and 3 were community hospitals . PATIENTS Women with uncomplicated pregnancies of 41 or more weeks ' gestation were r and omly assigned to induction of labour or serial antenatal monitoring . Of the 3418 women enrolled , no data were received on 11 . Therefore , results were based on data from 1701 women in the induction arm of the study and 1706 women in the monitoring arm . MAIN OUTCOME MEASURES Perinatal mortality and neonatal morbidity , rates of cesarean section and health care costs . Hospital costing models were developed specifically for the study . Data on use of major re sources ( e.g. , length of hospital stay , surgical procedures , major diagnostic tests and procedures , and medications ) for all trial participants were collected and combined with data on minor tests and procedures ( e.g. , laboratory tests ) abstract ed from a detailed review of medical records of a sample of patients . RESULTS Because the results of the clinical trial showed a nonsignificant difference in perinatal mortality and neonatal morbidity between the induction and monitoring arms , the authors conducted a cost-minimization rather than a cost-effectiveness analysis . The mean cost per patient with a postterm pregnancy managed through monitoring was $ 3132 ( 95 % confidence interval [ CI ] $ 3090 to $ 3174 ) and per patient who underwent induction of labour was $ 2939 ( 95 % CI $ 2898 to $ 2981 ) , for a difference of $ 193 . The significantly higher ( p < 0.0001 ) mean cost per patient in the monitoring arm was due mainly to the costs of additional monitoring and the significantly higher rates of cesarean section among these patients . Estimated conservatively , the savings result ing from a universal policy of managing postterm pregnancies by induction of labour in Canada may be as high as $ 8 million a year . CONCLUSIONS A policy of managing postterm pregnancy through induction of labour not only results in more favourable outcomes than a monitoring strategy but does so at a lower cost Post date pregnancy is estimated to occur in 3 % to 12 % of all gestations . Morbidity and mortality rates associated with this common obstetric problem are higher than those with term gestation . The incidence of fetal distress , birth injury , meconium aspiration , congenital malformations , macrosomia , and oligohydramnios is also greater in post date pregnancy . We prospect ively evaluated breast self-stimulation to determine its effect on the incidence of post date pregnancy . Two hundred low-risk patients at 39 weeks ' gestation were r and omly assigned to either a control group or a breast-stimulation group . Results showed that breast stimulation reduced the number of pregnancies managed as post date s from 17 per 100 ( 17 % ) to five per 100 ( 5 % ) ( p less than 0.01 ) , a 70 % reduction . It is concluded that breast stimulation in post date s pregnancies can decrease significantly the number of patients that must be monitored by biochemical or biophysical means In a prospect i ve r and omised study of mothers referred for prolonged pregnancy ( around the 42nd week ) 214 ( group 1 ) were su bmi tted to attempted induction of labour and 195 ( group 2 ) assigned to continue for a further week without intervention . Strict selection criteria were used for the certainty of term . Mothers in group 2 were given regular non-stress tests to ensure fetal wellbeing , as were those in group 1 in whom induction failed . In group 1 , 48 ( 23 % ) out of 210 first attempted inductions failed . In group 2 , 135 ( 69 % ) of the births started spontaneously as compared with 38 ( 18 % ) in group 1 . The mean duration of labour was 7.5 hours in each group . There was no significant difference in incidence of operative delivery , use of analgesics , or signs of perinatal asphyxia . Significantly more children in group 1 needed phototherapy for hyperbilirubinaemia . There was a clustering of births in the late afternoon and evening , which was most pronounced in group 1 . A policy of vigilant non-intervention up to the 44th completed week of pregnancy does not appear to jeopardize mother or fetus A prospect i ve trial was conducted to compare the effects of conservative management of prolonged pregnancy ( conservative group ) with routine induction of labour at 42 weeks ' gestation ( active group ) in otherwise uncomplicated pregnancies . Of the 402 pregnancies studied , 207 ( 51 % ) were allocated to conservative management and 195 ( 49 % ) were allocated to have labour induced . The groups were well matched for age , parity , and smoking habits . One hundred and sixty six ( 80 % ) of the patients in the conservative group went into spontaneous labour . Of the remainder , two underwent elective caesarean section , 19 had labour induced because of clinical concern , and the remaining 20 had labour induced at the patient 's own request . One hundred and twenty five ( 64 % ) of the patients in the planned active group underwent induction of labour . Of the remaining 70 , 49 went into spontaneous labour and 21 ( 11 % ) asked that they should not have labour induced . Comparison of the two groups showed no difference in the length of the first stage of labour but a trend towards an increased need for intervention for fetal distress ( p less than 0.06 ) in the active group . There were no differences in the length of the second stage , the need for intervention , or the mode of delivery . In terms of Apgar scores the neonatal outcome was not significantly different between the two groups , but a greater proportion of the babies ( 15 % v 8 % ) in the active group required intubation . Umbilical cord venous pH estimated in the last 183 consecutive deliveries in the study showed a significantly lower mean value in the active group ( p less than 0.05 ) . There was no difference in birth weight between the two groups . Two deaths occurred in the study . There was a stillbirth in the conservative group at 292 days after massive abruption , and one neonatal death in the active group owing to multiple congenital abnormalities . The outcome for mother and baby in patients from both groups who went into spontaneous labour was generally good . The outcome for patients for whom conservative management was planned but induction became necessary was no different from that of patients who underwent planned induction at term . Thus from our results we can find no evidence to support the view that women with normal prolonged pregnancy should undergo routine induction of labour at 42 weeks ' gestation 4997 of 7354 pregnant women had no clinical indication for an elective ultrasound examination at 12 weeks ' gestation . 2482 of these women were r and omly selected for ultrasound screening at 15 weeks and the remainder received the same st and ard antenatal care without the scan . Labour was less often induced among screened women both for all reasons ( 5.9 % vs 9.1 % , p less than 0.0001 ) and for suspected post-term pregnancy ( 1.7 % vs 3.7 % , p less than 0.0001 ) . Earlier detection of twins had no effect on neonatal outcome . Among babies born to screened women , fewer were of birthweight less than 2500 g ( 59 vs 95 , p = 0.005 ) and mean birthweight was 42 g higher ( p 0.008 ) . For babies born to screened women who smoked it was 75 g higher ( p 0.012 ) and for those of non-smokers 26 g ( not significant ) . The reason for the differences in mean birthweight could be that screened women reduced smoking in response to watching their fetus on the scan 510 of 1009 pregnant women in the Trondheim area ( Norway ) were r and omly selected for ultrasound examination at the 19th and 32nd weeks of pregnancy in addition to routine antenatal care . Among the screened women , twins were diagnosed earlier and there were slightly fewer post-term inductions ( 2.8 % versus 4.0 % ) and fewer low-weight births ( 2.2 % versus 3.6 % less than 2500 g ) , but none of these differences was statistically significant . There were no differences in the condition of the newborn . Small-for-gestational-age births were more often diagnosed antenatally in the screened group and the mothers received more active treatment . During pregnancy , screened women were admitted to hospital more often than unscreened women ( 15.5 % versus 9.2 % ) . The study revealed no adverse short-term biological effects from ultrasound . The cost of the screening programme , including associated costs such as extra hospital admissions , was about US$ 250 per pregnancy |
10,562 | 28,433,263 | RESULTS Most of the studies used neuropsychological tests and fMRI ; these methods are considered to have the greatest predictive ability for memory impairment .
Other less frequently used techniques included the Wada test and FDG-PET .
CONCLUSIONS Current evidence supports performing a presurgical assessment of memory function using both neuropsychological tests and functional MRI to predict memory outcome after surgery | INTRODUCTION Given that surgical treatment of refractory mesial temporal lobe epilepsy may cause memory impairment , determining which patients are eligible for surgery is essential .
However , there is little agreement on which presurgical memory assessment methods are best able to predict memory outcome after surgery and identify those patients with a greater risk of surgery-induced memory decline .
OBJECTIVE We conducted a systematic literature review to determine which presurgical memory assessment methods best predict memory outcome . | Objective : The present study aim ed to examine and compare memory processing in patients with unilateral temporal lobe epilepsy ( TLE ) before and after surgery using functional magnetic resonance imaging ( fMRI ) . Methods : Seventeen preoperative patients with unilateral TLE ( nine left , eight right ) and eight healthy controls were recruited . They performed a complex visual scene-encoding task during fMRI to measure memory activation in the mesial temporal lobe . Their memory performance was evaluated using st and ardised neuropsychological tests . After unilateral temporal lobe resection ( either temporal lobectomy , selective amygdalohippocampectomy or lesionectomy ) , the same fMRI paradigm and neuropsychological tests were administered to the patient group . Results : Left-TLE patients demonstrated a decline in verbal memory after left temporal lobe resection . Their postoperative verbal and visual memory performance was positively associated with postoperative functional activation in the right mesial temporal lobe , whereas the postoperative memory performance of right-TLE patients was positively associated with postoperative functional activation in the left mesial temporal lobe , contralateral to their respective side of resection . Conclusion : Postoperative memory performance was significantly associated with functional activation contralateral to the side of resection in patients with unilateral TLE , and the function of the contralateral mesial temporal lobe might play an important role in supporting memory performance after temporal lobe resection Objective : To develop a clinical ly applicable memory functional MRI ( fMRI ) method of predicting postsurgical memory outcome in individual patients . Methods : In this prospect i ve cohort study , 50 patients with temporal lobe epilepsy ( 23 left ) and 26 controls underwent an fMRI memory encoding paradigm of words with a subsequent out-of-scanner recognition assessment . Neuropsychological assessment was performed preoperatively and 4 months after anterior temporal lobe resection , and at equal time intervals in controls . An event-related analysis was used to explore brain activations for words remembered and change in verbal memory scores 4 months after surgery was correlated with preoperative activations . Individual lateralization indices were calculated within a medial temporal and frontal region and compared with other clinical parameters ( hippocampal volume , preoperative verbal memory , age at onset of epilepsy , and language lateralization ) as a predictor of verbal memory outcome . Results : In left temporal lobe epilepsy patients , left frontal and anterior medial temporal activations correlated significantly with greater verbal memory decline , while bilateral posterior hippocampal activation correlated with less verbal memory decline postoperatively . In a multivariate regression model , left lateralized memory lateralization index ( ≥0.5 ) within a medial temporal and frontal mask was the best predictor of verbal memory outcome after surgery in the dominant hemisphere in individual patients . Neither clinical nor functional MRI parameters predicted verbal memory decline after nondominant temporal lobe resection . Conclusion : We propose a clinical ly applicable memory fMRI paradigm to predict postoperative verbal memory decline after surgery in the language -dominant hemisphere in individual patients Temporal lobectomy is an effective therapy for medically refractory temporal lobe epilepsy ( TLE ) , but may be complicated by amnestic syndromes . Therefore , pre-surgical evaluation to assess the risk/benefit ratio for surgery is required . Intracarotid amobarbital testing ( IAT ) is currently the most widely used method for assessing pre-surgical memory lateralization , but is relatively invasive . Over the past decade functional MRI ( fMRI ) has been shown to correlate with IAT for language lateralization , and also for memory lateralization in a small number of patients . This study was carried out to compare fMRI during memory encoding with IAT testing for memory lateralization , and to assess the predictive value of fMRI during memory encoding for post-surgical memory outcome . Thirty-five patients with refractory TLE undergoing pre-surgical evaluation for temporal lobectomy and 30 normal subjects performed a complex visual scene-encoding task during fMRI scanning at 1.5 T using a 10-min protocol . Encoding performance was evaluated with subsequent recognition testing . Twenty-three patients also completed the same task again outside the scanner , an average of 6.9 months following surgery . A region of interest ( ROI ) analysis was used to quantify activation within hippocampal and a larger mesial temporal lobe ROI consisting of hippocampus , parahippocampus and fusiform gyrus ( HPF ) as defined by a published template . Normal subjects showed almost symmetrical activation within these ROI . TLE patients showed greater asymmetry . Asymmetry ratios ( ARs ) from the HPF ROI correlated significantly with memory lateralization by intracarotid amobarbital testing . HPF ARs also correlated significantly with memory outcome , as determined by a change in scene recognition between pre-surgical and post-surgical trials . When absolute activation within the HPF ROI was considered , a significant inverse correlation between activation ipsilateral to temporal lobectomy and memory outcome was observed , with no significant correlation in the contralateral HPF ROI . Although further technical improvements and prospect i ve clinical validation are required , these results suggest that mesial temporal memory activation detected by fMRI during complex visual scene encoding correlates with post-surgical memory outcome and supports the notion that this approach will ultimately contribute to patient management Objective : To assess the long-term effects of temporal lobe epilepsy surgery on verbal memory . Methods : We assessed verbal memory performance as measured by a verbal learning test ( “ 15 Words Test , ” a Dutch adaptation of Rey 's Auditory Verbal Learning Test ) before surgery and at three specific times after surgery : 6 months , 2 years , and 6 years in 85 patients ( 34 left temporal lobe [ LTL ] vs. 51 right temporal lobe [ RTL ] ) . An amygdalo-hippocampectomy and a neocortical temporal resection between 2.5 and 8 cm were carried out in all patients . Results : LTL patients showed an ongoing memory decline for consolidation and acquisition of verbal material ( both 2/3 SDs ) for up to 2 years after surgery . RTL patients at first showed a gain in both memory acquisition and consolidation , which vanished in the long term . Breaking the group up into a mesiotemporal ( MTS ) group and a non-MTS group showed clear differences . The group with pure MTS showed an overall lower verbal memory performance than the group without pure MTS , in the LTL group more pronounced than in the RTL group . After surgery , both pathology groups showed an ongoing decline for up to 2 years , but the degree of decline was greater for the LTL patients with MTS compared with the non-MTS group . Becoming and remaining seizure-free after surgery does not result in a better performance in the long term . Predictors of postoperative verbal memory performance at 6 years after surgery were side of surgery , preoperative memory score , and age . Conclusions : The results provide evidence for a dynamic decline of verbal memory functions up to 2 years after left temporal lobectomy , which then levels off PURPOSE Previous studies have shown that structural integrity ( i.e. , presence/absence of mesial temporal sclerosis ( MTS ) ) of the left mesial temporal lobe is associated with verbal memory outcome following left anterior temporal lobectomy ( ATL ) . However , the functional integrity of the left temporal lobe , as exemplified by preoperative verbal memory performance , has also been associated with verbal memory outcome following surgery . We investigated the risk of verbal memory loss in patients with known structural abnormality ( i.e. , left mesial temporal sclerosis by MRI ) and normal preoperative verbal memory performance who undergo left ATL . METHODS Seventeen patients with left temporal lobe epilepsy , MRI-based exclusive left MTS , and normal preoperative verbal memory were identified . Normal verbal memory was defined as performance on both Acquisition ( learning across trials 1 - 5 ) and Retrieval ( long delayed free recall ) portions of the California Verbal Learning Test ( CVLT ) above a T score of 40 ( > 16%ile ) . Postoperative verbal memory outcome was established by incorporating st and ardized regression-based ( SRB ) change scores . RESULTS Postoperative declines across both CVLT Retrieval T scores and Acquisition T scores ( average 20 % and average 15 % declines from baseline scores , respectively ) were measured for the group . The average CVLT Retrieval SRB change score was -2.5 , and the average CVLT Acquisition SRB change score was -1.0 . A larger proportion of patients demonstrated postoperative declines on Retrieval scores than Acquisition scores ( 64.7 % vs 17.6 % , respectively ) . CONCLUSIONS Even in the presence of left MTS , patients exhibiting normal presurgical verbal memory are at risk for verbal memory declines following ATL . These results suggest that the functional integrity of the left mesial temporal lobe may play an important role in the verbal memory outcome in this patient group The contribution of the Wada test ( intracarotid amytal procedure , IAP ) to predicting postoperative memory outcome in left temporal lobe epilepsy ( LTLE ) is becoming increasingly controversial when preoperative neuropsychological evaluation and MRI findings are available . We retrospectively analyzed 59 patients with LTLE who underwent en bloc temporal lobe resection . All patients had valid bilateral IAP test results , complete pre- and postoperative neuropsychological evaluation , and MRI grading on a 5-point scale integrating T 2 signal increase and degree of atrophy . Thirty percent of patients showed postoperative memory decline . Multiple regression analysis revealed that significant predictors of decline [ F(2.56)=22.71 , P<0.001 , r(2)=0.448 ] included preoperative memory learning score [ t=-5.89 , P<0.001 ] and MRI classification [ t=3.10 , P<0.003 ] , but not IAP scores . The IAP is of no added value in the prediction of postoperative memory outcome in LTLE in the presence of comprehensive neuropsychological and MRI data Purpose : In the surgical treatment of mesial temporal lobe epilepsy , there is converging evidence that individually tailored or selective approaches have a favorable cognitive outcome compared to st and ard resections . There is , however , also evidence that due to collateral damage , selective surgery can be less selective than suggested . As part of a prospect i ve transregional research project the present study evaluated the outcome in memory and nonmemory functions , following two selective approaches : a combined temporal pole resection with amygdalohippocampectomy ( TPR+ ) and transsylvian selective amygdalohippocampectomy ( SAH ) |
10,563 | 15,068,985 | Studies also relate heavy per-occasion alcohol use ( binge drinking ) to acute injury risks and alcohol-related life problems ( 4 , 22 ) .
Injury rates are higher for binge drinkers who consume 5 or more drinks on one occasion as infrequently as 3 to 6 times per year , even when average intake is not excessive ( 24 ) .
Even so , few primary care clinicians use recommended screening protocol s or offer treatment ( 33 ) .
Definitions No consistent definitions for the drinking patterns that should be the focus of primary care interventions are available from existing guidelines or research ; however , it is commonly held that less severe alcohol problems are appropriate for brief interventions in primary care , whereas more severe problems need specialty addiction treatment ( 41 ) . | Alcohol misuse , including risky and harmful drinking , alcohol abuse , and dependence , is associated with numerous health and social problems and with more than 100 000 deaths per year ( 1 ) .
Risky drinkers consume alcohol above recommended daily , weekly , or per-occasion amounts .
Harmful drinkers experience harm associated with their alcohol use but do not meet criteria for alcohol abuse or dependence ( 2 ) .
Persons who misuse alcohol have elevated risks for a host of health problems ( 3 - 6 ) , including violence-related trauma and injury ( 4 ) .
Most individuals who consume alcohol do so in moderation and without adverse consequences , however , and observational research suggests light or moderate use may be beneficial for some people ( 7 - 20 ) .
The assumption underlying brief behavioral counseling interventions in primary care is that , for identified risky or harmful drinkers , reducing overall alcohol consumption or adopting safer drinking patterns ( that is , fewer drinks per occasion and not drinking before driving ) will reduce the risk for medical , social , and psychological problems ( 21 ) .
Little experimental evidence supports this assumption , and most epidemiologic evidence relates health outcomes to existing drinking behaviors rather than to changes in drinking behaviors .
Cross-sectional and cohort studies have consistently related high average alcohol consumption to short- or long-term health consequences ( 4 , 22 ) .
In the United States , the National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) has proposed epidemiologically based alcohol use guidelines to limit risks for short- and long-term drinking-related consequences by establishing age- and sex-specific recommended consumption thresholds ( 25 ) .
Maximum recommended consumption is 1 or less st and ard drink per day for adult women and for anyone older than 65 years of age and 2 or fewer st and ard drinks per day for adult men .
These guidelines do not apply to persons ( such as adolescents , pregnant women , and persons with alcohol dependence or medical conditions or medication use ) for whom alcohol intake is contraindicated , or to circumstances ( driving ) in which no consumption is considered safe .
Primary care clinicians commonly see patients with a range of alcohol-related risks and problems .
Prevalence of these forms of alcohol misuse generally is higher in males and younger persons of all races and ethnicities ( 28 ) .
Our review addressed the following questions : Do behavioral counseling interventions in primary care reduce risky or harmful alcohol use ?
What are elements of effective interventions ?
Do such interventions improve health outcomes ?
What methods were used to identify risky/harmful drinkers for behavioral counseling interventions in primary care ?
What adverse effects are associated with interventions addressing risky/harmful drinkers in primary care ?
What health care system influences are present in effective interventions for risky and harmful drinkers in primary care ?
Risky or hazardous drinkers are at risk from consumption that exceeds daily , weekly , or per-occasion thresholds ( other terms further distinguish risky/harmful users who exceed longer-term thresholdshigh-average or heavy usersfrom heavy occasional or binge drinkers , who exceed per-occasion thresholds ) .
Harmful drinkers experience physical , social , or psychological harm from their above-threshold alcohol use without meeting criteria for dependence .
Alcohol-abusing/dependent drinkers continue to use alcohol despite significant negative physical , psychological , and social consequences ( 42 ) ; generally meet criteria for abuse or dependence as outlined in the Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( 43 ) ; and are c and i date s for specialty addiction treatment . | BACKGROUND AND PURPOSE Physical activity reduces the risk of premature death and cardiovascular disease , but the relationship to stroke is less well studied . The objective of this study was to investigate the association between leisure-time physical activity and ischemic stroke in an urban , elderly , multiethnic population . METHODS The Northern Manhattan Stroke Study is a population -based incidence and case-control study . Case subjects had first ischemic stroke , and control subjects were derived through r and om-digit dialing with 1:2 matching for age , sex , and race/ethnicity . Physical activity was recorded through a st and ardized in-person interview regarding the frequency and duration of 14 activities over the 2 prior weeks . Conditional logistic regression was used to calculate odds ratios ( OR ) and 95 % confidence intervals after adjustment for medical and socioeconomic confounders . RESULTS Over 30 months , 369 case subjects and 678 control subjects were enrolled . Mean age was 69.9 + /- 12 years ; 57 % were women , 18 % whites , 30 % blacks , and 52 % Hispanics . Leisure-time physical activity was significantly protective for stroke after adjustment for cardiac disease , peripheral vascular disease , hypertension , diabetes , smoking , alcohol use , obesity , medical reasons for limited activity , education , and season of enrollment ( OR = 0.37 ; 95 % confidence interval=0.25 to 0.55 ) . The protective effect of physical activity was detected in both younger and older groups , in men and women , and in whites , blacks , and Hispanics . A dose-response relationship was shown for both intensity ( light-moderate activity OR = 0.39 ; heavy OR = 0.23 ) and duration ( < 2 h/wk OR = 0.42 ; 2 to < 5 h/wk OR = 0.35 ; > or = 5 h/wk OR = 0.31 ) of physical activity . CONCLUSIONS Leisure-time physical activity was related to a decreased occurrence of ischemic stroke in our elderly , multiethnic , urban subjects . More emphasis on physical activity in stroke prevention campaigns is needed among the elderly Seventy two women drinking 21 units ( 210 g ) or more of alcohol per week were recruited from an opportunistic screening programme in eight English general practice s. The women were r and omized into control and treatment groups . Women in the treatment group received ten minutes advice from their general practitioner to reduce alcohol consumption . At one year follow-up , when analyzed by intention to treat , women in the treatment group had reduced their alcohol consumption from an average of 35 - 24 units per week . Similar reductions were found in the control group ( from 37 - 27 units per week ) . The lack of evidence for a treatment effect may be explained by contamination of the control group by informal interventions In a controlled evaluation of general practitioner (GP)-based brief intervention , 378 excessive drinkers identified opportunistically by screening in 40 group practice s in metropolitan Sydney were assigned to groups receiving : ( i ) a five-session intervention by the GP ( the Alcoholscreen Program ) ; ( ii ) a single session of 5 minutes ' advice by the GP plus a self-help manual ( minimal intervention ) ; ( iii ) an alcohol-related assessment but no intervention ; ( iv ) neither intervention nor assessment . Among all patients allocated to receive it , the Alcoholscreen Program did not result in a significantly greater reduction in consumption at follow-up than control conditions but patients offered Alcoholscreen reported a significantly greater reduction in alcohol-related problems in the period to 6 months follow-up . A greater proportion of patients who returned for the second Alcoholscreen visit were drinking below recommended levels at follow-up than in the remainder of the sample . There was no evidence that minimal intervention or alcohol-related assessment were effective in reducing alcohol consumption or problems . Implication s for further research into GP-based brief interventions are discussed Patients admitted to an emergency surgical ward were screened for alcohol problems and r and omized between an extensive alcohol counseling and a brief assessment followed by feedback of risky alcohol consumption . Some 165 patients were assessed for risk consumption and followed up 6 to 12 months , and it was found that patients in both interventions significantly reduced the amount they drank per occasion although they drank as often as before . The patients had also moved to a stage more ready to change . No differences in effect were found between the interventions . A brief assessment with feedback about risk consumption can be done on an emergency surgical ward by the surgical staff with a few hours of training and may reduce risky alcohol consumption significantly BACKGROUND The U.S. Congress m and ated evaluations , initiated in 1989 , to determine whether extending Medicare benefits to include preventive services would improve health status , reduce costs of care , and improve health risk behaviors of beneficiaries . METHODS The Johns Hopkins Medicare Preventive Services Demonstration was a r and omized trial in which Medicare beneficiaries were assigned either to an intervention group that was offered yearly preventive visits for 2 years and optional counseling visits to their primary care provider or to a control group that received usual care . This report describes the effect of the intervention over a period of 2 years on smoking , problem alcohol use , and sedentary lifestyle . RESULTS Differences were observed between the intervention and control groups in the extent to which changes occurred in smoking and problem alcohol use , but none of the differences was statistically significant . The proportion of smokers who quit was higher in the intervention group than in the control group ( 24.2 vs 17.9 % , P = 0.09 ) . However , a higher proportion of problem drinkers in the control group improved ( 67.1 vs 57.0 % , P = 0.183 ) . There was virtually no difference between the intervention and the control groups in the proportion with improvement in sedentary lifestyle . CONCLUSIONS This study demonstrates the difficulty of bringing about health behavior change in older patients in the course of a yearly preventive visit for 2 years with their primary care physician when the visit encompasses screening and immunizations , as well as health behavior counseling directed by the physician . Further study is required to determine whether a more intense program of counseling for health behavior change among older persons by their primary care providers would be effective OBJECTIVE To compare the effects of three brief methods of reducing alcohol consumption among family practice patients . DESIGN Patients r and omly assigned to one of three interventions were assessed initially and at 3- , 6- , and 12-month follow-up appointments . SETTING Family practice clinic composed of 12 primary care physicians seeing approximately 6000 adults monthly in a small urban community , population 40,000 . PARTICIPANTS Through a screening question naire , 134 men and 131 women were identified as hazardous drinkers ( five or more drinks at least once monthly ) during an 11-month screening of 1420 patients . Of 265 patients approached , 180 agreed to participate and 159 ( 83 men and 76 women ) actually participated in the study . INTERVENTIONS Three interventions were studied : brief physician advice ( 5 minutes ) , two 30-minute sessions with a physician using cognitive behavioural strategies or two 30-minute sessions with a nurse practitioner using identical strategies . MAIN OUTCOME MEASURES Quantity and frequency ( QF ) of drinking were used to assess reduction in hazardous drinking and problems related to drinking over 12 months of follow up . RESULTS No statistical difference between groups was found . The QF of monthly drinking was reduced overall by 66 % ( among men ) and 74 % ( among women ) for those reporting at least one hazardous drinking day weekly at assessment ( N = 96 ) . Men reported drinking significantly more than women . CONCLUSIONS These results indicated that offering brief , specific advice can motivate patients to reduce their alcohol intake . There was no difference in effect between brief advice from their own physician or brief intervention by a physician or a nurse Sixteen general practitioners participated in a controlled trial of the Scottish Health Education Group 's DRAMS ( drinking reasonably and moderately with self-control ) scheme . The scheme was evaluated by r and omly assigning 104 heavy or problem drinkers to three groups - a group participating in the DRAMS scheme ( n = 34 ) , a group given simple advice only ( n = 32 ) and a non-intervention control group ( n = 38 ) . Six month follow-up information was obtained for 91 subjects ( 87.5 % of initial sample ) . There were no significant differences between the groups in reduction in alcohol consumption , but patients in the DRAMS group showed a significantly greater reduction in a logarithmic measure of serum gamma-glutamyl-transpeptidase than patients in the group receiving advice only . Only 14 patients in the DRAMS group completed the full DRAMS procedure . For the sample as a whole , there was a significant reduction in alcohol consumption , a significant improvement on a measure of physical health and well-being , and significant reductions in the logarithmic measure of serum gamma-glutamyl transpeptidase and in mean corpuscular volume . The implication s of these findings for future research into controlled drinking minimal interventions in general practice are discussed OBJECTIVE : To determine effectiveness of advice from general practitioners to heavy drinkers to reduce their excessive alcohol consumption ( 35 U or more a week for men , 21 U or more for women ) . DESIGN : R and omised , controlled double blind trial over 12 months with interim assessment at six months . SETTING : Group practice s ( n = 47 ; list size averaging 10,000 ) recruited from Medical Research Council 's general practice research framework , mostly in rural or small urban setting s. PATIENTS : Patients recruited after question naire survey . Of total of 2571 ( 61.2 % ) of 4203 patients invited for interview who attended , 909 ( 35.4 % ) stated that in past seven days they had drunk above the limits set for study and had not received advice ; they were r and omised to control and treatment groups . INTERVENTIONS : Patients in treatment group were interviewed by general practitioner ( who had had a training session ) and received advice and information about how to reduce consumption and also given a drinking diary . END POINT : Study aim ed at detecting a reduction in proportion of men with excessive alcohol consumption of 30 % in treatment group and 20 % in control group ( for women 40 % and 20 % , respectively ) with a power of 90 % at 5 % level of significance . In addition , corroborative measures such as estimation of gamma-glutamyltransferase activity were included . MEASUREMENTS AND MAIN RESULTS : At one year a mean reduction in consumption of alcohol of 18.2 ( SE 1.5 ) U/week had occurred in treated men compared with a reduction of 8.1 ( 1.6 ) U/week in controls ( p less than 0.001 ) . The proportion of men with excessive consumption at interview had dropped by 43.7 % in the treatment group compared with 25.5 % in controls ( p less than 0.001 ) . A mean reduction in weekly consumption of 11.5 ( 1.6 ) U occurred in treated women compared with 6.3 ( 2.0 ) U in controls ( p less than 0.05 ) , with proportionate reductions of excessive drinkers in treatment and control groups of 47.7 % and 29.2 % respectively . Reduction in consumption increased significantly with number of general practitioner interventions . At one year the mean value for gamma-glutamyltransferase activity had dropped significantly more in treated men ( -2.4 (0.9)IU/l ) than in controls ( + 1.1(1.0)IU/l ; t = 2.7 , p less than 0.01 ) . Reduction in gamma-glutamyltransferase activity tended to increase with number of intervention sessions in men . Changes in gamma-glutamyltransferase activity in women and changes in other indicators in both sexes did not differ significantly between treatment and control groups . CONCLUSIONS : If the results of this study were applied to the United Kingdom intervention by general practitioners could each year reduce to moderate levels the alcohol consumption of some 250000 men and 67500 women who currently drink to excess . General practitioners and other members of the primary health care team should therefore be encouraged to include counselling about alcohol consumption in their preventive activities OBJECTIVE To evaluate the correspondence among measures of self-reported drinking , st and ard biological indicators and the reports of collateral informants , and to identify patient characteristics associated with observed discrepancies among these three sources of research data . METHOD Using data collected from a large-scale clinical trial of treatment matching with alcoholics ( N = 1,726 ) , these three alternative outcome measures were compared at the time of admission to treatment and at 12 months after the end of treatment . RESULTS Patient self-reports and collateral reports agreed most ( 97.1 % ) at treatment admission when heavy drinking was unlikely to be denied . In contrast , liver function tests were relatively insensitive , with positive serum gamma-glutamyl transpeptidase ( GGTP ) values obtained from only 39.7 % of those who admitted to heavy drinking . At 15-month follow-up the correspondence between client self-report and collateral report decreased to 84.7 % , but agreement with blood chemistry values increased to 51.6 % . When discrepancies occurred , they still indicated that the client ' s self-report is more sensitive to the amount of drinking than the biochemical measures . Patients who presented discrepant results tended to have more severe drinking problems , more previous treatments , higher levels of pretreatment drinking and significantly greater levels of cognitive impairment , all of which could potentially interfere with accurate recall . CONCLUSIONS In clinical trials using self-selected research volunteers , biochemical tests and collateral informant reports do not add sufficiently to self-report measurement accuracy to warrant their routine use . Re sources devoted to collecting these alternative sources of outcome data might be better invested in interview procedures design ed to increase the validity of self-report information BACKGROUND Alcohol use in older adults is common . It is associated with depression , hypertension , diabetes , drug interactions , accidents , and increased rates of emergency department visits and hospitalizations . METHODS A controlled clinical trial ( Project GOAL --Guiding Older Adult Lifestyles ) tested the efficacy of brief physician advice in reducing the alcohol use and use of health care services of older adult problem drinkers . Twenty-four community-based primary care practice s in Wisconsin ( 43 family physicians and internists ) participated in the trial . Of the 6073 patients screened , 105 men and 53 women met inclusion criteria and were r and omized into a control group ( n = 71 ) or an intervention group ( n = 87 ) . Intervention group patients received two 10- to 15-minute physician-delivered counseling sessions that included advice , education , and contracting using a scripted workbook . A total of 146 patients ( 92.4 % ) participated in the 12-month follow-up procedure . RESULTS No significant differences were found between the control and intervention groups at baseline in alcohol use , age , socioeconomic status , depression , onset of alcohol use , smoking status , activity level , or use of mood-altering drugs . The older adults who received the physician intervention demonstrated a significant reduction in 7-day alcohol use , episodes of binge drinking , and frequency of excessive drinking ( P < .005 ) compared with the control group at 3 , 6 , and 12 months after the intervention . There was a 34 % reduction in 7-day alcohol use , 74 % reduction in mean number of binge-drinking episodes , and 62 % reduction in the percentage of older adults drinking more than 21 drinks per week in the intervention group compared with the control group . There were no significant changes in health status . Patterns of health care utilization were not extensively analyzed because of the small number of events . CONCLUSIONS This study provides the first direct evidence that brief physician advice can decrease alcohol use by older adults in community-based primary care practice The aim of this research was to evaluate the effectiveness of long-term brief intervention in routine general practice . In five primary care out-patient clinics in a Finnish town , 296 male early-phase heavy drinkers consulting a general practitioner ( GP ) for various reasons were identified . Control group C ( n = 88 ) was informed of the risks of drinking after the screening and were advised at the subsequent feedback about 2 weeks later to reduce their drinking . Groups A ( n = 109 ) and B ( n = 99 ) were offered in addition seven and three brief intervention sessions , respectively . All GPs took part , whether or not they indicated a special interest . The main outcome measures were differences between beginning and end-point at 3 years in self-reported alcohol consumption , mean corpuscular volume ( MCV ) , and serum carbohydrate-deficient transferrin , aspartate aminotransferase , alanine aminotransferase and gamma-glutamyltransferase . There were no statistically significant differences between study groups A , B and C in mean changes in outcome measures . Within all the groups , MCV decreased . Depending on the outcome measure used and the study group analysed , clinical ly significant reduction of drinking was found in 25 - 53 % of the subjects . In routine general practice , giving additional sessions of brief intervention may not be as effective as in special research conditions . Factors reducing the effectiveness of brief intervention programmes should be investigated , so that primary health care staff can be better supported in their efforts AIMS To examine the long-term impact of brief and early interventions for hazardous and harmful alcohol consumption . DESIGN A 9-month and 10-year follow-up of subjects recruited into a r and omized controlled trial of a range of alcohol-related brief interventions . SETTING General practice s , the outpatient or acute care services of a major city hospital , and a privately run health screening programmeme . PARTICIPANTS The cohort of 554 ( non-dependent ) hazardous and harmful drinkers recruited into the Australian arm of the Phase II World Health Organization collaborative project on identification and treatment of persons with harmful alcohol consumption . INTERVENTION The effectiveness of three forms of intervention , ranging from 5 to 60 minutes in duration , were compared with a no-treatment control condition . MEASUREMENTS Included drinking behaviour and biological markers of alcohol use . In addition , at 10 years subjects were asked about symptoms of diagnosable alcohol use disorders and their experience of alcohol-related psychological , social and physical harm . Mortality was also assessed . FINDINGS Results provide further evidence for the short-term effectiveness of alcohol-related brief interventions . In comparison to controls , subjects offered intervention : ( 1 ) report significantly lower consumption ; and ( 2 ) less unsafe drinking at 9-month follow-up . The intensity of intervention was not related to the amount of change in drinking behaviour . Analysis at 10 years failed to find any differences in outcomes between intervention and control groups in median consumption , mean reduction in consumption from baseline to follow-up , mortality and ICD-10 diagnoses of alcohol dependence or harmful alcohol use . CONCLUSIONS This study failed to find evidence that brief advice and counselling without regular follow-up and reinforcement can sustain significant long-term reductions in drinking behaviour at 10-year follow-up OBJECTIVE To study the relation between alcohol intake and mortality in a large ambulatory population with attention to causes of death and differences related to age , sex , race , and baseline risk . DESIGN Prospect i ve cohort study . SETTING Prepaid comprehensive health care program facilities in Oakl and and San Francisco , California . PARTICIPANTS Adults ( n = 128,934 ) who supplied data at health evaluations between 1978 and 1985 . MEASUREMENTS Demographic data and health history were supplied using question naires . Death was ascertained by an automated linkage system and was individually vali date d. Relative risk for death at various levels of drinking was calculated by Cox proportional hazards models using lifelong nondrinkers as the reference and controlling for eight covariables . RESULTS Heavier drinkers were at greater risk for death from noncardiovascular causes ( relative risk at greater than or equal to 6 drinks per day compared with no alcohol = 1.6 , 95 % Cl , 1.3 to 2.0 ) especially cirrhosis , unnatural death , and tobacco-related cancers . This alcohol-associated risk was higher in women ( relative risk for death from all causes at greater than or equal to 6 drinks per day = 2.2 ; Cl , 1.4 to 3.8 ) and younger persons ( for persons less than 50 years of age , relative risk for death from all causes at greater than or equal to 6 drinks per day = 1.9 ; Cl , 1.3 to 2.9 ) . Lighter drinkers were at lower risk for death from cardiovascular disease , especially coronary heart disease ( relative risk at 1 to 2 drinks per day = 0.7 ; Cl , 0.6 to 0.9 ) , independent of baseline risk , with the greatest reduction of risk in older persons . Lighter drinkers over 60 years of age also had a slightly lower risk for noncardiovascular death , but this finding was not independent of baseline coronary heart disease risk . CONCLUSIONS Women and younger persons appear more susceptible to the increased mortality risk of heavy drinking . The reduced cardiovascular risk of lighter drinkers is more pronounced in older persons . Lower coronary disease prevalence may reduce the noncardiovascular mortality risk of lighter drinkers In a continuing screening and intervention programme in Malmó , elevated serum-gamma-glutamyltransferase ( GGT ) values were used for selection of heavy drinkers . The study population consisted of 585 individuals born 1926 - 1933 with two consecutive GGT values in the upper decile of the GGT distribution , r and omly allocated either to an intervention group of to a control group . The subjects in the intervention group were further investigated and 75 % of them were judged to have elevated GGT values caused by alcohol consumption . These individuals were repeatedly encouraged to lower their overall alcohol consumption and GGT measurements were used as biofeedback method in the treatment program . The controls were informed by letter to be restrictive with their alcohol consumption and that they should receive new invitations for measurements of their liver enzymes after 2 , 4 , and 6 years . The intervention and control groups were well matched and followed over a 2 - 6-year period . Two and 4 years after the screening investigation , the GGT values in both groups were significantly decreased . There were differences , however , between the two groups with regard to sick absenteeism , hospitalization , and mortality . A significant reduction was found in sick absence during 4 years by 80 % , in hospital days during 5 years by 60 % , and in mortality during 6 years by 50 % in the intervention group compared with the control group . Thus , the intervention program was effective in preventing medico-social consequences of heavy drinking OBJECTIVE The research ers evaluated the relative effectiveness of 2 interventions for patients with alcohol problems . STUDY DESIGN A nonr and omized intervention study was used to compare usual care ( control ) with a 5- to 15-minute physician-delivered message ( brief intervention ) and with the physician message plus a 30- to 60-minute visit by a recovering alcoholic ( peer intervention ) . Telephone follow-up was obtained up to 12 months after hospital discharge that focused on patient behaviors during the first 6 months following discharge . POPULATION The study included 314 patients with alcohol-related injuries admitted to an urban teaching hospital . OUTCOMES MEASURED Research ers measured complete abstinence from alcohol during the entire 6 months following hospital discharge , abstinence from alcohol during the sixth month following hospital discharge , and initiation of alcohol treatment or self-help within 6 months of hospital discharge . RESULTS Valid responses were obtained from 140 patients ( 45 % ) . Observed success rates were : 34 % , 44 % , and 59 % ( P=.012 ) for abstinence from alcohol since discharge in the usual care group , the brief intervention group , and the peer intervention group , respectively ; 36 % , 51 % , and 64 % ( P=.006 ) for abstinence at the sixth month following hospital discharge ; and 9 % , 15 % , and 49 % ( P & it.001 ) for initiation of treatment/self-help . During the telephone follow-up interview , several patients in the peer intervention group expressed gratitude for the help they received with their drinking problems while in the hospital . A few patients dramatically changed their lives . They went from being unemployed and homeless to full-time employment and having a permanent residence . They credited the peer intervention as being the most important factor that motivated them to seek help for their alcohol use disorder . One of these individuals serves as a volunteer , visiting hospitalized patients with drinking problems . CONCLUSIONS Among trauma victims with injuries severe enough to require hospital admission , brief advice from a physician followed by a visit with a recovering alcoholic appears to be an effective intervention . Although further study is needed to confirm these findings , in the meantime physicians can request that members of Alcoholics Anonymous ( AA ) visit their hospitalized patients who have alcohol use disorders . Interventions by recovering alcoholics are part of their twelfth-step work ( an essential part of the AA program ) and are simple , practical , involve no costs , and pose little patient risk . They can be arranged from the patient 's bedside telephone . Some patients will show a dramatic response to these peer visits BACKGROUND In a health survey of more than 21,000 men and women ages 12 - 62 years , measurement of gamma-glutamyltransferase ( GGT ) and answers on five questions on alcohol consumption were used as a basis for selecting an intervention population of early-stage risk drinkers . Altogether 290 men and 48 women met the criteria for inclusion . METHODS The 338 subjects were r and omized to a control group and two intervention groups . The minor intervention consisted of a single consultation during which possible reasons for the elevated GGT were discussed and a pamphlet with advice on changes in drinking habits was h and ed out . In the major intervention group the intervention was directed more specifically toward alcohol , with an extensive interview on drinking habits . In addition , the subjects in this group were offered follow-up consultations for new measurements of GGT . RESULTS All three groups were examined after 1 year with GGT determination and an interview on change in drinking habits during the past year . At follow-up , significant decreases in mean GGT ( 26.5 U/liter ) and self-reported alcohol intake ( 24.7 g/day ) were observed in the intervention groups compared with the control group . No significant differences were , however , observed between the intervention groups . CONCLUSION The study indicates that modest and simple interventions may yield important changes in drinking habits in early-stage risk drinkers OBJECTIVE Alcoholism is the leading risk factor for injury . The authors hypothesized that providing brief alcohol interventions as a routine component of trauma care would significantly reduce alcohol consumption and would decrease the rate of trauma recidivism . METHODS This study was a r and omized , prospect i ve controlled trial in a level 1 trauma center . Patients were screened using a blood alcohol concentration , gamma glutamyl transpeptidase level , and short Michigan Alcoholism Screening Test ( SMAST ) . Those with positive results were r and omized to a brief intervention or control group . Reinjury was detected by a computerized search of emergency department and statewide hospital discharge records , and 6- and 12-month interviews were conducted to assess alcohol use . RESULTS A total of 2524 patients were screened ; 1153 screened positive ( 46 % ) . Three hundred sixty-six were r and omized to the intervention group , and 396 to controls . At 12 months , the intervention group decreased alcohol consumption by 21.8+/-3.7 drinks per week ; in the control group , the decrease was 6.7+/-5.8 ( p = 0.03 ) . The reduction was most apparent in patients with mild to moderate alcohol problems ( SMAST score 3 to 8) ; they had 21.6+/-4.2 fewer drinks per week , compared to an increase of 2.3+/-8.3 drinks per week in controls ( p < 0.01 ) . There was a 47 % reduction in injuries requiring either emergency department or trauma center admission ( hazard ratio 0.53 , 95 % confidence interval 0.26 to 1.07 , p = 0.07 ) and a 48 % reduction in injuries requiring hospital admission ( 3 years follow-up ) . CONCLUSION Alcohol interventions are associated with a reduction in alcohol intake and a reduced risk of trauma recidivism . Given the prevalence of alcohol problems in trauma centers , screening , intervention , and counseling for alcohol problems should be routine BACKGROUND Providing doctors with new research findings or clinical guidelines is rarely sufficient to promote changes in clinical practice . An implementation strategy is required to provide clinicians with the skills and encouragement needed to alter established routines . AIM To evaluate the effectiveness and cost-effectiveness of different training and support strategies in promoting implementation of screening and brief alcohol intervention ( SBI ) by general practitioners ( GPs ) . METHOD Subjects were 128 GPs , one per practice , from the former Northern and Yorkshire Regional Health Authority , who agreed to use the ' Drink-Less ' SBI programme in an earlier dissemination trial . GPs were stratified by previous marketing conditions and r and omly allocated to three intensities of training and support : controls ( n = 43 ) received the programme with written guidelines only , trained GPs ( n = 43 ) received the programme plus practice -based training in programme usage , trained and supported GPs ( n = 42 ) received the programme plus practice -based training and a support telephone call every two weeks . GPs were requested to use the programme for three months . Outcome measures included proportions of GPs implementing the programme and numbers of patients screened and intervened with . RESULTS Seventy-three ( 57 % ) GPs implemented the programme and screened 11,007 patients for risk drinking . Trained and supported GPs were significantly more likely to implement the programme ( 71 % ) than controls ( 44 % ) or trained GPs ( 56 % ) ; they also screened , and intervened with , significantly more patients . Costs per patient screened were : trained and supported GPs , 1.05 Pounds ; trained GPs , 1.08 Pounds ; and controls , 1.47 Pounds . Costs per patient intervened with were : trained and supported GPs , 5.43 Pounds ; trained GPs , 6.02 Pounds ; and controls , 8.19 Pounds . CONCLUSION Practice -based training plus support telephone calls was the most effective and cost-effective strategy to encourage implementation of SBI by GPs The subjects were recruited from participants in a health examination of r and om sample s of the adult population in Stockholm county . Those aged 18 - 64 years who admitted a high alcohol consumption ( greater than 40 g 100 % ethanol/day ) among men and greater than 30 g among women ) or had an elevated value of serum-gammaglutamyltransferase ( GGT ) ( cut-off point 1.0 microkatal/l for men and 0.6 microkatal/l for women ) or had certain other indications of a high alcohol consumption were included . More severe cases , and those with an elevated GGT due to reasons other than alcohol , were excluded . The remaining subjects , 70 men and 13 women , were allocated at r and om to either an intervention or a comparison group . An elevated GGT was the main inclusion criteria . The subjects in the comparison group were advised by the general practitioner to cut their alcohol consumption , while those in the intervention group made further visits to their general practitioner , who gave general support and used an elevated GGT as an indication of the recent level of alcohol consumption at consecutive visits . There were three visits on average , so we are comparing a group receiving advice with a group receiving further minimal intervention . At the one-year follow-up there were greater , however not significant , reduction in GGT-level , in self-reported alcohol consumption and in a ' problem index ' in the minimal intervention group than in the comparison group BACKGROUND Few studies have estimated the economic costs and benefits of brief physician advice in managed care setting s. OBJECTIVE To conduct a benefit-cost analysis of brief physician advice regarding problem drinking . DESIGN Patient and health care costs associated with brief advice were compared with economic benefits associated with changes in health care utilization , legal events , and motor vehicle accidents using 6- and 12-month follow-up data from Project TrEAT ( Trial for Early Alcohol Treatment ) , a r and omized controlled clinical trial . SUBJECTS 482 men and 292 women who reported drinking above a threshold limit were r and omized into control ( n = 382 ) or intervention ( n = 392 ) groups . MEASURES Outcomes included alcohol use , emergency department visits , hospital days , legal events , and motor vehicle accidents . RESULTS No significant differences between control and intervention subjects were present for baseline alcohol use , age , socioeconomic status , smoking , depression or anxiety , conduct disorders , drug use , crimes , motor vehicle accidents , or health care utilization . The total economic benefit of the brief intervention was $ 423,519 ( 95 % CI : $ 35,947 , $ 884,848 ) , composed of $ 195,448 ( 95 % CI : $ 36,734 , $ 389,160 ) in savings in emergency department and hospital use and $ 228,071 ( 95 % CI : -$191,419 , $ 757,303 ) in avoided costs of crime and motor vehicle accidents . The average ( per subject ) benefit was $ 1,151 ( 95 % CI : $ 92 , $ 2,257 ) . The estimated total economic cost of the intervention was $ 80,210 , or $ 205 per subject . The benefit-cost ratio was 5.6:1 ( 95 % CI : 0.4 , 11.0 ) , or $ 56,263 in total benefit for every $ 10,000 invested . CONCLUSIONS These results offer the first quantitative evidence that implementation of a brief intervention for problem drinkers can generate positive net benefit for patients , the health care system , and society INTRODUCTION The study was design ed to test a brief intervention for reducing alcohol consumption among moderate to heavy ( hazardous ) drinkers in a busy HMO primary care setting . METHODS In a r and omized controlled trial , hazardous drinkers ( n = 516 ) were identified by the AUDIT screening question naire . Intervention included brief clinician advice ( 30 seconds ) , a 15-minute motivational session by counselors , and printed material s. RESULTS At six-month follow-up , intervention subjects reported fewer total st and ard drinks in the past three months ( 176 versus 216 , P = .04 , one-tailed ) and fewer drinking days per week ( 2.8 versus 3.3 , P = .02 ) than controls , but similar drinks per drinking day ( 3.3 versus 3.5 ; P = .13 ) . At 12 months , intervention subjects again reported fewer drinking days per week ( 2.7 versus 3.1 ; P = .04 ) than controls , but similar numbers of st and ard drinks ( 157 versus 179 ; P = .13 ) and drinks per drinking day ( 3.6 versus 3.3 ; P = .20 ) . Intervention subjects were somewhat more likely than controls to report drinking within daily recommended limits ( < or = 3 for men , < or = 2 for women ) at both six months ( 79 % versus 71 % ; P = .06 ) and 12 months ( 80 % versus 73 % ; P = .07 ) , but did not differ significantly from controls on other drinking outcomes ( percent abstinent , frequency of drinking > or = 6 drinks per drinking occasion , estimated peak blood alcohol concentration ) , or use of medical care in the year following intervention . CONCLUSIONS A one-time , brief motivational intervention using minimal clinician time supplemented by trained counselors result ed in a modest reduction in frequency of alcohol consumption in a busy primary care population . Future research should focus on strengthening and maintaining intervention effects Present methods to screen for alcohol abuse are generally obtrusive and result in referral to services that deal mainly with alcoholics . These factors deter physicians from identifying alcohol abuse patients at an early stage . In the present study , 81 % of all primary care physicians of a single city evaluated ( i ) the efficiency and the acceptability of a nonobtrusive screening method for the identification of problem drinkers and ( ii ) the effectiveness of brief cognitive behavioral counseling given by a nurse in a lifestyle context . Patients ( n = 15,686 ) attending the private practice s of 42 primary -care physicians were asked four alcohol-neutral trauma questions in the reception area . Physicians asked about alcohol use and alcohol-related problems only to patients with previous trauma . Problem drinkers by defined criteria were offered an appointment with a nurse who , by r and om assignment , gave either 3-hr of cognitive behavioral counseling over 1 year or simply advised patients to reduce their alcohol intake . The screening method identified 62 - 85 % of expected number of problem drinkers in this population . Following the application of exclusion criteria , 105 problem drinkers were entered in the intervention part of the study . After 1 year , patients who received counseling showed significant reductions in reported alcohol consumption ( -70 % ; p < 0.001 ) , psychosocial problems ( -85 % ; p < 0.001 ) and serum gamma glutamyl transferase ( -32 % to -58 % ; p < 0.02 ) . Physician visits were reduced ( -34 % ; p < 0.02 ) following counseling . Patients receiving only advice showed neither reductions in psychosocial problems nor in serum gamma glutamyl transferase or physician visits , but reported a 46 % reduction ( p < 0.01 ) in alcohol consumption . Data indicate that asking patients about recent trauma is efficient and is well accepted as the first screening instrument in the identification of the problem drinker . Cost of screening per patient is under one dollar . Counseling of 3 hr given by a nurse is markedly superior ( p < 0.05 ) to simple advice in reducing alcohol consumption , objective indicators of alcohol-related morbidity , and the frequency of physician visits OBJECTIVE Project TrEAT ( Trial for Early Alcohol Treatment ) was design ed to test the efficacy of brief physician advice in reducing alcohol use and health care utilization in problem drinkers . DESIGN R and omized controlled clinical trial with 12-month follow-up . SETTING A total of 17 community-based primary care practice s ( 64 physicians ) located in 10 Wisconsin counties . PARTICIPANTS Of the 17695 patients screened for problem drinking , 482 men and 292 women met inclusion criteria and were r and omized into a control ( n=382 ) or an experimental ( n=392 ) group . A total of 723 subjects ( 93 % ) participated in the 12-month follow-up procedures . INTERVENTION The intervention consisted of two 10- to 15-minute counseling visits delivered by physicians using a scripted workbook that included advice , education , and contracting information . MAIN OUTCOME MEASURES Alcohol use measures , emergency department visits , and hospital days . RESULTS There were no significant differences between groups at baseline on alcohol use , age , socioeconomic status , smoking status , rates of depression or anxiety , frequency of conduct disorders , lifetime drug use , or health care utilization . At the time of the 12-month follow-up , there were significant reductions in 7-day alcohol use ( mean number of drinks in previous 7 days decreased from 19.1 at baseline to 11.5 at 12 months for the experimental group vs 18.9 at baseline to 15.5 at 12 months for controls ; t=4.33 ; P<.001 ) , episodes of binge drinking ( mean number of binge drinking episodes during previous 30 days decreased from 5.7 at baseline to 3.1 at 12 months for the experimental group vs 5.3 at baseline to 4.2 at 12 months for controls ; t=2.81 ; P<.001 ) , and frequency of excessive drinking ( percentage drinking excessively in previous 7 days decreased from 47.5 % at baseline to 17.8 % at 12 months for the experimental group vs 48.1 % at baseline to 32.5 % at 12 months for controls ; t=4.53 ; P<.001 ) . The chi2 test of independence revealed a significant relationship between group status and length of hospitalization over the study period for men ( P<.01 ) . CONCLUSIONS This study provides the first direct evidence that physician intervention with problem drinkers decreases alcohol use and health re source utilization in the US health care system Behind the numbers What should primary care doctors do about screening for alcohol problems ? Beich and colleagues ( p 590 ) seem to have provided the answer : Nothing . Some will consider their results authoritative and conclude these activities are ineffective in general practice . But as with all systematic review s and meta-analyses , there can be devils in the details . Beich et al have addressed a clinical ly important question : “ How effective is screening in general practice for identifying drinkers who can and do benefit from brief intervention ? ” The most trustworthy answer would come from a r and omized controlled trial of screening and brief intervention compared with no systematic screening or intervention , but no such studies exist.1 The results of such a trial would provide a direct measurement of the number needed to screen ( NNS ) to benefit one patient.2 In the absence of studies evaluating such direct evidence , review ers are forced to examine and link separate bodies of evidence ( Is the screening test accurate ? How effective is the intervention ? ) . With the We studied 120 injured male patients of working age who were heavy drinkers or alcoholics , obtaining seven points or more in the Michigan Alcoholism Screening Test ( MAST ) . They were r and omly allocated either to an intervention group ( IG ) or to a control group ( CG ) . In addition to the MAST interview , the consumption of alcohol during the previous week prior to hospital admission was calculated and laboratory measures ( serum GGT , ASAT and ALAT ) were obtained . Counselling of the patients in the IG was carried out by a trained assistant nurse and a physician . Forty-nine patients in IG and 40 patients in CG were re-examined after 6 months . In the IG 45 % and in the CG 20 % of the patients were improved ( Chi square test , P less than 0.05 ) . Improvement criteria were a decrease in alcohol consumption by at least one-third and decrease of S-GGT by at least 20 % during the follow-up period . In respect to the laboratory measures the groups were identical at the beginning of the study and after 6 months ' follow-up . Our results are encouraging and suggest that the assessment of heavy drinking should be a routine in the treatment of alcohol-related injuries and that education and counselling must be intensive to be effective BACKGROUND Alcohol as a cause of death in middle-aged patients is well-known from clinical studies . A similarly important correlation in the general population of urban middle-aged men is highly underestimated . Health screening investigations have shown that mortality related to alcohol is five times more common in non participants than in participants . From the mid-70s , the Malmoe Screening and Intervention Study ( MSIS ) commenced screening investigations including a large number of residents of Malmoe . One goal was to find intervention programs for individuals in an early development of problem drinking , thereby preventing development of serious complications of endstage alcoholism . Herein , we report on the mortality of heavy drinkers ( drinking more than 40 g alcohol/day ) who were r and omized to an intervention or control procedure and whose median survival was 13 years postentry into the MSIS . METHODS Health-screened men , aged 45 - 49 years at the initial screening examination and displaying serum gamma-glutamyltransferase ( GT ) in the top decentile of the GT distribution , were included . A total of 978 out of 11,257 participants met this criteria . A r and omized intervention and control study was performed for four years and consisted of men ( n = 667 ) who were born between 1927 - 1937 and who had two consecutive high GT values within 3 weeks along with heavy alcohol consumption . Half the individuals were informed of the test results and invited for further assessment by a senior physician ( n = 365 ) . The principles for brief intervention ( DiClemente et al.,1991 ; Miller and Sanchez , 1993 ; National Institute of Alcohol Abuse and Alcoholism , 1999 ) were applied . The other half of the men ( n = 302 ) were left with the information that they had a high GT value and were followed up with laboratory checkups every 2nd year . Mortality was followed up until 1991 and information on deaths was obtained from hospital and police records , necropsy reports , and death certificates . RESULTS Long-term follow-up of mortality for 10 - 16 years ( median , 13 years ) showed that 124 of the 978 men had died ( 12.7 % ) . Autopsy was performed in 96.5 % of the cases . In 59 men ( 48 % ) , death was alcohol-related . In the intervention group ( n = 365 ) , 38 ( 10.4 % ) men were dead and in the control group ( n = 302 ) , 42 ( 13.9 % ) men had died . There was a statistically significant difference ( p = 0.026 ) , with advantage for treatment . Less alcohol-related deaths and deaths occurring later during follow-up were found in the intervention group compared with the control group . The difference between the groups in total mortality , coronary heart disease , and cancer death was not statistically significant . CONCLUSIONS These findings support previous results from the MSIS study indicating that long-term intervention in urban males with alcohol-induced GT increases may be beneficial in terms of survival We studied whether moderate alcohol drinkers have a lower total and coronary heart disease ( CHD ) mortality than nondrinkers . Among 276,802 U.S. men aged 40–59 enrolled in 1959 in an American Cancer Society prospect i ve study , 42,756 deaths , 18,771 from CHD , occurred during the following 12 years ( 3 % of the cohort was lost to follow-up ) . Using nondrinkers ( 55.3 % of the cohort ) as a reference category , age- and smoking-stratified relative risks ( RR ) of total mortality were 0.88 for occasional drinkers , 0.84 for those drinking_1_drink per day , 0.93 , 1.02 , 1.08 , 1.22 , and 1.38 for those drinking 2 , 3 , 4 , 5 , and 6 or more drinks per day , respectively . RRs of CHD mortality were 0.86 , 0.79 , 0.80 , 0.83 , 0.74 0.85 , and 0.92 , respectively . Multivariate analysis failed to identify other confounders . No changes in RRs were introduced by excluding subjects with poor health or history of chronic disease at enrollment ( 32.8 % of the cohort ) or excluding subjects who died during the first 6 years of follow-up . These data indicate an apparent protective effect of moderate alcohol intake on CHD mortality that can not be attributed to the inclusion of subjects with CHD or related diseases into the nondrinker OBJECTIVE To evaluate the effect of a nurse-conducted intervention on excessive drinkers . DESIGN R and omized , controlled trial . SETTING Vårby Health Centre , Stockholm . INTERVENTION The intervention group visited a nurse three times during a 12-month period . The controls met once with a general practitioner ( GP ) . PATIENTS Patients were recruited at a health screening on the basis of a raised gamma-glutamyl transferase ( GGT ) . Of 2338 subjects , aged 25 - 54 years , 222 had a screening GGT of > or = 0.9 mukat/l . 100 were r and omized to the treatment and 122 to the control group . MAIN OUTCOME MEASURES GGT , self-reported alcohol consumption ( g/week ) , sickness allowance and use of health care . RESULTS After 2 years a reduction of GGT from 1.52 to 1.21 mukat/l ( p = 0.02 ) had occurred in the treatment group . The controls increased their mean level of GGT from 1.75 to 2.16 mukat/l . Mean weekly alcohol consumption in the intervention group was reduced from 337 to 228 g/week ( p = 0.02 ) . The controls did not quantify their alcohol consumption initially , but reported a reduced weekly consumption at follow-up . CONCLUSION The intervention had an impact on GGT and self-reported consumption . The controls also reported decreased consumption possibly because their appointment with the GP functioned as a very brief intervention OBJECTIVE Brief interventions for hazardous and low-dependent drinkers in the primary care setting have considerable empirical support . The purpose of this study was to ( 1 ) evaluate the effects of brief advice ( BA ) and motivational enhancement ( ME ) interventions on alcohol consumption . In addition , a hindsight matching design was used to ( 2 ) study the moderator effects of patient readiness to change ( alcohol use ) on alcohol consumption . METHOD The subjects ( N = 301 , 70 % men ) were patients 21 years of age or older who presented for treatment at one of 12 primary care clinics . After screening for eligibility and providing consent to participate in the study , the patients completed a baseline assessment and were r and omly assigned to the BA , ME or st and ard care ( SC ) interventions condition . Follow-up assessment s were completed at 1- , 3- , 6- , 9- and 12-months postbaseline assessment . RESULTS Evaluation of the first hypothesis ( n = 232 for these analyses ) showed that all participants tended to reduce their alcohol use considerably between the baseline and 12-month assessment s. In addition , evaluation of the second hypothesis showed a moderator effect of readiness to change in predicting the number of drinks at 12 months , such that the BA intervention seemed more effective for patients relatively low in readiness to change compared to those higher in readiness . Readiness to change did not seem to be related to changes in drinking of participants in the SC or ME conditions . CONCLUSIONS The results confirm that , among primary care patients , substantial changes in alcohol consumption are possible . They further suggest that matching studies of patient readiness to change their alcohol use , as well as other variables , are warranted The objective of the study was to determine the effectiveness of advice from general practitioners to heavy drinking men ( consuming 350 - 1050 grams of alcohol per week ) to reduce their alcohol consumption . One hundred and fifty-four men recruited from eight general practice s were allocated r and omly to treatment and control groups . Men in the treatment group received advice from their own general practitioner . At one year follow-up , when analyzed according to intention to treat , the treatment group had reduced their consumption by an excess of 65 grams of alcohol per week when compared with the control group ( p less than 0.05 ) . General practitioners should be recommended to screen for alcohol consumption amongst their patients and to give advice to those found to be at risk because of their drinking This prospect i ve study evaluated changes in patients ' health-risk behavior one year after preventive intervention by primary care physicians . The trial used a quasiexperimental design with 2,218 adults ( 1,409 study subjects and 809 controls ) at five multispecialty , group practice sites in three regions of the United States . Pre- and postintervention surveys showed that the treated study patients with behavioral risks were more likely to report positive changes than were controls in regard to beginning regular exercise ( P = .02 ) , using auto seat belts , ( P less than .001 ) , losing weight ( P = .05 ) , decreasing alcohol intake ( P = .01 ) , and to performance of monthly breast self-examination by women ( P less than .001 ) . The smoking cessation rate was greater among the treated study group compared with the controls , although the change was not significantly different . Greater behavioral risk changes also occurred among the total study group ( treated and untreated ) in comparison with the control group . An additive index of these behavioral risks showed greater reduction among the treated and the total group of study patients compared with controls . These initial results suggest that clinical preventive services , which include risk factor education and counseling by primary care physicians , can improve short-term health-related behavior of patients Summary Baseline data were collected on 263 general hospital patients screened as problem drinkers , who were r and omly allocated to one of two groups . In one group an attempt was made to refer patients for treatment while no action was taken for the other . Both groups were followed up at 12 and 18 months . At 12 months the referred group had improved significantly more than the control group in terms of self-reported alcohol problems , personal happiness , period since last drinking and work performance . However , these effects had diminished at 18 months , largely because of improvements in the control group after the 12-months follow-up , which appeared to function as an intervention . These results suggest that intervention following screening is of benefit , and that such a strategy could usefully be incorporated into normal hospital routine This study evaluated the use of a brief motivational interview ( MI ) to reduce alcohol-related consequences and use among adolescents treated in an emergency room ( ER ) following an alcohol-related event . Patients aged 18 to 19 years ( N = 94 ) were r and omly assigned to receive either MI or st and ard care ( SC ) . Assessment and intervention were conducted in the ER during or after the patient 's treatment . Follow-up assessment s showed that patients who received the MI had a significantly lower incidence of drinking and driving , traffic violations , alcohol-related injuries , and alcohol-related problems than patients who received SC . Both conditions showed reduced alcohol consumption . The harm-reduction focus of the MI was evident in that MI reduced negative outcomes related to drinking , beyond what was produced by the precipitating event plus SC alone Context Brief interventions can reduce problem drinking , but physicians infrequently use them . Contribution This r and omized trial , from an academic primary care setting , tested whether prompting physicians with positive alcohol screening results that are linked to specific management recommendations works . Prompted faculty , but not residents , tended to discuss alcohol problems and counsel patients more often than did their counterparts who were not prompted . At 6 months , however , only patients of prompted residents had reduced their drinking . Implication s Prompting physicians with positive alcohol screening results and recommendations for action may or may not be effective , depending on patient , physician , and setting characteristics . The Editors Alcohol use disorders are a leading cause of disability and are as common and costly as coronary artery disease and depression ( 1 - 6 ) . Primary care setting s are ideal for alcohol screening and intervention ( 7 ) . Valid , brief , practical screening tools exist , and brief interventions can reduce drinking and improve health when delivered to primary care patients with alcohol problems ( 8 - 11 ) . However , alcohol problems are often unrecognized and untreated in primary care setting s ( 12 - 16 ) . Barriers to screening and intervention include issues related specifically to addictions ( such as patient readiness and physician discomfort , frustration , lack of confidence or skills , or pessimism about efficacy of intervention ) and issues related to the delivery of preventive services in general ( such as cost , acceptability , priorities , and time ) ( 17 , 18 ) . Physician prompting can improve the likelihood of cancer screening , administration of immunizations , and smoking cessation interventions ( 19 - 21 ) . Screening and intervention for alcohol problems , however , involve more complex assessment and intervention . The effectiveness of providing physicians with screening results and a prompt without training is unknown . Such a systems intervention would be easier and less costly to implement than training all physicians about addressing alcohol problems . We tested the hypotheses that providing physicians with patients ' alcohol screening results and simple individualized recommendations would increase physician alcohol counseling and decrease patient drinking . Methods Study Description The study was a cluster r and omized trial at the physician level because r and omization at the patient level would have risked contamination . The institutional review board of the Boston University Medical Center in Boston , Massachusetts , approved the study . Patients gave informed consent and were told that the physician may be given the results of alcohol screening questions . We obtained a Certificate of Confidentiality from the federal government . Participants Physicians were recruited , enrolled , and r and omly assigned before patients were enrolled . All faculty and resident primary care physicians in an urban academic practice ( excluding the authors ) were eligible . Physicians who had seen fewer than 80 patients in the previous 3 years or who anticipated leaving the practice within 6 months were excluded . We informed physicians that we would conduct a health screening study . We used a self-administered question naire to screen and enroll patients who spoke English or Spanish ( staff were available to assist ) ( 22 ) . This was done before a visit with one of the enrolled physicians . Eligible patients were current hazardous drinkers [ 23 ] , which was defined as having consumed alcohol in the past month and either 1 ) answered yes to one or more of the CAGE ( 24 - 26 ) alcohol screening questions ( modified to refer to the past year rather than lifetime ) [ 27 ] or 2 ) drank hazardous amounts in the past month ( 28 , 29 ) . Hazardous amounts for men and women , respectively , were defined as more than 4 st and ard drinks per occasion or 14 drinks per week and as more than 3 st and ard drinks per occasion or 7 drinks per week in the past 30 days ( 26 , 30 ) . Assessment s Before patients were enrolled , physicians completed a confidential written survey ( July 1997 ) . They were asked about their attitudes toward patients with addictions ; their professional satisfaction when caring for patients with alcohol problems ; whether they or someone they knew had an alcohol or drug problem ; and other issues related to alcohol and physicians , including the physician 's usual practice s ( 18 ) . A trained staff research er interviewed enrolled patients before and after their visits with a physician ( between February 1998 and August 1999 ) . All questions not available in Spanish ( 31 ) were translated , back-translated , and checked for accuracy . The assessment visit that occurred before the physician visit addressed demographic characteristics , previous counseling for alcohol problems , and readiness to change ( 32 , 33 ) . Patients were also asked about medication use , medical comorbidity ( 34 , 35 ) , psychiatric comorbidity ( 36 , 37 ) , and tobacco and other drug use . Immediately after the physician visit , patients were interviewed to determine whether counseling had occurred , drinking amounts ( 38 , 39 ) , the quality of communication with the physician ( 40 ) , alcohol dependence symptoms ( 41 ) , and alcohol problems ( Short Inventory of Problems [ SIP-2R ] ) ( 42 ) . Six months later , patients were interviewed by telephone to determine alcohol consumption in the past 30 days ; the vali date d Timeline Followback method was used ( 43 ) . Patients and staff research ers were not blinded to group assignment ( in addition , patients were not necessarily given this information ) ; at follow-up , interviews were done without knowledge of group assignment . R and omization and Intervention Physicians were stratified by level of training ( resident or faculty ) and were r and omly assigned to the intervention or control group at the start of the study . The computer-generated r and omization was done by off-site data management personnel who had no patient or physician contact . The staff research er attached the intervention , a sheet of paper , to the encounter record the physician routinely received immediately before each patient visit . One side of the paper provided the patient 's alcohol screening results , a preliminary assessment , and specific recommendations . The screening results included answers to each of the CAGE questions , reports of usual weekly and per occasion maximum drinking amounts , and the patient 's report of readiness to change on a 10-point scale ( 44 ) ( see Appendix Figure ) . For patients reporting hazardous drinking amounts but no affirmative CAGE question naire responses , the assessment was drinking hazardous amounts and the recommendation was consider advising safe drinking limits and consider providing patients with a pamphlet provided by the study titled How to Cut Down on Your Drinking ( 27 ) . For patients reporting any affirmative CAGE responses but no hazardous drinking amounts , the assessment was possible alcohol problems and recommendations were consider advising abstinence , provide the pamphlet , and referral to addiction treatment . For patients reporting affirmative CAGE question naire responses and hazardous drinking amounts , the assessment was both possible alcohol problems and drinking hazardous amounts and recommendations were consider advising abstinence and referral to addiction treatment . The other side of the paper provided the predictive value of CAGE based on the prevalence of alcohol abuse or dependence in the practice ( 26 , 31 ) , definitions of hazardous drinking , an approach for patients who are not ready to change , a list of abuse or dependence symptoms , and referral information . To increase counseling rates ( not for data collection ) , we attached a Post-it note to the encounter form asking physicians to indicate whether alcohol was discussed and , if not , why ( 45 ) . Physicians in the control group did not receive any information from the study . Statistical Analysis All analyses were performed by using SAS software , version 8.1 [ SAS Institute , Inc. , Cary , North Carolina ] . The primary prespecified outcomes of the study were the occurrence of physician discussion s regarding alcohol problems during the physicianpatient encounter and a decrease in patient drinking . Patients were asked whether they had 1 ) received alcohol counseling , defined as advice on safe drinking limits , advice to cut down or abstain , or referral to an alcohol specialist or treatment program ; 2 ) received any advice [ including counseling ] ; or 3 ) participated in any discussion about alcohol ( including advice ) . An example question was : Did the doctor give you any advice about your drinking habits ? Drinks per drinking day was the primary drinking outcome . We examined additional measures in secondary analyses : days drinking ( any day on which a drink was taken ) , days binge drinking ( any day on which per occasion amounts noted previously were exceeded ) , proportion drinking hazardous amounts , proportion binge drinking , and proportion abstinent . We compared sociodemographic characteristics , level of training , and mean number of patients enrolled for physicians in the intervention and control groups by using the two independent sample s t-test and the Fisher exact test , as applicable . We then compared patients who were seen by physicians in the intervention and control groups with respect to measured characteristics . We compared patients who were available and unavailable at the 6-month follow-up by r and omized group , physician level of training , and sociodemographic characteristics . Outcomes were compared between physicians in the intervention and control groups by using an intention-to-treat analysis ( physicians were analyzed in the groups to which they were r and omly assigned ) . Generalized estimating equations ( GEE ) were used to adjust for clustering of patients by physician ( PROC GENMOD , SAS software , version 8.1 ) ( 46 ) . For continuous outcomes , we specified the identity link function ; for dichotomous outcomes , we specified the logit link BACKGROUND Today , heavy drinking is a common health hazard among women . The evidence in favor of providing some kind of brief intervention to reduce drinking is quite convincing . However , we do not know if intervention works in a natural environment of routine health care . The purpose of this study was to evaluate the effectiveness of long-lasting , brief alcohol intervention counseling for women in a routine general practice setting . METHODS In five primary care outpatient clinics in a Finnish town , 118 female early-phase heavy drinkers who consulted their general practitioners for various reasons were given brief alcohol intervention counseling . Intervention groups A ( n = 40 ) and B ( n = 38 ) were offered seven and three brief intervention sessions , respectively , over a 3-yr period . The control group C ( n = 40 ) was advised to reduce drinking at baseline . Main outcome measures were self-reported weekly alcohol consumption , carbohydrate-deficient transferrin , mean corpuscular volume ( MCV ) , aspartate aminotransferase , alanine aminotransferase , and gamma-glutamyltransferase . RESULTS Depending on the outcome measure and the study group , clinical ly meaningful reduction of drinking was found in 27 % to 75 % of the heavy drinkers . Within all the groups , MCV significantly decreased . However , there were no statistically significant differences between study groups A , B , and C in the mean changes between the beginning and endpoint in the main outcome measures . CONCLUSIONS The present study indicated that minimal advice , as offered to group C , was associated with reduced drinking as much as the brief intervention , as offered to groups A and B , given over a 3-yr period . Furthermore , in the routine setting of the general practice office , the effectiveness of the brief intervention may not be as good as in special research conditions . The factors possibly reducing the effectiveness in a routine setting are unknown . Thus , different methods of implementing brief intervention need to be evaluated to find better ways to support general practice personnel in their efforts to help heavy-drinking female patients to reduce their drinking OBJECTIVE The project was design ed to compare the effectiveness of brief intervention ( BI ) versus simple advice ( SA ) in the secondary prevention of hazardous alcohol consumption . METHODS A r and omized controlled trial with a 12-month follow-up was conducted . A total of 74 community-based primary care practice s ( 328 physicians ) located in 13 Spanish autonomous regions were recruited initially . Out of 546 men screened , only 229 were r and omized into BI ( n = 104 ) and SA ( n = 125 ) ; 44.6 % of practice s finalized the study . The interventions on the BI group consisted of a 15-minute counselling visit carried out by physicians which included : ( i ) alcohol quantification , ( ii ) information on safe limits , ( iii ) advice , ( iv ) drinking limits agreement , ( v ) self-informative booklet with drinking diary record and ( vi ) unscheduled reinforcement visits . The SA group spent 5 minutes which included ( i ) , ( ii ) and ( iii ) . RESULTS There were no significant differences between both groups at baseline on alcohol use , age , socioeconomic status and CAGE score . After the 12-month follow-up there was a significant decrease in frequency of excessive drinkers ( 67 % of BI group reached targeted consumption , versus 44 % of SA ; P < 0.001 ) as well as weekly alcohol intake reduction ( BI reached 52 versus 32 % in SA ; P < 0.001 ) . A trend to improve outcome with the number of reinforcement visits was found with BI . The only predictor of success was the initial alcohol consumption level . CONCLUSIONS Brief intervention is more effective than simple advice to reduce alcohol intake on adult men who attend primary care services in Spain From a population of 2,114 patients attending somatic outpatient clinics , 78 patients were selected who had either an excessive consumption of alcohol according to question naires or a raised gamma glutamyltransferase ( GGT ) value ( above 0.6 mu kat/l ) due to alcohol . They had not undergone treatment for problem drinking previously , and had no serious alcohol dependence . They were thereby classified as excessive consumers of alcohol , and r and omly allocated to an intervention ( n = 36 ) or to a control group ( n = 42 ) . Those in the intervention group were followed up by a nurse once a month and by a doctor every third month for a total of 12 months . Laboratory tests were taken monthly . Consumption of alcohol , GGT and triglyceride levels , and sickness allowance days were decreased in the intervention group compared to the time before intervention . In contrast , the number of sickness allowance days in the control group increased . There was also a tendency towards a positive effect of intervention on the number of consultations made with a statistically not significant decrease of consultations after intervention . The study thus indicates that an early and relatively simple intervention programme for problem drinkers may be effective and can be carried out at a low cost and with a positive response from the patients OBJECTIVE This study was undertaken to determine the diagnostic test characteristics of the alcohol screening strategy recommended in the National Institute on Alcoholism and Alcohol Abuse ( NIAAA ) " Physicians ' Guide to Helping Patients with Alcohol Problems . " METHOD A research interview was performed on patients who presented to one urban emergency department ( N = 395 ; 61 % women ) . It asked three alcohol consumption questions , the CAGE question naire , and about past alcohol problems . The NIAAA-recommended screen was considered positive for alcohol consumption in excess of 14 drinks per week or 4 drinks per occasion for men , or 7 drinks per week or 3 drinks per occasion for women , or a CAGE score of 1 or greater . A sample of patients ( n = 250 ) received the Composite International Diagnostic Interview substance abuse module , a gold st and ard interview , to determine lifetime or prior 12-month alcohol abuse or dependence ; results were adjusted for verification bias . RESULTS The prevalence of lifetime : alcohol abuse or dependence was 13 % , for which the NIAAA strategy was 81 % sensitive and 80 % specific . The prevalence of alcohol abuse or dependence in the prior 12 months was 10 % , for which the strategy was 83 % sensitive and 84 % specific . Its positive likelihood ratio exceeded that of the CAGE , augmented CAGE or consumption questions alone , and its negative likelihood ratio was the lowest . CONCLUSIONS The screening strategy combining alcohol consumption and CAGE questions recommended in the NIAAA " Physicians ' Guide " is valid , and has superior test characteristics compared to the CAGE alone , in this predominantly black ( 86 % ) emergency department population . Its brevity and simple interpretation recommend wider dissemination of the NIAAA " Physicians ' Guide , " although future research should examine its test characteristics in other clinical setting s and with other population BACKGROUND There is a need for primary care providers to have brief effective methods to intervene with high-risk drinkers during a regular outpatient visit . OBJECTIVE To determine whether brief physician- and nurse practitioner-delivered counseling intervention is efficacious as part of routine primary care in reducing alcohol consumption by high-risk drinkers . METHODS Academic medical center-affiliated primary care practice sites were r and omized to special intervention or to usual care . From a screened population of 9772 patients seeking routine medical care with their primary care providers , 530 high-risk drinkers were entered into the study . Special intervention included training providers in a brief ( 5- to 10-minute ) patient-centered counseling intervention , and an office support system that screened patients , cued providers to intervene , and made patient education material s available . The primary outcome measures were change in alcohol use from baseline to 6 months as measured by weekly alcohol consumption and frequency of binge drinking episodes . RESULTS Participants in the special intervention and usual care groups were similar on important background variables and potential confounders except that special intervention participants had significantly higher baseline levels of alcohol usage ( P = .01 ) . At 6-month follow-up , in the 91 % of the cohort who provided follow-up information , alcohol consumption was significantly reduced when adjusted for age , sex , and baseline alcohol usage ( special intervention , -5.8 drinks per week ; usual care , -3.4 drinks per week ; P = .001 ) . CONCLUSIONS This study provides evidence that screening and very brief ( 5- to 10-minute ) advice and counseling delivered by a physician or nurse practitioner as part of routine primary care significantly reduces alcohol consumption by high-risk drinkers BACKGROUND Alcohol consumption has both adverse and beneficial effects on survival . We examined the balance of these in a large prospect i ve study of mortality among U.S. adults . METHODS Of 490,000 men and women ( mean age , 56 years ; range , 30 to 104 ) who reported their alcohol and tobacco use in 1982 , 46,000 died during nine years of follow-up . We compared cause-specific and rates of death from all causes across categories of base-line alcohol consumption , adjusting for other risk factors , and related drinking and smoking habits to the cumulative probability of dying between the ages of 35 and 69 years . RESULTS Causes of death associated with drinking were cirrhosis and alcoholism ; cancers of the mouth , esophagus , pharynx , larynx , and liver combined ; breast cancer in women ; and injuries and other external causes in men . The mortality from breast cancer was 30 percent higher among women reporting at least one drink daily than among nondrinkers ( relative risk , 1.3 ; 95 percent confidence interval , 1.1 to 1.6 ) . The rates of death from all cardiovascular diseases were 30 to 40 percent lower among men ( relative risk , 0.7 ; 95 percent confidence interval , 0.7 to 0.8 ) and women ( relative risk , 0.6 ; 95 percent confidence interval , 0.6 to 0.7 ) reporting at least one drink daily than among nondrinkers , with little relation to the level of consumption . The overall death rates were lowest among men and women reporting about one drink daily . Mortality from all causes increased with heavier drinking , particularly among adults under age 60 with lower risk of cardiovascular disease . Alcohol consumption was associated with a small reduction in the overall risk of death in middle age ( ages 35 to 69 ) , whereas smoking approximately doubled this risk . CONCLUSIONS In this middle-aged and elderly population , moderate alcohol consumption slightly reduced overall mortality . The benefit depended in part on age and background cardiovascular risk and was far smaller than the large increase in risk produced by tobacco This r and omized trial evaluated an intervention for reducing at-risk drinking practice s in a sample of 307 patients . Eligible drinking patterns included chronic drinking ( > or = 2 drinks per day in the past month ) , binge drinking ( > or = 5 drinks per occasion at least twice in the past month ) , and drinking and driving ( driving after > 2 drinks in the past month ) . Members of the intervention group received a message from their physician during their regularly scheduled visit , a self-help manual , written personalized feedback , and up to 3 telephone counseling calls . Dropout was significantly higher in the intervention than control group |
10,564 | 29,025,194 | This up date d meta- analysis of individual participant data from 12 countries shows that the use of procalcitonin to guide initiation and duration of antibiotic treatment results in lower risks of mortality , lower antibiotic consumption , and lower risk for antibiotic-related side effects .
Results were similar for different clinical setting s and types of ARIs , thus supporting the use of procalcitonin in the context of antibiotic stewardship in people with ARIs . | BACKGROUND Acute respiratory infections ( ARIs ) comprise of a large and heterogeneous group of infections including bacterial , viral , and other aetiologies .
In recent years , procalcitonin ( PCT ) , a blood marker for bacterial infections , has emerged as a promising tool to improve decisions about antibiotic therapy ( PCT-guided antibiotic therapy ) .
Several r and omised controlled trials ( RCTs ) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient population s with ARIs and different setting s ranging from primary care setting s to emergency departments , hospital wards , and intensive care units .
However , the effect of using procalcitonin on clinical outcomes is unclear .
This is an up date of a Cochrane review and individual participant data meta- analysis first published in 2012 design ed to look at the safety of PCT-guided antibiotic stewardship . | BACKGROUND Therapy with antibiotics influences recovery only in selected cases of COPD exacerbations . We evaluated the efficacy and safety of procalcitonin guidance compared to st and ard therapy with antibiotic prescriptions in patients experiencing exacerbations of COPD . METHODS A total of 208 consecutive patients requiring hospitalization for COPD exacerbation were r and omized at the index exacerbation to procalcitonin-guided or st and ard antibiotic therapy . Patients receiving procalcitonin-guided therapy were treated with antibiotics according to serum procalcitonin levels ; st and ard-therapy patients received antibiotics according to the attending physician . The primary outcome was the antibiotic exposure at the index exacerbation and the subsequent antibiotic requirement for COPD exacerbation within 6 months . Secondary outcomes were clinical recovery , symptom scores , length of hospitalization , ICU stay , death , lung function , exacerbation rate , and time to next exacerbation . RESULTS At the index exacerbation , procalcitonin guidance reduced antibiotic prescription ( 40 % vs 72 % , respectively ; p < 0.0001 ) and antibiotic exposure ( relative risk [ RR ] , 0.56 ; 95 % confidence interval [ CI ] , 0.43 to 0.73 ; p < 0.0001 ) compared to st and ard therapy . Moreover , procalcitonin guidance at the index exacerbation allowed a significant sustained reduction in total antibiotic exposure for up to 6 months ( RR , 0.76 ; 95 % CI , 0.64 to 0.92 ; p = 0.004 ) . Clinical outcome and improvement in FEV(1 ) at 14 days and 6 months did not differ between groups . Within 6 months , the exacerbation rate ( 0.62 vs 0.64 , respectively ) , the rehospitalization rate ( 0.21 vs 0.24 , respectively ) , and mean ( + /- SD ) time to the next exacerbation ( 70.0 + /- 46.1 vs 70.4 + /- 51.9 days , respectively ; p = 0.523 ) were similar in both groups . CONCLUSIONS Procalcitonin guidance for exacerbations of COPD offers a sustained advantage over st and ard therapy in reducing antibiotic use for up to 6 months with a number-needed-to-treat of 3 BACKGROUND The value of azithromycin for treatment of acute bronchitis is unknown , even though this drug is commonly prescribed . We have investigated this question in a r and omised , double-blind , controlled trial . METHODS Adults diagnosed with acute bronchitis , without evidence of underlying lung disease , were r and omly assigned azithromycin ( n=112 ) or vitamin C ( n=108 ) for 5 days ( total dose for each 1.5 g ) . All individuals were also given liquid dextromethorphan and albuterol inhaler with a spacer . The primary outcome was improvement in health-related quality of life at 7 days ; an important difference was defined as 0.5 or greater . Analysis was by intention to treat . FINDINGS The study was stopped by the data -monitoring and safety committee when 220 patients had been recruited . On day 7 , the adjusted difference in health-related quality of life was small and not significant ( difference 0.03 [ 95 % CI -0.20 to 0.26 ] , p=0.8 ) . 86 ( 89 % ) of 97 patients in the azithromycin group and 82 ( 89 % ) of 92 in the vitamin C group had returned to their usual activities by day 7 ( difference 0.5 % [ -10 % to 9 % ] , p>0.9 ) . There were no differences in the frequency of adverse effects ; three patients in the vitamin C group discontinued the study medicine because of perceived adverse effects , compared with none in the azithromycin group . Most patients ( 81 % ) reported benefit from the albuterol inhaler . INTERPRETATION Azithromycin is no better than low-dose vitamin C for acute bronchitis . Further studies are needed to identify the best treatment for this disorder BACKGROUND Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units . We aim ed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting . METHODS In this multicentre , prospect i ve , parallel-group , open-label trial , we used an independent , computer-generated r and omisation sequence to r and omly assign patients in a 1:1 ratio to procalcitonin ( n=311 patients ) or control ( n=319 ) groups ; investigators were masked to assignment before , but not after , r and omisation . For the procalcitonin group , antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations ; the control group received antibiotics according to present guidelines . Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician . Patients were expected to stay in the intensive care unit for more than 3 days , had suspected bacterial infections , and were aged 18 years or older . Primary endpoints were mortality at days 28 and 60 ( non-inferiority analysis ) , and number of days without antibiotics by day 28 ( superiority analysis ) . Analyses were by intention to treat . The margin of non-inferiority was 10 % . This trial is registered with Clinical Trials.gov , number NCT00472667 . FINDINGS Nine patients were excluded from the study ; 307 patients in the procalcitonin group and 314 in the control group were included in analyses . Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 ( 21.2 % [ 65/307 ] vs 20.4 % [ 64/314 ] ; absolute difference 0.8 % , 90 % CI -4.6 to 6.2 ) and day 60 ( 30.0 % [ 92/307 ] vs 26.1 % [ 82/314 ] ; 3.8 % , -2.1 to 9.7 ) . Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group ( 14.3 days [ SD 9.1 ] vs 11.6 days [ SD 8.2 ] ; absolute difference 2.7 days , 95 % CI 1.4 to 4.1 , p<0.0001 ) . INTERPRETATION A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes . FUNDING Assistance Publique-Hôpitaux de Paris , France , and Brahms , Germany CONTEXT In previous smaller trials , a procalcitonin ( PCT ) algorithm reduced antibiotic use in patients with lower respiratory tract infections ( LRTIs ) . OBJECTIVE To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes . DESIGN , SETTING , AND PATIENTS A multicenter , noninferiority , r and omized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerl and with an open intervention of 1359 patients with mostly severe LRTIs r and omized between October 2006 and March 2008 . INTERVENTION Patients were r and omized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics ( PCT group ) or according to st and ard guidelines ( control group ) . Serum PCT was measured locally in each hospital and instructions were Web-based . MAIN OUTCOME MEASURES Noninferiority of the composite adverse outcomes of death , intensive care unit admission , disease-specific complications , or recurrent infection requiring antibiotic treatment within 30 days , with a predefined noninferiority boundary of 7.5 % ; and antibiotic exposure and adverse effects from antibiotics . RESULTS The rate of overall adverse outcomes was similar in the PCT and control groups ( 15.4 % [ n = 103 ] vs 18.9 % [ n = 130 ] ; difference , -3.5 % ; 95 % CI , -7.6 % to 0.4 % ) . The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients ( 5.7 vs 8.7 days ; relative change , -34.8 % ; 95 % CI , -40.3 % to -28.7 % ) and in the subgroups of patients with community-acquired pneumonia ( n = 925 , 7.2 vs 10.7 days ; -32.4 % ; 95 % CI , -37.6 % to -26.9 % ) , exacerbation of chronic obstructive pulmonary disease ( n = 228 , 2.5 vs 5.1 days ; -50.4 % ; 95 % CI , -64.0 % to -34.0 % ) , and acute bronchitis ( n = 151 , 1.0 vs 2.8 days ; -65.0 % ; 95 % CI , -84.7 % to -37.5 % ) . Antibiotic-associated adverse effects were less frequent in the PCT group ( 19.8 % [ n = 133 ] vs 28.1 % [ n = 193 ] ; difference , -8.2 % ; 95 % CI , -12.7 % to -3.7 % ) . CONCLUSION In patients with LRTIs , a strategy of PCT guidance compared with st and ard guidelines result ed in similar rates of adverse outcomes , as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N95122877 Introduction Patients with severe acute exacerbations of asthma often receive inappropriate antibiotic treatment . We aim ed to determine whether serum procalcitonin ( PCT ) levels can effectively and safely reduce antibiotic exposure in patients experiencing exacerbations of asthma . Methods In this r and omized controlled trial , a total of 216 patients requiring hospitalization for severe acute exacerbations of asthma were screened for eligibility to participate and 169 completed the 12-month follow-up visit . Patients were r and omized to either PCT-guided ( PCT group ) or st and ard ( control group ) antimicrobial therapy . In the control group , patients received antibiotics according to the attending physician ’s discretion ; in the PCT group , patients received antibiotics according to an algorithm based on serum PCT levels . The primary end point was antibiotic exposure ; secondary end points were clinical recovery , length of hospital stay , clinical and laboratory parameters , spirometry , number of asthma exacerbations , emergency room visits , hospitalizations and need for corticosteroid use due to asthma . Results PCT guidance reduced antibiotic prescription ( 48.9 % versus 87.8 % , respectively ; P < 0.001 ) and antibiotic exposure ( relative risk , 0.56 ; 95 % confidence interval , 0.44 to 0.70 ; P < 0.001 ) compared to st and ard therapy . There were no significant differences in clinical recovery , length of hospital stay or clinical , laboratory and spirometry outcomes in both groups . Number of asthma exacerbations , emergency room visits , hospitalizations and need for corticosteroid use due to asthma were similar during the 12-month follow-up period . Conclusion A PCT-guided strategy allows antibiotic exposure to be reduced in patients with severe acute exacerbation of asthma without apparent harm . Trial registration Chinese Clinical Trial Register ChiCTR-TRC-12002534 ( registered 26 September 2012 Objective : For patients in intensive care units , sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis . The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation , guided by daily measurements of the biomarker procalcitonin , could reduce the time to appropriate therapy , thus improving survival . Design : R and omized controlled open-label trial . Setting : Nine multidisciplinary intensive care units across Denmark . Patients : A total of 1,200 critically ill patients were included after meeting the following eligibility requirements : expected intensive care unit stay of ≥24 hrs , nonpregnant , judged to not be harmed by blood sampling , bilirubin < 40 mg/dL , and triglycerides < 1000 mg/dL ( not suspensive ) . Interventions : Patients were r and omized either to the “ st and ard-of-care-only arm , ” receiving treatment according to the current international guidelines and blinded to procalcitonin levels , or to the “ procalcitonin arm , ” in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements . Measurements and Main Results : The primary end point was death from any cause at day 28 ; this occurred for 31.5 % ( 190 of 604 ) patients in the procalcitonin arm and for 32.0 % ( 191 of 596 ) patients in the st and ard-of-care-only arm ( absolute risk reduction , 0.6 % ; 95 % confidence interval [ CI ] −4.7 % to 5.9 % ) . Length of stay in the intensive care unit was increased by one day ( p = .004 ) in the procalcitonin arm , the rate of mechanical ventilation per day in the intensive care unit increased 4.9 % ( 95 % CI , 3.0–6.7 % ) , and the relative risk of days with estimated glomerular filtration rate < 60 mL/min/1.73 m2 was 1.21 ( 95 % CI , 1.15–1.27 ) . Conclusions : Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit . The procalcitonin strategy like the one used in this trial can not be recommended IMPORTANCE High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress . Procalcitonin-guided antimicrobial therapy may hasten the diagnosis of sepsis , but effect on outcome is unclear . OBJECTIVE To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality . DESIGN , SETTING , AND PARTICIPANTS The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis ( SISPCT ) , a multicenter , r and omized , clinical , 2 × 2 factorial trial performed in 33 intensive care units in Germany , was conducted from November 6 , 2009 , to June 6 , 2013 , including a 90-day follow-up period . INTERVENTIONS Patients were r and omly assigned to receive an initial intravenous loading dose of sodium selenite , 1000 µg , followed by a continuous intravenous infusion of sodium selenite , 1000 µg , daily until discharge from the intensive care unit , but not longer than 21 days , or placebo . Patients also were r and omized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance . MAIN OUTCOMES AND MEASURES The primary end point was 28-day mortality . Secondary outcomes included 90-day all-cause mortality , intervention-free days , antimicrobial costs , antimicrobial-free days , and secondary infections . RESULTS Of 8174 eligible patients , 1089 patients ( 13.3 % ) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite ( 543 patients [ 49.9 % ] ) with placebo ( 546 [ 50.1 % ] ) and procalcitonin guidance ( 552 [ 50.7 % ] ) vs no procalcitonin guidance ( 537 [ 49.3 % ] ) . The 28-day mortality rate was 28.3 % ( 95 % CI , 24.5%-32.3 % ) in the sodium selenite group and 25.5 % ( 95 % CI , 21.8%-29.4 % ) ( P = .30 ) in the placebo group . There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance ( 25.6 % [ 95 % CI , 22.0%-29.5 % ] ) vs no procalcitonin guidance ( 28.2 % [ 95 % CI , 24.4%-32.2 % ] ) ( P = .34 ) . Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5 % reduction of antimicrobial exposure . CONCLUSIONS AND RELEVANCE Neither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis . These findings do not support administration of high-dose sodium selenite in these patients ; the application of a procalcitonin-guided algorithm needs further evaluation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00832039 Objectives : To prospect ively vali date that the inability to decrease procalcitonin levels by more than 80 % between baseline and day 4 is associated with increased 28-day all-cause mortality in a large sepsis patient population recruited across the United States . Design : Blinded , prospect i ve multicenter observational clinical trial following an Food and Drug Administration-approved protocol . Setting : Thirteen U.S.-based emergency departments and ICUs . Patients : Consecutive patients meeting criteria for severe sepsis or septic shock who were admitted to the ICU from the emergency department , other wards , or directly from out of hospital were included . Interventions : Procalcitonin was measured daily over the first 5 days . Measurements and Main Results : The primary analysis of interest was the relationship between a procalcitonin decrease of more than 80 % from baseline to day 4 and 28-day mortality using Cox proportional hazards regression . Among 858 enrolled patients , 646 patients were alive and in the hospital on day 4 and included in the main intention-to-diagnose analysis . The 28-day all-cause mortality was two-fold higher when procalcitonin did not show a decrease of more than 80 % from baseline to day 4 ( 20 % vs 10 % ; p = 0.001 ) . This was confirmed as an independent predictor in Cox regression analysis ( hazard ratio , 1.97 [ 95 % CI , 1.18–3.30 ; p < 0.009 ] ) after adjusting for demographics , Acute Physiology and Chronic Health Evaluation II , ICU residence on day 4 , sepsis syndrome severity , antibiotic administration time , and other relevant confounders . Conclusions : Results of this large , prospect i ve multicenter U.S. study indicate that inability to decrease procalcitonin by more than 80 % is a significant independent predictor of mortality and may aid in sepsis care Objectives To quantify the diagnostic accuracy of selected inflammatory markers in addition to symptoms and signs for predicting pneumonia and to derive a diagnostic tool . Design Diagnostic study performed between 2007 and 2010 . Participants had their history taken , underwent physical examination and measurement of C reactive protein ( CRP ) and procalcitonin in venous blood on the day they first consulted , and underwent chest radiography within seven days . Setting Primary care centres in 12 European countries . Participants Adults presenting with acute cough . Main outcome measures Pneumonia as determined by radiologists , who were blind to all other information when they judged chest radiographs . Results Of 3106 eligible patients , 286 were excluded because of missing or inadequate chest radiographs , leaving 2820 patients ( mean age 50 , 40 % men ) of whom 140 ( 5 % ) had pneumonia . Re- assessment of a subset of 1675 chest radiographs showed agreement in 94 % ( κ 0.45 , 95 % confidence interval 0.36 to 0.54 ) . Six published “ symptoms and signs models ” varied in their discrimination ( area under receiver operating characteristics curve ( ROC ) ranged from 0.55 ( 95 % confidence interval 0.50 to 0.61 ) to 0.71 ( 0.66 to 0.76 ) ) . The optimal combination of clinical prediction items derived from our patients included absence of runny nose and presence of breathlessness , crackles and diminished breath sounds on auscultation , tachycardia , and fever , with an ROC area of 0.70 ( 0.65 to 0.75 ) . Addition of CRP at the optimal cut off of > 30 mg/L increased the ROC area to 0.77 ( 0.73 to 0.81 ) and improved the diagnostic classification ( net reclassification improvement 28 % ) . In the 1556 patients classified according to symptoms , signs , and CRP > 30 mg/L as “ low risk ” ( < 2.5 % ) for pneumonia , the prevalence of pneumonia was 2 % . In the 132 patients classified as “ high risk ” ( > 20 % ) , the prevalence of pneumonia was 31 % . The positive likelihood ratio of low , intermediate , and high risk for pneumonia was 0.4 , 1.2 , and 8.6 respectively . Measurement of procalcitonin added no relevant additional diagnostic information . A simplified diagnostic score based on symptoms , signs , and CRP > 30 mg/L result ed in proportions of pneumonia of 0.7 % , 3.8 % , and 18.2 % in the low , intermediate , and high risk group respectively . Conclusions A clinical rule based on symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough performed best in patients with mild or severe clinical presentation . Addition of CRP concentration at the optimal cut off of > 30 mg/L improved diagnostic information , but measurement of procalcitonin concentration did not add clinical ly relevant information in this group RATIONALE In patients with community-acquired pneumonia , guidelines recommend antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial infections , and its dynamics have prognostic implication s. OBJECTIVE To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia . METHODS In a r and omized intervention trial , 302 consecutive patients with suspected community-acquired pneumonia were included . Data were assessed at baseline , after 4 , 6 , and 8 d , and after 6 wk . The control group ( n = 151 ) received antibiotics according to usual practice . In the procalcitonin group ( n = 151 ) , antibiotic treatment was based on serum procalcitonin concentrations as follows : strongly discouraged , less than 0.1 microg/L ; discouraged , less than 0.25 microg/L ; encouraged , greater than 0.25 microg/L ; strongly encouraged , greater than 0.5 microg/L. The primary endpoint was antibiotic use ; secondary endpoints were measures of clinical , laboratory , and radiographic outcome . RESULTS At baseline , both groups were similar regarding clinical , laboratory , and microbiology characteristics , and Pneumonia Severity Index . Procalcitonin guidance reduced total antibiotic exposure ( relative risk , 0.52 ; 95 % confidence interval , 0.48 - 0.55 ; p < 0.001 ) , antibiotic prescriptions on admission ( 85 vs. 99 % ; p < 0.001 ) , and antibiotic treatment duration ( median , 5 vs. 12 d ; p < 0.001 ) compared with patients treated according to guidelines . After adjustment for Pneumonia Severity Index , the hazard ratio of antibiotic discontinuation was higher in the procalcitonin group than in the control group ( 3.2 ; 95 % confidence interval , 2.5 to 4.2 ) . Outcome was similar in both groups , with an overall success rate of 83 % . CONCLUSIONS Procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia . These findings may have important clinical and public health implication Recent studies have suggested that procalcitonin ( PCT ) is a safe marker for the discrimination between bacterial and viral infection , and that PCT-guided treatment may lead to substantial reductions in antibiotic use . The present objective was to evaluate the effect of a single PCT measurement on antibiotic use in suspected lower respiratory tract infections ( LRTIs ) in a Danish hospital setting . In a r and omized , controlled intervention study , 223 adult patients admitted to the hospital because of suspicion of LRTI were included with 210 patients available for analysis . Patients were r and omized to either PCT-guided treatment or st and ard treatment . Antibiotic treatment duration in the PCT group was based on the serum PCT value at admission . The cut-off point for recommending antibiotic treatment was PCT > or = 0.25 microg/L. Physicians could overrule treatment guidelines . The mean duration of hospital stay was 5.9 days in the PCT group vs. 6.7 days in the control group ( p 0.22 ) . The mean duration of antibiotic treatment during hospitalization in the PCT group was 5.1 days on average , as compared to 6.8 days in the control group ( p 0.007 ) . In a subgroup analysis of chronic obstructive pulmonary disease patients , the mean length of stay was reduced from 7.1 days in the control group to 4.8 days in the PCT group ( p 0.009 ) . It was concluded that the determination of a single PCT value at admission in patients with suspected LRTIs can lead to a reduction in the duration of antibiotic treatment by 25 % without compromising outcome . No effect on the length of hospital stay was found BACKGROUND Acute respiratory tract infections are the most common reason for antibiotic therapy in primary care despite their mainly viral etiology . A laboratory test measuring procalcitonin levels in blood specimens was suggested as a tool to reduce unnecessary prescribing of antibiotics . We consider whether antibiotic therapy guided by procalcitonin reduces the use of antibiotics without increasing the restrictions experienced by patients by more than 1 day . METHODS Fifty-three primary care physicians recruited 458 patients , each patient with an acute respiratory tract infection and , in the physician 's opinion , in need of antibiotics . Patients were central ly r and omized to either a procalcitonin-guided approach to antibiotic therapy or to a st and ard approach . For patients r and omized to procalcitonin-guided therapy , the use of antibiotics was more or less strongly discouraged ( procalcitonin level , < or = 0.1 or < or = 0.25 microg/L , respectively ) or recommended ( procalcitonin level , > 0.25 microg/L ) . Follow-up data were collected at 7 days by treating physicians and at 14 and 28 days by blinded interviewers . RESULTS Adjusted for baseline characteristics , the mean increase at 14 days in days in which activities were restricted was 0.14 with procalcitonin-guided therapy ( 95 % confidence interval [ CI ] , -0.53 to 0.81 days ) , which met our criterion of an increase in days in which activities were restricted by no more than 1 day . With procalcitonin-guided therapy , the antibiotic prescription rate was 72 % lower ( 95 % CI , 66%-78 % ) than with st and ard therapy . Both approaches led to a similar proportion of patients reporting symptoms of ongoing or relapsing infection at 28 days ( adjusted odds ratio , 1.0 [ 95 % CI , 0.7 - 1.5 ] ) . CONCLUSIONS As an adjunct to guidelines , procalcitonin-guided therapy markedly reduces antibiotic use for acute respiratory tract infections in primary care without compromising patient outcome . In practice , this could be achieved with 1 to 2 procalcitonin measurements in patients for whom the physician intends to prescribe antibiotics Background This r and omized controlled trial aim ed to evaluate whether the serum procalcitonin ( PCT ) level can be utilized to guide the use of antibiotics in the treatment of acute exacerbations of asthma . Methods A total of 293 consecutive patients with suspected asthma attacks from February 2005 to July 2010 participated in this study . 225 patients completed the study . Serum PCT levels , and other inflammatory biomarkers of all patients were measured . In addition to the st and ard treatment , the control group received antibiotics according to the attending physicians ’ discretions , while the patients in the PCT group were treated with antibiotics according to serum PCT concentrations . Antibiotics usage was strongly discouraged when the PCT concentration was below 0.1 μg/L ; discouraged when the PCT concentration was between 0.1 μg/L and 0.25 μg/L ; or encouraged when the PCT concentration was above 0.25 μg/L. The primary endpoint was the determination of antibiotics usage . The second endpoints included the diagnostic accuracy of PCT and other laboratory biomarkers the effectiveness of asthma control , secondary ED visits , hospital re-admissions , repeated needs for steroids or dosage increase , needs for antibiotics , WBC count , PCT levels and FEV1 % . Results At baseline , two groups were identical regarding clinical , laboratory and symptom score . Probability of the antibiotics usage in the PCT group ( 46.1 % ) was lower than that in the control group ( 74.8 % ) ( χ2 = 21.97 , p < 0.001 . RR = 0.561 , 95 % CI 0.441 - 0.713 ) . PCT and IL-6 showed good diagnostic significance for bacterial asthma ( r = 0.705 , p = 0.003 ) . The degrees of asthma control in patients were categorized to three levels and were comparable between the two groups at the six weeks follow-up period ( χ2 = 1.62 , p = 0.45 ) . There were no significant difference regarding other secondary outcomes ( p > 0.05 ) . Conclusions The serum PCT concentration can be used to effectively determine whether the acute asthma patients have bacterial infections in the respiratory tract , and to guide the use of antibiotics in the treatment of acute asthma exacerbations , which may substantially reduce unnecessary antibiotic use without compromising the therapeutic outcomes .Trial registration In order to evaluate the use of an algorithm based on a procalcitonin ( PCT ) cut-off value as a means of guiding antibiotic therapy , 319 hospitalised children with uncomplicated community-acquired pneumonia ( CAP ) were r and omised 1:1 to be treated on the basis of the algorithm or in accordance with st and ard guidelines . The children in the PCT group did not receive antibiotics if their PCT level upon admission was < 0.25 ng/mL , and those receiving antibiotics from the time of admission were treated until their PCT level was ≥ 0.25 ng/mL. The final analysis was based on 155 patients in the PCT group and 155 in the control group . In comparison with the controls , the PCT group received significantly fewer antibiotic prescriptions ( 85.8 % vs 100 % ; p < 0.05 ) , were exposed to antibiotics for a shorter time ( 5.37 vs 10.96 days ; p < 0.05 ) , and experienced fewer antibiotic-related adverse events ( 3.9 % vs 25.2 % ; p < 0.05 ) , regardless of CAP severity . There was no significant between-group difference in recurrence of respiratory symptoms and new antibiotic prescription in the month following enrollment . The results of this first prospect i ve study using a PCT cut-off value to guide antibiotic therapy for pediatric CAP showed that this approach can significantly reduce antibiotic use and antibiotic-related adverse events in children with uncomplicated disease . However , because the study included mainly children with mild to moderate CAP and the risk of the use of the algorithm-based approach was not vali date d in a relevant number of severe cases , further studies are needed before it can be used in routine clinical practice Introduction The development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment . Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting . Until recently , no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction ; however , over the past years , procalcitonin ( PCT ) is the first among a large array of inflammatory variables that offers this possibility . The present study aim ed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients . Methods All patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible . Patients were r and omly assigned to either a PCT-guided ( study group ) or a st and ard ( control group ) antibiotic regimen . Antibiotic therapy in the PCT-guided group was discontinued , if clinical signs and symptoms of infection improved and PCT decreased to < 1 ng/ml or the PCT value was > 1 ng/ml , but had dropped to 25 to 35 % of the initial value over three days . In the control group antibiotic treatment was applied as st and ard regimen over eight days . Results A total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high- grade suspected infections were enrolled in this study . In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly . The control group comprised 53 patients with a st and ardized duration of antibiotic therapy over eight days . Demographic and clinical data were comparable in both groups . However , in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls ( 5.9 + /- 1.7 versus 7.9 + /- 0.5 days , P < 0.001 ) without negative effects on clinical outcome . Conclusions Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients . This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine . Annotation Results were previously published in German in Anaesthesist 2008 ; 57 : 571–577 ( PMID : 18463831).Trial registration IS RCT Objective : We sought to evaluate whether procalcitonin was superior to C-reactive protein in guiding antibiotic therapy in intensive care patients with sepsis . Design : R and omized open clinical trial . Setting : Two university hospitals in Brazil . Patients : Patients with severe sepsis or septic shock . Interventions : Patients were r and omized in two groups : the procalcitonin group and the C-reactive protein group . Antibiotic therapy was discontinued following a protocol based on serum levels of these markers , according to the allocation group . The procalcitonin group was considered superior if the duration of antibiotic therapy was at least 25 % shorter than in the C-reactive protein group . For both groups , at least seven full-days of antibiotic therapy were ensured in patients with Sequential Organ Failure Assessment greater than 10 and /or bacteremia at inclusion , and patients with evident resolution of the infectious process had antibiotics stopped after 7 days , despite biomarkers levels . Measurements and Main Results : Ninety-four patients were r and omized : 49 patients to the procalcitonin group and 45 patients to the C-reactive protein group . The mean age was 59.8 ( SD , 16.8 ) years . The median duration of antibiotic therapy for the first episode of infection was 7.0 ( Q1–Q3 , 6.0–8.5 ) days in the procalcitonin group and 6.0 ( Q1–Q3 , 5.0–7.0 ) days in the C-reactive protein group ( p = 0.13 ) , with a hazard ratio of 1.206 ( 95 % CI , 0.774–1.3 ; p = 0.13 ) . Overall , protocol overruling occurred in only 13 ( 13.8 % ) patients . Twenty-one patients died in each group ( p = 0.836 ) . Conclusions : C-reactive protein was as useful as procalcitonin in reducing antibiotic use in a predominantly medical population of septic patients , causing no apparent BACKGROUND AND OBJECTIVE Use of antibiotics in out patients with community-acquired pneumonia ( CAP ) is empirical , which may lead to overuse and selection pressure for resistance . Procalcitonin ( PCT ) levels may predict the severity of CAP and may be used to guide antibiotic use in hospitalized patients . This study evaluated the value of PCT measurements for guiding antibiotic use in low-risk out patients with CAP . METHODS This was a r and omized intervention trial conducted between February 2005 and December 2008 that included 172 consecutive patients with suspected CAP , of whom 156 completed the study . The control group received antibiotics according to current guidelines . In the PCT group , antibiotic treatment was based on PCT levels as follows : < 0.1 µg/L , strongly discouraged ; ≤0.25 µg/L , discouraged ; > 0.25 µg/L , encouraged . The primary end-points were total antibiotic use and duration of antibiotic treatment ; laboratory and clinical outcomes were measured . RESULTS Prescription of antibiotics on admission ( 84.4 % vs 97.5 % ; P = 0.004 ) , total antibiotic exposure ( relative risk 0.55 , 95 % CI : 0.51 - 0.60 ; P = 0.003 ) and duration of antibiotic treatment ( median 5 days vs 7 days ; P < 0.001 ) were reduced in the PCT guidance group , compared with patients treated according to current guidelines . At 4-week follow up , all patients had survived and laboratory and clinical outcomes were similar in the two groups . CONCLUSIONS Under PCT guidance , antibiotic use was reduced and duration of antibiotic treatment was shortened in low-risk out patients with CAP , without apparent harm Objective Some patients with the phenotype of severe sepsis may have no overt source of infection or identified pathogen . We investigated whether a procalcitonin-based algorithm influenced antibiotic use in patients with non-microbiologically proven apparent severe sepsis . Design This multicentre , r and omised , controlled , single-blind trial was performed in two parallel groups . Setting Eight intensive care units in France . Participants Adults with the phenotype of severe sepsis and no overt source of infection , negative microbial cultures from multiple matrices and no antibiotic exposure shortly before intensive care unit admission . Intervention The initiation and duration of antibiotic therapy was based on procalcitonin levels in the experimental arm and on the intensive care unit physicians ’ clinical judgement without reference to procalcitonin values in the control arm . Main outcome measure The primary outcome was the proportion of patients on antibiotics on day 5 postr and omisation . Results Over a 3-year period , 62/1250 screened patients were eligible for the study , of whom 31 were r and omised to each arm ; 4 later withdrew their consent . At day 5 , 18/27 ( 67 % ) survivors were on antibiotics in the experimental arm , versus 21/26 ( 81 % ) controls ( p=0.24 ; relative risk=0.83 , 95 % CI : 0.60 to 1.14 ) . Only 8/58 patients ( 13 % ) had baseline procalcitonin < 0.25 µg/l ; in these patients , physician complied poorly with the algorithm . Conclusions In intensive care unit patients with the phenotype of severe sepsis or septic shock and without an overt source of infection or a known pathogen , the current study was unable to confirm that a procalcitonin-based algorithm may influence antibiotic exposure . However , the premature termination of the trial may not allow definitive conclusions Background This study was conducted to investigate whether point-of-care ( POC ) procalcitonin ( PCT ) measurement can reduce redundant antibiotic treatment in patients hospitalized with acute exacerbation of COPD ( AE COPD ) . Methods One-hundred and twenty adult patients admitted with AE COPD were enrolled in this open-label r and omized trial . Patients were allocated to either the POC PCT-guided intervention arm ( n=62 ) or the control arm , in which antibiotic therapy followed local guidelines ( n=58 ) . Results The median duration of antibiotic exposure was 3.5 ( interquartile range [ IQR ] 0–10 ) days in the PCT-arm vs 8.5 ( IQR 1–11 ) days in the control arm ( P=0.0169 , Wilcoxon ) for the intention-to-treat population . The proportion of patients using antibiotics for ≥5 days within the 28-day follow-up was 41.9 % ( PCT-arm ) vs 67.2 % ( P=0.006 , Fisher ’s exact ) in the intention-to-treat population . For the per- protocol population , the proportions were 21.1 % ( PCT-arm ) vs 73.9 % ( P<0.00001 , Fisher ’s exact ) . Within 28-day follow-up , one patient died in the PCT-arm and two died in the control arm . A composite harm end point consisting of death , rehospitalization , or intensive care unit admission , all within 28 days , showed no apparent difference . Conclusion Our study shows that the implementation of a POC PCT-guided algorithm can be used to substantially reduce antibiotic exposure in patients hospitalized with AE COPD , with no apparent harm Background Urinary tract infections ( UTIs ) are common drivers of antibiotic use . The minimal effective duration of antibiotic therapy for UTIs is unknown , but any reduction is important to diminish selection pressure for antibiotic resistance , costs , and drug-related side-effects . The aim of this study was to investigate whether an algorithm based on procalcitonin ( PCT ) and quantitative pyuria reduces antibiotic exposure . Methods From April 2012 to March 2014 , we conducted a factorial design r and omized controlled open-label trial . Immunocompetent adults with community-acquired non-catheter-related UTI were enrolled in the emergency department of a tertiary-care 600-bed hospital in northwestern Switzerl and . Clinical presentation was used to guide initiation and duration of antibiotic therapy according to current guidelines ( control group ) or with a PCT-pyuria-based algorithm ( PCT-pyuria group).The primary endpoint was overall antibiotic exposure within 90 days . Secondary endpoints included duration of the initial antibiotic therapy , persistent infection 7 days after end of therapy and 30 days after enrollment , recurrence and rehospitalizations within 90 days . Results Overall , 394 patients were screened , 228 met predefined exclusion criteria , 30 declined to participate , and 11 were not eligible . Of these , 125 ( 76 % women ) were enrolled in the intention-to-treat ( ITT ) analysis and 96 patients with microbiologically confirmed UTI constituted the per protocol group ; 84 of 125 ( 67 % ) patients had a febrile UTI , 28 ( 22 % ) had bacteremia , 5 ( 4 % ) died , and 3 ( 2 % ) were lost to follow-up . Overall antibiotic exposure within 90 days was shorter in the PCT-pyuria group than in the control group ( median 7.0 [ IQR , 5.0–14.0 ] vs. 10.0 [ IQR , 7.0–16.0 ] days , P = 0.011 ) in the ITT analysis . Mortality , rates of persistent infections , recurrences , and rehospitalizations were not different . Conclusions A PCT-pyuria-based algorithm reduced antibiotic exposure by 30 % when compared to current guidelines without apparent negative effects on clinical outcomes .Trial registration Current controlled trials IS RCT N13663741 , date applied : 22/05/2012 , date assigned : 03/07/2012 , last edited : 28/01/2014 Background The duration of antibiotic treatment of exacerbations of COPD ( E COPD ) is controversial . Serum procalcitonin ( PCT ) is a biomarker of bacterial infection used to identify the cause of E COPD . Methods and Findings We investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe E COPD . For this multicenter , r and omized , non-inferiority trial , we enrolled 184 patients hospitalized with E COPD from 18 hospitals in Italy . Patients were assigned to receive antibiotics for 10 days ( st and ard group ) or for either 3 or 10 days ( PCT group ) . The primary outcome was the rate of E COPD at 6 months . Having planned to recruit 400 patients , we r and omized only 183 : 93 in the PCT group and 90 in the st and ard group . Thus , the completed study was underpowered . The E COPD rate at 6 months between PCT-guided and st and ard antibiotic treatment was not significant ( % difference , 4.04 ; 90 % confidence interval [ CI ] , −7.23 to 15.31 ) , but the CI included the non-inferiority margin of 15 . In the PCT-guided group , about 50 % of patients were treated for 3 days , and there was no difference in primary or secondary outcomes compared to patients treated for 10 days . Conclusions Although the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group , the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT can not be substantiated statistically . Thus , the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the st and ard antibiotic treatment . The study was funded by Agenzia Italiana del Farmaco ( AIFA-FARM58J2XH ) . Clinical trial registered with www . clinical trials.gov ( NCT01125098 ) . Trial Registration Clinical Trials.gov Object : To assess the clinical value of procalcitonin to guide antibiotic therapy in acute exacerbations of idiopathic pulmonary fibrosis . Methods : Patients with acute exacerbations of idiopathic pulmonary fibrosis were r and omly assigned to the procalcitonin-guided group ( antibiotic use guided by a procalcitonin threshold of 0.25 ng/ml ) or the routine treatment group ( antibiotic use according to routine practice ) . Follow up of clinical outcomes were assessed at baseline and 30 days later . Results : Baseline characteristics including demographics , clinical characteristics and laboratory results were similar between groups . PCT guidance result ed in a significant reduction of antibiotic treatment duration ( 8.7±6.6 compared to 14.2±5.2 days in the routine treatment group ) . Fewer patients were exposed to antibiotics treatment in the PCT group ( 26 patients ) compared with the control group ( 35 patients ) . Treatment success , mortality rate , days of hospitalization and ventilation therapy were similar between the two groups . Conclusion : Procalcitonin-guided antibiotic therapy of patients with acute exacerbation of idiopathic pulmonary fibrosis may result in reduced exposure to antibiotics without adversely affecting patient outcomes In patients with ventilator-associated pneumonia ( VAP ) , guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy . In a multicentre , r and omised , controlled trial , 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines ( control group ) or to serum procalcitonin concentrations ( procalcitonin group ) with an antibiotic regimen selected by the treating physician . The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis . Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset ( 13 ( 2–21 ) days versus 9.5 ( 1.5–17 ) days ) . This translated into a reduction in the overall duration of antibiotic therapy of 27 % in the procalcitonin group ( p = 0.038 ) . After adjustment for age , microbiology and centre effect , the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines ( hazard rate 1.6 , 95 % CI 1.02–2.71 ) . The number of mechanical ventilation-free days alive , intensive care unit-free days alive , length of hospital stay and mortality rate on day 28 for the two groups were similar . Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia Objective To assess the effect of general practitioner testing for C reactive protein ( disease approach ) and receiving training in enhanced communication skills ( illness approach ) on antibiotic prescribing for lower respiratory tract infection . Design Pragmatic , 2 × 2 factorial , cluster r and omised controlled trial . Setting 20 general practice s in the Netherl and s. Participants 40 general practitioners from 20 practice s recruited 431 patients with lower respiratory tract infection . Main outcome measures The primary outcome was antibiotic prescribing at the index consultation . Secondary outcomes were antibiotic prescribing during 28 days ’ follow-up , reconsultation , clinical recovery , and patients ’ satisfaction and enablement . Interventions General practitioners ’ use of C reactive protein point of care testing and training in enhanced communication skills separately and combined , and usual care . Results General practitioners in the C reactive protein test group prescribed antibiotics to 31 % of patients compared with 53 % in the no test group ( P=0.02 ) . General practitioners trained in enhanced communication skills prescribed antibiotics to 27 % of patients compared with 54 % in the no training group ( P<0.01 ) . Both interventions showed a statistically significant effect on antibiotic prescribing at any point during the 28 days ’ follow-up . Clinicians in the combined intervention group prescribed antibiotics to 23 % of patients ( interaction term was non-significant ) . Patients ’ recovery and satisfaction were similar in all study groups . Conclusion Both general practitioners ’ use of point of care testing for C reactive protein and training in enhanced communication skills significantly reduced antibiotic prescribing for lower respiratory tract infection without compromising patients ’ recovery and satisfaction with care . A combination of the illness and disease focused approaches may be necessary to achieve the greatest reduction in antibiotic prescribing for this common condition in primary care . Trial registration Current Controlled Trials IS RCT N85154857 Increasing worldwide development of antimicrobial resistance and the association of resistance development and antibiotic overuse make it necessary to seek strategies for safely reducing antibiotic use and selection pressure . In a first step , in a non-interventional study , the antibiotic prescription rates , initial procalcitonin ( PCT ) levels and outcome of 702 patients presenting with acute respiratory infection at 45 primary care physicians were observed . The second part was a r and omised controlled non-inferiority trial comparing st and ard care with PCT-guided antimicrobial treatment in 550 patients in the same setting . Antibiotics were recommended at a PCT threshold of 0.25 ng·mL−1 . Clinical overruling was permitted . The primary end-point for non-inferiority was number of days with significant health impairment after 14 days . Antibiotics were prescribed in 30.3 % of enrolled patients in the non-interventional study . In the interventional study , 36.7 % of patients in the control group received antibiotics as compared to 21.5 % in the PCT-guided group ( 41.6 % reduction ) . In the modified intention-to-treat analysis , the numbers of days with significant health impairment were similar ( mean 9.04 versus 9.00 for PCT-guided and control group , respectively ; difference 0.04 ; 95 % confidence interval -0.73–0.81 ) . This was also true after adjusting for the most important confounders . In the PCT group , advice was overruled in 36 cases . There was no significant difference in primary end-point when comparing the PCT group treated as advised , the overruled PCT group and the control group ( 9.008 versus 9.250 versus 9.000 days ; p = 0.9605 ) . A simple one-point PCT measurement for guiding decisions on antibiotic treatment is non-inferior to st and ard treatment in terms of safety , and effectively reduced the antibiotic treatment rate by 41.6 % Abstract Background : Whether or not antibiotic stewardship protocol s based on procalcitonin levels results in cost savings remains unclear . Herein , our objective was to assess the economic impact of adopting procalcitonin testing among patients with suspected acute respiratory tract infection ( ARI ) from the perspective of a typical US integrated delivery network ( IDN ) with a 1,000,000 member catchment area or enrollment . Methods : To conduct an economic evaluation of procalcitonin testing versus usual care we built a cost-impact model based on patient-level meta- analysis data of r and omized trials . The meta-analytic data was adapted to the US setting by applying the meta-analytic results to US lengths of stay , costs , and practice patterns . We estimated the annual ARI visit rate for the one million member cohort , by setting ( inpatient , ICU , outpatient ) and ARI diagnosis . Results : In the inpatient setting , the costs of procalcitonin-guided compared to usual care for the one million member cohort was $ 2,083,545 , compared to $ 2,780,322 , result ing in net savings of nearly $ 700,000 to the IDN for 2014 . In the ICU and outpatient setting s , savings were $ 73,326 and $ 5,329,824 , respectively , summing up to overall net savings of $ 6,099,927 for the cohort . Results were robust for all ARI diagnoses . For the whole US insured population , procalcitonin-guided care would result in $ 1.6 billion in savings annually . Conclusions : Our results show substantial savings associated with procalcitonin protocol s of ARI across common US treatment setting s mainly by direct reduction in unnecessary antibiotic utilization . These results are robust to changes in key parameters , and the savings can be achieved without any negative impact on treatment outcomes BACKGROUND Procalcitonin-guided antibiotic therapy for community-acquired pneumonia is effective and safe . However , the usefulness of procalcitonin for aspiration pneumonia and its nutrition-related outcomes are unknown . METHODS We conducted a noninferiority r and omized controlled study in patients with aspiration pneumonia who were admitted to our hospital between September 2010 and January 2012 . We r and omly assigned 105 patients to groups with different duration s of antibiotic therapy based on the procalcitonin levels upon admission ( procalcitonin group ) or according to the st and ard guidelines ( control group ) . The primary endpoints were relapse of aspiration pneumonia and death within 30 days , with a predefined noninferiority boundary of 10 % . Secondary endpoints included duration of antibiotic exposure . Furthermore , we conducted a retrospective analysis of the prognostic factors that determined continuation of oral nutritional intake , relapse of pneumonia , and in-hospital death . RESULTS The rate of relapse and death within 30 days were similar in the procalcitonin and control groups ( 25 % versus 37.5 % ; difference , -12.5 % ; 95 % confidence interval , -30.9 % to 5.9 % ) . Procalcitonin-guided antibiotic therapy significantly shortened the median duration of antibiotic exposure ( 5 versus 8 days ; p<0.0001 ) ; however , the continuation of oral intake was not increased ( 56 % versus 50 % ; p=0.54 ) . A multivariable analysis showed a significant association between the continuation of oral nutritional intake and the body mass index upon admission . CONCLUSIONS Procalcitonin-guided antibiotic therapy for aspiration pneumonia can shorten the duration of antibiotic exposure , but it does not increase the continuation of oral intake ( UMIN000004800 ) Clinicians have used procalcitonin ( PCT ) ( biomarker to differentiate bacterial from non-bacterial sepsis ) to guide use of antibiotics in patients . As the data for utility of PCT to discontinue antibiotics in an antimicrobial stewardship program ( ASP ) are lacking , we aim to describe the outcomes of patients in whom PCT was used to discontinue antibiotics under our ASP . An antimicrobial stewardship ( AS ) team intervened to discontinue antibiotics in patients with persistent fever or leucocytosis , source of sepsis unknown or negative bacteriological cultures , who had completed an adequate course of antibiotic therapy and had a PCT of < 0.5 μg/L. Main outcomes evaluated were 14-day re-infection , 30-day mortality and readmission . Antibiotic therapy was discontinued in 42 patients in 1 year . Unknown source of sepsis was found in 38 % of the patients ( including possible malignant fever ) and culture-negative pneumonia was found in 21 % . Two patients died of advanced cancer . One patient decided for comfort care and died one week later . One patient died due to a second episode of pneumonia 37 days after first PCT test . Six patients were readmitted within 30 days due to non-infectious causes . Three patients were readmitted due to culture-negative pneumonia . None had a 14-day re-infection . PCT used to discontinue antibiotics under our ASP did not compromise patients ’ outcome Febrile neutropenia ( FN ) requires immediate use of antibiotics ( ATB ) , and procalcitonin ( PCT ) is proven to be useful in guiding antibiotic therapy in different setting s. This study investigated the use of PCT as a guide for the duration of ATB in FN . A r and omized controlled trial was carried out from January – December 2010 . A total of 62 hematological adult patients with FN were r and omized , in 1:1 ratio , into two groups : ( 1 ) PCT group : length of ATB guided by institutional protocol plus PCT dynamics , and ( 2 ) control group : duration of ATB in accordance with institutional protocol . There was no difference between groups regarding the use of ATB for the first episode of fever ( HR 1.14 , 95 % CI 0.66–1.95 , p = 0.641 ) , with equivalent median duration of ATB therapy ( PCT group 9.0 days and control group 8.0 days , p = 0.67 ) , and median number of days without ATB ( 0 days , IQR 0–2 days for both groups , p = 0.96 ) . We observed no difference in clinical cure rate ( p = 0.68 ) , infection relapse ( p = 1.0 ) , superinfection ( p = 0.85 ) , length of hospitalization ( p = 0.64 ) , and mortality at 28 days ( p = 0.39 ) and at 90 days ( p = 0.72 ) . Considering the cut-off of 0.5 ng/ml , PCT was correlated with bacteremia ( sensitivity of 51.9 % and specificity of 76.5 % ) . In this r and omized controlled trial , adding a PCT-guided protocol to the st and ard recommendations did not reduce the use of antibiotics in febrile neutropenia , although no apparent harm was caused . PCT proved to be a marker of bacteremia in this setting INTRODUCTION Procalcitonin ( PCT ) is a thyroid gl and prohormone , and its serum concentration is elevated in systemic bacterial infections . The diagnostic cut-off value of PCT in patients early after cardiac surgery remains unclear . OBJECTIVE We investigated whether procalcitonin-guidance could reduce antibiotic usage safely . METHODS The prospect i ve study included 205 patients who underwent open heart surgery . The patients were r and omly assigned for procalcitonin-guided antibiotic treatment ( PCT-group ; n = 102 ) or st and ard care ( st and ard group ; n = 103 ) . On the basis of serum procalcitonin concentrations , usage of antibiotics was encouraged ( PCT > or = 0.5 ng/mL ) or discouraged . RESULTS A relative risk of antibiotic exposure in the st and ard group compared with the PCT-group was 3.81 ( 95 % CI = 2.03 - 7.17 ; p < 0.0001 ) . The mean cost of antibiotics per patient in procalcitonin group was Euro 193.3 + /- 636.6 vs. Euro 372.1 + /- 841.1 ( p = 0.206 ) in the st and ard group , while the mean cost per hospital day was Euro 8.0 + /- 18.4 vs. Euro 17.8 + /- 36.3 ( p = 0.028 ) . We found that non-infectious complications occurred in 40/102 vs. 41/103 ( p = 0.592 ) while infections appeared in 5/102 vs. 22/103 ( p = 0.001 ) cases . A statistically significant difference was observed in the treatment of urinary infections between PCT-group and st and ard group ; 1/102 vs. 9/103 ( p = 0.016 ) . In the PCT-group , the ICU stay was 5.74 + /- 11.49 days and in the st and ard group 6.97 + /- 11.61 ( p = 0.812 ) . The hospital stay was 12.08 + /- 11.28 vs. 12.93 + /- 10.73 ( p > 0.05 ) days , respectively . Mortality rates were equal in both groups of patients ( p = 0.537 ) . CONCLUSION Procalcitonin-guided antibiotic treatment is safe and can significantly reduce the cost of postoperative care . Additionally , the antibiotic use during immediate postoperative course should be timely controlled and limited to documented bacterial infections Objectives : To test the usefulness of procalcitonin serum level for the reduction of antibiotic consumption in intensive care unit patients . Design : Single-center , prospect i ve , r and omized controlled study . Setting : Five intensive care units from a tertiary teaching hospital . Patients : All consecutive adult patients hospitalized for > 48 hrs in the intensive care unit during a 9-month period . Interventions : Procalcitonin serum level was obtained for all consecutive patients suspected of developing infection either on admission or during intensive care unit stay . The use of antibiotics was more or less strongly discouraged or recommended according to the Muller classification . Patients were r and omized into two groups : one using the procalcitonin results ( procalcitonin group ) and one being blinded to the procalcitonin results ( control group ) . The primary end point was the reduction of antibiotic use expressed as a proportion of treatment days and of daily defined dose per 100 intensive care unit days using a procalcitonin-guided approach . Secondary end points included : a posteriori assessment of the accuracy of the infectious diagnosis when using procalcitonin in the intensive care unit and of the diagnostic concordance between the intensive care unit physician and the infectious-disease specialist . Measurements and Main Results : There were 258 patients in the procalcitonin group and 251 patients in the control group . A significantly higher amount of withheld treatment was observed in the procalcitonin group of patients classified by the intensive care unit clinicians as having possible infection . This , however , did not result in a reduction of antibiotic consumption . The treatment days represented 62.6 ± 34.4 % and 57.7 ± 34.4 % of the intensive care unit stays in the procalcitonin and control groups , respectively ( p = .11 ) . According to the infectious-disease specialist , 33.8 % of the cases in which no infection was confirmed , had a procalcitonin value > 1µg/L and 14.9 % of the cases with confirmed infection had procalcitonin levels < 0.25 µg/L. The ability of procalcitonin to differentiate between certain or probable infection and possible or no infection , upon initiation of antibiotic treatment was low , as confirmed by the receiving operating curve analysis ( area under the curve = 0.69 ) . Finally , procalcitonin did not help improve concordance between the diagnostic confidence of the infectious-disease specialist and the ICU physician . Conclusions : Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aim ing at decreasing the antibiotic consumption in intensive care unit patients Objective : The diagnosis of infection in critically ill patients is challenging because traditional markers of infection are often misleading . For example , serum concentrations of calcitonin pre‐cursors are increased in patients with infections . However , their predictive accuracy for the diagnosis of sepsis in unselected patients in a medical intensive care unit ( ICU ) is unknown . Therefore , we compared the usefulness of serum concentrations of calcitonin precursors , C‐reactive protein , interleukin‐6 , and lactate for the diagnosis of sepsis in consecutive patients suffering from a broad range of diseases with an anticipated stay of ≥ 24 hrs in a medical ICU . Design : Prospect i ve cohort study . Setting : Medical intensive care unit in a university medical center . Patients : 101 consecutive critically ill patients . Intervention : None . Measurements and Main Results : Blood sample s were collected at various time points during the course of the disease . Systemic inflammatory response syndrome , sepsis , severe sepsis , and septic shock were diagnosed according to st and ardized criteria , and patients were reclassified daily without prior knowledge of the serum concentrations of calcitonin precursors or interleukin‐6 . At admission , 99 % of the patients had systemic inflammatory response syndrome , 53 % had sepsis , and 5 % developed sepsis during their stay in the ICU . Calcitonin precursors , C‐reactive protein , interleukin‐6 , and lactate levels increased with the severity of infection ( p < .01 , one‐way analysis of variance ) . In a receiver operating characteristic curve analysis , calcitonin precursors were found to be the most reliable laboratory variable for the diagnosis of sepsis as compared with C‐reactive protein , interleukin‐6 , and lactate ( p < .01 , for each comparison ) . Calcitonin precursor concentrations of > 1 ng/mL had sensitivity of 89 % and specificity of 94 % for the diagnosis of sepsis . High serum concentrations of calcitonin precursors were associated with poor prognosis ( p = .01 ) . Conclusions : In a medical ICU , serum calcitonin precursor concentrations are more sensitive and are specific markers of sepsis as compared with serum C‐reactive protein , interleukin‐6 , and lactate levels Abstract Background : Procalcitonin ( PCT ) is increasingly being used for the diagnostic and prognostic work up of patients with suspected infections in the emergency department ( ED ) . Recently , B·R·A·H·M·S PCT direct , the first high sensitive point-of-care test ( POCT ) , has been developed for fast PCT measurement on capillary or venous blood sample s. Methods : This is a prospect i ve , international comparison study conducted in three European EDs . Consecutive patients with suspicion of bacterial infection were included . Duplicate determination of PCT was performed in capillary ( fingertip ) and venous whole blood ( EDTA ) , and compared to the reference method . The diagnostic accuracy was evaluated by correlation and concordance analyses . Results : Three hundred and three patients were included over a 6-month period ( 60.4 % male , median age 65.2 years ) . The correlation between capillary or venous whole blood and the reference method was excellent : r2=0.96 and 0.97 , sensitivity 88.1 % and 93.0 % , specificity 96.5 % and 96.8 % , concordance 93 % and 95 % , respectively at a 0.25 μg/L threshold . No significant bias was observed ( –0.04 and –0.02 for capillary and venous whole blood ) although there were 6.8 % and 5.1 % outliers , respectively . B·R·A·H·M·S PCT direct had a shorter time to result as compared to the reference method ( 25 vs. 144 min , difference 119 min , 95 % CI 110–134 min , p<0.0001 ) . Conclusions : This study found a high diagnostic accuracy and a faster time to result of B·R·A·H·M·S PCT direct in the ED setting , allowing shortening time to therapy and a more wide-spread use of PCT OBJECTIVE To evaluate the value of serum procalcitonin ( PCT ) on antibiotic use in treatment of community acquired pneumonia ( CAP ) in outpatient . METHODS From November 2006 to February 2008 , a total of 127 patients with CAP in outpatient were r and omly assigned into two groups : PCT group ( n = 63 ) and control group ( n = 64 ) . PCT levels of all patients were measured after study admission . On the base of similarly normal treatment , the control group received antibiotics according to the attending physicians and the PCT group were treated with antibiotics according to serum PCT levels : antibiotic treatment was applied with PCT level > or = 0.25 microg/L and was discouraged with PCT level < 0.25 microg/L. Clinical efficacy , rate of antibiotics use , duration courses and costs of antibiotics were observed . RESULTS Clinical efficacy of the PCT group was similar with the control group ( 92.1 % vs 87.5 % , P > 0.05 ) ; rate and costs of antibiotics use was lower , antibiotic duration of the PCT group was shorter than that of the control group ( P < 0.05 , P < 0.001 , P < 0.001 ) . CONCLUSION PCT could be used in treatment of CAP for antibiotic use in outpatient , which may reduce antibiotic use , shorten antibiotic duration and lower costs of antibiotic The empiric antibiotic therapy can result in antibiotic overuse , development of bacterial resistance and increasing costs in critically ill patients . The aim of the present study was to evaluate the effect of procalcitonin ( PCT ) guide treatment on antibiotic use and clinical outcomes of patients admitted to intensive care unit ( ICU ) with systemic inflammatory response syndrome ( SIRS ) . A total of 60 patients were enrolled in this study and r and omly divided into two groups , cases that underwent antibiotic treatment based on serum level of PCT as PCT group ( n=30 ) and patients who undergoing antibiotic empiric therapy as control group ( n=30 ) . Our primary endpoint was the use of antibiotic treatment . Additional endpoints were changed in clinical status and early mortality . Antibiotics use was lower in PCT group compared to control group ( P=0.03 ) . Current data showed that difference in SOFA score from the first day to the second day after admitting patients in ICU did not significantly differ ( P=0.88 ) . Patients in PCT group had a significantly shorter median ICU stay , four days versus six days ( P=0.01 ) . However , hospital stay was not statistically significant different between two groups , 20 days versus 22 days ( P=0.23 ) . Early mortality was similar between two groups . PCT guidance administers antibiotics reduce antibiotics exposure and length of ICU stay , and we found no differences in clinical outcomes and early mortality rates between the two studied groups OBJECTIVE To investigate the significance of dynamic monitoring of procalcitonin ( PCT ) in guiding the use of antibiotics for treating patients with sepsis in intensive care unit ( ICU ) . METHODS Eighty-two patients with sepsis from January 2012 to June 2013 hospitalized in ICU of First Hospital of Jilin University were enrolled , and they were r and omly divided into regular antibiotic therapy group ( RAT group , n=40 ) and PCT monitoring in guiding the use of antibiotics group ( PCT group , n=42 ) . Patients in RAT group were treated according to principle of antibiotics usage , while in PCT group patients ' PCT value was observed everyday . When no active symptoms of infection were shown , and acute physiology and chronic health evaluation II ( APACHEII ) scores declined , PCT value decreased over 90 % or PCT value lower than 0.25 μg/L time point were selected as drug withdrawal indication . The general status of the patient , antimicrobial drug use time , and prognosis were compared between the two groups , and Kaplan-Meier method was used for survival curve analysis . Variance analysis was used for repeating measurement to observe dynamic serum PCT level of the two groups of patients for survival and death during 7 days . RESULTS Mann-Whitney U test or χ(2 ) test showed that there were no statistical significance in age , gender , APACHEII score , blood culture positive rate , sputum culture positive rate , cardiac insufficiency , renal failure , respiratory failure , and ventilator and hemofiltration usage ( all P>0.05 ) . Log Rank test results showed that the time of antimicrobial drug usage was significantly reduced in PCT group than that in RAT group [ days : 8.1±0.3 , 95 % confidence interval ( 95%CI 8.3 - 9.7 ) vs. 9.3±0.3 ( 95%CI 8.7 - 10.1 ) , P=0.013 ] . Kaplan-Meier univariate survival curves showed that the speed of curve declination in PCT group was faster significantly than that in RAT group , suggesting that the time of using antimicrobial drug was shortened . There was no significant difference in length of hospital stay , ICU stay time , number of death in 28 days , number of cases of recurrence in 28 days and clinical cure rate between two groups ( all P>0.05 ) . PCT level in non-survivors in both groups was significantly higher than that in the survivors , exceeding more than 10 μg/L in the early and late stages of treatment . CONCLUSIONS Dynamic monitoring of PCT can effectively reduce antimicrobial drug use in ICU patients with sepsis , but there is no significant difference in patients ' prognosis We report an evaluation of the utility of serum procalcitonin ( PCT ) measurement as an additional diagnostic tool to support initiating or withholding antibiotics in clinical situations where there is a clinical suspicion of infection but the diagnosis is uncertain . During a six-month period , 99 patients on the medical admission unit ( MAU ) with suspected infection , and 42 patients on the intensive care unit ( ICU ) with clinical signs or physiological parameters suggesting possible new infection , had serum PCT concentration measured with the result available within 90min of the request . The test was initiated by the microbiology/infection team during clinical consultations to support the antibiotic decision . On the basis of low PCT values , antibiotics were withheld in MAU on 52 occasions and in ICU on 42 occasions . Patients were followed up prospect ively for a week . There was neither progression of bacterial infection requiring antibiotics , nor complications or infection-related mortality in any patients who were denied antibiotics on either MAU or ICU . Without the PCT value it is likely that all of these patients would have received empirical antibiotics . Reduction in unnecessary antibiotic usage was made without any adverse effects on these patients and there was a clear reduction in antibiotic prescribing with cost reduction implication s. PCT has the potential to become a valuable tool in antibiotic management BACKGROUND Cost-impact models have indicated that in the USA , the use of antibiotic stewardship protocol s based on procalcitonin ( PCT ) levels for patients with suspected acute respiratory tract infection results in cost savings . Our objective was to assess the cost impact of adopting PCT testing among patients with acute respiratory infections ( ARI ) from the perspective of a typical hospital system in urban China . METHODS To conduct an economic evaluation of PCT testing versus usual care we built a cost-impact model based on a previously published patient-level meta- analysis data of r and omized trials including Chinese sites . The data were adapted to the China setting by applying the results to mean lengths of stay , costs , and practice patterns typically found in China . We estimated the annual ARI visit rate for the typical hospital system ( assumed to be 1650 beds ) and ARI diagnosis . RESULTS In the inpatient setting , the costs of PCT-guided care compared to usual care for a cohort of 16,405 confirmed ARI patients was almost 1.1 million Chinese yuan ( CNY ) , compared to almost 1.8 million CNY for usual care , result ing in net savings of 721,563 CNY to a typical urban Chinese hospital system for 2015 . In the ICU and outpatient setting s , savings were 250,699 CNY and 2.4 million CNY , respectively . The overall annual net savings of PCT-guided care was nearly 3.4 million CNY . CONCLUSIONS Substantial savings are associated with PCT protocol s of ARI across common China hospital treatment setting s mainly by direct reduction in unnecessary antibiotic utilization BACKGROUND Guidelines recommend blood culture sampling from hospitalized patients with suspected community-acquired pneumonia ( CAP ) . However , the yield of true-positive results is low . We investigated the benefit of procalcitonin ( PCT ) on hospital admission to predict blood culture positivity in CAP . METHODS This was a prospect i ve cohort study with a derivation and validation set including 925 patients with CAP who underwent blood culture sampling on hospital admission . RESULTS A total of 73 ( 7.9 % ) patients had true bacteremia ( 43 of 463 in the derivation cohort , 30 of 462 in the validation cohort ) . The area under the receiver operating characteristics curve of PCT in the derivation and validation cohorts was similar ( derivation cohort , 0.83 ; 95 % CI , 0.78 - 0.89 ; validation cohort , 0.79 ; 95 % CI , 0.72 - 0.88 ) . Overall , PCT was a significantly better predictor for blood culture positivity than WBC count , C-reactive protein , and other clinical parameters . In multivariate regression analysis , only antibiotic pretreatment ( adjusted odds ratio , 0.25 ; P < .05 ) and PCT serum levels ( adjusted odds ratio , 3.72 ; P < .001 ) were independent predictors . Overall , a PCT cutoff of 0.1 microg/L would enable reduction of the total number of blood cultures by 12.6 % and still identify 99 % of the positive blood cultures . Similarly , 0.25 microg/L and 0.5 microg/L cutoffs would enable reduction of blood cultures by 37 % and 52 % , respectively , and still identify 96 % and 88 % , respectively , of positive blood cultures . CONCLUSIONS Initial PCT level accurately predicted blood culture positivity in patients with CAP . PCT measurement has the potential to reduce the number of drawn blood cultures in the emergency department and to implement a more targeted allocation of limited health-care re sources Abstract Background . Viral lower respiratory tract illness ( LRTI ) frequently causes adult hospitalization and is linked to antibiotic overuse . European studies suggest that the serum procalcitonin ( PCT ) level may be used to guide antibiotic therapy . We conducted a trial assessing the feasibility of using PCT algorithms with viral testing to guide antibiotic use in a US hospital . Methods . Three hundred patients hospitalized with nonpneumonic LRTI during October 2013–April 2014 were r and omly assigned at a ratio of 1:1 to receive st and ard care or PCT-guided care and viral PCR testing . The primary outcome was antibiotic exposure , and safety was assessed at 1 and 3 months . Results . Among the 151 patients in the intervention group , viruses were identified in 42 % ( 63 ) , and 83 % ( 126 ) had PCT values of < 0.25 µg/mL. There were no significant differences in antibiotic use or adverse events between intervention patients and those in the nonintervention group . Subgroup analyses revealed fewer subjects with positive results of viral testing and low PCT values who were discharged receiving antibiotics ( 20 % vs 45 % ; P = .002 ) and shorter antibiotic duration s among algorithm-adherent intervention patients versus nonintervention patients ( 2.0 vs 4.0 days ; P = .004 ) . Compared with historical controls ( from 2008–2011 ) , antibiotic duration in nonintervention patients decreased by 2 days ( 6.0 vs 4.0 days ; P < .001 ) , suggesting a study effect . Conclusions . Although antibiotic use was similar in the 2 arms , subgroup analyses of intervention patients suggest that physicians responded to viral and biomarker data . These data can inform the design of future US studies . Clinical Trials Registration . NCT01907659 Background : Diagnosis of neonatal early-onset sepsis is difficult because clinical signs and laboratory tests are non-specific . Early antibiotic therapy is crucial for treatment success . Objective : To evaluate the effect of procalcitonin (PCT)-guided decision-making on duration of antibiotic therapy in suspected neonatal early-onset sepsis . Methods : This single-center , prospect i ve , r and omized intervention study was conducted in a tertiary neonatal and pediatric intensive care unit in the Children ’s Hospital of Lucerne , Switzerl and , between June 1 , 2005 and December 31 , 2006 . All term and near-term infants ( gestational age ≧34 weeks ) with suspected early-onset sepsis were r and omly assigned either to st and ard treatment based on conventional laboratory parameters ( st and ard group ) or to PCT-guided treatment ( PCT group ) . Minimum duration of antibiotic therapy was 48–72 h in the st and ard group , whereas in the PCT group antibiotic therapy was discontinued when two consecutive PCT values were below predefined age-adjusted cut-off values . Results : 121 newborns were r and omly assigned either to the st and ard group ( n = 61 ) or the PCT group ( n = 60 ) . The two groups were similar for baseline demographics , risk factors for early-onset sepsis , likelihood of infection as assessed by the attending physician and early conventional laboratory findings . There was a significant difference in the proportion of newborns treated with antibiotics ≧72 h between the st and ard group ( 82 % ) and the PCT group ( 55 % ) ( absolute risk reduction 27 % ; odds ratio 0.27 ( 95 % CI 0.12–0.62 ) , p = 0.002 ) . On average , PCT-guided decision-making result ed in a shortening of 22.4 h of antibiotic therapy . Clinical outcome was similar and favorable in both groups but sample size was insufficient to exclude rare adverse events . Conclusion : Serial PCT determinations allow to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis . Before this PCT-guided strategy can be recommended , its safety has to be confirmed in a larger cohort of neonates BACKGROUND Lower respiratory tract infections are often treated with antibiotics without evidence of clinical ly relevant bacterial disease . Serum calcitonin precursor concentrations , including procalcitonin , are raised in bacterial infections . We aim ed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay . METHODS 243 patients admitted with suspected lower respiratory tract infections were r and omly assigned st and ard care ( st and ard group ; n=119 ) or procalcitonin-guided treatment ( procalcitonin group ; n=124 ) . On the basis of serum procalcitonin concentrations , use of antibiotics was more or less discouraged ( < 0.1 microg/L or < 0.25 microg/L ) or encouraged ( > or = 0.5 microg/L or > or = 0.25 microg/L ) , respectively . Re-evaluation was possible after 6 - 24 h in both groups . Primary endpoint was use of antibiotics and analysis was by intention to treat . FINDINGS Final diagnoses were pneumonia ( n=87 ; 36 % ) , acute exacerbation of chronic obstructive pulmonary disease ( 60 ; 25 % ) , acute bronchitis ( 59 ; 24 % ) , asthma ( 13 ; 5 % ) , and other respiratory affections ( 24 ; 10 % ) . Serological evidence of viral infection was recorded in 141 of 175 tested patients ( 81 % ) . Bacterial cultures were positive from sputum in 51 ( 21 % ) and from blood in 16 ( 7 % ) . In the procalcitonin group , the adjusted relative risk of antibiotic exposure was 0.49 ( 95 % CI 0.44 - 0.55 ; p<0.0001 ) compared with the st and ard group . Antibiotic use was significantly reduced in all diagnostic subgroups . Clinical and laboratory outcome was similar in both groups and favourable in 235 ( 97 % ) . INTERPRETATION Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections . Withholding antimicrobial treatment did not compromise outcome . In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections , treatment based on procalcitonin measurement could have important clinical and financial implication Background Adequate indication and duration of administration are central issues of modern antibiotic treatment in intensive care medicine . The biochemical variable procalcitonin ( PCT ) is known to indicate systemically relevant bacterial infections with high accuracy . In the present study , we aim ed to investigate the clinical usefulness of PCT for guiding antibiotic treatment in surgical intensive care patients with severe sepsis . Patients and methods Patients were r and omly assigned to a PCT-guided or a control group requiring antibiotic treatment . All patients received a calculated antibiotic regimen according to the presumed microbiological spectrum . In the PCT-guided group , antibiotic treatment was discontinued if clinical signs of infection improved and the PCT value was either < 1 ng/ml or decreased to < 35 % of the initial concentration within three consecutive days . In the control group , antibiotic treatment was directed by empirical rules . Results The PCT-guided group ( n = 14 patients ) and the control group ( n = 13 patients ) did not differ in terms of biological variables , underlying diseases , and overall disease severity . PCT guidance led to a significant reduction of antibiotic treatment from 6.6 ± 1.1 days ( mean ± SD ) compared with 8.3 ± 0.7 days in control patients ( p < 0.001 ) along with a reduction of antibiotic treatment costs of 17.8 % ( p < 0.01 ) without any adverse effects on outcome . Conclusions Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients with severe sepsis . This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistances and costs in intensive care medicine OBJECTIVE The aim of the study was to evaluate the impact of procalcitonin ( PCT ) measurement on antibiotic use in children with fever without source . METHOD Children aged 1 to 36 months presenting to a pediatric emergency department ( ED ) with fever and no identified source of infection were eligible to be included in a r and omized controlled trial . Patients were r and omly assigned to 1 of 2 groups as follows : PCT+ ( result revealed to the attending physician ) and PCT- ( result not revealed ) . Patients from both groups also had complete blood count , blood culture , urine analysis , and culture performed . Chest radiography or lumbar puncture could be performed if required . RESULTS Of the 384 children enrolled and equally r and omized into the PCT+ and PCT- groups , 62 ( 16 % ) were diagnosed with a serious bacterial infection ( urinary tract infection , pneumonia , occult bacteremia , or bacterial meningitis ) by primary ED investigation . Ten were also found to be neutropenic ( < 500 x 10(6)/L ) . Of the remaining undiagnosed patients , 14 ( 9 % ) of 158 received antibiotics in the PCT+ group vs 16 ( 10 % ) of 154 in the PCT- group ( Delta -2 % ; 95 % confidence interval [ CI ] , -8 to 5 ) . A strategy to treat all patients with PCT of 0.5 ng/mL or greater with prophylactic antibiotic in this group of patients would have result ed in an increase in antibiotic use by 24 % ( 95 % CI , 15 - 33 ) . CONCLUSION Semiquantitative PCT measurement had no impact on antibiotic use in children aged 1 to 36 months who presented with fever without source . However , a strategy to use prophylactic antibiotics in all patients with abnormal PCT results would have result ed in an increase use of antibiotics OBJECTIVE The majority of patients with acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) have low serum procalcitonin ( PCT ) values . The aim of this study was to determine whether these patients may benefit from antibiotic treatment . METHODS A total of 457 patients with AE COPD were screened ; 194 patients with AE COPD and PCT < 0.1 ng/ml were assigned r and omly to an antibiotic group or a control group . In the per- protocol ( PP ) population , the antibiotic group subjects were required to have used antibiotics for at least 3 days , and the control group subjects were required not to have used antibiotics within the 10 days after admission . The intention-to-treat ( ITT ) population was defined as the patients who were r and omized . The primary outcome was the treatment success rate on day 10 after admission . Secondary outcomes were symptoms assessed on a visual analog scale ( VAS ) , length of hospitalization , mortality , exacerbation rate , and re-hospitalization within 30 days of follow-up ( study registered at chictr.org.cn : ChiCTR-TRC-14004726 ) . RESULTS 95 patients in the antibiotic group and 96 patients in the control group completed the study . In the ITT population , the overall treatment success rate in the control group ( 95.8 % ) was similar to that in the antibiotic group ( 93.7 % ) , with no significant difference ( p=0.732 ) . Five patients in the antibiotic group died , either in hospital or within 30 days of discharge . In the control group , two died within 30 days of discharge . Antibiotic use in the control group was 17.7 % ( 17/96 ) , and age ≥75 years was a predictive risk factor for requiring antibiotic therapy in the control group ( odds ratio 4.055 , 95 % confidence interval 1.297 - 12.678 ; p=0.012 ) . According to the PP analysis , the treatment success rate on day 10 after admission was 98.7 % ( 78/79 ) in the control group and 93.7 % ( 89/95 ) in the antibiotic group , also with no significant difference ( p=0.193 ) . No secondary outcome was significantly different between the two groups . CONCLUSION Antibiotic treatment is no better than placebo in AE COPD with a PCT level < 0.1 ng/ml OBJECTIVE To investigate the clinical usefulness of procalcitonin ( PCT ) for guiding duration of antibiotic therapy in patients with severe acute pancreatitis ( SAP ) . METHODS A total of 71 patients with confirmed severe acute pancreatitis from March 2009 to September 2011 in the Department of Critical Care Medicine of Huizhou Municipal Central Hospital , Guangdong , China were enrolled in this study . Procalcitonin was measured daily by a semi-quantitative immunoassay in the study group . Patients were r and omly assigned into 2 groups including a PCT-guided group ( study group ) and a prophylactic antibiotic therapy ( control group ) . Antibiotic therapy in the study group was not applied until clinical signs and symptoms of infection appeared ( PCT value was > 0.5ng/ml ) . We discontinued the antibiotic therapy if clinical signs and symptoms of infection improved and PCT was < 0.5ng/ml over 3 days . In the control group , antibiotic therapy was administrated for 2 weeks , or antibiotic therapy was continued because of confirmed infection until clinical signs and symptoms of infection disappeared over 3 days . RESULTS In the study group ( 35 patients ) , the duration of antibiotic therapy and hospitalization was significantly shorter than the control group ( 36 patients ) ( 10.89+/-2.85 versus 16.06+/-2.48 days , p<0.001 , and 16.66+/-4.02 days versus 23.81+/-7.56 days , p<0.001 ) without negative clinical effects and the cost of hospitalization was significantly lower . CONCLUSION Procalcitonin is a helpful and safe tool for guiding duration of antibiotic treatment in patients with severe acute pancreatitis RATIONALE The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse , increasing the risk of developing bacterial resistance . OBJECTIVES To test the hypothesis that an algorithm based on serial measurements of procalcitonin ( PCT ) allows reduction in the duration of antibiotic therapy compared with empirical rules , and does not result in more adverse outcomes in patients with severe sepsis and septic shock . METHODS In patients r and omly assigned to the intervention group , antibiotics were stopped when PCT levels had decreased 90 % or more from the initial value ( if clinicians agreed ) but not before Day 3 ( if baseline PCT levels were < 1 microg/L ) or Day 5 ( if baseline PCT levels were > /=1 microg/L ) . In control patients , clinicians decided on the duration of antibiotic therapy based on empirical rules . MEASUREMENTS AND MAIN RESULTS Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects ( intention-to-treat , n = 79 , P = 0.15 ) . In patients in whom a decision could be taken based on serial PCT measurements , PCT guidance result ed in a 4-day reduction in the duration of antibiotic therapy ( per protocol , n = 68 , P = 0.003 ) and a smaller overall antibiotic exposure ( P = 0.0002 ) . A similar mortality and recurrence of the primary infection were observed in PCT and control groups . A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group ( P = 0.03 ) . CONCLUSIONS Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm Biomarkers such as procalcitonin ( PCT ) have been studied to guide duration of antibiotic therapy . We aim ed to assess whether a decrease in PCT levels could be used to reduce the duration of antibiotic therapy in intensive care unit ( ICU ) patients with a proven infection without risking a worse outcome . We assessed 265 patients with suspected sepsis , severe sepsis , or septic shock in our ICU . Of those , we r and omized 81 patients with a proven bacterial infection into 2 groups : an intervention group in which the duration of the antibiotic therapy was guided by a PCT protocol and a control group in which there was no PCT guidance . In the per- protocol analysis , the median antibiotic duration was 9 days in the PCT group ( n = 20 ) versus 13 days in the non-PCT group ( n = 31 ) , P = 0.008 . This study demonstrates that PCT can be a useful tool for limiting antimicrobial therapy in ICU patients with documented bacterial infection BACKGROUND In critically ill patients , antibiotic therapy is of great importance but long duration of treatment is associated with the development of antimicrobial resistance . Procalcitonin is a marker used to guide antibacterial therapy and reduce its duration , but data about safety of this reduction are scarce . We assessed the efficacy and safety of procalcitonin-guided antibiotic treatment in patients in intensive care units ( ICUs ) in a health-care system with a comparatively low use of antibiotics . METHODS We did a prospect i ve , multicentre , r and omised , controlled , open-label intervention trial in 15 hospitals in the Netherl and s. Critically ill patients aged at least 18 years , admitted to the ICU , and who received their first dose of antibiotics no longer than 24 h before inclusion in the study for an assumed or proven infection were eligible to participate . Patients who received antibiotics for presumed infection were r and omly assigned ( 1:1 ) , using a computer-generated list , and stratified ( according to treatment centre , whether infection was acquired before or during ICU stay , and dependent on severity of infection [ ie , sepsis , severe sepsis , or septic shock ] ) to receive either procalcitonin-guided or st and ard-of-care antibiotic discontinuation . Both patients and investigators were aware of group assignment . In the procalcitonin-guided group , a non-binding advice to discontinue antibiotics was provided if procalcitonin concentration had decreased by 80 % or more of its peak value or to 0·5 μg/L or lower . In the st and ard-of-care group , patients were treated according to local antibiotic protocol s. Primary endpoints were antibiotic daily defined doses and duration of antibiotic treatment . All analyses were done by intention to treat . Mortality analyses were completed for all patients ( intention to treat ) and for patients in whom antibiotics were stopped while being on the ICU ( per- protocol analysis ) . Safety endpoints were reinstitution of antibiotics and recurrent inflammation measured by C-reactive protein concentrations and they were measured in the population adhering to the stopping rules ( per- protocol analysis ) . The study is registered with Clinical Trials.gov , number NCT01139489 , and was completed in August , 2014 . FINDINGS Between Sept 18 , 2009 , and July 1 , 2013 , 1575 of the 4507 patients assessed for eligibility were r and omly assigned to the procalcitonin-guided group ( 761 ) or to st and ard-of-care ( 785 ) . In 538 patients ( 71 % ) in the procalcitonin-guided group antibiotics were discontinued in the ICU . Median consumption of antibiotics was 7·5 daily defined doses ( IQR 4·0 - 12·7 ) in the procalcitonin-guided group versus 9·3 daily defined doses ( 5·0 - 16·6 ) in the st and ard-of-care group ( between-group absolute difference 2·69 , 95 % CI 1·26 - 4·12 , p<0·0001 ) . Median duration of treatment was 5 days ( 3 - 9 ) in the procalcitonin-guided group and 7 days ( 4 - 11 ) in the st and ard-of-care group ( between-group absolute difference 1·22 , 0·65 - 1·78 , p<0·0001 ) . Mortality at 28 days was 149 ( 20 % ) of 761 patients in the procalcitonin-guided group and 196 ( 25 % ) of 785 patients in the st and ard-of-care group ( between-group absolute difference 5·4 % , 95 % CI 1·2 - 9·5 , p=0·0122 ) according to the intention-to-treat analysis , and 107 ( 20 % ) of 538 patients in the procalcitonin-guided group versus 121 ( 27 % ) of 457 patients in the st and ard-of-care group ( between-group absolute difference 6·6 % , 1·3 - 11·9 , p=0·0154 ) in the per- protocol analysis . 1-year mortality in the per- protocol analysis was 191 ( 36 % ) of 538 patients in the procalcitonin-guided and 196 ( 43 % ) of 457 patients in the st and ard-of-care groups ( between-group absolute difference 7·4 , 1·3 - 13·8 , p=0·0188 ) . INTERPRETATION Procalcitonin guidance stimulates reduction of duration of treatment and daily defined doses in critically ill patients with a presumed bacterial infection . This reduction was associated with a significant decrease in mortality . Procalcitonin concentrations might help physicians in deciding whether or not the presumed infection is truly bacterial , leading to more adequate diagnosis and treatment , the cornerstones of antibiotic stewardship . FUNDING Thermo Fisher Scientific RATIONALE The role of procalcitonin ( PCT ) , a widely used sepsis biomarker , in critically ill patients with sepsis is undetermined . OBJECTIVES To investigate the effect of a low PCT cut-off on antibiotic prescription and to describe the relationships between PCT plasma concentration and sepsis severity and mortality . METHODS This was a multicenter ( 11 Australian intensive care units [ ICUs ] ) , prospect i ve , single-blind , r and omized controlled trial involving 400 patients with suspected bacterial infection/sepsis and expected to receive antibiotics and stay in ICU longer than 24 hours . The primary outcome was the cumulative number of antibiotics treatment days at Day 28 . MEASUREMENTS AND MAIN RESULTS PCT was measured daily while in the ICU . A PCT algorithm , including 0.1 ng/ml cut-off , determined antibiotic cessation . Published guidelines and antimicrobial stewardship were used in all patients . Primary analysis included 196 ( PCT ) versus 198 st and ard care patients . Ninety-three patients in each group had septic shock . The overall median ( interquartile range ) number of antibiotic treatment days were 9 ( 6 - 21 ) versus 11 ( 6 - 22 ) , P = 0.58 ; in patients with positive pulmonary culture , 11 ( 7 - 27 ) versus 15 ( 8 - 27 ) , P = 0.33 ; and in patients with septic shock , 9 ( 6 - 22 ) versus 11 ( 6 - 24 ) , P = 0.64 ; with an overall 90-day all-cause mortality of 35 ( 18 % ) versus 31 ( 16 % ) , P = 0.54 in the PCT versus st and ard care , respectively . Using logistic regression , adjusted for age , ventilation status , and positive culture , the decline rate in log(PCT ) over the first 72 hours independently predicted hospital and 90-day mortality ( odds ratio [ 95 % confidence interval ] , 2.76 [ 1.10 - 6.96 ] , P = 0.03 ; 3.20 [ 1.30 - 7.89 ] , P = 0.01 , respectively ) . CONCLUSIONS In critically ill adults with undifferentiated infections , a PCT algorithm including 0.1 ng/ml cut-off did not achieve 25 % reduction in duration of antibiotic treatment . Clinical trial registered with http://www.anzctr.org.au ( ACTRN12610000809033 ) |
10,565 | 21,723,712 | Unipolar depression was characterised by reduced brain volume in areas involved in emotional processing , including the frontal cortex , orbitofrontal cortex , cingulate cortex , hippocampus and striatum .
There was also evidence of pituitary enlargement and an excess of white matter hyperintensity volume in unipolar depression . | Previous meta-analyses of structural MRI studies have shown diffuse cortical and sub-cortical abnormalities in unipolar depression .
However , the presence of duplicate publications , recruitment of particular age groups and the selection of specific regions of interest means that there is uncertainty about the balance of current research .
Moreover , the lack of systematic exploration of highly significant heterogeneity has prevented the generalisability of finding .
Possible publication bias , and the impact of various study design characteristics on the magnitude of the observed effect size were systematic ally explored . | BACKGROUND The hippocampus , amygdala and related functional circuits have been implicated in the regulation of emotional expression and memory processes , which are affected in major depression . Several recent investigations have reported abnormalities in these structures in adult and elderly depressives . METHODS Elderly DSM-III-R unipolar depressives ( N = 40 ) and normal controls ( N = 46 ) participated in a magnetic resonance imaging study ( 1.0 T ) . Brain images were obtained in the coronal plane . Using established anatomical guidelines for structure delineation , volumetric measurements of left and right hippocampus and anterior hippocampus/amygdala complex were completed under blinded conditions using a semi-automated computer mensuration system , with patients and controls in r and om order . RESULTS Medial temporal volumes did not significantly distinguish either elderly depressed and age-similar normal control subjects , or late onset and early onset depressed patients ( ANCOVA ) . Major overlap of measured volumes existed between patient and control groups . In depressives , hippocampal volumes significantly correlated with age , and cognitive and depression ratings , but not with number of prior depressive episodes or age-at-onset of first depression . CONCLUSIONS Hippocampal volumes do not discriminate a typical clinical population of elderly depressed patients from age-similar normal control subjects . If hippocampal dysfunction contributes to a diagnosis of syndromal depression in the elderly , such dysfunction does not appear to be regularly reflected in structural abnormalities captured by volumetric measurement as conducted . On the other h and , relationships between hippocampal volumes and clinical phenomena in depressives , but not controls , suggest potentially meaningful interactions between hippocampal structure and the expression of major depression in the elderly Subjects at their first psychotic episode show an enlarged volume of the pituitary gl and , but whether this is due to hypothalamic – pituitary – adrenal ( HPA ) axis hyperactivity , or to stimulation of the prolactin-secreting cells by antipsychotic treatment , is unclear . We measured pituitary volume , using 1.5-mm , coronal , 1.5 T , high-resolution MRI images , in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls . In all , 18 patients were antipsychotic-free ( 12 of these were antipsychotic-naïve ) , 26 were receiving atypical antipsychotics , and 33 were receiving typical antipsychotics . As hypothesized , patients had a larger pituitary volume than controls ( + 22 % , p<0.001 ) . When divided by antipsychotic treatment , and compared to controls , the pituitary volume was 15 % larger in antipsychotic-free patients ( p=0.028 ) , 17 % larger in patients receiving atypicals ( p=0.01 ) , and 30 % larger in patients receiving typicals ( p<0.001 ) . Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together ( + 11 % , p=0.08 ) . When divided by diagnosis , and compared to controls , the pituitary volume was 24 % larger in patients with schizophrenia/schizophreniform disorder ( n=40 , p<0.001 ) , 19 % larger in depressed patients ( n=13 , p=0.022 ) , 16 % larger in bipolar patients ( n=16 , p=0.037 ) , and 12 % larger in those with other psychoses ( n=9 , p=0.2 ) . In conclusion , the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment , and this could be due to activation of the HPA axis . Typical antipsychotics exert an additional enlarging effect on pituitary volume , likely to be related to activation of prolactin-secreting cells . This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis BACKGROUND Previous studies have shown that major depression is frequently accompanied by hypercortisolemia . There is some evidence suggesting that an increase in the glucocorticoid levels may make hippocampal cells more vulnerable to insults caused by hypoxia , hypoglycemia , or excitatory neurotransmitters . Using magnetic resonance imaging ( MRI ) , the hippocampi of patients with major depression were measured and compared with values observed in control subjects . METHODS Thirty-eight patients with primary unipolar major depression were recruited . Twenty control subjects were matched for age , gender , and years of education . The hippocampal volume was measured from coronal MRI scans in all of the subjects . Patients were also grouped and compared as responders and nonresponders to treatment with fluoxetine of 20 mg/day , for 8 weeks . Hamilton Depression Rating Scale ( HDRS ) was used to determine the severity of depression . RESULTS No significant differences were observed between the hippocampal volumes of patients with major depression and control subjects ; however , a significant correlation was observed between the left hippocampal volume of men and their HDRS baseline values . In addition , female responders had a statistically significant higher mean right hippocampal volume than nonresponders . CONCLUSIONS The results of our study indicate no reduction in the volume of the hippocampus in patients with major depression . Nonetheless , the results do suggest that the effects of disease severity , gender , and treatment response may influence hippocampal volume THE amygdala is a key structure in the brain 's integration of emotional meaning with perception and experience.1 Patients with depression have impaired functioning in emotional tasks involving the amygdala,2 and have abnormal resting amygdala blood flow.3 To better underst and the anatomical basis for these functional changes we measured the volumes of the total amygdala and of the core amygdala nuclei in 20 patients with a history of depression and 20 pair-wise matched controls . Depressed subjects had bilaterally reduced amygdala core nuclei volumes and no significant differences in total amygdala volumes or in whole brain volumes . Since patients with a depression history have bilateral hippocampal volume reduction4 the volume loss in this closely related structure suggests a shared effect on both structures , potentially glucocorticoid-induced neurotoxicity5 mediated by the extensive reciprocal glutamatergic connections BACKGROUND The amygdala has a central role in processing emotions , particularly fear . During functional magnetic resonance imaging ( fMRI ) amygdala activation has been demonstrated outside of conscious awareness using masked emotional faces . METHODS We applied the masked faces paradigm to patients with major depression ( n = 11 ) and matched control subjects ( n = 11 ) during fMRI to compare amygdala activation in response to masked emotional faces before and after antidepressant treatment . Data were analyzed using left and right amygdala a priori regions of interest , in an analysis of variance block analysis and r and om effects model . RESULTS Depressed patients had exaggerated left amygdala activation to all faces , greater for fearful faces . Right amygdala did not differ from control subjects . Following treatment , patients had bilateral reduced amygdala activation to masked fearful faces and bilateral reduced amygdala activation to all faces . Control subjects had no differences between the two scanning sessions . CONCLUSIONS Depressed patients have left amygdala hyperarousal , even when processing stimuli outside conscious awareness . Increased amygdala activation normalizes with antidepressant treatment The purpose of our study was to examine the neuroanatomical correlates of late-onset minor and major depression and to compare them with similar measures obtained from nondepressed controls . Our study groups were comprised of 18 patients with late-onset minor depression , 35 patients diagnosed with late-onset major depression , and 30 nondepressed controls . All subjects were scanned by using a 1 . 5-tesla MRI scanner . Absolute whole brain volume and normalized measures of prefrontal and temporal lobe volumes were obtained and used for comparison among groups . Our findings indicate that patients with minor depression present with specific neuroanatomical abnormalities that are comparable with the major depression group but significantly different from the controls . Normalized prefrontal lobe volumes show a significant linear trend with severity of depression , with volumes decreasing with illness severity . Whole brain volumes did not differ significantly among groups . These findings have broad implication s for the biology of late-life depression and suggest that there may be common neurobiological substrates that underlie all clinical ly significant forms of late-onset mood disturbances Behavioral studies suggest that emotional reactivity in depressed persons predicts subsequent symptom reduction . Using functional magnetic resonance imaging in a prospect i ve study , we show that greater amygdala activation to emotional facial expressions among depressed patients predicts symptom reduction 8 months later , controlling for initial depression severity and medication status . Functional magnetic resonance imaging may thus be used as a method to identify neural markers in depressed patients at risk for poor outcome BACKGROUND Previous magnetic resonance imaging ( MRI ) studies of patients with major depressive disorder ( MDD ) have consistently shown bilateral and unilateral reductions in hippocampal volume relative to healthy controls . Recent structural MRI studies have addressed the question of whether changes in the volume of hippocampal subregions may be associated with MDD . METHODS We used a comprehensive and reliable 3-dimensional tracing protocol that enables delineation of hippocampal subregions ( head , body , tail ) to study changes in the hippocampus of patients with MDD . We recruited 39 MDD patients ( 16 medicated , 23 unmedicated ) and 34 healthy age- and sex-matched controls . We acquired images using a magnetization-prepared rapid acquisition gradient echo sequence on a 1.5-T scanner with a spatial resolution of 1.5 mm x 0.5 mm x 0.5 mm . We performed volumetric analyses , blinded to diagnosis , using the interactive software package Display . All volumes were adjusted for intracranial volume . RESULTS We found a significant reduction in the volume of the hippocampal tail bilaterally , right hippocampal head and right total hippocampus in MDD patients . Medicated MDD patients showed increased hippocampal body volume compared with both healthy controls and unmedicated patients . LIMITATIONS This study was cross-sectional . Further prospect i ve studies are needed to determine the direct effect of antidepressant treatment . CONCLUSION Our results suggest that decreased hippocampal tail and hippocampal head volumes could be trait changes , whereas hippocampal body changes may be dependent on treatment . We showed that long-term antidepressant treatment may affect hippocampal volume in patients with MDD It has been hypothesized that one of the effects of antidepressants is to increase functional connectivity between the cortical mood-regulating and the limbic mood-generating regions . One consequence of this antidepressant effect is thought to be decreased limbic activation in response to negative emotional stimuli . Twelve unmedicated unipolar depressed patients and 11 closely matched healthy comparison subjects completed two magnetic resonance imaging ( MRI ) scanning sessions at baseline and after 6 weeks . Depressed patients received treatment with sertraline between the two sessions . During each MRI session , subjects completed a resting state functional connectivity scan and a conventional block- design negative vs. neutral pictures regional brain activation scan . After 6 weeks of sertraline treatment resting state , functional connectivity between the ACC and limbic regions increased while limbic activation in response to negative versus neutral pictures decreased . The results of this study are consistent with the hypothesis that antidepressant treatment has reciprocal effects on corticolimbic functional connectivity and limbic activation in response to emotional stimuli Abstract Resting state activity in the ventral cingulate may be an important neural marker of symptomatic improvement in depression . The number of task related functional magnetic resonance imaging ( fMRI ) studies correlating blood oxygenation level dependent ( BOLD ) response with symptomatic improvement is limited and method ologies are still evolving . We measured BOLD responses to sad and happy facial stimuli in 12 severely depressed individuals in the early stages of antidepressant treatment ( Time 1 ) and 12 weeks later ( Time 2 ) using event-related fMRI . We calculated correlations between temporal changes in BOLD response and changes in symptom scores . Most subjects improved markedly by Time 2 . At Time 1 , depression severity correlated positively with responses to sad stimuli in the right visual cortex , subgenual cingulate , anterior temporal pole and hippocampus and correlated negatively with responses to happy stimuli in left visual cortex and right cau date . Decreases in individual effect sizes of right subgenual cingulate and right visual cortical responses to sad , but not happy , facial stimuli were correlated with decreases in symptom scores . There are contrasting cortical and subcortical responses to sad and happy stimuli in severe depression . Responses to sad stimuli show the strongest correlates of clinical improvement , particularly in the subgenual cingulate BACKGROUND Hippocampal volumes obtained from a group of medication-free , remitted subjects with recurrent major depressive disorder ( MDD ) were compared against corresponding measures from healthy controls . METHODS Thirty-one subjects with recurrent MDD in full remission , and 57 healthy controls underwent high resolution magnetic resonance imaging ( MRI ) on a GE 3 T scanner . Eight patients with MDD were medication-naive , and twenty-three MDD patients were off antidepressant medications for a mean of 30 months at the time of the MRI study . RESULTS Patients showed smaller total and posterior hippocampal volume relative to controls . Anterior hippocampal volume did not differ between patients and controls . CONCLUSIONS Recurrent depression is associated with smaller hippocampal volume which is most prominent in the posterior hippocampus . Smaller hippocampal volume appears to be a trait characteristic for MDD BACKGROUND Depression has been linked to stress , memory deficits , and hypercortisolemia . However , the relationships between depression , hippocampal structure and function , and cortisol levels are unclear and the effects of antidepressant treatment on the measures are not well studied . METHODS Whole hippocampal volume , performance on verbal and visual declarative memory function and cortisol status was evaluated in 38 subjects with major depressive disorder ( MDD ) and 33 healthy subjects . All measures were repeated in a subgroup ( n = 22 ) of depressed patients after successful selective serotonin reuptake inhibitor ( SSRI ) treatment . RESULTS Hippocampal volume was not significantly different between patients with untreated MMD and healthy subjects , after controlling for whole brain volume , age and gender . However , depressed subjects had significantly greater deficits in delayed memory and percent retention on the verbal portion of the Wechsler Memory Scale-Revised ( WMS-R ) compared with healthy subjects , without significant differences in visual memory , attention , vigilance , or distractibility . Baseline plasma or urinary free cortisol ( UFC ) was not related to either hippocampal volume or memory deficits . Successful treatment with antidepressants did not change hippocampal volume but did result in a significant improvement in memory function and a reduction in UFC excretion . CONCLUSIONS Medication-free nonelderly depressed out patients without alcohol dependence or adverse experiences in childhood had normal hippocampal volume . Focal declarative memory deficits in depression supported localized hippocampal dysfunction in depressed patients . Treatment with antidepressants significantly improved memory and depression but did not alter hippocampal volume , suggesting that antidepressants may improve hippocampal function in the absence of detectable structural changes BACKGROUND Previous research examining the amygdala volumes in major depressive disorder ( MDD ) has found conflicting evidence for association . Furthermore , few of these studies have examined differences in individuals with an onset during childhood or adolescence . This study examined amygdala volume and its potential association with early onset major depression . METHODS A community-based sample of 47 right-h and ed young adult female monozygotic and dizygotic twin pairs was examined . For 29 twin pairs , one twin per pair had a lifetime history of MDD , while 18 age-matched control twin pairs had no lifetime history of MDD or other Axis I disorder . Core , noncore , and total amygdala volumes were estimated based on a combination of manual tracing , automated segmentation , and expert rater regional boundary definitions . RESULTS No significant differences were found in amygdala volumes between depressed , high-risk , or control subjects . However , analyses comparing control monozygotic twins to r and omly created control subject pairs suggest that there are familial , perhaps genetic , influences on core and total amygdala volumes . CONCLUSIONS Findings suggest that although there were no significant differences in amygdala volumes between groups , familial factors influence amygdala volumes . Discrepancies between studies measuring amygdala volume in MDD may be due to differences in amygdala boundary definitions BACKGROUND The aim of our study was to test the hypothesis that amygdala volumes are reduced in patients with recurrent major depression compared with first episode patients . METHODS Using structural magnetic resonance imaging , we compared 30 in patients with first-episode depression and 27 in patients with recurrent major depression ( DSM-IV ) with healthy volunteer subjects from the local community matched for age , gender , and h and edness . RESULTS Patients with first-episode depression showed enlarged amygdala volumes compared with patients with recurrent major depression and healthy control subjects . No significant differences were found between patients with recurrent depression and healthy control subjects . No significant correlations were found between amygdala volumes and age of onset , illness duration , or severity of depression . CONCLUSIONS Larger amygdala volumes in patients with first-episode depression may result from higher amygdala metabolism and blood flow . Additionally , disease progression with stress-related excitotoxic processes during recurrent depressive episodes might result in decreased amygdala volumes . Prospect i ve investigations to investigate amygdala changes during the course of depression are needed |
10,566 | 30,377,935 | Conclusions Eight out of ten of the most prevalent symptoms in glioma patients are related to the central nervous system and therefore specific for glioma .
Our findings emphasize the importance of tailored symptom care for glioma patients and may aid in the development of specific PROMs for glioma patients in different phases of the disease | Background Glioma patients suffer from a wide range of symptoms which influence quality of life negatively .
The aim of this review is to give an overview of symptoms most prevalent in glioma patients throughout the total disease trajectory , to be used as a basis for the development of a specific glioma Patient Reported Outcome Measure ( PROM ) for early assessment and monitoring of symptoms in glioma patients . | BACKGROUND The main goal of this study was to assess frequency , clinical correlates , and independent predictors of fatigue in a homogeneous cohort of well-defined glioblastoma patients at baseline prior to combined radio-chemotherapy . METHODS We prospect ively included 65 glioblastoma patients at postsurgical baseline and assessed fatigue , sleepiness , mean bedtimes , mood disturbances , and clinical characteristics such as clinical performance status , presenting symptomatology , details on neurosurgical procedure , and tumor location and diameter as well as pharmacological treatment including antiepileptic drugs , antidepressants , and use of corticosteroids . Data on fatigue and sleepiness were measured with the Fatigue Severity Scale and the Epworth Sleepiness Scale , respectively , and compared with 130 age- and sex-matched healthy controls . RESULTS We observed a significant correlation between fatigue and sleepiness scores in both patients ( r = 0.26 ; P = .04 ) and controls ( r = 0.36 ; P < .001 ) . Only fatigue appeared to be more common in glioblastoma patients than in healthy controls ( 48 % vs 11 % ; P < .001 ) but not the frequency of sleepiness ( 22 % vs 19 % ; P = .43 ) . Female sex was associated with increased fatigue frequency among glioblastoma patients but not among control participants . Multiple linear regression analyses identified depression , left-sided tumor location , and female sex as strongest associates of baseline fatigue severity . CONCLUSIONS Our findings indicate that glioblastoma patients are frequently affected by fatigue at baseline , suggesting that factors other than those related to radio- or chemotherapy have significant impact , particularly depression and tumor localization BACKGROUND Recurrent glioblastoma multiforme ( GBM ) is resistant to most therapeutic endeavors , with low response rates and survival rarely exceeding six months . There are no clearly established chemotherapeutic regimens and the aim of treatment is palliation with improvement in the quality of life . PATIENTS AND METHODS We report an open-label , uncontrolled , multicenter phase II trial of temozolomide in 138 patients ( intent-to-treat [ ITT ] population ) with glioblastoma multiforme at first relapse and a Karnofsky performance status ( KPS ) > or = 70 . One hundred twenty-eight patients were histologically confirmed with GBM or gliosarcoma ( GS ) by independent central review . Chemotherapy-naïve patients were treated with temozolomide 200 mg/m2/day orally for the first five days of a 28-day cycle . Patients previously treated with nitrosourea-containing adjuvant chemotherapy received 150 mg/m2/day for the first five days of a 28-day cycle . In the absence of grade 3 or 4 toxicity , patients on the 150 mg/m2 dose schedule were eligible for a 200 mg/m2 dose on the next cycle . RESULTS The primary endpoint was six-month progression-free survival assessed with strict radiological and clinical criteria . Secondary endpoints included radiological response and Health-related Quality of Life ( HQL ) . Progression-free survival at six months was 18 % ( 95 % confidence interval ( CI ) : 11%-26 % ) for the eligible-histology population . Median progression-free survival and median overall survival were 2.1 months and 5.4 months , respectively . The six-month survival rate was 46 % . The objective response rate ( complete response and partial response ) determined by independent central review of gadolinium-enhanced magnetic resonance imaging ( MRI ) scans was 8 % for both the ITT and eligible-histology population s , with an additional 43 % and 45 % of patients , respectively , having stable disease ( SD ) . Objective ly assessed response and maintenance of a progression-free status were both associated with HQL benefits ( characterized by improvements over baseline in HQL domains ) . Temozolomide had an acceptable safety profile , with only 9 % of therapy cycles requiring a dose reduction due to thrombocytopenia . There was no evidence of cumulative hematologic toxicity . CONCLUSIONS Temozolomide demonstrated modest clinical efficacy , with an acceptable safety profile and measurable improvement in quality of life in patients with recurrent GBM . The use of this drug should be explored further in an adjuvant setting and in combination with other agents The objective was to set the basis for a prospect i ve , multicentre data collection on newly diagnosed adult glioblastoma patients diagnosed in Lombardia by means of a common data base used by neurological and neurosurgical units of various hospitals , providing epidemiological , therapy and follow-up data . All adult patients with a newly diagnosed glioblastoma in 9 Lombardia hospitals from 31 March 2003 to 31 March 2004 were followed prospect ively by a form elaborated by the Lombardia Neuro-oncology Group . Demographic data were recorded , as well as symptoms at onset , entity of tumour resection , post-surgical Karnofsky Performance Score , radio- and chemotherapy , presence/absence of venous thrombosis , type of antiepileptic treatment , time to tumour progression and survival time ( ST ) . One hundred and thirty-four newly diagnosed glioblastoma patients were enrolled during the first year of the study . Male/female ratio was 1.6:1 . Median age was 61 years . The most common single sign/symptom at disease onset included seizures , followed by mood/cognition changes and headache . In 71 patients , the tumour involved 1 brain lobe at diagnosis . Twenty-five patients underwent biopsy , 51 partial removal and 51 grossly total removal . At analysis of predictive value on ST , grossly total resection and chemotherapy were significantly associated with a longer ST . Age younger than 50 showed a trend to predictive value . A very high proportion of patients were treated with antiepileptic drugs , even in the absence of seizures . Median ST was 12 months in our cohort . Data in newly diagnosed glioblastoma patients in Lombardia are in line with other case series reported in other population BACKGROUND Patients with advanced , incurable cancer receiving anticancer treatment often experience multidimensional symptoms . We hypothesize that real-time monitoring of both symptoms and clinical syndromes will improve symptom management by oncologists and patient outcomes . PATIENTS AND METHODS In this prospect i ve multicenter cluster-r and omized phase-III trial , patients with incurable , symptomatic , solid tumors , who received new outpatient chemotherapy with palliative intention , were eligible . Immediately before the weekly oncologists ' visit , patients completed the palm-based E-MOSAIC assessment ( Edmonton-Symptom- Assessment -Scale , ≤3 additional symptoms , estimated nutritional intake , body weight change , Karnofsky Performance Status , medications for pain , fatigue , nutrition ) . A cumulative , longitudinal monitoring sheet ( LoMoS ) was printed immediately . Eligible experienced oncologists were defined as one cluster each and r and omized to receive the immediate print-out LoMoS ( intervention ) or not ( control ) . Primary analysis limited to patients having uninterrupted ( > 4/6 visits with same oncologist ) patient-oncologist sequences was a mixed model for the difference in patients global quality of life ( G-QoL ; items 29/30 of EORTC-QlQ-c30 ) between baseline ( BL ) and week 6 . Intention-to-treat ( ITT ) analysis included all eligible patients . RESULTS In 8 centers , 82 oncologists treated 264 patients ( median 66 years ; overall survival intervention 6.3 , control 5.4 months ) with various tumors . The between-arm difference in G-QoL of 102 uninterrupted patients ( intervention : 55 ; control : 47 ) was 6.8 ( P = 0.11 ) in favor of the intervention ; in a sensitivity analysis ( oncologists treating ≥2 patients ; 50 , 39 ) , it was 9.0 ( P = 0.07 ) . ITT analysis revealed improvement in symptoms ( difference last study visit-BL : intervention -5.4 versus control 2.1 , P = 0.003 ) and favored the intervention for communication and coping . More patients with high symptom load received immediate symptom management ( chart review , nurse-patient interview ) by oncologists getting the LoMoS. CONCLUSION Monitoring of patient symptoms , clinical syndromes and their management clearly reduced patients ' symptoms , but not QoL. Our results encourage the implementation of real-time monitoring in the routine workflow of oncologist with a computer solution This retrospective study of 133 patients with glioblastoma multiforme evaluates survival times post-radiation in patients stratified in respect to age , presenting symptoms , tumour location , extent of surgery , and radiation dose delivered . Presenting features were coded as seizure , loss of consciousness , headache , speech or visual disturbance , weakness and confusion , as were tumour sites within the brain . Other parameters assessed included side of brain , age , extent of surgery and radiation dose . Statistical evaluation was undertaken by univariate and multivariate analyses to identify factors leading to enhanced survival . The median survival post-radiation was 10 months . A trend to improved early survival was demonstrated in patients presenting with acute and debilitating symptoms . The data presented reveals improved outcomes for patients younger than 60 years , particularly if radical surgery is undertaken with higher dose radiation . It is postulated that patients presenting with acute signs and symptoms are investigated earlier and are referred more promptly for treatment Purpose Optimal long-lasting treatment with sunitinib and sorafenib is limited by dose modifications ( DMs ) due to adverse events ( AEs ) . These AEs may be underrecognized and their influence on health-related quality of life ( HRQL ) underestimated . Improved insight into the relationship between AEs and therapy decisions is needed . To improve decision making around managing symptoms and reduce DMs , this study was set up to explore the influence of patient-reported symptoms on therapy decisions . Methods In this multicenter cohort study , patient characteristics , reasons for and different forms of used dose modifications , and AEs were prospect ively obtained from cancer patients on sunitinib/sorafenib treatment . Used instruments to get insight into AEs were the patient-scored Utrecht Symptom Diary ( USD ) and the professional-scored Common Terminology Criteria for AEs version 3.0 . Results Median total treatment duration in 42 patients was 16 weeks . Median time till dose modification was 10 weeks . DMs occurred mostly due to multiple mild AEs . By using the USD , a higher prevalence of most AEs was found compared to the literature . Sixty percent of the patients experienced a decreased HRQL due to multiple AEs . Conclusions Because severe AEs due to sunitinib/sorafenib treatment seldom occur , it is more important to focus on treating and preventing multiple mild AEs with higher impact on HRQL , when trying to avoid dose modifications . Using patient self-reported measurement methods helps to early recognize symptoms and to differentiate among symptom intensities . This systematic approach might help to achieve the optimal dosing , which might improve PFS and OS PURPOSE Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme ( GBM ) . This phase II study was performed to determine the safety , tolerability , and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM . PATIENTS AND METHODS Sixty-four patients were enrolled onto this open-label , phase II trial . Temozolomide ( 75 mg/m(2)/d x 7 d/wk for 6 weeks ) was administered orally concomitant with fractionated radiotherapy ( 60 Gy total dose : 2 Gy x 5 d/wk for 6 weeks ) followed by temozolomide monotherapy ( 200 mg/m(2)/d x 5 days , every 28 days for six cycles ) . The primary end points were safety and tolerability , and the secondary end point was overall survival . RESULTS Concomitant radiation plus temozolomide therapy was safe and well tolerated . Nonhematologic toxicities were rare and mild to moderate in severity . During the concomitant treatment phase , grade 3 or 4 neutropenia , thrombocytopenia , or both were observed in 6 % of patients , including two severe infections with Pneumocystis carinii . During adjuvant temozolomide , 2 % and 6 % of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia , respectively . Median survival was 16 months , and the 1- and 2-year survival rates were 58 % and 31 % , respectively . Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome . CONCLUSION Continuous daily temozolomide and concomitant radiation is safe . This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma . Further investigation is warranted , and a r and omized trial is ongoing BACKGROUND Most patients with glioblastoma are older than 60 years , but treatment guidelines are based on trials in patients aged only up to 70 years . We did a r and omised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma . METHODS Patients with newly diagnosed glioblastoma were recruited from Austria , Denmark , France , Norway , Sweden , Switzerl and , and Turkey . They were assigned by a computer-generated r and omisation schedule , stratified by centre , to receive temozolomide ( 200 mg/m(2 ) on days 1 - 5 of every 28 days for up to six cycles ) , hypofractionated radiotherapy ( 34·0 Gy administered in 3·4 Gy fractions over 2 weeks ) , or st and ard radiotherapy ( 60·0 Gy administered in 2·0 Gy fractions over 6 weeks ) . Patients and study staff were aware of treatment assignment . The primary endpoint was overall survival . Analyses were done by intention to treat . This trial is registered , number IS RCT N81470623 . FINDINGS 342 patients were enrolled , of whom 291 were r and omised across three treatment groups ( temozolomide n=93 , hypofractionated radiotherapy n=98 , st and ard radiotherapy n=100 ) and 51 of whom were r and omised across only two groups ( temozolomide n=26 , hypofractionated radiotherapy n=25 ) . In the three-group r and omisation , in comparison with st and ard radiotherapy , median overall survival was significantly longer with temozolomide ( 8·3 months [ 95 % CI 7·1 - 9·5 ; n=93 ] vs 6·0 months [ 95 % CI 5·1 - 6·8 ; n=100 ] , hazard ratio [ HR ] 0·70 ; 95 % CI 0·52 - 0·93 , p=0·01 ) , but not with hypofractionated radiotherapy ( 7·5 months [ 6·5 - 8·6 ; n=98 ] , HR 0·85 [ 0·64 - 1·12 ] , p=0·24 ) . For all patients who received temozolomide or hypofractionated radiotherapy ( n=242 ) overall survival was similar ( 8·4 months [ 7·3 - 9·4 ; n=119 ] vs 7·4 months [ 6·4 - 8·4 ; n=123 ] ; HR 0·82 , 95 % CI 0·63 - 1·06 ; p=0·12 ) . For age older than 70 years , survival was better with temozolomide and with hypofractionated radiotherapy than with st and ard radiotherapy ( HR for temozolomide vs st and ard radiotherapy 0·35 [ 0·21 - 0·56 ] , p<0·0001 ; HR for hypofractionated vs st and ard radiotherapy 0·59 [ 95 % CI 0·37 - 0·93 ] , p=0·02 ) . Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation ( 9·7 months [ 95 % CI 8·0 - 11·4 ] vs 6·8 months [ 5·9 - 7·7 ] ; HR 0·56 [ 95 % CI 0·34 - 0·93 ] , p=0·02 ) , but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy ( HR 0·97 [ 95 % CI 0·69 - 1·38 ] ; p=0·81 ) . As expected , the most common grade 3 - 4 adverse events in the temozolomide group were neutropenia ( n=12 ) and thrombocytopenia ( n=18 ) . Grade 3 - 5 infections in all r and omisation groups were reported in 18 patients . Two patients had fatal infections ( one in the temozolomide group and one in the st and ard radiotherapy group ) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed . INTERPRETATION St and ard radiotherapy was associated with poor outcomes , especially in patients older than 70 years . Both temozolomide and hypofractionated radiotherapy should be considered as st and ard treatment options in elderly patients with glioblastoma . MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide . FUNDING Merck , Lion 's Cancer Research Foundation , University of Umeå , and the Swedish Cancer Society Background : High- grade gliomas are the most frequent primary brain tumors . Despite improvement in diagnostics and treatment , survival is still poor and quality -of-life issues are of major importance . Little is known regarding the clinical signs and symptoms of dying patients with glioblastoma . Objective : The aim of this study was to investigate signs and symptoms as well as therapeutic strategies in patients with glioblastoma in the end-of-life phase in order to improve end-of-life care . Methods : In this prospect i ve single-center study , clinical data were obtained using a st and ardized protocol . We descriptively analyzed signs , symptoms , and therapeutic strategies on a daily basis . Results : A total of 57 patients , who died due to glioblastoma in a hospital setting , were included . The most frequent signs and symptoms in the last 10 days before death were decrease in level of consciousness ( 95 % ) , fever ( 88 % ) , dysphagia ( 65 % ) , seizures ( 65 % ) , and headache ( 33 % ) . Concerning medication , 95 % received opioids . There was a high need for nonsteroidal anti-inflammatory drugs ( 77 % ) and anticonvulsants ( 75 % ) . Steroids were given to 56 % . Conclusion : Due to a decrease in level of consciousness and cognitive impairment , assessment of clinical signs and symptoms such as headache at the end of life is difficult . Based on the signs and symptoms in the last days before death in patients with glioblastoma , supportive drug treatment remains challenging . Our study emphasizes the importance of st and ardized guidelines for end-of-life care in patients with glioblastoma In our institution , 103 glioblastoma multiforme ( GBM ) patients aged from 55 to 83 years were treated since November 1994 as follows . All patients underwent surgical intervention ( gross total resection , n=35 ; subtotal resection , n=38 ; stereotactic biopsy , n=30 ) . Subsequently all patients were offered radiotherapy and chemotherapy with CCNU . Results were as follows : 101 patients started radiotherapy , 93 patients completed it ( 96 % of the patients aged < 65 years and 85 % of the patients ≥65 years ) . All patients received at least 1 cycle of chemotherapy ( median 3 cycles ) . Chemotherapy-associated toxicity was generally mild , more pronounced in females and did not increase with age . Median time to progression was 10.5±3.2 months for the patients < 65 years and 5.1±1 months for patients ≥65 years . median overall survival was 17.5±3.8 months in patients < 65 years and 8.6±1 months in patients ≥65 years ( p<0.0001 ) . In multivariate analysis , age and female sex remained independent prognostic factors . Our data indicate that a treatment concept including concomitant radio- and chemotherapy is feasible even in elderly patients with GBM BACKGROUND Glioblastoma , the most common primary brain tumor in adults , is usually rapidly fatal . The current st and ard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible , followed by adjuvant radiotherapy . In this trial we compared radiotherapy alone with radiotherapy plus temozolomide , given concomitantly with and after radiotherapy , in terms of efficacy and safety . METHODS Patients with newly diagnosed , histologically confirmed glioblastoma were r and omly assigned to receive radiotherapy alone ( fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks , for a total of 60 Gy ) or radiotherapy plus continuous daily temozolomide ( 75 mg per square meter of body-surface area per day , 7 days per week from the first to the last day of radiotherapy ) , followed by six cycles of adjuvant temozolomide ( 150 to 200 mg per square meter for 5 days during each 28-day cycle ) . The primary end point was overall survival . RESULTS A total of 573 patients from 85 centers underwent r and omization . The median age was 56 years , and 84 percent of patients had undergone debulking surgery . At a median follow-up of 28 months , the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone . The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 ( 95 percent confidence interval , 0.52 to 0.75 ; P<0.001 by the log-rank test ) . The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone . Concomitant treatment with radiotherapy plus temozolomide result ed in grade 3 or 4 hematologic toxic effects in 7 percent of patients . CONCLUSIONS The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma result ed in a clinical ly meaningful and statistically significant survival benefit with minimal additional toxicity PURPOSE To describe the quality of life ( QOL ) in elderly patients with glioblastoma ( GBM ) treated with an abbreviated course of radiation therapy ( RT ; 40 Gy in 15 fractions ) plus concomitant and adjuvant temozolomide ( TMZ ) . METHODS AND MATERIAL S Health-related QOL ( HRQOL ) was assessed by European Organisation for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire Core-30 ( QLQ-C30 , version 3 ) and EORTC Quality of Life Question naire Brain Cancer Module ( QLQ-BN20 ) . Changes from baseline in the score of 9 preselected domains ( global QLQ , social functioning , cognitive functioning , emotional functioning , physical functioning , motor dysfunction , communication deficit , fatigue , insomnia ) were determined 4 weeks after RT and thereafter every 8 weeks during the treatment until disease progression . The proportion of patients with improved HRQOL scores , defined as a change of 10 points or more , and duration of changes were recorded . RESULTS Sixty-five patients completed the question naires at baseline . The treatment was consistently associated with improvement or stability in most of the preselected HRQOL domains . Global health improved over time ; mean score differed by 9.6 points between baseline and 6-month follow-up ( P=.03 ) . For social functioning and cognitive functioning , mean scores improved over time , with a maximum difference of 10.4 points and 9.5 points between baseline and 6-month follow-up ( P=.01 and P=.02 ) , respectively . By contrast , fatigue worsened over time , with a difference in mean score of 5.6 points between baseline and 4-month follow-up ( P=.02 ) . CONCLUSIONS A short course of RT in combination with TMZ in elderly patients with GBM was associated with survival benefit without a negative effect on HRQOL until the time of disease progression |
10,567 | 30,736,783 | Conclusions In this meta- analysis , gait speed and peak hip flexion within 3 months after surgery were significantly higher in the DAA group than in the ALA group . | Background Comparative studies of total hip arthroplasty using the direct anterior approach ( DAA ) compared with the anterolateral approach ( ALA ) by gait analysis compared the results of the two groups , the damage to the abductor muscle , with objective and detailed kinematic as well as kinetic data of actual gait .
The purpose of this systematic review was to analyze the differences in gait such as time-dependent parameters , kinetics , and kinematics after THA using the DAA compared with ALA . | BACKGROUND A prospect i ve study was conducted to compare the effect of an anterolateral approach in the supine position ( ALS ) with that of a direct lateral ( DL ) approach on gait motion , including trunk deflection , in walking after total hip arthroplasty . We hypothesized that trunk deflection in walking after ALS would be significantly improved in comparison with use of the DL approach . METHODS The subjects were 15 patients , with 7 in the ALS group and 8 in the DL group . Walking before and 9 and 28 weeks after surgery was analyzed using 3-dimensional motion analysis . RESULTS Walking velocity , stride length , hip joint range of motion in the sagittal plane in walking , and locomotion range of trunk inclination were significantly improved 28 weeks after surgery in both groups . In gait analysis , there were no significant differences between the 2 groups . CONCLUSION This study was conducted to compare the effect of ALS with that of a DL approach on locomotion in walking after total hip arthroplasty . Hip pain at 9 weeks after surgery was significantly improved using ALS compared to the DL approach , but there were no significant differences in gait function at 28 weeks after surgery using ALS or DL approach . Further long-term studies are required to examine differences between these procedures Introduction Minimally invasive total hip arthroplasty ( THA ) is cl aim ed to be superior to the st and ard technique , due to the potential reduction of soft tissue damage via a smaller and tissue-sparing approach . As a result of the lack of objective evidence of fewer muscle and tendon defects , controversy still remains as to whether minimally invasive total hip arthroplasty truly minimizes muscle and tendon damage . Therefore , the objective was to compare the influence of the surgical approach on abductor muscle trauma and to analyze the relevance to postoperative pain and functional recovery . Material s and methods Between June 2006 and July 2007 , 44 patients with primary hip arthritis were prospect ively included in the study protocol . Patients underwent cementless unilateral total hip arthroplasty either through a minimally invasive anterolateral approach ( ALMI ) ( n = 21 ) or a modified direct lateral approach ( mDL ) ( n = 16 ) . Patients were evaluated clinical ly and underwent MR imaging preoperatively and at 3 and 12 months postoperatively . Clinical assessment contained clinical examination , performance of abduction test and the survey of a function score using the Harris Hip Score , a pain score using a numeric rating scale ( NRS ) of 0–10 , as well as a satisfaction score using an NRS of 1–6 . Additionally , myoglobin and creatine kinase were measured preoperatively , and 6 , 24 and 96 h postoperatively . Evaluation of the MRI images included fatty atrophy ( rating scale 0–4 ) , tendon defects ( present/absent ) and bursal fluid collection of the abductor muscle . Results Muscle and tendon damage occurred in both groups , but more lateral gluteus medius tendon defects [ mDL 3/12mth . : 6 (37%)/4 ( 25 % ) ; ALMI : 3 (14%)/2 ( 9 % ) ] and muscle atrophy in the anterior part of the gluteus medius [ mean-st and ard ( 12 ) : 1.75 ± 1.8 ; mean-MIS ( 12 ) : 0.98 ± 1.1 ] were found in patients with the mDL approach . The clinical outcome was also poorer compared to the ALMI group . Significantly , more Trendelenburg ’s signs were evident and lower clinical scores were achieved in the mDL group . No differences in muscle and tendon damage were found for the gluteus minimus muscle . A higher serum myoglobin concentration was measured 6 and 24 h postoperatively in the mDL group ( 6 h : 403 ± 168 μg/l ; 24 h : 304 ± 182 μg/l ) compared to the ALMI group ( 6 h : 331 ± 143 μg/l ; 24 h : 268 ± 145 μg/l ) . Conclusion Abductor muscle and tendon damage occurred in both approaches , but the gluteus medius muscle can be spared more successfully via the minimally invasive approach and is accompanied by a better clinical outcome . Therefore , going through the intermuscular plane , without any detachment or dissection of muscle and tendons , truly minimizes perioperative soft tissue trauma . Furthermore , MRI emerges as an important imaging modality in the evaluation of muscle trauma in THA BACKGROUND Total hip replacement using a minimally invasive surgical approach is cl aim ed to enable recovering of motor function more quickly . The purpose of this prospect i ve As per the stylesheet , kindly provide section headings for abstract . and r and omized study was to test this cl aim by evaluating early patient functional outcomes by gait analysis . METHODS Seventeen patients were operated on using a traditional anterolateral approach ( AL ) , 16 using a minimally invasive direct anterior approach ( DA ) . Gait analysis was performed the day before surgery , and at 6 and 12 weeks after surgery . Time-distance and kinematics analyses were performed by a recently proposed anatomically-based gait analysis protocol . A static double-leg stance and five walking trials at self-selected speeds were recorded on a 9-m walkway . FINDINGS At 6 weeks follow-up , but in the DA group only , a statistically significant improvement with respect to preoperative status was observed for the percentage of single support and for the stride time . Between 6- and 12-week follow-up , the DA group showed a significant improvement in cadence , stride time and length , walking speed , hip flexion at foot contact , maximum hip flexion in swing , and hip total range of motion in the sagittal and the coronal planes . Between 6 and 12 weeks , the AL group showed significant improvements in opposite foot contact and step time , and in flexion at foot contact , maximum flexion in swing , and range of flexion at the hip joint . INTERPRETATION Minimally invasive DA patients improved in a larger number of gait parameters than patients receiving the traditional AL approach . The majority of improvements occurred between the 6- and 12-week follow-ups OBJECTIVE To investigate the differences in gait biomechanics on the basis of surgical approach 1 year after surgery . DESIGN This was a descriptive laboratory study to investigate the side-to-side differences in walking mechanics at a self-selected walking speed as well as a functional assessment 1 year after total hip arthroplasty ( THA ) . Temporospatial , kinetic , and kinematic data as well as functional outcomes were collected . Two-way analysis of variance was used to assess for between-group differences and limb-to-limb asymmetries . SETTING A controlled laboratory study . PARTICIPANTS This study examined 35 patients with primary , unilateral THA . The THA surgical approaches that were used in these patients included 12 direct lateral , 18 posterior , and 11 anterolateral . All the patients were assessed 1 year after THA . Patients were excluded from the study if they had contralateral hip pain or pathology , or any prior lower extremity total joint replacements . MAIN OUTCOME MEASUREMENTS Three-dimensional lower extremity kinematics and kinetics as well as spatiotemporal variables were collected . In addition , a series of physical performance measures were collected . RESULTS No main effects for the physical performance measures or biomechanical variables were observed among the approach groups . Significant limb-to-limb asymmetries were observed among all the patients , with decreased sagittal plane range of motion , peak extension , and peak vertical ground reaction forces on the operative side . CONCLUSION The results of this study indicated that no significant differences existed among the different surgical approach groups for any study variable . However , 1 year after THA , the patients demonstrated asymmetric gait patterns regardless of surgical approach , which indicated the potential need for continued intervention through physical therapy to regain normal side-to-side symmetry after THA This study examined the effect of the surgical approach used in total hip arthroplasty ( THA ) on gait mechanics six months following surgery . Quantitative gait analysis was performed on 29 subjects : 10 anterolateral ( A-L ) and 10 posterolateral ( P-L ) THA patients and nine able-bodied , velocity-matched subjects . Discriminant function analysis was used to determine the distinction of the groups with respect to sagittal plane hip range of motion , index of symmetry , trunk inclination , pelvic drop , hip abduction , and foot progression angles . The A-L group had the largest trunk inclination ( 3.0+/-2.4 degrees ) and the smallest hip range of motion ( 34.0+/-7.4 degrees ) . Both THA groups demonstrated greater asymmetry as expressed by the smaller symmetry index ( 0.97+/-0.04 for A-L and 0.98+/-0.05 for the P-L ) than the able-bodied group ( 0.99+/-0.01 ) . The classification procedure correctly classified 89 % of the control group cases , 90 % of the A-L cases , and 50 % of the P-L cases . These results support the conclusion that six months following surgery , the gait of the majority ( 85 % ) of THA patients has not returned to normal . The A-L patients displayed distinct gait patterns , while a small percentage ( 30 % ) of the P-L patients demonstrated normal gait . While these differences are statistically significant , the clinical significance is unknown and linked to the duration that they persist BACKGROUND Minimally invasive total hip arthroplasty is purported to allow an improved and faster rehabilitation in the immediate postoperative period because of reduced soft-tissue damage compared with total hip arthroplasty performed with use of a st and ard approach . In the present study , a minimally invasive approach was compared with a traditional st and ard approach in terms of the effect on gait kinematics as demonstrated with gait analysis and electromyography . METHODS Twenty r and omized patients who underwent a primary total hip replacement with use of a minimally invasive modified Watson-Jones approach ( minimally invasive group ) were compared with a group of twenty patients who underwent a total hip arthroplasty with use of a st and ard transgluteal Hardinge approach ( st and ard group ) . All patients received the same cementless implant , inserted with use of st and ard instruments , and all operations were performed by a single , experienced surgeon . The patients were evaluated with use of three-dimensional gait analysis and dynamic electromyograms at three time points : preoperatively , ten days postoperatively , and twelve weeks postoperatively . Temporospatial and joint-kinematic parameters were evaluated . RESULTS There were no significant differences between the two groups with regard to the temporospatial variables of velocity , cadence , step length , and stride length at any tested time point . With regard to the range of motion of the operatively treated hip , the minimally invasive group had a smaller decrease at the ten-day time point in comparison with the st and ard group . However , this finding was not significant . The reduction in the range of motion was mainly caused by reduced hip extension . A compensatory increase in the pelvic tilt was observed in both groups . One patient in the st and ard group showed a positive Trendelenburg gait ten days postoperatively ; it had disappeared completely at the twelve-week time point . CONCLUSIONS With regard to gait kinematics in the early postoperative period ( three months ) , the present study showed no significant benefit for patients who underwent a total hip arthroplasty through a minimally invasive Watson-Jones approach in comparison with those who were managed with a st and ard transgluteal approach Purported advantages of total hip arthroplasty performed with minimally invasive surgical ( MIS ) approaches are less muscle damage and faster recovery . There are little data scientifically evaluating these cl aims . Twenty-four consecutive hips were r and omized to total hip arthroplasty through 1 of 3 MIS approaches ( 2-incision , mini-posterior , and mini-anterolateral ) . Each patient underwent preoperative and postoperative gait analysis . Gait parameters included vertical ground reaction force , velocity , single-leg stance time , limb-loading rate , and abductor torque . All 3 groups demonstrated overall improvements in gait parameters at 6 weeks postoperatively . The anterolateral approach patients showed a decrease in the vertical ground reaction force at mid-stance , whereas the 2-incision and posterior approaches demonstrated no significant change . These results fail to demonstrate any significant advantage of the 2-incision approach over the posterior approach in kinetic gait parameters . Furthermore , the anterolateral approach demonstrates a gait pattern consistent with abductor muscle injury in the early recovery period , despite the MIS approach AIM Different surgical approaches are used in total hip arthroplasty . The present study confronted two surgical techniques , analysing functional recovery in terms of activities of daily living , and ambulation using gait analysis , after a st and ardized rehabilitation protocol . Our hypothesis was that the increased surgical damage could modify the gait pattern and functional recovery . METHODS Thirty patients were r and omly assigned to two homogeneous groups : Group A was treated with intermuscular minimally invasive surgery ( MIS ) ; Group B was treated with st and ard lateral transmuscular approach . Follow up was planned at 30 and 90 days . Instrumental evaluation using gait analysis and functional evaluation using vali date d scales were performed at follow up . RESULTS No differences could be found as for functional scales . At the first follow up , the MIS approach proved to be the most favourable : data showed a longer duration of the swing phase , an improved range of motion of the non-treated hip , a reduced adduction ( all P<0.005 ) and a correct timing of activation of the gluteus medium muscle on the treated side . At the second evaluation , gait analysis demonstrated some benefits of the intermuscular approach ( a better flexion of both hips , and a minor obliquity of the pelvis during the terminal stance ) , but also advantages in the transmuscular group ( better hip extension ) . CONCLUSION Gait pattern after THA seems to be strictly dependent on surgical access and on the extent and location of surgical damage . It appears important to consider these elements in order to correctly manage the rehabilitation treatment after surgery Anterolateral minimally invasive hip surgery ( ALMIS ) is a challenging procedure that is thought to offer a more expedient and a better functional outcome . Seventy-nine patients receiving primary hip arthroplasty were r and omized . Röttinger ALMIS technique was used for 42 patients , whereas 41 received the st and ard lateral transgluteal Hardinge approach . Operative time was longer with ALMIS ( P = .000078 ) , whereas blood loss was less ( P = .008 ) . Surgical and postoperative complication rates , morphine consumption , and length and cost of hospitalization were similar . At 1 year , Harris , Postel and Merle d'Aubigné , and Short Form-36v1 scores were similar . Gait analysis revealed similar results . Computed tomographic analysis revealed no significant difference in implant position , heterotopic ossification , and loosening . Röttinger ALMIS is a valid approach for hip arthroplasty . However , it offers no advantages at 1 year Surgical approach for total hip arthroplasty ( THA ) is determined by clinician preference from limited prospect i ve data . This study aim ed to examine the effect of surgical approach ( direct lateral , posterior , and anterolateral ) on 6-week postoperative gait mechanics . Thirty-five patients ( direct lateral , 8 ; posterior , 12 ; anterolateral , 15 ) were tested preoperatively and 6 weeks after THA . Patients underwent a gait analysis at a self-selected walking speed . A 2-way analysis of variance was used for analysis . Stride length , step length , peak hip extension , and walking speed increased after THA . The 3 surgical approach variables were not significantly different for any of the study variables after THA . All patients showed some increase in selected variables after THA regardless of surgical approach . In this study , surgical approach did not appear to significantly influence the early postoperative gait mechanics that were quantified Background Minimally invasive techniques in THA are intended to minimize periarticular muscle trauma . The lateral approach has a risk of partial gluteal insufficiency , while the anterolateral approach carries the risk of damaging the tensor fasciae latae through intermuscular nerve and compression injury . Questions / purpose sWe assessed the surgical influence of the anterolateral minimally invasive approach and the modified direct lateral approach on the tensor fasciae latae and gluteus medius . Methods We prospect ively r and omized 44 patients with primary coxarthrosis to receive a cementless THA via the anterolateral minimally invasive approach or the modified direct lateral approach . We performed clinical and MRI examinations preoperatively and 3 and 12 months postoperatively , including Harris hip and pain scores . MRI analysis included assessment of the tensor fasciae latae and gluteus medius with regard to fatty atrophy and changes in the muscle cross-sectional area . Results Clinical scores were similar in the two groups but a low- grade Trendelenburg sign was observed more frequently in the lateral group . MRI showed a pronounced , postoperative fatty atrophy of the anterior part of the gluteus medius more often ; and a compensatory hypertrophy of the tensor fasciae latae occurred . Higher- grade atrophy of the tensor fasciae latae and gluteus medius did not occur with the anterolateral approach . Conclusions We found no increased damage to the tensor fasciae latae with the anterolateral approach . The lateral approach was associated with increased partial gluteus atrophy and a compensatory hypertrophy of the tensor fasciae latae . Based on fewer structural changes in the musculature , we recommend the anterolateral minimally invasive approach |
10,568 | 30,868,279 | Summary TNFi therapy improves bone density but not vertebral fracture rates .
Secukinumab improves symptoms and may slow radiographic progression .
Data is lacking regarding the effects of secukinumab on BMD and fractures . | Purpose of Review Osteoporosis in axial spondyloarthritis may be modified by therapy . | We have genotyped 14,436 nonsynonymous SNPs ( nsSNPs ) and 897 major histocompatibility complex ( MHC ) tag SNPs from 1,000 independent cases of ankylosing spondylitis ( AS ) , autoimmune thyroid disease ( AITD ) , multiple sclerosis ( MS ) and breast cancer ( BC ) . Comparing these data against a common control data set derived from 1,500 r and omly selected healthy British individuals , we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis , ARTS1 and IL23R , and confirmation of the previously reported association of AITD with TSHR and FCRL3 . These findings , enabled in part by increased statistical power result ing from the expansion of the control reference group to include individuals from the other disease groups , highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major ' seronegative ' diseases Objective . Ankylosing spondylitis ( AS ) is characterized by chronic inflammation leading to ankylosis , but also to low bone mineral density ( BMD ) and vertebral fractures ( VFx ) . Treatment with tumor necrosis factor-α blockers decreases inflammation and has shown to be effective in increasing BMD . We studied the effects of etanercept ( ETN ) on BMD and VFx in patients with AS after 2 years of treatment . Further , we studied changes in bone turnover markers and radiological damage . Methods . Patients with active AS , treated with ETN for 2 years , were included . BMD lumbar spine and hip were measured at baseline and after 2 years , as well as radiological damage ( modified Stoke Ankylosing Spondylitis Spinal Score with the addition of the thoracic spine ) , VFx ( Genant method ) , and change in bone turnover markers . Results . Forty-nine patients with AS were included . After 2 years of ETN , hip BMD increased by 2.2 % ( p = 0.014 ) and lumbar spine BMD by 7.0 % ( p < 0.001 ) . The Bath Ankylosing Spondylitis Disease Activity Index decreased significantly ( p < 0.001 ) , as well as C-reactive protein and erythrocyte sedimentation rate ( p < 0.001 ) . Despite ETN therapy , the number of patients with VFx more than doubled ( from 6 to 15 patients , p = 0.003 ) . Also , the radiological damage increased significantly over time ( from 12.1 to 18.5 , p < 0.001 ) ; however , no significant change in bone turnover markers was found . Conclusion . This prospect i ve longitudinal observational cohort study showed that after 2 years of ETN , BMD of the hip and spine increased significantly , but the number of patients with VFx and the severity of VFx increased as well . Besides that , radiological progression , including the thoracic spine , increased significantly . Thus , the favorable bone-preserving effect is accompanied by unfavorable outcomes on VFx and radiological damage OBJECTIVE To determine the changes in body weight , body composition , and bone density in patients with spondyloarthropathy ( SpA ) receiving anti-tumor necrosis factor-alpha ( TNF-alpha ) treatment . METHODS One hundred six patients with SpA ( 80 men , 26 women ) aged 20 - 71 years were included in a 2-year prospect i ve open study . Fifty-nine patients received infliximab ( 3 or 5 mg/kg/infusion each 6 or 8 weeks ) ; and 47 patients received etanercept ( 25 mg twice a week ) because of persistent active disease despite an optimal treatment , according to ASsessment s in Ankylosing Spondylitis Working Group criteria . Body weight , total body composition ( lean mass , fat mass ) , and spine and femoral bone mineral density ( BMD ; dual-energy x-ray absorptiometry ) were measured at baseline and at 1 and 2 years . RESULTS There was a significant increase in body weight after 1 year ( 2.2 + /- 3.9 kg , i.e. , 3.4 % ; p < 0.0001 ) and 2 years ( 2.2 + /- 4.7 kg , 3.5 % ; p < 0.0001 ) , mostly due to a significant gain in fat mass at 1 year ( 1.4 + /- 2.6 kg , 12.1 % ; p < 0.0001 ) and 2 years ( 1.5 + /- 3.1 kg , 14.5 % , p < 0.0001 ) . Gain in lean mass was also significant at 1 year ( 0.8 + /- 2.2 kg , 1.9 % ; p < 0.0001 ) and 2 years ( 0.9 + /- 2.5 kg , 2 % ; p < 0.0001 ) . At 2 years , lumbar spine and femur BMD increased : + 5.8 + /- 13 % ( p < 0.0001 ) and + 2.26 + /- 4.5 % ( p = 0.001 ) , respectively . CONCLUSION This 2-year prospect i ve study showed a significant increase in body weight at 1 year and 2 years , mostly due to a gain in fat mass and a significant increase in BMD , in patients with SpA receiving anti-TNF-alpha treatment BACKGROUND Ankylosing spondylitis is a chronic immune-mediated inflammatory disease characterised by spinal inflammation , progressive spinal rigidity , and peripheral arthritis . Interleukin 17 ( IL-17 ) is thought to be a key inflammatory cytokine in the development of ankylosing spondylitis , the prototypical form of spondyloarthritis . We assessed the efficacy and safety of the anti-IL-17A monoclonal antibody secukinumab in treating patients with active ankylosing spondylitis . METHODS We did a r and omised double-blind proof-of-concept study at eight centres in Europe ( four in Germany , two in the Netherl and s , and two in the UK ) . Patients aged 18 - 65 years were r and omly assigned ( in a 4:1 ratio ) to either intravenous secukinumab ( 2 × 10 mg/kg ) or placebo , given 3 weeks apart . R and omisation was done with a computer-generated block r and omisation list without a stratification process . The primary efficacy endpoint was the percentage of patients with a 20 % response according to the Assessment of SpondyloArthritis international Society criteria for improvement ( ASAS20 ) at week 6 ( Bayesian analysis ) . Safety was assessed up to week 28 . This study is registered with Clinical Trials.gov , number NCT00809159 . FINDINGS 37 patients with moderate-to-severe ankylosing spondylitis were screened , and 30 were r and omly assigned to receive either intravenous secukinumab ( n=24 ) or placebo ( n=6 ) . The final efficacy analysis included 23 patients receiving secukinumab and six patients receiving placebo , and the safety analysis included all 30 patients . At week 6 , ASAS20 response estimates were 59 % on secukinumab versus 24 % on placebo ( 99·8 % probability that secukinumab is superior to placebo ) . One serious adverse event ( subcutaneous abscess caused by Staphylococcus aureus ) occurred in the secukinumab-treated group . INTERPRETATION Secukinumab rapidly reduced clinical or biological signs of active ankylosing spondylitis and was well tolerated . It is the first targeted therapy that we know of that is an alternative to tumour necrosis factor inhibition to reach its primary endpoint in a phase 2 trial . FUNDING Novartis Introduction The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha ( TNF-α ) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers ( BTM ) for treatment discontinuation in patients with ankylosing spondylitis ( AS ) . Methods This is a prospect i ve cohort study of 111 consecutive AS out patients who started TNF-α blocking therapy . Clinical assessment s and BTM were assessed at baseline , three and six months , as well as at one , two , and three years . Z-scores of BTM were calculated to correct for age and gender . Bone mineral density ( BMD ) was assessed yearly . Results After three years , 72 patients ( 65 % ) were still using their first TNF-α blocking agent . In these patients , TNF-α blocking therapy result ed in significantly increased bone-specific alkaline phosphatase , a marker of bone formation ; decreased serum collagen-telopeptide ( sCTX ) , a marker of bone resorption ; and increased lumbar spine and hip BMD compared to baseline . Baseline to three months decrease in sCTX Z-score ( HR : 0.394 , 95 % CI : 0.263 to 0.591 ) , AS disease activity score ( ASDAS ; HR : 0.488 , 95 % CI : 0.317 to 0.752 ) , and physician 's global disease activity ( HR : 0.739 , 95 % CI : 0.600 to 0.909 ) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance . Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity , physical function and quality of life . Conclusions Three years of TNF-α blocking therapy results in a bone turnover balance that favors bone formation , especially mineralization , in combination with continuous improvement of lumbar spine BMD . Early change in sCTX can serve as an objective measure in the evaluation of TNF-α blocking therapy in AS , in addition to the currently used more subjective measures OBJECTIVE To study the effect of tumor necrosis factor α ( TNFα ) inhibitors on progressive spinal damage in patients with ankylosing spondylitis ( AS ) . METHODS All AS patients meeting the modified New York criteria who had been monitored prospect ively and had at least 2 sets of spinal radiographs a minimum of 1.5 years apart were included in the study ( n=334 ) . The patients received st and ard therapy , which included nonsteroidal antiinflammatory drugs and TNFα inhibitors . Radiographic severity was assessed by the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ) . Patients with a rate of AS progression that was ≥1 mSASSS unit/year were considered progressors . Univariable and multivariable regression analyses were done . Propensity score matching and sensitivity analysis were performed . A zero-inflated negative binomial ( ZINB ) model was used to analyze the effect of TNFα inhibitors on the change in the mSASSS with varying followup periods . Potential confounders , such as disease activity ( as assessed by the Bath Ankylosing Spondylitis Disease Activity Index ) , the erythrocyte sedimentation rate , C-reactive protein level , HLA-B27 positivity , sex , age at onset , smoking burden ( number of pack-years ) , and baseline damage , were included in the model . RESULTS TNFα inhibitor treatment was associated with a 50 % reduction in the odds of progression , with an odds ratio ( OR ) of 0.52 ( 95 % confidence interval [ 95 % CI ] 0.30 - 0.88 , P=0.02 ) . Patients with a delay of > 10 years in starting therapy were more likely to experience progression as compared to those who started earlier ( OR 2.4 [ 95 % CI 1.09 - 5.3 ] , P=0.03 ) . In the ZINB model , the use of TNFα inhibitors significantly reduced disease progression when the gap between radiographs was > 3.9 years . The protective effect of TNFα inhibitors was stronger after propensity score matching . CONCLUSION Treatment with TNFα inhibitors appears to reduce radiographic progression in AS patients , especially with early initiation and with longer duration of followup Objective . To evaluate the effect of anti-tumor necrosis factor ( TNF ) therapy on bone mineral density ( BMD ) in patients with active ankylosing spondylitis ( AS ) with low BMD . Methods . Eighty-nine patients with active AS with low BMD were r and omly divided into either a study group or a control group . The study group received etanercept ( 50 mg/week ) or adalimumab ( 40 mg/2 week ) subcutaneously for 1 year . BMD of lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry , and bone turnover markers serum C telopeptide of type-I collagen ( sCTX ) and serum procollagen type-I N propeptide ( PINP ) were detected by ELISA at baseline and at end of study . Results . After 1 year , compared with baseline , there was a significant increase in spine and femoral neck BMD by a mean ± SD of 14.9 % ± 15.6 % ( p < 0.0001 ) and 4.7 % ± 7.9 % ( p < 0.0001 ) in the study group . In the control group , there was a significant decrease in spine and femoral neck BMD by a mean ± SD of −8.6 % ± 9.7 % ( p < 0.0001 ) and −9.8 % ± 11.5 % ( p < 0.0001 ) . Compared with baseline , sCTX was significantly decreased in the study group ( −40 % at 1 yr , p < 0.0001 ) , but bone-specific alkaline phosphatase and PINP increased ( 45.6 % , p < 0.0001 and 30.8 % , p < 0.0001 , respectively ) . Conclusion . In patients with active AS with low BMD , the spine and femoral neck BMD increased after anti-TNF therapy for 1 year , and it was accompanied by a significant decrease in bone resorption markers and an increase in bone formation markers Objective To evaluate the effect of secukinumab , an interleukin-17A inhibitor , on clinical signs and symptoms and radiographic changes through 2 years in patients with ankylosing spondylitis ( AS ) . Methods In the phase III MEASURE 1 study , patients were r and omised to receive intravenous secukinumab 10 mg/kg ( at baseline , week 2 and week 4 ) followed by subcutaneous secukinumab 150 mg ( intravenous 150 mg ; n=125 ) or 75 mg ( intravenous 75 mg ; n=124 ) every four weeks , or matched placebo ( n=122 ) . Placebo-treated patients were re-r and omised to subcutaneous secukinumab 150 or 75 mg from week 16 . Clinical efficacy assessment s included Assessment of SpondyloArthritis international Society 20 ( ASAS20 ) response rates through week 104 . Radiographic changes at week 104 were assessed using the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ) . Results 97 ( 77.6 % ) and 103 ( 83.1 % ) patients in the intravenous 150 mg and intravenous 75 mg groups , respectively , completed week 104 . In the full analysis set ( intent-to-treat ) , ASAS20 response rates at week 104 were 73.7 % and 68.0 % in the intravenous 150 mg and intravenous 75 mg groups , respectively . Among patients with evaluable X-rays who were originally r and omised to secukinumab ( n=168 ) , mean change in mSASSS from baseline to week 104 was 0.30±2.53 . Serious adverse events were reported in 12.2 % and 13.4 % of patients in the 150 mg and 75 mg groups , respectively . Conclusions Secukinumab improved AS signs and symptoms through 2 years of therapy , with no unexpected safety findings . Data from this study suggest a low mean progression of spinal radiographic changes , which will need to be confirmed in longer-term controlled studies . Trial registration number NCT01358175 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 OBJECTIVE To study the prevalence of osteoporosis ( OP ) and osteopenia in ankylosing spondylitis ( AS ) and to investigate the relationship between symptomatic and structural severity , the indices of bone turnover , and body composition . METHODS Eighty patients with AS were enrolled prospect ively : 52 men ( 65 % ) and 28 women , mean age 36.7 years + /- 11.5 ( range 18 - 67 ) ; they were studied clinical ly , radiologically , and by dual energy x-ray absorptiometry . Sixty-three underwent biological assessment of bone turnover markers . RESULTS OP and osteopenia as defined by the World Health Organization ( T score < -2.5 SD and between -1 and -2.5 SD , respectively ) were observed in 15 ( 18.7 % ) and 25 patients ( 31.2 % ) at the lumbar spine and in 11 ( 13.7 % ) and 33 patients ( 41.2 % ) at the femoral neck , respectively . Patients with OP had a lower body mass index ( BMI ) and fat mass percentage . There was a trend to a lower disease duration in patients with OP at the spine than in healthy subjects . Bone resorption markers ( urinary D-pyridinoline or C-telopeptide concentrations ) were increased in 34 patients ( 53.9 % ) . Bone turnover markers were positively correlated with C-reactive protein concentration and Larsen radiological hip score ; they were negatively correlated with Schober index and fat mass percentage . CONCLUSION ( 1 ) OP is frequent in AS and can be observed in early stages of the disease . ( 2 ) Patients with AS are more susceptible to develop OP when they have low BMI , low fat mass percentage , and active and severe disease . OP was observed in parallel with increased bone resorption |
10,569 | 31,147,987 | Conclusions Nicor and il can improve coronary microcirculation and left ventricular function of patients with AMI after PCI .
Interestingly , female patients may benefit more from nicor and il than male patients in improving heart function | Aims To study the effect of nicor and il on prognosis of patients with acute myocardial infa rct ion ( AMI ) undergoing percutaneous coronary intervention ( PCI ) . | BACKGROUND Nicor and il in conjunction with percutaneous coronary intervention ( PCI ) has been reported to reduce reperfusion injury events and improve cardiac function in patients with acute myocardial infa rct ion ( AMI ) . This multicenter study was undertaken to determine the effectiveness and optimal administration of nicor and il in AMI patients . METHODS AND RESULTS Ninety-two patients with first AMI were r and omly assigned to 1 of 3 groups : intracoronary administration of nicor and il ( Group A ) , combined intravenous and intracoronary administration of nicor and il ( Group B ) , and no nicor and il administration ( Group C ) . The primary endpoint was a composite of the incidence of reperfusion-induced arrhythmia , chest pain , and no-reflow/slow-reflow . The secondary endpoint was the combined rate of improvement in the Thrombolysis in Myocardial Infa rct ion frame count ( cTFC ) and ST resolution ( STR ) . A significant difference was observed in the primary endpoint for Group B as compared with Group C ( p<0.05 ) . In the meantime , a significant improvement was shown in the secondary endpoint for Group B compared with Group C ( p=0.04 and 0.006 for cTFC and STR , respectively ) . CONCLUSIONS Combined intravenous and intracoronary administration of nicor and il reduces reperfusion injury during PCI and improves the cTFC and STR in AMI , and appears to be preferable to intracoronary administration alone A major limitation of the rotational atherectomy ( RA ) procedure is the occurrence of the no-reflow/slow flow phenomenon and the optimal strategy is still evolving . Recent clinical studies have demonstrated the beneficial effects of nicor and il , an adenosine triphosphate (ATP)-sensitive potassium channel opener , on no-reflow in patients with acute myocardial infa rct ion . The purpose of this study was to evaluate the effect of nicor and il on no-reflow/slow flow phenomenon during RA procedures . Sixty-one patients who underwent RA of complex coronary lesions were r and omly divided into 2 groups : ( i ) nicor and il cocktail ( n=24 patients , 37 lesions ) and ( ii ) verapamil cocktail ( n=37 patients , 63 lesions ) . In each group , the drug cocktail mixed with pressurized saline was infused through the 4Fr Teflon sheath of the rotablator system during the RA procedure . In the nicor and il group , the drug cocktail consisted of 24 mg of nicor and il , 5 mg of nitroglycerin , and 10,000 U of heparin . In the verapamil group , the drug cocktail consisted of 10 mg of verapamil , 5 mg of nitroglycerin , and 10,000 U of heparin . Baseline and procedure characteristics did not differ between the 2 groups . RA was performed successfully , and death , Q-wave myocardial infa rct ion , or emergency coronary artery bypass surgery did not occur in any patients . The no-reflow/slow flow phenomenon was observed in 11/63 ( 17.4 % ) lesions of the verapamil group , but in only 1/37 ( 2.7 % ) lesions of the nicor and il group ( p=0.03 ) . No untoward complications were observed during nicor and il infusion . These data indicate that the intracoronary continuous infusion of nicor and il during RA procedures is easy and safe , and prevents no-reflow/slow flow phenomenon more effectively than infusion of verapamil BACKGROUND The objectives of this study were to evaluate the incidence of no-reflow as independent predictor of adverse events and to assess whether baseline pre-procedural treatment options may affect clinical outcomes . METHODS Data were derived from the ISACS-TC registry ( NCT01218776 ) from October 2010 to January 2015 . No-reflow was defined as post-PCI TIMI flow grade s 0 - 1 , in the absence of post-procedural significant ( ≥25 % ) residual stenosis , abrupt vessel closure , dissection , perforation , thrombus of the original target lesion , or epicardial spasm . The outcome measure was in-hospital mortality . RESULTS No-reflow was identified in 128 of 5997 patients who have undergone PCI ( 2.1 % ) . On multivariate analysis , patients with no-reflow were more likely to be older ( OR : 1.20 , 95 % CI : 1.01 - 1.44 ) , to have a history of hypercholesterolemia ( OR : 1.95 , 95 % CI : 1.31 - 2.91 ) and to be admitted with a diagnosis of STEMI ( OR : 2.96 , 95 % CI : 1.85 - 4.72 ) . Angiographic characteristics associated with no-reflow phenomenon were : stenosis ≥50 % of the right coronary artery , presence of multivessel disease and pre-procedural TIMI blood flow grade s 0 - 1 . No-reflow was highly predictive of in-hospital mortality ( 17.2 % vs. 4.2 % ; adjusted OR : 4.60 , 95 % CI : 2.61 - 8.09 ) . Administration of pre-procedural unfractioned heparin or 600 mg clopidogrel loading dose was associated with less incidence of no-reflow ( OR : 0.65 , 95 % CI : 0.43 - 0.99 and 0.61 , 95 % CI : 0.37 - 1.00 , respectively ) . Aspirin , enoxaparin , and 300 mg clopidogrel loading dose , did not significantly impact the occurrence of the no-reflow . CONCLUSIONS We found that pre-procedural administration of 600 mg loading dose of clopidogrel and /or unfractioned heparin is associated with reduced incidence of no-reflow OBJECTIVE Stress hyperglycemia increases the risk of mortality and poor outcomes in patients with acute myocardial infa rct ion ( AMI ) . We aim ed to assess effects of intravenous nicor and il administered before reperfusion on AMI patients with stress hyperglycemia . RESEARCH DESIGN AND METHODS This study consisted of 158 consecutive first AMI patients with stress hyperglycemia who underwent percutaneous coronary intervention ( PCI ) within 24 h from the onset . They were r and omly assigned to receive 12 mg of nicor and il ( n = 81 ) or a placebo ( n = 77 ) intravenously just before reperfusion . Stress hyperglycemia was defined as a blood glucose level > or = 10 mmol/l ( 180 mg/dl ) . We examined various aspects of epicardial flow and microvascular function as immediate data and major adverse cardiac events ( MACEs ) ( coronary heart disease death or unplanned readmission due to congestive heart failure ) as late-phase data . RESULTS The incidence of slow flow after PCI was lower in the nicor and il group ( 13.6 vs. 27.3 % , P < 0.04 ) . ST segment resolution > 50 % was observed in 70.4 and 53.2 % on nicor and il and placebo , respectively ( P < 0.03 ) . Patients treated with nicor and il had a lower peak creatine kinase level ( 3,137 + /- 2,577 vs. 4,333 + /- 3,608 , P < 0.02 ) . Upon Kaplan-Meier analysis , 5 years ' freedom from MACEs was 86.4 % in the nicor and il group and 74.0 % in the placebo ( P < 0.05 ) . CONCLUSIONS Adjunctive therapy with administration of intravenous nicor and il before reperfusion on AMI patients with stress hyperglycemia significantly improves epicardial flow and prevents the occurrence of severe microvascular reperfusion injury , result ing in better outcomes in these patients Nicor and il , an adenosine triphosphate – sensitive potassium channel opener , reduces plasma norepinephrine concentration in patients with ischemic heart disease . However , long-term effects on cardiac sympathetic nerve activity ( CSNA ) as evaluated by 123I-metaiodobenzylguanidine ( MIBG ) scintigraphy have not been determined for patients with acute myocardial infa rct ion ( AMI ) . Methods : We studied 40 patients with their first AMI who were treated with intravenous nicor and il before and after primary coronary angioplasty . After suspension of the initial intravenous nicor and il treatment , 20 patients were r and omized to receive oral nicor and il ( 15 mg/d ) ( group A ) and the other 20 patients received a placebo ( group B ) . All patients were also treated with an angiotensin-converting enzyme ( ACE ) inhibitor or β-blockers . The delayed heart-to-mediastinum count ratio ( H/M ratio ) , delayed total defect score ( TDS ) , and washout rate ( WR ) were determined from 123I-MIBG scintigraphy 3 wk and 6 mo after angioplasty . The left ventricular ( LV ) end-diastolic volume ( EDV ) , LV end-systolic volume ( ESV ) , and LV ejection fraction ( EF ) were determined by contrast left ventriculography , whereas plasma procollagen type III amino-terminal peptide ( PIIINP ) concentrations were also measured at the same time points . Results : Three weeks after angioplasty , TDS , H/M ratios , WR , LVEDV , LVESV , and LVEF were similar in both groups . After 6 mo , all of these parameters had improved in both groups . However , the extent of change in TDS was −9 ± 6 in group A and −5 ± 6 in group B ( P < 0.05 ) , whereas that in the H/M ratio was 0.15 ± 0.13 and 0.07 ± 0.11 ( P < 0.05 ) and that in the WR was −12 % ± 8 % and −5 % ± 11 % ( P < 0.05 ) . The extent of change in LVEDV , LVESV , and LVEF in group A tended to exceed that in group B , but these changes were not statistically significant . We found significant correlations between the percent change in PIIINP and that of TDS from baseline to 6 mo in group A ( r = 0.456 , P < 0.05 ) . Conclusion : Long-term nicor and il therapy can be more beneficial for CSNA and LV remodeling than short-term therapy in patients with AMI Background It has been reported that nicor and il restores blood flow to reperfused myocardium in patients with acute myocardial infa rct ion . However , whether nicor and il might decrease infa rct size remains unclear . The aim of this study was to assess the effect of nicor and il on infa rct size with thallium-201/ ® -methyl-p-iodophenyl pentadecanoic acid ( BMI PP ) dual-isotope single photon emission computed tomography . Methods A total of 62 patients were r and omly assigned to receive intravenous nicor and il ( 4 mg in 5 minutes at admission , immediately followed by 6mg/hr over a 24-hour period ) or placebo . All patients were divided into 4 groups : Group N-a , 16 patients with preexisting angina treated with nicor and il ; N-b , 15 patients without preexisting angina treated with nicor and il ; Ca , 14 patients with preexisting angina given placebo ; C-b , 17 patients without preexisting angina given placebo . Tl-201/ BMI PP imaging was performed in the 62 patients within 7 days after admission . Dual-isotope single photon emission computed tomographic images were quantified by severity index with a polar map . Results The BMI PP severity index was similar among the 4 groups . Only the thallium severity index in the N-a group was significantly less ( P < .05 ) . The ratio of the thallium severity index to that of BMI PP in the N-a group was significantly decreased compared with those of the other groups . Conclusion Nicor and il has a protective effect in patients with acute myocardial infa rct ion and preexisting angina treated with primary balloon angioplasty BACKGROUND Intravenous nicor and il infusion with percutaneous coronary intervention ( PCI ) has been reported to reduce reperfusion injury events and improve cardiac function in patients with acute myocardial infa rct ion ( MI ) . However , there is limited information on the use of intracoronary nicor and il . METHODS AND RESULTS In the present study , 73 patients with acute ST segment elevation MI undergoing PCI were r and omly assigned to the Nicor and il Group ( n=37 ) or the Control Group ( n=36 ) . The composite endpoints were the incidences of ventricular arrhythmia , no-reflow and slow flow . A significant difference in the composite endpoint was observed in the Nicor and il Group when compared with the Control Group ( p=0.037 ) . The occurrence of post Thrombolysis In Myocardial Infa rct ion ( TIMI ) grade 3 was significantly higher in the Nicor and il Group ( p=0.019 ) . Major adverse cardiac events during hospitalization and within 30 days of treatment were similar between the 2 groups . CONCLUSION Administration of intracoronary nicor and il reduced the occurrence of no-reflow , slow reflow , and reperfusion arrhythmia , and improved the myocardial perfusion grade , TIMI flow during PCI and improved clinical outcomes in patients with acute MI Introduction Prevention of the no-reflow phenomenon has a crucial role in primary percutaneous coronary intervention ( P-PCI ) procedures . Aim To assess the effects of early intracoronary administration of nicor and il ( NIC ) during P-PCI on myocardial microcirculation in patients with acute myocardial infa rct ion ( AMI ) . Material and methods A total of 120 patients with first acute anterior wall ST segment elevation myocardial infa rct ion who underwent P-PCI were r and omly divided into two groups : the NIC group ( A , n = 60 ) and the placebo group ( B , n = 60 ) . Before stent placement , NIC or normal saline was injected using a guiding catheter . The thrombolysis in myocardial infa rct ion ( TIMI ) grade , TIMI myocardial perfusion grade ( TMPG ) , resolution of ST segment elevation ( defined as > 50 % decrease in ST elevation ) 1 h after surgery , and 99Tcm-methoxyisobutyl isocyanide ( MIBI ) rest myocardial perfusion imaging ( MPI ) via single-photon emission computed tomography ( 99Tcm-MIBI SPECT ) findings 10 days after surgery were compared between the two groups . Results The number of patients who achieved TIMI grade 3 ( 96.67 % vs. 86.67 % ; p = 0.047 ) and TMPG 3 ( 95 % vs. 83.33 % ; p = 0.040 ) was higher in the NIC group than in the placebo group . Resolution of ST segment elevation occurred in 95 % and 81.67 % of the patients in the NIC and placebo groups , respectively ( p = 0.023 ) ; the MPI score of the two groups was 4.1 ±1.89 and 7.3 ±2.65 , respectively ( p = 0.014 ) . Conclusions Early coronary administration of NIC can significantly reduce the damage in the myocardial microcirculation caused by P-PCI and the myocardial infa rct size in patients with AMI Background This study aim ed to investigate intracoronary nicor and il treatment on the no-reflow phenomenon ( NRP ) during primary percutaneous coronary intervention ( PCI ) in patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) and to compare nicor and il with sodium nitroprusside . Material / Methods Patients with sustained acute STEMI who underwent primary PCI ( N=120 ) were r and omly assigned to three groups : the nicor and il-treated group ( N=40 ) had 2 mg of nicor and il injected into the coronary artery at 2 mm beyond the occlusion with balloon pre-dilation ; the sodium nitroprusside-treated group ( N=40 ) underwent the same procedure , but with 200 μg of sodium nitroprusside ; the control group ( N=40 ) received PCI and balloon pre-dilation only . Coronary angiography , incidence of NRP , hypotensive episodes , ST-segment resolution ( STR ) rate , levels of N-terminal pro-brain natriuretic peptide ( NT-proBNP ) , creatine kinase-MB ( CK-MB ) , cardiac troponin I ( cTnI ) , wall motion score index ( WMSI ) , and left ventricular ejection fraction ( LVEF ) were measured before and after primary PCI . Major adverse cardiovascular events ( MACEs ) post-PCI and at three-month follow-up were recorded . Results Patients in the sodium nitroprusside and nicor and il groups had significantly improved thrombolysis in myocardial infa rct ion ( TIMI ) scores , TIMI myocardial perfusion grade ( TMPG ) , and ST-segment elevation resolution ( STR ) ( P<0.05 ) , and a significantly lower incidence of NRP ( P=0.013 ) . The incidence of intraoperative hypotension in the sodium nitroprusside group was significantly greater than the nicor and il and control groups ( P=0.035 ) . Conclusions Patients with sustained acute STEMI undergoing primary PCI , treated with intracoronary nicor and il had a reduced incidence of the NRP , improved myocardial perfusion and cardiac function This study was design ed to assess the cardioprotective effect of intravenous nicor and il , a potassium channel opener , in preventing reperfusion injury in acute myocardial infa rct ion . Seventy patients were treated with placebo or nicor and il concomitant with reperfusion therapy in a prospect i ve , r and omized , double-blind fashion within 6 h after the onset of acute myocardial infa rct ion . Nicor and il was administered before reperfusion as a 2-mg bolus iv injection followed by continuous infusion of 2 - 6 mg/h for the next 3 h. Thirty-six patients ( 17 in the placebo group , 19 in the nicor and il group ) who demonstrated both complete occlusion of an infa rct -related vessel before treatment and successful reperfusion were included in the final analysis . No significant changes in left ventricular ejection fraction were observed between the immediate and chronic phases in each group . In the analysis of regional ventricular function , the placebo group did not show any significant change in regional chord shortening ( 26.8+/-8.2 vs 24.3+/-7.3 % , NS ) or hypocontractile perimeter ( 36.4+/-28.2 % vs 28.3+/-24.8 % , NS ) between immediate and chronic phase left ventriculograms . In contrast , in the nicor and il group , a significant increase in regional chord shortening ( 21.5+/-11.0 % vs 25.8+/-11.3 % , p<0.05 ) and a significant decrease in hypocontractile perimeter ( 33.3+/-19.6 % vs 25.6+/-24.3 % , p<0.05 ) were observed in the chronic phase left ventriculogram . Thus , nicor and il may be a useful adjunctive therapy for preserving myocardial contractile function in patients with acute myocardial infa rct ion undergoing reperfusion therapy Objective : To compare the effects of nicor and il ( a hybrid ATP sensitive potassium channel ( K+ATP channel ) opener/nitric oxide donor ) with those of isosorbide dinitrate ( ISDN ) on myocardial microcirculation and cardiac function in patients with acute myocardial infa rct ion ( AMI ) who had undergone reperfusion treatment by direct balloon angioplasty . Design : Double blind r and omised study . Patients : 60 patients with AMI in Killip class I. Interventions : Patients were assigned into two treatment groups : a nicor and il group ( n = 30 ) and an ISDN group ( n = 30 ) . Each drug was infused intravenously at 6 mg/h for 72 hours starting at admission and was administered directly to the treated coronary artery immediately after angioplasty . Results : Compared with ISDN , nicor and il more frequently caused recovery of ST segment elevation just after reperfusion ( 15 of 27 ( 55.5 % ) in the nicor and il group v 5 of 26 ( 19.2 % ) in the ISDN group , p = 0.006 ) . The nicor and il group had higher values of averaged peak velocity 40 minutes after reperfusion ( mean ( SD ) 24.8 ( 13.3 ) cm/s v 16.0 ( 11.1 ) cm/s , p = 0.045 ) and higher values of regional wall motion of the infa rct ed area three weeks after onset of AMI ( –1.78 ( 1.11 ) v –2.50 ( 1.04 ) SD/chord , p = 0.046 ) . Conclusions : A combination of nicor and il drip infusion starting before reperfusion and intracoronary injection immediately after reperfusion is more effective than a similarly performed infusion of ISDN in preserving myocardial microcirculation in the reperfused AMI area . The nicor and il regimen result ed in better left ventricular regional wall motion In this pilot study , we compared the infa rct and edema size in acute myocardial infa rct ion ( MI ) patients treated by nicor and il with those treated by nitrate , using cardiac magnetic resonance ( CMR ) imaging . Fifty-two acute MI patients who underwent emergency percutaneous coronary intervention ( PCI ) were enrolled , and were assigned to receive nicor and il or nitrate at r and om just before reperfusion . For the assessment of infa rct and edema areas , short-axis delayed enhancement ( DE ) and T2-weight ( T2w ) CMR images were acquired 6.1 ± 2.4 days after the onset of MI . A significant correlation was observed between the peak creatinine kinase ( CK ) level and the infa rct size on DE CMR ( r = 0.62 , p < 0.05 ) , as well as the edema size on T2w CMR ( r = 0.70 , p < 0.05 ) in patients treated by nicor and il ( 28 patients ) . A similar correlation was seen between the peak CK level and the infa rct size on DE CMR ( r = 0.84 , p < 0.05 ) , as well as the edema size on T2w CMR ( r = 0.84 , p < 0.05 ) in patients treated by nitrate ( 24 patients ) . The maximum CK level was significantly lower in patients treated by nicor and il rather than nitrate ( 1991 ± 1402 , 2785 ± 2121 IU/L , respectively , p = 0.03 ) . Both the edema size on T2w CMR and the infa rct size on DE CMR were significantly smaller in patients treated by nicor and il rather than nitrate ( 17.7 ± 9.9 , 21.9 ± 13.7 % ; p = 0.03 , 10.3 ± 6.0 , 12.7 ± 6.9 % , p = 0.03 , respectively ) . The presence and amount of microvascular obstruction were significantly smaller in patients treated by nicor and il rather than nitrate ( 39.2 , 64.7 % ; p = 0.03 ; 2.2 ± 1.3 , 3.4 ± 1.5 cm2 ; p = 0.02 , respectively ) . Using CMR imaging , we demonstrated that the complementary use of intravenously and intracoronary administered nicor and il during PCI favorably acts more on the damaged myocardium after MI than nitrate . We need a further powered prospect i ve study on the use of nicor and il Background —Intravenous nicor and il , a hybrid compound of ATP-sensitive potassium channel opener and nitric oxide donor , has been reported to ameliorate early functional and clinical problems in patients with acute myocardial infa rct ion . However , its effects on the late phase remain unclear . Methods and Results —This follow-up study to 5 years of a r and omized , double-blinded trial was conducted among 368 patients with first ST-segment – elevation myocardial infa rct ion undergoing percutaneous coronary intervention ( PCI ) . They were r and omly assigned to receive 12 mg of nicor and il or a placebo intravenously just before reperfusion . We analyzed incidence of cardiovascular death or rehospitalization for congestive heart failure after PCI as well as various aspects of epicardial flow and microvascular function . Mean follow-up was 2.4 years ( SD , 1.4 ) . A total of 12 ( 6.5 % ) patients receiving nicor and il and 30 ( 16.4 % ) receiving placebo had cardiovascular death or hospital admission for congestive heart failure ( hazard ratio , 0.39 ; 95 % CI , 0.20 to 0.76 ; P=0.0058 ) . Postprocedural TIMI 3 flow was obtained in 89.7 % of the nicor and il group and in 81.4 % of the placebo ( hazard ratio , 1.99 ; 95 % CI , 1.09 to 3.65 ; P=0.025 ) . Corrected TIMI frame count was furthermore lower in the nicor and il group ( 21.0±9.1 versus 25.1±14.1 ; P=0.0009 ) . ST-segment resolution > 50 % was observed in 79.5 % and 61.2 % of the nicor and il and placebo groups , respectively ( hazard ratio , 2.45 ; 95 % CI , 1.54 to 3.90 ; P=0.0002 ) . Conclusions —The addition of intravenous nicor and il to PCI leads to beneficial clinical outcomes and prevents cardiovascular events of long duration and death in patients with ST-segment – elevation myocardial infa rct ion Published reports have indicated that prodromal angina before acute myocardial infa rct ion ( AMI ) is associated with better outcomes and that nicor and il has cardioprotective effects on ischemic hearts . We compared cardioprotective effects of intravenous nicor and il with preconditioning effects by prodromal angina in patients with AMI who underwent percutaneous coronary intervention ( PCI ) . In total , 368 patients with first ST-elevation AMI who underwent PCI were r and omly assigned to receive nicor and il 12 mg or a placebo intravenously just before PCI . Subjects were assigned to 1 of 4 groups : 52 patients with prodromal angina were given placebo , 129 patients without prodromal angina were given nicor and il , 56 patients with prodromal angina were given nicor and il , and 131 patients without prodromal angina were given placebo . Coronary microvascular impairment after PCI was prevented at similar frequencies in groups with prodromal angina and groups on nicor and il . Five-year rates for freedom from major cardiac events were similar across groups with prodromal angina given placebo , without prodromal angina given nicor and il , and with prodromal angina given nicor and il ( 92.3 % , 93.8 % , and 92.9 % , respectively ) but were significantly lower in the group without prodromal angina given placebo ( 80.2 % , p = 0.0019 , 0.044 , and 0.042 , respectively ) . In conclusion , intravenous administration of nicor and il before PCI exerts pharmacologic cardioprotective effects similar to ischemic preconditioning in patients with AMI OBJECTIVES We assessed whether the intravenous administration of nicor and il , an adenosine triphosphate (ATP)-sensitive K+ channel opener , exerts beneficial effect on microvascular function and functional and clinical outcomes in patients with acute myocardial infa rct ion ( AMI ) . BACKGROUND Experimental studies documented that ATP-sensitive K+ channel opener exerts cardioprotection after prolonged ischemia . METHODS We r and omly divided 81 patients with a first anterior AMI into two groups , nicor and il ( n = 40 ) and control groups ( n = 41 ) . All patients received successful coronary angioplasty within 12 h after the symptom onset and underwent myocardial contrast echcardiography ( MCE ) with the intracoronary injection of sonicated microbubbles . In the nicor and il group , we injected 4 mg of nicor and il followed by the infusion at 6 mg/h for 24 h and by oral nicor and il ( 15 mg/day ) . RESULTS The improvement in regional left ventricular function , wall motion score and regional wall motion was significantly better in the nicor and il group then in the control group . Intractable congestive heart failure , malignant ventricular arrhythmia and pericardial effusion were more frequently found in the control group than in the nicor and il group ( 15 % vs. 37 % , 5 % vs. 20 % and 8 % vs. 37 % , p < 0.05 , respectively ) . The frequency of sizable MCE no reflow phenomenon was significantly lower in the nicor and il group than in the control group ( 15 % vs. 33 % , p < 0.05 ) . CONCLUSIONS Intravenous nicor and il in conjunction with coronary angioplasty is associated with better functional and clinical outcomes compared to angioplasty alone in patients with an anterior AMI . Myocardial contrast echocardiography findings imply that an improvement in microvascular function with nicor and il may be attributable to this better outcome Purpose In patients undergoing primary percutaneous coronary intervention ( PCI ) for the treatment of ST-segment elevation myocardial infa rct ion ( STEMI ) , coronary microvascular dysfunction is associated with poor prognosis . Coronary microvascular resistance is predominantly regulated by ATP-sensitive potassium ( KATP ) channels . The aim of this study wasto clarify whether nicor and il , a hybrid KATP channel opener and nitric oxide donor , may be a good c and i date for improving microvascular dysfunction even when administered after primary PCI . Methods We compared the beneficial effects of nicor and il and nitroglycerin on microvascular function in 60 consecutive patients with STEMI . After primary PCI , all patients received single intracoronary administrations of nitroglycerin ( 250 μg ) and nicor and il ( 2 mg ) in a r and omized order ; 30 received nicor and il first , while the other 30 received nitroglycerin first . Microvascular dysfunction was evaluated with the index of microcirculatory resistance ( IMR ) , defined as the distal coronary pressure multiplied by the hyperemic mean transit time . Results As a first administration , nicor and il decreased IMR significantly more than did nitroglycerin ( median [ interquartile ranges ] : 10.8[5.2–20.7 ] U vs. 2.1[1.0–6.0 ] U , p = 0.0002).As a second administration , nicor and il further decreased IMR , while nitroglycerin did not ( median [ interquartile ranges ] : 6.0[1.3–12.7 ] U vs. −1.4[−2.6 to 1.3 ] U , p < 0.0001 ) . The IMR after the second administration was significantly associated with myocardial blush grade , angiographic TIMI frame count after the procedure , and peak creatine kinase level . Conclusion Intracoronary nicor and il reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI , probably via its KATP channel-opening effect Objective : To investigate the effect of intracoronary administration of nicor and il prior to primary percutaneous coronary intervention ( PPCI ) on myocardial perfusion and short-term clinical outcomes in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) . Methods : A total of 158 patients with STEMI undergoing PPCI from January 2014 to December 2015 in Fuzhou General Hospital were enrolled consecutively in this prospect i ve controlled r and omized trial . Patients were assigned into three groups with r and om number table : the nicor and il group ( patients received intracoronary administration of 6 mg nicor and il after guide wire or balloon successfully crossed the target lesion , n=53 ) , the nitroglycerin group ( patients received intracoronary administration of 300 μg nitroglycerin after after guide wire or balloon successfully crossed the target lesion , n=52 ) and the control group ( patients received routine treatment , n=53 ) . The primary outcomes were myocardial perfusion , including the levels of corrected TIMI frame count ( cTFC ) , and the incidence of no reflow or slow flow after PPCI . The secondary outcomes included the incidence of major adverse cardiovascular events ( MACE ) during hospitalization ( all-cause death , reperfusion arrhythmia within 2 hours after PPCI , angina within 24 hours after PPCI , new heart failure or worsening cardiac function , and repeat revascularization ) and within 3 months of follow-up ( all-cause death , nonfatal myocardial infa rct ion , repeat revascularization , post-infa rct ion angina , and re-hospitalization for congestive heart failure ) . Results : The age of enrolled patients was ( 62.9±11.3 ) years old , and 130 cases ( 82.3 % ) of them were male . The median time of symptom-onset to balloon was 4.50 ( 3.20 , 6.43 ) hours . There were significantly difference in cTFC immediately after PPCI((21.68±7.43)frames , (24.74±8.66)frames , and (27.06±10.40)frames ) , incidence of no reflow or slow flow after PPCI(5.7%(3/53 ) , 13.5%(7/52 ) , and 22.6%(12/53 ) ) , ST-segment resolution at 2 hours after procedure(90.6%(48/53 ) , 84.6%(44/52 ) , and 74.5%(38/53 ) ) , and reperfusion arrhythmia at 2 hours after procedure(15.1%(8/53 ) , 36.6%(19/52 ) , and 34.0%(18/53 ) ) among the 3 groups(P<0.01 or 0.05 ) . In the multivariate logistic regression models , intracoronary administration of nicor and il could lower the cTFC level ( OR=0.17 , 95%CI 0.10 - 0.41 , P=0.001 ) , acted as a protecting factor on lowering the incidence of no reflow or slow flow ( OR=0.13 , 95%CI 0.02 - 0.96 , P=0.045 ) and reperfusion arrhythmia ( OR=0.26 , 95%CI 0.09 - 0.74 , P=0.012 ) , as well as facilitating the ST-segment resolution at 2 hours after procedure ( OR=4.62 , 95%CI 1.14 - 18.82 , P=0.033 ) . However , observed parameters were similar between intracoronary administration of nitroglycerin group compared with control group ( all P>0.05 ) . MACE within 3 months of follow-up were similar among the 3 groups(all P>0.05 ) . Conclusion : Intracoronary administration of nicor and il prior to balloon dilation can significantly improve the myocardial perfusion and reduce the occurrence of reperfusion arrhythmia during PPCI for STEMI , but does not affect the short-term prognosis in STEMI patients BACKGROUND Early reperfusion therapy improves the clinical outcomes of patients with acute myocardial infa rct ion ( AMI ) , but benefits are limited by reperfusion injury in some patients . We examined the effect of nicor and il , a hybrid of K(ATP ) channel opener and nicotinamide nitrate , on reactive oxygen species ( ROS ) formation and clinical outcomes after primary percutaneous coronary intervention ( PCI ) for AMI . METHODS Fifty-eight patients with AMI were r and omized into control ( n = 25 ) and nicor and il pretreatment groups ( n = 33 ) . In the nicor and il group , nicor and il ( 4 mg as a bolus injection followed by constant infusion at 8 mg/hour for 24 hours ) was administered just after admission . ROS formation was assessed by measuring urinary excretion of 8-epi-prostagl and in F2alpha ( PGF2alpha ) and compared between the 2 groups . Cardiac function and the incidence of reperfusion injury and cardiac events were also compared . RESULTS Urinary 8-epi-PGF2alpha excretion was increased 2-fold at 60 to 90 minutes after PCI in the control group , whereas it was unchanged after PCI in the nicor and il group ( P < .0001 between the 2 groups ) . The incidence of no-reflow phenomenon was lower in the nicor and il group than in the control group . Left ventricular ejection fraction and cardiac index at 6 months were greater in the nicor and il group than in controls . Plasma brain natriuretic peptide level at 6 months was lower in the nicor and il group . Incidences of inhospital cardiac events and rehospitalization were lower in the nicor and il group than in controls . CONCLUSIONS Nicor and il improves cardiac function and clinical outcomes in patients with AMI . Suppression of ROS formation may be involved in the mechanism Background Nicor and il ( NCR ) has been reported to have cardioprotective effects in patients with AMI . And collateral flow and TIMI flow are also important determinants of final salvaged myocardium in patients with AMI . There is no evidence as to whether TIMI or collateral flow modifies the cardioprotective effects of NCR in patients with AMI . Methods and Results We studied 68 initial AMI patients without restenosis which was defined as 50 % diameter reduction of the intervention site in the chronic period . On initial CAG , 41 patients with poor flow ( collateral : Rentrop 0 or 1 and TIMI 0 or 1 ) were NCR/Non-NCR = 20/21 . Twenty-seven patients with good flow ( collateral : Rentrop 2 or 3 or TIMI 2 or 3 ) were NCR/Non-NCR = 13/14 . NCR was administered intravenously ( 4 mg ) via intracoronary injection ( 2 mg ) or continuously ( 4 mg/h).99mTc-tetrofosmin ( TF ) and 123I- BMI PP SPECT were performed in the subacute and chronic ( 6 Mo ) periods . In 20 SPECT segments , summed defect scores ( TDS ) and regional wall motion ( WMS:-1 = dyskinesis ∼ 4 = normal ) of AMI segments using TF-QGS were estimated . In poor flow patients , the following values for NCR patients were higher ( p < 0.05 ) than for Non-NCR patients in the improvement degree of TDS ( BMI PP ) ( NCR : 6.5 ± 3.9 vs. Non-NCR : 4.0 ± 3.4 ) , the improvement degree of TDS ( TF ) ( NCR : 5.7 ± 4.6 vs. Non-NCR : 2.2 ± 4.6 ) , and delta WMS ( NCR : 1.4 ± 1.1 vs. Non-NCR : 0.9 ± 1.0 ) . In good flow patients , the following values for NCR patients were better ( p < 0.05 ) than for Non-NCR patients in TDS ( BMI PP ) ( subacute ) ( NCR : 9.9 ± 5.2 vs. Non-NCR : 16.5 ± 10.4 ) and ( chronic ) ( NCR : 5.1 ± 5.2 vs. Non-NCR : 12.4 ± 8.5 ) , WMS ( subacute ) ( NCR : 1.7 + 1.3 vs. Non-NCR : 1.0 ± 1.0 ) , and WMS ( chronic ) ( NCR : 3.0 ± 1.5 vs. Non-NCR : 2.1 ± 1.3 ) . Conclusion We conclude that the cardioprotective effects of nicor and il administration are observable in both AMI patients with poor collateral and TIMI flow and good flow before reperfusion therapy In acute inferior myocardial infa rct ion ( AIM I ) , numerous conventional drugs that are used to improve the myocardial microcirculation can significantly reduce blood pressure ( BP ) and coronary perfusion pressure , aggravate bradyarrhythmia and cause a deterioration in the hemodynamic state of the whole body , which greatly limits the application of these drugs in clinical setting s. The aim of the present study was to assess the effect of anisodamine and nicor and il regimens on the prevention of no-reflow ( NR ) and the amelioration of myocardial reperfusion in patients with AIM I undergoing primary percutaneous coronary intervention ( PCI ) . A total of 104 consecutive patients with AIM I were included in this study and r and omly assigned to one of four groups : A ( control group ) , B ( anisodamine group ) , C ( nicor and il group ) and D ( anisodamine and nicor and il group ) . Patients underwent PCI via transradial artery access and the angiographic results were evaluated . Coronary diastolic BP ( DBP ) and systolic and mean BPs were measured by invasive catheterization . The primary end-point was a post-PCI Thrombolysis In Myocardial Infa rct ion ( TIMI ) myocardial perfusion grade ( TMPG ) of 3 . Composite end-points ( mortality + new MI + target vessel revascularization ) were evaluated during the hospital stay and 30 days after discharge . Following the procedure , the proportion of patients achieving TMPG 3 was significantly higher in group D than that in the other groups ( P=0.014 ) ; furthermore , the incidence of a postprocedural TIMI score of 3 was the highest in group D. Three days after the procedure , the peak creatine kinase-MB and cardiac troponin I levels were the lowest and the left ventricular ejection fraction was the highest in group D. A thrombus score of 3/4 and low DBP were the independent risk factors for poor myocardial reperfusion ( expressed as TMPG < 3 ) , while 2 mg anisodamine plus 2 mg nicor and il prior to PCI was protective for optimal myocardial reperfusion following the procedure . The combination of anisodamine and nicor and il can effectively ameliorate myocardial reperfusion and protect cardiac function in patients with AIM I undergoing primary PCI BACKGROUND Nicor and il , an adenosine triphosphate-sensitive potassium channel opener , improves left ventricular ( LV ) remodeling after myocardial infa rct ion in rat models . However , the effects of chronic nicor and il therapy on cardiac sympathetic nerve activity in patients with ischemic cardiomyopathy have not been determined . METHODS Thirty-six patients with ischemic cardiomyopathy ( LV ejection fraction [ LVEF ] < 40 % ) who underwent successful revascularization procedure before 6 months were treated by st and ard conventional therapy . Eighteen patients were r and omized to additionally receive nicor and il ( 15 mg/d ) , whereas the other 18 patients received isosorbide mononitrate ( 40 mg/d ) . The delayed heart-to-mediastinum count ratio ( H/M ratio ) , delayed total defect score ( TDS ) , and washout rate ( WR ) were determined from (123)I-meta-iodobenzylguanidine ( MIBG ) scintigraphy before and 6 months after treatment . Left ventricular end-diastolic volume ( LVEDV ) and LVEF were determined by echocardiography . RESULTS Total defect score , H/M ratio , WR , LVEDV , and LVEF at baseline were similar for both groups . After treatment , in patients receiving nicor and il , TDS decreased from 50 + /- 6 to 40 + /- 11 ( P < .005 ) , H/M ratio increased from 1.68 + /- 0.23 to 1.79 + /- 0.26 ( P = .005 ) , and WR decreased from 46 % + /- 9 % to 40 % + /- 12 % ( P < .005 ) . In addition , LVEDV decreased from 178 + /- 31 to 157 + /- 30 mL ( P < .0005 ) , and LVEF increased from 33 % + /- 6 % to 39 % + /- 7 % ( P < .05 ) . In patients receiving isosorbide mononitrate , no significant changes were observed in these parameters . Moreover , there was a significant correlation between the percent change of LVEF and that of TDS from baseline to 6 months in the patients receiving nicor and il ( r = -0.569 , P < .05 ) . CONCLUSIONS The present study demonstrates improvements in cardiac (123)I-MIBG scintigraphic and echocardiographic parameters with nicor and il treatment . These findings indicate that nicor and il can improve cardiac sympathetic nerve activity and LV function in patients with ischemic cardiomyopathy BACKGROUND It has been reported that both nicor and il and magnesium have a cardioprotective effect in experimental ischemia - reperfusion models . In the present study , the cardioprotective effects of nicor and il and magnesium as an adjunct to reperfusion therapy in patients with acute myocardial infa rct ion ( AMI ) were compared . METHODS AND RESULTS Forty consecutive patients with AMI caused by occlusion of anterior descending coronary artery were r and omized into 3 groups : ( 1 ) Group N : nicor and il was given as 4 mg iv and 4 mg ic before reperfusion , followed by continuous infusion at 4 mg/h for 24 h ; ( 2 ) Group M : magnesium was administered at 10 mmol iv before reperfusion , followed by continuous infusion at 0.4 mmol/h for 24 h ; and ( 3 ) Group C : neither nicor and il nor magnesium was given . Left ventriculography was performed immediately after reperfusion and 3 months later . There was no significant change in regional wall motion ( RWM ) in either Group C or M , whereas that of group N improved significantly . The change in RWM in Group N was significantly greater than in Group C ( Group N : 0.92+/-0.92 , Group M : 0.44+/-0.80 , Group C : -0.01+/-0.65 , p<0.05 ) . CONCLUSIONS The early administration of nicor and il as an adjunct to reperfusion is useful for cardioprotection in AMI , but magnesium is not INTRODUCTION It has been found that nicor and il can attenuate myocardial no-reflow . However , the exact cause of this beneficial effect has remained unclear . We investigated whether the beneficial effect of nicor and il on myocardial no-reflow could be partly due to its protection against endothelial dysfunction . METHODS Ligation area and area of no-reflow were determined echocardiographically and pathologically in sixty-two animals r and omized into 7 study groups : 9 controls , 9 nicor and il-treated , 8 glibenclamide ( K(ATP ) channel blocker)-treated , 10 N(G)-monomethyl-L-arginine ( L-NMMA , nonselective nitric oxide synthase antagonist)-treated , 10 nicor and il and glibenclamide-treated , 8 nicor and il and L-NMMA-treated and 8 sham-operated . The acute myocardial infa rct ion and reperfusion model was created with one 3-h occlusion of the left anterior descending coronary artery followed by 2 h of reperfusion . Constitutive nitric oxide synthase ( cNOS ) activity and inducible nitric oxide synthase ( iNOS ) activity were also quantified . RESULTS Compared with the control group , nicor and il significantly improved ventricular function , increased coronary blood flow volume ( P<0.01 ) , decreased area of no-reflow and reduced necrosis area . Nicor and il also increased the cNOS activity and decreased iNOS activity ( P<0.05 ) . L-NMMA and glibenclamide abrogated the effects of nicor and il on ventricular function , coronary blood flow volume , area of no-reflow , necrosis area and cNOS activity , but not iNOS activity . CONCLUSIONS The beneficial effect of nicor and il on myocardial no-reflow could be due to its protection of endothelial function via the activation of K(ATP ) channel |
10,570 | 26,403,335 | The available evidence from RCTs is insufficient to establish the relative effectiveness of the various interventions used in the rehabilitation of adults with fractures of the distal radius . | BACKGROUND Fracture of the distal radius is a common clinical problem , particularly in older people with osteoporosis .
There is considerable variation in the management , including rehabilitation , of these fractures .
This is an up date of a Cochrane review first published in 2002 and last up date d in 2006 .
OBJECTIVES To examine the effects of rehabilitation interventions in adults with conservatively or surgically treated distal radial fractures . | Objective To study the effect of an incident wrist fracture on functional status in women enrolled in the Study of Osteoporotic Fractures . Design Prospect i ve cohort study . Setting Baltimore , Minneapolis , Portl and , and the Monongahela valley in Pennsylvania , USA Participants 6107 women aged 65 years and older without previous wrist or hip fracture recruited from the community between September 1986 and October 1988 . Main outcome measure Clinical ly important functional decline , defined as a functional deterioration of 5 points in five activities of daily living each scored from 0 to 3 ( equivalent to one st and ard deviation decrease in functional ability ) . Results Over a mean follow-up of 7.6 years , 268 women had an incident wrist fracture and 41 ( 15 % ) of these developed clinical ly important functional decline . Compared with women without wrist fractures , those with incident wrist fractures had greater annual functional decline after adjustment for age , body mass index , and health status . Occurrence of a wrist fracture increased the odds of having a clinical ly important functional decline by 48 % ( odds ratio 1.48 , 95 % confidence interval 1.04 to 2.12 ) , even after adjustment for age , body mass index , health status , baseline functional status , lifestyle factors , comorbidities , and neuromuscular function . Conclusions Wrist fractures contribute to clinical ly important functional decline in older women BACKGROUND There are relatively few studies in the literature that specifically evaluate accelerated rehabilitation protocol s for distal radial fractures treated with open reduction and internal fixation ( ORIF ) . The purpose of this study was to compare the early postoperative outcomes ( at zero to twelve weeks postoperatively ) of patients enrolled in an accelerated rehabilitation protocol with those of patients enrolled in a st and ard rehabilitation protocol following ORIF for a distal radial fracture . We hypothesized that patients with accelerated rehabilitation after volar ORIF for a distal radial fracture would have an earlier return to function compared with patients who followed a st and ard protocol . METHODS From November 2007 to November 2010 , eighty-one patients with an unstable distal radial fracture were prospect ively r and omized to follow either an accelerated or a st and ard rehabilitation protocol after undergoing ORIF with a volar plate for a distal radial fracture . Both groups began with gentle active range of motion at three to five days postoperatively . At two weeks , the accelerated group initiated wrist/forearm passive range of motion and strengthening exercises , whereas the st and ard group initiated passive range of motion and strengthening at six weeks postoperatively . Patients were assessed at three to five days , two weeks , three weeks , four weeks , six weeks , eight weeks , twelve weeks , and six months postoperatively . Outcomes included Disabilities of the Arm , Shoulder and H and ( DASH ) scores ( primary outcome ) and measurements of wrist flexion/extension , supination , pronation , grip strength , and palmar pinch . RESULTS The patients in the accelerated group had better mobility , strength , and DASH scores at the early postoperative time points ( zero to eight weeks postoperatively ) compared with the patients in the st and ard rehabilitation group . The difference between the groups was both clinical ly relevant and statistically significant . CONCLUSIONS Patients who follow an accelerated rehabilitation protocol that emphasizes motion immediately postoperatively and initiates strengthening at two weeks after volar ORIF of a distal radial fracture have an earlier return to function than patients who follow a more st and ard rehabilitation protocol . LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence OBJECTIVE To examine the relative effectiveness of ice therapy and /or pulsed electromagnetic field in reducing pain and swelling after the immobilization period following a distal radius fracture . METHODS A total of 83 subjects were r and omly allocated to receive 30 minutes of either ice plus pulsed electromagnetic field ( group A ) ; ice plus sham pulsed electromagnetic field ( group B ) ; pulsed electromagnetic field alone ( group C ) , or sham pulsed electromagnetic field treatment for 5 consecutive days ( group D ) . All subjects received a st and ard home exercise programme . A visual analogue scale was used for recording pain ; volumetric displacement for measuring the swelling of the forearm ; and a h and -held goniometer for measuring the range of wrist motions before treatment on days 1 , 3 and 5 . RESULTS At day 5 , a significantly greater cumulative reduction in the visual analogue scores as well as ulnar deviation range of motion was found in group A than the other 3 groups . For volumetric measurement and pronation , participants in group A performed better than subjects in group D but not those in group B. CONCLUSION The addition of pulsed electromagnetic field to ice therapy produces better overall treatment outcomes than ice alone , or pulsed electromagnetic field alone in pain reduction and range of joint motion in ulnar deviation and flexion for a distal radius fracture after an immobilization period of 6 weeks Fractures of the proximal humerus , forearm , and wrist account for approximately one third of total osteoporotic fractures in the elderly . Several risk factors for these fractures were evaluated in this prospect i ve study of 739 men and 1,105 women aged > or = 60 years in Dubbo , Australia . During follow-up ( 1989 - 1996 ) , the respective incidences of humerus and of forearm and wrist fractures , per 10,000 person-years , were 22.6 and 33.8 for men and 54.8 and 124.6 for women . Independent predictors of humerus fracture were femoral neck bone mineral density ( FNBMD ) ( relative risk ( RR ) = 2.3 , 95 % confidence interval ( CI ) : 1.2 , 4.5 ) in men and FNBMD ( RR = 2.4 , 95 % CI : 1.7 , 3.5 ) and height loss ( RR = 1.1 , 95 % CI : 1.0 , 1.2 ) in women . For forearm and wrist fractures , risk factors were FNBMD ( men : RR = 1.5 , 95 % CI : 1.0 , 2.3 ; women : RR = 1.5 , 95 % CI : 1.2 , 1.9 ) and height loss ( men : RR = 1.2 , 95 % CI : 1.0 , 1.3 ; women : RR = 1.1 , 95 % CI : 1.0 , 1.2 ) . In addition , dietary calcium ( men : RR = 2.0 , 95 % CI : 1.0 , 3.6 ) and a history of falls ( women : RR = 1.9 , 95 % CI : 1.4 , 2.6 ) were also significant . These data suggest that elderly men and women largely share common risk factors for upper limb fractures and that FNBMD is the primary risk factor Background Distal radius fractures are among the most common fractures and account for approximately one-sixth of all fractures diagnosed . Therapy results after distal radius fracture , especially of elderly patients , are often suboptimal . The inevitable immobilization for several weeks leads to reduction in range of motion , deterioration of muscle strength , malfunction of fine motor skills as well as changes of motor and sensory representations in the brain . Currently , there are no strategies to counteract these immobilization problems . The overall aim of the study is to investigate the therapeutic potential of motor-cognitive approaches ( mental practice or mirror therapy ) on h and function after wrist fracture . Methods / Design This study is a controlled , r and omized , longitudinal intervention study with three intervention groups . One experimental group imagines movements of the fractured upper extremity without executing them ( mental practice ) . The second experimental group receives a mirror therapy program consisting of the performance of functional movement synergies using the unaffected forearm , wrist , and h and . The control group completes a relaxation training regime . Additionally , all patients receive usual care by the general practitioner . We include women aged 60 years and older having a distal radius fracture and sufficient cognitive function . All groups are visited at home for therapy sessions 5 times per week for the first 3 weeks and 3 times per week for weeks 4 to 6 . Measurements are taken at therapy onset , and after 3 , 6 and 12 weeks . The primary outcome measure will assess upper extremity functioning ( Patient-Rated Wrist Evaluation [ PRWE ] ) , while secondary outcome measures cover subjective wrist function ( Disabilities of the Arm and Shoulder ; [ DASH ] , objective impairment ( range of motion , grip force ) and quality of life ( EuroQol-5D , [ EQ5D ] ) . Discussion Results from this trial will contribute to the evidence on motor-cognitive approaches in the early therapy of distal radius fractures . Trial registration The trial is registered at Clinical Trials.gov with registration number NCT01394809 and was granted permission by the Medical Ethical Review Committee of the University of Tübingen in June 2011 Abstract Colles ’ fracture patients who received physiotherapy immediately following cast removal were compared with patients who received no active therapy following cast removal in a prospect i ve r and omised study . Patients who attended physiotherapy achieved significantly greater increases in wrist extension and grip strength after 6 weeks compared to patients who received no active therapy OBJECTIVES to describe changes in physical functioning after fall-related injuries to the limbs in independently living older people . DESIGN prospect i ve cohort study , including a pre-injury assessment and post-injury assessment s at 8 weeks and 5 and 12 months . SETTING the study is part of the larger , population -based prospect i ve and longitudinal Groningen Longitudinal Aging Study on the determinants of health-related quality of life of people aged 57 and over , who are living independently in the north of the Netherl and s. SUBJECTS 171 patients who sustained injuries at various sites on the limbs and who had completed all four assessment s ( 66 % of the eligible population ) . Patients were grouped according to injury site . OUTCOME MEASURE self-reported grade s of difficulties with performing basic and instrumental activities of daily living as measured by the Groningen Activity Restriction Scale . RESULTS 1 year after the injury , pre-injury ( mean ) levels of functioning were not regained in any of the groups studied . However , only those with fractures of the wrist or hip experienced a substantial decrease in ability to perform basic and instrumental activities of daily living between baseline and the final assessment . Furthermore , of the 44 subjects with wrist fractures , seven ( 15.9 % ) needed help with at least one relevant activity at baseline and 18 ( 40.9 % ) at 12 months . Of the 34 subjects with hip fractures , four ( 11.8 % ) needed help with at least one activity at baseline and 18 ( 52.9 % ) at 12 months . Practically no changes were found in any of the groups after 5 months post-injury . CONCLUSIONS not only hip fractures , but also wrist fractures may reduce older people 's chances of remaining independent . Prospect s of further recovery are minimal 5 - 6 months after the injury OBJECTIVE To determine the effect of 2 different postoperative therapy approaches after operative stabilization of the wrist fractures : treatment by a physical therapist with 12 sessions and an unassisted home exercise program . DESIGN R and omized controlled cohort study . SETTING Hospital-based care , primary center of orthopedic surgery . PARTICIPANTS Volunteers ( N=48 ) with fractures of the distal radius after internal fixation with locking plates . There were 46 patients available for follow-up after exclusion of 2 participants due to physiotherapy sessions in excess of the study protocol . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Evaluation of grip strength using a Jamar dynamometer , range of motion ( ROM ) , and Patient Related Wrist Evaluation ( PRWE ) . RESULTS After a 6-week period of postoperative treatment , the patients ( n=23 ) performing an independent home exercise program using a training diary showed a significantly greater improvement of the functionality of the wrist . Grip strength reached 54 % ( P=.003 ) , and ROM in extension and flexion 79 % ( P<.001 ) of the uninjured side . Ulnar and radial abduction was also higher in this group . In contrast , patients who were treated by a physical therapist achieved grip strength equal to 32 % , and ROM in extension and flexion of 52 % of the uninjured side . Patients who were performing the home training after operation recorded an improved wrist function with a nearly 50 % lower value ( P<.001 ) in the PRWE score . CONCLUSIONS In the postoperative rehabilitation of wrist fractures , instructions in a home exercise program are an effective alternative to prescribed physical therapy treatment Background Fracture of the distal radius is a common clinical problem , particularly in older white women with osteoporosis . We report our work towards evidence -based and patient-centred care for adults with these injuries . Methods We developed a systematic programme of research that built on our systematic review of the evidence of effectiveness of treatment interventions for these fractures . We devised schemata showing ' typical ' care pathways and identified over 100 patient management questions . These depicted the more important decisions taken when progressing along each care pathway . We compiled a comprehensive document summarising the evidence available for each decision point from our review s of r and omised trials of treatment interventions . Using these documents , we undertook a formal and structured consultation process involving key players , including a patient representative , to obtain their views on the available evidence and to establish a research agenda . The result ing feedback was then processed and interpreted , using systematic methods . Results Some evidence from 114 r and omised trials was available for 31 of the 117 patient management questions . However , there was sufficient evidence to base some conclusions of effectiveness for particular interventions in only five of these . Though only 60 % of those approached responded , the responses received from the consultation group were often comprehensive and provided important insights into treatment practice and policy . There was a clear acceptance of the aims of the project and , aside from some suggestions for the more explicit inclusion of secondary prevention and management of complications , of the care pathways scheme . Though some respondents stressed that r and omised trials were not always appropriate , there was no direct overall criticism of the evidence document and underlying processes . We were able to identify important core themes that underpin management decisions and research from the feedback of the consultation exercise . Conclusions Overall , this project is an important advance towards evidence -based and patient-centred management of adults with distal radial fractures . It exposes the serious deficiency in the available evidence but also provides a template for further action . As well as being a valuable basis for viewing and informing current practice , the insights gained from this project should inform a future research agenda Forty patients participated in a study of the importance of early occupational therapy for the prognosis in stable Colles ' fractures . Seventeen patients were treated by an occupational therapist 1 - 3 days after the injury , and the need for appliances and home-care was estimated . Twenty-three patients completed the usual treatment . Five weeks after the injury , we found significantly ( p less than 0.05 ) better function of the h and in the 17 patients with early occupational therapy . This difference in function could not be found after 13 weeks . The rate of complications was the same in the two groups . The results indicate that contact with the occupational therapist shortly after the injury is valuable in patients with stable Colles ' fractures Background The Patient-rated Wrist Evaluation ( PRWE ) is a commonly used instrument in upper extremity surgery and in research . However , to recognize a treatment effect expressed as a change in PRWE , it is important to be aware of the minimum clinical ly important difference ( MCID ) and the minimum detectable change ( MDC ) . The MCID of an outcome tool like the PRWE is defined as the smallest change in a score that is likely to be appreciated by a patient as an important change , while the MDC is defined as the smallest amount of change that can be detected by an outcome measure . A numerical change in score that is less than the MCID , even when statistically significant , does not represent a true clinical ly relevant change . To our knowledge , the MCID and MDC of the PRWE have not been determined in patients with distal radius fractures . Questions / Purpose sWe asked : ( 1 ) What is the MCID of the PRWE score for patients with distal radius fractures ? ( 2 ) What is the MDC of the PRWE ? Methods Our prospect i ve cohort study included 102 patients with a distal radius fracture and a median age of 59 years ( interquartile range [ IQR ] , 48–66 years ) . All patients completed the PRWE question naire during each of two separate visits . At the second visit , patients were asked to indicate the degree of clinical change they appreciated since the previous visit . Accordingly , patients were categorized in two groups : ( 1 ) minimally improved or ( 2 ) no change . The groups were used to anchor the changes observed in the PRWE score to patients ’ perspectives of what was clinical ly important . We determined the MCID using an anchor-based receiver operator characteristic method . In this context , the change in the PRWE score was considered a diagnostic test , and the anchor ( minimally improved or no change as noted by the patients from visit to visit ) was the gold st and ard . The optimal receiver operator characteristic cutoff point calculated with the Youden index reflected the value of the MCID . Results In our study , the MCID of the PRWE was 11.5 points . The area under the curve was 0.54 ( 95 % CI , 0.37–0.70 ) for the pain subscale and 0.71 ( 95 % CI , 0.57−0.85 ) for the function subscale . We determined the MDC to be 11.0 points . Conclusions We determined the MCID of the PRWE score for patients with distal radius fractures using the anchor-based approach and verified that the MDC of the PRWE was sufficiently small to detect our MCID . Clinical Relevance We recommend using an improvement on the PRWE of more than 11.5 points as the smallest clinical ly relevant difference when evaluating the effects of treatments and when performing sample -size calculations on studies of distal radius fractures QUESTIONS Does the addition of cyclic pneumatic soft-tissue compression during the 6-week immobilisation period following fracture of the distal radius result in a faster recovery of muscle strength and joint range of motion ? Does it result in a larger recovery of muscle strength and joint range of motion immediately after the immobilisation period ( at 6 weeks ) or four weeks after the immobilisation period ( at 10 weeks ) ? DESIGN R and omised controlled trial with concealed allocation and assessor blinding . PARTICIPANTS 21 patients with fracture of the distal radius . INTERVENTION The experimental group received cyclic pneumatic soft-tissue compression during the 6-week immobilisation period whereas the control group received usual care . Both groups were instructed to actively make a fist 100 times per day during the 6-week immobilisation period and were given an exercise program during the 4-week post-immobilisation period . OUTCOME MEASURES Function was measured as power grip , pinch grip , key grip , and supination strength using dynamometry from Week 1 to 10 as well as wrist flexion/extension and forearm supination/pronation range of motion using goniometry from Week 6 to 10 . The outcome measures are presented as a percentage of the intact side . RESULTS The experimental group improved significantly faster than the control group in muscle strength from Week 1 to 10 ( p ? 0.001 ) but not in joint range of motion from Week 6 to 10 ( p > 0.05 ) . By Week 6 , the experimental group was 12 - 26 % stronger and had 8 - 14 % more range of motion than the control group . By Week 10 , the experimental group was 24 - 29 % stronger and had 10 - 15 % more range of motion than the control group . CONCLUSION The findings indicate that a larger clinical trial is warranted and should incorporate direct measures of fracture healing BACKGROUND In high-income countries , 6 % of all women will have sustained a fracture of the wrist ( distal radius ) by the age of 80 years and 9 % by the age of 90 years . Advances in orthopaedic surgery have improved the outcome for patients : many such fractures can be treated in a plaster cast alone , but others require surgical fixation to hold the bone in place while they heal . The existing evidence suggests that modern locking-plate fixation provides improved functional outcomes , but costs more than traditional wire fixation . METHODS In this multicentre trial , we r and omly assigned 461 adult patients having surgery for an acute dorsally displaced fracture of the distal radius to either percutaneous Kirschner-wire fixation or locking-plate fixation . The primary outcome measure was the Patient-Rated Wrist Evaluation © ( PRWE ) question naire at 12 months after the fracture . In this surgical trial , neither the patients nor the surgeons could be blind to the intervention . We also collected information on complications and combined costs and quality -adjusted life-years ( QALYs ) to assess cost-effectiveness . RESULTS The baseline characteristics of the two groups were well balanced and over 90 % of patients completed follow-up . Both groups of patients recovered wrist function by 12 months . There was no clinical ly relevant difference in the PRWE question naire score at 3 months , 6 months or 12 months [ difference at 12 months : -1.3 ; 95 % confidence interval ( CI ) -4.5 to 1.8 ; p=0.398 ] . There was no difference in the number of complications in each group and small differences in QALY gains ( 0.008 ; 95 % CI -0.001 to 0.018 ) ; Kirschner-wire fixation represents a cost-saving intervention ( -£727 ; 95 % CI -£588 to -£865 ) , particularly in younger patients . CONCLUSIONS Contrary to the existing literature , and against the increasing use of locking-plate fixation , this trial shows that there is no difference between Kirschner wires and volar locking plates for patients with dorsally displaced fractures of the distal radius . A Kirschner-wire fixation is less expensive and quicker to perform . TRIAL REGISTRATION Current Controlled Trials IS RCT N31379280 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 19 , No. 17 . See the NIHR Journals Library website for further project information OBJECTIVE To evaluate the effects of cross-education ( contralateral effect of unilateral strength training ) during recovery from unilateral distal radius fractures on muscle strength , range of motion ( ROM ) , and function . DESIGN R and omized controlled trial ( 26-wk follow-up ) . SETTING Hospital , orthopedic fracture clinic . PARTICIPANTS Women older than 50 years with a unilateral distal radius fracture . Fifty-one participants were r and omized and 39 participants were included in the final data analysis . INTERVENTIONS Participants were r and omized to st and ard rehabilitation ( Control ) or st and ard rehabilitation plus strength training ( Train ) . St and ard rehabilitation included forearm casting for 40.4±6.2 days and h and exercises for the fractured extremity . Nonfractured h and strength training for the training group began immediately postfracture and was conducted at home 3 times/week for 26 weeks . MAIN OUTCOME MEASURES The primary outcome measure was peak force ( h and grip dynamometer ) . Secondary outcomes were ROM ( flexion/extension ; supination/pronation ) via goniometer and the Patient Rated Wrist Evaluation question naire score for the fractured arm . RESULTS For the fractured h and , the training group ( 17.3±7.4 kg ) was significantly stronger than the control group ( 11.8±5.8 kg ) at 12 weeks postfracture ( P<.017 ) . There were no significant strength differences between the training and control groups at 9 ( 12.5±8.2 kg ; 11.3±6.9 kg ) or 26 weeks ( 23.0±7.6 kg ; 19.6±5.5 kg ) postfracture , respectively . Fractured h and ROM showed that the training group had significantly improved wrist flexion/extension ( 100.5 ° ±19.2 ° ) than the control group ( 80.2 ° ±18.7 ° ) at 12 weeks postfracture ( P<.017 ) . There were no significant differences between the training and control groups for flexion/extension ROM at 9 ( 78.0 ° ±20.7 ° ; 81.7 ° ±25.7 ° ) or 26 weeks ( 104.4 ° ±15.5 ° ; 106.0 ° ±26.5 ° ) or supination/pronation ROM at 9 ( 153.9 ° ±23.9 ° ; 151.8 ° ±33.0 ° ) , 12 ( 170.9 ° ±9.3 ° ; 156.7 ° ±20.8 ° ) or 26 weeks ( 169.4 ° ±11.9 ° ; 162.8 ° ±18.1 ° ) , respectively . There were no significant differences in Patient Rated Wrist Evaluation question naire scores between the training and control groups at 9 ( 54.2±39.0 ; 65.2±28.9 ) , 12 ( 36.4±37.2 ; 46.2±35.3 ) , or 26 weeks ( 23.6±25.6 ; 19.4±16.5 ) , respectively . CONCLUSIONS Strength training for the nonfractured limb after a distal radius fracture was associated with improved strength and ROM in the fractured limb at 12 weeks postfracture . These results have important implication s for rehabilitation strategies after unilateral injuries Abstract . In this r and omized trial , we enrolled 30 patients treated for a distal radius Colles ' type fracture . The fractures were reduced if necessary and fixed in a below-elbow plaster cast for 5 weeks . One group consisting of 14 patients received instructions for shoulder ; elbow and finger exercise and the other group consisting of 16 patients had occupational therapy . At 5 weeks , 3 and 9 months we measured the functional scores . There were no statistically significant differences between the groups at any time . It seems that for non-surgically treated patients with a distal radius fracture only instructions are necessary . Résumé . Etude r and omisée de 30 patients traités d'une fracture distale du radius de type Pouteaux-Colles . Les fractures furent réduites si nécessaire et fixées dans une manchette plâtrée durant 5 semaines . L'un des groupes était constitué de 14 patients qui avaient reçu des instructions d'exercices pour l'épaule , le coude et les doigts . L'autre groupe était constitué de 16 patients qui ont bénéficié d'une ergothérapie . Une évaluation a été faite après 5 semaines , 3 et 9 mois . Il n'avait aucune différence significative entre les 2 groupes en aucune période . Il semble ainsi suffisant , dans les fractures distales du radius traitées orthopédiquement , d'instruire les patients en vue d'une autoréeducation BACKGROUND The use of orthoses is a question able rehabilitation method for patients with the distal radius fracture at typical site . The aim of this study was to compare the effects of the rehabilitation on patients with radius fracture at the typical site , who wore circumferential static wrist orthoses , with those who did not wear them . METHODS Thirty patients were divided into 3 equal groups , 2 experimental groups , and 1 control group . The patients in the experimental groups were given the rehabilitation program of wearing serially manufactured ( off-the-shelf ) , as well as custom-fit orthoses . Those in the control group did not wear wrist orthoses . Evaluation parameters were pain , edema , the range of the wrist motion , the quality of cylindrical , spherical , and pinch-spherical grasp , the strength of pinch and h and grasp , and patient 's assessment of the effects of rehabilitation . RESULTS No significant difference in the effects of rehabilitation on the patients in experimental groups as opposed to control group was found . Patients in the first experimental group , and in control group were more satisfied with the effects of rehabilitation , as opposed to the patients in the second experimental group ( p<0.05 ) . CONCLUSION The effects of circumferential static wrist orthoses in the rehabilitation of patients with distal radius fracture at the typical site were not clinical ly significant . There was no significant difference between the custom and off-the-shelf orthoses The aim of this study was to evaluate the efficacy of manual lymph drainage , as described by Vodder , in reducing oedema in the h and after a traumatic injury . During a period of 10 months in 1996 - 7 , a total of 26 consecutive patients with a fracture of the distal radius that was treated by external fixation were included in the study . Patients were r and omised into an experimental ( n = 12 ) and a control group ( n = 14 ) . Treatment started 11 days after application of the external fixator . All patients had the same conventional treatment with exercises , movement , oedema control , and education . The experimental group was given 10 treatments of manual lymph drainage in addition . Oedema was measured four times with the volumeter , and the injured h and was always compared with the uninjured one . The first measurement was made three days after removal of the external fixation . The difference in h and volume showed that the experimental group had significantly less oedema in the injured h and . This result indicates that manual lymph drainage is a useful method for reducing post-traumatic oedema in the h and The capacity for physiotherapy to improve the outcome after fracture of the distal radius is unproven . We carried out a r and omised controlled trial on 96 patients , comparing conventional physiotherapy with a regime of home exercises . The function of the upper limb was assessed at the time of removal of the plaster cast and at three and six months after injury . Factors which may predict poor outcome in these patients were sought . Grip strength and h and function did not significantly differ between the two groups . Flexion and extension of the wrist were the only movements to improve with physiotherapy at six months ( p = 0.001 ) . Predictors of poor functional outcome were malunion and impaired function before the fracture . These patients presented with pain , decreased rotation of the forearm and low functional scores at six weeks . Our study has shown that home exercises are adequate rehabilitation after uncomplicated fracture of the distal radius , and routine referral for a course of physiotherapy should be discouraged . The role of physiotherapy in patients at high risk of a poor outcome requires further investigation SUMMARY . This study compared the outcomes of using two passive mobilizing techniques , passive sustained stretches and oscillations , to treat post-immobilization sequelae of Colles ' fractures types I and III . The study used a type of single subject , multi-element design , to enable comparisons of the two techniques in the same subject , when rapid change and limited reversibility was expected and research had to occur concurrently with treatment . Eight female subjects were r and omly assigned to pre design ed sets of treatment conditions for six consecutive sessions . Each subject had completed the usual 6 weeks of immobilization of their affected arm within 3 days of commencing the study . Results indicate that both passive mobilizing techniques increased the range of wrist extension , but , if pain was present , oscillations were more effective . Consistent with this , sustained stretches were more effective in the absence of pain or later in a series of treatments . Copyright 2000 Harcourt Publishers Objective : To investigate the effects of adding core stabilisation exercises to traditional rehabilitation in patients with arm injuries . Design : R and omized controlled trial . Setting : Outpatient clinic . Subjects : Twenty-seven patients with elbow and wrist injuries were r and omized to a stabilisation or control group . Interventions : The stabilisation group received core stabilisation training and traditional arm rehabilitation and the control group received traditional arm rehabilitation alone for three days/week for six weeks . Main measures : Pre- and post-treatment assessment s comprising an analysis of compensatory movement patterns and trunk muscle strength as well as functional measurements of the arm , including pain , range of motion , disabilities of arm , shoulder and h and question naire and endurance and fatigue severity were performed . Results : Inter-group comparison revealed significantly greater improvements in the degree of mean change ( SD ) in total compensation ( in degrees ) of the head ( –14.47 ( 21.65 ) ) and trunk ( –5.56 ( 5.71 ) ) as well as total compensation ( –50.02 ( 48.62 ) ) for the stabilisation group than for the control group ( p < 0.05 ) . Increase in trunk muscle strength ( 2.43 ( 3.46 ) ) was statistically significant in the stabilisation group compared with the control group . No significant differences were found for functional measures , including pain , range of motion , disabilities of arm , shoulder and h and or endurance and fatigue severity between the groups , although trends towards greater improvement were observed in the stabilisation group . Conclusions : Adding core stabilisation exercises to traditional arm rehabilitation for patients with traumatic arm injury reduces compensatory movement patterns . Trends towards better functional outcomes in the stabilisation group are worth testing in a large-scale trial INTRODUCTION Although Colles ' fracture i.e. a dorsally displaced distal radius fracture ( DRF ) is one of the most common fractures , there is no enough evidence to determine the best form of rehabilitation . OBJECTIVE To assess whether the use of pulsed electromagnetic field ( PEMF ) therapy during cast immobilization of DRF provides beneficial effects on pain , edema , wrist range of motion and function , as well as on the frequency of complications immediately after cast removal . METHODS The prospect i ve r and omized controlled study included 60 women over the age of 55 years with extra-articular displaced DRF treated with reduction and cast immobilization . The patients were alternately allocated to either a PEMF group ( n = 30 , received 10 days of PEMF therapy during immobilization ) , or a control group ( n = 30 , without PEMF therapy ) . Pain , function , h and circumference , wrist and forearm range of motion and frequency of complications for each patient was evaluated within two to three days of cast removal . RESULTS Better mean values for the majority of examined parameters were recorded in the PEMF group than in the control group , but the difference was statistically significant just for edema ( p < 0.001 ) , flexion , extension and supination range ( p < 0.01 ) . CONCLUSION During immobilization PEMF therapy in DRF patients gave better results immediately after cast removal in terms of edema and wrist range of motion ( ROM ) Abstract Purpose : This feasibility study sought to determine if compliance and underst and ing of a home exercise program following a traumatic h and injury is improved when patients are provided with a DVD and a brochure when compared to using brochures only . Method : Patients who presented with a traumatic h and injury and commenced on a h and therapy protocol were r and omly assigned into two groups . The control group received brochures while the experimental group were provided with exercise instructions on DVD as well as brochures . Compliance was measured through the use of exercise diaries , clinic attendance , a checklist to measure correctness and underst and ing of exercises and a follow-up survey . Results : No significant improvement was found in the mean exercise compliance score ( p = 0.344 ) between the intervention and control groups . From the survey results almost half of all participants reported that pain interfered in their ability to perform their home exercises and a third acknowledged that time limited their ability to perform their exercises . Conclusion : Findings demonstrate the multidimensional nature of compliance . The provision of DVD technology , while not shown to cause a statistically significant change in overall compliance , did help improve underst and ing of exercises ; as such DVDs could be utilised as part of a program that facilitates the patient -- therapist relationship . Implication s for Rehabilitation Limited time and level of pain are highlighted as reasons for non compliance with exercise and treatment programs . The use of DVDs can improve underst and ing and execution of exercises and can be part of a treatment program that facilitates increased patient therapist contact for rural and remote clients This study investigated whether passive mobilisation added to the effectiveness of an advice and exercise regimen for patients following distal radial fractures . Thirty-nine patients were r and omly allocated to one of two groups . Patients in the first group received advice and exercises ; patients in the second group also received a six-week course of passive mobilisation . Range of movement , function and pain were measured pre-treatment , and three and six weeks later . Significant improvements were found over time for all outcome measures . No significant differences were detected between groups for any outcomes except flexion , where the difference was not clinical ly important . Routine passive mobilisation does not appear to incur additional benefit over an advice and exercise regimen for this patient group Objective : To investigate whether progressive early digit mobilization result ed in better outcomes for h and stiffness and related functional results , as well as the effects on the bone healing process . Design : Prospect i ve , pilot r and omized controlled trial . Setting : A university hospital in southern Taiwan . Participants : Twenty-two patients with distal radius fracture r and omized into two groups : early digit mobilization or control . Interventions : The intervention group received 45 minutes per treatment session and three sessions per week until the external fixator was removed 6 weeks after fracture . The control group received usual home programmes . After removing fixators , both groups received regular rehabilitation programmes until 12 weeks after surgery . Main measures : H and strength , dexterity and functional outcomes were obtained using a dynamometer , Purdue pegboard and self-report assessment , respectively , and X-rays of the distal radius were taken to reveal bone healing 1 , 3 , 6 and 12 weeks after surgery . A motion tracking system measured various kinematic parameters . Results : The recovery rates between the groups showed statistically significant differences in both thumb workspace ( 81.55 % vs. 69.54 % , P = 0.04 ) and finger workspace ( 89.22 % vs. 59.97 % , P = 0.03 ) 12 weeks after injury . However , no statistical differences were found in finger dexterity , strength and self-reported outcomes . The radiographic assessment showed no significant differences between the groups for radial inclination , radial height and volar tilt throughout the examinations . Conclusions : The findings suggest that early rehabilitative intervention for digits is applicable for distal radius fracture treatment , and does not produce additional bone deformities QUESTION Does an advice and exercise program improve outcome for adults following distal radius fracture ? DESIGN R and omised trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS Fifty-six patients whose fracture had been managed with pins and /or cast . INTERVENTION The experimental group received a physiotherapist-directed program of advice and exercises . The control group did not receive any physiotherapy intervention . OUTCOME MEASURES The primary outcome was wrist extension ( measured with a goniometer ) . Secondary outcomes were the other wrist ranges of motion ( measured with a goniometer ) , grip strength ( measured with a dynamometer ) , pain , and activity limitations ( measured with question naires ) . These outcomes were measured initially , then three and six weeks later . Participants also rated their satisfaction with physiotherapy intervention at Week 6 . RESULTS No difference was found between groups for the primary outcome of wrist extension ( mean difference 6 deg , 95 % CI -3 to 14 ) , nor for the secondary outcomes of other range of motion data and grip strength . The difference between groups for pain was -16 points out of 100 ( 95 % CI -27 to -5 ) at Week 3 , and -14 points ( 95 % CI -25 to -3 ) points at Week 6 , and for activity was -13 points out of 100 ( 95 % CI -24 to -2 ) at Week 3 ; in favour of the experimental group . The experimental group was also more satisfied with the amount of physiotherapy intervention . CONCLUSION An advice and exercise program provided some additional benefits over no intervention for adults following distal radius fracture We followed forty women with functional deficits in the wrist and h and after sustaining a Colles ' fracture . The women participated in occupational therapy three times a week for three weeks . At the initial evaluation , after three weeks , and at a three month evaluation , we measured the following : range of joint movement , grip strength , h and volume ( oedema ) , pain and ADL . There was significant improvement in most of the parameters measured after three weeks of occupational therapy , with a less significant improvement from three weeks to three months . Seventeen of the forty women received twenty minutes of intermittent pneumatic compression before occupational therapy . These patients showed significant improvement in wrist extension , compared with the control group of twenty-three patients . Occupational therapy is recommended for patients showing a functional deficit after Colles ' fracture . Intermittent pneumatic compression is recommended as a supplement to occupational therapy Introduction : Physiotherapy is considered by some authorities to be an important aspect of management in patients following distal radius fractures . There is evidence of improvement in impairment with physiotherapy ; however , there is no evidence to support early return of functional activity . Traditional physiotherapy management has focussed on improving impairment ; however , there are no trials with emphasis on skill acquisition via motor re-learning principles . Material s and methods : Forty-one participants with conservatively managed distal radius fractures were studied in a r and omised , single-blinded , prospect i ve trial . Two treatment options were compared : exercise and advice versus activity-focussed physiotherapy with measurement periods of 6 weeks after removal of cast and follow-up at 24 weeks . Results : Participants allocated to the exercise and advice group consulted a physiotherapist an average of 0.9 ( SD 0.4 ) times , while the participants allocated to the more intensive activity-focussed group consulted with physiotherapy a mean of 4.4 ( SD 2.3 ) times . At both 6 and 24 weeks there were no significant differences between the groups for change in impairment ( as measured by grip strength , range of motion of wrist flexion and extension and pain intensity ) , activity limitation and participation restriction , as measured by the Patient-Rated Wrist Evaluation ( PRWE ) . Exercise and advice given by a physiotherapist were equally as effective as activity-focussed physiotherapy in recovery both at 6 and 24 weeks . Conclusion : The results suggest that after removal of cast from fracture of distal radius , patients may routinely require no more than a single session of advice and exercise provided by a physiotherapist The use of Orthoplast cast-bracing to allow early h and function in the treatment of displaced Colles ' fractures was investigated in 243 patients . They were r and omly allocated into three groups : in the first a conventional Colles ' type plaster was used ; in the second an above-elbow cast-brace with the forearm in supination ; and in the third a below-elbow cast-brace . Radiographic measurements were made at each stage of treatment , and the final anatomical result was scored using Sarmiento 's ( 1975 ) criteria . Function was assessed at three months and at six months . The anatomical result was not influenced by the method of immobilisation but was related to the efficacy of reduction . Loss of position in the braces was no greater than in plaster . The functional result at three months also was uninfluenced by the method of immobilisation ; it was , however , related to the severity of the initial displacement , and ( to a lesser degree ) to the anatomical result , an effect which was lost at six months . Early h and function and the supinated position advocated by Sarmiento were found to confer no anatomical or functional advantage ; we could see no reason to change from the use of conventional plaster casts in the treatment of uncomplicated Colles ' fractures Thirty-eight patients with dorsally-displaced distal radial fractures were prospect ively studied to assess the clinical effects of low frequency ultrasound treatment , started immediately after plaster removal . Nineteen of the patients represented the control group and a double-blind protocol was followed . Assessment took place on the day of plaster removal and 2 and 8 weeks later . There was no significant difference in wrist motion and duration of follow-up between the treated and control patients STUDY DESIGN R and omized controlled clinical trial . INTRODUCTION Manual edema mobilization ( MEM ) is a method of edema reduction based on the lymphatic system 's ability to drain and resolve subacute edema . PURPOSE OF THE STUDY To investigate the effect of a modified MEM approach and compare it with a traditional edema technique in patients with subacute h and /arm edema after a distal radius fracture . METHOD The patients were r and omized into one of two treatment groups : a group that received traditional edema treatment and a group that received a modified MEM treatment . All patients were examined for edema , active range of motion ( AROM ) , pain , and activities of daily living ( ADL ) . The number of edema sessions and the number of all sessions were counted . RESULT No statistically significant changes were observed in edema reduction , AROM , pain , and ADL at six and nine weeks between the treatment groups . A statistically significant improvement was observed in ADL after three weeks after inclusion ( p=0.03 ) in the modified MEM group compared with the control group . Furthermore , fewer edema treatment sessions were needed ( p=0.03 ) in the modified MEM group . At six weeks , we observed a difference between the two groups ' needs for further edema treatment ( p=0.04 ) . CONCLUSION Neither the traditional nor the modified MEM treatment program was superior in terms of edema reduction , although the modified MEM result ed in fewer sessions to decrease subacute h and /arm edema compared with using traditional edema reduction techniques in patients after distal radius fracture . LEVEL OF EVIDENCE 1 The purpose s of this study were to determine the overall incidence of distal radius fracture ( DRF ) complications , determine the incidence and types of DRF complications in a consecutive cohort of 250 patients with DRFs , describe DRF complications reported by patients compared with those reported by physicians , and formulate a DRF complication checklist to improve recording of DRF complications . We found that the overall complication rates vary widely ( 6 % to 80 % ) . Physician-reported complication data were collected for 236 patients , and a physician-reported complication rate of 27 % was determined . A patient-reported complication rate of 21 % was found for 207 patients whose patient-reported data were collected . We also noted that patients and physicians assess DRF complications differently : patients are more focused on symptoms than diagnoses . A DRF complication checklist was developed to improve prospect i ve data collection . The checklist includes a classification for all DRF complications and allows for assessment of severity of each complication We evaluated the responsiveness of patient question naires and physical testing in the assessment of recovery after distal radius fracture . Patients ( n = 59 ) were assessed at their baseline clinic visit and again 3 and 6 months after injury . At each visit patients completed a short form-36 , Disability of the Arm , Shoulder , and H and question naire , and patient-rated wrist evaluation ( PRWE ) . At 3 and 6 months grip strength , range of motion , and dexterity were analyzed . St and ardized response means ( SRM ) and effects sizes were calculated to indicate responsiveness . The PRWE was the most responsive . Both the PRWE ( SRM = 2.27 ) and the Disability of the Arm , Shoulder , and H and ( SRM = 2.01 ) question naire were more responsive than the short form-36 ( SRM = 0.92 ) . The physical component summary score of the short form-36 was similar to that of the physical component subscales . Question naires were highly responsive during the 0- to 3-month time period when physical testing could not be performed . Of the physical tests , grip strength was most responsive , followed by range of motion . Responsive patient-rating scales and physical performance evaluations can assist with outcome evaluation of patients with distal radius fracture QUESTION Do dynamic splints reduce contracture following distal radial fracture ? DESIGN Assessor-blinded , r and omised controlled trial . PARTICIPANTS Forty out patients with contracture following distal radial fracture . INTERVENTION The control group received routine care consisting of exercises and advice for 8 weeks . In addition to routine care , during the day the experimental group received a dynamic splint , which stretched the wrist into extension but allowed intermittent movement . OUTCOME MEASURES The primary outcomes were passive wrist extension and the Patient Rated H and Wrist Evaluation ( PRHWE ) . The secondary outcomes were active wrist extension , flexion , radial deviation , and ulnar deviation , and the performance and satisfaction items of the Canadian Occupational Performance Measure ( COPM ) . All outcomes were measured at commencement , at the end of 8 weeks of treatment , and at 12 weeks ( ie , 1 month follow-up ) . RESULTS The mean between-group difference for passive wrist extension and PRHWE at 8 weeks were 4 deg ( 95 % CI -4 to 12 ) and -2 points ( 95 % CI -8 to 4 ) , respectively . The corresponding values at 12 week follow-up were 6 deg ( 95 % CI 1 to 12 ) and 2 points ( 95 % CI -5 to 9 ) . There were no sufficiently important between-group differences for any of the secondary outcome measures at 8 or 12 weeks . CONCLUSION It is unclear whether dynamic splints following distal radial fracture have therapeutic effects on passive wrist extension or PRHWE , but they clearly do not have any therapeutic effects on active wrist extension , flexion , radial or ulnar deviation , or on the performance or satisfaction items of the COPM . The ongoing use of dynamic splints following distal radial fracture is difficult to justify . TRIAL REGISTRATION ACTRN12608000309381 PURPOSE Patient-rated instruments are increasingly used to measure orthopedic outcomes . However , the clinical relevance of modest score changes on such instruments is often unclear . This study was design ed to define the minimal clinical ly important differences ( MCIDs ) of the Disabilities of the Arm , Shoulder , and H and ( DASH ) , QuickDASH ( subset of DASH ) , and Patient-Rated Wrist Evaluation ( PRWE ) question naires for atraumatic conditions of the h and , wrist , and forearm . METHODS We prospect ively analyzed 102 patients undergoing nonoperative treatment for isolated tendinitis , arthritis , or nerve compression syndromes from the forearm to the h and . By phone , patients completed the DASH , QuickDASH , and PRWE at enrollment and at 2 weeks ( n = 78 used in the analysis ) and 4 weeks ( n = 24 used in the analysis ) after initiating treatment . Patients reporting clinical improvement each contributed a single data point categorized as no change ( n = 41 ) , minimal improvement ( n = 30 ) , or marked improvement ( n = 31 ) via a vali date d anchor-based approach . We calculated the MCID as the mean change score for each outcome measure in the minimal improvement group . RESULTS The MCID ( 95 % confidence interval ) for the DASH was 10 ( 5 - 15 ) . The MCID for the QuickDASH was 14 ( 9 - 20 ) . The MCID was 14 ( 8 - 20 ) for the PRWE . The MCID values were significantly different from changes in these outcome measures at times of either no change or marked improvement . The MCID values positively correlated with baseline outcome measure scores to a greater degree than final outcome measure scores . CONCLUSIONS Longitudinal changes on the DASH of 10 points , on the QuickDASH of 14 points , and on the PRWE of 14 points represent minimal clinical ly important changes . We recommend application of these MCID values for group-level analysis when conducting research and interpreting data examining groups of patients as opposed to assessing individual patients . These MCID values may provide a basis for sample size calculations for future investigation using these common patient-rated outcome measures . TYPE OF STUDY /LEVEL OF EVIDENCE Diagnostic III INTRODUCTION The beneficial effect of compression treatment for soft tissue swelling is undisputed . Yet it is only a subordinated option in trauma therapy and is used if at all preferably for the lower extremities . In a preliminary study we were able to show that fitted compression gloves had a positive effect . MATERIAL S AND METHOD In a prospect i ve r and omised study the effect of compression treatment on the rehabilitation period was examined . RESULTS In this study including 57 patients it was shown that due to a quicker reduction of swelling , measured via the circumference and volume of the forearm the range of motion increased faster than in the control group without compression treatment . Volume differed by 16 % between the injured and healthy arm in the compression group , yet by 25 % in the control group , representing a significant difference . An improvement in range of motion was seen , but did not reach statistical significance . CONCLUSION Fitted compression gloves as a rehabilitation means after surgical treatment of distal radius fractures can lead to a quicker restoration of function and thereby decrease the treatment duration BACKGROUND The effect of formal occupational therapy on recovery after open reduction and volar plate fixation of a fracture of the distal part of the radius is uncertain . We hypothesized that there would be no difference in wrist function and arm-specific disability six months after open reduction and volar plate fixation of a distal radial fracture between patients who receive formal occupational therapy and those with instructions for independent exercises . METHODS Ninety-four patients with an unstable distal radial fracture treated with open reduction and volar locking plate fixation were enrolled in a prospect i ve r and omized controlled trial comparing exercises done under the supervision of an occupational therapist with surgeon-directed independent exercises . The primary study question addressed combined wrist flexion and extension six months after surgery Secondary study questions addressed wrist motion , grip strength , Gartl and and Werley scores , Mayo wrist scores , and DASH ( Disabilities of the Arm , Shoulder and H and ) scores at three months and six months after surgery . RESULTS There was a significant difference in the mean arc of wrist flexion and extension six months after surgery ( 118 ° versus 129 ° ) , favoring patients prescribed independent exercises . Three months after surgery , there was a significant difference in mean pinch strength ( 80 % versus 90 % ) , mean grip strength ( 66 % versus 81 % ) , and mean Gartl and and Werley scores , favoring patients prescribed independent exercises . At six months , there was a significant difference in mean wrist extension ( 55 ° versus 62 ° ) , ulnar deviation ( 82 % versus 93 % ) , mean supination ( 84 ° versus 90 ° ) , mean grip strength ( 81 % versus 92 % ) , and mean Mayo score , favoring patients prescribed independent exercises . There were no differences in arm-specific disability ( DASH score ) at any time point . CONCLUSIONS Prescription of formal occupational therapy does not improve the average motion or disability score after volar locking plate fixation of a fracture of the distal part of the radius |
10,571 | 26,141,572 | In preterm infants with respiratory distress , the application of CDP as CPAP or CNP is associated with reduced respiratory failure and mortality and an increased rate of pneumothorax . | BACKGROUND Respiratory distress syndrome ( RDS ) is the single most important cause of morbidity and mortality in preterm infants .
In infants with progressive respiratory insufficiency , intermittent positive pressure ventilation ( IPPV ) with surfactant is the st and ard treatment for the condition , but it is invasive , potentially result ing in airway and lung injury .
Continuous distending pressure ( CDP ) has been used for the prevention and treatment of RDS , as well as for the prevention of apnoea , and in weaning from IPPV .
Its use in the treatment of RDS might reduce the need for IPPV and its sequelae .
OBJECTIVES To determine the effect of continuous distending pressure ( CDP ) on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress . | BACKGROUND There are limited data to inform the choice between early treatment with continuous positive airway pressure ( CPAP ) and early surfactant treatment as the initial support for extremely-low-birth-weight infants . METHODS We performed a r and omized , multicenter trial , with a 2-by-2 factorial design , involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation . Infants were r and omly assigned to intubation and surfactant treatment ( within 1 hour after birth ) or to CPAP treatment initiated in the delivery room , with subsequent use of a protocol -driven limited ventilation strategy . Infants were also r and omly assigned to one of two target ranges of oxygen saturation . The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks ( with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30 % oxygen ) . RESULTS A total of 1316 infants were enrolled in the study . The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group ( 47.8 % and 51.0 % , respectively ; relative risk with CPAP , 0.95 ; 95 % confidence interval [ CI ] , 0.85 to 1.05 ) after adjustment for gestational age , center , and familial clustering . The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks ( rates of primary outcome , 48.7 % and 54.1 % , respectively ; relative risk with CPAP , 0.91 ; 95 % CI , 0.83 to 1.01 ) . Infants who received CPAP treatment , as compared with infants who received surfactant treatment , less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia ( P<0.001 ) , required fewer days of mechanical ventilation ( P=0.03 ) , and were more likely to be alive and free from the need for mechanical ventilation by day 7 ( P=0.01 ) . The rates of other adverse neonatal outcomes did not differ significantly between the two groups . CONCLUSIONS The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants . ( Clinical Trials.gov number , NCT00233324 . OBJECTIVE . Our objective was to determine whether continuous positive airway pressure therapy would safely reduce the need for up-transfer of infants with respiratory distress from nontertiary centers . METHODS . We r and omly assigned 300 infants at > 30 weeks of gestation with respiratory distress to receive either Hudson prong bubble continuous positive airway pressure therapy or headbox oxygen treatment ( st and ard care ) . The primary end point was “ up-transfer or treatment failure . ” Secondary end points included death , length of nursery stay , time receiving oxygen therapy , cost of care , and other measures of morbidity . RESULTS . Of 151 infants who received continuous positive airway pressure therapy , 35 either were up-transferred or experienced treatment failure , as did 60 of the 149 infants given headbox oxygen treatment . There was no difference in the length of stay or the duration of oxygen treatment . For every 6 infants treated with continuous positive airway pressure therapy , there was an estimated cost saving of $ 10000 . Pneumothorax was identified for 14 infants in the continuous positive airway pressure group and 5 in the headbox group . There was no difference in any other measure of morbidity or death . CONCLUSIONS . Hudson prong bubble continuous positive airway pressure therapy reduces the need for up-transfer of infants with respiratory distress in nontertiary centers . There is a clinical ly relevant but not statistically significant increase in the risk of pneumothorax . There are significant benefits associated with continuous positive airway pressure use in larger nontertiary centers A sequential controlled trial of continuous negative pressure versus oxygen in treatment of severe respiratory distress syndrome ( Pa O 2 O 2 70 per cent or greater ) was performed . CNP was applied by means of a newly design ed , inexpensive plastic chamber . Twenty-nine infants with RDS who weighed > 1,000 Gm . and who had no congenital malformations were studied ; there were 14 in the oxygen-treated control group and 15 in the CNP-treated group . Following the study , seven additional infants were treated with CNP . Birth weights , sex , gestational ages , ages , and blood gases at the time of admission to the study were similar . Study failure was defined as a Pa O A controlled trial of elective intervention with continuous inflating pressure ( CIP ) was performed in infants with severe hyaline membrane disease who weighed more than 1000 g at birth . Infants entered the trial if their arterial oxygen tension ( PaO2 ) fell below 60 mmHg while breathing a fractional inspired oxygen concentration ( F1O2 ) greater than 0 - 95 . 11 out of 12 infants in the CIP-treated group and 10 out of 12 in the control group survived . 7 treated and 6 control infants required mechanical ventilation . When CIP was started the Pao2 of the treated infants increased , and they breathed high concentrations of oxygen for a significantly shorter period than the control infants . During the 31-month duration of the trial 107 other infants with severe hyaline membrane disease were admitted who did not meet the criteria for entry to the trial . 37 survived after breathing high concentrations of oxygen ( F1O2 greater than 0 - 60 ) spontaneously without any ventilatory assistance , and the remaining 70 infants were already being ventilated on their arrival in the unit , usually because they had required mechanical ventilation during transfer from other hospitals . The neonatal survival rate for those infants born in this hospital during the study period was 88 % ( 50 out of 57 infants ) and for those referred from other hospitals it was 69 % ( 51 out of 74 infants ) . The maximum further increase in overall survival rate that might have been achieved in our population of infants if CIP had been initiated very early in the course of the illness was 5%--i.e . from 77 % ( 101/131 ) to 82 % ( 107/131 ) OBJECTIVE To determine whether very low birth weight infants ( VLBWIs ) , initially supported with continuous positive airway pressure ( CPAP ) and then selectively treated with the INSURE ( intubation , surfactant , and extubation to CPAP ; CPAP/INSURE ) protocol , need less mechanical ventilation than those supported with supplemental oxygen , surfactant , and mechanical ventilation if required ( Oxygen/mechanical ventilation [ MV ] ) . STUDY DESIGN In a multicenter r and omized controlled trial , spontaneously breathing VLBWIs weighing 800 - 1500 g were allocated to receive either therapy . In the CPAP/INSURE group , if respiratory distress syndrome ( RDS ) did not occur , CPAP was discontinued after 3 - 6 hours . If RDS developed and the fraction of inspired oxygen ( FiO(2 ) ) was > 0.35 , the INSURE protocol was indicated . Failure criteria included FiO(2 ) > 0.60 , severe apnea or respiratory acidosis , and receipt of more than 2 doses of surfactant . In the Oxygen/MV group , in the presence of RDS , supplemental oxygen without CPAP was given , and if FiO(2 ) was > 0.35 , surfactant and mechanical ventilation were provided . RESULTS A total of 256 patients were r and omized to either the CPAP/INSURE group ( n = 131 ) or the Oxygen/MV group ( n = 125 ) . The need for mechanical ventilation was lower in the CPAP/INSURE group ( 29.8 % vs 50.4 % ; P = .001 ) , as was the use of surfactant ( 27.5 % vs 46.4 % ; P = .002 ) . There were no differences in death , pneumothorax , bronchopulmonary dysplasia , and other complications of prematurity between the 2 groups . CONCLUSION CPAP and early selective INSURE reduced the need for mechanical ventilation and surfactant in VLBWIs without increasing morbidity and death . These results may be particularly relevant for re source -limited regions OBJECTIVE To determine whether early versus late treatment with porcine surfactant ( Curosurf ) reduces the requirement of mechanical ventilation in very preterm infants primarily supported by nasal continuous positive airway pressure ( nasal CPAP ) . DESIGN Multicenter r and omized , controlled trial . PATIENTS The study population comprised 60 infants < 30 weeks ' gestation with respiratory distress syndrome ( RDS ) who had an arterial to alveolar oxygen tension ratio ( a/APO2 ) of 0.35 to 0.22 . The cohort from which the study population was generated comprised 397 infants . RESULTS The need for mechanical ventilation or death within 7 days of age was reduced from 63 % in the late-treated infants to 21 % in early-treated infants . Increasing numbers of antenatal steroid doses also improved the outcome , especially in the early-treated infants . Six hours after r and omization mean a/APO2 rose to 0.48 in the early-treated infants compared with 0.36 in the late-treated . The need of mechanical ventilation before discharge was reduced from 68 % in the late-treated to 25 % in the early-treated infants . CONCLUSIONS Nasal CPAP in combination with early treatment with Curosurf significantly improves oxygenation and reduces the subsequent need for mechanical ventilation in infants < 30 weeks ' gestational age with RDS OBJECTIVE : Early surfactant followed by extubation to nasal continuous positive airway pressure ( nCPAP ) compared with later surfactant and mechanical ventilation ( MV ) reduce the need for MV , air leaks , and bronchopulmonary dysplasia . This r and omized , controlled trial investigated whether prophylactic surfactant followed by nCPAP compared with early nCPAP application with early selective surfactant would reduce the need for MV in the first 5 days of life . METHODS : A total of 208 inborn infants who were born at 25 to 28 weeks ' gestation and were not intubated at birth were r and omly assigned to prophylactic surfactant or nCPAP within 30 minutes of birth . Outcomes were assessed within the first 5 days of life and until death or discharge of the infants from hospital . RESULTS : Thirty-three ( 31.4 % ) infants in the prophylactic surfactant group needed MV in the first 5 days of life compared with 34 ( 33.0 % ) in the nCPAP group ( risk ratio : 0.95 [ 95 % confidence interval : 0.64–1.41 ] ; P = .80 ) . Death and type of survival at 28 days of life and 36 weeks ' postmenstrual age and incidence of main morbidities of prematurity ( secondary outcomes ) were similar in the 2 groups . A total of 78.1 % of infants in the prophylactic surfactant group and 78.6 % in the nCPAP group survived in room air at 36 weeks ' postmenstrual age . CONCLUSIONS : Prophylactic surfactant was not superior to nCPAP and early selective surfactant in decreasing the need for MV in the first 5 days of life and the incidence of main morbidities of prematurity in spontaneously breathing very preterm infants on nCPAP This prospect i ve study was undertaken to investigate the efficacy of nasal continuous positive airway pressure ( nCPAP ) in a group of extremely small infants denied access to a neonatal intensive care unit ( NICU ) in South Africa . Consecutive infants weighing less than 1200 g and /or of a gestational age below 28 weeks admitted to the neonatal ward with respiratory distress syndrome ( RDS ) , and who were refused admission to the NICU , received either nCPAP ( Infant Flow System E.M.E. , UK ) of headbox oxygen . Of 22 infants , 11 infants were included in the treatment group ( nCPAP ) and 10 in the control group . Within the first 24 h , two infants ( 18 per cent ) in the nCPAP group and eight infants ( 80 per cent ) in the control group died ( p = 0.007 ) ( survival OR = 18 ; RR = 4.09 ) . A statistically significant improvement in the arterial-alveolar ( a/A ) oxygen ratio occurred in the nCPAP group between postnatal day 1 and day 3 of life ( 0.17 vs. 0.36 ; p < 0.005 ) . Neonatal complications occurred in six ( 55 per cent ) infants who survived the first 24 h of life . Eighty per cent of the infants with intraventricular haemorrhage ( IVH ) died , as well as all the infants who were born before arrival at the hospital . At the time of discharge from hospital , 45 per cent ( five infants ) in the nCPAP group survived vs. 20 per cent ( two infants ) in the control group . The neurodevelopmental outcome of six of the surviving seven infants were evaluated at 1 year of corrected age . The neurodevelopmental outcome as assessed by the Griffith Score was within normal limits in all infants . One infant has sensorineural deafness and one is deaf and has a possible mild spastic diplegia ( both in the treatment group ) . We conclude that nCPAP significantly improves the short-term survival of very low birth-weight ( VLBW ) infants with moderate to severe respiratory distress syndrome who could not be admitted to intensive care . nCPAP significantly improves the a/A oxygen ratio between day 1 and day 3 of life The influence of continuous positive airway pressure ( CPAP ) and positive end-expiratory pressure ( PEEP ) on mortality and complication rates in severe hyaline membrane disease ( HMD ) was evaluated in a r and omized , prospect i ve study . Patients were admitted to the study if the Po2 was less than 50 mm Hg with FiO2 greater than 0.6 . Twenty-four patients in each of three weight groups were equally divided between treatment and control groups . The treatment regimen included CPAP ( 6 to 14 cm H2O ) for spontaneously breathing patients and PEEP for patients requiring mechanical ventilation for apnea or hypercapnia ( Pco2 greater than 65 mm Hg ) . Control patients received oxygen and were mechanically ventilated if they had apnea , hypercapnia , or Po2 less than 50 mm Hg with FiO2 greater than 0.8 . Oxygenation improved after the start of CPAP or PEEP ; however , Pco2 rose after CPAP was initiated . There was no significant difference between treatment and control groups in mortality , requirement for mechanical ventilation , or incidence of pulmonary sequelae . The incidence of pulmonary air-leak was increased with Peep . the findings suggest that CPAP and PEEP have not significantly altered the outcome of HMD BACKGROUND Bronchopulmonary dysplasia is associated with ventilation and oxygen treatment . This r and omized trial investigated whether nasal continuous positive airway pressure ( CPAP ) , rather than intubation and ventilation , shortly after birth would reduce the rate of death or bronchopulmonary dysplasia in very preterm infants . METHODS We r and omly assigned 610 infants who were born at 25-to-28-weeks ' gestation to CPAP or intubation and ventilation at 5 minutes after birth . We assessed outcomes at 28 days of age , at 36 weeks ' gestational age , and before discharge . RESULTS At 36 weeks ' gestational age , 33.9 % of 307 infants who were assigned to receive CPAP had died or had bronchopulmonary dysplasia , as compared with 38.9 % of 303 infants who were assigned to receive intubation ( odds ratio favoring CPAP , 0.80 ; 95 % confidence interval [ CI ] , 0.58 to 1.12 ; P=0.19 ) . At 28 days , there was a lower risk of death or need for oxygen therapy in the CPAP group than in the intubation group ( odds ratio , 0.63 ; 95 % CI , 0.46 to 0.88 ; P=0.006 ) . There was little difference in overall mortality . In the CPAP group , 46 % of infants were intubated during the first 5 days , and the use of surfactant was halved . The incidence of pneumothorax was 9 % in the CPAP group , as compared with 3 % in the intubation group ( P<0.001 ) . There were no other serious adverse events . The CPAP group had fewer days of ventilation . CONCLUSIONS In infants born at 25-to-28-weeks ' gestation , early nasal CPAP did not significantly reduce the rate of death or bronchopulmonary dysplasia , as compared with intubation . Even though the CPAP group had more incidences of pneumothorax , fewer infants received oxygen at 28 days , and they had fewer days of ventilation . ( Australian New Zeal and Clinical Trials Registry number , 12606000258550 . ) BACKGROUND A previous r and omised trial of continuous negative extrathoracic pressure ( CNEP ) versus st and ard treatment for newborn infants with respiratory distress syndrome raised public concerns about mortality and neonatal morbidity . We studied the outcome in late childhood of children entered into the trial to establish whether there were long-term sequelae attributable to either mode of ventilation . METHODS Outpatient assessment of neurological outcome , cognitive function , and disability was done by a paediatrician and a psychologist using st and ardised tests . 133 of 205 survivors from the original trial were assessed at 9 - 15 years of age . Of the original pairs r and omly assigned to each ventilation mode , the results from 65 complete pairs were available . The primary outcome was death or severe disability . FINDINGS Primary outcome was equally distributed between groups ( odds ratio for the CNEP group 1.0 ; 95 % CI 0.41 - 2.41 ) . In unpaired analysis there was no significant difference between treatment modalities ( 1.05 ; 0.54 - 2.06 ) . Full IQ did not differ significantly between the groups , but mean performance IQ was 6.8 points higher in the CNEP group than in the conventional-treatment group ( 95 % CI 1.5 - 12.1 ) . Results of neuropsychological testing were consistent with this finding , with scores on language production and visuospatial skills being significantly higher in the CNEP group . INTERPRETATION We saw no evidence of poorer long-term outcome after neonatal CNEP whether analysis was by original pairing or by unpaired comparisons , despite small differences in adverse neonatal outcomes . The experience of our study indicates that future studies of neonatal interventions with the potential to influence later morbidity should be design ed with longer-term outcomes in mind Aim : To evaluate whether very preterm babies can be extubated successfully to nasal continuous positive airway pressure ( nCPAP ) within one hour of birth after receiving one dose of surfactant in the treatment of respiratory distress syndrome ( RDS ) . Methods : Forty‐two infants of 25 to 28 + 6 wk of gestation were intubated at birth and given one dose of surfactant . They were then r and omized within one hour of birth to either continue with conventional ventilation or to be extubated to nCPAP . Results : Eight out of 21 ( 38 % ) babies r and omized to nCPAP did not require subsequent reventilation . ( Ventilation rates of 62 % vs 100 % , p= 0.0034 ) . The smallest baby successfully extubated weighed 745 g. There were also significantly fewer infants intubated in the nCPAP group at 72 h of age ( 47 % vs 81 % , p= 0.025 ) . There was no significant difference between the two groups in the number of babies that died , developed chronic lung disease or severe intraventricular haemorrhage OBJECTIVE : To test whether the introduction of early bubble continuous positive airway pressure ( CPAP ) results in improved respiratory outcomes in extremely low birth-weight infants . STUDY DESIGN : Outcomes of all infants between 401 and 1000 g born in a level 3 neonatal intensive care units ( NICU ) between July 2000 and October 2001 ( period 2 ) were compared using historical controls ( period 1 ) . Early bubble ( CPAP ) was prospect ively introduced in the NICU during period 1 . Univariate and adjusted comparisons were made across time periods . RESULTS : Delivery room intubations , days on mechanical ventilation and use of postnatal steroids decreased ( p<0.001 ) in period 2 , while mean days on CPAP , number of babies on CPAP at 24 hours ( p<0.001 ) and mean weight at 36 weeks corrected gestation also increased ( p<0.05 ) after introduction of early bubble CPAP . CONCLUSIONS : Early bubble CPAP reduced delivery room intubations , days on mechanical ventilation , postnatal steroid use and was associated with increased postnatal weight gain with no increased complications OBJECTIVE : We design ed a multicenter r and omized trial to compare 3 approaches to the initial respiratory management of preterm neonates : prophylactic surfactant followed by a period of mechanical ventilation ( prophylactic surfactant [ PS ] ) ; prophylactic surfactant with rapid extubation to bubble nasal continuous positive airway pressure ( intubate-surfactant-extubate [ ISX ] ) or initial management with bubble continuous positive airway pressure and selective surfactant treatment ( nCPAP ) . DESIGN / METHODS : Neonates born at 2607 to 2967 weeks ' gestation were enrolled at participating Vermont Oxford Network centers and r and omly assigned to PS , ISX , or nCPAP groups before delivery . Primary outcome was the incidence of death or bronchopulmonary dysplasia ( BPD ) at 36 weeks ' postmenstrual age . RESULTS : 648 infants enrolled at 27 centers . The study was halted before the desired sample size was reached because of declining enrollment . When compared with the PS group , the relative risk of BPD or death was 0.78 ( 95 % confidence interval : 0.59–1.03 ) for the ISX group and 0.83 ( 95 % confidence interval : 0.64–1.09 ) for the nCPAP group . There were no statistically significant differences in mortality or other complications of prematurity . In the nCPAP group , 48 % were managed without intubation and ventilation , and 54 % without surfactant treatment . CONCLUSIONS : Preterm neonates were initially managed with either nCPAP or PS with rapid extubation to nCPAP had similar clinical outcomes to those treated with PS followed by a period of mechanical ventilation . An approach that uses early nCPAP leads to a reduction in the number of infants who are intubated and given surfactant OBJECTIVE In uncontrolled clinical trials , negative extrathoracic pressure has been shown to be an effective respiratory support . We aim ed to assess its role in the context of current neonatal intensive care . DESIGN A r and omized controlled trial , with sequential analysis of matched pairs of infants . Matching was undertaken by stratified r and omization from 15 groups divided according to gestational age , oxygen requirement , and whether patients were intubated at 4 hours of age . SETTING Two neonatal intensive care units . PATIENTS Two hundred forty-four patients ( birth weight 1.53 + /- 0.69 kg ( mean + /- SD ) ; gestational age 30.4 + /- 3.5 weeks ) with respiratory failure . INTERVENTIONS Patients were r and omized at 4 hours of age to receive either st and ard neonatal intensive care , or st and ard care plus continuous negative extrathoracic pressure ( CNEP , -4 to -6 cmH2O ) applied within a purpose - design ed neonatal incubator . OUTCOME SCORES : Clinical scores were calculated for each infant at 56 days of age , or death if earlier . Scores included measures for mortality , respiratory outcome , the presence of cerebral ultrasound abnormalities , patent arterial duct , necrotizing enterocolitis , and retinopathy . The treatment given for the higher score for each pair was recorded and the cumulative net number of pairs favoring CNEP plotted in the sequential analysis to provide an ethical early termination strategy . Individual components of the outcome score and other secondary measurements were analyzed on completion of the trial . RESULTS The sequential analysis reached a decision boundary after 122 out of a possible maximum of 124 pairs were completed . The overall outcome score showed an overall significant benefit for CNEP . Secondary analysis showed that the use of CNEP was associated with an increase in mortality , cranial ultrasound abnormalities , and pneumothoraces , which were not statistically significant . However , 5 % fewer patients were intubated ( 95 % confidence interval [ CI ] , 0 - 10 ) , and the total duration of oxygen therapy among surviving infants at 56 days was lower ( 20.5 days , compared with 38.9 in controls ; difference 18.4 days , 95 % CI 3.8 to 33.0 ) . Among all infants , the mean total duration of oxygen therapy was 18.3 days among CNEP-treated infants compared with 33.6 days among the controls ( difference -15.3 days , 95 % CI -0.2 to -30.4 ) . This reduction in mean levels is entirely attributable to substantially fewer patients requiring prolonged oxygen therapy , the median duration of treatment being very similar in the two groups . As a result , commensurately fewer surviving infants showed chronic lung disease of prematurity . CONCLUSIONS The use of continuous negative pressure improves the respiratory outcome for neonates with respiratory failure BACKGROUND . Chronic lung disease is one of the most frequent and serious complications of premature birth . Because mechanical ventilation is a major risk factor for chronic lung disease , the early application of nasal continuous positive airway pressure has been used as a strategy for avoiding mechanical ventilation in premature infants . Surfactant therapy improves the short-term respiratory status of premature infants , but its use is traditionally limited to infants being mechanically ventilated . Administration of very early surfactant during a brief period of intubation to infants treated with nasal continuous positive airway pressure may improve their outcome and further decrease the need for mechanical ventilation . OBJECTIVE . Our goal was to determine if very early surfactant therapy without m and atory ventilation improves outcome and decreases the need for mechanical ventilation when used in very premature infants treated with nasal continuous positive airway pressure soon after birth . DESIGN / METHODS . Eight centers in Colombia participated in this r and omized , controlled trial . Infants born between 27 and 31 weeks ’ gestation with evidence of respiratory distress and treated with supplemental oxygen in the delivery room were r and omly assigned within the first hour of life to intubation , very early surfactant , extubation , and nasal continuous positive airway pressure ( treatment group ) or nasal continuous airway pressure alone ( control group ) . The primary outcome was the need for subsequent mechanical ventilation using predefined criteria . RESULTS . From January 1 , 2004 , to December 31 , 2006 , 279 infants were r and omly assigned , 141 to the treatment group and 138 to the control group . The need for mechanical ventilation was lower in the treatment group ( 26 % ) compared with the control group ( 39 % ) . Air-leak syndrome occurred less frequently in the treatment group ( 2 % ) compared with the control group ( 9 % ) . The percentage of patients receiving surfactant after the first hour of life was also significantly less in the treatment group ( 12 % ) compared with the control group ( 26 % ) . The incidence of chronic lung disease ( oxygen treatment at 36 weeks ’ postmenstrual age ) was 49 % in the treatment group compared with 59 % in the control group . All other outcomes , including mortality , intraventricular hemorrhage , and periventricular leukomalacia were similar between the groups . CONCLUSIONS . In premature infants treated with nasal continuous positive airway pressure early after birth , the addition of very early surfactant therapy without m and atory ventilation decreased the need for subsequent mechanical ventilation , decreased the incidence of air-leak syndrome , and seemed to be safe . Reduction in the need for mechanical ventilation is an important outcome when medical re sources are limited and may result in less chronic lung disease in both developed and developing countries |
10,572 | 25,977,708 | The evidence to support to use of padded socks is limited .
There is a suggestion these simple-to-use interventions could be of value , particularly in terms of plantar pressure reduction .
The socks were generally of a sophisticated design with complex use of knit patterns and yarn content .
This systematic review provides limited support for the use of padded socks in the diabetic population to protect vulnerable feet . | Padded socks to protect the at-risk diabetic foot have been available for a number of years .
However , the evidence base to support their use is not well known .
We aim ed to undertake a systematic review of padded socks for people with diabetes . | Specially design ed Thor-Lo footwear has been shown to reduce the in-shoe foot pressures in diabetic patients at risk of foot ulceration when compared to their own footwear . Fifty at high risk patients 32 ( 64 % ) males , 17 ( 34 % ) type 1 diabetes ) have been provided with this foot wear and have been followed up for 6 months . Mean age was 57.6 ( range , 34 - 78 ) years , duration of diabetes 22.4 ( range , 4 - 50 ) years , Neuropathy Symptom Score 3.36 + /- 2.96 ( mean + /- S.D. ) , Neuropathy Disability Score 16.8 + /- 6.83 , VPT 43.4 + /- 11.8 Volts while 43 ( 86 % ) could not feel a 5.07 or smaller Semmes-Weinstein monofilament . Forty-two ( 84 % ) patients were re-examined at an interim visit 3 months after baseline , while 37 ( 74 % ) completed the study . In-shoe peak forces and pressures were measured using the F-Scan system . No difference was found among the peak force among baseline ( 95.5 + /- 26 kg ) , interim ( 96.5 + /- 33 ) and final visit ( 97.7 + /- 25.2 , P + NS ) . There was no difference in peak pressures at the baseline ( 3.98 + /- 1.42 kg.cm-2 ) , second visit ( 4.13 + /- 2.30 ) and the final visit ( 4.25 + /- 1.51 ) . Nine ( 18 % ) patients developed foot problems and one died during the study . We conclude that no changes in foot pressures were found over a period of 6 months of continuous usage of the specially design ed footwear in a group of diabetic patients at risk of foot ulceration . Further prospect i ve studies are required to evaluate the impact of specially design ed footwear in reducing the rate of foot ulceration OBJECTIVE Little prospect i ve research exists on risk factors for diabetic foot ulcer that considers the independent effects of multiple potential etiologic agents . We prospect ively studied the effects of diabetes characteristics , foot deformity , behavioral factors , and neurovascular function on foot ulcer risk among 749 diabetic veterans with 1,483 lower limbs . RESEARCH DESIGN AND METHODS Eligible subjects included all diabetic enrollees of a general internal medicine clinic without foot ulcer , of whom 83 % agreed to participate . Baseline assessment included history and lower-limb physical examination , tests for sensory and autonomic neuropathy , and measurements of macro- and microvascular perfusion in the foot . Subjects were followed for the occurrence of a full thickness skin defect on the foot that took > 14 days to heal , with a mean follow-up of 3.7 years . RESULTS Using stepwise Cox regression analysis , the following factors were independently related to foot ulcer risk : foot insensitivity to the 5.07 monofilament ( relative risk [ 95 % CI ] ) 2.2 ( 1.5 - 3.1 ) , past history of amputation 2.8 ( 1.8 - 4.3 ) or foot ulcer 1.6 ( 1.2 - 2.3 ) , insulin use 1.6 ( 1.1 - 2.2 ) , Charcot deformity 3.5 ( 1.2 - 9.9 ) , 15 mmHg higher dorsal foot transcutaneous PO2 0.8 ( 0.7 - 0.9 ) , 20 kg higher body weight 1.2 ( 1.1 - 1.4 ) , 0.3 higher ankle-arm index 0.8 ( 0.7 - 1.0 ) , poor vision 1.9 ( 1.4 - 2.6 ) , and 13 mmHg orthostatic blood pressure fall 1.2 ( 1.1 - 1.5 ) . Higher ulcer risk was associated with hammer/claw toe deformity and history of laser photocoagulation in certain subgroups . Unrelated to foot ulcer risk in multivariate models were diabetes duration and type , race , smoking status , diabetes education , joint mobility , hallux blood pressure , and other foot deformities . CONCLUSIONS Certain foot deformities , reduced skin oxygenation and foot perfusion , poor vision , greater body mass , and both sensory and autonomic neuropathy independently influence foot ulcer risk , thereby providing support for a multifactorial etiology for diabetic foot ulceration 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 OBJECTIVE Custom-made footwear is the treatment of choice to prevent foot ulcer recurrence in diabetes . This footwear primarily aims to offload plantar regions at high ulcer risk . However , ulcer recurrence rates are high . We assessed the effect of offloading-improved custom-made footwear and the role of footwear adherence on plantar foot ulcer recurrence . RESEARCH DESIGN AND METHODS We r and omly assigned 171 neuropathic diabetic patients with a recently healed plantar foot ulcer to custom-made footwear with improved and subsequently preserved offloading ( ∼20 % peak pressure relief by modifying the footwear ) or to usual care ( i.e. , nonimproved custom-made footwear ) . Primary outcome was plantar foot ulcer recurrence in 18 months . Secondary outcome was ulcer recurrence in patients with an objective ly measured adherence of ≥80 % of steps taken . RESULTS On the basis of intention-to-treat , 33 of 85 patients ( 38.8 % ) with improved footwear and 38 of 86 patients ( 44.2 % ) with usual care had a recurrent ulcer ( relative risk −11 % , odds ratio 0.80 [ 95 % CI 0.44–1.47 ] , P = 0.48 ) . Ulcer-free survival curves were not significantly different between groups ( P = 0.40 ) . In the 79 patients ( 46 % of total group ) with high adherence , 9 of 35 ( 25.7 % ) with improved footwear and 21 of 44 ( 47.8 % ) with usual care had a recurrent ulcer ( relative risk −46 % , odds ratio 0.38 [ 0.15–0.99 ] , P = 0.045 ) . CONCLUSIONS Offloading-improved custom-made footwear does not significantly reduce the incidence of plantar foot ulcer recurrence in diabetes compared with custom-made footwear that does not undergo such improvement , unless it is worn as recommended OBJECTIVE To assess the efficacy of in-shoe orthoses that were design ed based on shape and barefoot plantar pressure in reducing the incidence of submetatarsal head plantar ulcers in people with diabetes , peripheral neuropathy , and a history of similar prior ulceration . RESEARCH DESIGN AND METHODS Single-blinded multicenter r and omized controlled trial with subjects r and omized to wear shape- and pressure-based orthoses ( experimental , n = 66 ) or st and ard-of-care A5513 orthoses ( control , n = 64 ) . Patients were followed for 15 months , until a study end point ( forefoot plantar ulcer or nonulcerative plantar forefoot lesion ) or to study termination . Proportional hazards regression was used for analysis . RESULTS There was a trend in the composite primary end point ( both ulcers and nonulcerative lesions ) across the full follow-up period ( P = 0.13 ) in favor of the experimental orthoses . This trend was due to a marked difference in ulcer occurrence ( P = 0.007 ) but no difference in the rate of nonulcerative lesions ( P = 0.76 ) . At 180 days , the ulcer prevention effect of the experimental orthoses was already significant ( P = 0.003 ) when compared with control , and the benefit of the experimental orthoses with respect to the composite end point was also significant ( P = 0.042 ) . The hazard ratio was 3.4 ( 95 % CI 1.3–8.7 ) for the occurrence of a submetatarsal head plantar ulcer in the control compared with experimental arm over the duration of the study . CONCLUSIONS We conclude that shape- and barefoot plantar pressure – based orthoses were more effective in reducing submetatarsal head plantar ulcer recurrence than current st and ard-of-care orthoses , but they did not significantly reduce nonulcerative lesions Various foot structures are thought to influence forefoot plantar pressures during walking . High peak plantar pressures ( PPP ) during walking in people with diabetes mellitus ( DM ) and peripheral neuropathy ( PN ) can cause skin breakdown . The question addressed by this study is " What are the primary forefoot structural factors that predict regional PPP during walking in groups of people with and without DM and PN ? " Twenty people with DM and PN ( mean age 55+/-9 years , 6 female , 14 male , BMI = 33+/-8 ) and 20 people without DM , matched for gender , age , and BMI were tested . Measures of foot structure were taken from three-dimensional images constructed from spiral X-ray computed tomography . Peak plantar pressure data were recorded during walking . Hierarchical multiple regression analysis was used to predict regional PPP at the great toe and five metatarsal heads from selected structural and walking variables . Metatarsal phalangeal joint angle ( hammer toe deformity ) was the most important variable predicting pressure , accounting for 19 - 45 % of the PPP variance at five of the six locations in the DM group . Soft tissue thickness , hallux valgus , and forefoot arthropathy were the most important predictors of PPP in the control group . Combinations of structural and walking variables accounted for 47 - 71 % of the variance in the DM group and 52 - 83 % of the variance of PPP during walking in the control group . These structural variables , especially hammer toe deformity , should be considered in attempts to develop strategies to reduce excessive forefoot PPP that may contribute to skin breakdown or other injury 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 A longitudinal double-blind study was conducted to determine the effect of sock fiber composition on the frequency and size of blistering events in long-distance runners . Thirty-five long-distance runners participated in this study . Two different socks were tested , which were identical in every aspect of construction except fiber composition . One test sock was composed of 100 % acrylic fibers , and the other test sock was composed of 100 % natural cotton fibers . The results showed that acrylic fiber socks were associated with fewer blistering events and smaller blisters ( mm2 ) , when compared directly to cotton fiber socks The Difoprev system constituted by a sock loaded with nanocapsules containing a hydrating agent in the diabetic foot is tested . A total of 30 neuropathic out patients with foot anhydrosis were r and omized into group A , treated with the application of the sock with the nanocapsules , and group B wearing only the socks without the nanocapsules . Patients were blindly evaluated with a clinical score , hygrometry , transepidermal water loss , skin temperature , and skin hardness at baseline and after 6 weeks . No difference between the groups emerged at baseline . Although group B showed no changes at the end of the treatment , group A significantly ( P < .05 ) improved in all the parameters evaluated . No adverse events were recorded in both groups during the study . The use of hydrating agents carried by nanocapsules-loaded socks is safe and effective for the neuropathic diabetic foot It should now be possible to achieve a reduction in the incidence of foot ulceration and amputations as knowledge about pathways that result in both these events increases . However , despite the universal use of patient education and the hope of reducing the incidence of ulcers in high-risk patients , there are no appropriately design ed large , r and omized controlled trials actually confirming that education works . It has been recognized for some years that education as part of a multidisciplinary approach to care of the diabetic foot can help to reduce the incidence of amputations in certain setting s. Ultimately , however , a reduction in neuropathic foot problems will only be achieved if we remember that the patients with neuropathic feet have lost their prime warning signal — pain — that ordinarily brings patients to their doctor . Very little training is offered to health care professionals as to how to deal with such patients . Much can be learned about the management of such patients from the treatment of individuals with leprosy : if we are to succeed , we must realize that with loss of pain there is also diminished motivation in the healing of and prevention of injury AIMS We assessed baseline clinical foot shape for 2939 feet of diabetic subjects who were monitored prospect ively for foot ulceration . METHODS Assessment s included hammer/claw toes , hallux valgus , hallux limitus , prominent metatarsal heads , bony prominences , Charcot deformity , plantar callus , foot type , muscle atrophy , ankle and hallux mobility , and neuropathy . Risk factors were linked to ulcer occurrence and location via a Cox proportional hazards model . RESULTS Hammer/claw toes ( hazard ratio [ HR ] ( 95 % confidence interval [CI])=1.43 ( 1.06 , 1.94 ) p=0.02 ) , marked hammer/claw toes ( HR=1.77 ( 1.18 , 2.66 ) p=0.006 ) , bony prominences ( HR=1.38 ( 1.02 , 1.88 ) , p=0.04 ) , and foot type ( Charcot or drop foot vs. neutrally aligned ) ( HR=2.34 ( 1.33 , 4.10 ) , p=0.003 ) were significant risk factors for ulceration adjusting for age , body mass index , insulin medication , ulcer history and amputation history . With adjustment for neuropathy only hammer/claw toes ( HR=1.40 ( 1.03 , 1.90 ) , p=0.03 ) and foot type ( HR=1.76 ( 1.04 , 3.04 ) , p=0.05 ) were significantly related to ulceration . However , there was no relationship between ulcer location and foot deformity . CONCLUSIONS Certain foot deformities were predictive of ulceration , although there was no relationship between clinical foot deformity and ulcer location |
10,573 | 21,631,835 | Types of outcome measures The primary outcome was the relief or reduction of post-operative pain .
Results Overall , there is no strong evidence to support the use of any intervention even though a few interventions showed some benefits .
However , evidence for these benefits was often based on single studies .
Most of the included studies showed that there was no difference between the interventions and the usual care with both being found equally effective .
Implication s for practice There was no strong evidence to support a particular practice .
No intervention was found to be harmful ; however , this does not presume to be evidence of safety . | Objectives The primary objective of this systematic review was to assess the effectiveness of nursing interventions for the relief/reduction of post-operative pain when compared with either st and ard care or other nursing interventions . | The pharmacy and nursing time requirements , quality of postoperative pain control , and cost of patient-controlled analgesia ( PCA ) and intramuscular ( i.m . ) analgesic therapy were studied . All timings were conducted with a stopwatch on a single nursing unit that primarily receives gynecologic surgery patients . The various work elements involved in each type of therapy were timed individually . Both quality of analgesia and cost were evaluated in a prospect i ve , r and omized study in hysterectomy patients . I.M. patients received meperidine hydrochloride 75 - 100 mg every three to four hours as needed . PCA patients had access to morphine sulfate 1 mg or meperidine hydrochloride 10 mg , with a six-minute lockout period . The patients scored their pain every four hours . Direct costs for PCA were calculated as drug cost plus tubing cost plus form cost plus maintenance cost plus depreciation cost . Direct costs for i.m . therapy consisted of the cost of drugs . The total mean nursing time per patient was 16.9 minutes for PCA and 10.7 minutes for i.m . therapy . Pharmacy time per patient was 5.1 minutes longer for PCA than for i.m . therapy . Thirty-six hysterectomy patients ( 17 i.m . and 19 PCA ) were enrolled in the study of pain control and cost . Among i.m . patients , 64 % of the pain scores were mild or worse , compared with 40 % for PCA patients . The median pain scores were moderate for i.m . patients and mild for PCA patients . Scores tended to be lower for PCA patients at 16 and 20 hours . Although equal numbers of patients in the two groups experienced nausea , i.m . patients needed more doses of antiemetics than PCA patients . ( ABSTRACT TRUNCATED AT 250 WORDS & NA ; Cardiovascular diseases cause more disability and economic loss in industrialized nations than any other group of diseases . In previous work [ Nurs Res 49 ( 2000a ) 1 ] , most coronary artery bypass graft patients ( CABG , N=225 ) reported unrelieved pain and received inadequate analgesics . This study proposed to evaluate a preadmission education intervention to reduce pain and related activity interference after CABG surgery . Patients ( N=406 ) were r and omly assigned to ( a ) st and ard care or ( b ) st and ard care+pain booklet group . Data were examined at the preadmission clinic and across days 1–5 after surgery . Outcomes were pain‐related interference ( BPI‐I ) , pain ( MPQ‐SF ) , analgesics ( chart ) , concerns about taking analgesics ( BQ‐SF ) , and satisfaction ( American Pain Society‐POQ ) . The impact of sex was explored related to primary and secondary outcomes . The intervention group did not have better overall pain management although they had some reduction in pain‐related interference in activities ( t(355)=2.54 , P<0.01 ) and fewer concerns about taking analgesics ( F(1,313)=2.7 , P<0.05 ) on day 5 . Despite moderate 24‐h pain intensity across 5 days , patients in both groups received inadequate analgesics ( i.e. 33 % prescribed dose ) . Women reported more pain and pain‐related interference in activities than men . The booklet was rated as helpful , particularly by women . In conclusion , the intervention did not result in a clinical ly significant improvement in pain management outcomes . In future , an intervention that considers sex‐specific needs and also involves educating the health professionals caring for these patients may influence these results Immediately before they underwent femoral angiography , 45 patients were given one of three types of audiotapes : a relaxation response tape recorded for this study , a tape of contemporary instrumental music , or a blank tape . All patients were instructed to listen to their audiotape during the entire angiographic procedure . Each audiotape was played through earphones . Radiologists were not told the group assignment or tape contents . The patients given the audiotape with instructions to elicit the relaxation response ( n = 15 ) experienced significantly less anxiety ( P less than .05 ) and pain ( P less than .001 ) during the procedure , were observed by radiology nurses to exhibit significantly less pain ( P less than .001 ) and anxiety ( P less than .001 ) , and requested significantly less fentanyl citrate ( P less than .01 ) and diazepam ( P less than .01 ) than patients given either the music ( n = 14 ) or the blank ( n = 16 ) control audiotapes . Elicitation of the relaxation response is a simple , inexpensive , efficacious , and practical method to reduce pain , anxiety , and medication during femoral angiography and may be useful in other invasive procedures The purpose of this comparative study was to examine differences in pain intensity , sleep disturbance , sleep effectiveness , fatigue , and vigor between patients undergoing cholecystectomy who received either patient-controlled analgesia ( PCA ) or intramuscular ( IM ) injections of narcotics for postoperative pain . The PCA group consisted of 16 women , aged 22 - 58 ; the IM group consisted of 10 women , aged 22 - 60 . Data were collected on patients ' postoperative days 1 and 2 . Findings indicated that patients receiving PCA reported less pain on postoperative day 1 and less fatigue on postoperative day 2 than patients receiving IM injections of narcotics BACKGROUND In previous studies comparing patient-controlled-analgesia and intramuscular pain management have been unable to provide conclusive evidence of the benefits of either method of postoperative pain control . AIM The purpose of the study was to compare the efficacy and cost-effectiveness of intravenous patient-controlled-analgesia with intermittent intramuscular morphine for Chinese women in the first 24 hours following elective gynaecological surgery . METHODS A r and omized control design was used . The main outcomes were level of pain and cost for the two types of pain management . Participants indicated their level of pain at rest and when deep breathing or coughing on a 100 mm Visual Analogue Scale , on seven occasions within 24 postoperative hours . Costs for the two types of pain management were based on the costs of equipment , drugs and nursing time . RESULTS A total of 125 women participated in the study . Mean pain level over the 24 hours in the patient-controlled-analgesia group was significantly lower than in the intramuscular group ( P < 0.001 ) . Mean pain level over the seven occasions for the patient-controlled-analgesia group was 11.83 points ( 95 % CI 7.14 - 16.52 ) lower when at rest and 11.73 points ( 95 % CI 5.96 - 17.50 ) lower during motion than the intramuscular group . Cost per patient was $ 81.10 ( Hong Kong ) higher for patient-controlled-analgesia than for intramuscular pain management . Women in the patient-controlled-analgesia group had significantly greater satisfaction with pain management than those in the intramuscular group ( P < 0.001 ) , but reported significantly more episodes of nausea ( P < 0.05 ) . CONCLUSIONS While patient-controlled-analgesia was more costly , it was also more effective than conventional on-dem and intramuscular opioid injections after laparotomy for gynaecological surgery Background and Objectives : To compare the use of patient-controlled analgesia to intermittent intramuscular injections of morphine following major gynecological laparoscopic procedures in order to assess differences in level of pain , sedation , episodes of nausea and /or vomiting , hospitalization time and patient satisfaction with their postoperative analgesia . Methods : Seventy-two patients undergoing major gynecological laparoscopic surgery were r and omized to receive either postoperative analgesia via intermittent intramuscular injection of morphine ( Group 1 ) or patient controlled analgesia ( PCA - Group 2 ) . All patients received anesthesia via a st and ardized protocol . Postoperative pain levels were recorded via a 10 cm visual analogue scale , and sedation scores were recorded on a st and ard PCA form . Episodes of nausea and vomiting were also recorded on the same form . Results : There were no statistically significant differences between intramuscular analgesia and PCA for any of the factors studied . Most significantly it was found that most patients ceased to require either form of parenteral analgesia within 24 hours of their procedure , regardless of the operating time . Conclusion : It is important for the surgeon to be aware of the effects of postoperative analgesia on his or her patients ' level of satisfaction . We do not recommend the use of PCA analgesia following major laparoscopic gynecological surgery Colonic surgery patients were studied to measure : the influence of continuous thoracic epidural analgesia ( TEA ) on a postoperative pain score , the time till onset of defaecation , blood loss , postoperative temperature elevations , rate of bacterial contamination of wounds and urine , and general surgical complications . Group I patients ( n = 57 ) received general anaesthesia and TEA for the operation , followed by continuous TEA ( 0·25 per cent bupivacaine ) for 72 h. Group II patients ( n = 59 ) received general anaesthesia for the operation , followed by systemic analgesia on request . Significant beneficial effects of TEA in group I were demonstrated by lower pain scores in the first 24 h after surgery and earlier defaecation . However , there were fewer temperature elevations in group II . There was no significant difference between the groups in terms of positive bacteriological cultures , blood loss , need for postoperative mechanical ventilation and complications . However , there was a trend toward a higher rate of rectal anastomotic breakdown , increased blood replacement and intensive care therapy , and longer hospitalization in group I. These results do not suggest any significant beneficial therapeutic effect of continuous TEA in colonic surgery compared with a conventional systemic analgesic regimen . In selected patients ( i.e. those with severe pain or those prone to develop postoperative ileus ) continuous TEA may be beneficial OBJECTIVE To examine the effects of adjunctive postoperative massage and vibration therapy on short-term postsurgical pain , negative affect , and physiologic stress reactivity . DESIGN Prospect i ve , r and omized controlled trial . The treatment groups were : ( 1 ) usual postoperative care ( UC ) ; ( 2 ) UC plus massage therapy ; or ( 3 ) UC plus vibration therapy . SETTING The University of Virginia Hospital Surgical Units , Gynecology-Oncology Clinic , and General Clinical Research Center . SUBJECTS One hundred and five ( N = 105 ) women who underwent an abdominal laparotomy for removal of suspected cancerous lesions . INTERVENTIONS All patients received UC with analgesic medication . Additionally , the massage group received st and ardized 45-minute sessions of gentle Swedish massage on the 3 consecutive evenings after surgery and the vibration group received 20-minute sessions of inaudible vibration therapy ( physiotones ) on the 3 consecutive evenings after surgery , as well as additional sessions as desired . OUTCOME MEASURES Sensory pain , affective pain , anxiety , distress , analgesic use , systolic blood pressure , 24-hour urine free cortisol , number of postoperative complications , and days of hospitalization . RESULTS On the day of surgery , massage was more effective than UC for affective ( p = 0.0244 ) and sensory pain ( p = 0.0428 ) , and better than vibration for affective pain ( p = 0.0015 ) . On postoperative day 2 , massage was more effective than UC for distress ( p = 0.0085 ) , and better than vibration for sensory pain ( p = 0.0085 ) . Vibration was also more effective than UC for sensory pain ( p = 0.0090 ) and distress ( p = .0090 ) . However , after controlling for multiple comparisons and multiple outcomes , no significant differences were found . CONCLUSIONS Gentle Swedish massage applied postoperatively may have minor effects on short-term sensory pain , affective pain , and distress among women undergoing an abdominal laparotomy for removal of suspected malignant tissues Although epidural opioids frequently are used to provide postoperative analgesia , several articles have suggested that the analgesia after epidural fentanyl is similar to that after an equal dose of fentanyl given intravenously . To address this issue further , 29 postthoracotomy patients were studied in a r and omized , double-blinded trial comparing a lumbar epidural fentanyl infusion with an intravenous fentanyl infusion for analgesia , plasma fentanyl pharmacokinetics , and respiratory effects for 20 h postoperatively . In all patients in both groups , good analgesia was achieved ( pain score less than 3 , maximum 10 ) over a similar time course , although the patients receiving epidural infusion required a significantly larger fentanyl infusion dose than did the patients receiving intravenous infusion ( group receiving epidural fentanyl infusion : 1.95 + /- 0.45 micrograms.kg-1.h-1 ; group receiving intravenous fentanyl infusion : 1.56 + /- 0.36 micrograms.kg-1.h-1 ; P = 0.0002 ) . The time course for the plasma fentanyl concentrations was similar in the two groups , and plasma fentanyl concentrations were not significantly different at any sampling period ( T7-T20 ; group receiving epidural fentanyl infusion : 1.8 + /- 0.5 ng/ml ; group receiving intravenous fentanyl infusion : 1.6 + /- 0.6 ng/ml ; P = 0.06 ) . Similarly , calculated clearance values for the two groups were not significantly different ( group receiving epidural fentanyl infusion : 0.95 + /- 0.26 l.kg-1.h-1 ; group receiving intravenous fentanyl infusion : 0.87 + /- 0.25 l.kg-1.h-1 ; P = 0.3 ) . Both groups demonstrated a similar degree of mild to moderate respiratory depression postoperatively , which was assessed with continuous respiratory inductance plethysmography and sequential arterial blood gas analysis . Side effects ( nausea , vomiting , pruritus ) were mild and did not differ between groups . ( ABSTRACT TRUNCATED AT 250 WORDS AIMS We investigated the effects of relaxation , music , and the combination of relaxation and music on postoperative pain , across and between two days and two activities ( ambulation and rest ) and across ambulation each day . This secondary analysis of a r and omized controlled trial was conducted from 1995 to 1997 . BACKGROUND After surgery , patients do not always receive sufficient relief from opioids and may have undesired side-effects . More complete relief ( 10 - 30 % ) was found recently with adjuvant interventions of relaxation , music , and their combination . Comparison of effects between days and treatments have not been examined longitudinally . METHODS With a repeated measures design , abdominal surgery patients ( n = 468 ) in five US hospitals were assigned r and omly to one of four groups ; relaxation , music , their combination , and control . With institutional approval and written informed consent , subjects were interviewed and taught interventions preoperatively . Postoperative testing was at ambulation and rest on days 1 and 2 using visual analogue ( VAS ) sensation and distress of pain scales . RESULTS Multivariate analysis indicated that although pain decreased by day 2 , interventions were not different between days and activities . They were effective for pain across ambulation on each day , across ambulation and across rest over both days ( all P < 0.001 ) , and had similar effects by day and by activity . CONCLUSION Nurses can safely recommend any of these interventions for pain on both postoperative days and at both ambulation and rest We have compared intermittent bolus and continuous infusion of extradural local anaesthetic for pain relief in a r and omized , double-blind study of 48 patients who underwent major abdominal gynaecological surgery . Each patient received 5 ml of 0.375 % bupivacaine hourly , either as a bolus over 5 min or as a constant infusion . Patients who received the intermittent administration technique maintained a more extensive sensory block , reported marginally better analgesia and had a lower requirement for rescue medication . The intermittent bolus technique was not associated with an increase in side effects UNLABELLED This study , conducted before and after the implementation of an acute pain service ( APS ) in a 1000-bed hospital , describes the process of the implementation of an APS . The nursing , anesthesia , and surgery departments were involved . In this study we sought to evaluate the results of a continuous quality improvement program by defining quality indicators and using quality tools . A quality program in accordance with current st and ards of acute pain treatment ( multimodal ) was worked out to enhance pain relief for all surgical in patients . A survey of nurses ' knowledge with regard to postoperative pain was conducted , and a visual analog scale ( VAS ) was introduced to assess pain intensity . Both nurses and physicians became familiar with evidence -based guidelines concerning postoperative pain . The entire process was monitored in three consecutive surveys and enrolled 2383 surgical in patients . Pain indicators based on VAS and analgesic consumption were recorded during the first 72 postoperative hours . After a baseline survey about current practice s of pain treatment , a nurse-based , anesthesiologist-supervised APS was implemented . The improvement in pain relief , expressed as VAS scores , was assessed in two further surveys . A quality manual was written and implemented . A major improvement in pain scores was observed after the APS inception ( P < 0.001 ) . IMPLICATION S The implementation of an acute pain service , including pain assessment by a visual analog scale , st and ard multimodal pain treatment , and continuous quality evaluation , improved postoperative pain relief . Establishing teams of surgeons , anesthesiologists , and nurses is the prerequisite for this improvement A r and omized , controlled clinical trial was conducted on 66 patients undergoing elective cardiac surgery to compare patient-controlled analgesia ( PCA ) to nurse-controlled analgesia ( NCA ) with continuous morphine infusion . Hourly assessment of pain ( at rest and on movement ) using a visual analogue scale ( VAS ) , of respiratory rate , and level of sedation took place for the 24 h following extubation . The incidence of nausea was also recorded . Mean pain scores were calculated , and peak pain and sedation scores , together with lowest respiratory rates , were identified . Morphine consumption was measured at 24 h. No significant differences were found between the groups ' scores for pain or sedation . The PCA group had significantly lower respiratory rates ( P = 0.02 ) and a lower incidence of nausea ( P = 0.008 ) . The PCA group also consumed significantly more morphine ( P = 0.0001 ) . The study suggests a beneficial effect from PCA after cardiac surgery in reducing nausea , compared to NCA . It confirms nurse-controlled infusion analgesia as an effective form of pain relief in an intensive care and high-dependency setting The present prospect i ve survey was conducted in a 1200-bed hospital to examine postoperative patients ' current pain intensity , most intense pain experienced , satisfaction with postoperative pain management , and differences regarding pain and satisfaction levels . All adult patients admitted to a hospital in Hong Kong for surgery , except those receiving local anesthesia , were eligible to enter this study . The patient outcome question naire developed by the American Pain Society was used to solicit data about patients ' pain and satisfaction with pain relief . The subjects were 294 postoperative patients . Approximately 85 % complained about varying degrees of pain during the 24 h prior to the assessment of their pain . When interviewed , most patients complained of mild to moderate pain ( median = 2 on a 10-point scale ) , while the median for ' worst pain intensity ' was 5 . Approximately 80 % of the subjects indicated that both the nurses and physicians reminded them to report pain when it occurred . Only 143 ( 48.6 % ) agreed that the nurses and physicians sufficiently emphasized the importance of pain relief . Those who received acute pain services , provided by anesthetists , reported lower levels of current pain intensity . Over 65 % of the subjects were satisfied with all levels of health care providers , regarding their postoperative pain management We have compared patients ' and nurses ' assessment s of postoperative pain and anxiety after different analgesic treatments . Sixty orthopaedic patients were allocated r and omly to receive i.v . piritramide ( either nurse-controlled or patient-controlled ) or subarachnoid bupivacaine ( nurse-controlled or patient-controlled ) . Patients and nurses assessed pain and anxiety using a visual analogue scale ( VAS ; 1 - 100 mm ) . Pain and anxiety ratings of patients and nurses were significantly correlated ( Spearman 's r > or = 0.69 ; P < 0.001 ) . In general , patients ' pain scores were higher than nurses ' scores ( patients ' median VAS = 34 ( range 1 - 76 ) mm ; nurses VAS 21 ( 1 - 59 ) mm ) and for all groups except the patient-controlled subarachnoid bupivacaine group , where they were significantly higher ( P < 0.01 ) . Discrepancy in pain estimates between patients and nurses increased with the level of pain . The relationship between patients ' and nurses ' anxiety scores was less clearly defined and did not depend on the level of anxiety The aim of the study was to evaluate the effect of preparatory information on a patient 's post-operative physical coping outcomes following a Total Hip Replacement ( THR ) . The research design was quasi-experimental . Eighty-two healthy individuals , scheduled for an elective THR were used and selected using non-r and om techniques , and placed into one of two groups on an alternating basis . The subjects in the experimental group were given procedural , sensory and coping information relating to the whole surgical procedure of a THR . In addition , written information was provided for each experimental subject to support the verbal information . Subjects in the control group only received the advice and support that would routinely be given to THR patients by ward , medical and nursing staff . The study measured a number of physical outcomes using a " Physical Indicators of Coping Question naire " developed to measure physiological and physical outcomes post-operatively . In addition , a Linear Analogue Coping Scale was developed to assess a patient 's personal perception of their overall coping ability with the THR . The study demonstrated that preparatory information , given pre-operatively , post-operatively and pre-discharge had positive effects on the physical recovery and coping outcomes measured . Subjects in the experimental group had significantly less post-operative intramuscular analgesia , mobilized sooner with a Zimmer frame and walking sticks and lastly , their length of stay was on average , 2 days less than the control group . The Linear Analogue Coping Scale demonstrated that patients in the experimental group did perceive they were coping more effectively post-operatively . Preparatory information of various types and in different forms appear to have positive effects on the ability of patients to cope with and recover physically from a THR in the immediate post-operative period Acupuncture has been shown to be effective in experimental and clinical acute pain setting s. This study aims to evaluate the effect of preoperative electroacupuncture ( EA ) on intraoperative and postoperative analgesic ( alfentanil and morphine ) requirement in patients scheduled for gynaecologic lower abdominal surgery . Ninety patients were r and omly assigned to one of three groups : Group I ( control group ) –received placebo EA for 45 minutes before induction of general anaesthesia ( GA ) ; Group II –preoperative EA instituted 45 minutes before induction of GA ; Group III – 45 minutes of postoperative EA . The Bispectral Index monitor was used intraoperatively to monitor the hypnotic effect of anaesthetic drugs , and alfentanil was titrated to maintain the blood pressure and pulse rate within ±15 % of basal values . Postoperative pain was managed by intravenous morphine via a patient-controlled analgesia ( PCA ) device . Patients in Group II ( 0.44 ± 0.15μg/kg/min ) received less alfentanil than those in Group III ( 0.58 ± 0.22μg/kg/min ) ( p=0.024 ) , but not significantly less than those in Group I ( 0.51 ± 0.21μg/kg/min ) ( p=0.472 ) . Postoperative morphine consumption was numerically lower in Group II compared with the other groups ; however , the difference was statistically significant only during the period of 6–12 hours between Group II [ 0.03 ( 0.05 ) mg/kg ] and Group I [ 0.10 ( 0.11 ) mg/kg ] ( p=0.015 ) , and Group II and Group III [ 0.08 ( 0.10 ) mg/kg ] ( p=0.010 ) . The 24-hour cumulative morphine consumption for Group II ( 0.52 ± 0.19mg/kg ) was less than that for either Group I ( 0.68 ± 0.38mg/kg ) or Group III ( 0.58 ± 0.27mg/kg ) , but the difference did not reach significance . In conclusion , preoperative EA leads to a reduced intraoperative alfentanil consumption , though this effect may not be specific , and has a morphine sparing effect during the early postoperative period The aim of this r and omized controlled trial was to determine the effect of jaw relaxation , music and the combination of relaxation and music on postoperative pain after major abdominal surgery during ambulation and rest on postoperative days 1 and 2 . Opioid medication provided for pain , following abdominal surgery , does not always give sufficient relief and can cause undesired side effects . Thus , additional interventions such as music and relaxation may provide more complete relief . Previous studies have found mixed results due to small sample sizes and other method ological problems . In a rigorous experimental design , 500 subjects aged 18 - 70 in five Midwestern hospitals were r and omly assigned by minimization to a relaxation , music , relaxation plus music , or control group . Interventions were taught preoperatively and tested postoperatively . The same amount of time was spent with subjects in the control group . Pain was measured with the visual analogue sensation and distress of pain scales . Demographic and surgical variables , and milligrams of parenteral or oral opioids in effect at the time of testing were not significantly different between the groups , nor did they correlate with pain scores . Controlling for pretest sensation and distress , orthogonal a priori contrasts and multivariate analysis of covariance indicated that the three treatment groups had significantly less pain than the controls , ( P = 0.028 - 0.000 ) which was confirmed by the univariate analysis of covariance ( P = 0.018 - 0.000 ) . Post hoc multivariate analysis revealed that the combination group had significantly less sensation and distress of pain than the control group on all post-tests ( P = 0.035 - 0.000 ) , and the relaxation and music groups had significantly less on all tests ( P = 0.022 - 0.000 ) except after ambulation . At post ambulation those using relaxation did not have significantly less pain than the controls on both days and those using music did not on day 1 , although there were some univariate effects . A corresponding significant decrease in mastery of the interventions from pre to post ambulation suggests the need for reminders to focus on the intervention during this increased activity . Physicians and nurses preparing patients for surgery and caring for them afterward , should encourage patients to use relaxation and music as adjuvants to medication for postoperative pain Patient-controlled i.v . administration and intramuscular administration of morphine sulfate were compared in a crossover study to determine their relative effectiveness in relieving postoperative pain . Twenty adult patients scheduled for abdominal surgery were r and omly assigned to one of two groups ; one group received i.v . morphine sulfate for 24 hours using a patient-controlled analgesia ( PCA ) device , after which they were given morphine sulfate i.m . for 24 hours . The treatment order was reversed for the other group . Amount of narcotic administered , respiratory rate , and levels of discomfort , activity , and sedation were assessed by the nursing staff every two hours . At the end of each 24-hour treatment phase , patients ranked their level of pain , amount of pain relief , level of sedation , ability to sleep , and ability to perform pulmonary toilet . Patients were also asked whether they preferred PCA or i.m . analgesic therapy for future surgery . Patients reported significantly less discomfort while using PCA than during i.m . morphine administration . No significant differences in amount of narcotic used , respiratory rate , nausea and vomiting , or levels of activity or sedation were noted for the two regimens . Patients ' rankings of the two treatment modes did not differ significantly , but a majority of patients indicated a preference for future use of PCA . In these postoperative patients , administration of i.v . morphine sulfate by PCA was as safe as i.m . administration and possibly more effective in relieving pain The report of the joint working party of the Royal College of Surgeons of Engl and , Pain after Surgery , raised many questions in relation to the way pain is managed after surgery . This report question ed many of the existing practice s of pain control and highlighted the need for the development of regular pain assessment . The report raised questions regarding PRN ( pro-re nata , as needed ) prescribing and reinforced the importance of the role of the nurse . This study review s the way pain is managed in this hospital with regard to analgesia prescribing and analgesia administration trends as well as the documentation of pain . The study was conducted by retrospective review of r and omly selected patient charts . The results of this study conclude that documentation of pain following surgery is poor , and needs improvement . Existing prescription trends , in particular PRN prescribing , may be hindering both good practice and the pre-emptive administration of analgesia BACKGROUND There is little published evidence of the analgesic efficacy of patient-controlled epidural analgesia ( PCEA ) for postoperative pain relief . The aim of this study was to compare the analgesic efficacy of epidural infusion of bupivacaine 0.125 % and fentanyl 4 microg ml(-1 ) administered by either PCEA with a background infusion or nurse-administered continuous epidural infusion ( CEI ) after major intra-abdominal surgery . METHODS In a double-blind , r and omized clinical trial , 205 adult patients undergoing colonic resection by laparotomy received either PCEA or CEI . Pain scores were recorded via a four-point verbal rating scale at 1 , 2 , 3 , 4 , 8 , 12 , 24 , 48 , and 72 h after surgery . The administration of epidural top-ups and systemic analgesia over the same period was also recorded , and patient satisfaction question naires completed . RESULTS The median area under the curve of pain against time was significantly lower in the PCEA group ( 2 vs 24 , P<0.001 ) as were median summary pain scores on movement ( 0.67 vs 1.33 , P<0.001 ) . Significantly fewer patients in the PCEA group received one or more epidural top-ups ( 13 vs 36 % , P = 0.0002 ) or any systemic analgesics ( 41 vs 63 % , P = 0.0021 ) . Patients in the PCEA group were significantly more likely to be very satisfied than in the CEI group ( 76 vs 43 % , P<0.0001 ) . CONCLUSIONS PCEA provides greater analgesic efficacy than CEI for postoperative analgesia after major intra-abdominal surgery , and a decreased requirement for physician or nurse intervention PURPOSE When using strong oral opioids for postoperative pain management , dem and titration is desirable . A device for patient controlled oral analgesia ( PCORA ) and first results of its use for oral titration of morphine are presented . METHODS The PCORA-device is a modified Baxter-PCA-on-dem and system ( maximum bolus volume : 0.5 ml ; flow rate for filling bolus volume : 0.5 ml.hr-1 ) . The dem and PCORA-volumes were measured at specific time intervals and PCORA was compared with customarily prescribed pain therapy ( CPPT ) for postoperative pain management . On the first postoperative day , 20 orthopaedic ASA I or II patients received , in a r and omised , cross-over trial , either PCORA ( 300 min ) followed by CPPT ( 300 min ) ( Group I ) or vice versa ( Group II ) . The PCORA-device permitted a maximum dose of 15 mg morphine per 60 min and CPPT was performed by the ward doctor or nurse . Pain intensity ( 101-point numerical rating scale ) and side effects were evaluated at 30 min intervals . RESULTS The accuracy of the bolus volume delivered by the PCORA-device was 89.2 + /- 0.85 % ( mean + /- SEM ) , of manufacturer 's specifications . PCORA pain intensity decreased over time whereas CPPT pain intensity did not ( P < 0.001 ) . PCORA-morphine requirements were 61.5 + /- 5.2 mg ( Group I ) and 52.5 + /- 8.5 mg ( Group II ) ( NS ; mean + /- SEM ) . The h and ling of the PCORA-device presented no problem to any patient . CONCLUSION Patient controlled oral analgesia is an effective and non-invasive mode of postoperative pain management . The PCORA-device is reliable and easy to use This investigation evaluated patient – controlled analgesia ( PCA ) for subjective well – being and mood in the postoperative period in comparison with the intramuscular ( i m ) administration of morphine given on dem and . Patients scheduled for elective upper abdominal surgery were assigned at r and om to either PCA ( n = 17 ) or i m morphine ( n= 14 ) . The PCA group experienced significantly more pain relief and consumed more morphine than those who received i m morphine . The PCA patients suffered from more fatigue and showed less vigour than the i m group . Neither preoperative trait anxiety nor locus of control was associated with postoperative pain in either of the groups Background : Patient‐controlled analgesia ( PCA ) with intravenous piritramide and subarachnoid bupivacaine was studied during postoperative pain management in comparison with nurse‐administered bolus injections & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies The benefits of two dosing methods , patient-controlled analgesia ( PCA ) with morphine sulfate ( MS ) alone and PCA plus continuous infusion of morphine sulfate ( PCA + CI ) were clinical ly evaluated in a r and omized , single-blinded study of 30 adult abdominal surgery patients . Doses were adjusted based on pain and sedation ratings . Respirations , pulse , blood pressure , pain and sedation ratings were assessed . Subjects rated their pain twice daily using a visual analog scale for 72 hr postoperatively . The subjects reported pain relief with both dosing regimens . No statistically significant differences between the groups were found in pain and sedation ratings , or length of time using the device , with the exception of a higher amount of MS used on postoperative day two by the infusion group ( p less than 0.003 ) . There seems to be a trend for the PCA + CI group to have less fluctuation in sedation between days and better pain control ( as demonstrated by verbal and visual analog pain scores ) on the third postoperative day . Statistical significance was not found , however . PCA plus continuous infusion of MS may be a beneficial approach to the management of postoperative pain in selected patients ; studies to identify these patients need to be done BACKGROUND Continuous passive motion after major knee surgery optimizes the functional prognosis but causes severe pain . The authors tested the hypothesis that postoperative analgesic techniques influence surgical outcome and the duration of convalescence . METHODS Before st and ardized general anesthesia , 56 adult scheduled for major knee surgery were r and omly assigned to one of three groups , each to receive a different postoperative analgesic technique for 72 h : continuous epidural infusion , continuous femoral block , or intravenous patient-controlled morphine ( dose , 1 mg ; lockout interval , 7 min ; maximum dose , 30 mg/4 h ) . The first two techniques were performed using a solution of 1 % lidocaine , 0.03 mg/ml morphine , and 2 microg/ml clonidine administered at 0.1 ml x kg(-1 ) x h(-1 ) . Pain was assessed at rest and during continuous passive motion using a visual analog scale . The early postoperative maximal amplitude of knee flexion was measured during continuous passive motion at 24 h and 48 h and compared with the target levels prescribed by the surgeon . To evaluate functional outcome , the maximal amplitudes were measured again on postoperative day 5 , at hospital discharge ( day 7 ) , and at 1- and 3-month follow-up examinations . When the patients left the surgical ward , they were admitted to a rehabilitation center , where their length of stay depended on prospect ively determined discharge criteria RESULTS The continuous epidural infusion and continuous femoral block groups showed significantly lower visual analog scale scores at rest and during continuous passive motion compared with the patient-controlled morphine group . The early postoperative knee mobilization levels in both continuous epidural infusion and continuous femoral block groups were significantly closer to the target levels prescribed by the surgeon than in the patient-controlled morphine group . On postoperative day 7 , these values were 90 degrees ( 60 - 100 degrees)(median and 25th-75th percentiles ) in the continuous epidural infusion group , 90 degrees ( 60 - 100 degrees ) in the continuous femoral block group , and 80 degrees ( 60 - 100 degrees ) in the patient-controlled morphine group ( P < 0.05 ) . The duration s of stay in the rehabilitation center were significantly shorter : 37 days ( range , 30 - 45 days ) in the continuous epidural infusion group , 40 days ( range , 31 - 60 days ) in the continuous femoral block group , and 50 days ( range , 30 - 80 days ) in the patient-controlled morphine group ( P < 0.05 ) . Side effects were encountered more frequently in the continuous epidural infusion group . CONCLUSION Regional analgesic techniques improve early rehabilitation after major knee surgery by effectively controlling pain during continuous passive motion , thereby hastening convalescence BACKGROUND Opioid analgesia alone may not fully relieve all aspects of acute postoperative pain . Complementary medicine techniques used as adjuvant therapies have the potential to improve pain management and palliate postoperative distress . STUDY DESIGN This prospect i ve r and omized clinical trial compared pain relief after major operations in 202 patients who received one of three nursing interventions : massage , focused attention , or routine care . Interventions were performed twice daily starting 24 hours after the operation through postoperative day 7 . Perceived pain was measured each morning . RESULTS The rate of decline in the unpleasantness of postoperative pain was accelerated by massage ( p = 0.05 ) . Massage also accelerated the rate of decline in the intensity of postoperative pain but this effect was not statistically significant . Use of opioid analgesics was not altered significantly by the interventions . CONCLUSIONS Massage may be a useful adjuvant therapy for the management of acute postoperative pain . Its greatest effect appears to be on the affective component ( ie , unpleasantness ) of the pain Anecdotal reports support research findings in documenting the high incidence of negative postoperative outcomes after gynecologic ( GYN ) laparoscopic surgery . Three outcome measures , postoperative pain , postoperative nausea and vomiting ( PONV ) , and length of stay , have received considerable attention . Two nursing interventions frequently suggested for their positive effects are guided imagery and music therapy . An experimental pilot study was conducted to determine the effects of these nursing inventions on postoperative pain , PONV , and length of stay for GYN laparoscopic patients ( n = 84 ) . During the perioperative period , patients were r and omly assigned to one of 3 interventions : guided imagery audiotapes ( GI ) , music audiotapes ( MU ) , or st and ard care ( C ) , and outcome measures were evaluated . Results indicated that patients in both the guided imagery and music groups had significantly less pain on PACU discharge to home than the patients in the control group . These findings suggest that both guided imagery and music are effective strategies in improving pain , a difference that becomes apparent when the patient is ready to be discharged . It is possible that these interventions act as distractions in reducing the report of negative postoperative outcomes Background Laparoscopic cholecystectomy is associated with a high incidence of postoperative pain , nausea , and vomiting . Pneumoperitoneum created during the operation and residual gas after the operation are two of the factors in postoperative pain and nausea . We studied the effects of a subdiaphragmatic gas drain , which is intended to decrease the residual gas , on postoperative pain , nausea , and vomiting after laparoscopic cholecystectomy . Patients and methods Seventy patients were r and omized into two demographically and clinical ly comparable groups : drainage and control . Postoperative pain , nausea , and vomiting were measured by verbal grading and visual analog scale 2–72 h postoperatively . Analgesic and antiemetic use and incidence of retching , vomiting and other complaints were also recorded . Results Subdiaphragmatic drain effectively reduced the incidence and amount of subdiaphragmatic gas bubble . The incidence and severity of nausea was lower in the drainage group at 72 h. Although severity of pain was lower at 8 and 12 h in the drainage group , the difference was not significant . There was also no difference between the groups in regard to analgesic and antiemetic use . Conclusions Subdiaphragmatic drain offers only minor , if any , benefit on postoperative pain , nausea , and vomiting after laparoscopic cholecystectomy , and this effect is probably clinical ly irrelevant Background : Patient‐controlled analgesia ( PCA ) techniques and intrathecal morphine are the most widely used treatments for post‐Caesarean section pain . However these methods have not been compared with respect to analgesic quality and cost differences & NA ; We have compared analgesic requirements , perceived pain , and self‐ assessment of ‘ health locus of control ’ for 72 h in 88 subjects after cholecystectomy , r and omized to either a st and ard technique of self‐administration of meperidine ( patient‐controlled analgesia , PCA ) or to intramuscular injections on dem and ( i.m . ) . Multivariate analysis revealed no statistical differences between group scores for pain ( over any 24 h period ) and only minor differences in total meperidine administered . However , the PCA group received significantly less analgesic in the first 24 h ( P < 0.01 ) and described significantly more pain over the first 4 h ( P < 0.01 ) . Assessment of ‘ health locus of control ’ did not show any marked changes . Analysis of patient question naires suggests more enthusiasm for patient‐controlled analgesia , but in this study , it was difficult to clearly demonstrate any significant advantage for pain management or amount of opiate administered The purpose of this r and omized controlled trial was to investigate the effect of three nonpharmacologic nursing interventions : relaxation , music , and the combination of relaxation and music on pain following gynecologic ( GYN ) surgery . A total of 311 patients , ages 18 to 70 , from five Midwestern hospitals , were r and omly assigned using minimization to either three intervention groups or a control group and were tested during ambulation and rest on postoperative days 1 and 2 . Pain sensation and distress were measured using visual analogue scales . Multivariate analysis of covariance of posttest sensation and distress was used with pretest control and a priori contrasts . The intervention groups had significantly less posttest pain than the control group ( p = .022-.001 ) on both days . The three interventions were similar in their effect on pain . Patients who received the interventions plus patient-controlled analgesia ( PCA ) had 9 % to 29 % less pain than controls who used PCA alone . Reduced pain was related to amount of activity ( ambulation or rest ) , mastery of the use of the intervention , and decreased pulse and respiration . Those who slept well had less pain the following day . Nurses who care for GYN surgical patients can provide soft music and relaxation tapes and instruct patients to use them during postoperative ambulation and also at rest on days 1 and 2 There are no comparisons of IV patient controlled analgesia ( IV PCA ) versus nurse-administered subcutaneous ( NA SC ) morphine for acute postoperative pain . We undertook a prospect i ve , r and omized , controlled clinical trial of 80 cardiac surgical patients to compare IV PCA with NA SC morphine for postoperative pain control . Visual analog scale ( VAS ) pain scores at rest and with movement , daily verbal pain relief scores , and side effect profiles were not significantly different . Total morphine requirements in the two groups were not significantly different . A physiotherapist 's evaluation of the effectiveness of analgesia for chest physiotherapy revealed no difference between the two groups . We conclude that NA SC morphine , administered as required ( up to hourly ) , is a satisfactory alternative to IV PCA morphine after cardiac surgery . Implication s : In a prospect i ve , r and omized study , we have shown that nurse-administered subcutaneous morphine is a satisfactory alternative to IV patient-controlled analgesia after cardiac surgery . ( Anesth Analg 1998;87:11 - 5 OBJECTIVE To examine the difference between the prescribed and actually administered dose of analgesic and sedative drugs in critically ill patients . DESIGN Prospect i ve survey . SETTING University hospital surgical intensive care unit . SUBJECTS One hundred fifty consecutive adult patients admitted to a surgical intensive care unit over a 3-month period . METHODS Data were gathered on a daily basis . The sedation and analgesia given were compared with the daily physician orders . RESULTS Narcotics and benzodiazepines were most commonly used . On average only 22 % to 52 % of the mean ordered dose of intravenous and intramuscular morphine was actually administered . Larger doses of morphine were administered to intubated patients than to nonintubated ones . Patients receiving intravenous fentanyl infusions generally were administered more than the ordered dose . The actual and prescribed doses of epidural fentanyl were well matched . Midazolam was the most frequently prescribed benzodiazepine . Like morphine , the amount administered was below the maximum ordered by the physicians . CONCLUSIONS Physicians tended to write fairly nonspecific orders that were used by the nursing staff as very broad guidelines . A need exists to educate physicians as to what patients actually receive for sedation and analgesia and at the same time improve the dialogue between nurses and physicians as to what patients actually require The primary objective of this study was to test whether specific information given prior to surgery can help patients obtain better pain relief after total knee arthroplasty ( TKA ) . Secondary objectives were to study the impact of preoperative information on state and trait anxiety , satisfaction with pain management and satisfaction with nursing care . The study was an intervention study with two groups of equal size ( n=30 ) . The intervention group was given specific information while the control group received routine information . Pain assessment s were made preoperatively and every 3h for the first three postoperative days , using the visual analogue scale ( VAS ) . The results of this study suggest that information does influence the experience of pain after surgery and related psychological factors . The postoperative pain declined more rapidly for patients in the treatment group , the degree of preoperative state anxiety was lower and they were more satisfied with the postoperative pain management Background and Objectives . Patient-controlled analgesia ( PCA ) offers effective postoperative pain management . However , the evidence of economic benefits associated with its use is lacking . Although suggestive , the potential economic advantages of PCA in saving nursing time and shortening hospital stay need objective documentation . Methods . This study compared the effects of morphine administered by PCA systems with intra-muscular ( IM ) morphine injection on patient analgesic response , satisfaction , nursing time requirements , and postoperative recovery in 23 patients undergoing “ open ” cholecystectomy and 44 patients undergoing lumbar laminectomy and bony fusion . After the operation , patients in the PCA group received 1.5 - 2 mg morphine with a lockout of 5 - 10 minutes on dem and , whereas those in the IM group received 0.15 - 0.2 mg/kg every 4 hours on dem and . Visual analog scale ( VAS ) pain scores and satisfaction scores were evaluated at 4-hour intervals while nursing time spent on both analgesia-related and non-analgesia-related activities was recorded continuously by a team of independent observers on the ward . Recovery time profile for the return of bowel function , activities of daily living , ambulation without support , and length of hospital stay was also recorded . Results . It was found that morphine consumption , VAS , and satisfaction scores were similar in both PCA and IM treatment groups following both types of surgery . However , the delay in nurse response to IM morphine request ranged from 27.2 ± 3.2 to 42.1 ± 11.8 minutes . The dem and of nursing time on analgesia administration was less with PCA . The magnitude of time saving was 10 min/patient/d in chole-cystectomy patients and 13 min/patient/d in laminectomy patients . The speed of post-operative patient recovery was similar between the two analgesia groups . Length of hospital stay following cholecystectomy was shorter—92.0 ± 5.9 hours with PCA versus 128.6 ± 22.2 hours with IM ( not statistically significant)—whereas that following laminectomy was not different . Conclusions . Data in this study have demonstrated some beneficial effects of PCA on nursing time requirements when it was used following cholecystectomy and lumbar laminectomy at the University of Toronto ; however , the magnitude of these benefits was less than previously reported . The effects of PCA on postoperative recovery and hospital stay , however , were not significantly different from IM therapy The purpose of this study was to assess the effect of external venous support on edema and pain in the saphenous graft leg of patients who had coronary artery bypass graft surgery ( CABG ) 5 days and 1 month after surgery . Fifty-six patients who had CABG surgery were r and omly assigned to the experimental ( n = 24 ) or control ( n = 32 ) group . Subjects in the experimental group wore grade d compression support hose . Edema was assessed by using ankle , calf , and thigh circumference measurements . Pain was measured on a visual analog scale . Hose were effective in preventing edema during hospitalization , but results at 1 month were inconclusive . There was no difference in leg pain for experimental and control subjects . That a number of patients in the experimental group were unable to complete the study suggests that off-the-shelf , thigh-high support hose may not be useful for individuals with disproportionately large thighs . Further investigation of the long-term effects of support hose is warranted The aim of this study was to evaluate the impact of an intervention design ed to improve postoperative pain assessment and recording by nurses An equivalent groups design with a treatment group of 19 patients and a control group of 20 patients was used to investigate the impact of massage therapy on patients ' perceptions of post-operative pain . Data were analysed using analysis of covariance repeated measures ( within subjects ) design . Controlling for age , the results indicated that massage produced a significant reduction in patients ' perceptions of pain over a 24 hour period . A linear positive relationship emerged between patients ' age and the duration of the massage . The study indicates that further investigation of the potential for massage to reduce pain is warranted BACKGROUND Because of the widely presumed association between heart disease and psychological wellbeing , the use of so-called ' complementary ' therapies as adjuncts to conventional treatment modalities have been the subject of considerable debate . The present study arose from an attempt to identify a safe and effective therapeutic intervention to promote wellbe ing , which could be practicably delivered by nurses to patients in the postoperative recovery period following coronary artery bypass graft ( CABG ) surgery . Aim . To investigate the impact of foot massage and guided relaxation on the wellbeing of patients who had undergone CABG surgery . METHOD Twenty-five subjects were r and omly assigned to either a control or one of two intervention groups . Psychological and physical variables were measured immediately before and after the intervention . A discharge question naire was also administered . RESULTS No significant differences between physiological parameters were found . There was a significant effect of the intervention on the calm scores ( ANOVA , P=0.014 ) . Dunnett 's multiple comparison showed that this was attributable to increased calm among the massage group . Although not significant the guided relaxation group also reported substantially higher levels of calm than control . There was a clear ( nonsignificant ) trend across all psychological variables for both foot massage and , to a lesser extent , guided relaxation to improve psychological wellbeing . Both interventions were well received by the subjects . CONCLUSIONS These interventions appear to be effective , noninvasive techniques for promoting psychological wellbeing in this patient group . Further investigation is indicated The visual analog scale ( VAS ) is one of the most commonly used measures of pain intensity in pain research . However , there remain important unanswered questions concerning interpretation of specific VAS ratings and change scores . To address these questions , we performed a re analysis of data from 2 r and omized controlled trials of postoperative pain ( N = 123 and N = 125 ) to determine the meaning of VAS pain intensity ratings and change scores . The findings suggested that 100-mm VAS ratings of 0 to 4 mm can be considered no pain ; 5 to 44 mm , mild pain ; 45 to 74 mm , moderate pain ; and 75 to 100 mm , severe pain . As predicted , in assessment of the amount of change corresponding to differing levels of pain relief , percentage change in a patient 's VAS score was less biased by pretreatment pain than was absolute change score . The findings also suggested that a 33 % decrease in pain represents a reasonable st and ard for determining that a change in pain is meaningful from the patient 's perspective The investigators examined whether elders who have been taught pain management communication skills and pain management information obtain greater postoperative pain relief than elders not taught this information . Thirty-one elders were r and omly assigned preoperatively to a control or communication group in this posttest-only experiment with repeated measures . Communication group participants were taught pain management , pain communication skills , and the use of two pain-intensity scales . Control group participants were taught to use the two pain-intensity scales . Pain was measured with the McGill Pain Question naire Short Form . The communication group elders reported less postoperative pain over the course of their hospital stay . Pain management knowledge alone may have enabled the elders to obtain greater pain relief . Nurses may want to incorporate similar pain management information and pain communication skills when teaching elders how to obtain greater postoperative pain relief BACKGROUND Administration of analgesics per patient request or r and om pain assessment s may provide inadequate pain management . OBJECTIVE To examine the impact of nurses ' use of a st and ardized pain flowsheet to document pain assessment and pharmacologic management on patient-reported pain intensity . METHODS A pre-post intervention design was used to compare 61 patients . In the preimplementation group , traditional charting of pain presence or absence was documented in the narrative notes and pharmacologic management was recorded on the medication profile . In the postimplementation group , the intensity of pain and pharmacologic management were documented on a pain flowsheet . Within 24 hours after transfer to the step-down unit , patients were interviewed regarding pain intensity experienced in the surgical heart unit and at the time of question ing . The distribution of these pain intensity scores was compared . RESULTS The postimplementation group reported significantly lower pain intensity ratings for the average amount of pain experienced while in the surgical heart unit , the least amount of pain experienced while in the surgical heart unit , and the pain experienced at the moment of question ing . CONCLUSIONS Use of a st and ardized pain flowsheet to assess pain intensity and document pharmacologic intervention may improve pain management in postsurgical cardiovascular patients The aim of this study was to investigate post-operative pain intensity , analgesic consumption and the incidence of chronic pain in women after different types of breast cancer surgery . Patients were r and omized to either patient-controlled analgesia or nurse-administered analgesia . Opioid-consumption was registered for 24 h. A division of the patient- material into four subgroups was performed : ( 1 ) mastectomy ; ( 2 ) mastectomy and axillary lymph node dissection ; ( 3 ) mastectomy and reconstruction ; and ( 4 ) mastectomy , reconstruction and axillary lymph node dissection . Visual analogue scale was used to measure pain intensity . Four years after surgery , a question naire regarding persistent pain was completed . Patients undergoing reconstruction scored higher pain levels than the others . Patient-controlled analgesia provided better pain relief but also considerably higher consumption of opioids by the women who underwent breast reconstruction . The incidence of remaining pain was 25 % after 3 - 4 years . Immediate breast reconstruction causes severe post-operative pain that can respond poorly to opioids . Chronic pain after breast cancer surgery is common and should be further analysed aim ing at better prevention and treatment options Background and Objectives . Adequate postoperative pain relief has been achieved in orthopedic patients by subarachnoid bolus administration of plain bupivacaine . This prospect i ve r and omized study compares bolus injections of bupivacaine with a patient controlled infusion via subarachnoid 28‐gauge microcatheters for postoperative analgesia after elective hip replacement . Methods . Forty‐two patients ( mean age , 69 ± 11 years ) were r and omly allocated to one of two groups . Group 1 patients received a constant subarachnoid infusion of 0.6 mg/h of bupivacaine by a patientcontrolled device and were allowed to self‐administer 0.6 mg every 30 minutes Group 2 patients received a nurse‐administered bolus of 3.75 mg of plain bupivacaine on request . Pain was assessed by patients and nurses by a visual analog scale ( VAS ) every hour . The degree of motor block and the level of analgesia were documented every 4 hours . Hemodynamic and respiratory parameters were recorded hourly . Differences between groups were tested by analysis of variance for repeated measurement . Results . Technical problems occurred in six patients were more frequent in group 1 but none in group 2 . Patient‐controlled analgesia result ed in lower pain scores than bolus application during 18 postoperative hours ( VAS score 19 ± 19 mm in group 1 and 39 ± 30 mm in group 2 ; P < .01 ) . Lower total doses of bupivacaine were required in group 1 ( 17.6 ± 4 mg ) than in group 2 ( 22.3 ± 7 mg : P < .05 ) . The groups did not differ with respect to the degree of motor block ( Bromage score 3.5 ± 0.5 ) , the sensory level ( L1‐2 ± 1 ) , or hemodynamic or respiratory parameters . Conclusion . In spite of a higher incidence of technical problems , patient‐controlled analgesia with a continuous background infusion via microspinal catheters provides more effective postoperative analgesia , without hemodynamic or respiratory side effects , than bolus administration This study was design ed to test the effectiveness of brief relaxation training on postoperative pain , replicating and extending a study of Flaherty and Fitzpatrick ( 1978 ) . A two-group pre- and post-test experimental design was used to determine if vital signs , analgesic consumption , anxiety , self-reported incisional pain sensation and distress differ in postsurgical patients who have or have not received relaxation training . Seventy-two adult , elective abdominal surgery patients were r and omly assigned to treatment groups . Subjects in both groups were visited on the eve of surgery . Experimental subjects were taught a relaxation technique . Equal time was spent with control subjects . Following surgery all subjects were observed during ambulation . Vital signs were measured pre- and postoperatively , as were self-report of pain sensation and distress . Results showed that distress caused by painful sensations was significantly lower for experimental subjects ( F ( 1 , 53 ) = 4.69 , p = 0.03 ) . Vital signs , analgesic consumption and self-reported pain sensation were not altered by relaxation training . These findings only partially agree with those of Flaherty and Fitzpatrick . Additional analyses by type of surgery ( cholecystectomy and hysterectomy ) showed hysterectomy subjects reported less pain sensation and distress and used less analgesics than cholecystectomy subjects The factors that account for patient satisfaction with acute pain management remain a mystery . Consistently , there has been an inverse , but very small association between pain severity and patient satisfaction ; most patients are in severe pain , yet report they are satisfied with pain management . The hypothesis that perceived control mediates the relationship between pain severity and patient satisfaction was examined in 137 patients who underwent elective inpatient orthopedic surgery . Postoperatively , patients rated their pain severity ( the highest level of pain experienced ) , their perceptions of control over the pain and taking pain medication , and their satisfaction with the relief they obtained from analgesics . Path analysis using LISREL was used to test for mediation . Pain severity was associated inversely with perceptions of control over pain and with satisfaction . There was a significant association between perceived control and satisfaction and perceived control partially mediated the relationship between pain severity and satisfaction . Although individuals who report experiencing severe pain are less satisfied with pain relief than individuals with less pain , it is the interpretation or perception of having control over the pain that most relates to satisfaction with pain relief . Clinical ly , it is important to examine ways in which individuals control their pain , teach them methods to exert control , and educate them that it is preferable to not allow pain to become severe -- it is easier to " control " pain if you intervene at an early point Debilitating gas pain is a common sequel for patients who have undergone abdominal surgery . Result ing from impaired motility induced by the mechanical and psychological stresses of surgery , as well as the effects of anaesthetic and analgesic agents , accumulated gas in the bowel often leads to longer and more unpleasant hospital stays . In this article , the authors describe ongoing research aim ed at mediating gas effects in women post-hysterectomy . Using rocking as a moderator of the surgical stress response , the study hypothesizes a more rapid resumption of GI motility with decreased gaseous distention and associated pain , and less emotional distress for patients who follow a regimen of rocking in addition to ambulation . A sample of 34 patients is being studied , and data are being collected during a preadmission process and 5 postoperative days Background Many studies have shown in the efficacy of patient‐controlled analgesia ( PCA ) . However , it is not clear whether PCA has clinical or economic benefits in addition to efficient analgesia . The current study was design ed to evaluate these issues by comparing PCA with regularly administered intramuscular injections of opioids after hysterectomy . Methods This prospect i ve study included 126 patients who underwent abdominal hysterectomy and were r and omly assigned to receive PCA or regularly timed intramuscular injections of morphine during a period of 48 h. Doses were adjusted to provide satisfactory analgesia in both treatment groups . Pain at rest and with movement , functional recovery , drug side effects , and patient satisfactory were measured using rating scales and question naires . The costs of PCA and intramuscular therapy were calculated based on personnel time and drug and material requirements . Results Comparable analgesia was observed with the two treatment methods , with no significant differences in the incidence of side effects or patient satisfaction . The medication dosage had to be adjusted significantly more frequently in the intramuscular group than in the PCA patients . The PCA did not favor a faster recuperation time compared with intramuscular therapy in terms of times of ambulation , resumption of liquid and solid diet , passage of bowel gas , or hospital discharge . The results of the economic evaluation , which used a cost‐minimization model and sensitivity analyses , showed that PCA was more costly than regular intramuscular injections despite the fact that no costs for the pump were included in the analyses . Cost differences in nursing time favoring PCA were offset by drug and material costs associated with this type of treatment . Conclusions Compared with regularly scheduled intramuscular dosing , PCA is more costly and does not have clinical advantages for pain management after hysterectomy . Because of the comparable outcomes , the general use of PCA in similar patients should be question ed Background : A preoperative preparatory program may help morbidly obese patients cope with postoperative pain and vomiting , and reduce length of nursing care . Methods : A preoperative preparatory program was given to r and omly selected morbidly obese women about to undergo a Lap-B and ® stomach reduction operation . Results : Statistical testing of the results of the program against a control group of patients who did not receive the program revealed beneficial differences between the two groups in terms of postoperative pain , analgesic use , postoperative vomiting , and duration of nursing care . Conclusion : The differences were not statistically significant , although the reaction of patients who received the program was positive In a double- study , using patients ' subjective reports as indices of analgesia , the relative analgesic potency of intramuscular nalbuphine and morphine was determined in 56 postoperative patients . A total of 28 crossover comparisons ( utilizing the twin passover , balanced four-point incomplete block design ) were performed in two sequentially related experiments , each assay comparing 4 and 8 mg of morphine with either 3 and 6 or 6 and 12 mg of nalbuphine . When both intensity and duration of analgesia are considered ( i.e. , total analgesic effect ) , nalbuphine was 0.8 to 0.9 times as potent as morphine . In terms of peak analgesic effect , nalbuphine was 0.7 to 0.8 times as potent . Both the time-effect curves and the relative potency estimates suggest that nalbuphine has a slightly longer duration of action than morphine at doses that are equianalgesic in terms of peak effect . Side effects of the type usually noted after the administration of potent injectable analgesics to postoperative patients were observed after both morphine and nalbuphine . Although nalbuphine is a potent narcotic antagonist , no psychotomimetic reactions were observed Background : After total knee arthroplasty , patients regularly suffer from severe pain . It is unclear whether epidural or systemic pain therapy is superior in terms of postoperative pain relief , patients ’ comfort and side effects . A new therapeutic approach , intraarticular opioids , has been suggested with the detection of opioid receptors in inflamed tissue . This method has proven suitable for clinical use in small operations ( e.g. knee arthroscopy ) . In this study , we compared epidural analgesia and intraarticular application of morphine plus “ on‐dem and ” intravenous analgesia to “ on‐dem and ” intravenous analgesia alone PURPOSE / OBJECTIVES To obtain preliminary data and determine the feasibility of a large-scale experimental study to test the efficacy of the Rogerian Science of Unitary Human Beings-based intervention of dialogue and therapeutic touch ( TT ) on pre- and postoperative anxiety and mood and postoperative pain from breast cancer surgery . DESIGN Experimental . SETTING Mid-Atlantic region ; ambulatory . SAMPLE 29 Caucasian and 2 African American English-speaking women with positive breast cancer biopsy ( experimental , n = 14 ; control , n = 17 ) , ranging in age from 31 - 84 years old ( F = 55.6 ) . METHODS Treatments administered in subjects ' homes within seven days prior to surgery and 24 hours after hospital discharge . Experimental treatment consisted of 10 minutes of TT and 20 minutes of dialogue . Control treatment consisted of 10 minutes of quiet time and 20 minutes of dialogue . Data ( Spielberger State-Trait Anxiety Inventory . Affects Balance Scale , and Visual Analog Scale-Pain ) were collected at the conclusion of each home visit . MAIN RESEARCH VARIABLES Anxiety , mood , and pain . FINDINGS The experimental group had lower preoperative state anxiety than the control groups ( p = 0.008 ) . No difference was found for preoperative mood . No differences were found for any postoperative measure . CONCLUSIONS A large-scale study of dialogue and TT would require changes in design and recruitment strategies . IMPLICATION S FOR NURSING PRACTICE Nurses may provide more comprehensive care by incorporating dialogue and TT or quiet time into their pre- and postoperative care . Additional research , however , is recommended to determine the differential effects of dialogue , TT , and quiet time on women 's experiences with breast cancer prior to incorporating these noninvasive modalities into clinical practice We conclude that the intravenous PCA method is acceptable , easy to use , does not depend on the patients ' level of education , and is safe for Thai patients . The average pain scores at 48 hours postoperation of the PCA group was significantly lower than for the conventional and the I.M. groups . Satisfaction was quite difficult to assess . Thai culture might influence how much pain is accepted and the patients had not experienced other techniques , so they could not make a comparison . The amount of morphine used by the PCA group was intermediate between that used by the other two groups Fentanyl by continuous i.v . infusion ( 1.5 microgram kg-1 min-1 or 0.5 microgram kg-1 min-1 ) was compared with placebo infusion as an analgesic regimen for 24 h after hysterectomy . The drugs were infused using a new disposable device which required no external power source . All patients were allowed morphine i.m . if they experienced pain . Patients in the higher dose fentanyl group dem and ed less i.m . morphine and had better pain relief after operation , without important respiratory depression The purpose of this quasiexperimental clinical study was to investigate differences in postoperative pain management within the h and surgical population . The research question proposed : Is there a difference in the pain experience between postoperative patients who receive an analgesic upon onset of sensation and those who receive an analgesic upon onset of pain ? The effectiveness of pain management was compared for two groups of r and omly assigned , adult , orthopaedic patients who had undergone elective h and surgery using axillary block anesthesia . The results of this study concluded that more effective pain control was achieved when patients were medicated upon onset of sensation versus onset of pain Physiological responses to pain create harmful effects that prolong the body 's recovery after surgery . Patients routinely report mild to moderate pain even though pain medications have been administered . Complementary strategies based on sound research findings are needed to supplement postoperative pain relief using pharmacologic management . Foot and h and massage has the potential to assist in pain relief . Massaging the feet and h and s stimulates the mechanoreceptors that activate the " nonpainful " nerve fibers , preventing pain transmission from reaching consciousness . The purpose of this pretest-posttest design study was to investigate whether a 20-minute foot and h and massage ( 5 minutes to each extremity ) , which was provided 1 to 4 hours after a dose of pain medication , would reduce pain perception and sympathetic responses among postoperative patients . A convenience sample of 18 patients rated pain intensity and pain distress using a 0 to 10 numeric rating scale . They reported decreases in pain intensity from 4.65 to 2.35 ( t = 8.154 , p < .001 ) and in pain distress from 4.00 to 1.88 ( t = 5.683 , p < .001 ) . Statistically significant decreases in sympathetic responses to pain ( i.e. , heart rate and respiratory rate ) were observed although blood pressure remained unchanged . The changes in heart rate and respiratory rate were not clinical ly significant . The patients experienced moderate pain after they received pain medications . This pain was reduced by the intervention , thus supporting the effectiveness of massage in postoperative pain management . Foot and h and massage appears to be an effective , inexpensive , low-risk , flexible , and easily applied strategy for postoperative pain management Forty patients recovering from upper abdominal surgery were allocated r and omly to receive i.m . morphine 0.15 mg kg-1 as required or patient-controlled analgesia ( PCA ) , with i.v . morphine 1 mg and a 5-min lock out time . Arterial oxygen saturation ( SpO2 ) was measured continuously the night before and for 24 h immediately after surgery . A significantly greater proportion of patients in the PCA group ( nine of 19 ) rated their analgesia as excellent compared with the i.m . group ( two of 20 ) ( P < 0.05 ) . There was no significant difference in the incidence of postoperative hypoxaemia in the two treatment groups . Severe postoperative hypoxaemia ( SpO2 < 85 % for more than 6 min h-1 ) was seen in three patients receiving i.m . analgesia and one patient in the PCA group The effect of adding a continuous infusion of morphine 1 mg/hr to patient-controlled intravenous analgesia was studied in a r and omized double-blind trial . Ninety-six patients scheduled for abdominal surgery were enrolled ; 38 received PCA and continuous infusion ( PCA + C ) , 45 received PCA alone and 13 were excluded because of protocol violations . PCA was delivered via an ABBOTT 4200 pump with setting s of morphine 1 mg bolus and five-minute lockout in both groups . A separate pump delivered a continuous infusion of morphine 1 mg/ml ( PCA + C ) or 9 % normal saline ( PCA ) at 1 ml/hr for three postoperative days . Pain was assessed by hourly verbal pain scores ( VPS ) and daily visual analog pain scores at rest and on movement ( VASrest , VASmove ) . PCA delivered morphine and the dem and to delivery ratio ( D/D ratio ) were used as indirect indicators of pain . These were assessed during daytime ( 0800–2200 hours ) , sleep ( 2200–0500 hours ) and on first waking ( 0500–0800 hours ) . Patient demographics were similar . Patients receiving a continuous infusion had lower pain scores during the first 24 hours but not thereafter ( VPS P=0.04 , VASmove P=0.02 ) . The PCA group delivered more PCA morphine during 0500–0800 hours and 0800–2200 hours on the first day only . There was no significant difference in the D/D ratio for any time period during the three days . Total morphine delivery was greater in the PCA + C group on the second and third postoperative days ( P= 0.009 and P=0.0001 respectively ) . The incidence of respiratory depression and the total number of complications were significantly higher in those receiving continuous infusion ( P=0.04 and P=0.011 respectively . ) Adding a continuous morphine infusion of 1 mg/hr to the described PCA setting s for three days following abdominal surgery improved analgesia during the first 24 hours but was associated with a greater incidence of complications Abstract We compared the use of patient-controlled analgesia ( PCA ) morphine and p.r.n . intravenous morphine in an intensive care unit setting . Thirty-eight patients scheduled for admission to the Surgical Intensive Care Unit ( SICU ) were prospect ively r and omized to either a PCA group or a p.r.n . intravenous morphine group . Assessment s included pain and sedation scores , respiratory rates , pulse oximetry , and morphine utilization . PCA was found to be comparable in safety and efficacy to nurse-administered morphine in the intensive care environment . An unexpected finding was the higher initial morphine utilization seen in the patients utilizing PCA Patient-controlled analgesia ( PCA ) with intravenous pethidine was compared with nurse-controlled pethidine infusions for pain relief in 200 patients after major abdominal or thoracic surgery . Pain , level of sedation , nausea and presence of other adverse effects , in addition to cumulative pethidine requirement , were measured for the first 24 hours after surgery . Both groups were similar for age , weight and type of surgery . There was no significant difference between the quality of analgesia achieved in both groups . The frequency and severity of adverse effects was also similar . The cumulative pethidine dose administered to both groups was identical . It is concluded that nurse-controlled opioid infusions are as effective as PCA and may be used as an alternative to PCA where this is either unavailable or unsuitable Oral controlled release morphine ( CRM ) was compared in a double-blind study with epidural morphine ( EM ) for postoperative pain relief in 20 patients undergoing knee arthrotomy under epidural anesthesia . Ten patients received 30 mg CRM orally and saline epidurally ( CRM group ) , and ten patients received placebo tablets orally and 4 mg morphine epidurally ( EM group ) , both at the time of skin incision and then every 8 hr for 48 hr during which patients evaluated pain intensity using a visual analog scale . Nine of the ten patients in the EM group had good relief of pain throughout the study period . Seven of the ten patients in the CRM group needed rescue analgesics within 6 hr of the initiation of the study ( P < 0.01 ) . We conclude that CRM is not suitable for the control of early postoperative pain , whereas epidural morphine is excellent The effectiveness of patients ' participation in self-care aim ed at expediting the rate of recovery from surgery and increasing satisfaction with care received was tested with adult patients undergoing pyelolithotomy and nephrolithotomy . Forty subjects participating in the study were r and omly assigned to either an experimental ( n = 20 ) or a control group ( n = 20 ) . Patients in the experimental group participated in their self-care through nurse-patient interaction in addition to the usual care received in the setting . Results of the study indicated that patients in the experimental group had significantly less pain sensation and distress , used fewer analgesics , ambulated more , had fewer complications , and had higher satisfaction with care than patients in the control group . Since the experimental intervention was based on Orem 's and King 's theories , these findings support the value of application of these two nursing theories in practice This study compared epidural and intravenous fentanyl infusions for pain relief for the first 20 h after thoracotomy , in order to examine whether an thoracic epidural fentanyl infusion offers clinical advantage over an intravenous infusion . Forty patients were assigned r and omly to receive either fentanyl epidurally and saline intravenously or fentanyl intravenously and saline epidurally in a double-blind fashion . For each patient the fentanyl infusion was titrated to a rate required for pain relief ( pain score less than 3 , maximum 10 ) . Patients reported similar median pain scores , but in the epidural group the required mean fentanyl infusion rate was less ( 0.95 + /- 0.23 vs. 1.67 + /- 0.46 micrograms.kg-1.h-1 , P = 0.0001 ) and plasma fentanyl concentrations were less at 4 and 18 h ( 4 h : 0.81 + /- 0.27 vs. 1.38 + /- 0.36 ng.ml-1 , P = 0.0001 ; 18 h : 0.94 + /- 0.32 vs. 1.54 + /- 0.65 ng.ml-1 , P = 0.0007 ) than those in the intravenous group . Respiratory function was better preserved and the incidence of nausea and sedation was less in the epidural group than in the intravenous group . In conclusion there appears to be a clinical advantage to the epidural infusion over the intravenous infusion of fentanyl for analgesia after thoracotomy Sixty-four patients undergoing oesophageal surgery were r and omly allocated to receive either a continuous lumbar epidural infusion of morphine or fentanyl , or , intramuscular morphine for postoperative analgesia . There was no statistical difference in analgesic requirements between the patients who underwent a thoracotomy for their procedure ( n = 50 ) and those who did not ( n = 14 ) , as assessed by the total dose of opioid administered , visual analogue scale ( VAS ) and pain score ( PS ) comparison . However , by these criteria , epidural morphine infusion provided the most satisfactory analgesia ( P < 0.05 ) . Despite the variable quality of analgesia achieved with the three regimens , the postoperative lung function tests were similar for all groups , and we conclude that routine lung function tests are not an appropriate method of comparing analgesic efficacy . Prophylactic administration of loratadine to 15 % of our patients was not shown to be effective in diminishing the incidence of pruritus Use of patient-controlled analgesia ( PCA ) was compared with nurse-administered intermittent intramuscular ( NM ) Injections of morphine in older adults during their postoperative recovery . Data analyses indicated that the PCA and IM groups did not dyfer in pain intensity , pain distress , and satisfaction . The PCA group had significantly less sleep disturbance from pain than the IM group . Neither group was considered to have acceptable pain management Morphine sulphate was used for the control of pain following major abdominal surgery for a period of three days either as patient-controlled or continuous infusion . The two groups of patients were comparable with regard to patient and operation details , duration of infusion , pain scores and complications . The only significant difference was a reduced dose requirement of morphine in the patient-controlled analgesia group ( P < 0.005 ) . Some possible explanations for this finding are given . It is suggested that a properly supervised continuous infusion of morphine is as good as patient-controlled administration . There was a negative correlation between the age of the patient and the dose of morphine used Purpose / objective To evaluate the usefulness of arm massage from a significant other following lymph node dissection surgery . Design : R and omized clinical trial with a pretest-posttest design . Data were collected prior to surgery , within 24 hours post surgery , within 10 to 14 days post surgery , and 4 months post surgery . Sample 59 women , aged 21 to 78 undergoing lymph node dissection surgery and who had a significant other with them during the postoperative period . Methods Subjects were r and omly assigned to intervention and control groups . Subjects ' significant others in the intervention group were first taught , then performed arm massage as a postoperative support measure . Research main variables Variables included postoperative pain , family strengths and stressors , range of motion , and health related costs . Findings Participants reported a reduction in pain in the immediate postoperative period and better shoulder function . Conclusion Arm massage decreased pain and discomfort related to surgery , and promoted a sense of closeness and support amongst subjects and their significant other . Implication for nursing practice Postoperative massage therapy for women with lymph node dissection provided therapeutic benefits for patients and their significant other . Nurses can offer effective alternative interventions along with st and ard procedures in promoting optimal health Continuous bupivacaine epidural analgesia was compared with conventional methods of systemic analgesic administration in the management of postoperative pain in 30 patients for 3 days following total knee replacement surgery . Patients given continuous epidural analgesia had significantly better pain relief ( visual analogue scale , global evaluation ) , needed significantly fewer supplementary analgesics , and had significantly fewer side effects . In the epidural group , sensory block averaged six dermatomes on day 1 and four dermatomes on day 3 . The number of patients with complete ( or almost complete ) motor block of the lower limbs decreased from eight on day 1 to five on day 3 . The mean dosage of bupivacaine decreased from 21.0 ± 5.7 ( SD ) mg/hr on day 1 to 15.1 ± 8.5 mg/hr on day 3 . No signs of accumulation of or toxic reactions to bupivacaine were seen Background and Objectives . Patient‐assisted epidural analgesia , a mode of epidural analgesic delivery in which self‐administered epidural boluses supplement a baseline continuous epidural infusion , was compared to continuous epidural infusion in 62 postsurgical patients . Methods . Patients were r and omly assigned to receive continuous epidural infusion ( n = 31 ) or patient‐assisted epidural analgesia ( n = 31 ) consisting of fentanyl 10 mcg/mL and bupivacaine 1 mg/mL for the first 2 days after the operation . Variables examined included the adequacy of analgesia , amount of epidural infusion solution used , use of supplemental opioids , as well as incidence of side effects including nausea , pruritus , sedation , urinary retention , and respiratory depression . Results . Visual analog pain scores on days 1 and 2 after the operation , mean total epidural fentanyl consumption , and use of supplemental opioids were all significantly ( P < .05 ) lower in the patient‐assisted epidural group than in the continuous infusion group . There was no significant difference in the incidence of side effects between groups . The effects of age and operation type were not significant . Conclusions . Patient‐assisted epidural analgesia can provide superior pain control as compared to continuous epidural infusions while also reducing opioid dosages . Despite the reduction in total analgesic administered no reduction in side effects was seen with this mode of administration Numerous instruments have been developed for the measurement of pain with various clinical population s. This study was design ed to compare pain measures for research in a sample of postoperative patients . The Brief Pain Inventory-Short Form ( BPI-SF ) was administered along with the Short-Form McGill Pain Question naire ( SF-MPQ ) and two visual analogue scales , one for pain while at rest ( VAS-R ) and one for pain upon movement ( VAS-M ) , in r and om order , to 115 hospitalized patients twice following their surgery . An additional 29 patients completed the instruments once . Correlations between the visual analogue scales , BPI-SF , and SF-MPQ ranged from .33 to .76 ( p < .01 ) , suggesting that the instruments measure different aspects of pain and that instructions can influence the results . Recommendations for the selection of pain measures in patients experiencing acute pain and for future research are described We examined whether pre‐operative information benefited patients receiving patient‐controlled analgesia ( PCA ) after major surgery . We investigated whether patients felt better informed about PCA and also whether pre‐operative information altered the use of PCA , the adequacy of pain relief , worries about addiction and safety , and knowledge of side‐effects . We investigated the effectiveness of information provided in two ways , namely by a patient‐determined leaflet or an interview by a trained nurse from the pain team , compared with routine pre‐operative information . We studied 225 patients , 75 in each group . Patients in the leaflet group were better informed about PCA , became familiar with using PCA more quickly and were less confused about PCA than the control group . However , there were no effects on pain relief , worries about addiction and safety , and knowledge of side effects . The pre‐operative interview result ed in no benefits . Our findings indicate that the detailed provision of pre‐operative information failed to improve patients ' experiences of PCA The Foster Pain Intervention ( FPI ) is a 24-minute videotape of a nurse showing breathing and movement skills with four postoperative mobility activities to a patient . Its preoperative use incorporates self-efficacy concepts to teach techniques that can improve postoperative pain and mobility . This study compared the effects of the FPI on postoperative pain and mobility and the relationship with self-efficacy in 70 elective hysterectomy patients . The treatment group ( n = 35 ) received the FPI and routine information , whereas the control group ( n = 35 ) received routine information through videotaped instruction . The treatment group had significantly less pain ( p < .0001 ) , higher observed mobility ( p < .0001 ) , and higher preoperative self-efficacy and was ready to go home sooner than the control group ( p < .0001 ) . These results suggest that the FPI enhances self-efficacy , decreases pain associated with postoperative activities , and promotes earlier independent mobilization This study tests for the impact of client-nurse interaction , an essential element lacking in earlier research on preoperative instruction . An experimental design compared the effects of three models of intervention : Facilitator , Informational and Routine Treatment on postoperative pain and anxiety in 91 cholecystectomy patients . Planned comparisons showed that subjects in both experimental conditions reported significantly less postoperative anxiety than subjects who received the routine treatment . There were no differences in anxiety levels between the two experimental groups or in pain scores among the three groups . Refinements in the facilitator model are recommended to enhance the problem-solving nature of the interaction and to strengthen future research . The findings support the importance of providing the patient with sensation information and postoperative exercise instruction Patients who undergo surgery usually experience fear and apprehension about their surgical procedures . Guided imagery is a simple , low-cost therapeutic tool that can help counteract surgical patients ' fear and anxiety . The authors r and omly assigned 130 patients undergoing elective colorectal surgical procedures into two groups . Members of one group received routine perioperative care . Members of the other group listened to guided imagery tapes for three days before their surgical procedures , during anesthesia induction , intraoperatively , in the postanesthesia care unit , and for six days after surgery . The authors measured patients ' anxiety levels , pain perceptions , and narcotic medication requirements . The patients in the guided imagery group experienced considerably less preoperative and postoperative anxiety and pain , and they required almost 50 % less narcotic medications after their surgical procedures than patients in the control group This experimental study compared the effects of jaw relaxation and music , individually and combined , on sensory and affective pain following surgery . Abdominal surgical patients ( N = 84 ) were r and omly assigned to four groups : relaxation , music , a combination of relaxation and music , and control . Interventions were taught preoperatively and used by subjects during the first ambulation after surgery . Indicators of the sensory component of pain were sensation and 24-hour narcotic intake . Indicator of the affective component of pain were distress and anxiety of pain . With preambulatory sensation , distress , narcotic intake , and preoperative anxiety as covariates , the four groups were compared using orthogonal a priori contrasts and analysis of covariance . The interventions were neither effective nor significantly different from one another during ambulation . However , after keeping the taped interventions for 2 postoperative days , 89 % of experimental subjects reported them helpful for sensation and distress of pain The management of postoperative pain with continuous epidural fentanyl infusion was compared with continuous intravenous fentanyl infusion . In a r and omized , double-blind protocol we prospect ively studied 20 patients undergoing repair of the anterior cruciate ligament of the knee . The quality of analgesia and the incidence of side effects were documented . Compared with patients receiving continuous intravenous fentanyl infusion , at 18 h postoperatively patients given continuous epidural fentanyl infusion reported similar pain scores both at rest ( 22 ± 25 vs 27 ± 21 P = 0.52 ) and with ambulation ( 59 ± 18 vs 56 ± 22 , P = 0.82 ) . Plasma fentanyl levels were 1.8 ± 0.4 and 1.7 ± 0.4 ng/m . L ( P = 0.91 ) for the intravenous and epidural groups , respectively . There were no significant differences in the incidence of nausea , pruritus , or urinary retention . There was no respiratory depression in either group . We conclude that when compared with continuous intravenous fentanyl infusion , continuous epidural fentanyl infusion offers no clinical advantages for the management of postoperative pain after knee surgery AIM OF STUDY To measure the effect of specific preoperative information on postoperative anxiety , satisfaction with information , and dem and for analgesia , of Chinese males having transurethral resection of the prostate ( TURP ) . DESIGN A controlled experimental design . The research ers allocated all patients ( n = 30 ) undergoing TURP in a general hospital in Hong Kong , during a 3-month period , to one of two groups . The experimental group ( n = 15 ) received a specific information pamphlet and a general preoperative counselling video . The control group ( n = 15 ) received a video alone . PROCEDURE AND MEASURES : Following ethical approval , a research er took baseline measures of state and trait anxiety using the Chinese State-Trait Anxiety Inventory ( C -STAI ) . Five days after surgery the research er administered the C-STAI ( A-State ) , a patients ' satisfaction question naire , and , recorded requests for analgesia during the first 5 postoperative days . RESULTS Experimental subjects reported significantly lower anxiety levels post-operatively and a significantly higher level of satisfaction with the preoperative information , than controls . Postoperative dem and for analgesia did not significantly differ between groups . CONCLUSIONS The findings support the importance of providing patients with specific , written preoperative information about their surgery and its effects to minimize their postoperative anxiety levels , and improve their satisfaction with the care provided OBJECTIVE To compare st and ard nurse-based pain therapy with a patient-controlled analgesia ( PCA ) regimen . DESIGN Prospect i ve , r and omized study . SETTING Single-institutional , clinical investigation in an urban , university-affiliated hospital . PARTICIPANTS Sixty patients undergoing elective first-time cardiac surgery were included . INTERVENTIONS In 30 patients , a st and ard analgesic regimen was used , and in 30 patients , a PCA regimen was used . The perioperative and postoperative management was similar for all patients . MEASUREMENTS AND MAIN RESULTS Degree of sedation , satisfaction , and pain ( by visual analog scale [ VAS ] ) was assessed within the first 3 postoperative days . Vital capacity ( VC ) and forced expiratory volume in 1 second ( FEV1 ) were measured using a portable spirometry system . Cortisol and troponin T ( TnT ) plasma levels were also measured . The expectation of pain was similar in both groups , and the postoperative pain score was significantly lower in the PCA than in the st and ard group throughout the study period . Significantly more piritramid was used in the PCA ( total , 75.6 + /- 33.4 mg ) than in the st and ard group ( total , 20.1 + /- 31.9 mg ) . VC and FEV1 were significantly lower in the st and ard group compared with the PCA patients . Cortisol and TnT plasma levels were similar in both groups . Frequency of side effects were similar for both groups . CONCLUSION Because of the beneficial effects with regard to degree of pain and satisfaction , pain management using PCA systems can be recommended for cardiac surgery patients . It appears to be superior to st and ard nurse-based pain therapy Little has been documented regarding postoperative nursing interventions that are effective in decreasing postoperative recovery time , improving patient outcomes , or optimizing discharge readiness . A r and omized study was conducted to evaluate 2 methods of recovery positioning and to examine factors that affect home readiness ( eg , voiding , intake ) for postsurgical laparoscopy patients . Participants were r and omized into 2 groups . The control group was recovered in traditional hospital beds , while subjects in the experimental group recovered in a " recliner-chair , " which was adjustable by the patient for comfort . The results showed that patients who recovered in adjustable recliner-chairs reached home readiness sooner and experienced greater comfort levels than patients who recovered in traditional hospital beds . Furthermore , patients in the recliner-chair group had fewer adverse symptoms such as nausea , severe pain , and delayed voiding . This is a U.S. government work . There are no restrictions on its use OBJECTIVE To compare nurses ' and patients ' assessment s of pain and sedation in patients receiving epidural or intravenous patient-controlled analgesia ( PCA ) after cesarean section . DESIGN Prospect i ve , r and omized study . SETTING The perinatal unit and labor and delivery unit in a 1,036-bed university hospital in the mid-Atlantic region . PARTICIPANTS Twenty-six patients receiving epidural PCA or intravenous PCA . Nurses participating in the study were assigned as caregivers to the 26 patients . MAIN OUTCOME MEASURES Pain and sedation were assessed using 10-cm visual analogue scales completed by both the patient and the patient 's nurse twice daily on the day of surgery and on the 1st and 2nd postoperative days . RESULTS No significant correlation was found between the nurses ' and patients ' pain or sedation scores . Chi-square analysis showed that the nurse was as likely to underestimate as to overestimate the patient 's pain score . The nurse underestimated the patient 's sedation score 85 % of the time . CONCLUSIONS The results suggest that nurses ' and patients ' assessment s of pain and sedation differ . The routine use of a st and ardized self- assessment tool , such as the visual analogue scale , is recommended to ensure that analgesic treatment is based on the subjective nature of the patient 's pain experience rather than the nurse 's judgment In the current study , 55 patients undergoing elective cholecystectomy were r and omly allocated to receive postoperative analgesia ( morphine sulfate ) administered through either patient-controlled intravenous ( PCA ) or st and ard intramuscular ( IM ) routes . There were no significant differences in length of hospitalization or required dose of morphine sulfate . Patients r and omized to PCA reported significantly improved subjective relief from pain and a smaller percentage of time in pain during each of the first two postoperative days . In addition , they reported less sedation and less interference with both postoperative breathing and pulmonary recovery than patients who received IM morphine . Theoretically , PCA regimens can deliver narcotic analgesia at a higher and more varied rate ( with fewer side effects ) compared with st and ard IM narcotic delivery , which is more limited by considerations of clinical doses . In PCA dosing , patients should experience less time in pain and sedation . The results of the current study support this premise AIM Clinical experience in gastrointestinal surgery demonstrated that a multimodal approach can improve the outcome and reduce the length of hospital stay . In this paper we investigate the impact of a multimodal clinical program , based on mininvasive surgery , epidural anesthesia and early feeding and mobilization , on postoperative morbidity and hospitalization after abdominal aortic surgery . METHODS A 2-armed study was design ed . All patients undergoing abdominal aortic surgery between May 2000 and April 2001 were enrolled in a multidisciplinary clinical program including thoracic epidural anesthesia and analgesia , left sub-costal minilaparotomy without evisceration , encouragement to feed and mobilize soon after surgery ( Multidisciplinary group : n=82 ) . For comparison purpose s , a retrospective analysis was conducted using the data of all patients operated on between January and December 1997 , receiving st and ard anesthesia care and a st and ard surgical and nursing program ( St and ard group : n=64 ) . RESULTS In the Multidisciplinary group we observed significantly better pain relief ( p<0.01 ) , earlier restoration of ambulation ( p<0.01 ) , earlier feeding ( p<0.01 ) and passage of stools ( p<0.01 ) . The incidence of complications was significantly lower in the Multidisciplinary group : pulmonary ( 0 % vs 14.1 % ) , cardiac ( 2.4 % vs 9.4 % ) and gastrointestinal ( 0 % vs 10.9 % ) . None of the patients in the Multidisciplinary group required admission to Intensive Care . Median postoperative hospitalization was 3 days in the Multidisciplinary group compared to 9 days in the St and ard group ( p<0.01 ) . CONCLUSION These results suggest that a multidisciplinary intervention with review of the traditional surgical care program would enhance recovery , decrease morbidity and hospitalization after abdominal aortic surgery |
10,574 | 22,711,192 | This study clearly demonstrates that smoking increases the risk of cutaneous squamous cell carcinoma ; however , smoking does not appear to modify the risk of basal cell carcinoma | OBJECTIVE To perform a systematic review and meta- analysis to collate evidence of the effects of smoking on the risk of nonmelanoma skin cancer . | BACKGROUND Malignant melanoma has been one of the most rapidly increasing cancers within the United States with few modifiable risk factors . This study investigates risk related to dietary factors , which are potentially modifiable . METHODS Newly diagnosed patients with melanoma ( n = 502 ) were recruited from pigment lesion clinics and controls ( n = 565 ) were recruited from outpatient clinics . To investigate the relationship between melanoma and dietary factors in this case-control study , study subjects were requested to complete a food frequency question naire , which assessed diet over the previous year . Using logistic regression , odds ratios ( ORs ) for melanoma were computed for nutrient and alcohol intake . RESULTS Persons in high versus low quintiles of energy-adjusted vitamin D , alpha-carotene , beta-carotene , cryptoxanthin , lutein , and lycopene had significantly reduced risk for melanoma ( ORs < or = 0.67 ) , which remained after adjustment for presence of dysplastic nevi , education , and skin response to repeated sun exposure . Addition of micronutrients from supplements did not add an additional reduction in risk . High alcohol consumption was associated with an increased risk for melanoma , which remained after adjustment for confounders [ OR ( 95 % confidence interval ) in highest versus lowest quintiles , 1.65 ( 1.09 - 2.49 ) ] . CONCLUSIONS Diets consisting of foods rich in vitamin D and carotenoids and low in alcohol may be associated with a reduction in risk for melanoma . These analyses should be repeated in large , prospect i ve studies In a prospect i ve study of 102 patients with pre-neoplasia and /or manifest squamous-cell carcinoma of the lower lip the synchronous occurrence of intra-oral , pharyngeal or laryngeal leukoplakia and carcinoma was assessed . There was a coincidence rate of almost 15 % leukoplakias , including individual carcinomas . This high coincidence is probably due to a combination of various " risk profiles " in patients with threatened or manifest lower-lip cancer . Chronic exposure to sunlight , especially in the presence of a genetic disposition , is the most important risk factor in lower-lip cancer and its preceding stages , while chronic alcoholism and smoking abuse have little etiological significance We prospect ively investigated whether alcohol intake and smoking affect the risk of basal cell carcinoma ( BCC ) in subjects from the United States Radiological Technologists ( USRT ) cohort study . We evaluated 68,371 radiological technologists certified during 1926 - 1982 who were free of cancer at the time they answered a first question naire ( 1983 - 1989 ) and who completed a second question naire ( 1994 - 1998 ) . The first question naire provided baseline information on numerous risk factors , including smoking and alcohol intake , and the second provided self-reported cancer diagnoses . During 698,190 person-years of follow-up , we identified 1,360 cases of BCC : 1,036 in women and 324 in men . Cox proportional hazards regression indicated that the trend in BCC was significantly associated with increased alcohol intake ( P for trend = 0.001 ) . Compared with those who reported no alcohol consumption , those who drank < 1 - 2 , 3 - 6 , 7 - 14 , and > 14 drinks/week had multivariate risks of 1.1 [ 95 % confidence interval ( CI ) , 0.9 - 1.3 ] , 1.3 ( 95 % CI , 1.1 - 1.5 ) , 1.4 ( 95 % CI , 1.2 - 1.7 ) , and 1.0 ( 95 % CI , 0.7 - 1.6 ) , respectively . We found no clear association between smoking and BCC . This is the second large prospect i ve study to report a significant but nonmonotonic trend in increased risk associated with alcohol consumption The aim of this study was to identify factors related to lip cancer ( LC ) considering individual characteristics and sociodemographic factors . A case – control study was carried out in the province of Granada ( And alusia , southern Spain ) . The cases were 105 males with squamous-cell carcinoma of the lip , diagnosed between 1987 and 1989 ( aged 20–70 years ) and identified by means of a population -based Cancer Registry . As controls , a r and omised population al sample of 239 males , stratified by age , was used . Multiple logistic regression analysis showed that risk factors are lifetime cumulative tobacco consumption and alcohol consumption . An interaction was found between alcohol consumption and the smoking habit ( leaving the cigarette on the lip ) : OR=23.6 ; 95 % CI : 3.9–142.0 . Other risk factors identified are clear eyes ( OR=3.5 ; CI : 95 % 1.5–8.0 ) , sun exposure early in life and cumulative sun exposure during outdoor work ( OR=11.9 ; 95 % : CI : 1.3–108.9 ) , and skin reaction to sun exposure ( Fitzpatrick levels ) . Another interaction was found between skin reaction and a previous history of common sporadic warts ( OR=4.4 ; 95 % CI : 1.01–19.1 ) . We conclude that LC is related to phenotype , skin reaction to sun exposure , cumulative and early sunlight exposure , and tobacco and alcohol consumption , as well as a low educational level . Leaving the cigarette on the lip is predictive of LC risk irrespective of cumulative tobacco consumption To determine the relationship between 25(OH ) vitamin D levels and non-melanoma skin cancer ( NMSC ) , we performed a nested case – control study in ambulatory , elderly men enrolled in the Osteoporotic Fractures in Men ( MrOS ) Study . Health habit and medical history , including self-reported history of NMSC were recorded and 25(OH)D levels were measured on serum collected at baseline from a r and om sample of Caucasian MrOS subjects . Mean age ( 73 ± 5 ) , BMI , daily vitamin D and calcium intake were similar in the men with ( n = 178 ) and without NMSC ( n = 930 ) , but higher levels of 25(OH)D were associated with a decreased risk of having a history of NMSC ( Ptrend = 0.04 ) . Men in the highest quintile of 25(OH)D ( > 30 ng/mL ) had 47 % lower odds of NMSC ( 95 % CI : 0.30–0.93 , p = 0.026 ) compared to those in the lowest quintile . Our results suggest that a diagnosis of NMSC is not a surrogate for adequate 25(OH)D levels or increased UV exposure , and high 25(OH)D levels may be associated with a reduced risk of NMSC OBJECTIVES This study evaluated the influence of occupational exposure on cancer risk among female Norwegian nurses . METHODS A historical prospect i ve cohort study was performed . The cohort was established from the Norwegian Board of Health 's registry of nurses and included women who graduated from a nursing school before 1985 . The cohort ( N=43 316 ) was linked to the Cancer Registry of Norway . The observed number of cases was compared with the expected number on the basis of national rates . Time since first employment , period of first employment , and duration of employment were used as indicators of exposure . Poisson regression analyses were used for internal comparisons , adjusting for age , period , and fertility . RESULTS The nurses were followed over 1473931 person-years . During the follow-up ( 1953 - 2002 ) , 6193 cancer cases were observed . The st and ardized incidence ratio ( SIR ) for all cancers combined was close to unity . Significantly lower risks were found for cancers with a known association with alcohol and tobacco consumption and sexual activity . A significantly increased risk was found for breast cancer ( SIR 1.14 , 95 % confidence interval ( 95 % CI ) 1.09 - 1.19 ) , ovarian cancer ( SIR 1.14 , 95 % CI 1.04 - 1.25 ) , malignant melanoma ( SIR 1.15 , 95 % CI 1.04 - 1.28 ) , and borderline significant risk appeared for other skin cancer ( SIR 1.12 , 95 % CI 0.98 - 1.29 ) . A positive trend for increasing time since first exposure was found for breast cancer and malignant melanoma . CONCLUSIONS The results indicate an association between working as a nurse and an increased risk of breast cancer and malignant melanoma . Decreased risks , found for several cancers , indicate favorable lifestyle habits among nurses In a prospect i ve study of self-reported demographic , constitutional , and life-style factors in relation to basal cell carcinoma of the skin , we followed a cohort of 73,366 nurses in the United States who were 34 to 59 years of age in 1980 and who had no previous skin or other cancer . In 4 years of follow-up , compared with women living in the Northeast , women residing in California ( age-adjusted relative risk [ RR ] = 1.57 ; 95 % confidence interval [ CI ] = 1.30 to 1.89 ) and Florida ( RR = 2.12 ; 95 % CI = 1.54 to 2.92 ) were more likely to develop basal cell carcinoma . Compared with women having naturally dark brown hair , the age-adjusted relative risk of basal cell carcinoma was increased among women with red ( RR = 2.45 ; 95 % CI = 1.89 to 3.19 ) , blonde ( RR = 1.37 ; 95 % CI = 1.09 to 1.71 ) , or light brown hair ( RR = 1.27 ; 95 % CI = 1.08 to 1.49 ) and was decreased among women with black hair ( RR = 0.66 ; 95 % CI = 0.41 to 1.06 ) . Risk was positively associated in a dose-response manner both with tendency to sunburn as a child or adolescent and with lifetime number of severe and painful sunburns on the face or arms . These risk factors remained significant predictors of disease when included simultaneously in multivariate analyses . Tendency to tan was associated with decreased risk , although this risk was not significant after controlling for the other constitutional determinants and region . Cigarette smoking did not alter the risk of basal cell carcinoma . These prospect i ve data emphasize the importance of sunlight , and skin response to sunlight , as determinants of basal cell carcinoma among women Objective : To investigate the association between total alcohol intake and intake of different types of alcoholic beverages in relation to the risk of basal cell ( BCC ) and squamous cell ( SCC ) carcinoma of the skin . Design : Prospect i ve cohort study . Setting : Follow-up data from a community-based skin cancer study in Australia . Subjects : R and omly selected sample of 1360 adult residents of the township of Nambour who completed a food frequency question naire in 1992 and were monitored for BCC and SCC until 31 December 2002 . Results : No significant association was found between overall BCC or SCC risk and total alcohol intake , or intake of beer , white wine , red wine or sherry and port . However , among those with a prior skin cancer history , there was a significant doubling of risk of SCC for above-median consumption of sherry and port ( multivariable adjusted relative risk 2.46 , 95 % confidence interval 1.06–5.72 ) compared with abstainers . Conclusions : There are no associations between first occurrence of skin cancers and alcoholic beverage consumption . People with a history of skin cancer who consume above-average quantities of sherry or port may be at a raised risk of SCC , although replication of these findings in different study population s is needed to confirm this possible role of specific alcoholic beverages in secondary keratinocytic skin cancer risk We prospect ively examined the intake of alcoholic beverages in relation to the risk of basal cell carcinoma BCC in two large cohorts of men and women . Alcohol intake was assessed with food frequency question naires every 2 - 4 years , and BCC was ascertained by self-report . We used a pooled logistic regression to model the association between alcohol intake and BCC adjusting for various health , sun exposure , and sun-sensitivity factors . During 8 years of follow-up in women ( 1986 - 1994 ) we recorded 3060 cases of BCC , and during 10 years ( 1986 - 1996 ) , we recorded 3028 cases in men . Significant positive associations were observed between total alcohol intake ( P for trend < 0.0001 ) , alcohol from liquor ( P for trend = 0.003 ) , and white wine ( P for trend = 0.01 ) intake and risk of BCC . Compared with those who abstained , those who drank 0.1 - 4.9 g , 5.0 - 14.9 g , 15.0 - 14.9 g , and 30 g or more alcohol a day had multivariate relative risks of 1.11 [ 95 % confidence interval ( CI ) , 1.03 , 1.19 ] , 1.26 ( 95 % CI , 1.12 , 1.41 ) , 1.29 ( 95 % CI , 1.18 , 1.42 ) , and 1.12 ( 95 % CI , 1.01 , 1.26 ) , respectively . Alcohol from beer had no association with BCC in either cohort , and red wine appeared to have an inverse association in women ( P for trend = 0.004 ) but not in men . These associations remained unchanged after adjustment for individual vitamins , multivitamin use , outdoor walking , and exclusion of follow-up time after last physical examination among those who never had BCC . Alcohol intake was associated with BCC , but the association appeared to be different for each type of alcoholic beverage . Other studies are needed to confirm these results The authors examined the relation of constitutional factors and sun exposure to risk of basal cell carcinoma of the skin ( BCC ) in a prospect i ve cohort of 44,591 predominantly Caucasian US male health professionals , 40 - 75 years of age and free of cancer at enrollment in 1986 . During 8 years of follow-up , 3,273 cases of self-reported BCC were documented . The following variables were each associated with an elevated risk of BCC : having red hair ; green , hazel , or blue eyes ; a tendency to sunburn ; and north European ancestry . The lifetime number of blistering sunburns was also positively associated with BCC risk ( p trend < 0.0001 ) . Compared with men who as teenagers had been outside less than once a week , men who had been outside weekly ( relative risk ( RR ) = 1.30 ; 95 % confidence interval ( CI ) : 1.14 , 1.47 ) and daily ( RR = 1.42 ; 95 % CI : 1.24 , 1.63 ) had an elevated risk of BCC . Living in a region of residence with high solar radiation as an adult was also associated with an increased risk of BCC ( RR = 1.48 ; 95 % CI : 1.36 , 1.60 ) , whereas living in such a region only in childhood did not increase BCC risk . These results confirm the role of constitutional factors and suggest that adult sun exposure increases BCC risk BACKGROUND Few epidemiologic studies are available that quantify the magnitude of the risk of squamous cell carcinoma ( SCC ) of the skin associated with sun exposure and related factors such as skin type . In addition , several studies have found an association between cigarette smoking and SCC . PURPOSE We prospect ively examined the risk of developing SCC in relation to phenotype and the effects of sun exposure , as well as to cigarette smoking and other factors , during 8 years of follow-up in a cohort of 107,900 predominantly white women aged 30 - 55 years at base line in 1976 . METHODS Question naires regarding medical history and health-related variables were sent to Nurses ' Health Study participants every 2 years , beginning in 1976 . Information on constitutional factors ( natural hair color , childhood and adolescent tendency to sunburn and tan , and lifetime number of severe sunburns ) , lifestyle factors ( regular time spent outdoors in the summer and sunscreen use ) , the state lived in at birth and at ages 15 and 30 years , and cigarette smoking habits were ascertained by question naire . A total of 197 women with first-incident , histologically confirmed , invasive SCCs that were diagnosed from 1982 to 1990 were included in this analysis . Multivariate analysis using proportional hazards models was used to calculate the relative risks ( RRs ) and corresponding 95 % confidence intervals ( CIs ) , with adjustment for confounders . RESULTS The risk of SCC was increased in women living in California ( RR = 1.8 ; 95 % CI = 1.3 - 2.6 ) and Florida ( RR = 2.1 ; 95 % CI = 1.1 - 3.9 ) at base line , compared with those living in the northeastern states . This risk was higher for women living in those states at birth and at 15 years of age ( RR = 2.5 ; 95 % CI = 1.4 - 4.4 for California and RR = 3.0 ; 95 % CI = 0.7 - 1.2 for Florida ) . Red ( RR = 2.0 ; 95 % CI = 1.1 - 3.7 ) and light brown ( RR = 1.7 ; 95 % CI = 1.2 - 2.4 ) hair colors were associated with an increased risk of SCC , compared with dark brown hair . After adjusting for the number of sunburns , women who tended to burn after 2 or more hours of sun exposure as children had a slightly higher risk of SCC than those who never burned ( RR = 1.5 ; 95 % CI = 0.9 - 2.5 for burn and RR = 1.1 ; 95 % CI = 0.6 - 2.0 for painful burn ) , although the actual number of severe burns appeared to be a more important factor ( RR = 2.4 ; 95 % CI = 1.5 - 4.0 for six or more burns ) . Finally , current cigarette smokers showed a 50 % increase in the risk of SCC compared with never smokers ( RR = 1.5 ; 95 % CI = 1.1 - 2.1 ) . CONCLUSION Exposure to the sun leading to sunburn , particularly at early ages , should be avoided to decrease the risk of incident SCC We conducted a hospital-based case-control study in Brisbane , Queensl and , to investigate the specific determinants of basal cell carcinoma ( BCC ) , as distinct from squamous cell carcinoma ( SCC ) , with emphasis on ancestry , residential history , pigmentary characteristics , sun sensitivity and other constitutional factors . The sample was recruited from a dermatology outpatient clinic during an eight-week period in 1991 , and comprised 51 incident or recently diagnosed cases of BCC , and 112 r and omly selected controls with no known history of BCC or SCC . Twenty-six cases with both BCC and SCC were analysed separately . We found no risk factor specific to BCC which might explain its extremely high prevalence . The strongest risk factors for BCC were advanced age , male sex and a propensity to freckle ( independent of skin colour and tendency to burn ) , all of which have previously been observed for SCC . A finding not previously reported was an apparent protective effect of increasing body mass , specific to BCC alone We determined the trends in incidence of skin basal cell carcinoma ( BCC ) using a primary care population ‐based cohort study in the UK . 11,113 adults with a BCC diagnosis were identified from a total of 7.22 million person‐years of data between 1996 and 2003 from the Health Improvement Network data base . From a r and om sub sample of BCC cases identified from the data base , 93 % were confirmed by hospital letter and /or pathology report . The incidence of BCC was 153.9 per 100,000 person‐years ( 95 % CI 151.1 , 156.8 ) and was slightly higher in men as compared to women ( Incidence Rate Ratio 1.10 , 95 % CI 1.06 , 1.14 ) . There was a 3 % increase year on year across the study period ( IRR 1.03 , 95 % CI 1.01 , 1.04 ) , with the largest increase in incidence seen in the 30–39 year age groups , although this did not reach statistical significance . Our study indicates 53,000 new cases of BCC are estimated every year in the UK and figures are continuing to rise on a yearly basis . Incidence rates are highest for men and in particular in the older age categories . These findings are consistent with those reported for various other population s. We have also found an increase in incidence in ages 30–39 , which may suggest a cohort effect of increasing ultraviolet exposure in successive younger generations . This may have a huge public and service impact in future years in countries such as the UK , with predominantly fair‐skinned population , with high leisure exposure to ultraviolet light . Our findings underline the need for more elaborate preventive measures . © 2007 Wiley‐Liss , The mortality experience of 10,322 men employed in woodworking industries was compared with that of 406,798 nonwoodworkers . All subjects were enrolled in an American Cancer Society study and followed prospect ively from 1959 through 1972 . Age-adjusted rates of death from all causes and from all cancers were not higher in the woodworker group , but excess rates were observed for cancers of the lung , stomach , and bladder , as well as nonmelanoma skin cancer and possibly leukemia . Woodworkers experienced significantly decreased rates of colon-rectum cancer and coronary heart disease . The elevated cancer rates could not be explained by cigarette smoking habits . If anything , there is evidence to suggest a possible interaction between employment in woodworking trades and heavy cigarette smoking , in increasing the risk of lung and bladder cancer |
10,575 | 15,976,422 | Significantly speedier return to normal activities and other improved secondary outcomes ( shorter duration of hospital stay and fewer unspecified infections or febrile episodes ) suggest that vaginal hysterectomy is preferable to abdominal hysterectomy where possible .
Where vaginal hysterectomy is not possible , laparoscopic hysterectomy is preferable to abdominal hysterectomy , although it brings a higher chance of bladder or ureter injury | OBJECTIVE To evaluate the most appropriate surgical method of hysterectomy ( abdominal , vaginal , or laparoscopic ) for women with benign disease . | The objective of this study was to assess the techniques by which hysterectomies are carried out and to determine the rate of total laparoscopic hysterectomy ( TLH ) . A transversal multicentre study was conducted in 23 gynaecology and obstetrics departments of French University Hospital Centres . The study population comprised only those patients for whom hysterectomy was indicated for benign disease without genital prolapse or urinary stress incontinence . Whereas the rates of performance of hysterectomy by laparotomy and by the vaginal route are comparable [ respectively 40.0 % ( 94 patients ) and 46.8 % ( 110 patients ) ] , the rate of performance of TLH is only 13.2 % ( 31 patients ) . All 23 centres ( 100 % ) carried out hysterectomy by laparotomy and 21 centres ( 91.3 % ) carried out vaginal hysterectomy ; however , only nine centres ( 39.1 % ) carried out TLH . Only seven centres ( 30.4 % ) performed all three types of operation . Of the eight centres whose rate of vaginal hysterectomy was > 60 % , six ( 75 % ) did not carry out TLH . The study suggests that the usage of the TLH technique appears to be limited . The extent of surgical training is a major factor in the choice of technique for hysterectomy OBJECTIVE To compare peroperative parameters of two variants of a laparovaginal hysterectomy in surgical management of gynecological conditions . METHODS A prospect i ve r and omized study of 70 laparovaginal hysterectomies performed by the same two surgeons for disease of female pelvic organs . The following criteria were studied : indication for surgery , previous surgery , duration of the procedure , recovery , hospital stay , blood loss , tissue damage markers , hysterectomy proportions and complication incidence . Statistical analysis was performed using the non-parametric chi(2)-test and non-parametric Fischer 's exact probability test when appropriate , with a level of significance P=0.05 . RESULTS Totals of 38 ( 54.3 % ) laparoscopy-assisted vaginal and 31 ( 45.7 % ) vaginally assisted laparoscopic hysterectomies were performed for fibroma as the main indication . Conversion to laparotomy was applied in only one patient . The VALH group ( P=0.01 ) showed both fewer procedures and shorter hospital stay with insignificant blood loss . CONCLUSION The two variants of a laparovaginal hysterectomy appear to be safe and appropriate , effective procedures for women with gynecological conditions . Furthermore , vaginally assisted laparoscopic hysterectomy has been shown to be superior to laparoscopy-assisted vaginal hysterectomy in terms of shorter operating time and greater palliative effect upon the complex of uterosacral ligaments . Laparoscopic surgery can alter the relationship between vaginal and abdominal hysterectomy Objective To compare laparoscopically assisted vaginal hysterectomy ( LAVH ) and total abdominal hysterectomy ( TAH ) in patients with uterine fibroids Objective To identify differences in the peri‐operative outcome of women undergoing hysterectomy with bilateral salpingo‐oophorectomy performed either by abdominal hysterectomy and bilateral salpingo‐oophorectomy or by laparoscopic‐assisted salpingo‐oophorectomy and vaginal hysterectomy . To identify any potential management implication s , including financial differences , between these two forms of operations Objective To compare the effects of laparoscopic hysterectomy and abdominal hysterectomy in the abdominal trial , and laparoscopic hysterectomy and vaginal hysterectomy in the vaginal trial . Design Two parallel , multicentre , r and omised trials . Setting 28 UK centres and two South African centres . Participants 1380 women were recruited ; 1346 had surgery ; 937 were followed up at one year . Primary outcome Rate of major complications . Results In the abdominal trial laparoscopic hysterectomy was associated with a higher rate of major complications than abdominal hysterectomy ( 11.1 % v 6.2 % , P = 0.02 ; difference 4.9 % , 95 % confidence interval 0.9 % to 9.1 % ) and the number needed to treat to harm was 20 . Laparoscopic hysterectomy also took longer to perform ( 84 minutes v 50 minutes ) but was less painful ( visual analogue scale 3.51 v 3.88 , P = 0.01 ) and result ed in a shorter stay in hospital after the operation ( 3 days v 4 days ) . Six weeks after the operation , laparoscopic hysterectomy was associated with less pain and better quality of life than abdominal hysterectomy ( SF-12 , body image scale , and sexual activity question naires ) . In the vaginal trial we found no evidence of a difference in major complication rates between laparoscopic hysterectomy and vaginal hysterectomy ( 9.8 % v 9.5 % , P = 0.92 ; difference 0.3 % , -5.2 % to 5.8 % ) , and the number needed to treat to harm was 333 . We found no evidence of other differences between laparoscopic hysterectomy and vaginal hysterectomy except that laparoscopic hysterectomy took longer to perform ( 72 minutes v 39 minutes ) and was associated with a higher rate of detecting unexpected pathology ( 16.4 % v 4.8 % , P = < 0.01 ) . However , this trial was underpowered . Conclusions Laparoscopic hysterectomy was associated with a significantly higher rate of major complications than abdominal hysterectomy . It also took longer to perform but was associated with less pain , quicker recovery , and better short term quality of life . The trial comparing vaginal hysterectomy with laparoscopic hysterectomy was underpowered and is inconclusive on the rate of major complications ; however , vaginal hysterectomy took less time Objective . The present study is a prospect i ve r and omized comparison of laparoscopically assisted vaginal hysterectomy ( LH ) with total abdominal hysterectomy ( TAH ) . OBJECTIVE We compared operative time , length of hospital stay , postoperative recovery , return to work , and costs for women undergoing laparoscopically assisted vaginal hysterectomy or abdominal hysterectomy . STUDY DESIGN A prospect i ve r and omized clinical trial of laparoscopically assisted vaginal hysterectomy ( n = 24 ) versus abdominal hysterectomy ( n = 24 ) was carried out in a tertiary care setting . The main outcome variables were operative time , length of hospital stay , and return to work . Secondary outcomes were postoperative pain and return to normal activity as determined by weekly visual analog scales and daily diary . Hospital costs were calculated . RESULTS The laparoscopically assisted vaginal hysterectomy group had longer operative times ( median and quartiles , laparoscopically assisted vaginal hysterectomy 180 [ 139 , 225 ] minutes vs abdominal hysterectomy 130 [ 97 , 155 ] minutes ) , lower requirements for postoperative intravenous analgesia ( patient-controlled analgesia pump , median and quartiles : laparoscopically assisted vaginal hysterectomy 22.1 [ 15.9 , 23.5 ] hours , abdominal hysterectomy 36.7 [ 26.2 , 45.0 ] hours ) , shorter length of hospital stay ( median and quartiles , laparoscopically assisted vaginal hysterectomy 1.5 [ 1.0 , 2.3 ] days , abdominal hysterectomy 2.5 [ 1.5 , 2.5 ] days ) , and quicker return to work ( Kaplan-Meier analysis , P = .03 ) . Both procedures had similar hospital costs ( P = .21 ) . CONCLUSION Laparoscopically assisted vaginal hysterectomy appears to allow patients a more rapid postoperative recovery and an earlier return to work with hospital costs similar to those of abdominal hysterectomy OBJECTIVE We evaluated the advantages and disadvantages of laparoscopic hysterectomy over a 2-year period when this new technique was introduced to several hospitals in Finl and . STUDY DESIGN A nationwide register was founded and a prospect i ve multicenter survey of 1165 laparoscopic hysterectomies was carried out from January 1993 to December 1994 . The operations were performed because of uterine fibroids ( 54 % ) , menorrhagia ( 27 % ) , dysmenorrhea ( 8 % ) , endometriosis ( 2 % ) , and other reasons ( 9 % ) by 68 gynecologists at 30 hospitals . RESULTS The mean operation time was 132 minutes . The patients stayed in hospital for an average of 3.3 days , and the mean convalescence period was 17.9 days , half that after abdominal hysterectomy . Complications occurred in 10.2 % of the procedures : infections in 5.6 % , vascular complications in 1.2 % , urinary tract complications in 2.7 % , and bowel complications in 0.4 % . CONCLUSIONS Laparoscopic hysterectomy offers a short hospital stay and convalescence time to the patient , but effective teaching is imperative to minimize , in particular , the risk of urinary tract injuries BACKGROUND To evaluate clinical outcome and tissue trauma after laparoscopic and abdominal hysterectomy . METHODS Fifty women scheduled for abdominal hysterectomy were r and omized to undergo either laparoscopic ( n = 25 ) or abdominal ( n = 25 ) hysterectomy . Surgical characteristics , hospital stay , convalescence and complications were analyzed . Blood sample s for assay of markers of tissue trauma ( interleukin-6 , C-reactive protein , tumor-associated trypsin inhibitor and tumor-associated antigen CA 125 ) were taken preoperatively , on the first , second and seventh postoperative day and at the follow-up visit four weeks after surgery . RESULTS In uncomplicated hysterectomies ( n = 18 ) the operating time ( 85.3 min versus 57.5 min , p < 0.00001 ) was longer for laparoscopic group but the hospital stay ( 2.1 days versus 3.4 days , p < 0.00001 ) and sick leave ( 21.4 days versus 38.5 days , p < 0.00001 ) were shorter in the laparoscopic group . Postoperative increases in all markers were significant in both groups . The interleukin-6 concentration was highest on the first postoperative day in both groups , that of C-reactive protein on the second postoperative day in both groups , tumor-associated trypsin inhibitor on the seventh postoperative day in the laparoscopic group and on the second postoperative day in the abdominal group and tumor-associated antigen CA 125 on the seventh postoperative day in both groups . Both interleukin-6 and C-reactive protein levels were lower in the laparoscopic group on the first ( p = 0.01 and p = 0.03 , respectively ) and on the second postoperative day ( p = 0.02 and p < 0.001 , respectively ) compared with the abdominal group . No differences were seen in tumor-associated trypsin inhibitor and tumor-associated antigen CA 125 levels between the groups . CONCLUSION Laparoscopic hysterectomy should replace abdominal hysterectomy whenever possible because of a more favorable clinical outcome and less tissue trauma Background . To determine under controlled conditions whether there are significant differences in the duration of hospitalization and recovery between abdominal and vaginal hysterectomy for indications other than uterovaginal prolapse The objective of this study was to compare the results of a modified laparoscopically assisted vaginal hysterectomy ( LAVH ) procedure , using light-endorsed transvaginal section by two puncture trocars , with those of total abdominal hysterectomy ( TAH ) in a prospect i ve , r and omized , short-term study . A new , modified LAVH technique using Endo GIA stapler and two puncture trocars was established . For the laparoscopic phase , each adnexum was dissected , and the vesicouterine junction was identified clearly with the laparoscopic light from the vaginal side . Vaginal-phase surgery was performed as usual . Two hundred patients scheduled for abdominal hysterectomy were r and omized to either LAVH ( n = 100 ) or TAH ( n = 100 ) . Duration of hospitalization , time of surgery , dose of analgesics , and rates of complications were significantly lower in the LAVH group ( p < 0.001 ) . The average operating time was 77 ± 30 min for LAVH and 102 ± 18 min for TAH . The duration of hospitalization was 3.2 ± 0.7 days for LAVH and 5.5 ± 1.3 days for TAH . There were three complications in the LAVH group and 15 in the TAH group . Postoperative meperidine requirements ( 1.2 vs. 3.7 ampoules , 1 ampoule = 50 mg ) were significantly fewer in the LAVH group . Regarding the training time , the mean operating time in the first 20 cases was 98 min , and in the last 20 cases it was 70.9 min . As compared with TAH and other modified LAVH procedures reported previously , the present technique is easy to learn and timesaving with fewer complications OBJECTIVE The objective of this study was to evaluate short-term results of laparoscopically assisted vaginal hysterectomy with those of total abdominal hysterectomy in a prospect i ve , r and omized , multicenter study . STUDY DESIGN One hundred sixteen patients referred for abdominal hysterectomy were r and omized to either laparoscopically assisted vaginal hysterectomy ( 58 patients ) or abdominal hysterectomy ( 58 patients ) . Inclusion criteria were one or more of the following , where a vaginal hysterectomy would be traditionally contraindicated : uterine size larger than 280 g , previous pelvic surgery , history of pelvic inflammatory disease , moderate or severe endometriosis , concomitant adnexal masses or indication for adnexectomy , and nulliparity with lack of uterine descent and limited vaginal access . An upper limit of uterine size was set at 16 weeks ' gestation ( ie , 700 g ) . RESULTS There were no differences in terms of patient 's age , parity , preoperative hemoglobin levels , mean uterine weight , and total operating time between the 2 groups . Estimated blood losses and postoperative day 1 hemoglobin drop were significantly lower for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy ( P<.05 ) . There were 1 major and 2 minor complications in the laparoscopically assisted vaginal hysterectomy group compared with 2 major and 5 minor complications in the abdominal hysterectomy group ( P not significant ) . Postoperative pain was lower for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy on postoperative days 1 , 2 , and 3 ( P<.05 ) . Postoperative hospital stay was significantly shorter for laparoscopically assisted vaginal hysterectomy than for abdominal hysterectomy ( P<.001 ) . CONCLUSIONS The present study demonstrates that , given adequate training in laparoscopic surgery , laparoscopically assisted vaginal hysterectomy may replace abdominal hysterectomy in most patients who require a hysterectomy and have contraindications to vaginal hysterectomy , with all the benefits associated with the vaginal route Objective : To compare outpatient laparoscopy-assisted vaginal hysterectomy with st and ard outpatient vaginal hysterectomy Methods : Fifty-six women scheduled for vaginal hysterectomy were r and omly assigned to undergo either a laparoscopy- assisted vaginal hysterectomy with endoscopic staples ( N=29 ) or a st and ard vaginal hysterectomy ( N=27 ) . There were no differences between the study groups with regard to age , gravidity , parity , preoperative indications , and previous operations Results : Twenty-eight of 29 laparoscopy-assisted vaginal hysterectomies and all 27 vaginal hysterectomies were completed without incident . When indicated , unilateral or bilateral oophorectomies were completed . The mean operating time was significantly longer for laparoscopy-assisted vaginal hysterectomy ( 120.1 versus 64.7 minutes ) . Fifty-three of the 55 patients completing surgery were discharged home by 12 hours from the time of admission . Complications with laparoscopic hysterectomy were related to the technical aspects of laparoscopy . The incidence of febrile morbidity was similar in the groups . Although patients having laparoscopy- assisted hysterectomy required statistically significantly more pain medication and had lower postoperative hematocrit measurements , this did not make a clinical difference in the postoperative courses . The mean hospital charge for laparoscopy-assisted vaginal hysterectomy was $ 7905 and for vaginal hysterectomy $ 4891 Conclusion : Other than cost , laparoscopy-assisted vaginal hysterectomy and st and ard vaginal hysterectomy appear comparable in patients who could otherwise undergo a vaginal hysterectomy STUDY OBJECTIVE To evaluate in a prospect i ve series whether , even in presence of a large uterus , total laparoscopic hysterectomy is feasible and safe , and may be substituted for abdominal hysterectomy . DESIGN R and omized comparison ( Canadian Task Force classification I ) . Setting . Center for Reconstructive Pelvic Endosurgery , Bologna , Italy . PATIENTS One hundred twenty-two women with large uterus ( > 14 wks ' gestation ) caused by myomas . INTERVENTION Total laparoscopic hysterectomy and total abdominal hysterectomy . MEASUREMENTS AND MAIN RESULTS Sixty women underwent laparoscopic hysterectomy ( group 1 ) and 62 abdominal hysterectomy ( group 2 ) . Mean longitudinal diameter of the uterus , mean number and diameter of myomas , operating time , and average drop in hemoglobin were similar in the groups . One conversion to laparotomy was necessary because of a bowel injury in a patient with severe pelvic adhesions . Cystotomy occurred in one woman in group 2 and was immediately repaired . Febrile morbidity was statistically more frequent in group 2 than in group 1 . Postoperative hospitalization and convalescence were statistically shorter in group 1 . CONCLUSION Laparoscopic hysterectomy is safe and feasible even in the presence of large uterus , and is a valid alternative to abdominal hysterectomy when the vaginal route is contraindicated Objective To detect differences in clinical short term outcome between total abdominal hysterectomy , vaginal hysterectomy and laparoscopic assisted vaginal hysterectomy BACKGROUND The aim of this study was to evaluate pain and pulmonary function the first two days after abdominal and laparoscopic hysterectomy . METHODS Women scheduled for abdominal hysterectomy were prospect ively r and omized to either laparoscopic ( n=20 ) or abdominal ( n=20 ) hysterectomy . Analgesics were self-administered by the patients by means of a programable infusion pump containing morphine . Postoperative pain was evaluated using a visual analog scale . Oxygen saturation was measured with an oxymeter . Pulmonary function was assessed using a peak flow meter measuring peak expiratory flow and a vitalograph measuring forced vital capacity and forced expiratory volume in one second . RESULTS Pain scores were lower after laparoscopic hysterectomy at the first ( p<0.05 ) and second postoperative day ( p<0.01 ) . Lung function was impaired on days 1 and 2 postoperatively , measured as peak expiratory flow , forced vital capacity and forced expiratory volume in one second , in both groups compared to the preoperative values . The patients undergoing laparoscopic hysterectomy had less impairment of lung function measured by peak expiratory flow ( p<0.01 ) , forced vital capacity ( p<0.05 ) and forced expiratory volume in one second ( p<0.05 ) the first postoperative day compared to the patients undergoing abdominal hysterectomy . The second postoperative day differences between the groups remained for peak expiratory flow ( p<0.05 ) and forced expiratory volume in one second ( p<0.05 ) . CONCLUSIONS Laparoscopic hysterectomy results in less pain and less impairment of respiratory function compared to abdominal hysterectomy OBJECTIVES To evaluate operative time , blood loss and inflammatory response in patients su bmi tted to hysterectomy . METHODS Sixty patients referred for hysterectomy were prospect ively r and omized to total abdominal hysterectomy ( n=20 ) , vaginal hysterectomy ( n=20 ) , or laparoscopic hysterectomy ( n=20 ) . The operative time , blood loss ( variation in erythrocyte and hemoglobin ) and inflammatory answer ( CRP and interleukin-6 dosages ) were compared by using Kruskal-Wallis , Dunn non-parametric test and variance analysis with repeated measurements . RESULTS Operative time was shorter for vaginal hysterectomy , and there was no significant difference between total abdominal hysterectomy and laparoscopic hysterectomy . Reduction in erythrocyte and hemoglobin was more noticeable after vaginal hysterectomy , followed by total abdominal hysterectomy and laparoscopic hysterectomy . CRP levels increased steadily from vaginal hysterectomy to laparoscopic hysterectomy and then to total abdominal hysterectomy . The increase in interleukin-6 was substantially higher in total abdominal hysterectomy , whereas no difference was noted between vaginal and laparoscopic hysterectomy . CONCLUSIONS Vaginal hysterectomy presents superior results in terms of operative time and inflammatory response when compared with total abdominal and laparoscopic hysterectomy and it should be the first option for hysterectomy . Laparoscopic hysterectomy should be considered when the vaginal approach is unfeasible , showing clear advantages over abdominal hysterectomy The present r and omized study was undertaken in order to compare the short-term results between total laparoscopic hysterectomy and abdominal hysterectomy in a centre with experience in laparoscopic surgery . From January 1997 to September 1998 inclusive , 102 women aged 44 - 71 years were r and omly assigned to either total laparoscopic hysterectomy ( n = 51 patients ) or abdominal hysterectomy ( n = 51 patients ) . The patients ' demographic characteristics were similar in both groups . Average intra-operative blood loss was lower in laparoscopic hysterectomy than in abdominal hysterectomy ( P < /= 0 . 001 ) . The average time employed for laparoscopic hysterectomy was 104.1 + /- 26.98 min ; according to the learning curve experienced in this study , the range was 72 - 163 min and the results after the plateau was reached showed no statistical difference between laparoscopic and abdominal operating times . The mean length of hospital stay was 2.38 + /- 0.30 days in the laparoscopic hysterectomy group versus 6.23 + /- 1.85 days in the abdominal hysterectomy group ( P < /= 0.001 ) . In conclusion , this study shows that total laparoscopic hysterectomy can be effectively performed within reasonable time limits , provided that operators are experienced surgeons in operative laparoscopy and that operating times are comparable with those of abdominal hysterectomy Background . The purpose of this study was to compare peri‐operative morbidity , preoperative sonographic estimation of uterine weight and postoperative outcomes of women with uterine fibroids larger than 6 cm in diameter or uteri estimated to weigh at least 450 g , undergoing either vaginal , laparoscopically assisted vaginal or abdominal hysterectomies Background . To evaluate changes in psychological well‐being and sexuality 1 year after laparoscopic and abdominal hysterectomy OBJECTIVE The purpose of this study was to compare advantages , disadvantages , and outcomes in patients who undergo vaginal or abdominal hysterectomy for enlarged symptomatic uteri . STUDY DESIGN In a prospect i ve , r and omized study , 60 vaginal hysterectomies ( study group ) were compared with 59 abdominal hysterectomies ( control group ) ; all of the hysterectomies were performed for symptomatic uterine fibroids from January 1997 through December 2000 . We excluded from the study the other common causes of hysterectomy such as prolapse , bleeding , adenomyosis , and endometrial or cervical carcinoma . In both groups , uterine weights ranged from 200 g to 1300 g. For enlarged uteri , vaginal hysterectomies were performed with the use of volume reduction techniques : Intramyometrial coring , corporal bisection , and morcellation . The evaluated parameters included patient age , weight , parity , uterine weight , operative time , blood loss , dem and for analgesics , eventual surgical complications , length of admission , and hospital charges . The Mann-Whitney U test and chi(2 ) tests were applied for statistical analysis . Probability values of < .05 were considered statistically significant . RESULTS There were no major differences in patient age , weight , parity , and uterine weight between the two groups . Operative time was significantly lower for the vaginal route as compared with the abdominal route ( 86 minutes vs 102 minutes , P < .001 ) . No intraoperative complications were noted both in the study and control groups or the control group . Surgical bleeding ( expressed by hemoglobin loss ) was not significantly different between the two groups . In the postoperative period , we found a higher incidence of fever ( 30.5 % vs 16.6 % , P < .05 ) and dem and for analgesics ( 86 % vs 66 % , P < .05 ) in the abdominal group as compared with the vaginal group . Significant advantages of vaginal hysterectomy were a reduction in the hospital stay ( 3 days vs 4 days , P < .001 ) and cost . CONCLUSION These results should lead to the choice of vaginal hysterectomy as a valid alternative to the abdominal hysterectomy , even for enlarged uteri BACKGROUND Laparoscopic-assisted vaginal hysterectomy ( LAVH ) can be used for the vaginal removal of large uteri ( 200 g ) , which are conventionally treated with an abdominal approach ( AH ) . METHODS Forty-eight women with a sonographically estimated uterine weight of > 200 g were prospect ively r and omized to undergo either LAVH ( n = 28 ) or AH ( n = 20 ) . RESULTS The median uterus weight was 334 g for LAVH vs 428 g for AH ( not significant ) . The median operative time ( 133 vs 132 min ) and duration of recuperation ( 42 vs 42 days ) were similar . LAVH was associated with significantly less intraoperative blood loss ( median , 200 vs 600 ml ; p < 0.05 ) , a lower pain index at postoperative day 4 ( median [ who scale ] , 0 VS 5 ; P < 0.05 ) , a lower decrease in hemoglobin ( median,-0.6 VS -1.55 MG/DL ; P < 0.05 ) , and a lower decrease in hematocrit ( median , -0.03 % VS -0.07 % ; P < 0.05 ) . There were no significant differences in the frequency of postoperative complications ( 14.3 % for LAVH VS 30 % for AH ) . Although all LAVH patients who answered the question naire said they would undergo the same procedure again , only 45 % of the AH group were satisfied ( P < 0.05 ) . CONCLUSION For the treatment of uteri > 200 g , LAVH has several advantages over AH : lower postoperative morbidity , quicker short-term recuperation , and better patient acceptance Objective To compare intraoperative and postoperative outcomes between laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy among patients who are not eligible for vaginal hysterectomy . Methods Study subjects were r and omly assigned to undergo laparoscopically assisted vaginal hysterectomy or st and ard abdominal hysterectomy . Intraoperative and post-operative management was similar for each group . Surgical characteristics , complications , length of hospital stay , charges , and convalescence were analyzed . Results Sixty-five women at three institutions underwent laparoscopically assisted vaginal hysterectomy ( n = 34 ) or abdominal hysterectomy ( n = 31 ) . Three patients in the laparoscopic group required conversion to abdominal hysterectomy . Mean operating time was significantly longer for laparoscopically assisted vaginal hysterectomy ( 179.8 versus 146.0 minutes ) . There were no differences in blood loss or incidence of intraoperative complications . There was a higher incidence of wound complications in the abdominal hysterectomy group , but no significant difference in the frequency of postoperative complications . Laparoscopically assisted vaginal hysterectomy required a significantly shorter mean hospital stay ( 2.1 days ) and convalescence ( 28.0 days ) than abdominal hysterectomy ( 4.1 days and 38.0 days , respectively ) . There were no significant differences in mean hospital charges between the study groups ( laparoscopic $ 8161 , abdominal $ 6974 ) . Conclusion Except for operating time , there are no differences between laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy regarding intraoperative characteristics among abdominal hysterectomy c and i date s. Postoperatively , laparoscopically assisted vaginal hysterectomy requires a shorter hospital stay and convalescence . Hospital charges are similar between the procedures . A larger number of cases will help determine the indications for laparoscopically assisted vaginal hysterectomy The goal of this study was to compare laparoscopically assisted vaginal hysterectomy ( LAVH ) with total abdominal hysterectomy ( TAH ) . We performed a prospect i ve comparison of the hospital courses of 30 women , 15 undergoing LAVH and 15 undergoing TAH , in a teaching hospital setting . Analysis of variance ( ANOVA ) was used , with statistical evaluation of differences by Student 's t-test for normally distributed data and Kruskal-Wallis for data with dissimilar variances . Fourteen of fifteen patients scheduled for LAVH had their surgery completed without need of a laparotomy . In the LAVH group , ( 1 ) mean surgical time was 50 minutes longer , ( 2 ) blood loss , complications , and hospital costs were not statistically different , ( 3 ) hospital days averaged 1 1/2 less , and ( 4 ) postoperative pain ratings and medication requirements were significantly decreased , compared with the TAH group . In many cases , LAVH may be reasonably performed instead of an indicated TAH Objectives To determine the safety , cost effectiveness and effect on quality of life of laparoscopicassisted vaginal hysterectomy ( LAVH ) compared with total abdominal hysterectomy ( TAH ) in the management of benign gynaecological disease |
10,576 | 18,625,004 | The superiority of the anti-emetic efficacy of cannabinoids was demonstrated through meta- analysis | null | null |
10,577 | 27,496,701 | Conclusion : The main barriers and facilitators to goal - setting during stroke rehabilitation have been identified .
They suggest that current methods of goal - setting during inpatient/early stage stroke or neurological rehabilitation are not fit for purpose | Objective : To identify the barriers and facilitators to goal - setting during rehabilitation for stroke and other acquired brain injuries . | Objectives : The recent National Service Framework for Long Term Conditions recommends that patients participate more in decision making about their care . However , few protocol s exist to support this . One potentially useful method is goal setting , but little has been done to evaluate the added value of increasing patient participation in this way . Therefore , this study examined the impact of an increased participation goal setting protocol in a neurorehabilitation setting . Design : The study was an AB optimised balance block design with each block lasting 3 months , over an 18 month period . Setting and participants : Patients ( n = 201 ) were recruited from an inpatient neurological rehabilitation unit . Interventions : Patients ( n = 100 ) recruited in phase A were involved in “ usual practice ” goal setting . Patients ( n = 101 ) recruited in phase B were involved in “ increased participation ” goal setting , which included a protocol to help them define and prioritise their own goals . Main outcome measures : Patients ’ perceptions of the relevance of goal setting and their autonomy within the process ; the number , type and outcome of goals ; and level of functional ability . Results : Phase B patients ( “ increased participation ” ) set fewer goals , of which significantly more were participation related . These patients perceived the goals to be more relevant , and expressed greater autonomy and satisfaction with goal setting . There were no differences in functional outcomes between the groups . Conclusion : This study has shown that patients prefer increased participation in the goal setting process over st and ard procedures , perceiving their goals as more relevant and rehabilitation more patient centred despite the absence of functional gains . Effective patient centred care can be realised by using structures that help support patients to identify and communicate their priorities . As such , our findings suggest patients would benefit from greater participation in this aspect of clinical decision making Objective : To examine the feasibility of and clinical experiences with goal attainment scaling when used for the evaluation of cognitive rehabilitation in people with acquired brain injury . Design : A prospect i ve observational longitudinal study . Setting : A 21-week cognitive rehabilitation programme and a cognitive programme with varying length in two different Dutch rehabilitation centres . Subjects : Forty-eight consecutive patients with acquired brain injury enrolled during a 15-month period . Interventions : Cognitive rehabilitation programme . Main measure : Goal attainment scaling ; the number of goals was counted ; time to set goals was recorded ; the number of different domains in which goals were set was counted ; goal attainment scaling score was calculated at baseline , one week after the end of the cognitive rehabilitation programme and at six months follow-up ; clinical experiences that could be useful for both clinical and research practice were recorded . Results : The mean ( SD ) age of the patients was 46.1 ( 10.7 ) years ; 29 ( 60 % ) were male ; 186 goals were set with a mean ( SD ) number of 4 ( 1 ) goals per patient . It was possible to set at least three realistic goals per patient within 30 minutes . Most goals were set in the cognitive domain ( i.e. memory and attention ) , followed by the behavioural domain ( i.e. fatigue and aggression ) . Conclusion : It proved possible to set three goals within an acceptable time-frame , to involve patients in the goal - setting procedure , to set realistic goals , and to set goals within relevant domains . Based on clinical experiences , goal attainment scaling is less feasible for research when patients lack insight , or suffer from comorbidity or mood problems Objective : To determine the acceptability and clinical application of two recently developed goal - setting interventions ( Goal Management Training and Identity Oriented Goal Training ) in people with traumatic brain injury . Design : A three parallel group , r and omized controlled pilot study . Setting : Inpatient and community rehabilitation facilities . Subjects : Thirty-four people with moderate to severe traumatic brain injury ( Goal Management Training , n = 12 ; Identity Oriented Goal Training , n = 10 ; usual care , n = 12 ) and their rehabilitation clinicians . Interventions : For both Goal Management Training and Identity Oriented Goal Training participants met face to face with their key worker weekly over a period of 6—8 weeks , during which time the key worker worked to engage them in goal setting and goal performance using the strategy prescribed by their group allocation . Usual care was provided to the other participants . Main measures : Largely qualitative using observation , individual interviews and focus groups . Participants also completed a Goal Attainment Scale at baseline , post intervention and at three months follow-up . Results : Both approaches were acceptable to the majority of participants with many reporting improved mood and goal attainment . Clinicians found working in a different way with patients both challenging and rewarding , with both experimental approaches enhancing a focus on the person 's own goals . Identity Oriented Goal Training seemed particularly helpful in engaging people in the goal - setting process while Goal Management Training appeared particularly helpful in providing a structured framework for error prevention in attempting goal performance . Conclusion : These theoretically informed approaches to goal setting showed promise but were time intensive and at times difficult for practitioners to utilize |
10,578 | 27,974,062 | There was mixed evidence for effectiveness of group CBT on symptoms of depression .
An RCT of debt advice found no effect but had poor uptake .
' Job-club ' interventions may be effective in reducing depressive symptoms in unemployed people , particularly those at high risk of depression . | BACKGROUND Job loss , debt and financial difficulties are associated with increased risk of mental illness and suicide in the general population .
Interventions targeting people in debt or unemployed might help reduce these effects . | In this paper , we employ a classical experiment to determine if welfare reform causes poor women to experience increased levels of clinical anxiety and depression . We organize our analyses around the insights provided by lifestyle change and ecosocial theories of illness . Our data come from the New Jersey Family Development Program ( FDP ) , one of the most highly publicized welfare experiments in the U.S. A sample of 8393 women was r and omly assigned into two groups , one which stressed welfare-to-work and the other which offered traditional welfare benefits . These women were followed from 1992 through 1996 and information on clinical diagnoses was collected quarterly from physician treatment cl aims to the government Medicaid program . Our intention-to-treat estimates show that for short-term welfare recipients FDP decreased the prevalence of anxiety by 40 % and increased depression by 8 % . For black women both anxiety and depression diagnoses declined while Hispanic women experienced a 68 % increase in depression . We discuss several public policy implication s which arise from our work This study aim ed to investigate ( a ) whether it is possible to increase emotional competence ( EC ) in adulthood ; ( b ) whether this improvement results in better mental , physical , and social adjustment ; ( c ) whether this improvement can be maintained 1 year later ; and ( d ) whether these benefits are accompanied by a reduction in stress-hormone secretion ( i.e. , cortisol ) . One hundred and thirty-two participants were r and omly assigned to an EC-enhancing intervention ( in group format ) or to a control group . Participants in the intervention group underwent a specifically design ed 15-hr intervention targeting the 5 core emotional competencies , complemented with a 4-week e-mail follow-up . Results reveal that the level of emotional competencies increased significantly in the intervention group in contrast with the control group . This increase result ed in lower cortisol secretion , enhanced subjective and physical well-being , as well as improved quality of social and marital relationships in the intervention group . No significant change occurred in the control group . Peer reports on EC and quality of relationships confirmed these results . These data suggest that emotional competencies can be improved , with effective benefits on personal and interpersonal functioning lasting for at least 1 year . The theoretical implication s of these results as well as their practical implication s for the construction and the development of effective emotional competencies interventions are discussed Background In the developing world , access to small , individual loans has been variously hailed as a poverty-alleviation tool – in the context of " microcredit " – but has also been criticized as " usury " and harmful to vulnerable borrowers . Prior studies have assessed effects of access to credit on traditional economic outcomes for poor borrowers , but effects on mental health have been largely ignored . Methods Applicants who had previously been rejected ( n = 257 ) for a loan ( 200 % annual percentage rate – APR ) from a lender in South Africa were r and omly assigned to a " second-look " that encouraged loan officers to approve their applications . This r and omized encouragement result ed in 53 % of applicants receiving a loan they otherwise would not have received . All subjects were assessed 6–12 months later with questions about demographics , socio-economic status , and two indicators of mental health : the Center for Epidemiologic Studies – Depression Scale ( CES-D ) and Cohen 's Perceived Stress scale . Intent-to-treat analyses were calculated using multinomial probit regressions . Results R and omization into receiving a " second look " for access to credit increased perceived stress in the combined sample of women and men ; the findings were stronger among men . Credit access was associated with reduced depressive symptoms in men , but not women . Conclusion Our findings suggest that a mechanism used to reduce the economic stress of extremely poor individuals can have mixed effects on their experiences of psychological stress and depressive symptomatology . Our data support the notion that mental health should be included as a measure of success ( or failure ) when examining potential tools for poverty alleviation . Further longitudinal research is needed in South Africa and other setting s to underst and how borrowing at high interest rates affects gender roles and daily life activities . CCT : IS RCT N 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 . This study evaluated benefits of a preventive intervention to the living st and ards of recently separated mothers . In the Oregon Divorce Study 's r and omized experimental design , data were collected 5 times over 30 months and evaluated with Hierarchical Linear Growth Models . Relative to their no-intervention control counterparts , experimental mothers had greater improvements in gross annual income , discretionary annual income , poverty threshold , income-to-needs ratios , and financial stress . Comparisons showed the intervention to produce a greater increase in income-to-needs and a greater rise-above-poverty threshold . Benefits to income-to-needs were statistically independent of maternal depressed mood , divorce status , child support , and repartnering . Financial stress reductions were explained by the intervention effect on income-to-needs . The importance of helping disadvantaged families with evidence -based programs is discussed Analyses of data from a r and omized field experiment with 1,801 participants ( A.D. Vinokur , R.H. Price . & Y.Schul , 1995 ) examined the long-term effects of a job- search workshop ( JOBS ) and the independent effects of demographic and psychological factors on reemployment and mental health outcomes . Two years after the JOBS workshop , the experimental group had significantly higher levels of reemployment and monthly income , lower levels of depressive symptoms , lower likelihood of experiencing a major depressive episode in the last year , and better role and emotional functioning compared with the control group . Baseline job- search motivation and sense of mastery had both direct and interactive effects ( with experimental condition ) on reemployment and mental health outcomes , respectively . The interactive effects demonstrated larger benefits for those who had initial low levels of job- search motivation and mastery Conducted process analysis of treatment mediation effects ( Judd & Kenney , 1981 ) on longitudinal data from a large r and omized field experiment with 928 recently unemployed persons . The experimental treatment included an intervention that succeeded in promoting quality reemployment outcomes , as described in earlier reports ( Caplan et al. , 1989 ; Vinokur et al. , 1991 ) . Using Ajzen 's theory of planned behavior ( Ajzen , 1985 , 1988 ) , the analyses examined the mediating effects of job- search self-efficacy , attitude , norms , and intention on job- search behavior . The results provided substantial support for the theory of planned behavior and demonstrated the mediational role of job- search self-efficacy . For both 1- and 4-month posttests , job- search self-efficacy was shown to mediate the effects of the intervention through its direct effects on job- search intention and on short term job- search behavior , as well as through its indirect effects on subjective norms and attitude . However , in the longer term 4-month posttest , exposure to the intervention had a direct effect on job- search behavior . This long-term direct effect of the intervention was hypothesized to reflect the influence of inoculation against setbacks which is essential for sustaining the long-term behavioral efforts involved in job seeking PURPOSE The purpose of this study was to determine the relationship between the working alliance and employment outcomes in persons with severe mental illness receiving vocational services . Another purpose of this study was to determine whether working alliance differences exist between clients receiving evidence -based supported employment services and those receiving traditional stepwise vocational services . DESIGN This study was a secondary analysis of a 2-year r and omized controlled trial comparing two employment programs providing services to people with severe mental illness . RESULTS Contrary to expectations , no overall relationship was found between the working alliance and employment outcomes . As predicted , supported employment participants each assigned to a single vocational worker had more positive working alliances than participants served by a team of vocational workers in the traditional vocational program . CONCLUSIONS / IMPLICATION S The lack of an association between the working alliance and employment outcomes is inconsistent with previous literature . Further research is needed using st and ardized working alliance measures and larger sample s that include both working and nonworking clients . Evidence -based supported employment , which employs individual caseloads , seems to foster better relationships than a team-based vocational approach , although future research is needed to replicate this finding The impact of preventive interventions for the unemployed may vary depending on the context of the labor policies and benefit systems of the country where it is implemented . The Työhön Job Search Program was based on a method developed in the United States for recently unemployed workers . This study examined outcomes of the intervention in the context of the European labor market for participants who had been unemployed for a longer period . A total of 1,261 unemployed Finnish job seekers participated in a r and omized field study . At the 6-month follow-up , the program had a beneficial impact on the quality of reemployment , especially among those who had been unemployed for a moderate time period . The program also significantly decreased psychological distress Drawing on coping re sources theory , we evaluate the impact of a job search intervention on depressive symptoms in a r and omized field experiment at three follow-up periods covering two and one-half years . Baseline depressive symptoms , low social assertiveness , and financial hardship were identified as significant risk variables predicting depressive symptoms at follow-up . These variables then were used to identify high- and low-risk individuals in both experimental and control groups . Results indicated that the job search intervention had its primary impact on persons identified as being at higher risk for depression . Furthermore , the intervention had an impact on both the incidence and prevalence of more severe depressive symptoms among high-risk individuals The process linking unemployment and economic hardship to depression and marital or relationship satisfaction in couples was examined . Using structural equation modeling , the authors tested models in which financial strain and partners ' symptoms of depression influence the behavioral exchange of the couples in terms of social support and social undermining and , in turn , the effects of support and undermining on relationship satisfaction and depressive symptoms . The analyses were based on longitudinal data from 815 recently unemployed job seekers and their spouses or partners . The results demonstrated that financial strain had significant effects on depressive symptoms of both partners , which in turn led the partner to withdraw social support and increase social undermining . Reduced supportive and increase undermining behaviors had additional adverse effects on satisfaction with the relationship and on depressive symptoms Cognitive theories of adherence to difficult courses of action and findings from previous survey research on coping with a major life event -- job loss -- were used to generate a preventive intervention , tested by a r and omized field experiment . The aim was to prevent poor mental health and loss of motivation to seek reemployment among those who continued to be unemployed and to promote high- quality reemployment . Ss were 928 recently unemployed adults from southeastern Michigan , representing a broad range of demographic characteristics ; they were r and omly assigned to either the experimental or control condition . The experimental intervention included training in job seeking with a problem-solving process emphasizing inoculation against setbacks and positive social reinforcement . A pretest was administered , followed by posttests 1 and 4 months after the experiment . The experimental condition yielded higher quality reemployment in terms of earnings and job satisfaction , and higher motivation among those who continued to be unemployed TOPIC Supported Employment ( SE ) can help transition age youth and young adults to obtain employment and develop meaningful careers and financial security . PURPOSE The purpose of this analysis is to examine the role of SE in achieving employment outcomes for youth ( ages 18 - 24 ) and young adults ( ages 25 - 30 ) , compared to outcomes for older adults . Given the importance of employment to the quality of life of young people in establishing work histories and starting careers , it is important to have a better underst and ing of what client and program characteristics result in better employment outcomes . SOURCES USED Data are from the Employment Intervention Demonstration Program ( EIDP ) , a multisite r and omized controlled trial of SE among 1,272 individuals with psychiatric disabilities in 7 states . CONCLUSIONS AND IMPLICATION S FOR PRACTICE Among all study participants , youth and young adults had significantly better outcomes in terms of any employment and competitive employment than older ( > 30 years ) adults . However , in multivariable models of participants r and omly assigned to SE , young adults had significantly better outcomes than youth or older adults . Other significant predictors of employment and competitive employment were future work expectations , not receiving Supplemental Security Income , and receipt of more hours of SE services . Characteristics of youth , young adults and SE programs that enhance employment are discussed in terms of policy and practice Objectives : The aim of the present study was to examine and compare the long-term effectiveness of the Integrated Supported Employment ( ISE ) programme , which consists of individual placement and support ( IPS ) and work-related social skills training , with the IPS programme on the vocational and non-vocational outcomes among individuals with severe mental illness ( SMI ) over a period of 3 years . Method : One hundred and eighty-nine participants with SMI were recruited from two non-government organizations and three day hospitals in Hong Kong and r and omly assigned into the ISE ( n = 58 ) , IPS ( n = 65 ) and traditional vocational rehabilitation ( TVR ) ( n = 66 ) groups . Vocational and non-vocational outcomes of the ISE and IPS participants were collected by a blind and independent assessor at 7 11 , 15 , 21 , 27 , 33 and 39 months after their admission , whereas the TVR groups were assessed only up to the 15th month follow up . Results : After 39 months of service provision , ISE participants obtained higher employment rate ( 82.8 % vs 61.5 % ) and longer job tenure ( 46.94 weeks vs 36.17 weeks ) than the IPS participants . Only 6.1 % of TVR participants were able to obtain employment before the 15th month follow up . Fewer interpersonal conflicts at the workplace were reported for the ISE participants . Advantages of the ISE participants over IPS participants on non-vocational outcomes were not conclusive . Conclusion : The long-term effectiveness of the ISE programme in enhancing employment rates and job tenures among individuals with SMI was demonstrated by this r and omized controlled trial Reports the results of the JOBS II r and omized field experiment that included a sample of 1,801 recent job losers , 671 of which participated in a modified version of the JOBS I intervention for unemployed workers ( Caplan , Vinokur , Price , & van Ryn , 1989 ) . The intervention focused on enhancing the sense of mastery through the acquisition of job- search and problem-solving skills , and on inoculation against setbacks . JOBS II was intended to prevent poor mental health and to promote high quality reemployment . The study tested whether the efficacy of the intervention could be increased by screening and oversampling respondents who were at higher risk for a significant increase in depressive symptoms . Results demonstrated that the intervention primarily benefited the reemployment and mental health outcomes of the high-risk respondents . This suggests the feasibility of enhancing the efficacy of this preventive intervention by targeting , it for high-risk unemployed workers who could be identified prospect ively BACKGROUND The principles of cognitive-behavioural therapy ( CBT ) have been applied successfully through individual psychotherapy to several psychiatric disorders . We adapted these principles to create a group -- training programme for a non-psychiatric group-long-term ( > 12 months ) unemployed people . The aim was to investigate the effects of the programme on measures of mental health , job-seeking , and job-finding . METHODS 289 volunteers ( of st and ard occupational classification professional groups ) were r and omly assigned to a CBT or control programme , matched for all variables other than specific content , that emphasised social support . 244 ( 134 CBT , 110 control ) people started the programmes and 199 ( 109 CBT , 90 control ) completed the whole 7 weeks of weekly 3 h sessions ( including three CBT , seven control participants who withdrew because they obtained employment or full-time training ) . Question naires completed before training , on completion , and 3 - 4 months later ( follow-up data available for 94 CBT , 89 control ) assessed mental health , job-seeking activities , and success in job-finding . Analyses were based on those who completed the programmes . Participants were not aware that two interventions were being used . Investigators were aware of group allocation , but were accompanied in all programmes by co-trainers who were non-investigators . FINDINGS Before training , 80 ( 59 % ) CBT-group participants and 59 ( 54 % ) controls scored 5 or more on the general health question naire ( GHQ ; taken to define psychiatric caseness ) . After training , 29 ( 21 % ) and 25 ( 23 % ) , respectively , scored 5 or more ( p < 0.001 for both decreases ) . Improvements in mean scores with training on the GHQ ( between-group difference 3.91 , p = 0.05 ) and in other measures of mental health were significantly greater in the CBT group than in the control group . There were no significant differences between the groups in job-seeking activity during or after training , but significantly more of the CBT group than of the control group had been successful in finding full-time work ( 38 [ 34 % ] vs 13 [ 13 % ] , p < 0.001 ) , by 4 months after completion of training . INTERPRETATION These results suggest that group CBT training can improve mental health and produce tangible benefits in job-finding . Application of CBT among the unemployed is likely to benefit both individuals and society in general OBJECTIVES We evaluated the effectiveness of a community-based participatory research -grounded intervention among women receiving Temporary Assistance for Needy Families ( TANF ) with chronic health conditions in increasing ( 1 ) health care visits , ( 2 ) Medicaid knowledge and skills , and ( 3 ) health and functional status . METHODS We used a r and omized controlled trial design to assign 432 women to a public health nurse case management plus Medicaid intervention or a wait-control group . We assessed Medicaid outcomes pre- and posttraining ; other outcomes were assessed at 3 , 6 , and 9 months . RESULTS Medicaid knowledge and skills improved ( P < .001 for both ) . Intervention group participants were more likely to have a new mental health visit ( odds ratio [ OR ] = 1.92 ; P = .007 ) , and this likelihood increased in higher-risk subgroups ( OR = 2.03 and 2.83 ; P = .04 and .006 , respectively ) . Depression and functional status improved in the intervention group over time ( P = .016 for both ) . No differences were found in routine or preventive care , or general health . CONCLUSIONS Health outcomes among women receiving TANF can be improved with public health interventions . Additional strategies are needed to further reduce health disparities in this population OBJECTIVES To determine whether increased postnatal support could influence maternal and child health outcomes . DESIGN This was a r and omised controlled trial comparing maternal and child health outcomes for women offered either of the support interventions with those for control women receiving st and ard services only . Outcome data were collected through question naires distributed 12 and 18 months postr and omisation . Process data were also collected . There was also an integral economic evaluation . SETTING AND PARTICIPANTS Women living in deprived enumeration districts in selected London boroughs were eligible for the trial if they gave birth between 1 January and 30 September 1999 . RESULTS The 731 participants were found to be well matched in terms of socio-economic characteristics and health and support variables ( 14 % of the participants were non-English speaking ) . Response rates at the two follow-up points were 90 % and 82 % . At both points there were no differences that could not be attributed to chance on the primary outcomes of maternal depression , child injury or maternal smoking . At the first follow-up , there was reduced use of general practitioners by support health visitor ( SHV ) children , but increased use of NHS health visitors and social workers by mothers . At the second follow-up , both community group support ( CGS ) and SHV mothers had less use of midwifery services ( fewer were pregnant ) , and SHV mothers were less worried about their child 's health and development . Uptake of the CGS intervention was low : 19 % , compared with 94 % for the SHV intervention . Satisfaction with the intervention among women in the SHV group was high . Based on the assumptions and conditions of the costing methods , the economic evaluation found no net economic cost or benefit of choosing either of the two interventions . CONCLUSIONS There was no evidence of impact on the primary outcomes of either intervention . The SHV intervention was popular with women , and was associated with improvement in some of the secondary outcomes . This suggests that greater emphasis on the social support role of health visitors could improve some measures of family well-being . Possible areas for future research include a systematic review of social support and its effect on health ; developing and testing other postnatal models of support that match more closely the age of the baby and the changing patterns of mothers ' needs ; evaluating other strategies for mobilising ' non-professional ' support ; developing and testing more culturally specific support interventions ; developing more culturally appropriate st and ardised measures of health outcomes ; providing longer term follow-up of social support interventions ; and exploring the role of social support on the delay in subsequent pregnancy Earlier analyses of the JOBS II intervention for unemployed job seekers demonstrated that the intervention facilitated reemployment , reduced depressive symptoms , and improved role and emotional functioning ( A. D. Vinokur , R. H. Price , & Y. Schul , 1995 ) . The present study focuses on mediational processes of the active ingredients targeted by the intervention . Structural equation modeling analysis demonstrated that an enhanced sense of mastery had mediating effects of reemployment , financial strain , and reduction in depressive symptoms . Another active ingredient , inoculation against setbacks , was shown to protect those who suffered the setback of losing a job after temporarily regaining one . The inoculation protected them from experiencing the high level of depressive symptoms that was typical of their counterparts in the control group Results are reported from a 2 1/2 year follow-up of respondents who participated in a r and omized field experiment that included the Jobs Program , a preventive intervention for unemployed persons . The intervention was intended to prevent poor mental health and loss of motivation to seek reemployment and to promote high- quality reemployment . The results of the long-term follow-up were consistent with those found 1 and 4 months after intervention ( Caplan , Vinokur , Price , & van Ryn , 1989 ) . The results demonstrate the continued beneficial effects of the intervention on monthly earnings , level of employment , and episodes of employer and job changes . These findings are supported by a benefit-cost analysis , which demonstrates large net benefits of the intervention to the participants and to the federal and state government programs that supported the project Labor market trends and expert opinion have recently highlighted the existence of an " older worker problem " that will require policy and programmatic remedies . This study details the findings of a longitudinal field experiment on the effectiveness of a promising behavioral/self-help job-finding program --the job club . Employment service clients ( N = 46 ) were r and omly assigned to receive the job club program or normally available ( control ) services . Twelve week follow-up data revealed a 74 % employment rate for job club participants versus 22 % for controls . Both groups obtained comparable placements . Study findings indicate the job club is an effective employment service for older job seekers BACKGROUND Despite the imminent expansion of Medicaid coverage for low-income adults , the effects of exp and ing coverage are unclear . The 2008 Medicaid expansion in Oregon based on lottery drawings from a waiting list provided an opportunity to evaluate these effects . METHODS Approximately 2 years after the lottery , we obtained data from 6387 adults who were r and omly selected to be able to apply for Medicaid coverage and 5842 adults who were not selected . Measures included blood-pressure , cholesterol , and glycated hemoglobin levels ; screening for depression ; medication inventories ; and self-reported diagnoses , health status , health care utilization , and out-of-pocket spending for such services . We used the r and om assignment in the lottery to calculate the effect of Medicaid coverage . RESULTS We found no significant effect of Medicaid coverage on the prevalence or diagnosis of hypertension or high cholesterol levels or on the use of medication for these conditions . Medicaid coverage significantly increased the probability of a diagnosis of diabetes and the use of diabetes medication , but we observed no significant effect on average glycated hemoglobin levels or on the percentage of participants with levels of 6.5 % or higher . Medicaid coverage decreased the probability of a positive screening for depression ( -9.15 percentage points ; 95 % confidence interval , -16.70 to -1.60 ; P=0.02 ) , increased the use of many preventive services , and nearly eliminated catastrophic out-of-pocket medical expenditures . CONCLUSIONS This r and omized , controlled study showed that Medicaid coverage generated no significant improvements in measured physical health outcomes in the first 2 years , but it did increase use of health care services , raise rates of diabetes detection and management , lower rates of depression , and reduce financial strain BACKGROUND The present study aim ed at analyzing whether training in emotional competences ( EC ) would increase the level of perceived EC among unemployed adults , whether the unemployment duration would moderate the effects of the training and whether the changes in EC would predict changes in the levels of perceived stress , somatic complaints , mental health , and mood states . METHODS Seventy-five participants were r and omly allocated to an EC training program , or a control group . Following a controlled experimental design , the participants completed all the measures prior to the intervention ( T1 ) , one month later ( T2 ) and six months after the first data collection ( T3 ) . RESULTS The results showed that change in EC after the training depended on the duration of unemployment . The difference between the experimental and control groups in EC after the training was significant when the participants had been unemployed for less time . In addition , the results indicated that changes in EC were found to be significant predictors of changes in perceived stress , mental health , somatic complaints , and vigor and confusion ( mood dimensions ) six months after the intervention . CONCLUSION The data suggest that unemployment duration plays a crucial role in determining the range and intensity of intervention effects |
10,579 | 26,694,507 | In conclusion , a strength training program including low to high intensity resistance exercises and plyometric exercises performed 2 - 3 times per week for 8 - 12 weeks is an appropriate strategy to improve RE in highly trained middle- and long-distance runners | Balsalobre-Fernández , C , Santos-Concejero , J , and Grivas , GV .
Effects of strength training on running economy in highly trained runners : a systematic review with meta- analysis of controlled trials .
J Strength Cond Res 30(8 ) : 2361 - 2368 , 2016-The purpose of this study was to perform a systematic review and meta- analysis of controlled trials to determine the effect of strength training programs on the running economy ( RE ) of high-level middle- and long-distance runners . | To investigate the effects of simultaneous explosive-strength and endurance training on physical performance characteristics , 10 experimental ( E ) and 8 control ( C ) endurance athletes trained for 9 wk . The total training volume was kept the same in both groups , but 32 % of training in E and 3 % in C was replaced by explosive-type strength training . A 5-km time trial ( 5 K ) , running economy ( RE ) , maximal 20-m speed ( V20 m ) , and 5-jump ( 5J ) tests were measured on a track . Maximal anaerobic ( MART ) and aerobic treadmill running tests were used to determine maximal velocity in the MART ( VMART ) and maximal oxygen uptake ( VO2 max ) . The 5 K time , RE , and VMART improved ( P < 0.05 ) in E , but no changes were observed in C. V20 m and 5J increased in E ( P < 0.01 ) and decreased in C ( P < 0.05 ) . VO2 max increased in C ( P < 0.05 ) , but no changes were observed in E. In the pooled data , the changes in the 5 K velocity during 9 wk of training correlated ( P < 0.05 ) with the changes in RE [ O2 uptake ( r = -0.54 ) ] and VMART ( r = 0.55 ) . In conclusion , the present simultaneous explosive-strength and endurance training improved the 5 K time in well-trained endurance athletes without changes in their VO2 max . This improvement was due to improved neuromuscular characteristics that were transferred into improved VMART and running economy Fifteen highly trained distance runners ( & OV0312;O2max 71.1 ± 6.0 ml·min−1·kg−1 , mean ± SD ) were r and omly assigned to a plyometric training ( PLY ; n = 7 ) or control ( CON ; n = 8) group . In addition to their normal training , the PLY group undertook 3 × 30 minutes PLY sessions per week for 9 weeks . Running economy ( RE ) was assessed during 3 × 4 minute treadmill runs ( 14 , 16 , and 18 km·h−1 ) , followed by an incremental test to measure & OV0312;O2max . Muscle power characteristics were assessed on a portable , unidirectional ground reaction force plate . Compared with CON , PLY improved RE at 18 km·h−1 ( 4.1 % , p = 0.02 ) , but not at 14 or 16 km·h−1 . This was accompanied by trends for increased average power during a 5-jump plyometric test ( 15 % , p = 0.11 ) , a shorter time to reach maximal dynamic strength during a strength quality assessment test ( 14 % , p = 0.09 ) , and a lower & OV0312;O2-speed slope ( 14 % , p = 0.12 ) after 9 weeks of PLY . There were no significant differences in cardiorespiratory measures or & OV0312;O2max as a result of PLY . In a group of highly-trained distance runners , 9 weeks of PLY improved RE , with likely mechanisms residing in the muscle , or alternatively by improving running mechanics In this study , we investigated whether a heavy strength training program , as an additive to an endurance running program , would cause significant improvements in 3-km run time in a group of recreationally fit women when compared with endurance-only ( EO ) training . Sixteen women aged between 18 and 27 years of age were r and omly assigned to either an EO group ( n = 9 ) or a concurrent strength and endurance ( CSE ) group ( n = 7 ) . A 10-week training program for both groups consisted of an endurance running program performed three afternoons per week . The CSE group also participated in strength training on the morning of each running session . Testing was conducted pre and post training in a 3-km time trial and measured & OV0312;o2peak , running economy , muscular strength ( 1 repetition maximum ) , and body composition and girth . There was a trend ( P = 0.07 ) toward greater improvement in 3-km performance time for the CSE group ( 106.7 ± 91.4 seconds ) when compared with the EO group ( 77.3 ± 93.0 seconds ) . Further , the CSE group showed an increase in strength levels when compared with the EO group . The CSE group showed significant increases ( P ≤ 0.05 ) in the parallel squat and hamstring curl , and a significant increase ( P ≤ 0.05 ) was also found in upper body strength for the bench press ( 11.9 % increase ) when compared with the EO group . There were no significant differences between the two groups for & OV0312;o2peak , running economy , body composition , or girth measurements . This study found no negative or compatibility problems when heavy strength training was added to an endurance running program , and a nonsignificant increase in improvement for 3-km times was evident The purpose of this study was to examine the efficacy of 11 wk of resistance training to failure vs. nonfailure , followed by an identical 5-wk peaking period of maximal strength and power training for both groups as well as to examine the underlying physiological changes in basal circulating anabolic and catabolic hormones . Forty-two physically active men were matched and then r and omly assigned to either a training to failure ( RF ; n = 14 ) , nonfailure ( NRF ; n = 15 ) , or control groups ( C ; n = 13 ) . Muscular and power testing and blood draws to determine basal hormonal concentrations were conducted before the initiation of training ( T0 ) , after 6 wk of training ( T1 ) , after 11 wk of training ( T2 ) , and after 16 wk of training ( T3 ) . Both RF and NRF result ed in similar gains in 1-repetition maximum bench press ( 23 and 23 % ) and parallel squat ( 22 and 23 % ) , muscle power output of the arm ( 27 and 28 % ) and leg extensor muscles ( 26 and 29 % ) , and maximal number of repetitions performed during parallel squat ( 66 and 69 % ) . RF group experienced larger gains in the maximal number of repetitions performed during the bench press . The peaking phase ( T2 to T3 ) after NRF result ed in larger gains in muscle power output of the lower extremities , whereas after RF it result ed in larger gains in the maximal number of repetitions performed during the bench press . Strength training leading to RF result ed in reductions in resting concentrations of IGF-1 and elevations in IGFBP-3 , whereas NRF result ed in reduced resting cortisol concentrations and an elevation in resting serum total testosterone concentration . This investigation demonstrated a potential beneficial stimulus of NRF for improving strength and power , especially during the subsequent peaking training period , whereas performing sets to failure result ed in greater gains in local muscular endurance . Elevation in IGFBP-3 after resistance training may have been compensatory to accommo date the reduction in IGF-1 to preserve IGF availability Abstract Ramírez-Campillo , R , Álvarez , C , Henríquez-Olguín , C , Baez , EB , Martínez , C , And rade , DC , and Izquierdo , M. Effects of plyometric training on endurance and explosive strength performance in competitive middle- and long-distance runners . J Strength Cond Res 28(1 ) : 97–104 , 2014—The purpose of this study was to examine the effect of a short-term plyometric training program on explosive strength and endurance performance in highly competitive middle- and long-distance runners . Athletes were r and omly assigned to a control group ( CG , n = 18 , 12 men ) and an explosive strength training group ( TG , n = 18 , 10 men ) . Drop jump ( DJ ) from 20 ( DJ20 ) and 40 cm ( DJ40 ) , countermovement jump with arms ( CMJA ) , 20-m sprint time , and 2.4-km endurance run time test were carried out before and after 6 weeks of explosive strength training . Also , the combined st and ardized performance ( CSP ) in the endurance and explosive strength test was analyzed . After intervention , the CG did not show any significant change in performance , whereas the TG showed a significant reduction in 2.4-km endurance run time ( −3.9 % ) and 20-m sprint time ( −2.3 % ) and an increase in CMJA ( + 8.9 % ) , DJ20 ( + 12.7 % ) , and DJ40 ( 16.7 % ) explosive performance . Strength training group also exhibited a significant increase in CSP , although the CG showed significant reduction . We conclude that properly programmed concurrent explosive strength and endurance training could be advantageous for middle- and long-distance runners in their competitive performance , especially in events characterized by sprinting actions with small time differences at the end of the race Sáez Sáez de villarreal , E , Izquierdo , M , and Gonzalez-Badillo , JJ . Enhancing jump performance after combined vs. maximal power , heavy-resistance , and plyometric training alone . J Strength Cond Res 25(12 ) : 3274–3281 , 2011—The purpose of this study was to examine the effects of 5 different stimuli on jumping ability and power production after 7 weeks of training . Sixty-five ( 47 men and 18 women ) physical education students were r and omly assigned to 5 experimental groups that performed : combination of all training methods ( A ) ; heavy-resistance training using full-squat exercise ( i.e. , 56–85 % of 1 RM for 3–6 repetitions ) ( B ) ; power-oriented strength training using a parallel-squat exercise ( i.e. , 100–130 % of load that maximizes power output for 2–6 repetitions ) ( C ) ; power-oriented strength training using a loaded countermovement jumping ( i.e. , 70–100 % of load that maximizes power output for 2–5 repetitions ; countermovement jump [ CMJ ] ) ( D ) ; and plyometric jumping ( E ) . The CMJ ( cm ) , loaded CMJ ( cm ) , maximum rate of force development ( RFDmax ) during early concentric phase of loaded CMJ ( N·s−1 ) and power output during early concentric phase of loaded CMJ ( watts ) were measured before and after 7 weeks of training . Significant improvements in CMJ ( from 7.8 to 13.2 % ) were observed in all groups . Significantly greater increases in power output during loaded jumps were observed in A ( 10–13 % ) and D ( 8–12 % ) groups compared with in the other groups . Significant increases in RFDmax were observed in A ( 20–30 % ) , C ( 18–26 % ) , and D ( 20–26 % ) groups . The results of this study provide evidence to suggest that if training program is design ed and implemented correctly , both traditional slow velocity training and faster power-oriented strength training alone , or in combination with plyometric training , would provide a positive training stimulus to enhance jumping performance The purpose of this study was to examine the effect of 3 volumes of heavy resistance , average relative training intensity ( expressed as a percentage of 1 repetition maximum that represented the absolute kilograms lifted divided by the number of repetitions performed ) programs on maximal strength ( 1RM ) in Snatch ( Sn ) , Clean & Jerk ( C&J ) , and Squat ( Sq ) . Twenty-nine experienced ( .3 years ) , trained junior weight-lifters were r and omly assigned into 1 of 3 groups : low-intensity group ( LIG ; n = 12 ) , moderate-intensity group ( MIG ; n = 9 ) , and high-intensity group ( HIG ; n = 8) . All subjects trained for 10 weeks , 4–5 days a week , in a periodized routine using the same exercises and training volume ( expressed as total number of repetitions performed at intensities equal to or greater than 60 % of 1RM ) , but different programmed total repetitions at intensities of .90–100 % of 1RM for the entire 10-week period : LIG ( 46 repetitions ) , MIG ( 93 repetitions ) , and HIG ( 184 repetitions ) . During the training period , MIG and LIG showed a significant increase ( p < 0.01–0.05 ) for C & J ( 10.5 % and 3 % for MIG and LIG , respectively ) and Sq ( 9.5 % and 5.3 % for MIG and LIG , respectively ) , whereas in HIG the increase took place only in Sq ( 6.9 % , p < 0.05 ) . A calculation of effect sizes revealed greater strength gains in the MIG than in HIG or LIG . There were no significant differences between LIG and HIG training volume-induced strength gains . All the subjects in HIG were unable to fully accomplish the repetitions programmed at relative intensities greater than 90 % of 1RM . The present results indicate that short-term resistance training using moderate volumes of high relative intensity tended to produce higher enhancements in weightlifting performance compared with low and high volumes of high relative training intensities of equal total volume in experienced , trained young weightlifters . Therefore , for the present population of weightlifters , it may be beneficial to use the MIG training protocol to improve the weightlifting program at least in a short-term ( 10 weeks ) cycle of training The present study examines changes in muscle structure and neuromuscular performance induced by 15 weeks of power training with explosive muscle actions . Twenty-three subjects , including 10 controls , volunteered for the study . Muscle biopsies were obtained from the gastrocnemius muscle before and after the training period , while maximal voluntary isometric contractions ( MVC ) and drop jump tests were performed once every fifth week . No statistically significant improvements in MVC of the knee extensor ( KE ) and plantarflexor muscles were observed during the training period . However , the maximal rate of force development ( RFD ) of KE increased from 18,836+/-4282 to 25,443+/-8897 N ( P<0.05 ) during the first 10 weeks of training . In addition , vertical jump height ( vertical rise of the center of body mass ) in the drop jump test increased significantly ( P<0.01 ) . Simultaneously , explosive force production of KE muscles measured as knee moment and power increased significantly ; however , there was no significant change ( P>0.05 ) in muscle activity ( electromyography ) of KE . The mean percentage for myosin heavy chain and titin isoforms , muscle fiber-type distributions and areas were unchanged . The enhanced performance in jumping as a result of power training can be explained , in part , by some modification in the joint control strategy and /or increased RFD capabilities of the KE PURPOSE The present study investigated the effect of maximal strength training on running economy ( RE ) at 70 % of maximal oxygen consumption ( V[spacing dot above]O2max ) and time to exhaustion at maximal aerobic speed ( MAS ) . Responses in one repetition maximum ( 1RM ) and rate of force development ( RFD ) in half-squats , maximal oxygen consumption , RE , and time to exhaustion at MAS were examined . METHODS Seventeen well-trained ( nine male and eight female ) runners were r and omly assigned into either an intervention or a control group . The intervention group ( four males and four females ) performed half-squats , four sets of four repetitions maximum , three times per week for 8 wk , as a supplement to their normal endurance training . The control group continued their normal endurance training during the same period . RESULTS The intervention manifested significant improvements in 1RM ( 33.2 % ) , RFD ( 26.0 % ) , RE ( 5.0 % ) , and time to exhaustion at MAS ( 21.3 % ) . No changes were found in V[spacing dot above]O2max or body weight . The control group exhibited no changes from pre to post values in any of the parameters . CONCLUSION Maximal strength training for 8 wk improved RE and increased time to exhaustion at MAS among well-trained , long-distance runners , without change in maximal oxygen uptake or body weight QUESTIONS Does the PEDro scale measure only one construct ie , the method ological quality of clinical trials ? What is the hierarchy of items of the PEDro scale from least to most adhered to ? Is there any effect of year of publication of trials on item adherence ? Are PEDro scale ordinal scores equivalent to interval data ? DESIGN Rasch analysis of two independent sample s of 100 clinical trials from the PEDro data base scored using the PEDro scale . RESULTS Both sample s of PEDro data showed fit to the Rasch model with no item misfit . The PEDro scale item hierarchy was the same in both sample s , ranging from the most adhered to item r and om allocation , to the least adhered to item therapist blinding . There was no differential item functioning by year of publication . Original PEDro ordinal scores were highly correlated with transformed PEDro interval scores ( r = 0.99 ) . CONCLUSION The PEDro scale is a valid measure of the method ological quality of clinical trials . It is valid to sum PEDro scale item scores to obtain a total score that can be treated as interval level measurement and subjected to parametric statistical analysis PURPOSE To determine whether the magnitude of improvement in athletic performance and the mechanisms driving these adaptations differ in relatively weak individuals exposed to either ballistic power training or heavy strength training . METHODS Relatively weak men ( n = 24 ) who could perform the back squat with proficient technique were r and omized into three groups : strength training ( n = 8 ; ST ) , power training ( n = 8 ; PT ) , or control ( n = 8) . Training involved three sessions per week for 10 wk in which subjects performed back squats with 75%-90 % of one-repetition maximum ( 1RM ; ST ) or maximal-effort jump squats with 0%-30 % 1RM ( PT ) . Jump and sprint performances were assessed as well as measures of the force-velocity relationship , jumping mechanics , muscle architecture , and neural drive . RESULTS Both experimental groups showed significant ( P < or = 0.05 ) improvements in jump and sprint performances after training with no significant between-group differences evident in either jump ( peak power : ST = 17.7 % + /- 9.3 % , PT = 17.6 % + /- 4.5 % ) or sprint performance ( 40-m sprint : ST = 2.2 % + /- 1.9 % , PT = 3.6 % + /- 2.3 % ) . ST also displayed a significant increase in maximal strength that was significantly greater than the PT group ( squat 1RM : ST = 31.2 % + /- 11.3 % , PT = 4.5 % + /- 7.1 % ) . The mechanisms driving these improvements included significant ( P < or = 0.05 ) changes in the force-velocity relationship , jump mechanics , muscle architecture , and neural activation that showed a degree of specificity to the different training stimuli . CONCLUSIONS Improvements in athletic performance were similar in relatively weak individuals exposed to either ballistic power training or heavy strength training for 10 wk . These performance improvements were mediated through neuromuscular adaptations specific to the training stimulus . The ability of strength training to render similar short-term improvements in athletic performance as ballistic power training , coupled with the potential long-term benefits of improved maximal strength , makes strength training a more effective training modality for relatively weak individuals Abstract Piacentini , MF , De Ioannon , G , Comotto , S , Spedicato , A , Vernillo , G , and La Torre , A. Concurrent strength and endurance training effects on running economy in master endurance runners . J Strength Cond Res 27(8 ) : 2295–2303 , 2013—Running economy ( RE ) has been seen to improve with concurrent strength and endurance training in young and elite endurance athletes . The purpose of this study was to evaluate the effects of 2 different strength training protocol s on RE and strength parameters in a group of regularly training master marathon runners . Sixteen participants were r and omly assigned to a maximal strength training program ( MST ; n = 6 ; 44.2 ± 3.9 years ) , a resistance training ( n = 5 ; 44.8 ± 4.4 years ) , and a control group ( n = 5 ; 43.2 ± 7.9 years ) . Before and after the experimental period , resting metabolic rate , body composition , 1 repetition maximum ( 1RM ) , squat jump , countermovement jump , and RE were evaluated . The MST group showed significant increases ( p < 0.05 ) in 1RM ( + 16.34 % ) and RE ( + 6.17 % ) at marathon pace . No differences emerged for the other groups ( p > 0.05 ) . Anthropometric data were unchanged after the training intervention ( p > 0.05 ) . Taken together , the results of this preliminary study indicate that master endurance athletes seem to benefit from concurrent strength and endurance training because the rate of force development may be crucial for RE improvement , one of the major determinants of endurance performance Bevan , HR , Bunce , PJ , Owen , NJ , Bennett , MA , Cook , CJ , Cunningham , DJ , Newton , RU , and Kilduff , LP . Optimal loading for the development of peak power output in professional rugby players . J Strength Cond Res 24(1 ) : 43 - 47 , 2010-The ability to develop high levels of muscular power is considered an essential component of success in many sporting activities ; however , the optimal load for the development of peak power during training remains controversial . Our aim in the present study was to determine the optimal load required to observe peak power output during the ballistic bench throw ( BBT ) and squat jump ( SJ ) in professional rugby players . Forty-seven , professional , male , rugby players of ( mean ± SD ) mass 101.3 ± 12.8 kg and height 1.82 ± 0.08 m volunteered and gave informed consent for this study , which was approved by a university ethics committee . Players performed BBT at loads of 20 , 30 , 40 , 50 , and 60 % of their predetermined 1 repetition maximum ( 1RM ) and SJ at loads of 0 , ( body mass only ) , 20 , 30 , 40 , 50 , and 60 % of their predetermined 1RM in a r and omized and balanced order . Power output ( PO ) was determined by measurement of barbell displacement with subsequent calculation of velocity , force , and power . Relative load had a significant effect on PO for both the BBT ( effect size & eegr;2 : 0.297 , p < 0.001 ) and SJ ( Effect Size & eegr;2 : 0.709 , p < 0.001 ) . Peak power output was produced when the athletes worked against an external load equal to 30 % 1RM for the upper body and 0 % 1RM for the lower body PURPOSE The purpose of this study was to examine the efficacy of 8 wk of resistance training to failure versus not to failure training regimens at both moderate and low volumes for increasing upper-body strength and power as well as cardiovascular parameters into a combined resistance and endurance periodized training scheme . METHODS Forty-three trained male rowers were matched and then r and omly assigned to four groups that performed the same endurance training but differed on their resistance training regimen : four exercises leading to repetition failure ( 4RF ; n = 14 ) , four exercises not leading to failure ( 4NRF ; n = 15 ) , two exercises not to failure ( 2NRF ; n = 6 ) , and control group ( C ; n = 8) . One-repetition maximum strength and maximal muscle power output during prone bench pull ( BP ) , average power during a 20-min all-out row test ( W 20 min ) , average row power output eliciting a blood lactate concentration of 4 mmol x L(-1 ) ( W 4 mmol x L(-1 ) ) , and power output in 10 maximal strokes ( W 10 strokes ) were assessed before and after 8 wk of periodized training . RESULTS 4NRF group experienced larger gains in one- repetition maximum strength and muscle power output ( 4.6 % and 6.4 % , respectively ) in BP compared with both 4RF ( 2.1 % and j1.2 % ) and 2NRF ( 0.6 % and -0.6 % ) . 4NRF and 2NRF groups experienced larger gains in W 10 strokes ( 3.6 % and 5 % ) and in W 20 min ( 7.6 % and 9 % ) compared with those found after 4RF ( -0.1 % and 4.6 % ) , whereas no significant differences between groups were observed in the magnitude of changes in W 4 mmol x L(-1 ) ( 4NRF = 6.2 % , 4RF = 5.3 % , 2NRF = 6.8 % , and C = 4.5 % ) . CONCLUSIONS An 8-wk linear periodized concurrent strength and endurance training program using a moderate number of repetitions not to failure ( 4NRF group ) provides a favorable environment for achieving greater enhancements in strength , muscle power , and rowing performance when compared with higher training volumes of repetitions to failure in experienced highly trained rowers The purpose of this study was to examine the effects of 3 resistance training volumes on maximal strength in the snatch ( Sn ) , clean & jerk ( C&J ) , and squat ( Sq ) exercises during a 10-week training period . Fifty-one experienced ( .3 years ) , trained junior lifters were r and omly assigned to one of 3 groups : a low-volume group ( LVG , n = 16 ) , a moderate-volume group ( MVG , n = 17 ) , and a high-volume group ( HVG , n = 18 ) . All subjects trained 4–5 days a week with a periodized routine using the same exercises and relative intensities but a different total number of sets and repetitions at each relative load : LVG ( 1,923 repetitions ) , MVG ( 2,481 repetitions ) , and HVG ( 3,030 repetitions ) . The training was periodized from moderate intensity ( 60–80 % of 1 repetition maximum [ 1RM ] ) and high number of repetitions per set ( 2–6 ) to high intensity ( 90–100 % of 1RM ) and low number of repetitions per set ( 1–3 ) . During the training period , the MVG showed a significant increase for the Sn , C&J , and Sq exercises ( 6.1 , 3.7 , and 4.2 % , respectively , p < 0.01 ) , whereas in the LVG and HVG , the increase took place only with the C&J exercise ( 3.7 and 3 % , respectively , p < 0.05 ) and the Sq exercise ( 4.6 % , p < 0.05 , and 4.8 % , p < 0.01 , respectively ) . The increase in the Sn exercise for the MVG was significantly higher than in the LVG ( p = 0.015 ) . Calculation of effect sizes showed higher strength gains in the MVG than in the HVG or LVG . There were no significant differences between the LVG and HVG training volume-induced strength gains . The present results indicate that junior experienced lifters can optimize performance by exercising with only 85 % or less of the maximal volume that they can tolerate . These observations may have important practical relevance for the optimal design of strength training programs for resistance-trained athletes , since we have shown that performing at a moderate volume is more effective and efficient than performing at a higher volume Abstract Sedano , S , Marín , PJ , Cuadrado , G , and Redondo , JC . Concurrent training in elite male runners : The influence of strength versus muscular endurance training on performance outcomes . J Strength Cond Res 27(9 ) : 2433–2443 , 2013—Much recent attention has been given to the compatibility of combined aerobic and anaerobic training modalities . However , few of these studies have reported data related to well-trained runners , which is a potential limitation . Therefore , because of the limited evidence available for this population , the main aim was to determine which mode of concurrent strength-endurance training might be the most effective at improving running performance in highly trained runners . Eighteen well-trained male runners ( age 23.7± 1.2 years ) with a maximal oxygen consumption ( V[Combining Dot Above]O2max ) more than 65 ml·kg−1·min−1 were r and omly assigned into 1 of the 3 groups : Endurance-only Group ( n = 6 ) , who continued their usual training , which included general strength training with Thera-b and latex-free exercise b and s and endurance training ; Strength Group ( SG ; n = 6 ) who performed combined resistance and plyometric exercises and endurance training ; Endurance-SG ( ESG ; n = 6 ) who performed endurance-strength training with loads of 40 % and endurance training . The study comprised 12 weeks of training in which runners trained 8 times a week ( 6 endurance and 2 strength sessions ) and 5 weeks of detraining . The subjects were tested on 3 different occasions ( countermovement jump height , hopping test average height , 1 repetition maximum , running economy ( RE ) , V[Combining Dot Above]O2max , maximal heart rate [ HRmax ] , peak velocity ( PV ) , rating of perceived exertion , and 3-km time trial were measured ) . Findings revealed significant time × group interaction effects for almost all tests ( p < 0.05 ) . We can conclude that concurrent training for both SG and ESG groups led to improved maximal strength , RE , and PV with no significant effects on the V[Combining Dot Above]O2 kinetics pattern . The SG group also seems to show improvements in 3-km time trial tests UNLABELLED Several training strategies such as plyometrics have been shown to improve running economy ; however , its physiological basis remains elusive . PURPOSE To examine the effect of plyometric training on the energy cost of running ( ECR , J · kg(-1 ) · min(-1 ) ) , titin , and myosin heavy chain ( MHC ) isoforms . METHODS Subjects were r and omly assigned to a 6-wk plyometric treatment ( P ; n = 11 ) or control group ( C ; n = 11 ) . Preintervention and postintervention outcomes included body composition , vertical jump , sit- and -reach , maximal oxygen consumption ( VO2max ) , speed at onset of blood lactate , 3-km time trial performance , ECR , and a vastus lateralis muscle biopsy for protein analysis . RESULTS Plyometric intervention result ed in improved time trial ( P , 2.6 % faster , P = 0.04 ; C , 1.6 % , P = 0.17 ) . VO2max improved in the P group ( 5.2 % , P = 0.03 ) , whereas the C group increased by 3.1 % ( P = 0.20 ) . The ECR decreased in the P group as the result of 6 wk of plyometric training ( P = 0.02 for stage 3 ) , whereas it increased in the C group ( P = 0.02 for stage 3 ) . The ECR correlated strongly with performance at stages 2 , 3 , and 4 ( r > 0.8 , P < 0.001 ) independent of group . There was no significant main effect of group , time , or interaction on any of the protein isoforms analyzed . A negative correlation was found between the ECR at stage 7 and MHC IIa ( r = -0.96 , P < 0.001 ) , and the ECR at stage 6 with titin isoform 1 (T1)/T2 ratio ( r = -0.69 , P = 0.007 ) independent of group . CONCLUSION Six weeks of plyometric training improved running performance and the ECR despite no measurable changes in MHC and titin isoforms . However , higher MHC IIa and lower T1/T2 isoform ratios correlated to lower ECR |
10,580 | 28,636,752 | There were no overall differences in effect sizes between enriched and nonenriched design s for pain intensity .
There was a significant difference for a reduction in any adverse events favouring enriched design s for opioids , but not for other analgesics or the outcome serious adverse events .
There was an association between effect size and method ological quality , with failure to blind the outcome assessor and failure to use intention-to-treat analysis being associated with larger effect sizes .
There is no evidence that the use of an enriched study design changes the treatment effect size estimate for pain .
There is some evidence that clinical trials that employ enriched design s report a reduced risk of adverse events in trials for chronic musculoskeletal pain , but it is unclear whether enriched design s influence estimates of serious adverse events .
Features of trial design and study quality were associated with treatment effect estimates | AIMS To investigate the use of an enriched study design on the estimates of treatment effect in analgesic trials for chronic musculoskeletal pain . | Correctable weaknesses in the design , conduct , and analysis of biomedical and public health research studies can produce misleading results and waste valuable re sources . Small effects can be difficult to distinguish from bias introduced by study design and analyses . An absence of detailed written protocol s and poor documentation of research is common . Information obtained might not be useful or important , and statistical precision or power is often too low or used in a misleading way . Insufficient consideration might be given to both previous and continuing studies . Arbitrary choice of analyses and an overemphasis on r and om extremes might affect the reported findings . Several problems relate to the research workforce , including failure to involve experienced statisticians and method ologists , failure to train clinical research ers and laboratory scientists in research methods and design , and the involvement of stakeholders with conflicts of interest . Inadequate emphasis is placed on recording of research decisions and on reproducibility of research . Finally , reward systems incentivise quantity more than quality , and novelty more than reliability . We propose potential solutions for these problems , including improvements in protocol s and documentation , consideration of evidence from studies in progress , st and ardisation of research efforts , optimisation and training of an experienced and non-conflicted scientific workforce , and reconsideration of scientific reward systems BACKGROUND AND OBJECTIVE Enrichment strategies which select subjects who appear to respond to the drug have been used in drug studies to demonstrate clinical efficacy . We have used clinical trial simulation techniques to examine factors that are relevant in clinical trial design based on enrichment where poor responders are excluded from the double-blind phase of the study . METHODS Simulations were performed for an analgesic trial design involving an open-dose titration phase ( enrichment phase ) followed by a double-blind , r and omized , placebo-controlled maintenance phase . Enrichment was examined by excluding subjects above a predefined pain score ( cutoff ) from analysis of efficacy for the maintenance phase . Cutoff pain scores ranging from 4 to 7 on a 0 to 10 categorical scale were examined . A data base consisting of chronic pain patients who participated in studies with a new formulation of buprenorphine was used to build the simulation model . Since no data were available for the key model variable " correlation between treatment and placebo response " , values of 0.25 , 0.5 , and 0.75 were used for the simulations . RESULTS A correlation between treatment and placebo effect ranging from 0.75 to 0.25 will cause the likelihood of trial success to vary from 50 % to 95 % . This model also shows that recruitment efficiency will decrease with the use of lower cutoff pain scores . CONCLUSION Prior to using enrichment techniques , investigators must consider the correlation between treatment effect and placebo response to optimize clinical trial design 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 OBJECTIVES Patients with chronic noncancer pain frequently report symptoms of depression and anxiety ( negative affect ) , which are associated with higher ratings of pain intensity and a greater likelihood of being prescribed chronic opioid therapy . The purpose of this secondary analysis was to test the hypothesis that initial levels of negative affect can predict treatment-related outcomes in a double-blind , placebo-controlled study of extended-release ( ER ) hydromorphone among opioid-tolerant patients with chronic low back pain . METHODS Four hundred fifty-nine ( N = 459 ) patients participated in the titration/conversion phase of a multicenter study , of which 268 were r and omized to receive once-daily hydromorphone or placebo . All patients completed the Hospital Anxiety and Depression Scale ( HADS ) at baseline and were divided evenly into Low ( N = 157 ) , Moderate ( N = 155 ) , and High ( N = 147 ) negative affect groups based on their scores . Group differences in numerical pain intensity measures at home and in the clinic , Rol and -Morris Disability ratings , and measures of symptoms from the Subjective Opiate Withdrawal Scale ( SOWS ) throughout the trial were analyzed . RESULTS Two hundred sixty-eight of the initial 459 subjects who entered the 2 to 4-week titration/conversion phase ( pretreatment ) were successfully r and omized to either placebo or ER hydromorphone ; a total of 110 patients then completed this double-blind phase of the study . Those in the Moderate and High negative affect groups tended to drop out more often during the titration/conversion phase because of the adverse effects or lack of efficacy of their prescribed opioid than those in the Low negative mood group ( P < 0.05 ) . Overall , those patients in the Moderate and High groups reported significantly higher pain intensity scores in at-home and in-clinic pain intensity ratings ( P < 0.05 ) , greater disability on the Rol and -Morris Scale ( P < 0.01 ) , and more withdrawal symptoms on the SOWS ( P < 0.05 ) than those in the Low group . Higher negative affect scores also predicted less favorable ratings of the study drug during the titration phase ( P < 0.05 ) . Interestingly , the High negative affect group showed the most improvement in pain in the placebo condition ( P < 0.05 ) . CONCLUSIONS Negative affect is associated with diminished benefit during a trial of opioid therapy and is predictive of dropout in a controlled clinical trial OBJECTIVE To compare the analgesic efficacy and safety of nonprescription doses of naproxen sodium , ibuprofen , and placebo in patients with osteoarthritis ( OA ) of the knee . METHODS In 2 identical multicenter , r and omized , double-blind , placebo-controlled , multidose , parallel- design studies , patients aged > or = 25 years with OA were r and omized to daily doses of naproxen sodium 660 mg , naproxen sodium 440 mg ( patients > or = 65 years ) , ibuprofen 1200 mg , or placebo , for 7 days . RESULTS For investigator and patient assessment of knee joint pain , naproxen sodium ( 440/660 mg ) and ibuprofen were clinical ly effective at relieving pain compared with placebo ( n = 444 ) ; both treatments reduced the mean symptom score by 30 - 45 % , compared with a 20 - 25 % reduction with placebo . Naproxen sodium ( 440/660 mg ) significantly improved all 7 symptoms from baseline compared with placebo , while ibuprofen significantly improved 5 of the symptoms . For the subgroup of patients aged > or = 65 years ( n = 183 ) , naproxen sodium 440 mg was significantly superior to placebo in all symptoms except pain on weight-bearing ; ibuprofen only significantly reduced day pain . For daily diary evaluations , naproxen sodium and ibuprofen were effective in reducing all 6 symptoms ; there was a trend toward higher efficacy for night-time pain with naproxen sodium 440/660 mg compared with ibuprofen . There were no significant differences in adverse event reporting between groups . CONCLUSION Over-the-counter doses of naproxen sodium ( 440/660 mg ) and ibuprofen ( 1200 mg ) effectively relieve pain in patients with mild to moderate OA of the knee . Naproxen sodium provided more effective pain relief for most variables compared with placebo , and for night pain compared with ibuprofen . Efficacy was combined with good safety and tolerability Background : The ancient Indian ( Asian ) Ayurvedic medicinal system uses herbomineral drugs to treat arthritis . Despite centuries of use , very few have been tested by drug trials . RA-11 ( ARTREX , MENDAR ) , a st and ardized multiplant Ayurvedic drug ( Withania somnifera , Boswellia serrata , Zingiber officinale , and Curcuma longa ) is currently used to treat arthritis . Objective : The objective of this study was to evaluate the efficacy and safety of RA-11 in patients with symptomatic osteoarthritis ( OA ) of the knees . Methods : A total of 358 patients with chronic knee pain were screened free-of-cost in “ arthritis camps ” in an Indian metropolis . Ninety patients with primary OA of the knees ( ACR classification ; Arthritis Rheum 1986;29:1039–1049 ) were found eligible ( postanalgesic washout pain visual analog score [ VAS ] ≥40 mm in either or both knees on body weight-bearing activities ) to enroll into a r and omized , double-blind , placebo-controlled , parallel efficacy , single-center , 32-week drug trial ( 80 % power to detect 25 % difference , P = 0.05 , 2-sided ) . Concurrent analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not allowed . Lifestyle and /or dietary restrictions , as per routine Ayurveda practice s , were not imposed . Pain VAS ( maximum pain in each knee recorded by the patient during the preceding 48 hours ) and modified WOMAC ( Western Ontario McMaster University OA Index , Likert scale , version 3.0 ) were the primary efficacy variables . The WOMAC section on “ physical function difficulty ” was modified for Indian use and vali date d before the trial . Routine laboratory testing was primarily done to monitor drug safety . At baseline , the groups ( active = 45 , placebo = 45 ) were well matched for several measures ( mean pain VAS : active = 6.17 ; placebo = 6.5 ) . Results :1 ) Efficacy : Compared with placebo , the mean reduction in pain VAS at week 16 ( active = 2.7 , placebo = 1.3 ) and week 32 ( active = 2.8 , placebo = 1.8 ) in the active group was significantly ( P < 0.05 , analysis of variance [ ANOVA ] ) better . Similarly , the improvement in the WOMAC scores at week 16 and week 32 were also significantly superior ( P < 0.01 , ANOVA ) in the active group . 2 ) Safety : Both the groups reported mild adverse events ( AE ) without any significant difference . 3 ) Withdrawals : Twenty-eight patients were discontinued . None reported drug-related toxicity . The majority failed follow up/compliance . No differences were observed between the groups . Conclusion : This controlled drug trial demonstrates the potential efficacy and safety of RA- 11 in the symptomatic treatment of OA knees over 32 weeks of therapy Properly conducted r and omised trials can aid clinical decision-making by providing unbiased estimates of the average size of treatment effects . This paper , the first of two , discusses how readers of clinical trials can extract simple estimates of treatment effect size from trial reports when trial outcomes are measured on a continuous scale . When making decisions about therapy for individual patients , these estimates can be modified on the basis of patient characteristics . Modified estimates of treatment effect size can be used to determine if the effect of treatment is likely to be large enough to be " clinical ly worthwhile " . This approach optimises clinical decision-making by combining unbiased estimates of the size of treatment effect from clinical trials with clinical intuition and patient preferences OBJECTIVE To compare the efficacy of etoricoxib 30 mg with the generally maximum recommended dose of celecoxib , 200 mg , in the treatment of osteoarthritis ( OA ) in two identically design ed studies . METHODS Two multi-centre , 26-week , double-blind , placebo-controlled , non-inferiority studies were conducted , enrolling patients who were prior non-steroidal anti-inflammatory drug ( NSAID ) or acetaminophen users . There were 599 patients in study 1 and 608 patients in study 2 r and omized 4:4:1:1 to etoricoxib 30 mg qd , celecoxib 200 mg qd or one of two placebo groups for 12 weeks . After 12 weeks , placebo patients were evenly distributed to etoricoxib or celecoxib based on their initial enrollment r and omization schedule . The primary hypothesis was that etoricoxib 30 mg would be at least as effective as celecoxib 200 mg for the time-weighted average change from baseline over 12 weeks for Western Ontario and McMaster ( WOMAC ) Pain Subscale , WOMAC Physical Function Subscale and Patient Global Assessment of Disease Status . Active treatments were also assessed over the full 26 weeks . Adverse experiences were collected for safety assessment . RESULTS In both studies , etoricoxib was non-inferior to celecoxib for all three efficacy outcomes over 12 and 26 weeks ; both were superior to placebo ( P < 0.001 ) for all three outcomes in each study over 12 weeks . The safety and tolerability of etoricoxib 30 mg qd and celecoxib 200 mg qd were similar over 12 and 26 weeks . CONCLUSIONS Etoricoxib 30 mg qd was at least as effective as celecoxib 200 mg qd and had similar safety in the treatment of knee and hip OA ; both were superior to placebo . Clinical Trials.gov Identifiers : NCT00092768 ; NCT00092791 Abstract Objective : To demonstrate that a fixed-dose combination of enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg has comparable efficacy to celecoxib for knee osteoarthritis . Research design and methods : Two r and omized , double-blind , parallel-group , placebo-controlled , multicenter phase III studies ( PN400 - 307 and PN400 - 309 ) enrolled patients aged ≥50 years with symptomatic knee osteoarthritis . Following an osteoarthritis flare , patients received naproxen/esomeprazole magnesium twice daily , celecoxib 200 mg once daily , or placebo for 12 weeks . Clinical trial registration : NCT00664560 and NCT00665431 . Main outcome measures : Three co- primary efficacy endpoints were mean change from baseline to week 12 in Western Ontario and McMaster Osteoarthritis Index ( WOMAC ) pain and function subscales , and Patient Global Assessment of osteoarthritis using a visual analog scale ( PGA-VAS ) . Results : In Study 307 , 619 patients were r and omized and 614 treated . In Study 309 , 615 patients were r and omized and 610 treated . Both naproxen/esomeprazole magnesium and celecoxib were associated with improvements ( least squares mean change from baseline to week 12 ) in WOMAC pain ( Study 307 : −42.0 and −41.8 , respectively ; Study 309 : −44.2 and −42.9 , respectively ) , WOMAC function ( Study 307 : −36.4 and −36.3 , respectively ; Study 309 : −38.9 and −36.8 , respectively ) , and PGA-VAS ( Study 307 : 21.2 and 21.6 , respectively ; Study 309 : 29.0 and 25.6 , respectively ) . A prespecified non-inferiority margin of 10 mm between naproxen/esomeprazole magnesium and celecoxib was satisfied for each co- primary endpoint at week 12 in both studies . Significant improvements were observed with naproxen/esomeprazole magnesium versus placebo in both studies ( p < 0.05 ) . Celecoxib was significantly different from placebo in Study 307 ( p < 0.05 ) ; however , the improvements were not significant in Study 309 . Acetaminophen use and patient expectation of receiving active treatment ( 80 % probability ) may have contributed to a high placebo response observed . Conclusions : Naproxen/esomeprazole magnesium has comparable efficacy to celecoxib for the management of pain associated with osteoarthritis of the knee over 12 weeks ABSTRACT Objective : To compare the lower osteoarthritis ( OA ) dose of rofecoxib to the recommended dose of celecoxib in two identically design ed studies . Methods : Patients with knee OA were r and omized ( 2:2:1 ratio : rofecoxib 12.5 mg once daily ( qd ) , celecoxib 200 mg qd , or placebo , respectively ) . The primary endpoint was patient global assessment of response to therapy ( PGART ) averaged over 6 weeks on a five-point scale . Rofecoxib would be declared at least as effective as celecoxib if the lower bound of the 95 % confidence interval ( 95 % CI ) for difference in means was no lower than –0.5 . Additional endpoints included Pain and Physical Function subscales of the Western Ontario and McMaster ( WOMAC ) OA Index . Adverse experiences ( AEs ) were recorded and combined from the two studies for analysis . Results : Study 1 enrolled 395 patients ( rofecoxib , n = 160 ; celecoxib , n = 157 ; placebo , n = 78 ) . Study 2 enrolled 413 patients ( rofecoxib , n = 159 ; celecoxib , n = 169 ; placebo , n = 85 ) . Rofecoxib 12.5 mg was at least as effective as celecoxib 200 mg by PGART ( Study 1 difference –0.09 [ 95 % CI : –0.32 , 0.14 ] and Study 2 difference 0.02 [ 95 % CI : –0.20 , 0.24 ] ) , and both were significantly ( p < 0.001 ) more effective than placebo . Comparable efficacy was also seen for WOMAC Pain and Physical Function subscales with the active treatments . There was a significantly higher ( p < 0.05 ) incidence of serious AEs with celecoxib than rofecoxib or placebo , none of which was drug-related . There were no significant differences in the pre-specified measurements of safety including drug-related AEs or discontinuations due to AEs , and the medications demonstrated similar safety as assessed by spontaneous reporting . Conclusions : Rofecoxib 12.5 mg and celecoxib 200 mg provided comparable efficacy over 6 weeks , and both were significantly more efficacious than placebo . The medications demonstrated similar safety compared to one another and placebo . The primary limitations of these studies were that they were only 6 weeks long and were powered for efficacy . Therefore , conclusions about long-term safety can not be inferred BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . OBJECTIVE To compare the effects of continuous and intermittent celecoxib treatment in patients with knee or hip osteoarthritis in flare . METHODS In this 24-week , prospect i ve , r and omised , double-blind , placebo-controlled study , patients were r and omly assigned to receive continuous ( n = 62 ) or intermittent ( n = 61 ) treatment with celecoxib 200 mg once daily . The primary efficacy end point was the area under the curve ( AUC ) of the change in the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) total scores between baseline and week 24 divided by the time interval . Secondary end points included the percentage of days with intake of the flare drug , the AUC of the change in the WOMAC total scores , the mean change from baseline in the WOMAC scores , and the patient 's and physician 's global assessment of osteoarthritis . RESULTS There were no significant differences between patients r and omised to continuous or intermittent treatment in the primary end point or most of the secondary end points , although a consistent trend supporting continuous treatment was observed . The percentage of days with intake of the flare drug was significantly lower ( p = 0.031 ) in the group receiving continuous versus intermittent celecoxib . Both treatment regimens were well tolerated . CONCLUSION The results of this pilot study indicate a potential clinical difference between continuous and intermittent treatment with celecoxib , and may be useful in design ing future trials . A larger trial on both efficacy and safety outcomes is required for conclusive evidence in favour of either continuous or intermittent treatment OBJECTIVE Bisphosphonates have slowed the progression of osteoarthritis ( OA ) in animal models and have decreased pain in states of high bone turnover . The Knee OA Structural Arthritis ( KOSTAR ) study , which is the largest study to date investigating a potential structure-modifying OA drug , tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA . METHODS The study group comprised 2,483 patients with medial compartment knee OA and 2 - 4 mm of joint space width ( JSW ) , as determined using fluoroscopically positioned , semiflexed-view radiography . Patients were enrolled in 2 parallel 2-year studies in North America and the European Union . These studies evaluated the efficacy of risedronate at dosages of 5 mg/day , 15 mg/day , 35 mg/week ( in Europe ) , and 50 mg/week ( in North America ) compared with placebo in reducing signs and symptoms , as measured by the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index and patient global assessment ( PGA ) scores , and in slowing radiographic progression . RESULTS A reduction of approximately 20 % in signs and symptoms , as measured by WOMAC subscales and PGA scores , was observed in all groups , with no treatment effect of risedronate demonstrated . Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression ( joint space loss of > or=0.6 mm ) . Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years . A dose-dependent reduction in the level of C-terminal crosslinking telopeptide of type II collagen , a cartilage degradation marker associated with progressive OA , was seen in patients who received risedronate . No increase in the number of adverse events was demonstrated for risedronate compared with placebo . CONCLUSION Although risedronate ( compared with placebo ) did not improve signs or symptoms of OA , nor did it alter progression of OA , a reduction in the level of a marker of cartilage degradation was observed . A sustained clinical ly relevant improvement in signs and symptoms was observed in all treatment and placebo groups Nonprescription doses of naproxen sodium , acetaminophen , and placebo were compared to determine their efficacy and safety in osteoarthritis of the knee . In two identical multicenter , r and omized , double-blind , placebo-controlled , multidose , parallel- design studies , patients with osteoarthritis aged ( mean ± SD ) 60.6 ± 12.8 years were r and omized to daily doses of 660 mg naproxen sodium ( 440 mg naproxen sodium in patients ≥65 years ) , 4000 mg acetaminophen , or placebo for 7 days . Naproxen sodium ( 440/660 mg ) provided significantly greater improvements in pain at rest , on passive motion , on weight-bearing , stiffness after rest ( morning ) , day and night pain compared with placebo , and significantly greater relief from resting pain than acetaminophen ( P < 0.05 ) . Acetaminophen provided significantly greater improvements in day pain compared with placebo . Daily evaluations showed naproxen sodium ( 440/660 mg ) provided superior pain relief to acetaminophen and was significantly better than acetaminophen at reducing difficulties experienced in walking several blocks and difficulties in bending , lifting , and stooping . Naproxen sodium ( 440/660 mg ) and acetaminophen ( 4000 mg ) were significantly more effective than placebo in improving mobility level , household tasks , and walking and bending . Patient and investigator evaluation scores were significantly higher in naproxen sodium and acetaminophen groups compared with placebo ; no differences were observed between active treatments . Naproxen sodium and acetaminophen had similar safety profiles to placebo . Nonprescription doses of naproxen sodium ( 440/660 mg ) effectively relieve pain and other symptoms of osteoarthritis . Naproxen sodium is an alternative in the initial treatment of osteoarthritis and may be preferred to acetaminophen as first-line therapy in patients with moderate or severe pain Objectives To systematic ally identify and critically assess clinical trials that use enriched enrollment r and omized withdrawal ( EERW ) trial design as a methodology for assessing the effect of analgesics pain . Methods A comprehensive literature search was conducted through April 2007 in Medline and Embase to identify all r and omized controlled trials that use EERW trial design s. Data were collected from relevant trials and tabulated . Results were categorized on the basis of study design s , preenrichment and postenrichment disposition , discontinuation rates , primary and secondary efficacy results , and respective P values . Results The literature search identified 2875 unique citations , most of which were deemed inappropriate for this analysis . The primary reasons for exclusion included inappropriate study design , no available abstract , not a clinical study , and therapeutic area not related to chronic pain . Eight EERW clinical trials of analgesics were identified . Half of the trials were in chronic low back pain , and 5 of 8 trials used an opioid as the active drug . Of the 8 trials , 5 used a parallel design and 3 used crossover design s. The primary efficacy parameter used was pain scores or time to discontinuation , and statistically and clinical ly significant effects in active treatments relative to placebo were observed after r and omization in all trials . The median magnitude of effect was 1.7 on a 10-point scale . Time to exit was a more statistically powerful endpoint than mean pain intensity . Discussion sEERW trials are an emerging type of study design that in certain setting s may offer advantages over traditional trial design s in characterizing the effects of analgesic medications OBJECTIVE Nonsteroidal anti-inflammatory drug ( NSAID ) responses in osteoarthritis ( OA ) are highly variable , often requiring multiple medication changes . We sought to determine pre-r and omization predictors of response to NSAIDs in OA . METHODS Data were pooled from two identical 26-week double-blind , r and omized flare design trials comparing etoricoxib 30 mg/day ( N=475 ) , celecoxib 200 mg/day ( N=488 ) , and placebo ( N=244 ) in patients with OA of the hip or knee . This analysis was limited to the 12-week placebo-controlled period . Response at Week 12 was defined using Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International ( OMERACT-OARSI ) criteria . Factors were analyzed using logistic regression and included age , race , gender , body mass index , index joint , screening ( pre-washout ) and baseline ( post-washout ) Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index pain , physical function , and stiffness , and patient global assessment of disease status , prior NSAID/coxib or acetaminophen use , American Rheumatology Association functional class , and disease duration . RESULTS We found that screening WOMAC physical function was the only factor that predicted response in all treatment groups ; worse function was associated with lower odds of achieving an OMERACT-OARSI response at 12 weeks ( odds ratio 0.84 placebo ; 0.87 etoricoxib ; 0.89 celecoxib ; P<0.05 for all ) . However , the differences in WOMAC physical function between responders and nonresponders were small ( ∼5 mm on a 100-mm scale ) . No factor discriminated between the ability to predict placebo response from active treatment response . CONCLUSIONS Lower levels of physical function decreased the odds of a response to NSAID treatment in OA , although the clinical significance is unknown given the small differences between responders and nonresponders . No other measured baseline variables consistently predicted response in these studies , which may reflect the known individual variability in NSAID response |
10,581 | 29,945,601 | Results The review demonstrated that stigma , cost of transportation , food deprivation and a woman ’s disclosure or non-disclosure of her HIV status to a partner , family and the community , could limit or define the extent of her adherence to prescribed antiretroviral drugs during pregnancy .
Furthermore , the review indicated that knowledge of HIV status , either before or during pregnancy , was significantly associated with medication adherence .
Women who knew their HIV status before pregnancy demonstrated good adherence while women who found out their HIV infection status during pregnancy were linked with non-adherence to ART .
Conclusion This review revealed several barriers and enablers of adherence among pregnant women taking ART in sub-Saharan Africa .
Major barriers included the fear of HIV infection status disclosure to partners and family members , stigma and discrimination .
A major enabler of adherence in women taking ART was women ’s knowledge of their HIV status prior to becoming pregnant . | Background The use of antiretroviral therapy ( ART ) is a core strategy proposed by the World Health Organization in preventing mother to child transmission ( MTCT ) of HIV .
This systematic review aim ed to examine the enablers and barriers of medication adherence among HIV positive pregnant women in sub-Saharan Africa . | Background Prevention of mother to child HIV transmission ( PMTCT ) programmes have great potential to achieve virtual elimination of perinatal HIV transmission provided that PMTCT recommendations are properly followed . This study assessed mothers and infants adherence to medication regimen for PMTCT and the proportions of exposed infants who were followed up in the PMTCT programme . Methods A prospect i ve cohort study was conducted among 282 HIV-positive mothers attending 15 health facilities in Addis Ababa , Ethiopia . Descriptive statistics , bivariate and mulitivariate logistic regression analyses were done . Results Of 282 mothers enrolled in the cohort , 232 ( 82 % , 95 % CI 77 - 86 % ) initiated medication during pregnancy , 154 ( 64 % ) initiated combined zidovudine ( ZDV ) prophylaxis regimen while 78 ( 33 % ) were initiated lifelong antiretroviral treatment ( ART ) . In total , 171 ( 60 % , 95 % CI 55 - 66 % ) mothers ingested medication during labour . Of the 221 live born infants ( including two sets of twins ) , 191 ( 87 % , 95 % CI 81 - 90 % ) ingested ZDV and single-dose nevirapine ( sdNVP ) at birth . Of the 219 live births ( twin births were counted once ) , 148 ( 68 % , 95 % CI 61 - 73 % ) mother-infant pairs ingested their medication at birth . Medication ingested by mother-infant pairs at birth was significantly and independently associated with place of delivery . Mother-infant pairs attended in health facilities at birth were more likely ( OR 6.7 95 % CI 2.90 - 21.65 ) to ingest their medication than those who were attended at home . Overall , 189 ( 86 % , 95 % CI 80 - 90 % ) infants were brought for first pentavalent vaccine and 115 ( 52 % , 95 % CI 45 - 58 % ) for early infant diagnosis at six-weeks postpartum . Among the infants brought for early diagnosis , 71 ( 32 % , 95 % CI 26 - 39 % ) had documented HIV test results and six ( 8.4 % ) were HIV positive . Conclusions We found a progressive decline in medication adherence across the perinatal period . There is a big gap between mediation initiated during pregnancy and actually ingested by the mother-infant pairs at birth . Follow up for HIV-exposed infants seem not to be organized and is inconsistent . In order to maximize effectiveness of the PMTCT programme , the rate of institutional delivery should be increased , the quality of obstetric services should be improved and missed opportunities to exposed infant follow up should be minimized Background The aim of this study was to describe barriers to accessing and accepting highly active antiretroviral therapy ( HAART ) by HIV-positive mothers in the Ug and an Kabarole District 's Programme for the Prevention of Mother to Child Transmission-Plus ( PMTCT-Plus ) . Methods Our study was a qualitative descriptive exploratory study using thematic analysis . Individual in-depth interviews ( n = 45 ) were conducted with r and omly selected HIV-positive mothers who attended this programme , and who : ( a ) never enrolled in HAART ( n = 17 ) ; ( b ) enrolled but did not come back to receive HAART ( n = 2 ) ; ( c ) defaulted/interrupted HAART ( n = 14 ) ; and ( d ) are currently adhering to HAART ( n = 12 ) . A focus group was also conducted to verify the results from the interviews . Results Results indicated that economic concerns , particularly transport costs from residences to the clinics , represented the greatest barrier to accessing treatment . In addition , HIV-related stigma and non-disclosure of HIV status to clients ' sexual partners , long waiting times at the clinic and suboptimal provider-patient interactions at the hospital emerged as significant barriers . Conclusions These barriers to antiretroviral treatment of pregnant and post-natal women need to be addressed in order to improve HAART uptake and adherence for this group of the population . This would improve their survival and , at the same time , drastically reduce HIV transmission from mother to child BACKGROUND The most effective highly active antiretroviral therapy ( HAART ) to prevent mother-to-child transmission of human immunodeficiency virus type 1 ( HIV-1 ) in pregnancy and its efficacy during breast-feeding are unknown . METHODS We r and omly assigned 560 HIV-1-infected pregnant women ( CD4 + count , > or = 200 cells per cubic millimeter ) to receive coformulated abacavir , zidovudine , and lamivudine ( the nucleoside reverse-transcriptase inhibitor [ NRTI ] group ) or lopinavir-ritonavir plus zidovudine-lamivudine ( the protease-inhibitor group ) from 26 to 34 weeks ' gestation through planned weaning by 6 months post partum . A total of 170 women with CD4 + counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine ( the observational group ) . Infants received single-dose nevirapine and 4 weeks of zidovudine . RESULTS The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery ( 96 % in the NRTI group , 93 % in the protease-inhibitor group , and 94 % in the observational group ) or throughout the breast-feeding period ( 92 % in the NRTI group , 93 % in the protease-inhibitor group , and 95 % in the observational group ) . By 6 months of age , 8 of 709 live-born infants ( 1.1 % ) were infected ( 95 % confidence interval [ CI ] , 0.5 to 2.2 ) : 6 were infected in utero ( 4 in the NRTI group , 1 in the protease-inhibitor group , and 1 in the observational group ) , and 2 were infected during the breast-feeding period ( in the NRTI group ) . Treatment-limiting adverse events occurred in 2 % of women in the NRTI group , 2 % of women in the protease-inhibitor group , and 11 % of women in the observational group . CONCLUSIONS All regimens of HAART from pregnancy through 6 months post partum result ed in high rates of virologic suppression , with an overall rate of mother-to-child transmission of 1.1 % . ( Clinical Trials.gov number , NCT00270296 . Background : Novel strategies are needed to increase retention in prevention of mother-to-child HIV transmission ( PMTCT ) services . We have recently shown that small , incremental cash transfers conditional on attending clinic result ed in increased retention along the PMTCT cascade . However , whether women who receive incentives to attend clinic visits are as adherent to antiretrovirals ( ARV ) as those who do not was unknown . Objective : To determine whether HIV-infected women who received incentives to remain in care were as adherent to antiretroviral treatment and achieved the same level of viral suppression at 6 weeks postpartum as those who did not receive incentives but also remained in care . Methods : Newly diagnosed HIV-infected women at ⩽32 weeks gestational age were recruited at antenatal care clinics in Kinshasa , Democratic Republic of Congo . Women were r and omized in a 1:1 ratio to an intervention or control group . The intervention group received compensation ( $ 5 , plus $ 1 increment at each subsequent visit ) conditional on attending scheduled clinic visits and accepting offered PMTCT services , whereas the control group received usual care . The proportion of participants who remained in care , were fully adherent ( took all their pills at each visit ) or with undetectable viral load at 6 weeks postpartum were compared across group . Results : Among 433 women r and omized ( 216 in intervention group and 217 in control group ) , 332 ( 76.7 % ) remained in care at 6 weeks postpartum , including 174 ( 80.6 % ) in the intervention group and 158 ( 72.8 % ) in the control group , ( P = 0.04 ) . Data on pill count were available for 297 participants ( 89.5 % ) , including 156 ( 89.7 % ) and 141 ( 89.2 % ) in the intervention and control groups , respectively ; 69.9 % ( 109/156 ) and 68.1 % ( 96/141 ) in the intervention and control groups had perfect adherence [ risk difference , 0.02 ; 95 % CI : −0.06 to 0.09 ] . Viral load results were available for 171 ( 98.3 % ) and 155 ( 98.7 % ) women in the intervention and control groups , respectively ; 66.1 % ( 113/171 ) in the intervention group and 69.7 % ( 108/155 ) in the control group had an undetectable viral load ( risk difference , −0.04 ; 95 % CI : −0.14 to 0.07 ) . Results were similar after adjusting for marital status , age , education , baseline CD4 count , viral load , gestational age , and initial ARV regimen . Conclusions : Although the provision of cash incentives to HIV-infected pregnant women led to higher retention in care at 6 weeks postpartum , among those retained in care , adherence to ARVs and virologic suppression did not differ by study group Causes for loss-to-follow-up , including early refusals of and stopping antiretroviral therapy ( ART ) , in Malawi ’s Option B+ program are poorly understood . This study examines the main barriers and facilitators to uptake and adherence to ART under Option B+ . In depth interviews were conducted with HIV-infected women who were pregnant or postpartum in Lilongwe , Malawi ( N = 65 ) . Study participants included women who refused ART initiation ( N = 10 ) , initiated ART and then stopped ( N = 26 ) , and those who initiated ART and remained on treatment ( N = 29 ) . The barriers to ART initiation were varied and included concerns about partner support , feeling healthy , and needing time to think . The main reasons for stopping ART included side effects and lack of partner support . A substantial number of women started ART after initially refusing or stopping ART . There were several facilitators for re-starting ART , including encouragement from community health workers , side effects subsiding , decline in health , change in partner , and fear of future sickness . Amongst those who remained on ART , desire to prevent transmission and improve health were the most influential facilitators . Reasons for refusing and stopping ART were varied . ART-related side effects and feeling healthy were common barriers to ART initiation and adherence . Providing consistent pre-ART counseling , early support for patients experiencing side effects , and targeted efforts to bring women who stop treatment back into care may improve long term health outcomes Introduction To prevent mother-to-child transmission ( MTCT ) of HIV in developing countries , new World Health Organization ( WHO ) guidelines recommend maternal combination antiretroviral therapy ( cART ) during pregnancy , throughout breastfeeding for 1 year and then cessation of breastfeeding ( COB ) . The efficacy of this approach during the first six months of exclusive breastfeeding has been demonstrated , but the efficacy of this approach beyond six months is not well documented . Methods A prospect i ve observational cohort study of 279 HIV-positive mothers was started on zidovudine/3TC and lopinavir/ritonavir tablets between 14 and 30 weeks gestation and continued indefinitely thereafter . Women were encouraged to exclusively breastfeed for six months , complementary feed for the next six months and then cease breastfeeding between 12 and 13 months . Infants were followed for transmission to 18 months and for survival to 24 months . Text message reminders and stipends for food and transport were utilized to encourage adherence and follow-up . Results Total MTCT was 9 of 219 live born infants ( 4.1 % ; confidence interval ( CI ) 2.2–7.6 % ) . All breastfeeding transmissions that could be timed ( 5/5 ) occurred after six months of age . All mothers who transmitted after six months had a six-month plasma viral load > 1,000 copies/ml ( p<0.001 ) . Poor adherence to cART as noted by missed dispensary visits was associated with transmission ( p=0.04 ) . Infant mortality was lower after six months of age than during the first six months of life ( p=0.02 ) . The cumulative rate of infant HIV infection or death at 18 months was 29/226 ( 12.8 % 95 CI : 7.5–20.8 % ) . Conclusions Maternal cART may limit MTCT of HIV to the UNAIDS target of < 5 % for eradication of paediatric HIV within the context of a clinical study , but poor adherence to cART and follow-up can limit the benefit . Continued breastfeeding can prevent the rise in infant mortality after six months seen in previous studies , which encouraged early COB Background Adherence to antiretroviral ( ARV ) drugs is essential for eliminating new pediatric infections of human immunodeficiency virus ( HIV ) . Since the Zambian government revised the national guidelines based on option A ( i.e. , maternal zidovudine and infant ARV prophylaxis ) of the World Health Organization ’s 2010 guidelines , no studies have assessed adherence to ARVs during pregnancy up to the postpartum period . This study aim ed to examine adherence to ARVs and identify the associated risk factors . Methods A prospect i ve cohort study was conducted in the Chongwe district from June 2011 to January 2014 . Self-reported adherence to ARVs was examined during pregnancy and at one week , six weeks , and 24 weeks postpartum among 321 HIV-positive women . The probability of remaining adherent to ARVs was estimated using the Kaplan-Meier method , and the risk factors for non-adherence were identified using the Cox proportional hazard regressions — treating loss to follow-up as non-adherence . The statuses of HIV in HIV-exposed infants were assessed in January 2014 . Results During the study period , 326 infants were born to HIV-positive women , 262 ( 80.4 % ) underwent HIV testing , and 11 ( 3.4 % ) had their HIV infection detected at the time that they had the latest HIV testing as of January 2014 . The ARV adherence rate was 82.5 % during pregnancy , 84.2 % at one week postpartum , 81.5 % at six weeks postpartum , and 70.5 % at 24 weeks postpartum . The probability of remaining adherent to ARVs was 0.61 at day 50 , 0.35 at day 100 , 0.18 at day 200 , and 0.06 at day 300 . Attending a referral health center ( HC ) was a risk factor for non-adherence compared with attending rural HCs that provided HIV care/treatment ( adjusted hazard ratio [ aHR ] 0.71 , 95 % confidence interval [ CI ] 0.57–0.88 ) and those that did not provide HIV care/treatment ( aHR 0.58 , 95 % CI 0.46–0.74 ) . A new diagnosis of HIV infection compared to a known HIV-positive status before pregnancy was another risk factor for non-adherence ( aHR 1.24 , 95 % CI 1.03–1.50 ) . Conclusions Maintaining adherence to ARVs through pregnancy to the postpartum period remains a crucial challenge in Zambia . To maximize the treatment benefits , adherence to ARVs and retention in care should be improved at all health facilities Objective : To compare compliance and infant HIV-1 infection risk at 6 weeks with the Thai-CDC and HIVNET-012 antiretroviral regimens in a field setting . Design : R and omized clinical trial . Setting : Tertiary hospital antenatal clinic in Nairobi , Kenya . Participants : HIV-1 infected women referred from primary care clinics . Interventions : Thai-CDC zidovudine regimen or HIVNET-012 nevirapine regimen . Main outcome measures : Women were considered compliant if they used ⩾ 80 % of the doses . Infants were tested for HIV-1 at 6 weeks . Results : Seventy women were r and omized to Thai-CDC and 69 to HIVNET-012 regimens . More women were compliant with the antenatal ( 86 % ) than the intrapartum ( 44 % ) Thai-CDC regimen doses ( P = 0.001 ) . Ninety-seven per cent took the maternal and 91 % gave the infant dose of the HIVNET-012 regimen ( P = 0.2 ) . Overall , 41 % were compliant with the Thai-CDC regimen and 87 % with the HIVNET-012 regimen ( P < 0.001 ) . Compliance with the Thai-CDC regimen was associated with partner support of antiretroviral use [ odds ratio ( OR ) , 3.0 ; , 95 % confidence interval ( CI ) , 1.0–9.1 ] and knowledge at recruitment that antiretroviral drugs could prevent infant HIV-1 ( OR , 2.9 ; 95 % CI , 1.0–8.1 ) . Compliance with the HIVNET-012 regimen was associated with partner notification ( OR , 8.0 ; 95 % CI , 1.5–50 ) and partner willingness to have HIV-1 testing ( OR , 7.5 ; 95 % CI , 1.4–40 ) . There was a trend for a higher risk of transmission with the HIVNET-012 regimen than with the Thai-CDC regimen ( 22 % versus 9 % ; P = 0.07 ) . Conclusion : Compliance with the Thai-CDC and HIVNET-012 regimens was comparable to that in efficacy trials . Partner involvement , support and education on perinatal HIV-1 prevention may improve compliance and increase the number of infants protected from HIV-1 infection Universal nevirapine ( NVP ) therapy ( provision of the drug without HIV testing ) has been suggested as potentially superior to targeted NVP therapy ( provision of the drug to seropositive patients identified through voluntary HIV counseling and testing [ VCT ] ) for perinatal HIV prevention in low-re source , high-prevalence setting s. The authors postulated that uptake ( the proportion of women who accept the strategy when offered ) may be higher for universal therapy , since it does not require a woman to learn her serostatus ; they further postulated that adherence ( the proportion of women who actually ingest the NVP tablet at labor onset ) may be higher for targeted therapy , since knowledge of serostatus could motivate better adherence . Two clinics in Lusaka , Zambia were assigned to provide either the targeted or universal strategy . Halfway through the study period , the approach offered at each clinic was crossed over . Adherence was assessed by liquid chromatographic assay for NVP of cord blood . Regarding uptake , 1524 pregnant women were offered participation , and 1025 ( 67 % ) accepted . Of 694 women offered enrollment in the universal strategy , 496 ( 71 % ) accepted ; of 830 women offered enrollment in the targeted strategy , 529 ( 64 % ) accepted ( p < .01 ) . Uptake was similar at both clinics for the universal strategy : 250 of 339 ( 74 % ) at clinic A and 246 of 355 ( 69 % ) at clinic B ( p = .2 ) , but differed significantly between clinics for the targeted strategy : 229 of 316 ( 72 % ) at clinic A and 300 of 514 ( 58 % ) at clinic B ( RR , 1.51 ; 95 % CI , 1.23 , 1.86 ) . Increased uptake correlated with having been offered the universal rather than the targeted strategy ( AOR , 1.5 ; 95 % CI , 1.1 , 2.1 ) , attendance at clinic A ( AOR , 1.4 ; 95 % CI , 1.01 , 2.0 ) , and maternal report of a prior fetal or infant death ( AOR , 1.6 ; 95 % CI , 1.1 , 2.5 ) . Regarding adherence , in the universal strategy , 40 of 103 women ( 39 % ) were nonadherent compared with 25 of 98 women ( 26 % ) in the targeted strategy ( RR , 1.5 ; 95 % CI , 1.004 , 2.3 ) . Failure to adhere correlated with participation in the universal strategy ( AOR , 2.0 ; 95 % CI , 1.04 , 4.2 ) and illiteracy ( AOR , 2.6 ; 95 % CI , 1.2 , 5.3 ) . In high-prevalence setting s with adequate VCT services , uptake of NVP using the universal or targeted approach appears comparable . However , the universal strategy may result in better uptake in clinics with less well-functioning VCT services ( as with clinic B ) . Adherence to the single-dose NVP intervention was lower among women who did not learn their HIV status . Programs that seek to save the greatest possible number of infants from perinatal HIV acquisition should consider a combination approach , in which women who desire HIV testing can access NVP through a targeted strategy , and women who do not desire testing can access NVP through a universal strategy Objective : To ascertain the field acceptability and effectiveness of the routine utilization of zidovudine in reducing mother-to-child transmission ( MTCT ) of HIV in breastfed children after a r and omized clinical trial demonstrated its efficacy in Côte d'Ivoire and Burkina Faso . Methods : Pregnant women aged 18 years or older , who had confirmed HIV-1 infection , haemoglobinemia greater than 7 g/dl were enrolled in an open label cohort at 36–38 weeks ’ gestation to receive an oral short course of zidovudine . Paediatric HIV infection was defined as a positive HIV-1 polymerase chain reaction , or if aged 15 months or older , a positive HIV serology . Results : The acceptability of HIV pretest counselling was significantly higher in the cohort ( 90.3 % ) than in the trial ( 83.7 % ) ( P < 0.001 ) , but the return rate for HIV test results and for inclusion was low . A similar proportion of women accepted starting zidovudine in the cohort , 30.4 % compared with 27.3 % in the trial ( P = 0.13 ) . The proportions of women who took more than 80 % of the expected zidovudine regimen were 81.8 % before labour , 86.7 % during labour , and 88.1 % during the postpartum period , compared with those observed during the trial , 78.1 , 81.1 , and 85 % , respectively . The MTCT probability at age 15 months was 19.6 % in the cohort ( n = 185 ) versus 21.2 % in the trial ( P = 0.52 ) . Conclusion : The major drawback with the implementation of a short zidovudine regimen to reduce MTCT is HIV counselling and testing procedures . For women who consent , zidovudine is well accepted and efficacious under routine circumstances Background : Provision of HIV testing in labor provides an opportunity to reach susceptible women and infants . Methods : As part of a cluster r and omized trial of labor ward-based prevention of mother-to-child transmission services in Lusaka , Zambia , we determined predictors of testing acceptance and nevirapine ( NVP ) administration in labor . HIV counseling and testing were offered to women unaware of their HIV status . NVP was administered to women who tested positive , and an inert ( calcium ) tablet was provided to women who tested negative , to avoid stigmatization . Results : Among the 2435 women who presented in labor , 393 ( 16 % ) were unaware of their HIV status , of whom 278 ( 71 % ) met eligibility criteria . We offered counseling to 217 ( 78 % ) of eligible women : 146 ( 67 % ) agreed , 82 ( 56 % ) of those counseled were tested for HIV , and 23 ( 28 % ) were seropositive . Testing rates were higher among primigravida women [ adjusted odds ratio ( AOR ) 1.5 ; 95 % confidence interval ( CI ) : 1.1 to 2.1 ] and among those not offered HIV testing during their pregnancy ( AOR 3.7 ; 95 % CI : 2.8 to 5.1 ) . Cervical dilation ≤3 cm at the time of admission was associated strongly with NVP ingestion > 1 hour ( AOR 11.5 ; 95 % CI : 4.5 to 29.2 ) and > 2 hours ( AOR 11.4 ; 95 % CI : 4.7 to 27.5 ) before delivery . Conclusion : Labor ward HIV testing is feasible in this re source -limited setting Background : HIV-infected women risk sexual and perinatal HIV transmission during conception , pregnancy , childbirth , and breastfeeding . We compared HIV-1 RNA suppression and medication adherence across periconception , pregnancy , and postpartum periods , among women on antiretroviral therapy ( ART ) in Ug and a. Methods : We analyzed data from women in a prospect i ve cohort study , aged 18–49 years , enrolled at ART initiation and with ≥1 pregnancy between 2005 and 2011 . Participants were seen quarterly . The primary exposure of interest was pregnancy period , including periconception ( 3 quarters before pregnancy ) , pregnancy , postpartum ( 6 months after pregnancy outcome ) , or nonpregnancy related . Regression models using generalized estimating equations compared the likelihood of HIV-1 RNA ⩽400 copies per milliliter , < 80 % average adherence based on electronic pill caps ( medication event monitoring system ) , and likelihood of 72-hour medication gaps across each period . Results : One hundred eleven women contributed 486 person-years of follow-up . Viral suppression was present at 89 % of nonpregnancy , 97 % of periconception , 93 % of pregnancy , and 89 % of postpartum visits , and was more likely during periconception ( adjusted odds ratio , 2.15 ) compared with nonpregnant periods . Average ART adherence was 90 % [ interquartile range ( IQR ) , 70%–98 % ] , 93 % ( IQR , 82%–98 % ) , 92 % ( IQR , 72%–98 % ) , and 88 % ( IQR , 63%–97 % ) during nonpregnant , periconception , pregnant , and postpartum periods , respectively . Average adherence < 80 % was less likely during periconception ( adjusted odds ratio , 0.68 ) , and 72-hour gaps per 90 days were less frequent during periconception ( adjusted relative risk , 0.72 ) and more frequent during postpartum ( adjusted relative risk , 1.40 ) . Conclusions : Women with pregnancy were virologically suppressed at most visits , with an increased likelihood of suppression and high adherence during periconception follow-up . Increased frequency of 72-hour gaps suggests a need for increased adherence support during postpartum periods Objective : Determine whether enhanced labor ward-based services for prevention of mother-to-child transmission of HIV ( PMTCT ) would improve nevirapine ( NVP ) coverage . Design : Cluster-r and omized trial at 12 public-sector delivery centers in Lusaka , Zambia . Methods : Following a baseline surveillance period , 12 labor wards were r and omized , six to offer opt-in HIV testing to women of unknown serostatus ( with NVP administration as indicated ) and to assess NVP adherence among known HIV-infected women . The six control labor wards provided the st and ard of care . The NVP coverage endpoint was defined as the proportion of HIV-infected/exposed women/infant pairs with confirmed NVP ingestion . We used generalized estimating equations ( GEE ) to determine the odds of coverage associated with the intervention and ultimately used the parameters for the estimated GEE model to estimate relative risk . Results : Between October 2005 and January 2006 , 7664 women gave birth at participating clinics . We collected anonymous-linked blood from 7592 ( 99 % ) umbilical cords ; tested 7438 ( 97 % ) for HIV , 1618 ( 22 % ) were seropositive , and of these , 1279 ( 79 % ) were tested for NVP . At baseline ( preintervention ) , the probability of HIV-infected/exposed women/infant pairs receiving NVP in treatment clinics ( 42 % ) was 0.89 times the probability of being covered in control clinics ( 53 % ) whereas during the intervention period the probability of treatment clinic coverage ( 52 % ) was 1.22 the probability control clinic coverage ( 43 % ) , representing a multiplicative effect of 1.37 upon the RR at baseline ( ratio of relative risks 1.37 , bootstrapped 95 % CI , 1.04–1.77 ) . Conclusion : Labor ward-based PMTCT programs are feasible and can have a significant , positive impact on NVP coverage |
10,582 | 28,533,136 | INTERPRETATION Artificial pancreas systems uniformly improved glucose control in outpatient setting s , despite heterogeneous clinical and technical factors . | BACKGROUND Closed-loop artificial pancreas systems have been in development for several years , including assessment in numerous varied outpatient clinical trials .
We aim ed to summarise the efficacy and safety of artificial pancreas systems in outpatient setting s and explore the clinical and technical factors that can affect their performance . | Background : Most patients with type 1 diabetes do not achieve their glycemic targets . We aim ed to assess the efficacy of glucose-responsive insulin and glucagon closed-loop delivery for controlling glucose levels in adults with type 1 diabetes . Methods : We conducted a r and omized crossover trial involving 15 adults with type 1 diabetes , comparing st and ard insulin-pump therapy with dual-hormone , closed-loop delivery . Patients were admitted twice to a clinical research facility and received , in r and om order , both treatments . Each 15-hour visit ( from 1600 to 0700 ) included an evening exercise session , followed by a medium-sized meal , a bedtime snack and an overnight stay . During visits that involved closed-loop delivery , basal insulin and glucagon miniboluses were delivered according to recommendations based on glucose sensor readings and a predictive dosing algorithm at 10-minute intervals . During visits involving st and ard insulin-pump therapy ( control visits ) , patients used conventional treatment . Results : Dual-hormone closed-loop delivery increased the percentage of time for which patients ’ plasma glucose levels were in the target range ( median 70.7 % [ interquartile range ( IQR ) 46.1%–88.4 % ] for closed-loop delivery v. 57.3 % [ IQR 25.2%–71.8 % ] for control , p = 0.003 ) and decreased the percentage of time for which plasma glucose levels were in the low range ( bottom of target range [ < 4.0 mmol/L ] , 0.0 % [ IQR 0.0%–3.0 % ] for closed-loop delivery v. 10.2 % [ IQR 0.0%–13.0 % ] for control , p = 0.01 ; hypoglycemia threshold [ < 3.3 mmol/L ] , 0.0 % [ IQR 0.0%–0.0 % ] for closed-loop delivery v. 2.8 % [ IQR 0.0%–5.9 % ] for control , p = 0.006 ) . Eight participants ( 53 % ) had at least 1 hypoglycemic event ( plasma glucose < 3.0 mmol/L ) during st and ard treatment , compared with just 1 participant ( 7 % ) during closed-loop treatment ( p = 0.02 ) . Interpretation : Dual-hormone , closed-loop delivery guided by advanced algorithms improved short-term glucose control and reduced the risk of hypoglycemia in a group of 15 adults with type 1 diabetes . Trial registration : Clinical Trials.gov , no. NCT01297946 OBJECTIVE We estimate the effect size of hypoglycemia risk reduction on closed-loop control ( CLC ) versus open-loop ( OL ) sensor-augmented insulin pump therapy in supervised outpatient setting . RESEARCH DESIGN AND METHODS Twenty patients with type 1 diabetes initiated the study at the Universities of Virginia , Padova , and Montpellier and Sansum Diabetes Research Institute ; 18 completed the entire protocol . Each patient participated in two 40-h outpatient sessions , CLC versus OL , in r and omized order . Sensor ( Dexcom G4 ) and insulin pump ( T and em t : slim ) were connected to Diabetes Assistant (DiAs)—a smartphone artificial pancreas platform . The patient operated the system through the DiAs user interface during both CLC and OL ; study personnel supervised on site and monitored DiAs remotely . There were no dietary restrictions ; 45-min walks in town and restaurant dinners were included in both CLC and OL ; alcohol was permitted . RESULTS The primary outcome —reduction in risk for hypoglycemia as measured by the low blood glucose ( BG ) index (LGBI)— result ed in an effect size of 0.64 , P = 0.003 , with a twofold reduction of hypoglycemia requiring carbohydrate treatment : 1.2 vs. 2.4 episodes/session on CLC versus OL ( P = 0.02 ) . This was accompanied by a slight decrease in percentage of time in the target range of 3.9–10 mmol/L ( 66.1 vs. 70.7 % ) and increase in mean BG ( 8.9 vs. 8.4 mmol/L ; P = 0.04 ) on CLC versus OL . CONCLUSIONS CLC running on a smartphone ( DiAs ) in outpatient conditions reduced hypoglycemia and hypoglycemia treatments when compared with sensor-augmented pump therapy . This was accompanied by marginal increase in average glycemia result ing from a possible overemphasis on hypoglycemia safety OBJECTIVE Inpatient studies suggest that model predictive control ( MPC ) is one of the most promising algorithms for artificial pancreas ( AP ) . So far , outpatient trials have used hypo/hyperglycemia-mitigation or medical-expert systems . In this study , we report the first wearable AP outpatient study based on MPC and investigate specifically its ability to control postpr and ial glucose , one of the major challenges in glucose control . RESEARCH DESIGN AND METHODS A new modular MPC algorithm has been design ed focusing on meal control . Six type 1 diabetes mellitus patients underwent 42-h experiments : sensor-augmented pump therapy in the first 14 h ( open-loop ) and closed-loop in the remaining 28 h. RESULTS MPC showed satisfactory dinner control versus open-loop : time-in-target ( 70–180 mg/dL ) 94.83 vs. 68.2 % and time-in-hypo 1.25 vs. 11.9 % . Overnight control was also satisfactory : time-in-target 89.4 vs. 85.0 % and time-in-hypo : 0.00 vs. 8.19 % . CONCLUSIONS This outpatient study confirms inpatient evidence of suitability of MPC-based strategies for AP . These encouraging results pave the way to r and omized crossover outpatient studies OBJECTIVE To evaluate the feasibility and efficacy of a fully integrated hybrid closed-loop ( HCL ) system ( Medtronic MiniMed Inc. , Northridge , CA ) , in day and night closed-loop control in subjects with type 1 diabetes , both in an inpatient setting and during 6 days at diabetes camp . RESEARCH DESIGN AND METHODS The Medtronic MiniMed HCL system consists of a fourth generation ( 4S ) glucose sensor , a sensor transmitter , and an insulin pump using a modified proportional-integral-derivative ( PID ) insulin feedback algorithm with safety constraints . Eight subjects were studied over 48 h in an inpatient setting . This was followed by a study of 21 subjects for 6 days at diabetes camp , r and omized to either the closed-loop control group using the HCL system or to the group using the Medtronic MiniMed 530 G with threshold suspend ( control group ) . RESULTS The overall mean sensor glucose percent time in range 70–180 mg/dL was similar between the groups ( 73.1 % vs. 69.9 % , control vs. HCL , respectively ) ( P = 0.580 ) . Meter glucose values between 70 and 180 mg/dL were also similar between the groups ( 73.6 % vs. 63.2 % , control vs. HCL , respectively ) ( P = 0.086 ) . The mean absolute relative difference of the 4S sensor was 10.8 ± 10.2 % , when compared with plasma glucose values in the inpatient setting , and 12.6 ± 11.0 % compared with capillary Bayer CONTOUR NEXT LINK glucose meter values during 6 days at camp . CONCLUSIONS In the first clinical study of this fully integrated system using an investigational PID algorithm , the system did not demonstrate improved glucose control compared with sensor-augmented pump therapy alone . The system demonstrated good connectivity and improved sensor performance BACKGROUND Artificial pancreas ( AP ) systems have shown an improvement in glucose control and a reduced risk of nocturnal hypoglycemia under controlled conditions but remain to be evaluated under daily-life conditions . OBJECTIVE To assess the feasibility , safety , and efficacy of the MD-Logic AP in controlling nocturnal glucose levels in the patient 's home . METHODS Two-arm study , each covering four consecutive nights comparing the MD-Logic AP ( ' closed-loop ' arm ) with sensor-augmented pump therapy ( ' control ' arm ) . Fifteen patients ( mean age 19 ± 10.4 yr , A1c 7.5 ± 0.5 % or 58 ± 5.9 mmol/mol , diabetes duration 9.9 ± 8.2 yr ) were r and omly assigned either to ' Group A ' ( first ' closed-loop ' , then ' control ' arm ) or to ' Group B ' ( vice versa ) . Investigators were masked to treatment intervention . Primary endpoints were the time spent with glucose levels below 70 mg/dL and the percentage of nights in which the mean overnight glucose levels were within 90 - 140 mg/dL. Endpoint analyses were based on unmodified sensor glucose readings of the four study nights . RESULTS Time of glucose levels spent below 70 mg/dL was significantly shorter on the closed-loop nights than on control nights , median and interquartile range 3.8 ( 0 , 11.6 ) and 48.7 ( 0.6 , 67.9 ) min , respectively ; p = 0.0034 . The percentage of individual nights in which mean overnight glucose level was within 90 - 140 mg/dL was 67 ( 33 , 88 ) , and 50 ( 25 , 75 ) , under closed-loop and control nights , respectively , with no statistical difference . Secondary endpoint analyses demonstrated significant improvements in hypoglycemia parameters . No serious adverse events were reported . CONCLUSION This interim analysis demonstrates the feasibility , safety , and efficiency of the MD-Logic AP system in home use , and demonstrates an improvement over sensor-augmented pump therapy . ( Clinical Trials.gov identifier NCT01726829 ) A total of 1,441 patients with IDDM were r and omly assigned to receive either intensive ( n = 711 ) or conventional ( n = 730 ) diabetes therapy in the Diabetes Control and Complications Trial ( DCCT ) . The patients were followed for an average of 6.5 years . Subjects were instructed to report all episodes of suspected severe hypoglycemia to their health care team . In addition , at quarterly follow-up visits , each subject was asked about the occurrence of severe hypoglycemia . There were 3,788 episodes of severe hypoglycemia ( requiring assistance ) ; 1,027 of these episodes were associated with coma and /or seizure . A total of 65 % percent of patients in the intensive group vs. 35 % of patients in the conventional group had at least one episode of severe hypoglycemia by the study end ; the overall rates of severe hypoglycemia were 61.2 per 100 patient-years vs. 18.7 per 100 patient-years in the intensive and conventional treatment groups , respectively , with a relative risk ( RR ) of 3.28 . The relative risk for coma and /or seizure was 3.02 for intensive therapy . The increased risk with intensive treatment persisted over each of the 9 years of follow-up in the DCCT and over the calendar years 1984 - 1993 during which the study was conducted . When baseline patient characteristics were examined for effects on the risk of severe hypoglycemia , the relative risk of hypoglycemia for intensive versus conventional treatment was > or = 2 for all subgroups . Several subgroups defined by baseline characteristics , including males , adolescents , and subjects with no residual C-peptide or with a prior history of hypoglycemia , had a particularly high risk of severe hypoglycemia in both treatment groups . Analyses of the cumulative incidence of successive episodes indicated that intensive treatment was also associated with an increased risk of multiple episodes within the same patient ( e.g. , 22 % experienced five or more episodes of severe hypoglycemia within the first 5 years of follow-up vs. 4 % in the conventional group ) . Within both treatment groups , patients who experienced severe hypoglycemia were at increased risk of subsequent episodes . Approximately 30 % of patients in each group experienced a second episode within the 4 months following the first episode of severe hypoglycemia . Within each treatment group , the number of prior episodes of hypoglycemia was the strongest predictor of the risk of future episodes , followed closely by the current HbA1c value . After adjustment for the current quarterly HbA1c level , intensive treatment was still associated with a significantly increased risk of hypoglycemia , indicating that the increased risk with intensive treatment is not completely explained by differences in HbA1c values BACKGROUND The safety and efficacy of continuous , multiday , automated glycaemic management has not been tested in outpatient studies of preadolescent children with type 1 diabetes . We aim ed to compare the safety and efficacy of a bihormonal bionic pancreas versus conventional insulin pump therapy in this population of patients in an outpatient setting . METHODS In this r and omised , open-label , crossover study , we enrolled preadolescent children ( aged 6 - 11 years ) with type 1 diabetes ( diagnosed for ≥1 year ) who were on insulin pump therapy , from two diabetes camps in the USA . With the use of sealed envelopes , participants were r and omly assigned in blocks of two to either 5 days with the bionic pancreas or conventional insulin pump therapy ( control ) as the first intervention , followed by a 3 day washout period and then 5 days with the other intervention . Study allocation was not masked . The autonomously adaptive algorithm of the bionic pancreas received data from a continuous glucose monitoring ( CGM ) device to control subcutaneous delivery of insulin and glucagon . Conventional insulin pump therapy was administered by the camp physicians and other clinical staff in accordance with their established protocol s ; participants also wore a CGM device during the control period . The co primary outcomes , analysed by intention to treat , were mean CGM-measured glucose concentration and the proportion of time with a CGM-measured glucose concentration below 3·3 mmol/L , on days 2 - 5 . This study is registered with Clinical Trials.gov , number NCT02105324 . FINDINGS Between July 20 , and Aug 19 , 2014 , 19 children with a mean age of 9·8 years ( SD 1·6 ) participated in and completed the study . The bionic pancreas period was associated with a lower mean CGM-measured glucose concentration on days 2 - 5 than was the control period ( 7·6 mmol/L [ SD 0·6 ] vs 9·3 mmol/L [ 1·7 ] ; p=0·00037 ) and a lower proportion of time with a CGM-measured glucose concentration below 3·3 mmol/L on days 2 - 5 ( 1·2 % [ SD 1·1 ] vs 2·8 % [ 1·2 ] ; p<0·0001 ) . The median number of carbohydrate interventions given per participant for hypoglycaemia on days 1 - 5 ( ie , glucose < 3·9 mmol/L ) was lower during the bionic pancreas period than during the control period ( three [ range 0 - 8 ] vs five [ 0 - 14 ] ; p=0·037 ) . No episodes of severe hypoglycaemia were recorded . Medium-to-large concentrations of ketones ( range 0·6 - 3·6 mmol/dL ) were reported on seven occasions in five participants during the control period and on no occasion during the bionic pancreas period ( p=0·063 ) . INTERPRETATION The improved mean glycaemia and reduced hypoglycaemia with the bionic pancreas relative to insulin pump therapy in preadolescent children with type 1 diabetes in a diabetes camp setting is a promising finding . Studies of a longer duration during which children use the bionic pancreas during their normal routines at home and school should be done to investigate the potential for use of the bionic pancreas in real-world setting s. FUNDING The Leona M and Harry B Helmsley Charitable Trust and the US National Institute of Diabetes and Digestive and Kidney Diseases OBJECTIVE To evaluate two widely used control algorithms for an artificial pancreas ( AP ) under nonideal but comparable clinical conditions . RESEARCH DESIGN AND METHODS After a pilot safety and feasibility study ( n = 10 ) , closed-loop control ( CLC ) was evaluated in a r and omized , crossover trial of 20 additional adults with type 1 diabetes . Personalized model predictive control ( MPC ) and proportional integral derivative ( PID ) algorithms were compared in supervised 27.5-h CLC sessions . Challenges included overnight control after a 65-g dinner , response to a 50-g breakfast , and response to an unannounced 65-g lunch . Boluses of announced dinner and breakfast meals were given at mealtime . The primary outcome was time in glucose range 70–180 mg/dL. RESULTS Mean time in range 70–180 mg/dL was greater for MPC than for PID ( 74.4 vs. 63.7 % , P = 0.020 ) . Mean glucose was also lower for MPC than PID during the entire trial duration ( 138 vs. 160 mg/dL , P = 0.012 ) and 5 h after the unannounced 65-g meal ( 181 vs. 220 mg/dL , P = 0.019 ) . There was no significant difference in time with glucose < 70 mg/dL throughout the trial period . CONCLUSIONS This first comprehensive study to compare MPC and PID control for the AP indicates that MPC performed particularly well , achieving nearly 75 % time in the target range , including the unannounced meal . Although both forms of CLC provided safe and effective glucose management , MPC performed as well or better than PID in all metrics BACKGROUND Additional benefits of the dual-hormone ( insulin and glucagon ) artificial pancreas compared with the single-hormone ( insulin alone ) artificial pancreas have not been assessed in young people in outpatient unrestricted conditions . We evaluated the efficacy of three systems for nocturnal glucose control in children and adolescents with type 1 diabetes . METHODS We did a r and omised , three-way , crossover trial in children aged 9 - 17 years with type 1 diabetes attending a diabetes camp in Canada . With use of sealed envelopes , children were r and omly assigned in a 1:1:1:1:1:1 ratio with blocks of six to different sequences of the three interventions ( single-hormone artificial pancreas , dual-hormone artificial pancreas , and conventional continuous subcutaneous insulin pump therapy ) . Each intervention was applied for 3 consecutive nights . Participants , study staff , and endpoint assessors were not masked . The primary outcome was the percentage of time spent with glucose concentrations lower than 4·0 mmol/L from 2300 h to 0700 h. Analysis was by intention to treat . A p value of less than 0·0167 was regarded as significant . This study is registered with Clinical Trials.gov , number NCT02189694 . FINDINGS Between June 30 , 2014 , and Aug 9 , 2014 , we enrolled 33 children of mean age 13·3 years ( SD 2·3 ; range 9 - 17 ) . The time spent at a glucose concentration lower than 4·0 mmol/L was median 0 % ( IQR 0·0 - 2·4 ) during nights with the dual-hormone artificial pancreas , 3·1 % ( 0·0 - 6·9 ) during nights with the single-hormone artificial pancreas ( p=0·032 ) , and 3·4 % ( 0 - 11·0 ) during nights with conventional pump therapy ( p=0·0048 compared with dual-hormone artificial pancreas and p=0·32 compared with single-hormone artificial pancreas ) . 15 hypoglycaemic events ( < 3·1 mmol/L for 20 min measured by sensor then confirmed with capillary glucose < 4·0 mmol/L ) were noted during nights with conventional pump therapy compared with four events with the single-hormone system and no events with the dual-hormone system . None of the assessed outcomes varied with the order in which children and young adults were assigned interventions . INTERPRETATION The dual-hormone artificial pancreas could improve nocturnal glucose control in children and adolescents with type 1 diabetes . Longer and larger outpatient studies are now needed . FUNDING Canadian Diabetes Association , Fondation J A De Sève OBJECTIVE To determine the safety and efficacy of an automated unified safety system ( USS ) in providing overnight closed-loop ( OCL ) control in children and adolescents with type 1 diabetes attending diabetes summer camps . RESEARCH DESIGN AND METHODS The Diabetes Assistant ( DIAS ) USS used the Dexcom G4 Platinum glucose sensor ( Dexcom ) and t : slim insulin pump ( T and em Diabetes Care ) . An initial inpatient study was completed for 12 participants to evaluate safety . For the main camp study , 20 participants with type 1 diabetes were r and omized to either OCL or sensor-augmented therapy ( control conditions ) per night over the course of a 5- to 6-day diabetes camp . RESULTS Subjects completed 54 OCL nights and 52 control nights . On an intention-to-treat basis , with glucose data analyzed regardless of system status , the median percent time in range , from 70–150 mg/dL , was 62 % ( 29 , 87 ) for OCL nights versus 55 % ( 25 , 80 ) for sensor-augmented pump therapy ( P = 0.233 ) . A per- protocol analysis allowed for assessment of algorithm performance . The median percent time in range , from 70–150 mg/dL , was 73 % ( 50 , 89 ) for OCL nights ( n = 41 ) versus 52 % ( 24 , 83 ) for control conditions ( n = 39 ) ( P = 0.037 ) . There was less time spent in the hypoglycemic range < 50 , < 60 , and < 70 mg/dL during OCL compared with the control period ( P = 0.019 , P = 0.009 , and P = 0.023 , respectively ) . CONCLUSIONS The DIAS USS algorithm is effective in improving time spent in range as well as reducing nocturnal hypoglycemia during the overnight period in children and adolescents with type 1 diabetes in a diabetes camp setting OBJECTIVE We evaluated the safety and efficacy of closed-loop basal insulin delivery during sleep and after regular meals and unannounced periods of exercise . RESEARCH DESIGN AND METHODS Twelve adolescents with type 1 diabetes ( five males ; mean age 15.0 [ SD 1.4 ] years ; HbA1c 7.9 [0.7]% ; BMI 21.4 [ 2.6 ] kg/m2 ) were studied at a clinical research facility on two occasions and received , in r and om order , either closed-loop basal insulin delivery or conventional pump therapy for 36 h. During closed-loop insulin delivery , pump basal rates were adjusted every 15 min according to a model predictive control algorithm informed by subcutaneous sensor glucose levels . During control visits , subjects ’ st and ard infusion rates were applied . Pr and ial insulin boluses were given before main meals ( 50–80 g carbohydrates ) but not before snacks ( 15–30 g carbohydrates ) . Subjects undertook moderate-intensity exercise , not announced to the algorithm , on a stationary bicycle at a 140 bpm heart rate in the morning ( 40 min ) and afternoon ( 20 min ) . Primary outcome was time when plasma glucose was in the target range ( 71–180 mg/dL ) . RESULTS Closed-loop basal insulin delivery increased percentage time when glucose was in the target range ( median 84 % [ interquartile range 78–88 % ] vs. 49 % [ 26–79 % ] , P = 0.02 ) and reduced mean plasma glucose levels ( 128 [ 19 ] vs. 165 [ 55 ] mg/dL , P = 0.02 ) . Plasma glucose levels were in the target range 100 % of the time on 17 of 24 nights during closed-loop insulin delivery . Hypoglycemia occurred on 10 occasions during control visits and 9 occasions during closed-loop delivery ( 5 episodes were exercise related , and 4 occurred within 2.5 h of pr and ial bolus ) . CONCLUSIONS Day- and -night closed-loop basal insulin delivery can improve glucose control in adolescents . However , unannounced moderate-intensity exercise and excessive pr and ial boluses pose challenges to hypoglycemia-free closed-loop basal insulin delivery Aims To assess the performance and safety of an integrated bihormonal artificial pancreas system consisting of one wearable device and two wireless glucose sensor transmitters during short‐term daily use at home . Methods Adult patients with type 1 diabetes using an insulin pump were invited to enrol in this r and omized crossover study . Treatment with the artificial pancreas started with a day and night in the clinical research centre , followed by 3 days at home . The control period consisted of 4 days of insulin pump therapy at home with blinded continuous glucose monitoring for data collection . Days 2–4 were predefined as the analysis period , with median glucose as the primary outcome . Results A total of 10 patients completed the study . The median [ interquartile range ( IQR ) ] glucose level was similar for the two treatments [ 7.3 ( 7.0–7.6 ) mmol/l for the artificial pancreas vs. 7.7 ( 7.0–9.0 ) mmol/l for the control ; p = 0.123 ] . The median ( IQR ) percentage of time spent in euglycaemia ( 3.9–10 mmol/l ) was longer during use of the artificial pancreas [ 84.7 (82.2–87.8)% for the artificial pancreas vs. 68.5 (57.9–83.6)% for the control ; p = 0.007 ] . Time in hypoglycaemia was 1.3 (0.2–3.2)% for the artificial pancreas and 2.4 (0.4–10.3)% for the control treatment ( p = 0.139 ) . Separate analysis of daytime and night‐time showed that the improvements were mainly achieved during the night . Conclusions The results of this pilot study suggest that our integrated artificial pancreas provides better glucose control than insulin pump therapy in patients with type 1 diabetes at home and that the treatment is safe BACKGROUND Studies of closed-loop control ( CLC ) systems have improved glucose levels in patients with type 1 diabetes . In this study we test a new CLC concept aim ing to " reset " the patient overnight to near-normoglycemia each morning , for several consecutive nights . SUBJECTS AND METHODS Ten insulin pump users with type 1 diabetes ( mean age , 46.4±8.5 years ) were enrolled in a two-center ( in the United States and Italy ) r and omized crossover trial comparing 5 consecutive nights of CLC ( 23:00 - 07:00 h ) in an outpatient setting versus sensor-augmented insulin pump therapy of the same duration at home . Primary end points included time spent in 80 - 140 mg/dL as measured by continuous glucose monitoring overnight and fasting blood glucose distribution at 7:00 h. RESULTS Compared with sensor-augmented pump therapy , CLC improved significantly time spent between 80 and 140 mg/dL ( 54.5 % vs. 32.2 % ; P<0.001 ) and between 70 and 180 mg/dL ( 85.4 % vs. 59.1 % ; P<0.001 ) ; CLC reduced the mean glucose level at 07:00 h ( 119.3 vs. 152.9 mg/dL ; P<0.001 ) and overnight mean glucose level ( 139.0 vs. 170.3 mg/dL ; P<0.001 ) using a marginally lower amount of insulin ( 6.1 vs. 6.8 units ; P=0.1 ) . Tighter overnight control led to improved daytime control on the next day : the overnight/next-day control correlation was r=0.52 , P<0.01 . CONCLUSIONS Multinight CLC of insulin delivery ( artificial pancreas ) results in significant improvement in morning and overnight glucose levels and time in target range , with the potential to improve daytime control when glucose levels were " reset " to near-normoglycemia each morning CONTEXT A challenge for automated glycemic control in type 1 diabetes ( T1D ) is the large variation in insulin needs between individuals and within individuals at different times in their lives . OBJECTIVES The objectives of the study was to test the ability of a third-generation bihormonal bionic pancreas algorithm , initialized with only subject weight ; to adapt automatically to the different insulin needs of adults and adolescents ; and to evaluate the impact of optional , automatically adaptive meal-priming boluses . DESIGN This was a r and omized controlled trial . SETTING The study was conducted at an inpatient clinical research center . PATIENTS Twelve adults and 12 adolescents with T1D participated in the study . INTERVENTIONS Subjects in each age group were r and omized to automated glycemic control for 48 hours with or without automatically adaptive meal-priming boluses . MAIN OUTCOME MEASURES Mean plasma glucose ( PG ) , time with PG less than 60 mg/dL , and insulin total daily dose were measured . RESULTS The 48-hour mean PG values with and without adaptive meal-priming boluses were 132 ± 9 vs 146 ± 9 mg/dL ( P = .03 ) in adults and 162 ± 6 vs 175 ± 9 mg/dL ( P = .01 ) in adolescents . Adaptive meal-priming boluses improved mean PG without increasing time spent with PG less than 60 mg/dL : 1.4 % vs 2.3 % ( P = .6 ) in adults and 0.1 % vs 0.1 % ( P = 1.0 ) in adolescents . Large increases in adaptive meal-priming boluses and shifts in the timing and size of automatic insulin doses occurred in adolescents . Much less adaptation occurred in adults . There was nearly a 4-fold variation in the total daily insulin dose across all cohorts ( 0.36 - 1.41 U/kg · d ) . CONCLUSIONS A single control algorithm , initialized only with subject weight , can quickly adapt to regulate glycemia in patients with TID and highly variable insulin requirements Aims /hypothesisThe aim of this multicentre , r and omised , controlled crossover study was to determine the efficacy of adding continuous glucose monitoring ( CGM ) to insulin pump therapy ( CSII ) in type 1 diabetes . Methods Children and adults ( n = 153 ) on CSII with HbA1c 7.5–9.5 % ( 58.5–80.3 mmol/mol ) were r and omised to ( CGM ) a Sensor On or Sensor Off arm for 6 months . After 4 months ’ washout , participants crossed over to the other arm for 6 months . Paediatric and adult participants were separately electronically r and omised through the case report form according to a predefined r and omisation sequence in eight secondary and tertiary centres . The primary outcome was the difference in HbA1c levels between arms after 6 months . Results Seventy-seven participants were r and omised to the On/Off sequence and 76 to the Off/On sequence ; all were included in the primary analysis . The mean difference in HbA1c was –0.43 % ( –4.74 mmol/mol ) in favour of the Sensor On arm ( 8.04 % [ 64.34 mmol/mol ] vs 8.47 % [ 69.08 mmol/mol ] ; 95 % CI −0.32 % , −0.55 % [ −3.50 , −6.01 mmol/mol ] ; p < 0.001 ) . Following cessation of glucose sensing , HbA1c reverted to baseline levels . Less time was spent with sensor glucose < 3.9 mmol/l during the Sensor On arm than in the Sensor Off arm ( 19 vs 31 min/day ; p = 0.009 ) . The mean number of daily boluses increased in the Sensor On arm ( 6.8 ± 2.5 vs 5.8 ± 1.9 , p < 0.0001 ) , together with the frequency of use of the temporary basal rate ( 0.75 ± 1.11 vs 0.26 ± 0.47 , p < 0.0001 ) and manual insulin suspend ( 0.91 ± 1.25 vs 0.70 ± 0.75 , p < 0.018 ) functions . Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm , respectively ( p = 0.40 ) . Conclusions /interpretationContinuous glucose monitoring was associated with decreased HbA1c levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII . More frequent self-adjustments of insulin therapy may have contributed to these effects . Trial registration Clinical Trials.gov registration no. NCT00598663 . Funding The study was funded by Medtronic International Trading Sarl Switzerl and OBJECTIVE To evaluate feasibility , safety , and efficacy of day- and -night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes under free-living conditions without remote monitoring or supervision . RESEARCH DESIGN AND METHODS In an open-label , r and omized , free-living , crossover study design , 12 adolescents receiving insulin pump therapy ( mean [ ±SD ] age 15.4 ± 2.6 years ; HbA1c 8.3 ± 0.9 % ; duration of diabetes 8.2 ± 3.4 years ) underwent two 7-day periods of sensor-augmented insulin pump therapy or hybrid closed-loop insulin delivery without supervision or remote monitoring . During the closed-loop insulin delivery , a model predictive algorithm automatically directed insulin delivery between meals and overnight ; pr and ial boluses were administered by participants using a bolus calculator . RESULTS The proportion of time when the sensor glucose level was in the target range ( 3.9–10 mmol/L ) was increased during closed-loop insulin delivery compared with sensor-augmented pump therapy ( 72 vs. 53 % , P < 0.001 ; primary end point ) , the mean glucose concentration was lowered ( 8.7 vs. 10.1 mmol/L , P = 0.028 ) , and the time spent above the target level was reduced ( P = 0.005 ) without changing the total daily insulin amount ( P = 0.55 ) . The time spent in the hypoglycemic range was low and comparable between interventions . CONCLUSIONS Unsupervised day- and -night hybrid closed-loop insulin delivery at home is feasible and safe in young people with type 1 diabetes . Compared with sensor-augmented insulin pump therapy , closed-loop insulin delivery may improve glucose control without increasing the risk of hypoglycemia in adolescents with suboptimally controlled type 1 diabetes OBJECTIVE Afternoon exercise increases the risk of nocturnal hypoglycemia ( NH ) in subjects with type 1 diabetes . We hypothesized that automated feedback-controlled closed-loop ( CL ) insulin delivery would be superior to open-loop ( OL ) control in preventing NH and maintaining a higher proportion of blood glucose levels within the target blood glucose range on nights with and without antecedent afternoon exercise . RESEARCH DESIGN AND METHODS Subjects completed two 48-h inpatient study periods in r and om order : usual OL control and CL control using a proportional-integrative-derivative plus insulin feedback algorithm . Each admission included a sedentary day and an exercise day , with a st and ardized protocol of 60 min of brisk treadmill walking to 65–70 % maximum heart rate at 3:00 p.m. RESULTS Among 12 subjects ( age 12–26 years , A1C 7.4 ± 0.6 % ) , antecedent exercise increased the frequency of NH ( reference blood glucose < 60 mg/dL ) during OL control from six to eight events . In contrast , there was only one NH event each on nights with and without antecedent exercise during CL control ( P = 0.04 vs. OL nights ) . Overnight , the percentage of glucose values in target range was increased with CL control ( P < 0.0001 ) . Insulin delivery was lower between 10:00 p.m. and 2:00 a.m. on nights after exercise on CL versus OL , P = 0.008 . CONCLUSIONS CL insulin delivery provides an effective means to reduce the risk of NH while increasing the percentage of time spent in target range , regardless of activity level in the mid-afternoon . These data suggest that CL control could be of benefit to patients with type 1 diabetes even if it is limited to the overnight period BACKGROUND The feasibility , safety , and efficacy of prolonged use of an artificial beta cell ( closed-loop insulin-delivery system ) in the home setting have not been established . METHODS In two multicenter , crossover , r and omized , controlled studies conducted under free-living home conditions , we compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes . The closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents . Participants used the closed-loop system for a 12-week period and sensor-augmented pump therapy ( control ) for a similar period . The primary end point was the proportion of time that the glucose level was between 70 mg and 180 mg per deciliter for adults and between 70 mg and 145 mg per deciliter for children and adolescents . RESULTS Among adults , the proportion of time that the glucose level was in the target range was 11.0 percentage points ( 95 % confidence interval [ CI ] , 8.1 to 13.8 ) greater with the use of the closed-loop system day and night than with control therapy ( P<0.001 ) . The mean glucose level was lower during the closed-loop phase than during the control phase ( difference , -11 mg per deciliter ; 95 % CI , -17 to -6 ; P<0.001 ) , as were the area under the curve for the period when the glucose level was less than 63 mg per deciliter ( 39 % lower ; 95 % CI , 24 to 51 ; P<0.001 ) and the mean glycated hemoglobin level ( difference , -0.3 % ; 95 % CI , -0.5 to -0.1 ; P=0.002 ) . Among children and adolescents , the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the control phase ( by 24.7 percentage points ; 95 % CI , 20.6 to 28.7 ; P<0.001 ) , and the mean nighttime glucose level was lower ( difference , -29 mg per deciliter ; 95 % CI , -39 to -20 ; P<0.001 ) . The area under the curve for the period in which the day- and -night glucose levels were less than 63 mg per deciliter was lower by 42 % ( 95 % CI , 4 to 65 ; P=0.03 ) . Three severe hypoglycemic episodes occurred during the closed-loop phase when the closed-loop system was not in use . CONCLUSIONS Among patients with type 1 diabetes , 12-week use of a closed-loop system , as compared with sensor-augmented pump therapy , improved glucose control , reduced hypoglycemia , and , in adults , result ed in a lower glycated hemoglobin level . ( Funded by the JDRF and others ; AP@home04 and APCam08 Clinical Trials.gov numbers , NCT01961622 and NCT01778348 . ) OBJECTIVE To assess the possibility of improving nocturnal glycemic control as well as meal glycemic response using closed-loop therapy in children aged < 7 years . RESEARCH DESIGN AND METHODS This was a r and omized controlled crossover trial comparing closed-loop with st and ard open-loop insulin pump therapy performed in an inpatient clinical research center . Ten subjects aged < 7 years with type 1 diabetes for > 6 months treated with insulin pump therapy were studied . Closed-loop therapy and st and ard open-loop therapy were compared from 10:00 p.m. to 12:00 p.m. on 2 consecutive days . The primary outcome was plasma glucose time in range ( 110–200 mg/dL ) during the night ( 10:00 p.m.–8:00 a.m. ) . Secondary outcomes included peak postpr and ial glucose levels , incidence of hypoglycemia , degree of hyperglycemia , and prelunch glucose levels . RESULTS A trend toward a higher mean nocturnal time within target range was noted for closed- versus open-loop therapy , although not reaching statistical significance ( 5.3 vs. 3.2 h , P = 0.12 ) . There was no difference in peak postpr and ial glucose or number of episodes of hypoglycemia . There was significant improvement in time spent > 300 mg/dL overnight with closed-loop therapy ( 0.18 vs. 1.3 h , P = 0.035 ) and the total area under the curve of glucose > 200 mg/dL ( P = 0.049 ) . Closed-loop therapy returned prelunch blood glucose closer to target ( 189 vs. 273 mg/dL on open loop , P = 0.009 ) . CONCLUSIONS Closed-loop insulin delivery decreases the severity of overnight hyperglycemia without increasing the incidence of hypoglycemia . The therapy is better able to reestablish target glucose levels in advance of a subsequent meal . Younger children with type 1 diabetes may reap significant benefits from closed-loop therapy OBJECTIVE This study evaluated the feasibility , safety , and efficacy of day- and -night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes under free-living conditions . RESEARCH DESIGN AND METHODS In an open-label r and omized crossover study , 12 suboptimally controlled adolescents on insulin pump therapy ( mean ± SD age 14.6 ± 3.1 years ; HbA1c 69 ± 8 mmol/mol [ 8.5 ± 0.7 % ] ; duration of diabetes 7.8 ± 3.5 years ) underwent two 21-day periods in which hybrid closed-loop insulin delivery was compared with sensor-augmented insulin pump therapy in r and om order . During the closed-loop intervention , a model predictive algorithm automatically directed insulin delivery between meals and overnight . Participants used a bolus calculator to administer pr and ial boluses . RESULTS The proportion of time that sensor glucose was in the target range ( 3.9–10 mmol/L ; primary end point ) was increased during the closed-loop intervention compared with sensor-augmented insulin pump therapy by 18.8 ± 9.8 percentage points ( mean ± SD ; P < 0.001 ) , the mean sensor glucose level was reduced by 1.8 ± 1.3 mmol/L ( P = 0.001 ) , and the time spent above target was reduced by 19.3 ± 11.3 percentage points ( P < 0.001 ) . The time spent with sensor glucose levels below 3.9 mmol/L was low and comparable between interventions ( median difference 0.4 [ interquartile range −2.2 to 1.3 ] percentage points ; P = 0.33 ) . Improved glucose control during closed-loop was associated with increased variability of basal insulin delivery ( P < 0.001 ) and an increase in the total daily insulin dose ( 53.5 [ 39.5–72.1 ] vs. 51.5 [ 37.6–64.3 ] units/day ; P = 0.006 ) . Participants expressed positive attitudes and experience with the closed-loop system . CONCLUSIONS Free-living home use of day- and -night closed-loop in suboptimally controlled adolescents with type 1 diabetes is safe , feasible , and improves glucose control without increasing the risk of hypoglycemia . Larger and longer studies are warranted We evaluated the safety and efficacy of closed-loop therapy with meal announcement during reduction and omission of meal insulin boluses in adolescents with type 1 diabetes ( T1D ) . Twelve adolescents with T1D [ six male ; mean ( s.d . ) age 15.9 ( 1.8 ) years ; mean ( s.d . ) glycated haemoglobin ( HbA1c ) 77 ( 27 ) mmol/mol ] were studied in a r and omized crossover study comparing closed-loop therapy with meal announcement with conventional pump therapy over two 24-h stays at a clinical research facility . Identical meals were given on both occasions . The evening meal insulin bolus was calculated to cover half of the carbohydrate content of the meal and no bolus was delivered for lunch . Plasma glucose levels were in the target range of 3.9 - 10 mmol/l for a median [ interquartile range ( IQR ) ] of 74 (55,86)% of the time during closed-loop therapy with meal announcement and for 62 (49,75)% of the time during conventional therapy ( p = 0.26 ) . Median ( IQR ) time spent with plasma glucose levels > 10 mmol/l [ 23 ( 13,39 ) vs. 27 (10,50)% ; p = 0.88 ] or < 3.9 mmol/l [ 1(0,4 ) vs. 5 (1,10)% ; p = 0.24 ] and mean [ st and ard deviation ( SD ) ] glucose levels [ 8.0 ( 7.6,9.3 ) vs. 7.7 ( 6.6,10.1 ) mmol/l , p = 0.79 ] were also similar . In conclusion , these results assist home testing of closed-loop delivery with meal announcement in adolescents with poorly controlled T1D who miscalculate or miss meal insulin boluses OBJECTIVE To evaluate feasibility , safety , and efficacy of overnight closed-loop insulin delivery in free-living youth with type 1 diabetes . RESEARCH DESIGN AND METHODS Overnight closed loop was evaluated at home by 16 pump-treated adolescents with type 1 diabetes aged 12–18 years . Over a 3-week period , overnight insulin delivery was directed by a closed-loop system , and on another 3-week period sensor-augmented therapy was applied . The order of interventions was r and om . The primary end point was time when adjusted sensor glucose was between 3.9 and 8.0 mmol/L from 2300 to 0700 h. RESULTS Closed loop was constantly applied over at least 4 h on 269 nights ( 80 % ) ; sensor data were collected over at least 4 h on 282 control nights ( 84 % ) . Closed loop increased time spent with glucose in target by a median 15 % ( interquartile range −9 to 43 ; P < 0.001 ) . Mean overnight glucose was reduced by a mean 14 ( SD 58 ) mg/dL ( P < 0.001 ) . Time when glucose was < 70 mg/dL was low in both groups , but nights with glucose < 63 mg/dL for at least 20 min were less frequent during closed loop ( 10 vs. 17 % ; P = 0.01 ) . Despite lower total daily insulin doses by a median 2.3 ( interquartile range −4.7 to 9.3 ) units ( P = 0.009 ) , overall 24-h glucose was reduced by a mean 9 ( SD 41 ) mg/dL ( P = 0.006 ) during closed loop . CONCLUSIONS Unsupervised home use of overnight closed loop in adolescents with type 1 diabetes is safe and feasible . Glucose control was improved during the day and night with fewer episodes of nocturnal hypoglycemia OBJECTIVE To evaluate the feasibility of day and night closed-loop insulin delivery in adults with type 1 diabetes under free-living conditions . RESEARCH DESIGN AND METHODS Seventeen adults with type 1 diabetes on insulin pump therapy ( means ± SD age 34 ± 9 years , HbA1c 7.6 ± 0.8 % , and duration of diabetes 19 ± 9 years ) participated in an open-label multinational three-center crossover study . In a r and om order , participants underwent two 8-day periods ( first day at the clinical research facility followed by 7 days at home ) of sensor-augmented insulin pump therapy ( SAP ) or automated closed-loop insulin delivery . The primary end point was the time when sensor glucose was in target range between 3.9 and 10.0 mmol/L during the 7-day home phase . RESULTS During the home phase , the percentage of time when glucose was in target range was significantly higher during closed-loop compared with SAP ( median 75 % [ interquartile range 61–79 ] vs. 62 % [ 53–70 ] , P = 0.005 ) . Mean glucose ( 8.1 vs. 8.8 mmol/L , P = 0.027 ) and time spent above target ( P = 0.013 ) were lower during closed loop , while time spent below target was comparable ( P = 0.339 ) . Increased time in target was observed during both daytime ( P = 0.017 ) and nighttime ( P = 0.013 ) . CONCLUSIONS Compared with SAP , 1 week of closed-loop insulin delivery at home reduces mean glucose and increases time in target without increasing the risk of hypoglycemia in adults with relatively well-controlled type 1 diabetes Integrated closed-loop control ( CLC ) , combining continuous glucose monitoring ( CGM ) with insulin pump ( continuous subcutaneous insulin infusion [ CSII ] ) , known as artificial pancreas , can help optimize glycemic control in diabetes . We present a fundamental modular concept for CLC design , illustrated by clinical studies involving 11 adolescents and 27 adults at the Universities of Virginia , Padova , and Montpellier . We tested two modular CLC constructs : st and ard control to range ( sCTR ) , design ed to augment pump plus CGM by preventing extreme glucose excursions ; and enhanced control to range ( eCTR ) , design ed to truly optimize control within near normoglycemia of 3.9–10 mmol/L. The CLC system was fully integrated using automated data transfer CGM→algorithm→CSII . All studies used r and omized crossover design comparing CSII versus CLC during identical 22-h hospitalizations including meals , overnight rest , and 30-min exercise . sCTR increased significantly the time in near normoglycemia from 61 to 74 % , simultaneously reducing hypoglycemia 2.7-fold . eCTR improved mean blood glucose from 7.73 to 6.68 mmol/L without increasing hypoglycemia , achieved 97 % in near normoglycemia and 77 % in tight glycemic control , and reduced variability overnight . In conclusion , sCTR and eCTR represent sequential steps toward automated CLC , preventing extremes ( sCTR ) and further optimizing control ( eCTR ) . This approach inspires compelling new concepts : modular assembly , sequential deployment , testing , and clinical acceptance of custom-built CLC systems tailored to individual patient needs BACKGROUND Recently developed technologies for the treatment of type 1 diabetes mellitus include a variety of pumps and pumps with glucose sensors . METHODS In this 1-year , multicenter , r and omized , controlled trial , we compared the efficacy of sensor-augmented pump therapy ( pump therapy ) with that of a regimen of multiple daily insulin injections ( injection therapy ) in 485 patients ( 329 adults and 156 children ) with inadequately controlled type 1 diabetes . Patients received recombinant insulin analogues and were supervised by expert clinical teams . The primary end point was the change from the baseline glycated hemoglobin level . RESULTS At 1 year , the baseline mean glycated hemoglobin level ( 8.3 % in the two study groups ) had decreased to 7.5 % in the pump-therapy group , as compared with 8.1 % in the injection-therapy group ( P<0.001 ) . The proportion of patients who reached the glycated hemoglobin target ( < 7 % ) was greater in the pump-therapy group than in the injection-therapy group . The rate of severe hypoglycemia in the pump-therapy group ( 13.31 cases per 100 person-years ) did not differ significantly from that in the injection-therapy group ( 13.48 per 100 person-years , P=0.58 ) . There was no significant weight gain in either group . CONCLUSIONS In both adults and children with inadequately controlled type 1 diabetes , sensor-augmented pump therapy result ed in significant improvement in glycated hemoglobin levels , as compared with injection therapy . A significantly greater proportion of both adults and children in the pump-therapy group than in the injection-therapy group reached the target glycated hemoglobin level . ( Funded by Medtronic and others ; Clinical Trials.gov number , NCT00417989 . OBJECTIVE To compare two vali date d closed-loop ( CL ) algorithms versus patient self-control with CSII in terms of glycemic control . RESEARCH DESIGN AND METHODS This study was a multicenter , r and omized , three-way crossover , open-label trial in 48 patients with type 1 diabetes mellitus for at least 6 months , treated with continuous subcutaneous insulin infusion . Blood glucose was controlled for 23 h by the algorithm of the Universities of Pavia and Padova with a Safety Supervision Module developed at the Universities of Virginia and California at Santa Barbara ( international artificial pancreas [ iAP ] ) , by the algorithm of University of Cambridge ( CAM ) , or by patients themselves in open loop ( OL ) during three hospital admissions including meals and exercise . The main analysis was on an intention-to-treat basis . Main outcome measures included time spent in target ( glucose levels between 3.9 and 8.0 mmol/L or between 3.9 and 10.0 mmol/L after meals ) . RESULTS Time spent in the target range was similar in CL and OL : 62.6 % for OL , 59.2 % for iAP , and 58.3 % for CAM . While mean glucose level was significantly lower in OL ( 7.19 , 8.15 , and 8.26 mmol/L , respectively ) ( overall P = 0.001 ) , percentage of time spent in hypoglycemia ( < 3.9 mmol/L ) was almost threefold reduced during CL ( 6.4 % , 2.1 % , and 2.0 % ) ( overall P = 0.001 ) with less time ≤2.8 mmol/L ( overall P = 0.038 ) . There were no significant differences in outcomes between algorithms . CONCLUSIONS Both CAM and iAP algorithms provide safe glycemic control BACKGROUND The artificial pancreas is an emerging technology for the treatment of type 1 diabetes and two configurations have been proposed : single-hormone ( insulin alone ) and dual-hormone ( insulin and glucagon ) . We aim ed to delineate the usefulness of glucagon in the artificial pancreas system . METHODS We did a r and omised crossover trial of dual-hormone artificial pancreas , single-hormone artificial pancreas , and conventional insulin pump therapy ( continuous subcutaneous insulin infusion ) in participants aged 12 years or older with type 1 diabetes . Participants were assigned in a 1:1:1:1:1:1 ratio with blocked r and omisation to the three interventions and attended a research facility for three 24-h study visits . During visits when the patient used the single-hormone artificial pancreas , insulin was delivered based on glucose sensor readings and a predictive dosing algorithm . During dual-hormone artificial pancreas visits , glucagon was also delivered during low or falling glucose . During conventional insulin pump therapy visits , patients received continuous subcutaneous insulin infusion . The study was not masked . The primary outcome was the time for which plasma glucose concentrations were in the target range ( 4·0 - 10·0 mmol/L for 2 h postpr and ially and 4·0 - 8·0 mmol/L otherwise ) . Hypoglycaemic events were defined as plasma glucose concentration of less than 3·3 mmol/L with symptoms or less than 3·0 mmol/L irrespective of symptoms . Analysis was by modified intention to treat , in which we included data for all patients who completed at least two visits . A p value of less than 0·0167 ( 0·05/3 ) was regarded as significant . This trial is registered with Clinical Trials.gov , number NCT01754337 . FINDINGS The mean proportion of time spent in the plasma glucose target range over 24 h was 62 % ( SD 18 ) , 63 % ( 18 ) , and 51 % ( 19 ) with single-hormone artificial pancreas , dual-hormone artificial pancreas , and conventional insulin pump therapy , respectively . The mean difference in time spent in the target range between single-hormone artificial pancreas and conventional insulin pump therapy was 11 % ( 17 ; p=0·002 ) and between dual-hormone artificial pancreas and conventional insulin pump therapy was 12 % ( 21 ; p=0·00011 ) . There was no difference ( 15 ; p=0·75 ) in the proportion of time spent in the target range between the single-hormone and dual-hormone artificial pancreas systems . There were 52 hypoglycaemic events with conventional insulin pump therapy ( 12 of which were symptomatic ) , 13 with the single-hormone artificial pancreas ( five of which were symptomatic ) , and nine with the dual-hormone artificial pancreas ( 0 of which were symptomatic ) ; the number of nocturnal hypoglycaemic events was 13 ( 0 symptomatic ) , 0 , and 0 , respectively . INTERPRETATION Single-hormone and dual-hormone artificial pancreas systems both provided better glycaemic control than did conventional insulin pump therapy . The single-hormone artificial pancreas might be sufficient for hypoglycaemia-free overnight glycaemic control . FUNDING Canadian Diabetes Association ; Fondation J A De Sève ; Juvenile Diabetes Research Foundation ; and Medtronic BACKGROUND An artificial pancreas ( AP ) that can be worn at home from dinner to waking up in the morning might be safe and efficient for first routine use in patients with type 1 diabetes . We assessed the effect on glucose control with use of an AP during the evening and night plus patient-managed sensor-augmented pump therapy ( SAP ) during the day , versus 24 h use of patient-managed SAP only , in free-living conditions . METHODS In a crossover study done in medical centres in France , Italy , and the Netherl and s , patients aged 18 - 69 years with type 1 diabetes who used insulin pumps for continuous subcutaneous insulin infusion were r and omly assigned to 2 months of AP use from dinner to waking up plus SAP use during the day versus 2 months of SAP use only under free-living conditions . R and omisation was achieved with a computer-generated allocation sequence with r and om block sizes of two , four , or six , masked to the investigator . Patients and investigators were not masked to the type of intervention . The AP consisted of a continuous glucose monitor ( CGM ) and insulin pump connected to a modified smartphone with a model predictive control algorithm . The primary endpoint was the percentage of time spent in the target glucose concentration range ( 3·9 - 10·0 mmol/L ) from 2000 to 0800 h. CGM data for weeks 3 - 8 of the interventions were analysed on a modified intention-to-treat basis including patients who completed at least 6 weeks of each intervention period . The 2 month study period also allowed us to asses HbA1c as one of the secondary outcomes . This trial is registered with Clinical Trials.gov , number NCT02153190 . FINDINGS During 2000 - 0800 h , the mean time spent in the target range was higher with AP than with SAP use : 66·7 % versus 58·1 % ( paired difference 8·6 % [ 95 % CI 5·8 to 11·4 ] , p<0·0001 ) , through a reduction in both mean time spent in hyperglycaemia ( glucose concentration > 10·0 mmol/L ; 31·6 % vs 38·5 % ; -6·9 % [ -9·8 % to -3·9 ] , p<0·0001 ) and in hypoglycaemia ( glucose concentration < 3·9 mmol/L ; 1·7 % vs 3·0 % ; -1·6 % [ -2·3 to -1·0 ] , p<0·0001 ) . Decrease in mean HbA1c during the AP period was significantly greater than during the control period ( -0·3 % vs -0·2 % ; paired difference -0·2 [ 95 % CI -0·4 to -0·0 ] , p=0·047 ) , taking a period effect into account ( p=0·0034 ) . No serious adverse events occurred during this study , and none of the mild-to-moderate adverse events was related to the study intervention . INTERPRETATION Our results support the use of AP at home as a safe and beneficial option for patients with type 1 diabetes . The HbA1c results are encouraging but preliminary . FUNDING European Commission Objective To compare the safety and efficacy of overnight closed loop delivery of insulin ( artificial pancreas ) with conventional insulin pump therapy in adults with type 1 diabetes . Design Two sequential , open label , r and omised controlled crossover , single centre studies . Setting Clinical research facility . Participants 24 adults ( 10 men , 14 women ) with type 1 diabetes , aged 18 - 65 , who had used insulin pump therapy for at least three months : 12 were tested after consuming a medium sized meal and the other 12 after consuming a larger meal accompanied by alcohol . Intervention During overnight closed loop delivery , sensor measurements of glucose were fed into a computer algorithm , which advised on insulin pump infusion rates at 15 minute intervals . During control nights , conventional insulin pump setting s were applied . One study compared closed loop delivery of insulin with conventional pump therapy after a medium sized evening meal ( 60 g of carbohydrates ) at 1900 , depicting the scenario of “ eating in . ” The other study was carried out after a later large evening meal ( 100 g of carbohydrates ) at 2030 , accompanied by white wine ( 0.75 g/kg ethanol ) and depicted the scenario of “ eating out . ” Main outcome measures The primary outcome was the time plasma glucose levels were in target ( 3.91 - 8.0 mmol/L ) during closed loop delivery and a comparable control period . Secondary outcomes included pooled data analysis and time plasma glucose levels were below target ( ≤3.9 mmol/L ) . Results For the eating in scenario , overnight closed loop delivery of insulin increased the time plasma glucose levels were in target by a median 15 % ( interquartile range 3 - 35 % ) , P=0.002 . For the eating out scenario , closed loop delivery increased the time plasma glucose levels were in target by a median 28 % ( 2 - 39 % ) , P=0.01 . Analysis of pooled data showed that the overall time plasma glucose was in target increased by a median 22 % ( 3 - 37 % ) with closed loop delivery ( P<0.001 ) . Closed loop delivery reduced overnight time spent hypoglycaemic ( plasma glucose ≤3.9 mmol/L ) by a median 3 % ( 0 - 20 % ) , P=0.04 , and eliminated plasma glucose concentrations below 3.0 mmol/L after midnight . Conclusion These two small crossover trials suggest that closed loop delivery of insulin may improve overnight control of glucose levels and reduce the risk of nocturnal hypoglycaemia in adults with type 1 diabetes . Trial registration Clinical Trials.gov NCT00910767 and NCT00944619 OBJECTIVE We evaluated the effect of the MD-Logic system on overnight glycemic control at patients ' homes . RESEARCH DESIGN AND METHODS Twenty-four patients ( aged 12–43 years ; average A1c 7.5 ± 0.8 % , 58.1 ± 8.4 mmol/mol ) were r and omly assigned to participate in two overnight crossover periods , each including 6 weeks of consecutive nights : one under closed loop and the second under sensor-augmented pump ( SAP ) therapy at patients ' homes in real-life conditions . The primary end point was time spent with sensor glucose levels below 70 mg/dL ( 3.9 mmol/L ) overnight . RESULTS Closed-loop nights significantly reduced time spent in hypoglycemia ( P = 0.02 ) and increased the percentage of time spent in the target range of 70–140 mg/dL ( P = 0.003 ) compared with nights when the SAP therapy was used . The time spent in substantial hyperglycemia above 240 mg/dL was reduced by a median of 52.2 % ( interquartile range [ IQR ] 4.8 , 72.9 % ; P = 0.001 ) under closed-loop control compared with SAP therapy . Overnight total insulin doses were lower in the closed-loop nights compared with the SAP nights ( P = 0.04 ) . The average daytime glucose levels after closed-loop operation were reduced by a median of 10.0 mg/dL ( IQR −2.7 , 19.2 ; P = 0.017 ) while lower total insulin doses were used ( P = 0.038 ) . No severe adverse events occurred during closed-loop control ; there was a single event of severe hypoglycemia during a control night . CONCLUSIONS The long-term home use of automated overnight insulin delivery by the MD-Logic system was found to be a feasible , safe , and an effective tool to reduce nocturnal hypoglycemia and improve overnight glycemic control in subjects with type 1 diabetes BACKGROUND We compared glycemia , treatment satisfaction , sleep quality , and cognition using a nighttime And roid-based hybrid closed-loop system ( And roid-HCLS ) with sensor-augmented pump with low-glucose suspend function ( SAP-LGS ) in people with type 1 diabetes . MATERIAL S AND METHODS An open-label , prospect i ve , r and omized crossover study of 16 adults ( mean [ SD ] age 42.1 [ 9.6 ] years ) and 12 adolescents ( 15.2 [ 1.6 ] years ) was conducted . All participants completed four consecutive nights at home with And roid-HCLS ( proportional integral derivative with insulin feedback algorithm ; Medtronic ) and SAP-LGS . PRIMARY OUTCOME percent continuous glucose monitoring ( CGM ) time ( 00:00 - 08:00 h ) within target range ( 72 - 144 mg/dL ) . Secondary endpoints : percent CGM time above target ( > 144 mg/dL ) ; below target ( < 72 mg/dL ) ; glycemic variability ( SD ) ; symptomatic hypoglycemia ; adult treatment satisfaction ; sleep quality ; and cognitive function . RESULTS The primary outcome for all participants was not statistically different between And roid-HCLS and SAP-LGS ( mean [ SD ] 59.4 [17.9]% vs. 53.1 [18]% ; p = 0.14 ) . Adults had greater percent time within target range ( 57.7 [18.6]% vs. 44.5 [14.5]% ; p < 0.006 ) ; less time above target ( 42.0 [18.7]% vs. 52.6 [16.5]% ; p = 0.034 ) ; lower glycemic variability ( 35 [ 10.7 ] mg/dL vs. 46 [ 10.7 ] mg/dL ; p = 0.003 ) ; and less ( median [ IQR ] ) time below target ( 0.0 [0.0 - 0.4]% vs. 0.80 [0.0 - 3.9]% ; p = 0.025 ) . In adolescents , time below target was lower with And roid-HCLS vs. SAP-LGS ( 0.0 [0.0 - 0.0]% vs. 1.8 [0.1 - 7.9]% ; p = 0.011 ) . Nocturnal symptomatic hypoglycemia was less ( 1 vs. 10 ; p = 0.007 ) in adolescents , but not adults ( 5 vs. 13 ; p = 0.059 ) . In adults , treatment satisfaction increased by 10 points ( p < 0.02 ) . Sleep quality and cognition did not differ . CONCLUSIONS And roid-HCLS in both adults and adolescents reduced nocturnal hypoglycemia and , in adults , improved overnight time in target range and treatment satisfaction compared with SAP-LGS OBJECTIVE This study determined the feasibility and efficacy of an automated proportional-integral-derivative with insulin feedback ( PID-IFB ) controller in overnight closed-loop ( OCL ) control of children and adolescents with type 1 diabetes over multiple days in a diabetes camp setting . RESEARCH DESIGN AND METHODS The Medtronic ( Northridge , CA ) And roid ™ ( Google , Mountain View , CA)-based PID-IFB system consists of the Medtronic Minimed Revel ™ 2.0 pump and Enlite ™ sensor , a control algorithm residing on an And roid phone , a translator , and remote monitoring capabilities . An inpatient study was completed for 16 participants to determine feasibility . For the camp study , subjects with type 1 diabetes were r and omized to either OCL or sensor-augmented pump therapy ( control conditions ) per night for up to 6 nights at diabetes camp . RESULTS During the camp study , 21 subjects completed 50 OCL nights and 52 control nights . Based on intention to treat , the median time spent in range , from 70 to 150 mg/dL , was greater during OCL at 66.4 % ( n = 55 ) versus 50.6 % ( n = 52 ) during the control period ( P = 0.004 ) . A per- protocol analysis allowed for assessment of algorithm performance with the median percentage time in range , 70 - 150 mg/dL , being 75.5 % ( n = 37 ) for OCL versus 47.6 % ( n = 32 ) for the control period ( P < 0.001 ) . There was less time spent in the hypoglycemic ranges < 60 mg/dL and < 70 mg/dL during OCL compared with the control period ( P = 0.003 and P < 0.001 , respectively ) . CONCLUSIONS The PID-IFB controller is effective in improving time spent in range as well as reducing nocturnal hypoglycemia during the overnight period in children and adolescents with type 1 diabetes in a diabetes camp setting BACKGROUND The safety and effectiveness of a continuous , day- and -night automated glycaemic control system using insulin and glucagon has not been shown in a free-living , home-use setting . We aim ed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity . METHODS We did a r and om-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA . Participants were r and omly assigned ( 1:1 ) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care ( conventional or sensor-augmented insulin pump therapy ) first , followed by the opposite intervention . Both study periods were 11 days in length , during which time participants continued all normal activities , including athletics and driving . The bionic pancreas was initialised with only the participant 's body mass . Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon . The co primary outcomes were the mean glucose concentration and time with continuous glucose monitoring ( CGM ) glucose concentration less than 3·3 mmol/L , analysed over days 2 - 11 in participants who completed both periods of the study . This trial is registered with Clinical Trials.gov , number NCT02092220 . FINDINGS We r and omly assigned 43 participants between May 6 , 2014 , and July 3 , 2015 , 39 of whom completed the study : 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first . The mean CGM glucose concentration was 7·8 mmol/L ( SD 0·6 ) in the bionic pancreas period versus 9·0 mmol/L ( 1·6 ) in the comparator period ( difference 1·1 mmol/L , 95 % CI 0·7 - 1·6 ; p<0·0001 ) , and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6 % ( 0·6 ) in the bionic pancreas period versus 1·9 % ( 1·7 ) in the comparator period ( difference 1·3 % , 95 % CI 0·8 - 1·8 ; p<0·0001 ) . The mean nausea score on the Visual Analogue Scale ( score 0 - 10 ) was greater during the bionic pancreas period ( 0·52 [ SD 0·83 ] ) than in the comparator period ( 0·05 [ 0·17 ] ; difference 0·47 , 95 % CI 0·21 - 0·73 ; p=0·0024 ) . Body mass and laboratory parameters did not differ between periods . There were no serious or unexpected adverse events in the bionic pancreas period of the study . INTERPRETATION Relative to conventional and sensor-augmented insulin pump therapy , the bihormonal bionic pancreas , initialised only with participant weight , was able to achieve superior glycaemic regulation without the need for carbohydrate counting . Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas . FUNDING National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health , and National Center for Advancing Translational Sciences Background : To improve type 1 diabetes mellitus ( T1DM ) management , we developed a model predictive control ( MPC ) algorithm for closed-loop ( CL ) glucose control based on a linear second-order deterministic-stochastic model . The deterministic part of the model is specified by three patient-specific parameters : Insulin sensitivity factor , insulin action time , and basal insulin infusion rate . The stochastic part is identical for all patients but identified from data from a single patient . Results of the first clinical feasibility test of the algorithm are presented . Methods : We conducted two r and omized crossover studies . Study 1 compared CL with open-loop ( OL ) control . Study 2 compared glucose control after CL initiation in the euglycemic ( CL-Eu ) and hyperglycemic ( CL-Hyper ) ranges , respectively . Patients were studied from 22:00–07:00 on two separate nights . Results : Each study included six T1DM patients ( hemoglobin A1c 7.2 % ± 0.4 % ) . In study 1 , hypoglycemic events ( plasma glucose < 54 mg/dl ) occurred on two OL and one CL nights . Average glucose from 22:00–07:00 was 90 mg/dl [ 74–146 mg/dl ; median ( interquartile range ) ] during OL and 108 mg/dl ( 101–128 mg/dl ) during CL ( determined by continuous glucose monitoring ) . However , median time spent in the range 70–144 mg/dl was 67.9 % ( 3.0–73.3 % ) during OL and 80.8 % ( 70.5–89.7 % ) during CL . In study 2 , there was one episode of hypoglycemia with plasma glucose < 54 mg/dl in a CL-Eu night . Mean glucose from 22:00–07:00 and time spent in the range 70–144 mg/dl were 121 mg/dl ( 117–133 mg/dl ) and 69.0 % ( 30.7–77.9 % ) in CL-Eu and 149 mg/dl ( 140–193 mg/dl ) and 48.2 % ( 34.9–72.5 % ) in CL-Hyper , respectively . Conclusions : This study suggests that our novel MPC algorithm can safely and effectively control glucose overnight , also when CL control is initiated during hyperglycemia BACKGROUND Recent studies have shown that an artificial-pancreas system can improve glucose control and reduce nocturnal hypoglycemia . However , it is not known whether such results can be replicated in setting s outside the hospital . METHODS In this multicenter , multinational , r and omized , crossover trial , we assessed the short-term safety and efficacy of an artificial pancreas system for control of nocturnal glucose levels in patients ( 10 to 18 years of age ) with type 1 diabetes at a diabetes camp . In two consecutive overnight sessions , we r and omly assigned 56 patients to receive treatment with an artificial pancreas on the first night and a sensor-augmented insulin pump ( control ) on the second night or to the reverse order of therapies on the first and second nights . Thus , all the patients received each treatment in a r and omly assigned order . The primary end points were the number of hypoglycemic events ( defined as a sensor glucose value of < 63 mg per deciliter [ 3.5 mmol per liter ] for at least 10 consecutive minutes ) , the time spent with glucose levels below 60 mg per deciliter ( 3.3 mmol per liter ) , and the mean overnight glucose level for individual patients . RESULTS On nights when the artificial pancreas was used , versus nights when the sensor-augmented insulin pump was used , there were significantly fewer episodes of nighttime glucose levels below 63 mg per deciliter ( 7 vs. 22 ) and significantly shorter periods when glucose levels were below 60 mg per deciliter ( P=0.003 and P=0.02 , respectively , after adjustment for multiplicity ) . Median values for the individual mean overnight glucose levels were 126.4 mg per deciliter ( interquartile range , 115.7 to 139.1 [ 7.0 mmol per liter ; interquartile range , 6.4 to 7.7 ] ) with the artificial pancreas and 140.4 mg per deciliter ( interquartile range , 105.7 to 167.4 [ 7.8 mmol per liter ; interquartile range , 5.9 to 9.3 ] ) with the sensor-augmented pump . No serious adverse events were reported . CONCLUSIONS Patients at a diabetes camp who were treated with an artificial-pancreas system had less nocturnal hypoglycemia and tighter glucose control than when they were treated with a sensor-augmented insulin pump . ( Funded by Sanofi and others ; Clinical Trials.gov number , NCT01238406 . ) CONTEXT The added benefit of glucagon in artificial pancreas systems for overnight glucose control in type 1 diabetes has not been fully explored . OBJECTIVE The objective of the study was to compare the efficacy of dual-hormone ( insulin and glucagon ) artificial pancreas , single-hormone ( insulin alone ) artificial pancreas , and conventional insulin pump therapy . DESIGN This study was a three-center , three-arm , open-label , r and omized , crossover controlled trial involving three interventions , each applied over a night after a high carbohydrate/high fat meal and a second after exercise to mimic real-life glycemic excursions . SETTING The study was conducted in a home setting . PATIENTS Twenty-eight type 1 diabetes participants ( 21 adults and seven adolescents ) participated in the study . INTERVENTIONS Dual-hormone artificial pancreas , single-hormone artificial pancreas , and conventional pump therapy was activated from 9:00 PM to 7:00 AM . MAIN OUTCOME The main outcome was a proportion of time in target ( 4 - 8 mmol/L ) by continuous glucose monitoring from 11:00 PM to 7:00 AM . Analysis was by intention to treat . RESULTS The median ( interquartile range ) percentage of time-in-target glucose range was 47 % ( 36%-71 % ) for conventional therapy , higher on both single-hormone ( 76 % [ 65%-91 % ] , P < .001 ) and dual-hormone artificial pancreas ( 81 [ 68%-93 % ] , P < .001 ) . The median ( interquartile range ) time spent below 4 mmol/L was 14 % ( 4%-28 % ) for conventional therapy , lower on both single-hormone ( 5 % [ 0%-13 % ] , P = .004 ) and dual-hormone artificial pancreas ( 1 % [ 0%-8 % ] , P < .001 ) . There were 14 hypoglycemic events on conventional therapy compared with six incidences on the single-hormone artificial pancreas ( P = .059 ) and three incidences on the dual-hormone artificial pancreas ( P = .017 ) . None of these outcomes differed significantly between single- and dual-hormone configurations . CONCLUSIONS Single- and dual-hormone artificial pancreas systems both provided better glucose control than conventional therapy . Although the dual-hormone configuration did not increase overnight time-in-target glucose levels , an effect on lowering hypoglycemia risk can not be ruled out Importance Previous clinical trials showing the benefit of continuous glucose monitoring ( CGM ) in the management of type 1 diabetes predominantly have included adults using insulin pumps , even though the majority of adults with type 1 diabetes administer insulin by injection . Objective To determine the effectiveness of CGM in adults with type 1 diabetes treated with insulin injections . Design , Setting , and Participants R and omized clinical trial conducted between October 2014 and May 2016 at 24 endocrinology practice s in the United States that included 158 adults with type 1 diabetes who were using multiple daily insulin injections and had hemoglobin A1c ( HbA1c ) levels of 7.5 % to 9.9 % . Interventions R and om assignment 2:1 to CGM ( n = 105 ) or usual care ( control group ; n = 53 ) . Main Outcomes and Measures Primary outcome measure was the difference in change in central -laboratory – measured HbA1c level from baseline to 24 weeks . There were 18 secondary or exploratory end points , of which 15 are reported in this article , including duration of hypoglycemia at less than 70 mg/dL , measured with CGM for 7 days at 12 and 24 weeks . Results Among the 158 r and omized participants ( mean age , 48 years [ SD , 13 ] ; 44 % women ; mean baseline HbA1c level , 8.6 % [ SD , 0.6 % ] ; and median diabetes duration , 19 years [ interquartile range , 10 - 31 years ] ) , 155 ( 98 % ) completed the study . In the CGM group , 93 % used CGM 6 d/wk or more in month 6 . Mean HbA1c reduction from baseline was 1.1 % at 12 weeks and 1.0 % at 24 weeks in the CGM group and 0.5 % and 0.4 % , respectively , in the control group ( repeated- measures model P < .001 ) . At 24 weeks , the adjusted treatment-group difference in mean change in HbA1c level from baseline was –0.6 % ( 95 % CI , –0.8 % to –0.3 % ; P < .001 ) . Median duration of hypoglycemia at less than < 70 mg/dL was 43 min/d ( IQR , 27 - 69 ) in the CGM group vs 80 min/d ( IQR , 36 - 111 ) in the control group ( P = .002 ) . Severe hypoglycemia events occurred in 2 participants in each group . Conclusions and Relevance Among adults with type 1 diabetes who used multiple daily insulin injections , the use of CGM compared with usual care result ed in a greater decrease in HbA1c level during 24 weeks . Further research is needed to assess longer-term effectiveness , as well as clinical outcomes and adverse effects . Trial Registration clinical trials.gov Identifier : BACKGROUND The safety and effectiveness of automated glycemic management have not been tested in multiday studies under unrestricted outpatient conditions . METHODS In two r and om-order , crossover studies with similar but distinct design s , we compared glycemic control with a wearable , bihormonal , automated , " bionic " pancreas ( bionic-pancreas period ) with glycemic control with an insulin pump ( control period ) for 5 days in 20 adults and 32 adolescents with type 1 diabetes mellitus . The automatically adaptive algorithm of the bionic pancreas received data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon . RESULTS Among the adults , the mean plasma glucose level over the 5-day bionic-pancreas period was 138 mg per deciliter ( 7.7 mmol per liter ) , and the mean percentage of time with a low glucose level ( < 70 mg per deciliter [ 3.9 mmol per liter ] ) was 4.8 % . After 1 day of automatic adaptation by the bionic pancreas , the mean ( ±SD ) glucose level on continuous monitoring was lower than the mean level during the control period ( 133±13 vs. 159±30 mg per deciliter [ 7.4±0.7 vs. 8.8±1.7 mmol per liter ] , P<0.001 ) and the percentage of time with a low glucose reading was lower ( 4.1 % vs. 7.3 % , P=0.01 ) . Among the adolescents , the mean plasma glucose level was also lower during the bionic-pancreas period than during the control period ( 138±18 vs. 157±27 mg per deciliter [ 7.7±1.0 vs. 8.7±1.5 mmol per liter ] , P=0.004 ) , but the percentage of time with a low plasma glucose reading was similar during the two periods ( 6.1 % and 7.6 % , respectively ; P=0.23 ) . The mean frequency of interventions for hypoglycemia among the adolescents was lower during the bionic-pancreas period than during the control period ( one per 1.6 days vs. one per 0.8 days , P<0.001 ) . CONCLUSIONS As compared with an insulin pump , a wearable , automated , bihormonal , bionic pancreas improved mean glycemic levels , with less frequent hypoglycemic episodes , among both adults and adolescents with type 1 diabetes mellitus . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; Clinical Trials.gov numbers , NCT01762059 and NCT01833988 . ) BACKGROUND Closed-loop insulin delivery is a promising option to improve glycaemic control and reduce the risk of hypoglycaemia . We aim ed to assess whether overnight home use of automated closed-loop insulin delivery would improve glucose control . METHODS We did this open-label , multicentre , r and omised controlled , crossover study between Dec 1 , 2012 , and Dec 23 , 2014 , recruiting patients from three centres in the UK . Patients aged 18 years or older with type 1 diabetes were r and omly assigned to receive 4 weeks of overnight closed-loop insulin delivery ( using a model-predictive control algorithm to direct insulin delivery ) , then 4 weeks of insulin pump therapy ( in which participants used real-time display of continuous glucose monitoring independent of their pumps as control ) , or vice versa . Allocation to initial treatment group was by computer-generated permuted block r and omisation . Each treatment period was separated by a 3 - 4 week washout period . The primary outcome was time spent in the target glucose range of 3·9 - 8·0 mmol/L between 0000 h and 0700 h. Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01440140 . FINDINGS We r and omly assigned 25 participants to initial treatment in either the closed-loop group or the control group , patients were later crossed over into the other group ; one patient from the closed-loop group withdrew consent after r and omisation , and data for 24 patients were analysed . Closed loop was used over a median of 8·3 h ( IQR 6·0 - 9·6 ) on 555 ( 86 % ) of 644 nights . The proportion of time when overnight glucose was in target range was significantly higher during the closed-loop period compared to during the control period ( mean difference between groups 13·5 % , 95 % CI 7·3 - 19·7 ; p=0·0002 ) . We noted no severe hypoglycaemic episodes during the control period compared with two episodes during the closed-loop period ; these episodes were not related to closed-loop algorithm instructions . INTERPRETATION Unsupervised overnight closed-loop insulin delivery at home is feasible and could improve glucose control in adults with type 1 diabetes . FUNDING Diabetes UK OBJECTIVE The Pediatric Artificial Pancreas ( PedArPan ) project tested a children-specific version of the modular model predictive control ( MMPC ) algorithm in 5- to 9-year-old children during a camp . RESEARCH DESIGN AND METHODS A total of 30 children , 5- to 9-years old , with type 1 diabetes completed an outpatient , open-label , r and omized , crossover trial . Three days with an artificial pancreas ( AP ) were compared with three days of parent-managed sensor-augmented pump ( SAP ) . RESULTS Overnight time-in-hypoglycemia was reduced with the AP versus SAP , median ( 25th–75th percentiles ) : 0.0 % ( 0.0–2.2 ) vs. 2.2 % ( 0.0–12.3 ) ( P = 0.002 ) , without a significant change of time-in-target , mean : 56.0 % ( SD 22.5 ) vs. 59.7 % ( 21.2 ) ( P = 0.430 ) , but with increased mean glucose 173 mg/dL ( 36 ) vs. 150 mg/dL ( 39 ) ( P = 0.002 ) . Overall , the AP granted a threefold reduction of time-in-hypoglycemia ( P < 0.001 ) at the cost of decreased time-in-target , 56.8 % ( 13.5 ) vs. 63.1 % ( 11.0 ) ( P = 0.022 ) and increased mean glucose 169 mg/dL ( 23 ) vs. 147 mg/dL ( 23 ) ( P < 0.001 ) . CONCLUSIONS This trial , the first outpatient single-hormone AP trial in a population of this age , shows feasibility and safety of MMPC in young children . Algorithm retuning will be performed to improve efficacy |
10,583 | 21,306,211 | In the meantime , with several recent systematic review s of published evidence supporting a robust and independent association of CKD with subsequent cerebrovascular disease risk , optimal implementation of established stroke risk reduction strategies in individuals with CKD might improve stroke outcomes . | Chronic kidney disease ( CKD ) , a growing public health concern , carries a substantial burden and is a well-known independent predictor of coronary artery disease outcomes .
In the last few years , attention has been focused on various CKD indices and their prognostic impact among individuals with , or at risk for , cerebrovascular disease .
Mounting evidence suggests that the presence of CKD in various forms ( filtration rate and barrier impairments ) , and even at mild stages , is associated with surrogate cerebrovascular disease markers , confers higher future risk of ischemic and hemorrhagic cerebrovascular events , and predicts poor clinical outcomes after an index stroke .
However , a better underst and ing of these links is required .
For instance , the direction and strength of the association of CKD with a heterogeneous vascular disease entity , such as cerebrovascular disease ( vs coronary artery disease ) , appears to be greatly influenced by stroke type and ischemic stroke subtype , as well as CKD index and CKD stage . | Objective To determine the prevalence and the prognostic significance of microalbuminuria in patients after aneurysmal subarachnoid hemorrhage ( SAH ) . Design Prospect i ve and observational clinical study . Setting Multidisciplinary intensive care unit . Patients Fifty-one consecutive patients who underwent aneurysm clipping or endovascular surgery after SAH ; 8 patients who underwent surgical clipping for unruptured intracerebral aneurysm served as control . InterventionNone . Measurements and Results General clinical and neurological data were recorded on admission . Urine was collected preoperatively and daily for up to 7 days postoperatively for measuring the urinary microalbumin/creatinine ratio . The Glasgow Coma Scale ( GCS ) score was also determined on admission and daily for up to 7 days after operation . Neurological outcome was assessed using the Glasgow Outcome Scale ( GOS ) at 3 months after stroke . The prevalence rates of microalbuminuria were 74.5 % in SAH and 37.5 % in the control . Among the 51 patients , 25 had unfavorable neurological outcome ( GOS 1–3 ) . The areas under the receiver operator characteristic curves showed that the highest urinary microalbumin/creatinine ratio and the lowest GCS score during the first 8 days were the significant predictors of unfavorable neurological outcome . The threshold value , sensitivity , specificity , and likelihood ratio for the highest urinary microalbumin/creatinine ratio were 200 mg/g , 60 % [ 95 % confidence interval ( CI ) 41–79 ] , 96 % ( 95 % CI 88–100 ) , and 15.6 ( 95 % CI 9.1–26.7 ) , respectively . Conclusions This study confirms a high prevalence of microalbuminuria in the SAH patients , and it suggests that the highest urinary microalbumin/creatinine ratio > 200 mg/g during the first 8 days is a significant predictor of unfavorable neurological outcome Background —Elevated urine albumin excretion ( UAER ) is a modifiable risk factor for renal and cardiovascular disease in type 2 diabetes . Blockade of the renin-angiotensin system lowers UAER , but whether this effect is independent of blood pressure ( BP ) reduction remains controversial . The MicroAlbuminuria Reduction With VALsartan ( MARVAL ) study was design ed to evaluate the BP-independent effect of valsartan on UAER in type 2 diabetic patients with microalbuminuria . Methods and Results —Three hundred thirty-two patients with type 2 diabetes and microalbuminuria , with or without hypertension , were r and omly assigned to 80 mg/d valsartan or 5 mg/d amlodipine for 24 weeks . A target BP of 135/85 mm Hg was aim ed for by dose-doubling followed by addition of bendrofluazide and doxazosin whenever needed . The primary end point was the percent change in UAER from baseline to 24 weeks . The UAER at 24 weeks was 56 % ( 95 % CI , 49.6 to 63.0 ) of baseline with valsartan and 92 % ( 95 % CI , 81.7 to 103.7 ) of baseline with amlodipine , a highly significant between-group effect ( P < 0.001 ) . Valsartan lowered UAER similarly in both the hypertensive and normotensive subgroups . More patients reversed to normoalbuminuria with valsartan ( 29.9 % versus 14.5%;P = 0.001 ) . Over the study period , BP reductions were similar between the two treatments ( systolic/diastolic 11.2/6.6 mm Hg for valsartan , 11.6/6.5 mm Hg for amlodipine ) and at no time point was there a between-group significant difference in BP values in either the hypertensive or the normotensive subgroup . Conclusions —For the same level of attained BP and the same degree of BP reduction , valsartan lowered UAER more effectively than amlodipine in patients with type 2 diabetes and microalbuminuria , including the subgroup with baseline normotension . This indicates a BP-independent antiproteinuric effect of valsartan Microalbuminuria is a strong and independent indicator of increased cardiovascular risk among individuals with and without diabetes . Therefore , microalbuminuria can be used for stratification of risk for cardiovascular disease . Once microalbuminuria is present , cardiovascular risk factor reduction should be more " aggressive . " The nature of the link between microalbuminuria and cardiovascular risk , however , remains poorly understood . There is no strong evidence that microalbuminuria causes atherothrombosis or that atherothrombosis causes microalbuminuria . Many studies have tested the hypothesis that a common risk factor underlies the association between microalbuminuria and cardiovascular disease but , again , have found no strong evidence in favor of this contention . At present , the most likely possibility is that a common pathophysiologic process , such as endothelial dysfunction , chronic low- grade inflammation , or increased transvascular leakage of macromolecules , underlies the association between microalbuminuria and cardiovascular disease , but more and prospect i ve studies of these hypotheses are needed Background —Microalbuminuria is associated with increased risk of cardiovascular events . We assessed whether therapeutic intervention aim ed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects ( 15 to 300 mg/24 hours ) . Methods and Results —From the Prevention of Renal and Vascular Endstage Disease ( PREVEND ) cohort ( n=8592 ) , 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial ( PREVEND IT ) . Of these subjects , 864 were r and omized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo . The mean follow-up was 46 months , and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity . Mean age was 51±12 years ; 65 % of subjects were male , and 3.4 % had a previous cardiovascular event . Mean cholesterol level was 5.8±1.0 mmol/L , mean systolic/diastolic blood pressure was 130±18/76±10 mm Hg , and median urinary albumin excretion was 22.8 ( 15.8 to 41.3 ) mg/24 hours . The primary end point occurred in 45 subjects ( 5.2 % ) . Fosinopril reduced urinary albumin excretion by 26 % ( P<0.001 ) . Subjects treated with fosinopril showed a 40 % lower incidence of the primary end point ( hazard ratio 0.60 [ 95 % CI 0.33 to 1.10 ] , P=0.098 , log-rank ) . Pravastatin did not reduce urinary albumin excretion , and subjects treated with pravastatin showed a 13 % lower incidence of the primary end point than subjects in the placebo group ( 0.87 [ 0.49 to 1.57 ] , P=0.649 , log-rank ) . Conclusions —In microalbuminuric subjects , treatment with fosinopril had a significant effect on urinary albumin excretion . In addition , fosinopril treatment was associated with a trend in reducing cardiovascular events . Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events Urinary albumin excretion is a predictor for cardiovascular mortality and morbidity . We investigated which parameters determine baseline urinary albumin excretion in nondiabetic subjects , without renal disease . In addition , we evaluated the parameters that predict the albuminuria-lowering efficacy of an angiotensin-converting enzyme inhibitor . In this sub study of the Prevention of Renal and Vascular Endstage Disease Intervention Trial , 384 microalbuminuric patients were included . Patient and biochemical characteristics were obtained at baseline and after 3 months of double-blinded , r and omized treatment ( fosinopril 20 mg or placebo ) . Mean age was 51.1±11.5 years , and 65.6 % were male . Median urinary albumin excretion was 22.2 mg per 24 hours . At baseline , mean arterial pressure ( & bgr;st and ardized=0.161 ; P=0.006 ) , urinary sodium excretion ( & bgr;st and ardized=0.154 ; P=0.011 ) , and estimated renal function were independently associated with albumin excretion . In these predominantly normotensive to prehypertensive subjects , fosinopril reduced albumin excretion by 18.5 % versus a 6.1 % increase on placebo after 3 months ( P<0.001 ) . Fosinopril use and blood pressure reduction independently predicted the change in urinary albumin excretion . Baseline urinary albumin excretion independently predicted the antialbuminuric effect of fosinopril ( & bgr;st and ardized=−0.303 ; P<0.001 ) . In conclusion , at baseline , sodium intake and blood pressure were positively associated with urinary albumin excretion . Fosinopril reduced albuminuria more than might be expected from its blood pressure – lowering effect alone , and this effect was more outspoken in subjects with higher baseline albumin excretion . Based on our data , we hypothesize that angiotensin-converting enzyme inhibition may result in superior cardiovascular protection when compared with other blood pressure – lowering agents in subjects with higher baseline levels of albuminuria BACKGROUND Silent brain infa rcts are frequently seen on magnetic resonance imaging ( MRI ) in healthy elderly people and may be associated with dementia and cognitive decline . METHODS We studied the association between silent brain infa rcts and the risk of dementia and cognitive decline in 1015 participants of the prospect i ve , population -based Rotterdam Scan Study , who were 60 to 90 years of age and free of dementia and stroke at base line . Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period . We performed Cox proportional-hazards and multiple linear-regression analyses , adjusted for age , sex , and level of education and for the presence or absence of subcortical atrophy and white-matter lesions . RESULTS During 3697 person-years of follow-up ( mean per person , 3.6 years ) , dementia developed in 30 of the 1015 participants . The presence of silent brain infa rcts at base line more than doubled the risk of dementia ( hazard ratio , 2.26 ; 95 percent confidence interval , 1.09 to 4.70 ) . The presence of silent brain infa rcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function . Silent thalamic infa rcts were associated with a decline in memory performance , and nonthalamic infa rcts with a decline in psychomotor speed . When participants with silent brain infa rcts at base line were subdivided into those with and those without additional infa rcts at follow-up , the decline in cognitive function was restricted to those with additional silent infa rcts . CONCLUSIONS Elderly people with silent brain infa rcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions Few data are available to clarify whether changes in albuminuria over time translate to changes in cardiovascular risk . The aim of the present study was to examine whether changes in albuminuria during 4.8 years of antihypertensive treatment were related to changes in risk in 8206 patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension ( LIFE ) study . Urinary albumin/creatinine ratio ( UACR ) was measured at baseline and annually . Time-varying albuminuria was closely related to risk for the primary composite end point ( ie , when UACR decreased during treatment , risk was reduced accordingly ) . When the population was divided according to median baseline value ( 1.21 mg/mmol ) and median year 1 UACR ( 0.67 mg/mmol ) , risk increased stepwise and significantly for the primary composite end point from those with low baseline/low year 1 ( 5.5 % ) , to low baseline/high year 1 ( 8.6 % ) , to high baseline/low year 1 ( 9.4 % ) , and to high baseline/high year 1 ( 13.5 % ) values . Similar significant , stepwise increases in risk were seen for the components of the primary composite end point ( cardiovascular mortality , stroke , and myocardial infa rct ion ) . The observation that changes in UACR during antihypertensive treatment over time translated to changes in risk for cardiovascular morbidity and mortality was not explained by in-treatment level of blood pressure . We propose that monitoring of albuminuria should be an integrated part of the management of hypertension . If albuminuria is not decreased by the patient ’s current antihypertensive and other treatment , further intervention directed toward blood pressure control and other modifiable risks should be considered Background and Purpose — The prevalence of silent brain infa rcts in healthy elderly people is high , and these lesions are associated with an increased risk of stroke . The incidence of silent brain infa rcts is unknown . We investigated the incidence and cardiovascular risk factors for silent brain infa rcts . Methods — The Rotterdam Scan Study is a prospect i ve , population -based cohort study of 1077 participants 60 to 90 years of age . All participants underwent cranial MRI in 1995 to 1996 , and 668 participants had a second MRI in 1999 to 2000 ( response rate , 70 % ) with a mean interval of 3.4 years . We assessed cardiovascular risk factors by interview and physical examination at baseline . Associations between risk factors and incident silent infa rcts were analyzed by multiple logistic regression . Results — Ninety-three participants ( 14 % ) had ≥1 new infa rcts on the second MRI ; of these , 81 had only silent and 12 had symptomatic infa rcts . The incidence of silent brain infa rcts strongly increased with age and was 5 times higher than that of symptomatic stroke . A prevalent silent brain infa rct strongly predicted a new silent infa rct on the second MRI ( age- and sex-adjusted odds ratio , 2.9 ; 95 % confidence interval , 1.7 to 5.0 ) . Age , blood pressure , diabetes mellitus , cholesterol and homocysteine levels , intima-media thickness , carotid plaques , and smoking were associated with new silent brain infa rcts in participants without prevalent infa rcts . Conclusions — The incidence of silent brain infa rcts on MRI in the general elderly population strongly increases with age . The cardiovascular risk factors for silent brain infa rcts are similar to those for stroke Background and Purpose — White matter hyperintensities have been associated with increased risk of stroke , cognitive decline , and dementia . Chronic kidney disease is a risk factor for vascular disease and has been associated with inflammation and endothelial dysfunction , which have been implicated in the pathogenesis of white matter hyperintensities . Few studies have explored the relationship between chronic kidney disease and white matter hyperintensities . Methods — The Northern Manhattan Study is a prospect i ve , community-based cohort of which a subset of stroke-free participants underwent MRIs . MRIs were analyzed quantitatively for white matter hyperintensities volume , which was log-transformed to yield a normal distribution ( log-white matter hyperintensity volume ) . Kidney function was modeled using serum creatinine , the Cockcroft-Gault formula for creatinine clearance , and the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate . Creatinine clearance and estimated glomerular filtration rate were trichotomized to 15 to 60 mL/min , 60 to 90 mL/min , and > 90 mL/min ( reference ) . Linear regression was used to measure the association between kidney function and log-white matter hyperintensity volume adjusting for age , gender , race – ethnicity , education , cardiac disease , diabetes , homocysteine , and hypertension . Results — Baseline data were available on 615 subjects ( mean age 70 years , 60 % women , 18 % whites , 21 % blacks , 62 % Hispanics ) . In multivariate analysis , creatinine clearance 15 to 60 mL/min was associated with increased log-white matter hyperintensity volume ( & bgr ; 0.322 ; 95 % CI , 0.095 to 0.550 ) as was estimated glomerular filtration rate 15 to 60 mL/min ( & bgr ; 0.322 ; 95 % CI , 0.080 to 0.564 ) . Serum creatinine , per 1-mg/dL increase , was also positively associated with log-white matter hyperintensity volume ( & bgr ; 1.479 ; 95 % CI , 1.067 to 2.050 ) . Conclusions — The association between moderate – severe chronic kidney disease and white matter hyperintensity volume highlights the growing importance of kidney disease as a possible determinant of cerebrovascular disease and /or as a marker of microangiopathy Chronic kidney disease ( CKD ) is associated with a high risk of cardiovascular disease , but evidence regarding the effectiveness of interventions to reduce that risk is lacking . The Perindopril Protection against Recurrent Stroke Study ( PROGRESS ) study enrolled 6105 participants with cerebrovascular disease and r and omly allocated them to perindopril-based blood pressure-lowering therapy or placebo . Individuals with CKD were at approximately 1.5-fold greater risk of major vascular events , stroke , and coronary heart disease , and were more than twice as likely to die ( all P < or = 0.002 ) . Perindopril-based treatment reduced the risk of major vascular events by 30 % and stroke by 35 % among subjects with CKD , and the absolute effects of treatment were 1.7-fold greater for those with CKD than for those without . Considering patients with CKD and a history of cerebrovascular disease , perindopril prevented one stroke or other cardiovascular event among every 11 patients treated over five years . In conclusion , kidney function should be considered when determining the need for blood pressure lowering therapy in patients with cerebrovascular disease Context Does cystatin C , glomerular filtration rate ( GFR ) , or creatinine better predict mortality ? Contribution This study examined long-term outcomes of 825 adults with nondiabetic chronic kidney disease who had participated in 2 trials of protein restriction in the early 1990s . Higher cystatin C and creatinine levels and lower GFR at baseline were all associated with an increased risk for kidney failure and for all-cause and cardiovascular mortality . Associations between cystatin C and cardiovascular mortality seemed slightly stronger than those between GFR or creatinine and cardiovascular mortality . Implication Cystatin C levels seem to be at least as strongly associated with mortality as either GFR or creatinine concentration in adults with nondiabetic chronic kidney disease . The Editors Mild to moderate reductions in kidney function are associated with a marked increase in the risk for cardiovascular disease ( CVD ) ( 14 ) . Assessing the degree of kidney function is now recognized as an important component of risk stratification for CVD morbidity and mortality . Cystatin C is a novel measure of kidney function ( 5 , 6 ) that seems to be less sensitive than creatinine to factors other than glomerular filtration rate ( GFR ) , particularly muscle mass ( 7 ) . Thus , the serum cystatin C level may be a better marker of kidney function than the serum creatinine concentration , especially in elderly persons and in the setting of mild kidney dysfunction ( 8 , 9 ) . Cystatin C is easily measured in serum , making it a practical alternative to measured GFR , which is too cumbersome for clinical practice . Studies in elderly persons suggest that the cystatin C level has a stronger association with CVD events than do creatinine concentration and GFR estimated from serum creatinine ( 1012 ) . No study has compared cystatin C and serum creatinine as risk factors for outcomes in persons with established chronic kidney disease ( CKD ) . Furthermore , no study has compared outcomes on the basis of cystatin C level versus measured GFR , the gold st and ard for measurement of kidney function . We examined the associations of cystatin C level , creatinine concentration , and measured GFR with all-cause and CVD mortality and kidney failure in patients with CKD stages 3 to 4 . Methods Study Sample The Modification of Diet in Renal Disease ( MDRD ) Study , conducted from 1989 to 1993 , was a r and omized , controlled trial of the effect of dietary protein restriction and blood pressure control on the progression of kidney disease ( 13 ) . In brief , 840 patients with predominantly nondiabetic kidney disease and reduced GFR were included in the MDRD Study . Key inclusion criteria were age 18 to 70 years and a serum creatinine concentration of 106.08 to 618.81 mol/L ( 1.2 to 7.0 mg/dL ) in women and 123.76 to 618.81 mol/L ( 1.4 to 7.0 mg/dL ) in men . Glomerular filtration rate was measured at screening and again after a 3-month baseline period , during which patients were instructed about the study procedures , dietary protein intake , and control of blood pressure . We use the term screening GFR to refer to the first baseline GFR for screening and the term 3-month baseline GFR to refer to the GFR measured at the end of the 3-month baseline period . The range of screening GFR ( 10 to 65 mL/min per 1.73 m2 ) was less restrictive than the range for 3-month baseline GFR ( 13 to 55 mL/min per 1.73 m2 ) . Patients were eligible for study A if their 3-month baseline GFR was 25 to 55 mL/min per 1.73 m2 and for study B if it was 13 to 24 mL/min per 1.73 m2 . Patients in studies A and B were combined for the current analyses . Because the measured GFR ranged from 13 to 55 mL/min per 1.73 m2 , with 6 % of the cohort having a GFR less than 15 mL/min per 1.73 m2 , the study sample consists predominantly of patients with stage 3 or 4 CKD , as defined by the National Kidney Foundation Kidney Disease Outcomes and Quality Initiative ( 14 ) . Baseline Measurement of Kidney Function Glomerular filtration rate was measured by using iothalamate clearance ( 15 ) . After subcutaneous injection of 125I-iothalamate , investigators collected 4 consecutive urine and 5 serum sample s after an equilibration period of 1 hour . Measurements of serum and urine radioactivity were performed at the central MDRD Study laboratory . Glomerular filtration rate was calculated as the time-weighted averages of urine excretion rates and the serum concentration of the marker over the collection periods and was adjusted for body surface area . Estimated GFR was calculated from baseline serum creatinine concentration by using the 4-variable MDRD Study equation : 186.3(serum creatinine concentration1.154)(age0.203)1.212 ( if black)0.742 ( if female ) ( 16 ) . Serum creatinine was measured at baseline at the Clevel and Clinic Foundation , Clevel and , Ohio , by using the kinetic alkaline picrate assay on a Beckman Astra CX3 ( Beckman , Fullerton , California ) . Cystatin C was measured in frozen sample s collected at baseline from 825 participants of the MDRD Study . Sample s were assayed for cystatin C by using a particle-enhanced immunonephelometric assay ( N Latex Cystatin C , Dade Behring , Deerfield , Illinois ) . Measurement of a quality control specimen was included in each analytic run . Calculation of the SD and the coefficient of variation demonstrated an interrun precision for the assay of 5.6 % ( mean cystatin C level , 1.62 mg/L [ SD , 0.09 ] ; n= 14 ) . Outcomes We assessed 4 outcomes : all-cause mortality , CVD mortality , kidney failure ( the need for renal replacement therapy with dialysis or transplantation ) , and a composite outcome of kidney failure and all-cause mortality . We ascertained survival status and cause of death from the National Death Index and ascribed deaths to CVD if the primary cause of death was International Classification of Diseases , Ninth Revision , codes 390 to 459 or if kidney disease was listed as the primary cause of death and CVD was the secondary cause . We defined survival time as the time from r and omization to death or end of follow-up ( 31 December 2000 ) . We obtained kidney failure outcomes from the U.S. Renal Data System . The institutional review boards of The Clevel and Clinic , Clevel and , Ohio , and TuftsNew Engl and Medical Center , Boston , Massachusetts , approved the data collection procedures . Statistical Analysis We compared baseline characteristics of the study sample across quartiles of serum cystatin C values and calculated P values for linear trend . We also compared baseline characteristics across quartiles of estimated GFR ( Appendix Table ) . Because serum cystatin C and creatinine vary as the inverse of GFR , we used the inverse of serum cystatin C ( 1/cystatin C ) and creatinine ( 1/creatinine ) to facilitate direct comparison with GFR . Pearson correlations were used to examine univariate associations among the 3 measures of kidney function . We calculated incidence rates for all-cause mortality , CVD mortality , and kidney failure by quartiles of each baseline measure of kidney function : 1/creatinine , GFR , estimated GFR , and 1/cystatin C. Appendix Table . Baseline Characteristics , by Quartile of Estimated Glomerular Filtration Rate * We compared the association of the baseline measures of kidney function with outcomes by using unadjusted and adjusted Cox proportional hazards models . Covariates specified a priori in the adjusted models were age , race , sex , smoking , history of diabetes and CVD , body mass index , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , systolic blood pressure , and log-transformed proteinuria . Models for kidney failure and the composite outcome were adjusted for cause of kidney disease in addition to the previously listed covariates . The models for the mortality outcomes included patients with kidney failure and were censored only at death or the end of follow-up . The models for kidney failure and the composite outcome were censored at kidney failure , death , or the end of follow-up . We repeated the adjusted Cox models for each of the 4 outcomes after additional adjustment for log-transformed C-reactive protein ( CRP ) level . We entered the measures of kidney function as continuous variables ( 1/creatinine , GFR , and 1/cystatin ) and calculated the hazard ratios and 95 % CIs per 1-SD change in each measure to allow a st and ardized comparison across measures with the same scale . We tested for nonlinearity by examining the functional form of the relationship of all-cause mortality risk and CVD mortality risk versus each marker of kidney function as a continuous variable while controlling for the covariates by fitting a cubic smoothing spline . We tested proportional hazards assumptions by using log(log ) survival plots and plots of Schoenfeld residuals versus survival time . We used S-Plus , version 6.2 ( Insightful Corp. , Seattle , Washington ) , and SPSS , version 14.0 ( SPSS , Chicago , Illinois ) , to perform the statistical analyses . Additional Analyses We repeated the adjusted Cox models for each outcome by using 2 additional measures of kidney function . First , we used estimated GFR because measuring GFR is impractical in clinical practice and research setting s and , hence , GFR estimated from the serum creatinine concentration is often used as a surrogate measure . Second , to reduce variability in GFR measurements , we used the average of 2 baseline iothalamate GFR measurements performed 3 months apart . Sensitivity Analyses Transformation of cystatin C and serum creatinine values may make the expressions of their effects relative to SDs less comparable than if no transformation had been performed . To address this issue , we repeated the unadjusted Cox models with hazard ratios comparing the 80th to the 20th percentile of decreasing kidney function . Because entry criteria into the MDRD Study were based on GFR values , the range of GFR , but not of cystatin C or creatinine , is artificially restricted by study design . To address this limitation , we performed 2 sets of sensitivity analyses . First , because study entry was based Serum cystatin C is a novel marker of renal function cl aim ed to be superior to plasma creatinine . We assessed both parameters in young normotensive subjects ( n = 12 ; 6 men ; mean age , 25 + /- 2 years ) and elderly normotensive and hypertensive subjects ( n = 41 ; 19 men ; mean age , 67 + /- 6 years ) . Glomerular filtration rate ( GFR ) was measured in all individuals using the inulin clearance ( C(in ) ) technique . Compared with young subjects , mean GFR was modestly but significantly ( P : < 0.001 ) less in elderly subjects ( young , 119 + /- 11 mL/min/1.73 m(2 ) versus elderly , 104 + /- 12 mL/min/1.73 m(2 ) ) . Mean plasma creatinine concentration was identical in both groups ( young , 0.93 + /- 0.11 mg/dL versus elderly , 0.93 + /- 0.10 mg/dL ; P : < 0.90 ) . Mean serum cystatin C concentration was significantly ( P : < 0.001 ) greater in elderly subjects ( 0.84 + /- 0.10 mg/L ) compared with young subjects ( 0.69 + /- 0.08 mg/L ) . In all but one elderly subject , plasma creatinine concentration was within the 95 % confidence interval of plasma creatinine concentration in young subjects . Eleven of 41 elderly subjects ( 27 % ) had GFRs less than the lower 95 % confidence interval , respectively , and 12 of 41 elderly subjects ( 29 % ) had a serum cystatin C concentration greater than the upper 95 % confidence interval in young subjects . The correlation between serum cystatin C concentration and C(in ) ( r = -0.65 ; P : < 0.001 ) was considerably better than between plasma creatinine concentration and C(in ) ( r = -0.30 ; P : < 0.02 ) . Serum cystatin C concentration is a better marker of renal dysfunction ( ie , reduced GFR ) than plasma creatinine concentration , at least in elderly subjects with plasma creatinine concentrations within the normal range BACKGROUND AND PURPOSE No prospect i ve studies have examined the rate of symptomatic ischemic or hemorrhagic stroke in patients with subcortical silent brain infa rct ion ( SSBI ) who were otherwise neurologically normal at entry into the study . This report investigates SSBI , detected by MRI , as a clinical stroke risk factor . METHODS MRI scans were performed in 933 neurologically normal adults ( 30 to 81 years ; mean age , 57.5 + /- 9.2 years ) without history of cerebrovascular diseases who received our health screening of the brain 1 to 7 years before investigation . We obtained information of their clinical stroke onset through sending out a question naire for subjects . We detected SSBI ( focal T2 hyperintensities larger than 3 mm with correlative T1 hypointensity ) , FWT2HL ( focal white matter T2 hypertensity lesions similar to SSBI but without correlative T2-hypointensity ) , and PVH ( periventricular hyperintensity ) by MRI . Age , sex , family history of stroke , history of hypertension , diabetes mellitus , lipids , hematocrit , blood pressure , fasting blood sugar , smoking , alcohol habits , ischemic changes on electrocardiogram , and sclerotic changes of retinal arteries were included in the analysis . RESULTS Incidence of SSBI was 10.6 % in all subjects . No cortical infa rct was detected in this series . Multiple logistic regression analysis showed that hypertension ( odds ratio [ OR ] , 4.07 ; 95 % CI , 2.57 to 6.45 ) , diabetes ( OR , 2.41 ; 95 % CI , 1.20 to 4.85 ) , alcohol habits > or = 58 g/day ( OR , 2.58 ; 95 % CI , 1.50 to 4.45 ) , retinal artery sclerosis ( OR , 2.14 ; 95 % CI , 1.32 to 2.38 ) , and age ( OR , 1.77 ; 95 % CI , 1.32 to 2.38 ) were significant and independent risk factors for SSBI . For FWT2HL , hypertension ( OR , 4.49 ; 95 % CI , 2.54 to 7.96 ) and age ( OR , 2.08 ; 95 % CI , 1.45 to 3.00 ) were also independent risk factors . Risk factors for PVH were age ( OR , 3.46 ; 95 % CI , 2.23 to 5.36 ) , hypertension ( OR , 3.06 ; 95 % CI , 1.62 to 5.78 ) , and retinal artery sclerosis ( OR , 2.25 ; 95 % CI , 1.02 to 4.96 ) . We found 14 brain infa rct ions , 4 brain hemorrhages , and 1 subarachnoid hemorrhage during observation . Annual incidence of clinical stroke was higher in the subjects with SSBI than in those without focal lesions ( 10.1 % versus 0.77 % ) . ORs for clinical stroke onset were 10.48 for SSBI ( 95 % CI , 3.63 to 30.21 ) and 4.81 for FWT2HL ( 95 % CI , 1.13 to 20.58 ) . The PVH did not relate to clinical stroke onset . CONCLUSIONS The strong association of SSBI , FWT2HL , and PVH with hypertension suggests a common underlying mechanism ( presumably small-vessel vasculopathy ) . The SSBI showed the most significant association for clinical subcortical stroke . The FWT2HL was also a risk factor for the stroke but was less significant than SSBI . The subjects with SSBI should be considered at high risk for clinical subcortical brain infa rct ion or brain hemorrhage BACKGROUND Although end-stage renal disease has been associated with cognitive impairment , the relation between lesser degrees of chronic kidney disease ( CKD ) and cognitive impairment is less well understood . METHODS Data for 1,015 women enrolled at 10 of the 20 Heart Estrogen/Progestin Replacement Study clinical sites were analyzed . All participants were younger than 80 years and had established coronary artery disease at study entry . Participants underwent 6 st and ard tests of cognitive function evaluating various domains . Unadjusted , residual age- and race-adjusted , and multivariable-adjusted linear and logistic regression models were used . Glomerular filtration rate ( GFR ) was estimated using the Modification of Diet in Renal Disease regression equation . In addition to analyses across the spectrum of GFRs , CKD was categorized as mild ( estimated GFR [ eGFR ] , 45 to 60 mL/min/1.73 m2 ) , moderate ( eGFR , 30 to 44 mL/min/1.73 m2 ) , and severe ( eGFR , < 30 mL/min/1.73 m2 ) according to a modification of recently established classification guidelines . RESULTS Mean eGFR was 57 + /- 14 mL/min/1.73 m2 . In multivariable analyses , eGFR was associated significantly with impairment in global cognition , executive function , language , and memory ( approximately 15 % to 25 % increase in risk for dysfunction/10-mL/min/1.73 m2 decrement in eGFR ) . Associations among eGFR and cognitive function were independent of residual effects of age and race ( 2 key determinants of GFR ) and the contributions of education , lifestyle factors , stroke , diabetes , and other laboratory variables . CONCLUSION CKD is associated with cognitive impairment in menopausal women with coronary artery disease BACKGROUND Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes . We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes . METHODS ACCORD was a parallel-group , r and omised trial done in 77 clinical sites in North America . People with diabetes , high HbA(1c ) concentrations ( > 7.5 % ) , and cardiovascular disease ( or > or=2 cardiovascular risk factors ) were r and omly assigned by central r and omisation to intensive ( target haemoglobin A(1c ) [ HbA(1c ) ] of < 6.0 % ) or st and ard ( 7.0 - 7.9 % ) glycaemic therapy . In this analysis , the prespecified composite outcomes were : dialysis or renal transplantation , high serum creatinine ( > 291.7 micromol/L ) , or retinal photocoagulation or vitrectomy ( first composite outcome ) ; or peripheral neuropathy plus the first composite outcome ( second composite outcome ) . 13 prespecified secondary measures of kidney , eye , and peripheral nerve function were also assessed . Investigators and participants were aware of treatment group assignment . Analysis was done for all patients who were assessed for microvascular outcomes , on the basis of treatment assignment , irrespective of treatments received or compliance to therapies . ACCORD is registered with Clinical Trials.gov , number NCT00000620 . FINDINGS 10 251 patients were r and omly assigned , 5128 to the intensive glycaemia control group and 5123 to st and ard group . Intensive therapy was stopped before study end because of higher mortality in that group , and patients were transitioned to st and ard therapy . At transition , the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the st and ard group ( HR 1.00 , 95 % CI 0.88 - 1.14 ; p=1.00 ) , and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 ( 0.96 , 0.89 - 1.02 ; p=0.19 ) . Results were similar at study end ( first composite outcome 556 of 5119 vs 586 of 5115 [ HR 0.95 , 95 % CI 0.85 - 1.07 , p=0.42 ] ; and second 1956 of 5119 vs 2046 of 5115 , respectively [ 0.95 , 0.89 - 1.01 , p=0.12 ] ) . Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes , but delayed the onset of albuminuria and some measures of eye complications and neuropathy . Seven secondary measures at study end favoured intensive therapy ( p<0.05 ) . INTERPRETATION Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality , increased weight gain , and high risk for severe hypoglycaemia . FUNDING US National Institutes of Health ; National Heart , Lung , and Blood Institute ; National Institute of Diabetes and Digestive and Kidney Diseases ; National Institute on Aging ; National Eye Institute ; Centers for Disease Control and Prevention ; and General Clinical Research Centers Excretion of albumin in the urine is highly variable , ranging from nondetectable quantities to milligrams of albumin and even grams of albumin . Microalbuminuria is defined as low levels of urinary albumin excretion of 30 to 300 mg/d . Microalbuminuria is highly prevalent ; in hypertensive and diabetic population s , its prevalence varies from 10 to 40 % . It is interesting that microalbuminuria also is found frequently in seemingly healthy individuals ( 5 to 7 % ) . The variable excretion of albumin in the urine is related to the risk for the individual to develop cardiovascular ( CV ) disease : Absence or very low levels of albuminuria is associated with low CV risk , whereas the CV risk increases markedly with increasing amount of albumin in the urine ( even within the now considered normal range ) . The predictive power of urinary albumin levels for CV risk is independent of other CV risk factors and not only is present in individual with diabetes and /or hypertension but also in healthy individuals . Treatments that lower albuminuria are associated with CV protection , as demonstrated in r and omized , controlled trials of patients with diabetes as well as in patients with hypertension . There is preliminary evidence that albuminuria lowering is CV protective in healthy individuals with an elevated albumin excretion rate . Differences between individuals in their level of albumin excretion are already observed at a very early age ( just after birth ) . In fact , the interindividual variability seems to be relatively constant in the first 5 decades of life , indicating that microalbuminuria is not necessarily a consequence of vascular damage at later age . Higher levels of urinary albumin seem to reflect the ordinary interindividual variability in ( renal and systemic ) endothelial function . Experimental data show that between strains and even within strains , rats at young age show a remarkable difference in individual endothelial function , and this is strongly related to the susceptibility of that rat to organ damage . In conclusion , albuminuria seems to be a sensitive marker very early in life for the susceptibility of an individual to CV disease . It therefore may be an ideal target for early primary prevention using CV-protective therapy regimens BACKGROUND Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes . We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors . METHODS In this r and omized study , 10,251 patients ( mean age , 62.2 years ) with a median glycated hemoglobin level of 8.1 % were assigned to receive intensive therapy ( targeting a glycated hemoglobin level below 6.0 % ) or st and ard therapy ( targeting a level from 7.0 to 7.9 % ) . Of these patients , 38 % were women , and 35 % had had a previous cardiovascular event . The primary outcome was a composite of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up . RESULTS At 1 year , stable median glycated hemoglobin levels of 6.4 % and 7.5 % were achieved in the intensive-therapy group and the st and ard-therapy group , respectively . During follow-up , the primary outcome occurred in 352 patients in the intensive-therapy group , as compared with 371 in the st and ard-therapy group ( hazard ratio , 0.90 ; 95 % confidence interval [ CI ] , 0.78 to 1.04 ; P=0.16 ) . At the same time , 257 patients in the intensive-therapy group died , as compared with 203 patients in the st and ard-therapy group ( hazard ratio , 1.22 ; 95 % CI , 1.01 to 1.46 ; P=0.04 ) . Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group ( P<0.001 ) . CONCLUSIONS As compared with st and ard therapy , the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events . These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 . BACKGROUND Effects of decreased estimated glomerular filtration rate ( eGFR ) on cardiovascular disease ( CVD ) mortality are uncertain in Chinese general population s. STUDY DESIGN Prospect i ve cohort study . SETTING & PARTICIPANTS 17,026 adults 50 years and older in Taiwan . A subset of 7,968 had repeated measurements . PREDICTOR Decreased eGFR and its progression . eGFR was calculated from serum creatinine level by using the Modification of Diet in Renal Disease Study equation . OUTCOMES Mortality from all causes and CVD , including coronary heart disease ( CHD ) and stroke , from the National Death Registry . MEASUREMENTS Hazard ratios ( HRs ) and Kaplan-Meier survival curves were calculated for participants with a moderate to severe decrease in eGFR ( < 60 mL/min/1.73 m(2 ) ) compared with those with normal eGFR ( > or = 90 mL/min/1.73 m(2 ) ) . HR of a rapid decrease ( > or = 20 % ) in eGFR was also calculated . RESULTS Mean age of all participants was 57.2 + /- 5.2 ( SD ) years . We observed 1,682 deaths in 15 years of follow-up . Participants with a moderate to severe decrease in eGFR had increased HRs for mortality from all causes ( 1.44 ; 95 % confidence interval [ CI ] , 1.22 to 1.70 ) , CVD ( 1.90 ; 95 % CI , 1.36 to 2.65 ) , CHD ( 2.07 ; 95 % CI , 1.26 to 3.41 ) , and stroke ( 2.16 ; 95 % CI , 1.29 to 3.62 ) after adjusting for confounders . Decreased eGFR was associated with ischemic stroke , but not hemorrhagic stroke . No significant interaction between decreased eGFR and anemia , diabetes , or smoking was found . There were 660 participants with a 20 % or greater decrease in eGFR from baseline during 18 months of follow-up . They had increased HRs for all causes ( 1.45 ; 95 % CI , 1.13 to 1.86 ) , CVD ( 2.48 ; 95 % CI , 1.58 to 3.89 ) , CHD ( 2.14 ; 95 % CI , 1.07 to 4.29 ) , and stroke ( 2.79 ; 95 % CI , 1.45 to 5.36 ) compared with those with less than a 20 % decrease in eGFR during the same period . LIMITATIONS Data for proteinuria were not available . Creatinine assay was not calibrated . CONCLUSIONS A moderate to severe or fast decrease in eGFR was associated with all-cause and CVD mortality in this ethnic Chinese cohort |
10,584 | 32,146,576 | The majority of studies find cognitive impairment in patients with cancer treated with chemotherapy .
Neuroimaging studies show changes in structure and activation in patients undergoing chemotherapy .
Non-pharmacological treatment is effective for improving cognition and quality of life .
This review highlights the importance of recognizing that this cognitive dysfunction is frequent , mild to moderate in nature but with great impact on quality of life | The aim of this review is to provide an up date d overview of chemotherapy-related cognitive impairment ( CRCI ) in patients with cancer outside central nervous system ( CNS ) , its incidence and prevalence , the cognitive pattern in neuropsychological studies , neuroimaging findings , and the relationship between chemobrain and aging .
Method ological limitations of studies are also discussed .
The body of the literature on breast cancer is the most abundant , but there are also studies on colorectal , testicular , and lung cancer .
The occurrence of CRCI during the course of treatment in people with different types of cancer is frequent . | Background Cancer-related cognitive dysfunction has mostly been attributed to chemotherapy ; this explanation , however , fails to account for cognitive dysfunction observed in chemotherapy-naïve patients . In a controlled , longitudinal , multisite study , we tested the hypothesis that cognitive function in breast cancer patients is affected by cancer-related post-traumatic stress . Methods Newly diagnosed breast cancer patients and healthy control subjects , age 65 or younger , underwent three assessment s within one year , including paper- and -pencil and computerized neuropsychological tests , clinical diagnostics of post-traumatic stress disorder ( PTSD ) , and self-reported cognitive function . Analysis of variance was used to compare three groups of participants - patients who did or did not receive chemotherapy and healthy control subjects-on age- and education-corrected cognitive performance and cognitive change . Differences that were statistically significant after correction for false discovery rate were investigated with linear mixed-effects models and mediation models . All statistical tests were two-sided . Results Of 226 participants ( 166 patients and 60 control subjects ) , 206 completed all assessment sessions ( attrition : 8.8 % ) . Patients demonstrated overall cognitive decline ( group*time effect on composite z -score : -0.13 , P = .04 ) and scored consistently worse on Go/Nogo errors . The latter effect was mediated by PTSD symptoms ( mediation effect : B = 0.15 , 95 % confidence interval = 0.02 to 0.38 ) . Only chemotherapy patients showed declined reaction time on a computerized alertness test . Overall cognitive performance correlated with self-reported cognitive problems at one year ( T = -0.11 , P = .02 ) . Conclusions Largely irrespective of chemotherapy , breast cancer patients may encounter very subtle cognitive dysfunction , part of which is mediated by cancer-related post-traumatic stress . Further factors other than treatment side effects remain to be investigated PURPOSE To examine the impact of age and cognitive reserve on cognitive functioning in patients with breast cancer who are receiving adjuvant treatments . PATIENTS AND METHODS Patients with breast cancer exposed to chemotherapy ( n = 60 ; mean age , 51.7 years ) were evaluated with a battery of neuropsychological and psychological tests before treatment and at 1 , 6 , and 18 months after treatment . Patients not exposed to chemotherapy ( n = 72 ; mean age , 56.6 years ) and healthy controls ( n = 45 ; mean age , 52.9 years ) were assessed at matched intervals . RESULTS Mixed-effects modeling revealed significant effects for the Processing Speed and Verbal Ability domains . For Processing Speed , a three-way interaction among treatment group , age , and baseline cognitive reserve ( P < .001 ) revealed that older patients with lower baseline cognitive reserve who were exposed to chemotherapy had lower performance on Processing Speed compared with patients not exposed to chemotherapy ( P = .003 ) and controls ( P < .001 ) . A significant group by time interaction for Verbal Ability ( P = .01 ) suggested that the healthy controls and no chemotherapy groups improved over time . The chemotherapy group failed to improve at 1 month after treatment but improved during the last two follow-up assessment s. Exploratory analyses suggested a negative effect of tamoxifen on Processing Speed ( P = .036 ) and Verbal Memory ( P = .05 ) in the no-chemotherapy group . CONCLUSION These data demonstrated that age and pretreatment cognitive reserve were related to post-treatment decline in Processing Speed in women exposed to chemotherapy and that chemotherapy had a short-term impact on Verbal Ability . Exploratory analysis of the impact of tamoxifen suggests that this pattern of results may be due to a combination of chemotherapy and tamoxifen Purpose Chemotherapy improves the survival rate of stage III colon cancer patients . The combination of oxaliplatin , 5-fluorouracil , and leucovorin ( the FOLFOX4 regimen ) has emerged as the st and ard of care . This prospect i ve study evaluates potential alterations in cognitive function in FOLFOX4-treated patients . Methods We evaluated 57 consecutive colorectal cancer patients who received adjuvant chemotherapy with FOLFOX4 . Patients underwent a complete battery of neuropsychological tests at three different times : before ( T0 ) , at the end ( T1 ) , and 6 months after treatment ( T2 ) . Results We have analyzed cognitive impairment ( Mini Mental State Examination , MMSE ) , visuo-spatial memory ( Clock Drawing Test , CDT , Rey Complex Figure , copy and recall ) , information processing speed ( Trial Making Test-A , TMT-A , and Trial Making Test-B , TMT-B ) , verbal memory ( Rey Auditory Verbal Learning Test , call and recall ) , emotional distress ( Psychological Distress Inventory , PDI ) , anxiety ( State and Trait Anxiety Inventory , STAI-Y1 and Y2 ) , and depression ( Beck Depression Inventory , BDI ) . Then we have calculated , for each test and for each interval of time , mean ± st and ard deviation for the mean . In a subsequent phase , we tested the significance of different results through the ANOVA analysis for repeated measures . In this case , we could not find any statistically significant modification in cognitive function , but we could notice an improvement in emotional performance , anxiety and depression a short time after chemotherapy administration . Conclusions We found no effect on cognitive function related to chemotherapy , the only little modification is about some emotional performance during chemotherapy . These findings may be explained by the central role of the psychological adaptation process , which occurs during the period from diagnosis to completion of treatment and is characterized by anxiety and adjustment depression . Our results seem to rule out any significant cognitive impairment due to adjuvant FOLFOX4 chemotherapy in colon cancer patients A subset of survivors has cognitive impairment after cancer treatment . This is generally subtle , but may be sustained . In October 2006 , the second international cognitive workshop was held in Venice . The workshop included neuropsychologists , clinical and experimental psychologists , medical oncologists , imaging experts , and patient advocates . The main developments since the first Cognitive Workshop in 2003 have been the following . ( i ) studies evaluating cognitive function in patients receiving chemotherapy for cancers other than breast cancer , and in patients receiving hormonal therapy for cancer . ( ii ) The publication of longitudinal prospect i ve studies which have shown that some patients already exhibit cognitive impairment on neuropsychological testing before receiving chemotherapy , and some patients have deterioration in cognitive functioning from pre- to postchemotherapy . ( iii ) Studies of the underlying mechanisms of cognitive impairment both in patients and in animal models . ( iv ) Use of structural and functional imaging techniques to study changes in brain morphology and activation patterns associated with chemotherapy . ( v ) At present cognitive research in cancer is limited by method ological challenges and the lack of st and ardization in neuropsychological studies . The current workshop addressed many of these issues and established an international task force to provide guidelines for future research and information on how best to manage these symptoms OBJECTIVE To evaluate the efficacy of a brief cognitive-behavioral therapy ( CBT ) that is being developed for management of cognitive dysfunction following chemotherapy among breast cancer survivors . Memory and Attention Adaptation Training ( MAAT ) is a brief CBT design ed to improve the quality of life and function among cancer survivors with post-chemotherapy cognitive complaints . METHODS An initial , two-group ( MAAT versus waitlist , no treatment control ) , r and omized clinical trial ( RCT ) was conducted . Forty stage I and II female breast cancer survivors ( mean age = 50 ; SD = 6.4 ) were r and omized to conditions and assessed at baseline , post-treatment ( 8 weeks ) and 2-month follow-up assessment points on measures of : ( 1 ) self-reported daily cognitive failures ; ( 2 ) quality of life ; and ( 3 ) neuropsychological performance . Participants were also assessed for satisfaction with MAAT . RESULTS With education and IQ as covariates , MAAT participants made significant improvements relative to controls on the spiritual well-being subscale of the quality of life measure and on verbal memory , but statistical significance was not achieved on self-report of daily cognitive complaints . However , moderate-to-large effect sizes were observed on these outcomes . Participants gave MAAT high satisfaction ratings . CONCLUSIONS Although this initial RCT is a small study , MAAT participants appear to improve on one measure of quality of life and verbal memory performance relative to no treatment controls and rate MAAT with high satisfaction . These data are encouraging and support the continued development and evaluation of MAAT efficacy Studies suggest that adjuvant chemotherapy for early stage breast cancer ( BC ) is associated with cognitive impairment related to attention , memory , and visuospatial functioning . However , other studies have failed to confirm that relationship . We report one of the first longitudinal , controlled studies of cognitive effects of chemotherapy in older post-menopausal women . Sixty-one post-menopausal women with non-metastatic BC were administered neuropsychological tests before adjuvant therapy ( Time1 ) , six months after treatment ( Time2 ) , and at a final 6-month follow-up ( Time3 ) . Thirty women were treated with chemotherapy ; thirty-one women who received no chemotherapy were controls . Cognitive domains measured included motor , language , attention/concentration/working memory , visuospatial , and memory ( verbal and visual ) . Time-by-treatment interaction was significant in the motor domain ( P = 0.007 ) with poorer performance in women treated with chemotherapy . For the other domains , scores did not significantly vary over time by group . In post-menopausal women , chemotherapy was not associated with changes in cognitive function in areas reported by BC survivors : attention , memory , and information processing . Motor slowing in women treated with chemotherapy could be secondary to peripheral neuropathy rather than an indication of more general declines in cognitive processing . Future studies should control for the independent effects of slowed motor functioning when looking to study possible chemotherapy related cognitive processing deficits Aim : To assess cognitive function prospect ively in women with early breast cancer before , during and after the administration of adjuvant chemotherapy OBJECTIVES To report on the longitudinal cognitive functioning of older women receiving adjuvant chemotherapy for breast cancer . DESIGN Neuropsychological and functional status testing were performed before chemotherapy and 6 months after chemotherapy . SETTING Cancer center . PARTICIPANTS Thirty-one patients aged 65 and older with Stage I to III breast cancer . Of the 31 patients enrolled , three refused post-testing , and 28 were evaluable . MEASUREMENTS The following domains of cognitive function were examined : attention ; verbal memory ; visual memory ; and verbal , spatial , psychomotor , and executive functions . RESULTS Participants had a mean age of 71 ( range 65 - 84 ) : 39 % Stage I , 50 % Stage II , and 11 % Stage III . The number of scores 2 st and ard deviations ( SDs ) below the norm were calculated for each patient before and 6 months after chemotherapy ; 14 ( 50 % ) had no change , 11 ( 39 % ) worsened , and three ( 11 % ) improved ( P=.05 ) . Seven patients ( 25 % ) experienced a decline in cognitive function , defined as a 1-SD decline from pre- to post-testing in two or more neuropsychological domains . Exploratory analyses revealed no significant difference between functional status , comorbidity , and depression scale scores and change in overall quality -of-life scores before and after chemotherapy . CONCLUSION In this cohort of older women receiving adjuvant chemotherapy , a subset experienced a decline in cognitive function from before chemotherapy to 6 months after chemotherapy . Further prospect i ve study is needed to confirm these observations and to identify the subgroup at special risk Long‐term chemotherapy‐related cognitive dysfunction ( CRCD ) affects a large number of cancer survivors . To the authors ' knowledge , to date there is no established treatment for this survivorship problem . The authors herein report results of a small r and omized controlled trial of a cognitive behavioral therapy ( CBT ) , Memory and Attention Adaptation Training ( MAAT ) , compared with an attention control condition . Both treatments were delivered over a videoconference device OBJECTIVE A number of cross-sectional studies have reported reduced cognitive function in cancer patients receiving chemotherapy compared with other cancer patients and healthy controls , suggesting that chemotherapy could be associated with cognitive side-effects . Recently published prospect i ve studies question this hypothesis , but it is still unclear whether cancer patients should regard cognitive problems as a potential risk when receiving chemotherapy . METHODS In the present study we examine whether cancer patients ( n=34 ) receiving chemotherapy differed in cognitive changes during treatment compared with cardiac patients ( n=12 ) and healthy controls ( n=12 ) tested at 3 - 4 months interval . RESULTS Our results showed no differences with respect to changes in cognitive performance over time between cancer patients in chemotherapy , cardiac patients , and healthy controls . In addition , the number of individuals showing reliable decline or improvement on cognitive tests did not differ between groups . CONCLUSION Taken together , our results do not support a hypothesis of cognitive side-effects of st and ard-dose chemotherapy in breast cancer patients PURPOSE Whether adjuvant therapy impairs cognitive function in women with breast cancer ( BC ) is unclear . We determined the effects of adjuvant therapy on cognitive function in women with early BC . METHODS We consecutively and prospect ively enrolled women aged 40 - 69 years who had a positive radiographic finding from the mammography screening program at Stockholm South General Hospital . All women completed the Headminder Web-based neuropsychological battery Cognitive Stability Index ( CSI ) for response speed , processing speed , memory , and attention before diagnosis ( T1 ) , after surgery and before adjuvant treatment ( T2 ) , 6 months after start of adjuvant treatment ( T3 ) , and after another 3 months of follow-up ( T4 ) . Women with BC were divided into those receiving chemotherapy , hormone therapy , or no adjuvant medical therapy . Women without a diagnosis of BC served as healthy controls . RESULTS Of the 146 women enrolled , 77 had BC of whom 18 received chemotherapy ; 45 , hormone therapy , and 14 , no adjuvant medical therapy ; 69 were healthy controls . Memory scores for women with BC were significantly lower than those for controls over time , even after controlling for age and education . Memory and response speed scores were lower after chemotherapy than before ( P<0.01 for both ) . Processing speed and attention improved significantly over time in all groups , a result consistent with a practice effect . CONCLUSION Our results indicate subtle changes related to time course and treatment . Especially , that chemotherapy may impair memory and response speed in women with BC , consistent with those reported by BC survivors after adjuvant medical treatment Retrospective trials have reported that chemotherapy‐induced cognitive dysfunction was experienced by a subset of patients with breast carcinoma . However , recent evidence indicated that a subset also exhibited impaired cognitive function at baseline , before the start of chemotherapy . A prospect i ve , longitudinal trial that incorporates baseline neuropsychologic evaluations is necessary to determine to what extent cognitive dysfunction is attributable to chemotherapy in this population Purpose Published cross-sectional studies have revealed that chemotherapy for breast cancer is associated with significant cognitive impairments . However , because these studies included no baseline assessment , it is unknown whether the cognitive impairments were pre-existent to cancer treatment or truly secondary to chemotherapy . To resolve this issue , this prospect i ve study aim ed to compare the effects of chemotherapy to the effect of radiotherapy on cognitive functioning in women treated for non-metastatic breast cancer . Patients and Methods A total of 81 breast cancer patients , 41 receiving chemotherapy as part of their breast cancer treatment regimen and 40 receiving radiotherapy without chemotherapy were evaluated using an extensive battery of neuropsychological tests at baseline ( ie , pre-chemotherapy or pre-radiotherapy ) , post-treatment ( ie , post-chemotherapy or post-radiotherapy ) and at a 3-month follow-up assessment . Results A mixed model covariance analysis revealed that receiving any kind of breast cancer treatment , with chemotherapy or not , was associated with impaired capacities for recruiting information in verbal memory . Moreover , the results showed that verbal fluency was impaired after breast cancer treatment , but only in patients who received chemotherapy . Conclusion Overall , this study reveals subtle cognitive impairments associated with breast cancer treatment . Specifically , it suggests that chemotherapy has a specific negative effect on verbal fluency , that breast cancer treatment in general negatively affects verbal memory , but that other cognitive functions are well preserved . Future studies should , however , attempt to better control the practice effect that may have masked other subtle alterations and use more ecologically valid measures of cognitive functioning It is believed widely that chemotherapy‐induced cognitive impairment occurs in a subgroup of patients with breast cancer . However , recent reports have provided no evidence that chemotherapy affects cognition . In this study , the authors question ed whether cognitive compromise in patients with breast cancer is attributable to chemotherapy . In addition , the effects of therapy‐induced menopause and of the erythropoiesis‐stimulating factor darbepoetin α on cognitive performance were assessed OBJECTIVE Several prospect i ve studies into the effects of adjuvant systemic therapy on cognitive functioning suggest that a proportion of breast cancer patients show cognitive deficits already before the start of systemic therapy . Owing to , among others , method ological inconsistency , studies report different rates of this pre-treatment cognitive impairment . We examined the impact of four different criteria of cognitive impairment and two types of reference groups ( a study -specific healthy reference group versus published normative data ) on the prevalence of cognitive impairment . METHODS Two hundred and five postmenopausal breast cancer patients underwent a battery of neuropsychological tests before the start of endocrine therapy , 124 healthy subjects underwent the same tests . Proportions of cognitive impaired patients were calculated for each of four criteria for cognitive impairment , using ( 1 ) study -specific healthy controls and ( 2 ) published norms of healthy controls as reference groups . RESULTS The prevalence of cognitive impairment varied greatly with the strictness of the criterion , as expected , but also was dependent on the reference group used . Cognitive impairment , relative to published norms , ranged from 1 % for the strictest to 36.6 % for the less strict criterion , cognitive impairment relative to study -specific healthy controls , ranged from 13.7 to 45.4 % for the same criteria . CONCLUSION This study highlights contrasting proportions of cognitive impairment by using different criteria for cognitive impairment and different reference groups . (Dis)advantages of the methods using a criterion for cognitive impairment , and of the use of published norms versus a study -specific reference group are discussed BACKGROUND Although high-dose chemotherapy is rapidly gaining acceptance as a treatment option for a number of cancers , the long-term toxic effects of such therapy are a concern . Cognitive deficits ( e.g. , problems with memory and concentration ) are not uncommon after chemotherapy , but they have not been documented systematic ally . In this study , we assessed the prevalence of cognitive deficits in a group of patients with high-risk breast cancer who were r and omly assigned to receive either high-dose or st and ard-dose adjuvant chemotherapy plus tamoxifen , and we investigated whether high-dose chemotherapy impaired cognitive functioning more than st and ard-dose chemotherapy . METHODS Cognitive functioning was evaluated by use of a battery of neuropsychologic tests . In addition , patients were interviewed with regard to cognitive problems , health-related quality of life , anxiety , and depression . Results from patients who received adjuvant systemic therapy were compared with results from patients who had early stage breast cancer not treated with such therapy ( control patients ) . RESULTS The study population consisted of 34 patients treated with high-dose chemotherapy plus tamoxifen , 36 patients treated with st and ard-dose chemotherapy plus tamoxifen , and 34 control patients . For all patients , the average time since the completion of last nonhormonal therapy was 2 years . Cognitive impairment was found in 32 % of the patients treated with high-dose chemotherapy , in 17 % of the patients treated with st and ard-dose chemotherapy , and in 9 % of the control patients . In comparison with the control patients , patients treated with high-dose chemotherapy appeared to have an 8.2-times higher risk of cognitive impairment ( odds ratio ; 95 % confidence interval [ CI ] = 1.8 - 37.7 ) ; in comparison with the patients who received st and ard-dose chemotherapy , this risk of impairment was 3.5-times higher ( 95 % CI = 1.0 - 12.8 ) . CONCLUSION High-dose chemotherapy appears to impair cognitive functioning more than st and ard-dose chemotherapy . Central nervous system toxicity may be a dose-limiting factor in high-dose chemotherapy regimens Purpose Cognitive impairment is reported frequently by cancer survivors . There are no proven treatments . We evaluated a cognitive rehabilitation program ( Insight ) and compared it with st and ard care in cancer survivors self-reporting cognitive symptoms . Patients and Methods We recruited adult cancer survivors with a primary malignancy ( excluding central nervous system malignancies ) who had completed three or more cycles of adjuvant chemotherapy in the previous 6 to 60 months and reported persistent cognitive symptoms . All participants received a 30-minute telephone consultation and were then r and omly assigned to the 15-week , home-based intervention or to st and ard care . Primary outcome was self-reported cognitive function ( Functional Assessment of Cancer Therapy Cognitive Function [ FACT-COG ] perceived cognitive impairment [ PCI ] subscale ) : difference between groups after intervention ( T2 ) and 6 months later ( T3 ) . Results A total of 242 participants were r and omly assigned : median age , 53 years ; 95 % female . The primary outcome of difference in FACT-COG PCI was significant , with less PCI in the intervention group at T2 ( P < .001 ) . This difference was sustained at T3 ( P < .001 ) . At T2 , there was a significant difference in all FACT-COG subscales , favoring the intervention . Neuropsychological results were not significantly different between the groups at T2 or T3 . There were significantly lower levels of anxiety/depression and fatigue in the intervention group at T2 . There were significant improvements in stress in the intervention group at both time points . There was no significant difference in quality of life between the groups at T2 , but the intervention group had better quality of life at T3 . Conclusion The intervention , Insight , led to improvements in cognitive symptoms compared with st and ard care . To our knowledge , this is the first large r and omized controlled trial showing an improvement in self-reported cognitive function in cancer survivors , indicating that this intervention is a feasible treatment Purpose The purpose of the study was to prospect ively examine changes in subjective and objective cognitive functions and quality of life ( QOL ) for pre- and peri-menopausal women receiving chemotherapy for breast cancer and to explore potential predictors of cognitive changes . Methods Participants were assessed as follows : prior to chemotherapy ( T1 ) , after cycle 3 ( T2 ) , within 2–3 weeks of completing adjuvant chemotherapy ( T3 ) ( N = 20 ) , and 8 + years later ( T4 ; n = 18 ) . Objective cognitive function was measured with the High Sensitivity Cognitive Screen ( T1 , T3 , T4 ) . Subjective measures for cognitive function , depressive symptoms , fatigue , and mental and physical QOL were assessed at all time points . Estradiol levels were measured at T1 , T2 , and T3 . The Functional Assessment of Cancer Therapy-Cognition and the MD And erson Cancer Symptom Inventory item for neuropathy were administered at T4 . Results No significant changes in objective cognitive function were found . However , participants reported decreased cognitive function over the course of treatment accompanied by depressive symptoms and fatigue . Depression and fatigue returned to near-baseline levels at T4 , but over half of the participants continued to report mild to moderate depression . Estradiol levels were not associated with cognitive function . Neuropathy and higher body mass index ( BMI ) were associated with persistent cognitive complaints at T4 ( adjusted R2 = 0.712 , p = 0.001 ) . Higher QOL was correlated with better subjective cognitive function ( r = 0.705 , p = 0.002 ) and lower body mass index ( r = − 0.502 , p = 0.017 ) at T4 . Conclusions Further investigation of BMI , neuropathy , and depressive symptoms as predictors of persistent cognitive dysfunction following chemotherapy for breast cancer is warranted Some breast cancer survivors experience cognitive decline following chemotherapy . We prospect ively examined changes in cognitive performance among high-risk breast cancer patients who had received high-dose chemotherapy with cyclophosphamide , thiotepa , and carboplatin ( CTC group ; n = 28 ) or st and ard-dose chemotherapy with 5-fluorouracil , epirubicin , and cyclophosphamide ( FEC group ; n = 39 ) ; stage-I breast cancer patients who had received no systemic chemotherapy ( no-CT group ; n = 57 ) ; and healthy control subjects ( n = 60 ) . All patients underwent neuropsychologic testing before and 6 months after treatment ( 12-month interval ) ; control subjects underwent repeated testing over a 6-month interval . No differences in cognitive functioning between the four groups were observed at the first assessment . More of the CTC group than the control subjects experienced a deterioration in cognitive performance over time ( 25 % versus 6.7 % ; odds ratio [ OR ] = 5.3 , 95 % confidence interval [ CI ] = 1.3 to 21.2 , P = .02 ) . No such difference was observed for the FEC or the no-CT groups ( FEC versus control : OR = 2.2 , 95 % CI = 0.5 to 9.1 , P = .27 ; no-CT versus Control : OR = 2.2 , 95 % CI = 0.6 to 8.0 ; P = .21 ) . Some cytotoxic treatment for breast cancer affects cognition in a subset of women The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen . We performed a population -based study in the county of North Jutl and , Denmark , including 120 women aged < 60 years who received adjuvant chemotherapy with seven cycles of cyclophosphamide , epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006 . They were compared with an aged-matched group of 208 women without previous cancer selected r and omly from the same population . Data were collected before start of adjuvant treatment and after 6 months by neuropsychological tests and question naires to evaluate cognitive function , quality of life and psychological distress . Neuropsychological tests did not reveal any differences in cognitive function between breast cancer patients after chemotherapy and healthy controls . Patients rated their own cognitive functions as improved after 6 months , and patients , who did not receive adjuvant medical treatment , reached the same level as controls within 6 months . Patients receiving chemotherapy or tamoxifen were up to three times more likely than controls to rate themselves as impaired at 6 months . Our results do not support that adjuvant chemotherapy is associated with cognitive side effects in breast cancer patients Numerous studies have shown that there are acute cognitive side-effects of chemotherapy for breast cancer . Presumably , patients are more concerned about chronic treatment effects . This report from a prospect i ve longitudinal study compares cognitive functioning in 56 breast cancer patients 1 year after chemotherapy to that of 56 healthy individuals . Neuropsychological test scores were combined into verbal memory , visual memory , working memory , and processing speed scores , as well as an overall summary score , and analyzed using multi-level growth modeling . Frequency of cognitive decline was assessed using regression-based change scores . There was significant rebound in the overall summary score from end of treatment to 1-year follow-up as well as a substantial reduction in the frequency of cognitive decline . However , more than one-third of the breast cancer patients who showed cognitive decline immediately following completion of chemotherapy showed persistent cognitive decline 1 year later . Furthermore , recovery was not seen in all cognitive domains . In fact , the rebound was significant only for working memory . Longer multi-site studies are recommended to explore the risk factors for and the permanence of these longer-term cognitive effects PURPOSE Cancer-related cognitive impairment ( CRCI ) is an important clinical problem in patients with breast cancer receiving chemotherapy . Nationwide longitudinal studies are needed to underst and the trajectory and severity of CRCI in specific cognitive domains . PATIENTS AND METHODS The overall objective of this nationwide , prospect i ve , observational study conducted within the National Cancer Institute Community Clinical Oncology Research Program was to assess trajectories in specific cognitive domains in patients with breast cancer ( stage I-IIIC ) receiving chemotherapy , from pre- ( A1 ) to postchemotherapy ( A2 ) and from prechemotherapy to 6 months postchemotherapy ( A3 ) ; controls were assessed at the same time-equivalent points . The primary aim assessed visual memory using the Cambridge Neuropsychological Test Automated Battery Delayed Match to Sample test by longitudinal mixed models including A1 , A2 , and A3 and adjusting for age , education , race , cognitive reserve score , and baseline anxiety and depressive symptoms . We also assessed trajectories of CRCI in other aspects of memory as well as in attention and executive function with computerized , paper-based , and telephone-based cognitive tests . RESULTS In total , 580 patients with breast cancer ( mean age , 53.4 years ) and 363 controls ( mean age , 52.6 years ) were assessed . On the Delayed Match to Sample test , the longitudinal mixed model results revealed a significant group-by-time effect ( P < .005 ) ; patients declined over time from prechemotherapy ( A1 ) to 6 months postchemotherapy ( A3 ; P = .005 ) , but controls did not change ( P = .426 ) . The group difference between patients and controls was also significant , revealing declines in patients but not controls ( P = .017 ) . Several other models of computerized , st and ard , and telephone tests indicated significantly worse performance by patients compared with controls from pre- to postchemotherapy and from prechemotherapy to 6 months postchemotherapy . CONCLUSION This nationwide study showed CRCI in patients with breast cancer affects multiple cognitive domains for at least 6 months postchemotherapy Micro‐ Abstract Cognitive dysfunction can occur after chemotherapy in cancer survivors but has not been widely investigated in colorectal cancer ( CRC ) . Among patients with stage II or III CRC who had been prospect ively assessed for neuropsychological function and had completed cognitive complaint question naires , those who had received fluoropyrimidine‐based adjuvant chemotherapy presented with declines in executive function after 12 months compared with those patients who had not received chemotherapy . Purpose : Chemotherapy‐related cognitive impairment can occur in cancer survivors after treatment , especially those patients who have undergone chemotherapy for breast cancer . The frequency and to what extent such toxicity develops in colorectal cancer ( CRC ) survivors is unknown . The present prospect i ve study evaluated the effects of adjuvant chemotherapy on the cognitive performance of patients with localized CRC compared with a control group who had not undergone chemotherapy . Patients and Methods : Consecutive patients with localized stage II and III CRC completed neuropsychological assessment s , self‐reported cognitive complaint question naires , and depressive symptom evaluations before starting fluoropyrimidine‐based adjuvant chemotherapy and after 12 months . Blood was collected for apolipoprotein E genotyping . Diffusion tensor imaging data were acquired from a subset of participants at both evaluation points . Results : From December 2012 to December 2014 , 137 patients were approached and 85 were included . Of these 85 patients , 49 had undergone chemotherapy and 26 had not , in accordance with the st and ard recommendations for adjuvant therapy for CRC . The mean age was 62.5 ± 9.4 years , 60 % were men , and the mean educational attainment was 7.6 ± 3.7 years . No difference was found in the global composite score ( P = .38 ) , attention ( P = .84 ) , or memory ( P = .97 ) between the 2 groups during the follow‐up period ( mean ± st and ard deviation , 375 ± 29 days ) . However , a statistically significant difference was found for executive function after adjustment for age , sex , education , and depressive symptoms at baseline ( & bgr ; −1.80 ; 95 % confidence interval , −3.50 to −0.11 ; P = .04 ) , suggesting worse performance for the chemotherapy group . For the 32 patients who had undergone magnetic resonance imaging , tract‐based spatial statistics did not show voxelwise significant differences in structural brain connectivity at baseline or during follow‐up . Apolipoprotein E polymorphisms were not predictive of cognitive dysfunction . Conclusion : Patients with CRC who received adjuvant 5‐fluorouracil with or without oxaliplatin presented with a decline in executive function after 12 months compared with patients with localized disease who had not received chemotherapy Abstract Background : Cancer and cancer treatments may impact the brain through several pathways leading to cognitive impairment . Neuroimaging evidence has begun to eluci date the neurobiological underpinnings of cancer-related cognitive impairment . The aim of this paper was to systematic ally review available literature on structural brain alterations following adult non- central nervous system ( CNS ) cancers and associated treatments . Methods : This review followed PRISMA guidelines and was registered in PROSPERO ( ID#107387 ) . Comprehensive search es were conducted in June 2018 using PubMed and Web of Science . Inclusion criteria were English peer- review ed journal articles of formal , controlled studies that examined structural neuroimaging outcomes in adult non-CNS cancer patients and survivors . Selected articles were assessed for quality and risk of bias using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies . Results : Thirty-six publications of prospect i ve and cross-sectional studies met inclusion criteria and were included . Structural brain alterations following cancer and its treatment were reported in a majority of the publications as evidence d by reduced global and local gray matter volumes , impaired white matter microstructural integrity , and brain network alterations . Structural alterations were most often evident when cancer-treated groups were compared with healthy controls , and more subtle when compared with cancer controls . Regarding the existence of pretreatment impairments , the evidence was equivocal . There was significant between- study heterogeneity in imaging analytical approaches and use of statistical adjustments . Over half reported associations with cognitive outcomes , though regions and associated cognitive domains were heterogeneous . Conclusions : Structural brain alterations following cancer and cancer treatments were reported in a majority of the review ed studies . However , the extent of observed alterations depended on the choice of comparison groups . Method ological issues exist that will need to be addressed systematic ally to ensure the validity of findings . Large-scale prospect i ve studies with extended assessment points are warranted to replicate and build upon initial findings BACKGROUND Whether systemic chemotherapy has a negative effect on cognitive function in patients , concern oncologists . In testicular cancer patients ( TCPs ) treated with cisplatin-based chemotherapy , only few cross-sectional studies have addressed this concern . We prospect ively studied neuropsychological functioning in TCPs . PATIENTS AND METHODS In a consecutive sampling , 122 TCPs were examined at baseline ( after orchidectomy , before any additional treatment ) and then at follow-up at a median of 12 months after end of treatment . The examinations included a neuropsychological test battery , interview on background variables and question naires on mental distress , fatigue and neurotoxic symptoms . Changes in neuropsychological functioning from baseline to follow-up were compared between three treatments groups : no chemotherapy ( N = 31 ) , one cycle of chemotherapy ( N = 38 ) and two or more cycles of chemotherapy ( N = 53 ) . Variables associated with a decline in neuropsychological test performance from baseline to follow-up were explored . RESULTS No statistically significant differences in proportions of TCPs with a decline in neuropsychological test performance were observed between the three treatment groups . Decline in neuropsychological test performance was not associated with demographic variables , distress , fatigue or with chemotherapy . CONCLUSION No negative effect of systemic chemotherapy on neuropsychological test performance in TCPs at 1-year follow-up was found in this study |
10,585 | 25,415,259 | Results Comprehensive interventions can prevent first pregnancy in adolescence by 15 % and repeat adolescent pregnancy by 37 % .
Appropriate birth spacing ( 18 - 24 months from birth to next pregnancy compared to short intervals < 6 months ) can significantly lower maternal mortality , preterm births , stillbirths , low birth weight and early neonatal deaths . | Introduction Preconception care recognizes that many adolescent girls and young women will be thrust into motherhood without the knowledge , skills or support they need .
Sixty million adolescents give birth each year worldwide , even though pregnancy in adolescence has mortality rates at least twice as high as pregnancy in women aged 20 - 29 years .
Reproductive planning and contraceptive use can prevent unintended pregnancies , unsafe abortions and sexually-transmitted infections in adolescent girls and women .
Smaller families also mean better nutrition and development opportunities , yet 222 million couples continue to lack access to modern contraception . | Abstract Objective : To estimate the association between maternal age and fetal death ( spontaneous abortion , ectopic pregnancy , stillbirth ) , taking into account a woman 's reproductive history . Design : Prospect i ve register linkage study . Subjects : All women with a reproductive outcome ( live birth , stillbirth , spontaneous abortion leading to admission to hospital , induced abortion , ectopic pregnancy , or hydatidiform mole ) in Denmark from 1978 to 1992 ; a total of 634 272 women and 1 221 546 pregnancy outcomes . Main outcome measures : Age related risk of fetal loss , ectopic pregnancy , and stillbirth , and age related risk of spontaneous abortion stratified according to parity and previous spontaneous abortions . Results : Overall , 13.5 % of the pregnancies intended to be carried to term ended with fetal loss . At age 42 years , more than half of such pregnancies result ed in fetal loss . The risk of a spontaneous abortion was 8.9 % in women aged 20–24 years and 74.7 % in those aged 45 years or more . High maternal age was a significant risk factor for spontaneous abortion irrespective of the number of previous miscarriages , parity , or calendar period . The risk of an ectopic pregnancy and stillbirth also increased with increasing maternal age . Conclusions : Fetal loss is high in women in their late 30s or older , irrespective of reproductive history . This should be taken into consideration in pregnancy planning and counselling Some fraction of any cohort of fetuses alive at a given gestational age will ultimately die before birth . The residual prospect i ve risk of stillbirth as a function of gestational age was calculated from records of the New York City Department of Health covering 370,051 reported births between 1987–1989 , including 2454 stillbirths . In the general population , the prospect i ve risk of stillbirth at 26 weeks was one in 150 and , because the time distributions of live births and stillbirths were not proportionate , the risk changed with gestational age . By 40 weeks ' gestation , it was one in 475 , rising progressively thereafter to one in 375 at 43 weeks . The prospect i ve risk of stillbirth was elevated in certain ethnic groups and increased significantly with advanced maternal age , multiple gestation , and lack of prenatal care . The prospect i ve risk of stillbirth is an important consideration in decisions regarding timing of delivery Recent evidence suggests that conditional cash transfer programs for schooling are effective in raising school enrollment and attendance . However , there is also reason to believe that such programs can affect other outcomes , such as the sexual behavior of their young beneficiaries . Zomba Cash Transfer Program is a r and omized , ongoing conditional cash transfer intervention targeting young women in Malawi that provides incentives ( in the form of school fees and cash transfers ) to current schoolgirls and recent dropouts to stay in or return to school . An average offer of US$ 10/month conditional on satisfactory school attendance – plus direct payment of secondary school fees – led to significant declines in early marriage , teenage pregnancy , and self-reported sexual activity among program beneficiaries after just one year of program implementation . For program beneficiaries who were out of school at baseline , the probability of getting married and becoming pregnant declined by more than 40 percent and 30 percent , respectively . In addition , the incidence of the onset of sexual activity was 38 percent lower among all program beneficiaries than the control group . Overall , these results suggest that conditional cash transfer programs not only serve as useful tools for improving school attendance , but may also reduce sexual activity , teen pregnancy , and early marriage To test the effectiveness of a special health care program for adolescent mothers ( 17 years old or younger ) and their infants , 243 mother-infant pairs were r and omly assigned to one of two groups . All of the mothers were unwed , on Medicaid , and black . The control group received routine well-baby care . The experimental group received routine care and services that included rigorous follow-up , discussion s with the mother about her plans for return to school and use of family planning methods , and extra health teaching . The dropout rate in the experimental group ( 60 % ) was significantly less after 18 months than the control group ( 82 % ) . In spite of the high dropout rate , 91 % of the mothers were located for the 18 month follow-up interview . The repeat pregnancy rate in the experimental group was 12 % after 18 months , and 28 % in the control group . There was no significant difference in the percentage returning to school . After 12 months , the infants in the experimental group were more likely to be fully immunized ( 33 % ) than the infants in the control group ( 18 % ) . Mothers in the special care program who continued to attend clinic used the emergency room less than the mothers who continued to attend in the control group . These results suggest that a comprehensive health care program is one way to bring about better outcomes for both adolescent mothers and their infants OBJECTIVES This study assessed the effects of the Safe Date s program on the primary and secondary prevention of adolescent dating violence . METHODS Fourteen schools were r and omly allocated to treatment conditions . Eighty percent ( n=1886 ) of the eighth and ninth grade rs in a rural county completed baseline question naires , and 1700 ( 90 % ) completed follow-up question naires . RESULTS Treatment and control groups were comparable at baseline . In the full sample at follow-up , less psychological abuse , sexual violence , and violence perpetrated against the current dating partner were reported in treatment than in control schools . In a sub sample of adolescents reporting no dating violence at baseline ( a primary prevention sub sample ) , there was less initiation of psychological abuse in treatment than in control schools . In a sub sample of adolescents reporting dating violence at baseline ( a secondary prevention sub sample ) , there was less psychological abuse and sexual violence perpetration reported at follow-up in treatment than in control schools . Most program effects were explained by changes in dating violence norms , gender stereotyping , and awareness of services . CONCLUSIONS The Safe Date s program shows promise for preventing dating violence among adolescents Abstract Objective : To determine whether a theoretically based sex education programme for adolescents ( SHARE ) delivered by teachers reduced unsafe sexual intercourse compared with current practice . Design : Cluster r and omised trial with follow up two years after baseline ( six months after intervention ) . A process evaluation investigated the delivery of sex education and broader features of each school . Setting : Twenty five secondary schools in east Scotl and . Participants : 8430 pupils aged 13 - 15 years ; 7616 completed the baseline question naire and 5854 completed the two year follow up question naire . Intervention : SHARE programme ( intervention group ) versus existing sex education ( control programme ) . Main outcome measures : Self reported exposure to sexually transmitted disease , use of condoms and contraceptives at first and most recent sexual intercourse , and unwanted pregnancies . Results : When the intervention group was compared with the conventional sex education group in an intention to treat analysis there were no differences in sexual activity or sexual risk taking by the age of 16 years . However , those in the intervention group reported less regret of first sexual intercourse with most recent partner ( young men 9.9 % difference , 95 % confidence interval −18.7 to −1.0 ; young women 7.7 % difference , −16.6 to 1.2 ) . Pupils evaluated the intervention programme more positively , and their knowledge of sexual health improved . Lack of behavioural effect could not be linked to differential quality of delivery of intervention . Conclusions : Compared with conventional sex education this specially design ed intervention did not reduce sexual risk taking in adolescents OBJECTIVE To determine whether the addition of a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) alone or with " boosters " could enhance ( either broaden or sustain or both ) the effect of a small group , face-to-face adolescent risk reduction intervention Focus on Kids ( FOK ) . METHODS A longitudinal , r and omized , community-based cohort study was conducted of 35 low-income , community-based , in-town setting s. A total of 817 black youths aged 12 to 16 years at baseline were studied . After completion of baseline measures , youths were r and omized to receive a face-to-face intervention alone ( FOK only ) , a face-to-face intervention and a parental monitoring intervention ( FOK plus ImPACT ) , or both of the above plus boosters ( FOK plus ImPACT plus boosters ) . Risk and protective behaviors were assessed at 6 and 12 months after intervention . RESULTS At 6 months ' follow-up , youths in families that were assigned to FOK plus ImPACT reported significantly lower rates of sexual intercourse , sex without a condom , alcohol use , and cigarette use and marginally lower rates of " risky sexual behavior " compared with youths in families that were assigned to FOK only . At 12 months after intervention , rates of alcohol and marijuana use were significantly lower and cigarette use and overall risk intention were marginally lower among FOK plus ImPACT youths compared with FOK only youths . With regard to the boosters delivered at 7 and 10 months , 2 risk behaviors -- use of crack/cocaine and drug selling -- were significantly lower among the youths who were assigned to receive the additional boosters compared with youths without the boosters . The rates of the other risk behaviors and intentions did not differ significantly . CONCLUSIONS The results of this r and omized , controlled trial indicate that the inclusion of a parental monitoring intervention affords additional protection from involvement in adolescent risk behaviors 6 and 12 months later compared with the provision of an intervention that targets adolescents only . At the same time , the results of the present study do not provide sufficient evidence that booster sessions further improve targeted behaviors enough to include them in a combined parent and youth intervention BACKGROUND Maternal obesity and diabetes are both associated with increased risk of congenital central nervous system ( CNS ) malformations in the offspring and may share a common underlying mechanism . Our objective was to evaluate whether gestational diabetes influenced the association of prepregnancy maternal obesity and risks for CNS birth defects . METHODS This Texas population -based case-control study evaluated births occurring January 1997 through June 2001 . Data came from structured telephone interviews . Cases ( n=477 ) were mothers of offspring with anencephaly ( n=120 ) , spina bifida ( n=184 ) , holoprosencephaly ( n=49 ) , or isolated hydrocephaly ( n=124 ) . Controls ( n=497 ) were mothers of live infants without abnormalities r and omly selected from the same hospitals as cases . Response rates were approximately 60 % for both cases and controls . We evaluated maternal obesity ( body mass index > or = 30.0 kg/m ) and risks for CNS birth defects , as well as whether gestational diabetes influenced the risks . RESULTS After adjusting for maternal ethnicity , age , education , smoking , alcohol use , and periconceptional vitamin use , obese women had substantially increased risks of delivering offspring with anencephaly ( odds ratio=2.3 ; 95 % confidence interval=1.2 - 4.3 ) , spina bifida ( 2.8 ; 1.7 - 4.5 ) , or isolated hydrocephaly ( 2.7 ; 1.5 - 5.0 ) , but not holoprosencephaly ( 1.4 ; 0.5 - 3.8 ) . Odds ratios were higher for the joint effects of maternal obesity and gestational diabetes , with evidence for interaction on a multiplicative scale . CONCLUSIONS Maternal obesity and gestational diabetes may increase the risk of CNS birth defects through shared causal mechanisms Since 1975 the Rome Microcythaemia Centre has carried out every year , under the auspices of the health authorities of the Latium region , a screening of thalassaemics among intermediate schoolchildren of Latium . From these campaigns , knowledge about thalassaemias among the young adult population has grown which , in its turn , has result ed in screening of these young adults . Through screening in schools between 1975 and 1982 , of 289 763 students examined , 6838 thalassaemics were identified , 6045 of whom were beta- or delta beta-thalassaemics . The total number of young thalassaemics who are identified at present in the Centre through screenings of schoolchildren and young adults is about 3300 per year . Furthermore , from January 1980 to April 1983 , 110 prospect i ve couples of child-bearing age at risk ( 94 of whom originated from Latium ) were identified at the Centre , and five homozygous fetuses ( three of which originated from Latium ) were diagnosed . These data derive from an area in which the frequency of thalassaemia is only 2.4 % , and they show that the programme in Latium for the prevention of Mediterranean anaemia has been successful OBJECTIVE : The aim of this study was to investigate the influence of maternal age on perinatal and obstetric outcome in women aged 40–44 years and those 45 years or older and to estimate whether adverse outcome was related to intercurrent illness and pregnancy complications . METHODS : National prospect i ve , population -based , cohort study in women aged 40–44 years and those 45 years or older and in a control group of women aged 20–29 years who delivered during the period 1987–2001 . Adjusted odds ratios ( OR ) were calculated after adjustments for significant malformations , maternal pre-existing diseases , and smoking . Main outcome measures were perinatal mortality , intrauterine fetal death , neonatal death , preterm birth , and preeclampsia . RESULTS : During the 15-year period , there were 1,566,313 deliveries ( 876,361 women were 20–29 years of age , 31,662 were 40–44 years , and 1,205 were ≥ 45 years ) . Perinatal mortality was 1.4 % , 1.0 % , and 0.5 % in women 45 years or older , 40–44 , and 20–29 years , respectively . Adjusted OR for perinatal mortality was 2.4 ( 95 % confidence interval [ CI ] 1.5–4.0 ) in women aged 45 years or older , compared with 1.7 ( 95 % CI 1.5–1.9 ) in women 40–44 years . Adjusted OR for intrauterine fetal death was 3.8 ( 95 % CI 2.2–6.4 ) in women aged 45 years or older , compared with 2.1 ( 95 % CI 1.8–2.4 ) in women 40–44 years . Preterm birth , gestational diabetes , and preeclampsia were more common among women 40–44 years of age and those 45 years or older . Perinatal mortality was increased in women with intercurrent illness or pregnancy complications compared with women without these conditions , but there was no evidence that these factors became more important with increasing age . CONCLUSION : Perinatal mortality , intrauterine fetal death , and neonatal death increased with age . There was also an increase in intercurrent illnesses and pregnancy complications with increasing age , but this did not entirely explain the observed increase in perinatal mortality with age . LEVEL OF EVIDENCE : PURPOSE To evaluate the efficacy of an abstinence-centered sex education program in adolescent pregnancy prevention , the TeenSTAR Program was applied in a high school in Santiago , Chile . METHODS A total of 1259 girls from a Santiago high school were divided into three cohorts depending on the year they started high school : the 1996 cohort of 425 students , which received no intervention ; the 1997 cohort , in which 210 students received an intervention and 213 ( control group ) did not ; and the 1998 cohort , in which 328 students received an intervention and 83 ( control group ) did not . Students were r and omly assigned to control and intervention groups in these cohorts , before starting with the program . We conducted a prospect i ve , r and omized study using the application of the TeenSTAR sex education program during the first year of high school to the intervention groups in the 1997 and 1998 cohorts . All cohorts were followed up for 4 years ; pregnancy rates were recorded and subsequently contrasted in the intervention and control groups . Pregnancy rates were measured and Risk Ratio with 95 % confidence interval were calculated for intervention and control groups in each cohort . RESULTS Pregnancy rates for the intervention and control groups in the 1997 cohort were 3.3 % and 18.9 % , respectively ( RR : 0.176 , CI : 0.076 - 0.408 ) . Pregnancy rates for the intervention and control groups in the 1998 cohort were 4.4 % and 22.6 % , respectively ( RR 0.195 , CI : 0.099 - 0.384 ) . CONCLUSIONS The abstinence-centered TeenSTAR sex education intervention was effective in the prevention of unintended adolescent pregnancy OBJECTIVES This study determined 4-year postintervention effects of Safe Date s on dating violence , booster effects , and moderators of the program effects . METHODS We gathered baseline data in 10 schools that were r and omly allocated to a treatment condition . We collected follow-up data 1 month after the program and then yearly thereafter for 4 years . Between the 2- and 3-year follow-ups , a r and omly selected half of treatment adolescents received a booster . RESULTS Compared with controls , adolescents receiving Safe Date s reported significantly less physical , serious physical , and sexual dating violence perpetration and victimization 4 years after the program . The booster did not improve the effectiveness of Safe Date s. CONCLUSIONS Safe Date s shows promise for preventing dating violence but the booster should not be used This study evaluated a community-based intervention to help at-risk teens develop healthy , nonabusive relationships with dating partners . Participants were 158 14 - 16-year-olds with histories of child maltreatment who were r and omly assigned to a preventive intervention group or a no-treatment control group . They completed measures of abuse and victimization with dating partners , emotional distress , and healthy relationship skills at bimonthly intervals when dating someone . Intervention consisted of education about healthy and abusive relationships , conflict resolution and communication skills , and social action activities . Growth curve analyses showed that intervention was effective in reducing incidents of physical and emotional abuse and symptoms of emotional distress over-time . Findings support involvement of youths in reducing the cycle of violence as they initiate dating in midadolescence Our objective was to explore the barriers and motivations to : 1 ) appropriate diffusion of genetic services into primary care practice ; and 2 ) primary care physicians ' ( PCPs ) willingness to participate in clinical studies to assess the safety and effectiveness of emerging genetic technologies . A r and om sample ( n = 994 ) of PCPs was invited to be interviewed . Of the 80 who agreed , 60 were interviewed , 52 by telephone . A semi-structured guide was used . A question naire mailed to 752 of the PCPs was used to elicit information from physicians who did not want to be interviewed . Among interviewees , uncertainty as to the clinical utility and clinical validity of predictive genetic testing were the leading barriers to incorporation of this technology into practice , being mentioned by 60 and 43 % of subjects , respectively . Of the 100 ( 13 . 3 % ) physicians returning the question naire who declined to be interviewed , 30 % said they would be willing to participate in research on the safety and effectiveness of predictive genetic tests . Of those who were interviewed , 92 % were willing to participate in such research . Most physicians do not see genetics as important in their practice today ; many anticipate greater importance in the future . The proportion of physicians interested in participating in research to assess the safety and effectiveness of genetic tests is sufficient to make large scale , collaborative , practice -based evaluation feasible . Additionally , participation in research may serve as an effective medium for physician education in genetics OBJECTIVE : To estimate the effect of maternal age on obstetric outcomes . METHODS : A prospect i ve data base from a multicenter investigation of singletons , the FASTER trial , was studied . Subjects were divided into 3 age groups : 1 ) less than 35 years , 2 ) 35–39 years , and 3 ) 40 years and older . Multivariable logistic regression analysis was used to assess the effect of age on outcomes after adjusting for race , parity , body mass index , education , marital status , smoking , medical history , use of assisted conception , and patient 's study site . RESULTS : A total of 36,056 women with complete data were available : 28,398 ( 79 % ) less than 35 years of age ; 6,294 ( 17 % ) 35–39 years ; and 1,364 ( 4 % ) 40 years and older . Increasing age was significantly associated with miscarriage ( adjusted odds ratio [adjOR]2.0 and 2.4 for ages 35–39 years and age 40 years and older , respectively ) , chromosomal abnormalities ( adjOR 4.0 and 9.9 ) , congenital anomalies ( adjOR 1.4 and 1.7 ) , gestational diabetes ( adjOR 1.8 and 2.4 ) , placenta previa ( adjOR 1.8 and 2.8 ) , and cesarean delivery ( adjOR 1.6 and 2.0 ) . Patients aged 35–39 years were at increased risk for macrosomia ( adjOR 1.4 ) . Increased risk for abruption ( adjOR 2.3 ) , preterm delivery ( adjOR 1.4 ) , low birth weight ( adjOR 1.6 ) , and perinatal mortality ( adjOR 2.2 ) was noted in women aged 40 years and older . CONCLUSION : Increasing maternal age is independently associated with specific adverse pregnancy outcomes . Increasing age is a continuum rather than a threshold effect . LEVEL OF EVIDENCE : CONTEXT . Rates of rapid second births among low-income black adolescent mothers range from 20 % to 50 % . Most efforts to prevent rapid second births have been unsuccessful . OBJECTIVES . There were 4 objectives : ( 1 ) to examine whether a home-based mentoring intervention was effective in preventing second births within 2 years of the adolescent mother 's first delivery ; ( 2 ) to examine whether greater intervention participation increased the likelihood of preventing a second birth ; ( 3 ) to examine whether second births were better predicted from a risk practice perspective or a family formation perspective , based on information collected at delivery ; and ( 4 ) to examine how risk practice s or family formation over the first 2 years of parenthood were related to a second birth . DESIGN . We conducted a r and omized , controlled trial of a home-based intervention curriculum , based on social cognitive theory , and focused on interpersonal negotiation skills , adolescent development , and parenting . The curriculum was delivered biweekly until the infant 's first birthday by college-educated , black , single mothers who served as mentors , presenting themselves as “ big sisters . ” The control group received usual care . Follow-up evaluations were conducted in the homes 6 , 13 , and 24 months after recruitment . METHODS . Participants were recruited from urban hospitals at delivery and were 181 first time , black adolescent mothers ( < 18 years of age ) ; 82 % ( 149 of 181 ) completed the 24-month evaluation . RESULTS . Intent-to-treat analyses revealed that control mothers were more likely than intervention mothers to have a second infant . The complier average causal effect was used to account for variability in intervention participation . Having ≥2 intervention visits increased the odds of not having a second infant more than threefold . Only 1 mother who completed ≥6 visits had a second infant . At delivery of their first infant , mothers who had a second infant were slightly older ( 16.7 vs 16.2 years ) and were more likely to have been arrested ( 30 % vs 14 % ) . There were no differences in baseline contraceptive use or other measures of risk or family formation . At 24 months , mothers who had a second infant reported high self-esteem , positive life events , and romantic involvement and residence with the first infant 's father . At 24 months , there were no differences in marital rates ( 2 % ) , risk practice s , or contraceptive use between mothers who did and did not have a second infant . Mothers who did not have a second infant were marginally more likely to report no plans for contraception in their next sexual contact compared with mothers who had a second infant ( 22 % vs 8 % , respectively ) . CONCLUSIONS . A home-based intervention founded on a mentorship model and targeted toward adolescent development , including negotiation skills , was effective in preventing rapid repeat births among low-income , black adolescent mothers . The effectiveness of the intervention could be seen after only 2 visits and increased over time . There were no second births among mothers who attended ≥8 sessions . There was no evidence that risk behavior or contraceptive use was related to rapid second births . There was some evidence that rapid second births among adolescent mothers were regarded as desirable and as part of a move toward increasing autonomy and family formation , thereby undermining intervention programs that focus on risk avoidance . Findings suggest the merits of a mentoring program for low-income , black adolescent mothers , based on a relatively brief ( 6–8 sessions ) curriculum targeted toward adolescent development and interpersonal negotiation skills St and ards of scientific reporting have evolved from the very beginning of scientific reporting . Virtually all journals now publish instructions for authors and most medical journals adhere to certain st and ards of publication . Such st and ards have been promoted by international groups such as the International Committee of Medical Journal Editors ( ICMJE ) and Committee on Publication Ethics ( COPE ) . The ICMJE has published general st and ards for crafting scientific articles : the “ Uniform Requirements for Manuscripts Su bmi tted to Biomedical Journals : Writing and Editing for Biomedical Publication ” [ 7 ] . These guidelines include suggestions not only for manuscript preparation , but also guidelines for ethical issues related to publishing . COPE , however , focuses on ethical issues [ 1 ] . CORR adheres to these guidelines ; authors may find links to these guidelines in our online Instructions for Authors . Such guidelines , as important as they are , lack sufficient detail to ensure all important information is included . Therefore , in addition to these general guidelines for preparing a manuscript , numerous international groups have published guidelines to ensure various sorts of studies contain all essential information . These include the CONSORT ( Consoli date d St and ards of Reporting Trials ) guidelines for r and omized trials [ 2 , 3 , 8 ] , QUORUM ( Quality of Reporting of Meta-analyses ) [ 6 ] and MOOSE ( Meta- analysis Of Observational Studies in Epidemiology ) [ 13 ] for meta-analyses , and STROBE ( Strengthening the Reporting of Observational Studies in Epidemiology ) for various sorts of observational studies ( the majority of clinical studies in surgical disciplines ) [ 12 , 15 ] . In essence , these guidelines tell investigators and authors what information is required to ensure readers ( and review ers ) can properly evaluate the study . Despite these st and ards , most reports of clinical studies lack such critical information . I suspect this is less by intent than lack of awareness of what information is required . In addition , although many journals , including CORR require a Level of Evidence [ 5 , 10 , 16 ] for studies involving patients , most clinical articles published in surgical journals have a relatively low level ; prospect i ve , r and omized trials are uncommon ( and often impractical ) , and even sufficiently large retrospective cohort studies to control for confounding variables may be unachievable for many conditions or treatments in single institutions . In the absence of high levels of evidence , systematic review s [ 9 , 11 , 17 ] and meta-analyses [ 4 ] have become increasingly common . My search of PubMed for articles limited to meta- analysis yielded 276 articles from 1950–1989 , 2116 from 1990–1994 , 3736 from 1995–1999 , 7920 from 2000–2004 , and 9313 from 2005 to 2009 . Most of these analyses undoubtedly collected information from lower level studies , thereby incurring the limitations of the individual studies . Virtually all systematic and meta-analyses we have recently published noted missing and variably reported data . In contrast to medical disciplines , surgical disciplines do not have the advantage of being able to conduct tightly design ed prospect i ve , r and omized , blinded , controlled trials . ( A PubMed search limited to r and omized controlled trials suggested The Journal of Bone and Joint Surgery and CORR had together published 556 RCTs and although I did not individually check these for quality , they reflect a small fraction of the articles both journals publish . ) For the foreseeable future , most of our information will arise from observational studies rather than prospect i ve trials . In this setting , it is especially important that each article contain all relevant information for future systematic review s and meta-analyses . The STROBE guidelines [ 12 ] provide authors with lists of critical information for reporting three sorts of observational studies : cohort ( longitudinal studies typically reporting outcomes of treatment in one or more cohorts ) , case-control ( studies identifying factors in outcomes ) , and cross-sectional studies ( studies to identify prevalence of factors or characteristics in a population at a single time ) . CORR now requires authors to adhere to CONSORT guidelines for r and omized clinical trials , QUORUM guidelines for meta-analyses , and STROBE guidelines for observational clinical studies . Authors will be able to download from our Instructions to Authors convenient templates for the various sorts of articles we publish ; these templates contain the information required . In addition , we request authors read and follow the guidelines in the Cochrane H and book for Systematic Review s of Interventions 4.2.6 [ 14 ] . Adherence to these st and ards will enhance our ability to answer key clinical questions in more definitive ways than we have in the past , and to answer more questions OBJECTIVE --To evaluate the uptake of cystic fibrosis carrier testing offered through primary health care services . DESIGN --Carrier testing for cystic fibrosis was offered to patients of reproductive age through primary health care services . SETTING --Three general practice surgeries and four family planning clinics in South West Hertfordshire District Health Authority . SUBJECTS -- Over 1000 patients aged 16 - 44 attending two general practice s and four family planning clinics and a stratified r and om sample of patients aged 16 - 44 from one general practice 's age-sex register . RESULTS --When screening was offered opportunistically the uptake was 66 % in general practice and 87 % in family planning clinics . Ten per cent of those offered a screening appointment by letter took up the invitation . Of the screened population , 76 % had previously heard of cystic fibrosis , 35 % realised it is inherited , and 18 % realised that carriers need not have any family history . If they found themselves in an " at risk " partnership 39 % would consider not having children and 26 % would consider terminating an affected pregnancy , but in each case most people were unsure how they would react . CONCLUSIONS --Most people offered a cystic fibrosis test opportunistically wish to be tested , and the responses of those tested indicate that knowledge of carrier state would be considered in future reproductive decisions Objective . To determine if sexually transmitted diseases ( STDs ) , including human immunodeficiency virus ( HIV ) infection , risk assessment , and education tools provided as part of office-based primary care reduce adolescent risky sexual behaviors . Design . A r and omized intervention trial with 3- and 9-month follow-up . Setting . Five staff-model managed care sites in Washington , DC ( n = 19 pediatricians ) . Patients . Consecutive 12- to 15-year-olds receiving a general health examination ; 81 % minority . Participation rate = 215/432 ( 50 % ) . Nine-month follow-up rate = 197/215 ( 92 % ) . Intervention . Audiotaped STD risk assessment and education about staying safe ( safer = condoms , safest = abstinence ) . Main Outcome Measures . Adolescent-reported sexual intercourse and condom use . Results . More intervention adolescents reported pediatrician discussion on 11/13 sexual topics . Although more vaginal intercourse ( odds ratio [ OR ] = 2.46 , 95 % confidence interval [ CI ] = 1.04–5.84 ) was reported in the intervention group at 3 months , this was not true of overall sexual intercourse ( OR = 1.55 , 95 % CI = .73–3.32 ) . More sexually active adolescents reported condom use in the intervention group at 3 months ( OR = 18.05 , 95 % CI = 1.27–256.03 ) . At 9 months , there were no group differences in sexual behaviors ; however , more signs of STD were reported by the control ( 7/103 ) than the intervention group ( 0/94 ) . Conclusions . STD risk assessment and education tools administered in a single office visit facilitated STD/HIV prevention education . Any impact on sexual activity and condom use was short-lived . Further research is needed to develop brief , office-based sexual risk reduction for young adolescents Purpose : To develop a model of offering population carrier screening for fragile X syndrome to nonpregnant women in primary care , using a program evaluation framework . Methods : A three-phase approach included : ( I ) needs assessment exploring staff and client attitudes , and informing development of educational material s , question naires and protocol s ; ( II ) offering screening to women , with question naires at baseline ( Q1 ) and another ( Q2 ) 1-month later ; ( III ) genetic counseling for test-positive women and interviews with a subgroup of participants . Results : Of 338 volunteering for Phase II , 94 % completed Q1 , 59 % completed Q2 , and 20 % ( N = 65 ) chose testing revealing one premutation carrier and three gray zone results ; 31 women were interviewed . Tested women had more positive attitudes toward screening ( Q1 : P < 0.001 ; Q2 : P < 0.001 ) compared with untested , although there was no significant difference in mean knowledge scores or anxiety . Women generally supported being offered prepregnancy screening ; however , reasons against being tested included : not currently planning a family ; perceiving benefits of screening as unimportant ; and having to return for testing . Conclusion : This is the first prospect i ve study exploring informed decision-making for fragile X syndrome carrier screening , using a thorough process of consultation , with no apparent harms identified . It provides a model for development of future genetic screening programs OBJECTIVES A theory-based curriculum design ed to delay the onset of intercourse and increase use of condoms was implemented in the classrooms of six Los Angeles middle schools . METHODS The curriculum activities were very interactive , emphasized skill building , and were implemented by well trained peer educators , including young HIV-positive males and teen mothers . To evaluate the impact of the curriculum , 102 classrooms of students were r and omly assigned to receive either the existing curriculum or the existing curriculum plus the intervention curriculum . Students completed confidential question naires before program implementation , five months later , and 17 months later . A total of 1,657 students completed both the baseline and 17-month follow-up question naires . RESULTS Analyses of these data revealed that the curriculum significantly increased knowledge , significantly improved only two out of 21 attitudes or beliefs , and did not significantly change sexual or contraceptive behaviors . CONCLUSIONS Well implemented programs that are based on upon theory , use interactive activities , and utilize well-trained peer educators do not always change important sexual attitudes and behaviors among middle school youth We examined the effects of short interpregnancy intervals on small-for-gestational age and preterm births in a biracial population using North Carolina birth certificate data from 1988 to 1994 . We defined small-for-gestational age birth as being below the 10th percentile on a race- , sex- , and parity-specific growth curve after a gestation of 37 - 42 weeks . We defined preterm birth as a gestation of less than 37 weeks . We analyzed birth records from all eligible singleton births to black or white women ages 15 - 45 years after an interpregnancy interval of 0 - 3 months ( N = 11,451 ) and a r and om sample of singleton births after an interval of 4 - 24 months ( N = 23,118 ) . We defined interpregnancy interval exposure categories as 0 - 3 , 4 - 12 , and 13 - 24 months . The multivariate adjusted odds ratio for small-for-gestational age births after interpregnancy intervals of 0 - 3 months compared with 13 - 24-month intervals was 1.6 ( 95 % confidence interval = 1.4 - 1.8 ) . The odds ratio for preterm birth after interpregnancy intervals of 0 - 3 months was 1.2 ( 95 % confidence interval = 1.1 - 1.3 ) . Odds ratios did not vary substantially by race for either outcome Background Children of adolescent mothers have higher rates of morbidity and unintentional injuries and hospitalizations during the first 5 years of life than do children of adult mothers . Objective The purpose of this study was to evaluate the 2-year postbirth infant health and maternal outcomes of an early intervention program ( EIP ) of home visitation by public health nurses ( PHNs ) . Methods In a r and omized controlled trial , a sample of predominantly Latina and African American adolescent mothers was followed from pregnancy through 2 years postpartum . The experimental group ( EIP , n = 56 ) received preparation-for-motherhood classes plus intense home visitation by PHNs from pregnancy through 1 year postbirth ; the control group ( TPHNC , n = 45 ) received traditional public health nursing care ( TPHNC ) . Health outcomes were determined based on medical record data ; other measures evaluated selected maternal behaviors , social competence , and mother-child interactions . Results The total days of non-birth-related infant hospitalizations during the first 24 months was significantly lower in the EIP ( 143 days ) than the TPHNC group ( 211 days ) and episodes of hospitalization were fewer ; more EIP than THHNC infants were never seen in the emergency room . The EIP mothers had 15 % fewer repeat pregnancies in the first 2 years postbirth than TPHNC mothers . The TPHNC mothers significantly increased marijuana use over time , whereas EIP mothers did not . Conclusions The EIP improved in selected areas of infant and maternal health , and these improvements were sustained for a period of 1 year following program termination . These findings have important implication s for healthcare services This study evaluated the effects of peer counseling in a culturally specific adolescent pregnancy prevention program for African American females . A r and om pretest and multiple posttest experimental and comparison group design was used to obtain data on a sample of 63 female African American adolescents , ages 12 to 16 , who lived in four public housing developments . Descriptive data and tests of significance revealed that none of the participants who received peer counseling became pregnant within three months of the intervention . Findings revealed a statistically significant increase in reproductive and other self-related knowledge topics among the experimental group when comparing pretest and eight-week posttest scores . Most participants had not had sexual intercourse ; the average age of sexual onset was 12 years in the experimental group and 11 years in the controls . Design ing and implementing culturally specific adolescent pregnancy prevention programs for adolescents younger than age 11 and /or before sexually active seems appropriate The aim of this study was to assess the attitudes and intentions of individuals planning a pregnancy with regard to preconceptional cystic fibrosis ( CF ) carrier screening and to determine factors associated with a positive and negative/neutral intention to have the test . A survey , based on a question naire , was conducted among a stratified r and om sample of 303 recently married couples ( 606 individuals ) . Of the eligible individuals , 70 % ( n = 380 ) participated . Of the respondents , 73 % had a positive attitude toward a routine offer of preconceptional CF carrier screening , and 56 % had the intention to participate in a screening program . A positive intention to have the test was associated with high perceived anticipation of regret , intended preconceptional behavior , high perceived pressure from experts , high perceived consequences of the test results , low perceived barriers , and low perceived negative consequences for family members . These results suggest that the offer of routine preconceptional CF carrier screening would lead to substantial acceptance among couples planning a pregnancy . Several variables related with intention were identified OBJECTIVE --To determine the acceptability and feasibility of screening for carriers of cystic fibrosis in a primary care setting . DESIGN --Follow up study over 15 months of patients offered carrier testing by mouthwash . SETTING --A general practice in inner London . SUBJECTS--5529 patients aged 18 - 45 invited by various methods and combinations of methods ( letter , booklet , personal approach ) for testing . MAIN OUTCOME MEASURES --Uptake of screening , anxiety , and knowledge of test . RESULTS --957 ( 17 % ) invitees were screened over the 15 months . 28 carriers and no carrier couples were detected . Uptake rates were 12 % ( 59/502 patients ) among patients invited by letter and tested by appointment ; 9 % ( 47/496 ) among patients invited by letter , with leaflet , and tested by appointment ; 4 % ( 128/2953 ) among patients invited by letter six weeks before the end of the study and tested by appointment ; 17 % ( 81/471 ) among patients offered passive opportunistic testing ; 70 % ( 453/649 ) among patients offered active opportunistic testing ; and 25 % ( 22/88 ) among patients offered active opportunistic testing by appointment . A short term rise in anxiety among those given a positive test result had dissipated by three months . At three months about one fifth and one third of those given positive and negative results respectively did not underst and their results correctly . CONCLUSION --These results suggest that the strongest variable in determining uptake of screening is the active approach by a health professional offering immediate testing . It remains to be resolved whether the high uptake rates achieved by active recruitment indicate a supply push for this new test rather than a dem and from the population CONTEXT It is estimated that half of unintended pregnancies could be averted if emergency contraception ( EC ) were easily accessible and used . OBJECTIVE To evaluate the effect of direct access to EC through pharmacies and advance provision on reproductive health outcomes . DESIGN , SETTING , AND PARTICIPANTS A r and omized , single-blind , controlled trial ( July 2001-June 2003 ) of 2117 women , ages 15 to 24 years , attending 4 California clinics providing family planning services , who were not desiring pregnancy , using long-term hormonal contraception or requesting EC . INTERVENTION Participants were assigned to 1 of the following groups : ( 1 ) pharmacy access to EC ; ( 2 ) advance provision of 3 packs of levonorgestrel EC ; or ( 3 ) clinic access ( control ) . MAIN OUTCOME MEASURES Primary outcomes were use of EC , pregnancies , and sexually transmitted infections ( STIs ) assessed at 6 months ; secondary outcomes were changes in contraceptive and condom use and sexual behavior . RESULTS Women in the pharmacy access group were no more likely to use EC ( 24.2 % ) than controls ( 21.0 % ) ( P = .25 ) . Women in the advance provision group ( 37.4 % ) were almost twice as likely to use EC than controls ( 21.0 % ) ( P<.001 ) even though the frequency of unprotected intercourse was similar ( 39.8 % vs 41.0 % , respectively , P = .46 ) . Only half ( 46.7 % ) of study participants who had unprotected intercourse used EC over the study period . Eight percent of participants became pregnant and 12 % acquired an STI ; compared with controls , women in the pharmacy access and advance provision groups did not experience a significant reduction in pregnancy rate ( pharmacy access group : adjusted odds ratio [ OR ] , 0.98 ; 95 % confidence interval [ CI ] , 0.58 - 1.64 ; P = .93 ; advance provision group : OR , 1.10 ; 95 % CI , 0.66 - 1.84 , P = .71 ) or increase in STIs ( pharmacy access group : adjusted OR , 1.08 , 95 % CI , 0.71 - 1.63 , P = .73 ; advance provision group : OR , 0.94 , 95 % CI , 0.62 - 1.44 , P = .79 ) . There were no differences in patterns of contraceptive or condom use or sexual behaviors by study group . CONCLUSIONS While removing the requirement to go through pharmacists or clinics to obtain EC increases use , the public health impact may be negligible because of high rates of unprotected intercourse and relative underutilization of the method . Given that there is clear evidence that neither pharmacy access nor advance provision compromises contraceptive or sexual behavior , it seems unreasonable to restrict access to EC to clinics OBJECTIVE The purpose of this study was to assess the influence of maternal age on obstetric indices of uterine efficiency in spontaneous nulliparous labor managed according to a st and ardized protocol in order to determine whether increasing maternal age is more commonly associated with dystocia . STUDY DESIGN Information was collected prospect ively and retrieved retrospectively from an obstetric data base for a 5-year period on a consecutive series of nulliparas in spontaneous term ( > or = 37 weeks ' gestation ) labor with singleton cephalic presentations . All women were managed according to an established Active Management protocol . Indices for dystocia , including need for oxytocin augmentation , prolonged labor ( > 12 hr ) , instrumental delivery , and cesarean section were compared between 5 maternal age categories ( < 20 years , 20 - 24 , 25 - 29 , 30 - 34 , and > or = 35 years ) . RESULTS The obstetric outcomes of 10,737 consecutive nulliparas in spontaneous term labor were analyzed for the 5 years 1998 to 2002 . The incidences of oxytocin augmentation , prolonged labor , instrumental delivery , and intrapartum cesarean section including cesareans for dystocia all increased significantly and progressively with increasing maternal age . Mean gestational age and birth weight were similar in each age category . CONCLUSION In a context of uniform labor management , all 4 indices of dystocia examined were increased progressively with maternal age , although oxytocin augmentation proved a generally effective intervention in all age categories . These findings have implication s for the analysis of intervention rates by health care providers , particularly in developed countries where the proportion of older nulliparas is increasing Postponing Sexual Involvement ( PSI ) is a widely implemented middle school curriculum design ed to delay the onset of sexual intercourse . In an evaluation of its effectiveness among seventh and eighth grade rs in California , 10,600 youths from schools and community-based organizations statewide were recruited and participated in r and omly assigned intervention or control groups ; the curriculum was implemented by either adult or youth leaders . Survey data were collected before the program was implemented , and at three months and 17 months afterward . At three months , small but statistically significant changes were found in fewer than half of the measured attitudes , behaviors and intentions related to sexual activity ; at 17 months , none of these significant positive effects of the PSI program had been sustained . At neither follow-up were there significant positive changes in sexual behavior ; Youths in treatment and control groups were equally likely to have become sexually active , and youths in treatment groups were not less likely than youths in control groups to report a pregnancy or a sexually transmitted infection . The evaluation suggests that PSI may be too modest in length and scope to have an impact on youths ' sexual behavior Social differences in late fetal death and infant mortality were examined in a population -based prospect i ve study . All singletons born to Nordic citizens in Sweden 1985 - 86 were included , 185,156 births in all . The overall rates of late fetal death and infant mortality were 3.5 and 5.3 per 1000 respectively . Socio-economic status of the household ( SES ) and mothers ' education were used as social indicators . Logistic regression analyses showed significant odds ratios between 1.3 and 1.8 for late fetal death for blue-collar workers and women with less than 12 years education . The analyses of neonatal mortality showed a U-shaped relationship : both unskilled blue-collar workers and high level white-collar workers had significant odds ratios ( OR ) as compared with intermediate level white-collar workers ( OR = 1.5 ) . Similar results were obtained when using the mothers ' education as indicator of social status : 9 years education or less or 15 years or more were associated with significant higher mortality rates than 12 years education ( OR = 1.6 ) . An inverse relationship between social status and post-neonatal mortality was seen in the crude analysis . Mothers ' education revealed more social differences than SES ( crude OR = 2.0 and 1.5 respectively in the least privileged group ) . However , when adjusting for the effects of maternal age , parity and smoking , no significant odds ratios for the social variables were obtained The first manual vacuum aspiration ( MVA ) services unit in Nepal was established in 1995 at the country 's largest national maternity hospital in Kathm and u. This research sought to assess and evaluate the safety , acceptability , and effectiveness of MVA services . This prospect i ve study was conducted during 12 months in 1998 , and follow-up was made at six weeks . Two groups of patients were compared : 529 patients treated in the MVA unit and 236 patients who were clinical ly eligible for treatment in the MVA unit but were treated instead in the main operation theatre ( OT ) owing to the unavailability of services in the MVA unit during the hours of their admission . The two groups differed with respect to some of their background characteristics but were similar in their clinical characteristics . The MVA group received contraceptive counselling and services and had significantly shorter stays in hospital . However , the direct cost incurred by the patients , regardless of the type of facility they used , was about the same . Follow-up at six weeks revealed that the MVA patients had significantly fewer complaints and were generally more satisfied with the services they had received than their counterparts . Slightly more than half of the women in the MVA group were using contraception at the time of follow-up compared to no women in the OT group . It is concluded that the MVA unit provided safe , effective , and efficient services to about 50 % of all the patients admitted to the hospital with post-abortion complications . An additional 25 % of the post-abortion patients could be served if the unit were kept open 24 hours a day , saving re sources and time for patients and hospital staff . As a parallel development , both MVA and main OT services would need to be more effectively integrated with outside antenatal and family-planning clinics to address the reproductive health needs of women , thereby reducing the number of patients requiring post-abortion care Conducted in diverse sociocultural communities in Los Angeles County , the project implemented and evaluated a family life education program design ed to prevent the negative outcomes of risky sexual behavior . A sample of 251 male and female early adolescents 9 through 14 years of age participated with their parents in this abstinence-based adolescent pregnancy prevention program . The project sought to improve parent-child communications and delay the onset of sex-related behaviors through direct involvement of parents in the education process . Naturally occurring community groups were r and omly assigned by site to treatment or delayed treatment conditions in a longitudinal quasi-experimental evaluation design . The evaluation demonstrated significant improvements in communication between parents and children immediately following the intervention ; however , these improvements were no longer present 12 months postintervention . The process and outcome evaluation methods employed in the study triangulated qualitative and quantitative data collection and analysis procedures . This combination provided other sources of data than the traditional outcome measures used in most evaluation studies , thus addressing some of the gaps in present program evaluations . Descriptions of the process evaluation , integrated with the outcome data , are intended to heighten nurses ’ awareness of the importance of this component of research and the rich qualitative data it may yield . The qualitative process components in the project captured the experience of the investigators when they encountered many of the complex challenges that confront research ers who implement and evaluate family life education programs among early adolescents . This experience provided the basis for suggested strategies that nurse clinicians and research ers can use in their work with early adolescents and their parents in clinical - , school- , and community-based setting BACKGROUND We have investigated a strategy for identifying and counseling carriers of recessively inherited disorders in developing countries where consanguineous marriage is common . In such communities , gene variants are trapped within extended families , so that an affected child is a marker of a group at high genetic risk . METHODS Fifteen large Pakistani families , 10 with a history of a hemoglobin disorder and 5 without any such history ( controls ) , were screened for beta-thalassemia and abnormal hemoglobins . All carriers and married couples consisting of two carriers received counseling , and eight families have been followed for two years . RESULTS In the control families , no carrier was found among 397 members tested . In the 10 families with an index case , 183 of 591 persons tested ( 31 percent ) were carriers ; carriers had a 25 percent risk of being in a marriage at risk for producing an affected child , and 17 of 214 married couples ( 8 percent ) consisted of two carriers . No couple at risk was identified among 350 r and omly selected pregnant women and their partners . All carriers reported that they have used the information provided in the testing and counseling process : carriers married to carriers with two or more healthy children have avoided further pregnancy , and most such couples with one or no healthy children have used prenatal diagnosis . Seven of eight new marriages and engagements are known not to be at risk . CONCLUSIONS Testing of extended families is a feasible way of deploying DNA-based genetic screening in communities in which consanguineous marriage is common AIM To determine the feasibility and acceptability of premarital screening for beta thalassemia/related hemoglobinopathies followed by prenatal diagnosis in India . MATERIAL S AND METHODS Premarital testing for thalassemia carrier state was carried out in ( 1 ) extended family members ( EFM ) of diagnosed cases of thalassemia/hemoglobinopathies , ( 2 ) unmarried adult cases of anemia attending the hospitals ' outpatient department ( OPD ) and ( 3 ) adult college students ( CG ) . Hemoglobin , red cell indices were measured by a cell counter and hemoglobin fractionation was carried out by high performance liquid chromatography ( HPLC ) . In cases with HbA2>3.5 % , or with variant hemoglobin , mutation screen was done by amplification refractory mutation system polymerase chain reaction ( ARMS-PCR ) . In high-risk prospect i ve couples , premarital genetic counseling was done and prenatal diagnosis possibilities were explained . RESULTS The yield of carriers from EFM , OPD and CG groups was 78.17 % ( 308/394 ) , 19.51 % ( 263/1348 ) and 4.04 % ( 38/939 ) , respectively . The number of prospect i ve high-risk couples detected were 154 , 48 and 2 from EFM , OPD and CG , respectively . As much as 99 % of prospect i ve carrier couples married even after knowing their high-risk status and opted for prenatal diagnosis . The program averted the birth of 33 thalassemic children ; 28 in EFM group ( by screening of 394 individuals ) , 4 in the OPD group ( by screening 1348 anemic patients ) , and 1 in CG group ( by screening of 939 students ) . CONCLUSION Premarital screening in extended family members , followed by prenatal diagnosis is acceptable and the most effective strategy for control of thalassemia in developing countries like India Summary A population -based case-control study of the determinants of stillbirths was conducted in Greece from 1989 to 1991 . All reported stillbirths after 28 weaks of pregnancy ( N=2,006 ) during the three year study period comprised the case group . The control group derived from r and om sampling of 10 % of all livebirths in Greece , during the same period ( N=30,705 ) . The data were analysed by modelling through multiple logistic regression . The adjusted relative risk of stillbirth was significantly higher for males compared to females . A statistically significant monotonic increase in relative risk was observed with shorter gestational age , low maternal education , and older maternal age . Birthweight and parity showed a statistically significant U-shaped association with stillbirth risk , with a higher risk being observed among both low and high birthweight deliveries , as well as among primiparous or multiparous ( 4 + ) mothers . Positive associations of stillbirth with multiple births , out-of-wedlock marriage and non-Greek-orthodox maternal religion were noted in crude analyses , but these associations almost disappeared in the logistic regression model . Maternal urban or rural residence showed no relation to risk . Overall , the prospect i ve risk of stillbirth after the 24th week of gestation in Greece has been estimated to be higher than that in Japan ( a more developed country ) with more than 40 % of stillbirths occurring after the 36th week of pregnancy . ZusammenfassungIn der griechischen Bevölkerung wurde eine Fall-Kontrollstudie über Risikofaktoren von Totgeburten zwischen 1989 und 1991 durchgeführt . Die während der 3 Jahre in ganz Griechenl and registrierten Totgeburten innerhalb der ersten 28 Schwangerschaftswochen ( n=2006 ) bildeten die Gruppe der Fälle . I m selben Zeitraum wurden 10 % der Lebendgeburten der L and es als Kontrollgruppe r and omisiert ausgewählt ( n=30705 ) . Mittels multipler linearer Regression wurden die Date n analysiert . Das angepasste relative Risiko des Todes war bei der männlichen Frucht signifikant höher als bei der weiblichen . Ein statistisch signifikantes und monotones Ansteigen des relativen Risikos zeigte sich bei verkürzter Gestationsdauer , tiefer Schulbildung und höherem Alter der Mutter . Geburtsgewicht und Parität verliefen mit intrauterinem Sterberisiko in einer U-förmigen Beziehung Dabei stieg das Risiko sowohl mit tiefer als auch mit höher werdendem Geburtsgewicht , und es war bei Pimiparae und Multiparae ( 4 und mehr Geburten ) höher als bei Müttern mit 2 bis 3 Geburten . Die nach den ersten Berechnungen positive Korrelation zwischen Totgeburt und Multiparität verschw and fast vollständig in der logarithmischen Regression , wenn die Mütter nicht verheiratet und nicht griechisch orthodox waren . Wohnsitz in der Stadt oder auf dem L and hatte keine Beziehung zum Risiko . Insgesamt war das Risiko einer Totgeburt in den ersten 24 Schwangerschaftswochen in Griechenl and grösser als i m höher entwickelten Japan , wo in den ersten 36 Schwangerschaftswochen mehr als 40 % aller Totgeburten auftreten . RésuméUne étude de cas-contrôle a été conduite sur des facteurs de risque de mort-né de la population grecque entre 1989 et 1991 . Tous les cas de morts-nés régistrés après 28 semaines de gestation ( n=2006 ) durant les trois années d'étude ont formés la groupe des cas . Parmis tous les nouveaux nés vivants du pays 10 % ont étés choisis comme groupe de contrôle ( n=30705 ) durant la même période . Les donnés ont été analysés par la régression linéaire multiple . Il se montait que le risque de mort-né fut plus élevé pour le sexe masculin comparé au féminine . Une montée statistiquement significant et monotone a été observée sur le risque relatif , si la durée de gestation diminuait , si une basse éducation maternelle et un âge maternal plus élevé . Le poids de naissance et la parité suivaient le risque de mort-né par une courbe de forme d'un U : Le risque se réduit si le poids de naissance devenait bas ou haut ainsi que si la mère était une primipara ou multipara ( 4 naissances ou plus ) . Selon les premières calculations la corrélation entre mort-né et multiparité était positive mais ce résultat disparaissait presque par la régression logarithmique , si les mères n'étaient ni mariées ni grecque-orthodoxes . Le risque ne dépendait pas du domicile urbain ou rural . Finallement le risque prospect if de mort-né pendant les premières 24 semaines de gestation en Grèce a été estimé plus élevé qu'en Japon , un pays plus développé , avec plus 40 % de tous les mort-nés se passent durant les premières 36 semaines de gestation OBJECTIVE This study quantified the impact of delayed childbearing ( maternal age greater-than-or-equal to 35 years ) on population rate changes in low birth weight ( LBW ; < 2500 g ) , preterm delivery ( < 37 weeks ) , multiple births , and small for gestational age ( SGA ; < 10th percentile ) in Alberta , Canada , between 1990 ( N = 42 930 ) and 1996 ( N = 37 710 ) . METHODS Data were obtained from the provincial notification of a live or stillbirth . Analyses included relative risk estimates and chi(2 ) tests for trend . Potential confounding attributable to in vitro fertilization was investigated . RESULTS The proportion of births to women greater-than-or-equal to 35 years of age was 8.4 % in 1990 and 12.6 % in 1996 , a 51.2 % increase . Among these women , LBW delivery increased 11 % , and preterm delivery increased 14 % . Delayed childbearing accounted for 78 % of the change in LBW rate in the population and 36 % of the change in preterm delivery rate in the population . Provincial multiple birth rates increased by 15 % for twins and 14 % for triplets . Delayed childbearing accounted for 15 % of the twin increase and 69 % of the triplet increase . When in vitro fertilization pregnancies were excluded , the change was 43 % for preterm rates , 100 % for LBW , 14 % for twins , and 9 % for triplets . Delayed childbearing did not contribute to changes in singleton SGA deliveries . CONCLUSIONS The findings suggest that the recent increase in LBW and preterm delivery is partly related to the population phenomenon of delayed childbearing . Maternal age was not related to changes in SGA , suggesting that the age effect is through pregnancy complications that lead to preterm delivery and LBW . Prospect i ve parents should be informed about the higher risk for neonatal morbidity associated with delayed childbearing . Health care providers should be aware of the impact of delayed childbearing on health care re sources Objectives : The United States Food and Drug Administration cited an absence of data on young adolescents as the reason the emergency contraceptive , Plan B , could not be moved over-the-counter . This study analyzed data on young adolescents with increased access to emergency contraception . Methods : We conducted an age-stratified analysis with previously published data from a r and omized , controlled trial of Plan B with a sample size of 2,117 , including 964 adolescents , 90 of whom were aged younger than 16 years . Participants were r and omly assigned to nonprescription pharmacy access , advance provision of 3 packs , or clinic access ( control ) . We measured contraceptive and sexual risk behaviors at baseline and 6-month follow-up and tested for pregnancy and sexually transmitted infections . We used contingency table and logistic regression analysis to measure the effect of the intervention on risk behaviors in young adolescents ( < 16 years ) , compared with middle adolescents ( 16–17 years ) , older adolescents ( 18–19 years ) , and adults ( 20–24 years ) . Results : Adolescents aged younger than 16 years behaved no differently in response to increased access to emergency contraception ( EC ) from the other age groups . As with adults , EC use was greater among adolescents in advance provision than in clinic access ( 44 % compared with 29 % ; P ≤ .001 ) , and other behaviors were unchanged by study arm , including unprotected intercourse , condom use , sexually transmitted infection acquisition , or pregnancy . Additionally , adolescents with increased access to EC did not become more vulnerable to unwanted sexual activity . Conclusion : Young adolescents with improved access to EC used the method more frequently when needed , but did not compromise their use of routine contraception nor increase their sexual risk behavior . Level of Evidence : OBJECTIVES An earlier report described desirable 1-month follow-up effects of the Safe Date s program on psychological , physical , and sexual dating violence . Mediators of the program-behavior relationship also were identified . The present report describes the 1-year follow-up effects of the Safe Date s program . METHODS Fourteen schools were in the r and omized experiment . Data were gathered by question naires in schools before program activities and 1 year after the program ended . RESULTS The short-term behavioral effects had disappeared at 1 year , but effects on mediating variables such as dating violence norms , conflict management skills , and awareness of community services for dating violence were maintained . CONCLUSIONS The findings are considered in the context of why program effects might have decayed and the possible role of boosters for effect maintenance The authors evaluated the effectiveness of a school-based sex education program in decreasing rates of sexual intercourse , improving birth control use , and decreasing the incidence of pregnancies among teenagers 16 years of age and younger . Twenty-one schools received either the McMaster Teen Program or the conventional didactic sex education program . Preprogram , the mean age of the students was 12.6 years . There were no statistically significant differences between groups in time to first sexual activity for males , χ2(1 ) = 2.93 , p = 0.09 ; time to first sexual activity for females , χ2(1 ) = 0.50 , p = 0.48 ; and time to first pregnancy , χ2(1 ) = 1.90 , p = 0.17 . Significantly more experimental group males reported always using birth control at year 1 ( difference 8.9 % ; 95 % confidence interval [ CI ] = 0.4,17.4 ) . Limitations of the program that may have influenced the results were the exclusion of contraception information and its short duration Knowledge of the opinions of physicians with regard to preconceptional cystic fibrosis ( CF ) carrier screening and the possible factors that are associated with their opinions is important for the implementation of such a screening program . Data were obtained from a study in which genetic knowledge , opinions with regard to genetic testing and related skills were investigated . A question naire , developed and used by American research ers , was adapted to the Dutch health care situation , and sent to r and omly selected general practitioners ( GPs ) ( n = 200 ) , gynecologists ( GYNs ) ( n = 300 ) , and pediatricians ( PEDs ) ( n = 265 ) . In this part of the study , their opinions with regard to genetic preconceptional CF carrier screening in different situations were assessed . The response rate for the GPs , GYNs , and PEDs was 64 % , 69 % , and 72 % , respectively . In total , 63 % of the GPs , 69 % of the GYNs and 72 % of the PEDs supported preconceptional CF carrier testing if a couple requested a test . Sixteen percent , 19 % and 25 % , respectively , were in favor of actively offering a test with 95 % test sensitivity to all couples who were planning a pregnancy . A positive opinion on preconceptional CF carrier screening was associated with the following variables : " considering the test sensitivity as less important " ( GPs , GYNs ) , " high perceived risk of having a child with CF " ( GYNs ) , " providing genetic counselling in their own practice " ( PEDs ) and " reassurance when both partners test negative " ( PEDs ) . Physicians are sympathetic toward preconceptional CF carrier screening if the couples themselves request a test . Physicians had reservations about routinely offering a CF carrier test In many countries , women treated for complications from spontaneous or unsafely induced abortion lack access to contraceptive services . As a result , many of them soon have a subsequent unplanned pregnancy or a repeat abortion , placing their health at increased risk . This report presents the results of a prospect i ve intervention study on postabortion family planning conducted in the two largest public hospitals in Zimbabwe . Women at Harare Central Hospital , in the capital , received a postabortion family planning intervention , and Mpilo Central Hospital , in Bulawayo , served as the control site . The study cohort was 982 women , 527 of whom were followed for a 12-month period . During the follow-up period , significantly more women used highly effective methods of contraception , significantly fewer unplanned pregnancies occurred , and fewer repeat abortions were performed at the intervention site than at the control site . These results offer compelling evidence that ward-based contraceptive services provided to women treated for incomplete abortion can significantly reduce subsequent unplanned pregnancies . The results also suggest that postabortion family planning services can reduce the incidence of repeat abortion Parent training was provided for 80 low-income , black teenage mothers during their infants ' first six months . Half of the mothers were visited biweekly in their homes to be instructed in caregiving and in sensorimotor and interaction exercises , and half were trained as CETA ( Comprehensive Employment Training ACT)-paid , teacher 's aides in a medical school infant nursery that provided care for their infants and infants of medical faculty . Growth and development during the first two years were superior for the infants whose mothers received training , particularly those who received paid parent training as teacher 's aides in the infant nursery . Repeat pregnancy rates were lower and return to work/school rates were higher for the infant nursery mothers , most of whom subsequently pursued nurse 's aide training Poor compliance with contraceptive regimens has been shown to be an important antecedent of adolescent pregnancy . The purpose of this study was to test prospect ively the effect of a peer v nurse counseling program on adolescent compliance with the use of oral contraceptives . Fifty-seven females aged 14 to 19 years from a lower socioeconomic background were r and omly assigned to a peer ( n = 26 ) or nurse ( n = 31 ) group . At the initial visit and at 1- , 2- , and 4-month follow-up visits , subjects received Ortho-Novum 1/35 combined with a tablet marker and were counseled by a nurse or peer . Noncompliance was measured using a Guttman scale consisting of : ( 1 ) avoidance of pregnancy , ( 2 ) appointment adherence , ( 3 ) pill count , and ( 4 ) urinary fluorescence for riboflavin . At the first and second follow-ups , the adolescents counseled by a peer had a significantly ( P less than or equal to .038 ) lower noncompliance level than the nurse-counseled group . Adolescents with more frequent sexual activity ( P less than or equal to .027 ) , with one sexual partner ( P less than .04 ) , and who worried that they might become pregnant ( P less than or equal to .01 ) had significantly lower levels of noncompliance when counseled by a peer than by a nurse . At the fourth month follow-up , adolescents who expressed feelings of hopelessness about the future had significantly ( P less than or equal to .036 ) higher levels of noncompliance when counseled by a nurse than when counseled by a peer . These results suggest that incorporating a peer counselor into the health care team may be an effective method of increasing adolescent compliance |
10,586 | 21,993,583 | The higher costs of frequent compared to conventional home hemodialysis were because of higher consumable usage due to dialysis frequency .
Thus , our findings reinforce the conclusions of previous studies showing that home-based conventional and more frequent hemodialysis may provide clinical benefit at reasonable costs | More intensive and /or frequent hemodialysis may provide clinical benefits to patients with end-stage renal disease ; however , these dialysis treatments are more convenient to the patients if provided in their homes .
Here we created a st and ardized model , based on a systematic review of available costing literature , to determine the economic viability of providing hemodialysis in the home that arrays costs and common approaches for assessing direct medical and nonmedical costs . | The London Daily/Nocturnal Hemodialysis Study , a prospect i ve , comparative , nonr and omized study , directly compared outcomes of quotidian ( daily ) hemodialysis patients with conventional thrice-weekly hemodialysis patients . Patients were assigned to either daily ( short-hours ) hemodialysis ( n = 11 ) or nocturnal hemodialysis ( n = 12 ) and followed up for 5 - 36 months ; all data were directly compared with matched control patients receiving conventional hemodialysis ( n = 22 ) . Outcomes evaluated were adequacy ( urea kinetics ) , nutrition , anemia management , blood pressure and volume control , calcium/phosphorus control , and patient quality of life . In addition , a detailed economic analysis was undertaken . The study showed that both quotidian hemodialysis regimens are more effective than conventional hemodialysis in improving weekly urea clearance . Significant clinical improvements were seen with quotidian therapy in the areas of nutrition ( short-hours daily ) , blood pressure ( both ) , volume control ( short-hours daily ) , calcium/phosphorus control ( nocturnal ) , and quality of life ( both ) . A nonsignificant trend for improvement in anemia management was suggested . The economic analysis showed substantial savings in annualized cost per quality -adjusted life-year in changing from conventional hemodialysis ( carried out in-center , in satellite units , or at home ) to home quotidian hemodialysis . The substantial clinical benefits of home quotidian hemodialysis , combined with the economic advantage shown by this study , clearly justify its expansion . ( The details of this study have recently been published in 11 articles in the American Journal of Kidney Diseases[2003;42(suppl 1 ) ] Observational studies suggest improvements with frequent hemodialysis ( HD ) , but its true efficacy and safety remain uncertain . The Frequent Hemodialysis Network Trials Group is conducting two multicenter r and omized trials of 250 subjects each , comparing conventional three times weekly HD with ( 1 ) in-center daily HD and ( 2 ) home nocturnal HD . Daily HD will be delivered for 1.5 - 2.75 h , 6 days/week , with target eK(t)/V(n ) > or = 0.9/session , whereas nocturnal HD will be delivered for > or = 6 h , 6 nights/week , with target stdK(t)/V of > or = 4.0/week . Subjects will be followed for 1 year . The composite of mortality with the 12-month change in ( i ) left ventricular mass index ( LVMI ) by magnetic resonance imaging , and ( ii ) SF-36 R AND Physical Health Composite ( PHC ) are specified as co- primary outcomes . The seven main secondary outcomes are between group comparisons of : change in LVMI , change in PHC , change in Beck Depression Inventory score , change in Trail Making Test B score , change in pre-HD serum albumin , change in pre-HD serum phosphorus , and rates of non-access hospitalization or death . Changes in blood pressure and erythropoiesis will also be assessed . Safety outcomes will focus on vascular access complications and burden of treatment . Data will be obtained on the cost of delivering frequent HD compared to conventional HD . Efforts will be made to reduce bias , including blinding assessment of subjective outcomes . Because no large-scale r and omized trials of frequent HD have been previously conducted , the first year has been design ated a Vanguard Phase , during which feasibility of r and omization , ability to deliver the interventions , and adherence will be evaluated BACKGROUND Although several studies have shown that simulated annual direct health care costs are substantially lower for patients undergoing more frequent hemodialysis ( HD ) , there is limited information about the economics of daily HD and nocturnal HD . METHODS The London Daily/Nocturnal Hemodialysis Study compared the economics of short daily HD ( n = 10 ) , long nocturnal HD ( n = 12 ) , and conventional thrice-weekly HD ( n = 22 ) in patients over 18 months . A retrospective analysis of patients ' conventional HD costs during the 12 months before study entry was conducted to measure the change in cost after switching to quotidian HD . RESULTS As the data show , annual costs ( in Canadian dollars ) for daily HD are substantially lower than for both nocturnal HD and conventional HD : approximately 67,300 Can dollars , 74,400 Can dollars , and 72,700 Can dollars per patient , respectively . Moreover , marginal changes in operating cost per patient year were - 9,800 Can dollars , -17,400 Can dollars , and + 3,100 Can dollars for the daily HD , nocturnal HD , and conventional HD groups . Because of the increase in number of treatments , treatment supply costs per patient for the daily HD and nocturnal HD study groups were approximately twice those for conventional HD patients . However , average costs for consults , hospitalization days , emergency room visits , and laboratory tests for quotidian HD patients tended to decline after study entry . The major cost saving in home quotidian HD derived from the reduction in direct nursing time , excluding patient training . Total annualized cost per quality -adjusted life-year for the daily HD and nocturnal HD groups were 85,442 Can dollars and 120,903 Can dollars , which represented a marginal change of - 15,090 Can dollars and - 21,651 Can dollars , respectively , reflecting both improved quality of life and reduced costs for quotidian HD patients . CONCLUSION Substantial clinical benefits of home quotidian HD , combined with the economic advantage shown by this study , clearly justify its expansion BACKGROUND Care of patients with end-stage renal disease ( ESRD ) is important and re source intense . To enable ESRD programs to develop strategies for more cost-efficient care , an accurate estimate of the cost of caring for patients with ESRD is needed . METHODS The objective of our study is to develop an up date d and accurate itemized description of costs and re sources required to treat patients with ESRD on dialysis therapy and contrast differences in re sources required for various dialysis modalities . One hundred sixty-six patients who had been on dialysis therapy for longer than 6 months and agreed to enrollment were followed up prospect ively for 1 year . Detailed information on baseline patient characteristics , including comorbidity , was collected . Costs considered included those related to outpatient dialysis care , inpatient care , outpatient nondialysis care , and physician cl aims . We also estimated separately the cost of maintaining the dialysis access . RESULTS Overall annual cost of care for in-center , satellite , and home/self-care hemodialysis and peritoneal dialysis were US $ 51,252 ( 95 % confidence interval [ CI ] , 47,680 to 54,824 ) , $ 42,057 ( 95 % CI , 39,523 to 44,592 ) , $ 29,961 ( 95 % CI , 21,252 to 38,670 ) , and $ 26,959 ( 95 % CI , 23,500 to 30,416 ) , respectively ( P < 0.001 ) . After adjustment for the effect of other important predictors of cost , such as comorbidity , these differences persisted . Among patients treated with hemodialysis , the cost of vascular access-related care was lower by more than fivefold for patients who began the study period with a functioning native arteriovenous fistula compared with those treated with a permanent catheter or synthetic graft ( P < 0.001 ) . CONCLUSION To maximize the efficiency with which care is provided to patients with ESRD , dialysis programs should encourage the use of home/self-care hemodialysis and peritoneal dialysis BACKGROUND Home nocturnal hemodialysis ( HNHD ) can improve clinical and biochemical factors in people with renal failure , but its cost-effectiveness relative to conventional in-center hemodialysis ( IHD ) is uncertain . We hypothesized that HNHD would provide more dialysis treatments at a lower total cost than IHD . METHODS A prospect i ve one-year descriptive costing study was performed at two centers in Toronto , Canada , involving patients enrolled from a HNHD program ( N = 33 ) , and a matched cohort from an IHD program ( N = 23 ) . All costs are expressed as mean weekly amount in Canadian year 2000 dollars . A projected mean annual cost ( PMA ) was calculated also . RESULTS The mean number of treatments per week was much higher with HNHD ( 5.7 vs. 3.0 , P = 0.004 ) . Cost categories found to be less expensive for HNHD were staffing ( weekly $ 210 vs. $ 423 , P < 0.001 , PMA $ 10,932 vs. $ 22,056 ) and overhead and support ( weekly $ 80 vs. $ 238 , P < 0.001 , PMA $ 4179 vs. $ 12,393 ) . There was a trend toward lower costs for hospital admissions and procedures ( weekly $ 23 vs. $ 134 , P = 0.355 , PMA $ 1173 vs. $ 6997 ) and for medications ( $ 172 vs. $ 231 , P = 0.082 , PMA $ 8989 vs. $ 12,029 ) . Costs found to be more expensive for HNHD were the cost of direct hemodialysis material s ( weekly $ 318 vs. $ 126 , P < 0.001 , PMA $ 16,587 vs. $ 6575 ) and capital costs ( weekly $ 118 vs. $ 17 , P < 0.001 , PMA $ 6139 vs. $ 871 ) , with a trend toward higher cost for laboratory tests ( weekly $ 33 vs. $ 26 , P = 0.094 , PMA $ 1744 vs. $ 1364 ) . Physician costs were the same at $ 128 per week ( PMA $ 6650 ) . The weekly mean total cost for health care delivery was 20 % less for HNHD ( $ 1082 vs. $ 1322 , P = 0.006 ) , with projected mean annual costs more than $ 10,000 lower ( $ 56,394 vs. $ 68,935 ) . CONCLUSIONS HNHD provides about three times as many treatment hours at nearly a one-fifth lower cost , with savings evident even when only program and funding -specific costs are considered |
10,587 | 29,461,969 | Globally , the animal studies showed a marked tendency towards a down-regulation of TLR2 and 4 expression accompagnied with , a reduced activation of nuclear factorkappaB ( NF-κB ) signaling and cytokine production , and an improvement in insulin sensitivity and body composition .
CONCLUSION While animal studies showed a marked tendency towards TLR2 and 4 down-regulation after chronic endurance exercise , the current evidence in human is not sufficiently robust to conclude any role of TLR in the anti-inflammatory properties of exercise | BACKGROUND Obesity and metabolic syndrome are disorders that correlate with the activation of pro-inflammatory pathways and cytokine production , to which Toll like receptors ( TLR ) contribute .
Exercise may act as an anti-inflammatory modulator , but there is no consensus about the role of the TLR in this tuning .
The present styudy aims to systematic ally review the current evidence on exercise-induced TLR regulation in animals and humans suffering from obesity and metabolic syndrome . | Exercise can have anti-inflammatory effects in obesity , but the optimal type and intensity of exercise are not clear . This study compared short-term high-intensity interval training ( HIIT ) with moderate-intensity continuous training ( MICT ) in terms of improvement in cardiorespiratory fitness , markers of inflammation , and glucose control in previously inactive adults at elevated risk of developing type 2 diabetes . Thirty-nine inactive , overweight/obese adults ( 32 women ) were r and omly assigned to 10 sessions over 2 wk of progressive HIIT ( n = 20 , four to ten 1-min sessions at ∼90 % peak heart rate , 1-min rest periods ) or MICT ( n = 19 , 20 - 50 min at ∼65 % peak heart rate ) . Before and 3 days after training , participants performed a peak O2 uptake test , and fasting blood sample s were obtained . Both HIIT ( 1.8 ± 0.4 vs. 1.9 ± 0.4 l/min , pre vs. post ) and MICT ( 1.8 ± 0.5 vs. 1.9 ± 0.5 l/min , pre vs. post ) improved peak O2 uptake ( P < 0.001 ) and lowered plasma fructosamine ( P < 0.05 ) . Toll-like receptor ( TLR ) 4 ( TLR4 ) expression was reduced on lymphocytes and monocytes after both HIIT and MICT ( P < 0.05 ) and on neutrophils after MICT ( P < 0.01 ) . TLR2 on lymphocytes was reduced after HIIT and MICT ( P < 0.05 ) . Plasma inflammatory cytokines were unchanged after training in both groups , but MICT led to a reduction in fasting plasma glucose ( P < 0.05 , 5.9 ± 1.0 vs. 5.6 ± 1.0 mmol/l , pre vs. post ) . Ten days of either HIIT or MICT can improve cardiorespiratory fitness and glucose control and lead to reductions in TLR2 and TLR4 expression . MICT , which involved a longer duration of exercise , may be superior for reducing fasting glucose Statin treatment and exercise training can reduce markers of inflammation when administered separately . The purpose of this study was to determine the effect of rosuvastatin treatment and the addition of exercise training on circulating markers of inflammation including C-reactive protein ( CRP ) , monocyte toll-like receptor 4 ( TLR4 ) expression , and CD14+CD16 + monocyte population size . Thirty-three hypercholesterolemic and physically inactive subjects were r and omly assigned to rosuvastatin ( R ) or rosuvastatin/exercise ( RE ) groups . A third group of physically active hypercholesterolemic subjects served as a control ( AC ) . The R and RE groups received rosuvastatin treatment ( 10 mg/d ) for 20 weeks . From week 10 to week 20 , the RE group also participated in an exercise training program ( 3d/wk ) . Measurements were made at baseline ( Pre ) , week 10 ( Mid ) , and week 20 ( Post ) , and included TLR4 expression on CD14 + monocytes and CD14+CD16 + monocyte population size as determined by 3-color flow cytometry . Serum CRP was quantified by enzyme-linked immunosorbent assay . TLR4 expression on CD14 + monocytes was higher in the R group at week 20 . When treatment groups ( R and RE ) were combined , serum CRP was lower across time . Furthermore , serum CRP and inflammatory monocyte population size were lower in the RE group compared with the R group at the Post time point . When all groups ( R , RE , and AC ) were combined , TLR4 expression was greater on inflammatory monocytes ( CD14+CD16 + ) compared with classic monocytes ( CD14+CD16⁻ ) at all time points . In conclusion , rosuvastatin may influence monocyte inflammatory response by increasing TLR4 expression on circulating monocytes . The addition of exercise training to rosuvastatin treatment further lowered CRP and reduced the size of the inflammatory monocyte population , suggesting an additive anti-inflammatory effect of exercise 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 Diet-induced weight gain increases disease risk via disruption of the innate immune system . Flow cytometry is commonly used to assess the immune system ; however , in mice such measurements traditionally require terminal procedures and tissue collection to generate sufficient sample . The present study refined an existing flow cytometry method to reduce the number of mice needed to longitudinally measure monocytes . CD-1 male mice were r and omly assigned to one of the three groups : DS ( diet-induced weight gain + sedentary ) , DE ( diet-induced weight gain + forced treadmill running [ total distance 35,755 ± 1832 m ] ) or NS ( normal weight gain + sedentary ) . DS and DE consumed a 60 % fat diet and NS consumed a 10 % fat diet ad libitum . Saphenous vein blood sample s were collected weekly for a period of six weeks and three-colour flow cytometry was used to measure changes in monocyte ( CD11b+/14 + ) concentration and cell-surface toll-like receptor 4 ( TLR4 ) expression . DS ( 18 % ) and DE ( 17 % ) gained more weight than NS ( P < 0.001 ) . On a group basis , DS expressed 17 % more TLR4 than DE and NS ( P = 0.005 ) . The present study demonstrates that a longitudinal survival model can be used to reduce the number of animals needed to complete flow cytometry experiments . Exercise during diet-induced weight prevented some ( decreased monocyte TLR4 expression ) but not all aspects of innate immune system function Obesity causes innate immune dysfunction , contributing to increased disease risk . Weight loss from a combination of caloric restriction and exercise is the most effective treatment of obesity . We compared forced and voluntary exercise as weight-loss treatments in diet-induced obese ( DIO ) mice and assessed the effects of weight loss on monocyte concentration and cell-surface expression of Toll-like receptor ( TLR ) 2 , TLR4 , CD80 , and CD86 . DIO CD1 male mice were allocated r and omly to 1 of 3 groups ( n = 6 per group ) : voluntary wheel running ( VEX ) ; forced treadmill running ( FEX ) ; and sedentary ( S ) . A fourth ( control ) group ( CN , n = 6 ) of nonDIO mice was included also . During the 8-wk weight-loss treatment , all 4 groups consumed a low-fat ( 10 % fat ) diet . Nonlethal saphenous vein blood sample s collected at baseline , week 4 , and week 8 were analyzed by flow cytometry to assess monocyte concentration and functional receptor expression . The VEX and FEX groups lost significantly more body weight ( 36 % and 27 % , respectively ) over the 8 wk of treatment than did other groups . VEX mice ran 4.4 times more than did FEX animals . VEX mice had higher monocyte concentrations ( 48 % and 58 % , respectively ) than did the CN and FEX groups . Compared with baseline , week 8 cell-surface expression of TLR2 ( 22 % ) , TLR4 ( 33 % ) , and CD86 ( 18 % ) was increased in VEX mice . At week 4 , CD80 expression was 42 % greater for VEX than S mice . The present study confirms that short-term exercise and low-fat diet consumption cause significant weight loss and altered immune profiles Introduction . Physical inactivity and obesity are independent risk factors for atherosclerosis . We analyzed the immunomodulatory capacity of 10-week intensified exercise training ( ET ) in obese and lean athletes . Markers of the innate immune response were investigated in obese ( ONE : ET≤40 km/week ) and lean athletes ( LNE : ET≤40 km/week and LE : ET≥55 km/week ) . Methods . Circulating dendritic cells ( DC ) were analyzed by flow-cytometry for BDCA-1/-2-expression . TLR-2/-4/-7 and MyD88 were analyzed by RT-PCR and Western blot . Circulating oxLDL levels were analyzed by ELISA . Results . BDCA-1 expression at baseline was lower in ONE compared to both other groups ( ONE 0.15 % ; LNE 0.27 % ; LE 0.33 % ; P < .05 ) , but significantly increased in ONE after training ( + 50 % ; P < .05 ) . In contrast , BDCA-2 expression at baseline was higher in ONE ( ONE 0.25 % ; LNE 0.11 % ; LE 0.09 % ; P < .05 ) and decreased in ONE after the 10-week training period ( −27 % ; P < .05 ) . Gene activations of TLR-4 and TLR-7 with corresponding protein increase were found for all three groups ( P < .01/P < .05 ) compared to pre training . A reduction of oxLDL levels was seen in ONE ( −61 % ; P < .05 ) . Conclusions . Intensified exercise induces an increase of BDCA-1 + DCs and TLR-4/-7 in obese athletes . We hereby describe new immune modulatory effects , which — through regular aerobic exercise — modulate innate immunity and pro-inflammatory cytokines in obesity |
10,588 | 29,651,257 | These treatments were successful for reducing dependence , craving , and other addiction-related symptoms by also improving mood state and emotion dysregulation .
The most effective approach was the combination of MBIs with TAU or other active treatments .
However , there is a lack of studies showing the maintenance of the effect over time .
Conclusion The revised literature shows support for the effectiveness of the MBIs . | Background Emotion (dys)regulation as well as the interventions for improving these difficulties are receiving a growing attention in the literature .
The aim of the present paper was to conduct a systematic review about the efficacy of mindfulness-based interventions ( MBIs ) in both substance and behavioral addictions ( BAs ) .
Results Mindfulness-based interventions were applied in a wide range of addictions , including substance use disorders ( from smoking to alcohol , among others ) and BAs ( namely , gambling disorder ) . | Although negative affect is a common precipitant of alcohol relapse , there are few interventions for alcohol dependence that specifically target negative affect . In this stage 1a/1b treatment development study , several affect regulation strategies ( e.g. , mindfulness , prolonged exposure , distress tolerance ) were combined to create a new treatment supplement called affect regulation training ( ART ) , which could be added to enhance cognitive-behavioral therapy ( CBT ) for alcohol dependence . A draft therapy manual was given to therapists and treatment experts before being administered to several patients who also provided input . After two rounds of manual development ( stage 1a ) , a pilot r and omized clinical trial ( N=77 ) of alcohol-dependent out patients who reported drinking often in negative affect situations was conducted ( stage 1b ) . Participants received 12-weekly , 90-minute sessions of either CBT for alcohol dependence plus ART ( CBT+ART ) or CBT plus a healthy lifestyles control condition ( CBT+HLS ) . Baseline , end-of-treatment , and 3- and 6-month posttreatment interviews were conducted . For both treatment conditions , participant ratings of treatment satisfaction were high , with CBT+ART rated significantly higher . Drinking outcome results indicated greater reductions in alcohol use for CBT+ART when compared to CBT+HLS , with moderate effect sizes for percent days abstinent , drinks per day , drinks per drinking day , and percent heavy drinking days . Overall , findings support further research on affect regulation interventions for negative affect drinkers OBJECTIVE To compare the efficacy of Mindfulness-Based Addiction Treatment ( MBAT ) to a Cognitive Behavioral Treatment ( CBT ) that matched MBAT on treatment contact time , and a Usual Care ( UC ) condition that comprised brief individual counseling . METHOD Participants ( N = 412 ) were 48.2 % African American , 41.5 % non-Latino White , 5.4 % Latino , and 4.9 % other , and 57.6 % reported a total annual household income < $ 30,000 . The majority of participants were female ( 54.9 % ) . Mean cigarettes per day was 19.9 ( SD = 10.1 ) . Following the baseline visit , participants were r and omized to UC ( n = 103 ) , CBT ( n = 155 ) , or MBAT ( n = 154 ) . All participants were given self-help material s and nicotine patch therapy . CBT and MBAT groups received 8 2-hr in-person group counseling sessions . UC participants received 4 brief individual counseling sessions . Biochemically verified smoking abstinence was assessed 4 and 26 weeks after the quit date . RESULTS Logistic r and om effects model analyses over time indicated no overall significant treatment effects ( completers only : F(2 , 236 ) = 0.29 , p = .749 ; intent-to-treat : F(2 , 401 ) = 0.9 , p = .407 ) . Among participants classified as smoking at the last treatment session , analyses examining the recovery of abstinence revealed a significant overall treatment effect , F(2 , 103 ) = 4.41 , p = .015 ( MBAT vs. CBT : OR = 4.94 , 95 % CI : 1.47 to 16.59 , p = .010 , Effect Size = .88 ; MBAT vs. UC : OR = 4.18 , 95 % CI : 1.04 to 16.75 , p = .043 , Effect Size = .79 ) . CONCLUSION Although there were no overall significant effects of treatment on abstinence , MBAT may be more effective than CBT or UC in promoting recovery from lapses . ( PsycINFO Data base OBJECTIVE Shame has long been seen as relevant to substance use disorders , but interventions have not been tested in r and omized trials . This study examined a group-based intervention for shame based on the principles of acceptance and commitment therapy ( ACT ) in patients ( N = 133 ; 61 % female ; M = 34 years old ; 86 % Caucasian ) in a 28-day residential addictions treatment program . METHOD Consecutive cohort pairs were assigned in a pairwise r and om fashion to receive treatment as usual ( TAU ) or the ACT intervention in place of 6 hr of treatment that would have occurred at that same time . The ACT intervention consisted of three 2-hr group sessions scheduled during a single week . RESULTS Intent-to-treat analyses demonstrated that the ACT intervention result ed in smaller immediate gains in shame , but larger reductions at 4-month follow-up . Those attending the ACT group also evidence d fewer days of substance use and higher treatment attendance at follow-up . Effects of the ACT intervention on treatment utilization at follow-up were statistically mediated by posttreatment levels of shame , in that those evidencing higher levels of shame at posttreatment were more likely to be attending treatment at follow-up . Intervention effects on substance use at follow-up were mediated by treatment utilization at follow-up , suggesting that the intervention may have had its effects , at least in part , through improving treatment attendance . CONCLUSIONS These results demonstrate that an approach to shame based on mindfulness and acceptance appears to produce better treatment attendance and reduced substance use BACKGROUND We have previously shown that Goal Management Training+Mindfulness Meditation ( GMT+MM ) improves executive functions in polysubstance users enrolled in outpatient treatment . The aim of this study was to establish if GMT+MM has similar positive effects on executive functions in polysubstance users in residential treatment , and if executive functions ' gains transfer to more ecologically valid goal -oriented tasks . METHODS Thirty-two polysbustance users were r and omly allocated to eight weeks of GMT+MM ( n=16 ) or control , i.e. , no-intervention ( n=16 ) ; both groups received treatment as usual . Outcome measures included performance in laboratory tasks of basic and complex executive functions ( i.e. , basic : working memory and inhibition ; complex : planning and self-regulation ) and in an ecological task of goal -directed behavior ( the Multiple Err and s Test - context ualized version , MET-CV ) measured post- interventions . RESULTS Results showed that GMT+MM was superior to control in improving basic measures of working memory ( Letter-number sequencing ; F=4.516 , p=0.049 ) and reflection impulsivity ( Information Sampling Test ; F=6.217 , p=0.018 ) , along with initial thinking times during planning ( Zoo Map Test ; F=8.143 , p=0.008 ) . In addition , GMT+MM was superior to control in improving performance in the MET-CV ( task failures ; F=8.485 , p=0.007 ) . CONCLUSION Our findings demonstrate that GMT+MM increases reflective processes and the achievement of goals in daily activities , furthermore ecological test can detects changes easily than laboratory tasks The current study investigates effects of a brief mindfulness-based instruction set , based on Marlatt 's " urge surfing " technique ( Marlatt & Gordon , 1985 ) , on smoking-related urges and behavior . Undergraduate smokers ( N = 123 ) who were interested in changing their smoking , but not currently involved in a cessation program , participated in a cue exposure paradigm design ed to elicit urges to smoke . They were r and omly assigned either to a group receiving brief mindfulness-based instructions or to a no-instruction control group . Results suggest that groups did not differ significantly on measures of urges . However , those in the mindfulness group smoked significantly fewer cigarettes over a 7-day follow-up period as compared to those in the control group . These findings suggest that the mindfulness techniques may not initially reduce urges to smoke but may change the response to urges . The study provides preliminary data for future studies examining both mechanisms and effectiveness of mindfulness-based interventions for cigarette smoking This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer Abstract Objective : Previous trials of catheter-based renal-artery denervation ( RDN ) as treatment modality in resistant hypertension ( rHT ) generated unconvincing results . In the Investigator-Steered Project on Intravascular Denervation for Management of Treatment-Resistant Hypertension ( INSPiRED ; NCT01505010 ) , we optimized selection and management of rHT patients . Methods : With ethical clearance to r and omize 18 patients , three Belgian hypertension centers screened 29 rHT patients on treatment with ≥3 drugs , of whom 17 after optimization of treatment ( age < 70 years ; systolic/diastolic office blood pressure ( BP ) ≥ 140/90 mm Hg ; 24-h BP ≥130/80 mm Hg ; glomerular filtration rate [ eGFR ] ≥ 45 mL/min/1.73 m2 ; body mass index < 40kg/m2 ) were r and omized and 15 were analyzed 6 months later , while medical treatment was continued ( n = 9 ) or combined with RDN by the EnligHTN ™ multi-electrode system ( n = 6 ) . Results : The baseline-adjusted between-group differences amounted to 19.5/10.4 mm Hg ( change in control vs. intervention group , + 7.6/+2.2 vs. −11.9/−8.2 mm Hg ; P = .088 ) for office BP , 22.4/13.1 mm Hg ( + 0.7/+0.3 vs. −21.7/−12.8 ; mm Hg ; P ≤ .049 ) for 24-h BP , the primary efficacy endpoint , and 2.5 mL/min/1.73 m2 ( + 1.5 vs. −1.1 mL/min/1.73 m2 ; P = .86 ) for eGFR , the primary safety endpoint . At 6 month , ECG voltages and the number of prescribed drugs ( P ≤ .036 ) were lower in RDN patients , but quality of life and adherence , captured by question naire and urine analysis were similar in both groups . Changes in BP and adherence were unrelated . No major complications occurred . Conclusions : The INSPiRED pilot suggests that RDN with the EnligHTN ™ system is effective and safe and generated insights useful for the design of future RDN trials Adolescence is a key developmental period for preventing substance use initiation , however prevention programs solely providing educational information about the dangers of substance use rarely change adolescent substance use behaviors . Recent research suggests that mind – body practice s such as yoga may have beneficial effects on several substance use risk factors , and that these practice s may serve as promising interventions for preventing adolescent substance use . The primary aim of the present study was to test the efficacy of yoga for reducing substance use risk factors during early adolescence . Seventh- grade students in a public school were r and omly assigned by classroom to receive either a 32-session yoga intervention ( n = 117 ) in place of their regular physical education classes or to continue with physical-education-as-usual ( n = 94 ) . Participants ( 63.2 % female ; 53.6 % White ) completed pre- and post-intervention question naires assessing emotional self-regulation , perceived stress , mood impairment , impulsivity , substance use willingness , and actual substance use . Participants also completed question naires at 6-months and 1-year post-intervention . Results revealed that participants in the control condition were significantly more willing to try smoking cigarettes immediately post-intervention than participants in the yoga condition . Immediate pre- to post-intervention differences did not emerge for the remaining outcomes . However , long-term follow-up analyses revealed a pattern of delayed effects in which females in the yoga condition , and males in the control condition , demonstrated improvements in emotional self-control . The findings suggest that school-based yoga may have beneficial effects with regard to preventing males ’ and females ’ willingness to smoke cigarettes , as well as improving emotional self-control in females . However additional research is required , particularly with regard to the potential long-term effects of mind – body interventions in school setting s. The present study contributes to the literature on adolescence by examining school-based yoga as a novel prevention program for substance use risk factors Craving , defined as the subjective experience of an urge or desire to use substances , has been identified in clinical , laboratory , and pre clinical studies as a significant predictor of substance use , substance use disorder , and relapse following treatment for a substance use disorder . Various models of craving have been proposed from biological , cognitive , and /or affective perspectives , and , collectively , these models of craving have informed the research and treatment of addictive behaviors . In this article we discuss craving from a mindfulness perspective , and specifically how mindfulness-based relapse prevention ( MBRP ) may be effective in reducing substance craving . We present secondary analyses of data from a r and omized controlled trial that examined MBRP as an aftercare treatment for substance use disorders . In the primary analyses of the data from this trial , Bowen and colleagues ( 2009 ) found that individuals who received MBRP reported significantly lower levels of craving following treatment , in comparison to a treatment-as-usual control group , which mediated subsequent substance use outcomes . In the current study , we extend these findings to examine potential mechanisms by which MBRP might be associated with lower levels of craving . Results indicated that a latent factor representing scores on measures of acceptance , awareness , and nonjudgment significantly mediated the relation between receiving MBRP and self-reported levels of craving immediately following treatment . The mediation findings are consistent with the goals of MBRP and highlight the importance of interventions that increase acceptance and awareness , and help clients foster a nonjudgmental attitude toward their experience . Attending to these processes may target both the experience of and response to craving Objective : This study investigated the effectiveness of mindfulness-based group therapy ( MBGT ) compared to the usual opioid dependence treatment (TAU).Thirty out patients meeting the DSM-IV-TR criteria for opioid dependence from Iranian National Center for Addiction Studies ( INCAS ) were r and omly assigned into experimental ( Mindfulness-Based Group Therapy ) and control groups ( the Usual Treatment).The experimental group undertook eight weeks of intervention , but the control group received the usual treatment according to the INCAS program . Methods : The Five Factor Mindfulness Question naire ( FFMQ ) and the Addiction Sevier Index ( ASI ) were administered at pre-treatment and post-treatment assessment periods . Thirteen patients from the experimental group and 15 from the control group completed post-test assessment s. Results : The results of MANCOVA revealed an increase in mean scores in observing , describing , acting with awareness , non-judging , non-reacting , and decrease in mean scores of alcohol and opium in MBGT patient group . Conclusion : The effectiveness of MBGT , compared to the usual treatment , was discussed in this paper as a selective protocol in the health care setting for substance use disorders Abstract Mindfulness training may disrupt the risk chain of stress-precipitated alcohol relapse . In 2008 , 53 alcohol-dependent adults ( mean age = 40.3 ) recruited from a therapeutic community located in the urban southeastern U.S. were r and omized to mindfulness training or a support group . Most participants were male ( 79.2 % ) . African American ( 60.4 % ) , and earned less than $ 20,000 annually ( 52.8 % ) . Self-report measures , psychophysiological cue-reactivity , and alcohol attentional bias were analyzed via repeated measures ANOVA . Thirty-seven participants completed the interventions . Mindfulness training significantly reduced stress and thought suppression , increased physiological recovery from alcohol cues , and modulated alcohol attentional bias . Hence , mindfulness training appears to target key mechanisms implicated in alcohol dependence , and therefore may hold promise as an alternative treatment for stress-precipitated relapse among vulnerable members of society This pilot study tested the efficacy of a brief intervention using motivational interviewing ( MI ) plus mindfulness meditation ( MM ) to reduce marijuana use among young adult females . Thirty-four female marijuana users between the ages of 18 and 29 were r and omized to either the intervention group ( n = 22 ) , consisting of two sessions of MI-MM , or an assessment -only control group ( n = 12 ) . The participants ' marijuana use was assessed at baseline and at 1 , 2 , and 3 months posttreatment . Fixed-effects regression modeling was used to analyze treatment effects . Participants r and omized to the intervention group were found to use marijuana on 6.15 ( z = -2.42 , p = .015 ) , 7.81 ( z = -2.78 , p = .005 ) , and 6.83 ( z = -2.23 , p = .026 ) fewer days at Months 1 , 2 , and 3 , respectively , than controls . Findings from this pilot study provide preliminary evidence for the feasibility and effectiveness of a brief MI-MM for young adult female marijuana users Smoking continues to take an enormous toll on society , and although most smokers would like to quit , most are unsuccessful using existing therapies . These findings call on research ers to develop and test therapies that provide higher rates of long-term smoking abstinence . We report results of a r and omized controlled trial comparing a novel smoking cessation treatment using mindfulness training to a matched control based on the American Lung Association 's Freedom From Smoking program . Data were collected on 175 low socioeconomic status smokers in 2011 - 2012 in a medium sized midwestern city . A significant difference was not found in the primary outcome ; intent-to-treat biochemically confirmed 6-month smoking abstinence rates were mindfulness=25.0 % , control=17.9 % ( p=0.35 ) . Differences favoring the mindfulness condition were found on measures of urges and changes in mindfulness , perceived stress , and experiential avoidance . While no significant differences were found in quit rates , the mindfulness intervention result ed in positive outcomes We report the results of a r and omized trial comparing a novel smoking cessation treatment Mindfulness Training for Smokers ( MTS ) to a usual care therapy ( Controls ) , which included the availability of a tobacco quit line and nicotine patches . Data were collected from 196 low socioeconomic status smokers in 2010–2011 in Madison , Wisconsin . Participants were r and omized to either MTS or a telephonic quit line . The primary outcome was 6-month smoking abstinence measured by carbon monoxide breath testing and Time-Line Follow-Back . Among treatment initiators ( r and omized participants who participated in the intervention ) , abstinence rates were significantly different between the MTS ( 38.7 % ) and control ( 20.6 % , p = .05 ) groups . Study limitations are also discussed . Results suggest that further study is warranted Objectives The purpose of this study was to investigate the effectiveness of emotional regulation training group therapy , based on Dialectical Behavioral Therapy ( DBT ) and Cognitive Therapy , on improving emotional regulation and distress tolerance skills and relapse prevention in addicts . Method In a quasiexperimental study , 39 patients with the diagnosis of opioid dependence based on DSM-IV criteria were r and omly assigned in to two experimental and one control groups . The experimental groups took 10 ninety-minute sessions of group therapy . The subjects were evaluated using the Opiate Treatment Index ( OPI ) , General Health Question naire-28 ( GHQ-28 ) , and Distress Tolerance and Difficulties in Emotion Regulation Scales prior to the start of treatment , and at the sixteenth session . The control group did not take group therapy and was merely treated with naltrexone . Data were analyzed using repeated measures ANOVA and χ2 test . Results Scheffe test showed that both emotion regulation training and cognitive therapy were more effective than naltrexone increasing distress tolerance , emotion regulation enhancement , and decreasing the amount of drug abuse , health improvement , social functioning , somatic symptoms , anxiety , social dysfunction and depression enhancement ( P<0.05 ) . In addition , emotion regulation training was more effective than cognitive therapy , increasing distress tolerance and emotional regulation enhancement ( p<0.05 ) . Conclusion It seems that DBT skill training increase the effectiveness of pharmacotherapy and is more effective than cognitive therapy More than 5 million deaths a year are attributable to tobacco smoking , but attempts to help people either quit or reduce their smoking often fail , perhaps in part because the intention to quit activates brain networks related to craving . We recruited participants interested in general stress reduction and r and omly assigned them to meditation training or a relaxation training control . Among smokers , 2 wk of meditation training ( 5 h in total ) produced a significant reduction in smoking of 60 % ; no reduction was found in the relaxation control . Resting-state brain scans showed increased activity for the meditation group in the anterior cingulate and prefrontal cortex , brain areas related to self-control . These results suggest that brief meditation training improves self-control capacity and reduces smoking ABSTRACT Stress is important in substance use disorders ( SUDs ) . Mindfulness training ( MT ) has shown promise for stress-related maladies . No studies have compared MT to empirically vali date d treatments for SUDs . The goals of this study were to assess MT compared to cognitive behavioral therapy ( CBT ) in substance use and treatment acceptability , and specificity of MT compared to CBT in targeting stress reactivity . Thirty-six individuals with alcohol and /or cocaine use disorders were r and omly assigned to receive group MT or CBT in an outpatient setting . Drug use was assessed weekly . After treatment , responses to personalized stress provocation were measured . Fourteen individuals completed treatment . There were no differences in treatment satisfaction or drug use between groups . The laboratory paradigm suggested reduced psychological and physiological indices of stress during provocation in MT compared to CBT . This pilot study provides evidence of the feasibility of MT in treating SUDs and suggests that MT may be efficacious in targeting stress BACKGROUND Cigarette smoking is the leading cause of preventable death in the world , and long-term abstinence rates remain modest . Mindfulness training ( MT ) has begun to show benefits in a number of psychiatric disorders , including depression , anxiety and more recently , in addictions . However , MT has not been evaluated for smoking cessation through r and omized clinical trials . METHODS 88 treatment-seeking , nicotine-dependent adults who were smoking an average of 20cigarettes/day were r and omly assigned to receive MT or the American Lung Association 's freedom from smoking ( FFS ) treatment . Both treatments were delivered twice weekly over 4 weeks ( eight sessions total ) in a group format . The primary outcomes were expired-air carbon monoxide-confirmed 7-day point prevalence abstinence and number of cigarettes/day at the end of the 4-week treatment and at a follow-up interview at week 17 . RESULTS 88 % of individuals received MT and 84 % of individuals received FFS completed treatment . Compared to those r and omized to the FFS intervention , individuals who received MT showed a greater rate of reduction in cigarette use during treatment and maintained these gains during follow-up ( F=11.11 , p=.001 ) . They also exhibited a trend toward greater point prevalence abstinence rate at the end of treatment ( 36 % vs. 15 % , p=.063 ) , which was significant at the 17-week follow-up ( 31 % vs. 6 % , p=.012 ) . CONCLUSIONS This initial trial of mindfulness training may confer benefits greater than those associated with current st and ard treatments for smoking cessation In many clinical setting s , there is a high comorbidity between substance use disorders , psychiatric disorders , and traumatic stress . Novel therapies are needed to address these co-occurring issues efficiently . The aim of the present study was to conduct a pragmatic r and omized controlled trial comparing Mindfulness-Oriented Recovery Enhancement ( MORE ) to group Cognitive-Behavioral Therapy ( CBT ) and treatment-as-usual ( TAU ) for previously homeless men residing in a therapeutic community . Men with co-occurring substance use and psychiatric disorders , as well as extensive trauma histories , were r and omly assigned to 10 weeks of group treatment with MORE ( n = 64 ) , CBT ( n = 64 ) , or TAU ( n = 52 ) . Study findings indicated that from pre-to post-treatment MORE was associated with modest yet significantly greater improvements in substance craving , post-traumatic stress , and negative affect than CBT , and greater improvements in post-traumatic stress and positive affect than TAU . A significant indirect effect of MORE on decreasing craving and post-traumatic stress by increasing dispositional mindfulness was observed , suggesting that MORE may target these issues via enhancing mindful awareness in everyday life . This pragmatic trial represents the first head-to-head comparison of MORE against an empirically-supported treatment for co-occurring disorders . Results suggest that MORE , as an integrative therapy design ed to bolster self-regulatory capacity , may hold promise as a treatment for intersecting clinical conditions IMPORTANCE Relapse is highly prevalent following substance abuse treatments , highlighting the need for improved aftercare interventions . Mindfulness-based relapse prevention ( MBRP ) , a group-based psychosocial aftercare , integrates evidence -based practice s from mindfulness-based interventions and cognitive-behavioral relapse prevention ( RP ) approaches . OBJECTIVE To evaluate the long-term efficacy of MBRP in reducing relapse compared with RP and treatment as usual ( TAU [ 12-step programming and psychoeducation ] ) during a 12-month follow-up period . DESIGN , SETTING , AND PARTICIPANTS Between October 2009 and July 2012 , a total of 286 eligible individuals who successfully completed initial treatment for substance use disorders at a private , nonprofit treatment facility were r and omized to MBRP , RP , or TAU aftercare and monitored for 12 months . Participants medically cleared for continuing care were aged 18 to 70 years ; 71.5 % were male and 42.1 % were of ethnic/racial minority . INTERVENTIONS Participants were r and omly assigned to 8 weekly group sessions of MBRP , cognitive-behavioral RP , or TAU . MAIN OUTCOMES AND MEASURES Primary outcomes included relapse to drug use and heavy drinking as well as frequency of substance use in the past 90 days . Variables were assessed at baseline and at 3- , 6- , and 12-month follow-up points . Measures used included self-report of relapse and urinalysis drug and alcohol screenings . RESULTS Compared with TAU , participants assigned to MBRP and RP reported significantly lower risk of relapse to substance use and heavy drinking and , among those who used substances , significantly fewer days of substance use and heavy drinking at the 6-month follow-up . Cognitive-behavioral RP showed an advantage over MBRP in time to first drug use . At the 12-month follow-up , MBRP participants reported significantly fewer days of substance use and significantly decreased heavy drinking compared with RP and TAU . CONCLUSIONS AND RELEVANCE For individuals in aftercare following initial treatment for substance use disorders , RP and MBRP , compared with TAU , produced significantly reduced relapse risk to drug use and heavy drinking . Relapse prevention delayed time to first drug use at 6-month follow-up , with MBRP and RP participants who used alcohol also reporting significantly fewer heavy drinking days compared with TAU participants . At 12-month follow-up , MBRP offered added benefit over RP and TAU in reducing drug use and heavy drinking . Targeted mindfulness practice s may support long-term outcomes by strengthening the ability to monitor and skillfully cope with discomfort associated with craving or negative affect , thus supporting long-term outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : OBJECTIVES This pilot study explores the feasibility of yoga as part of a treatment program for alcohol dependence . DESIGN Eighteen alcohol dependent patients were r and omized to receive either treatment as usual or treatment as usual plus yoga . Assessment s were taken at baseline and six month follow-up . SETTING ' Riddargatan 1 ' : an outpatient alcohol treatment clinic located in Stockholm , Sweden . INTERVENTIONS Treatment as usual consisted of psychological and pharmacological interventions for alcohol dependence . The 10-week yoga intervention included a weekly group yoga session . Participants were encouraged to practice the yoga movements at home once per day . MAIN OUTCOME MEASURES Alcohol consumption ( timeline follow-back method , DSM-IV criteria for alcohol dependence , and the Short Alcohol Dependence Data question naire ) , affective symptoms ( the Hospital Anxiety and Depression Scale ) , quality of life ( Sheehan Disability Scale ) and stress ( the Perceived Stress Scale and saliva cortisol ) . RESULTS Yoga was found to be a feasible and well accepted adjunct treatment for alcohol dependence . Alcohol consumption reduced more in the treatment as usual plus yoga group ( from 6.32 to 3.36 drinks per day ) compared to the treatment as usual only group ( from 3.42 to 3.08 drinks per day ) . The difference was , however , not statistically significant ( p = 0.17 ) . CONCLUSIONS Larger studies are needed to adequately assess the efficacy and long-term effectiveness of yoga as an adjunct treatment for alcohol dependence The problem gambling ( PG ) intervention literature is characterised by a variety of psychological treatments and approaches , with varying levels of evidence ( PGRTC in Guideline for screening , assessment and treatment in problem and pathological gambling . Monash University , Melbourne , 2011 ) . A recent PG systematic review ( Maynard et al. in Res Soc Work Pract , 2015 . doi:10.1177/1049731515606977 ) and the success of mindfulness-based interventions to effectively treat disorders commonly comorbid with PG suggested mindfulness-based interventions may be effective for treating PG . The current study tested the effectiveness of three interventions to treat PGs : 1 . case formulation driven Cognitive Behaviour Therapy ( CBT ) ; 2 . manualised CBT ; and 3 . mindfulness-based treatment . All three interventions tested returned large effect size improvements in PG behaviour after seven sessions ( Cohen ’s d range 1.46–2.01 ) , at post-treatment and at 3 and 6-month follow-up . All of the interventions were rated as acceptable by participants at post-treatment . This study suggests that the mindfulness-based and TAU interventions used in the current study appear to be effective at reducing PG behavior and associated distress and they also appear to generalise to improvements in other measures such as quality of life-mental functioning and certain mindfulness facets more effectively than the manualised form of CBT utilised used here . Secondly , a brief mindfulness intervention delivered after psycho-education and a brief CBT intervention may be a useful supplement to traditional CBT treatments by addressing transdiagnostic processes such as rumination and thought suppression . Thirdly , CBT interventions continue to report effectiveness in reducing PG behaviour and associated distress consistent with the prevailing literature and clinical direction Abstract Dysregulated processing of natural rewards may be a central pathogenic process in the etiology and maintenance of prescription opioid misuse and addiction among chronic pain patients . This study examined whether a Mindfulness-Oriented Recovery Enhancement ( MORE ) intervention could augment natural reward processing through training in savoring as indicated by event-related brain potentials ( ERPs ) . Participants were chronic pain patients at risk for opioid misuse who were r and omized to 8 weeks of MORE ( n = 11 ) or a support group control condition ( n = 18 ) . ERPs to images representing naturally rewarding stimuli ( e.g. , beautiful l and scapes , intimate couples ) and neutral images were measured before and after 8 weeks of treatment . Analyses focused on the late positive potential (LPP)—an ERP response in the 400–1,000 ms time window thought to index allocation of attention to emotional information . Treatment with MORE was associated with significant increases in LPP response to natural reward stimuli relative to neutral stimuli which were correlated with enhanced positive affective cue-responses and reductions in opioid craving from pre- to post-treatment . Findings suggest that cognitive training regimens centered on strengthening attention to natural rewards may remediate reward processing deficits underpinning addictive behavior Several theories have proposed that negative affect ( NA ) plays a large role in the maintenance of substance use behaviors - a phenomenon supported in laboratory-based and clinical studies . It has been demonstrated that mindfulness meditation can improve the regulation of NA , suggesting that mindfulness may be very beneficial in treating problematic substance use behavior . The current study tested whether a brief mindfulness meditation would lower levels of NA , increase willingness to experience NA , lower urges to drink , and increase time to next alcoholic drink in a sample of at-risk college student drinkers ( N = 207 ) . Participants were r and omized to one of three brief interventions ( mindfulness , relaxation , or control ) followed by an affect manipulation ( negative or neutral stimuli ) . Affect and urge were measured prior to intervention ( Time 1 [ T1 ] ) , after intervention but prior to affect manipulation ( Time 2 [ T2 ] ) , and immediately after the affect manipulation ( Time 3 [ T3 ] ) . Levels of mindfulness and relaxation were assessed from T1-T3 . The additional measures of willingness to continue watching NA images and time to next alcoholic drink were examined at T3 . Results indicated that the mindfulness intervention increased state mindfulness and relaxation , and decreased NA immediately following the mindfulness intervention . However , the mindfulness intervention did not influence responses to NA induction on any of the outcome variables at T3 . One potential explanation is that the mindfulness intervention was not robust enough to maintain the initial gains made immediately following the intervention OBJECTIVE A strong relation between negative affect and craving has been demonstrated in laboratory and clinical studies , with depressive symptomatology showing particularly strong links to craving and substance abuse relapse . Mindfulness-based relapse prevention ( MBRP ) , shown to be efficacious for reduction of substance use , uses mindfulness-based practice s to teach alternative responses to emotional discomfort and lessen the conditioned response of craving in the presence of depressive symptoms . The goal in the current study was to examine the relation between measures of depressive symptoms , craving , and substance use following MBRP . METHOD Individuals with substance use disorders ( N = 168 ; mean age 40.45 years , SD = 10.28 ; 36.3 % female ; 46.4 % non-White ) were recruited after intensive stabilization , then r and omly assigned to either 8 weekly sessions of MBRP or a treatment-as-usual control group . Approximately 73 % of the sample was retained at the final 4-month follow-up assessment . RESULTS Results confirmed a moderated-mediation effect , whereby craving mediated the relation between depressive symptoms ( Beck Depression Inventory ) and substance use ( Timeline Follow-Back ) among the treatment-as-usual group but not among MBRP participants . MBRP attenuated the relation between postintervention depressive symptoms and craving ( Penn Alcohol Craving Scale ) 2 months following the intervention ( f(2 ) = .21 ) . This moderation effect predicted substance use 4 months following the intervention ( f(2 ) = .18 ) . CONCLUSION MBRP appears to influence cognitive and behavioral responses to depressive symptoms , partially explaining reductions in postintervention substance use among the MBRP group . Although results are preliminary , the current study provides evidence for the value of incorporating mindfulness practice into substance abuse treatment and identifies a potential mechanism of change following MBRP Aims : The aim of this study was to evaluate posttreatment changes of individuals with a diagnosis of gambling disorder ( GD ) treated with group cognitive behavioral therapy ( CBT ) , to assess the potential moderator effect of sex on CBT outcome , and to explore the best predictors of posttreatment changes , relapse , and dropout rates . Methods : A cohort design was applied with a prospect i ve follow-up . The sample comprised 440 patients and the CBT intervention consisted of 16 weekly outpatient group sessions and a 3-month follow-up period . Results : Patients showed significant improvements in both the level of psychopathology and the severity of the gambling behavior . High self-transcendence and the involvement of the spouse or partner in the therapy predicted a higher risk of relapse . Younger age and low education predicted a higher risk of dropout . Conclusion : Many patients with GD can be treated with strategies to improve self-control and emotional regulation , but other techniques should be incorporated to address the individual characteristics of each patient . This is particularly important in group therapy , in which the same treatment is applied to several patients simultaneously . The involvement of a family member needs to be carefully considered since it may have a negative effect on the response to treatment if not adequately managed OBJECTIVE Opioid pharmacotherapy is now the leading treatment for chronic pain , a problem that affects nearly one third of the U.S. population . Given the dramatic rise in prescription opioid misuse and opioid-related mortality , novel behavioral interventions are needed . The purpose of this study was to conduct an early-stage r and omized controlled trial of Mindfulness-Oriented Recovery Enhancement ( MORE ) , a multimodal intervention design ed to simultaneously target mechanisms underpinning chronic pain and opioid misuse . METHOD Chronic pain patients ( N = 115 ; mean age = 48 ± 14 years ; 68 % female ) were r and omized to 8 weeks of MORE or a support group ( SG ) . Outcomes were measured at pre- and posttreatment , and at 3-month follow-up . The Brief Pain Inventory was used to assess changes in pain severity and interference . Changes in opioid use disorder status were measured by the Current Opioid Misuse Measure . Desire for opioids , stress , nonreactivity , reinterpretation of pain sensations , and re appraisal were also evaluated . RESULTS MORE participants reported significantly greater reductions in pain severity ( p = .038 ) and interference ( p = .003 ) than SG participants , which were maintained by 3-month follow-up and mediated by increased nonreactivity and reinterpretation of pain sensations . Compared with SG participants , participants in MORE evidence d significantly less stress arousal ( p = .034 ) and desire for opioids ( p = .027 ) , and were significantly more likely to no longer meet criteria for opioid use disorder immediately following treatment ( p = .05 ) ; however , these effects were not sustained at follow-up . CONCLUSIONS Findings demonstrate preliminary feasibility and efficacy of MORE as a treatment for co-occurring prescription opioid misuse and chronic pain . ( PsycINFO Data base Record ( c ) 2014 APA , all rights reserved ) Racial and ethnic disparities in the treatment of addiction have been acknowledged for several years , yet little is known about which empirically supported treatments for substance use disorders are more or less effective in treating racial and ethnic minority clients . The current study was a secondary analysis of a r and omized clinical trial of two evidence -based treatments , mindfulness-based relapse prevention ( MBRP ) and relapse prevention ( RP ) , as part of a residential addiction treatment program for women referred by the criminal justice system ( n=70 ) . At 15-week follow-up , regression analyses found that racial and ethnic minority women in MBRP , compared to non-Hispanic and racial and ethnic minority women in RP , reported significantly fewer drug use days ( d=.31 ) and lower addiction severity ( d=.65 ) , based on the Addiction Severity Index . Although the small sample size is a limitation , the results suggest that MBRP may be more efficacious than traditional treatments for racial and ethnic minority women Abstract The present study describes the development of the Mindfulness-Based Relapse Prevention Adherence and Competence Scale ( MBRP-AC ) , a measure of treatment integrity for mindfulness-based relapse prevention ( MBRP ) . MBRP is a newly developed treatment integrating core aspects of relapse prevention with mindfulness practice s. The MBRP-AC was developed in the context of a r and omized controlled trial ( RCT ) of MBRP efficacy and consists of two sections : Adherence ( adherence to individual components of MBRP and discussion of key concepts ) and Competence ( ratings of therapist style/approach and performance ) . Audio recordings from 44 r and omly selected group treatment sessions ( 50 % ) were rated by independent raters for therapist adherence and competence in the RCT . Findings evinced high interrater reliability for all treatment adherence and competence ratings , and adequate internal consistency for Therapist Style/Approach and Therapist Performance summary scales . Ratings on the MBRP-AC suggested that therapists in the recent RCT adhered to protocol , discussed key concepts in each session , and demonstrated the intended style and competence in treatment delivery . Finally , overall ratings on the Adherence section were positively related to changes in mindfulness over the course of the treatment Abstract The aim of this study was to explore the sequential use of risk malignancy index ( RMI ) combined with contrast-enhanced ultrasonography ( CEUS ) in identification diagnosis of adnexal masses . This study contained 2 steps : first , 151 patients were analyzed retrospectively with RMI 1 , RMI 2 , and RMI 3 indices ; receiver operating characteristic ( ROC ) curves were plotted to analyze area under the curves ( AUC ) , and then RMI cut-off value was obtained according to maximum Youden index ( YI , Sensitivity + Specificity − 1 ) and calculating diagnostic sensitivity , specificity , positive/negative predictive value , and accuracy . Second , 151 cases were divided into 2 groups r and omly ( 105 in study group and 46 in test group ) ; in the study group , the lower cut-off value ( LC ) , upper cut-off value ( UC ) , CEUS cut-off value according to maximum YI , and then these cut-offs were vali date d in test group . There was no statistical significance in 3 RMI models ( P = .35 ) , and RMI1 model was established r and omly for following study . When the RMI1 cut-off value was 149 , the YI was maximal ( 0.53 ) , and the sensitivity , specificity , positive/negative predictive value , and accuracy were 71.0 % , 81.7 % , 77.1 % , 75.6 % , and 76.2 % , respectively . The LC was 15 ( sensitivity was 98.0 % ) , the UC was 3000 ( specificity was 98.0 % ) , and the CEUS cut-off value was 7 ( maximal YI was 0.81 ) . In the test group ( 46 cases ) , combining RMI1 LC ( 15 ) and UC ( 3000 ) with CEUS cut-off value ( 7 ) , the sensitivity , specificity , positive/negative predictive value , and accuracy were up to 85.7 % , 92.0 % , 90.0 % , 88.5 % , and 89.1 % , respectively . CEUS can help RMI to make a more effective differential diagnosis of the adnexal mass . Further validation by additional multicenter prospect i ve trials is required |
10,589 | 28,056,967 | Research ers did not find consistent evidence supporting implementation of any specific type of adaptation nor increased efficacy with any particular cultural group . | Background Membership in diverse racial , ethnic , and cultural groups is often associated with inequitable health and mental health outcomes for diverse population s. Yet , little is known about how cultural adaptations of st and ard services affect health and mental health outcomes for service recipients .
This systematic review identified extant themes in the research regarding cultural adaptations across a broad range of health and mental health services and synthesized the most rigorous experimental research available to isolate and evaluate potential efficacy gains of cultural adaptations to service delivery . | Background : Patient navigation has been an effective intervention to increase cancer screening rates . This study focuses on predicting outcomes of screening colonoscopy for colorectal cancer among African Americans using different patient navigation formats . Methods : In a r and omized clinical trial , patients more than 50 years of age without significant comorbidities were r and omized into three navigation groups : peer-patient navigation ( n = 181 ) , pro-patient navigation ( n = 123 ) , and st and ard ( n = 46 ) . Pro-patient navigations were health care professionals who conducted culturally targeted navigation , whereas peer-patient navigations were community members trained in patient navigation who also discussed their personal experiences with screening colonoscopy . Two assessment s gathered sociodemographic , medical , and intrapersonal information . Results : Screening colonoscopy completion rate was 75.7 % across all groups with no significant differences in completion between the three study arms . Annual income more than $ 10,000 was an independent predictor of screening colonoscopy adherence . Unexpectedly , low social influence also predicted screening colonoscopy completion . Conclusions : In an urban African American population , patient navigation was effective in increasing screening colonoscopy rates to 15 % above the national average , regardless of patient navigation type or content . Impact : Because patient navigation successfully increases colonoscopy adherence , cultural targeting may not be necessary in some population s. Cancer Epidemiol Biomarkers Prev ; 22(9 ) ; 1577–87 . © 2013 AACR Background : Research comparing the effects of culturally targeted and generic but linguistically appropriate intervention programs is limited . We conducted a r and omized controlled trial comparing the efficacy of a culturally targeted video , a generic video , and a fact sheet ( control ) in promoting mammography screening among Chinese-American immigrants . Methods : We r and omized 664 Chinese-American women from the Washington , DC , and New York City areas who were older than 40 years and nonadherent to annual mammography screening guidelines to three study arms ( each with ∼221 women ) . The outcome was self-reported mammography screening 6 months post intervention . Measures of knowledge , Eastern cultural views , and health beliefs were administered before and after the intervention . Results : The culturally targeted video , the generic video , and the fact sheet increased mammography use by 40.3 % , 38.5 % , and 31.1 % from baseline , respectively . A significant intervention effect was observed only in one subgroup : The culturally targeted video significantly increased mammography screening among low-acculturated women over the fact sheet [ OR , 1.70 ; 95 % confidence interval ( CI ) , 1.04–2.78 ] . Overall , women who obtained a mammogram during the follow-up period reported significantly fewer barriers to screening after intervention than those who had not obtained screening . Both of the video groups reported fewer barriers after intervention than the control group . Conclusions : Both theoretically guided videos increased the likelihood of mammography use to a similar extent . Cultural targeting was only effective for low-acculturated women . Both videos reduced perceived barriers to screening and consequently increased screening behavior . Impact : The results of this study provide empirical evidence on the efficacy of cultural targeting for minority immigrants . Cancer Epidemiol Biomarkers Prev ; 21(11 ) ; 1923–32 . © 2012 AACR In this pilot trial , 15 phobic Asian Americans were r and omly assigned to st and ard one-session treatment ( OSTS ) , culturally adapted one-session treatment ( OST-CA ) , or manualized self-help . At posttreatment , OST ( combined st and ard and culturally adapted ) led to greater reductions in phobic avoidance and anxiety than self-help . Moreover , analyses comparing the two active treatments showed trends favoring OST-CA over OST-S. Results suggest that Asian Americans may benefit most from empirically supported treatments that consider Asian cultural values . ( PsycINFO Data base Record ( c ) 2010 APA , all rights reserved ) BACKGROUND Communication between African American patients and white health care providers has been shown to be of poorer quality when compared with race-concordant patient-provider communication . Fear on the part of patients that providers stereotype them negatively might be one cause of this poorer communication . This stereotype threat may be lessened by a values-affirmation intervention . METHODS In a blinded experiment , we r and omized 99 African American patients with hypertension to perform a values-affirmation exercise or a control exercise before a visit with their primary care provider . We compared patient-provider communication for the 2 groups using audio recordings of the visit analyzed with the Roter Interaction Analysis System . We also evaluated visit satisfaction , trust , stress , and mood after the visit by means of a question naire . RESULTS Patients in the intervention group requested and provided more information about their medical condition ( mean [ SE ] number of utterances , 66.3 [ 6.8 ] in the values-affirmation group vs 48.1 [ 5.9 ] in the control group [ P = .03 ] ) . Patient-provider communication in the intervention group was characterized as being more interested , friendly , responsive , interactive , and respectful ( P = .02 ) and less depressed and distressed ( P = .03 ) . Patient question naires did not detect differences in visit satisfaction , trust , stress , or mood . Mean visit duration did not differ significantly between the groups ( 19.2 minutes in the control group vs 20.5 minutes in the intervention group [ P = .29 ] ) . CONCLUSIONS A values-affirmation exercise improves aspects of patient-provider communication in race-discordant primary care visits . The clinical impact of the intervention must be defined before widespread implementation can be recommended OBJECTIVE Many targeted interventions have been developed and tested with African Americans ( AA ) ; however , AAs are a highly heterogeneous group . One characteristic that varies across AAs is Ethnic Identity ( EI ) . Little research has been conducted on how to incorporate EI into the design of health messages and programs . DESIGN We tested whether tailoring a print-based fruit and vegetable ( F & V ) intervention on EI would enhance program impact . AA adults were recruited from two integrated healthcare delivery systems and then r and omized to receive three newsletters focused on F & V behavior change over three months . One set of newsletters was tailored only on demographic and social cognitive variables ( control condition ) , whereas the other ( experimental condition ) was additionally tailored on EI . MAIN OUTCOME MEASURES The primary outcome for the study was F & V intake , assessed at baseline and three months later using the composite of two brief self-report frequency measures . RESULTS A total of 560 eligible participants were enrolled , of which 468 provided complete 3-month follow-up data . The experimental group increased their daily mean F & V intake by 1.1 servings compared to .8 servings in the control group ( p = .13 ) . Afrocentric experimental group participants showed a 1.4 increase in F & V servings per day compared to a .43 servings per day increase among Afrocentric controls ( p < .05 ) . CONCLUSIONS Although the overall between-group effects were not significant , tailoring dietary messages on ethnic identity may improve intervention impact for some AA subgroups Background : Limited empirical data are available on the effects of genetic counseling and testing among African American women . Objective : To evaluate the effects of genetic counseling and testing in African American women based on different levels of exposure : ( a ) women who were r and omized to culturally tailored ( CTGC ) and st and ard genetic counseling ( SGC ) to women who declined r and omization ( non-r and omized group ) , ( b ) participants and non- participants in genetic counseling , and ( c ) BRCA1 and BRCA2 ( BRCA1/2 ) test result acceptors and decliners . Design : R and omized trial of genetic counseling conducted from February 2003 to November 2006 . Measures : We evaluated changes in perceived risk of developing breast cancer and cancer worry . Results : Women r and omized to CTGC and SGC did not differ in terms of changes in risk perception and cancer worry compared to decliners . However , counseling participants had a significantly greater likelihood of reporting reductions in perceived risk compared to non- participants ( p = 0.03 ) . Test result acceptors also had a significantly greater likelihood of reporting decreases in cancer worry ( p = 0.03 ) . However , having a cancer history ( p = 0.03 ) and a BRCA1/2 prior probability ( p = 0.04 ) were associated with increases in cancer worry . Conclusions : Although CTGC did not lead to significant improvements in perceived risk or psychological functioning , African American women may benefit from genetic counseling and testing . Continued efforts should be made to increase access to genetic counseling and testing among African American women at increased risk for hereditary disease . But , follow-up support may be needed for women who have a personal history of cancer and those with a greater prior probability of having a BRCA1/2 mutation Comparative studies examining the difference between empirically supported substance abuse treatments versus their culturally accommo date d counterparts with participants from a single ethnic minority group are frequently called for in the literature but infrequently conducted in practice . This r and omized clinical trial was conducted to compare the efficacy of an empirically supported st and ard version of a group-based cognitive-behavioral treatment ( S-CBT ) to a culturally accommo date d version ( A-CBT ) with a sample of Latino adolescents primarily recruited from the juvenile justice system . Development of the culturally accommo date d treatment and testing was guided by the Cultural Accommodation Model for Substance Abuse Treatment ( CAM-SAT ) . Seventy Latino adolescents ( mean age = 15.2 ; 90 % male ) were r and omly assigned to 1 of 2 group-based treatment conditions ( S-CBT = 36 ; A-CBT = 34 ) with assessment s conducted at pretreatment , posttreatment , and 3-month follow-up . Longitudinal Poisson mixed models for count data were used to conduct the major analyses . The primary outcome variable in the analytic models was the number of days any substance was used ( including alcohol , except tobacco ) in the past 90 days . In addition , the variables ethnic identity , familism , and acculturation were included as cultural moderators in the analysis . Although both conditions produced significant decreases in substance use , the results did not support a time by treatment condition interaction ; however , outcomes were moderated by ethnic identity and familism . The findings are discussed with implication s for research and practice within the context of providing culturally relevant treatment for Latino adolescents with substance use disorders Colorectal cancer screening has clear benefits in terms of mortality reduction ; however , it is still underutilized and especially among medically underserved population s , including African Americans , who also suffer a disproportionate colorectal cancer burden . This study consisted of a theory-driven ( health belief model ) spiritually based intervention aim ed at increasing screening among African Americans through a community health advisor-led educational series in 16 churches . Using a r and omized design , churches were assigned to receive either the spiritually based intervention or a nonspiritual comparison , which was the same in every way except that it did not contain spiritual/religious content and themes . Trained and certified peer community health advisors in each church led a series of two group educational sessions on colorectal cancer and screening . Study enrollees completed a baseline , 1-month , and 12-month follow-up survey at their churches . The interventions had significant pre – post impact on awareness of all four screening modalities , and self-report receipt of fecal occult blood test , flexible sigmoidoscopy , and colonoscopy . There were no significant study group differences in study outcomes , with the exception of fecal occult blood test utilization , whereas those in the nonspiritual intervention reported significantly greater pre – post change . Both of these community-engaged , theory-driven , culturally relevant approaches to increasing colorectal cancer awareness and screening appeared to have an impact on study outcomes . Although adding spiritual/religious themes to the intervention was appealing to the audience , it may not result in increased intervention efficacy What kinds of evidence reliably support predictions of effectiveness for health and social care interventions ? There is increasing reliance , not only for health care policy and practice but also for more general social and economic policy deliberation , on evidence that comes from studies whose basic logic is that of JS Mill 's method of difference . These include r and omized controlled trials , case-control studies , cohort studies , and some uses of causal Bayes nets and counterfactual-licensing models like ones commonly developed in econometrics . The topic of this paper is the ' external validity ' of causal conclusions from these kinds of studies . We shall argue two cl aims . Cl aim , negative : external validity is the wrong idea ; cl aim , positive : ' capacities ' are almost always the right idea , if there is a right idea to be had . If we are right about these cl aims , it makes big problems for policy decisions . Many advice guides for grading policy predictions give top grade s to a proposed policy if it has two good Mill's- method -of difference studies that support it . But if capacities are to serve as the conduit for support from a method -of-difference study to an effectiveness prediction , much more evidence , and much different in kind , is required . We will illustrate the complexities involved with the case of multisystemic therapy , an internationally adopted intervention to try to diminish antisocial behaviour in young people Fotonovelas — small booklets that portray a dramatic story using photographs and captions — represent a powerful health education tool for low-literacy and ethnic minority audiences . This study evaluated the effectiveness of a depression fotonovela in increasing depression knowledge , decreasing stigma , increasing self-efficacy to recognize depression , and increasing intentions to seek treatment , relative to a text pamphlet . Hispanic adults attending a community adult school ( N = 157 , 47.5 % female , mean age = 35.8 years , 84 % immigrants , 63 % with less than high school education ) were r and omly assigned to read the fotonovela or a low-literacy text pamphlet about depression . They completed surveys before reading the material , immediately after reading the material , and 1 month later . The fotonovela and text pamphlet both produced significant improvements in depression knowledge and self-efficacy to identify depression , but the fotonovela produced significantly larger reductions in antidepressant stigma and mental health care stigma . The fotonovela also was more likely to be passed on to family or friends after the study , potentially increasing its reach throughout the community . Results indicate that fotonovelas can be useful for improving health literacy among underserved population s , which could reduce health disparities We examined treatment effects over a 6- to 24-month period posttreatment for 3 different interventions for externalizing behavior problems in young Mexican American ( MA ) children : a culturally modified version of Parent-Child Interaction Therapy ( PCIT ) , called Gui and o a Niños Activos ( GANA ) , st and ard PCIT , and treatment as usual ( TAU ) . Fifty-eight MA families with a 3- to 7-year-old child with clinical ly significant behavior problems were r and omly assigned to GANA , st and ard PCIT , or TAU . As previously reported , all three treatment approaches produced significant pre-post improvement in conduct problems across a wide variety of parent-report measures , and those effects remained significant over the follow-up period . GANA produced results that were significantly superior to TAU on 6 out of 10 parent-report measures 6 to 24months posttreatment , and GANA significantly outperformed PCIT on child internalizing symptoms . However , PCIT and TAU did not differ significantly from one another . These data suggest that both PCIT and GANA produce treatment gains that are maintained over time , and that GANA continues to outperform TAU over the long term This study is a 6-month follow-up of a r and omized pilot evaluation of st and ard one-session treatment ( OST-S ) versus culturally adapted OST ( OST-CA ) with phobic Asian Americans . OST-CA included seven cultural adaptations drawn from prior research with East Asians and Asian Americans . Results from 1-week and 6-month follow-up show that both OST-S and OST-CA were effective at reducing phobic symptoms compared with self-help control . Moreover , OST-CA was superior to OST-S for several outcomes . For catastrophic thinking and general fear , moderator analyses indicated that low-acculturation Asian Americans benefitted more from OST-CA than OST-S , whereas both treatments were equally effective for high-acculturation participants . Although cultural process factors ( e.g. , facilitating emotional control , exploiting the vertical therapist-client relationship ) and working alliance were predictive of positive outcomes , they did not mediate treatment effects . This study offers a potential model for evaluating cultural adaptation effects , as well as the mechanisms that account for such effects Colorectal cancer screening , while effective for reducing mortality , remains underutilized particularly among underserved population s such as African Americans . The present study evaluated a spiritually based approach to increasing Health Belief Model – based pre-screening outcomes in a Community Health Advisor – led intervention conducted in African American churches . Sixteen urban churches were r and omized to receive either the spiritually based intervention or a nonspiritual comparison of the same structure and core colorectal cancer content . Trained Community Health Advisors led a series of two educational sessions on colorectal cancer early detection . The educational sessions were delivered over a 1-month period . Participants ( N = 316 ) completed a baseline survey at enrollment and a follow-up survey one month after the first session . Both interventions result ed in significant pre/post increases in knowledge , perceived benefits of screening , and decreases in perceived barriers to screening . Among women , the spiritually based intervention result ed in significantly greater increases in perceived benefits of screening relative to the nonspiritual comparison . This finding was marginal in the sample as a whole . In addition , perceived benefits to screening were associated with behavioral intention for screening . It is concluded that in this population , the spiritually based was generally as effective as the nonspiritual ( secular ) communication BACKGROUND Despite significant medical advances , many ethnic and racial minority children who live in inner cities continue to experience disproportionately high levels of asthma morbidity and mortality compared with white children . As a result , a growing number of psychosocial asthma management interventions are being developed to address their needs ; however , only a few of these interventions have incorporated cultural variables into their treatments and have had their efficacy evaluated . OBJECTIVE To examine the efficacy of the Multifamily Asthma Group Treatment ( MFAGT ) , design ed to enhance asthma management and reduce emergency department ( ED ) visits among African American and Hispanic families . METHODS Twenty-four African American and Hispanic families who have children with asthma were r and omly assigned to either the MFAGT or the St and ard Psychoeducational Asthma Intervention . Differences in the number of ED visits and the level of asthma management in both groups were compared 1 year before and 1 year after the intervention . In addition , these groups were contrasted to a control group that did not receive any psychoeducational intervention . RESULTS The MFAGT was significantly ( P = .04 ) more effective than the St and ard Psychoeducational Asthma Intervention and the control in decreasing ED visits and increasing parental asthma knowledge . CONCLUSIONS These preliminary results suggest that the MFAGT is efficacious in enhancing asthma management and in reducing ED visits in inner-city African American and Hispanic children from a lower socioeconomic background This study utilized data from an ongoing r and omized controlled trial to compare a culturally tailored video promoting positive attitudes toward mammography among Chinese immigrant women to a linguistically appropriate generic video and print media . Intervention development was guided by the Health Belief Model . Five hundred and ninety-two immigrant Chinese Americans from the metropolitan Washington , DC , and New York City areas completed telephone interviews before and after intervention . Changes in knowledge , Eastern views of health care ( fatalism and self-care ) , health beliefs ( perceived susceptibility , severity , benefits and barriers ) and screening intentions were measured . Results showed that both videos improved screening knowledge , modified Eastern views of health care , reduced perceived barriers and increased screening intentions relative to print media ( all P < 0.05 ) . The generic video increased screening intention twice as much as the cultural video , although subgroup analysis showed the increase was only significant in women aged 50 - 64 years . Only Eastern views of health care were negatively associated with screening intentions after adjusting for all baseline covariates . These data suggest that a theoretically guided linguistically appropriate video that targets women from various ethnic groups is as efficacious in modifying attitudes toward mammography screening as a video that is exclusively tailored for Chinese immigrant women Low-income minorities often face system-based and personal barriers to screening colonoscopy ( SC ) . Culturally targeted patient navigation ( CTPN ) programs employing professional navigators ( Pro-PNs ) or community-based peer navigators ( Peer-PNs ) can help overcome barriers but are not widely implemented . In East Harlem , NY , USA , where approximately half the residents participate in SC , 315 African American patients referred for SC at a primary care clinic with a Direct Endoscopic Referral System were recruited between May 2008 and May 2010 . After medical clearance , 240 were r and omized to receive CTPN delivered by a Pro-PN ( n = 106 ) or Peer-PN ( n = 134 ) . Successful navigation was measured by SC adherence rate , patient satisfaction and navigator trust . Study enrollment was 91.4 % with no significant differences in SC adherence rates between Pro-PN ( 80.0 % ) and Peer-PN ( 71.3 % ) ( P = 0.178 ) . Participants in both groups reported high levels of satisfaction and trust . These findings suggest that CTPN Pro-PN and Peer-PN programs are effective in this urban primary care setting . We detail how we recruited and trained navigators , how CTPN was implemented and provide a preliminary answer to our questions of the study aims : can peer navigators be as effective as professionals and what is the potential impact of patient navigation on screening adherence This study examines the efficacy of targeted versus st and ard care smoking cessation material s among urban African American smokers . Five hundred smokers ( 250 to each group ) are r and omized to receive a culturally targeted or st and ard care videotape and print guide . Both groups receive 8 weeks of nicotine patches and reminder telephone calls at Weeks 1 and 3 . Process outcomes include material use and salience at 1 and 4 weeks postbaseline . Smoking outcomes include 7-day abstinence , smoking reduction , and readiness to quit at 4 weeks and 6 months postbaseline . Despite greater use of the targeted guide ( 68.8 % vs. 59.6 % , p < .05 ) , intervention participants do not perceive the targeted material s as more salient , and no significant differences are found between groups on the smoking outcomes . Findings point to the importance of greater audience segmentation and individual tailoring to better match intervention material s to the needs of the priority population OBJECTIVE No r and omized controlled trials ( RCTs ) for adults have compared the effectiveness of a well-specified psychotherapy and a culturally adapted version of the same treatment . This study evaluated the effectiveness of cognitive-behavioral therapy ( CBT ) and culturally adapted CBT ( CA-CBT ) in treating depressed Chinese-American adults . METHODS This RCT treated 50 Chinese Americans who met criteria for major depression and sought treatment at community mental health clinics . Screening of participants began in September 2008 , and the last assessment was conducted in March 2011 . Participants were stratified by whether they were already taking antidepressants when they first came to the clinic and r and omly assigned to 12 sessions of CBT or CA-CBT . The study did not influence regular prescription practice s. The primary outcomes were dropout rates and Hamilton Depression Rating Scale scores at baseline , session 4 , session 8 , and session 12 . RESULTS Participants in CA-CBT demonstrated a greater overall decrease in depressive symptoms compared with participants in CBT , but the groups had similarly high depression rates at week 12 . Differences in dropout rates for the two groups approached , but did not meet , statistical significance ( 7 % , CA-CBT ; 26 % , CBT ) . CONCLUSIONS Chinese Americans entered this study with very severe depression . Participants in both CBT and CA-CBT demonstrated significant decreases in depressive symptoms , but the majority did not reach remission . Results suggest that these short-term treatments were not sufficient to address such severe depression and that more intensive and longer treatments may be needed . Results also indicate that cultural adaptations may confer additional treatment benefits Research ers in migrant health clinics in Washington state found cost to be the single most commonly reported reason given by foreign-born Hispanic women for never having had a mammogram . The true significance of this finding beyond self-report was unknown . A r and omized intervention trial design ed to test the effect of fully subsidized mammograms on utilization was conducted within this population . Women in the intervention group received st and ard clinic instruction plus a voucher for a free mammogram . Controls received st and ard clinic instruction alone . Eighty-seven percent of women receiving vouchers obtained a mammogram within 30 days , compared with 17.5 % of controls . Logistic regression analysis revealed that women receiving vouchers were 47 times more likely to obtain a mammogram than controls . This confirms women 's self-report that cost is a major barrier to accessing screening mammograms in this low-income migrant population , and that women are more likely to utilize this service when financial barriers are removed This study compared the effects of 3 home-based exercise promotion programs for African Americans . Sixty , sedentary African-American adults were r and omly assigned to either a st and ard behavioral counseling group ( N=22 ) , a culturally sensitive counseling group ( N=20 ) , or a physician advice comparison group ( N=10 ) . The key study outcomes measured at baseline and after 6 months included cardiorespiratory fitness and physical activity . Acculturation was examined as a moderating variable . Participants in all 3 groups reported significant increases in walking , but significant improvements in fitness were observed only in the 2 intervention groups . Participants in the culturally sensitive intervention reported significantly higher levels of exercise social support compared to members of the other 2 groups . These findings show that home-based exercise counseling programs are effective for improving fitness , yet the addition of culturally tailored components may not be sufficient to produce better outcomes than st and ard behavioral counseling African-American women recruited from low-income housing projects in Chicago ( N = 106 ) were r and omly assigned to view 1 of 3 20-min videotapes : a st and ard public health service tape on prevention of acquired immunodeficiency syndrome ( AIDS ) , the same public health service tape but matching presenter and participant ethnicity and sex , or a tape that included the same content but was framed in a context specifically intended to increase cultural relevance . Participants who viewed the tapes presented by African-American women were significantly more sensitized to AIDS and were more likely to have discussed AIDS with friends , to be tested for human immunodeficiency virus ( HIV ) antibodies during the follow-up interval , and to request condoms at follow-up . These results support the use of culturally sensitive AIDS prevention messages targeted to specific population s , particularly to promote HIV-antibody testing OBJECTIVE Hypertension is known to have high rates among Chinese Americans . Identifying culturally specific interventions to reduce sedentary behavior may be effective in reducing hypertension . This study examines the effects of an 8-week walking program with and without cultural modification . DESIGN The study used a 2-group , pretest and posttest , quasi-experimental design . SAMPLE A total sample of 128 Chinese American immigrants with hypertension were assigned to walking groups . RESULTS The results showed that the walking program had no significant effects upon participant blood pressure or walking endurance . The results also revealed that individuals in the maintenance stage walked longer than those in the preparation stage . A comparison of demographic data showed that subjects with a lower level of education walked more minutes per week , which contributed to lower systolic blood pressures among this group as compared with those with a higher level of education . CONCLUSIONS These results suggest that this walking protocol , when translated into Chinese and when accompanied by a weekly telephone reminder and other interactions with a Chinese-speaking nurse , is appropriate to use without additional cultural modification . Future research should examine other components of Chinese culture or should apply this protocol for a longer period of time 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 This study compared the effectiveness of a culturally modified version of Parent – Child Interaction Therapy ( PCIT ) , called Gui and o a Niños Activos ( GANA ) , to the effectiveness of st and ard PCIT and Treatment as Usual ( TAU ) for young Mexican Amerian children with behavior problems . Fifty-eight Mexican Amerian families whose 3- to 7-year-old child had a clinical ly significant behavior problems were r and omly assigned to GANA , st and ard PCIT , or TAU . All three treatment approaches produced significant pre – post improvement in conduct problems across a wide variety of parent-report measures . GANA produced results that were significantly superior to TAU across a wide variety of both parent report and observational indices ; however , GANA and PCIT did not differ significantly from one another . PCIT was superior to TAU on two of the parent report indices and almost all of the observational indices . There were no significant differences between the three groups on treatment dropout , and families were more satisfied with both GANA and PCIT than with TAU BACKGROUND It is widely accepted that disease prevention efforts should consider cultural factors when addressing the needs of diverse population s , yet there is surprisingly little evidence that doing so enhances effectiveness . The Institute of Medicine has called for r and omized studies directly comparing approaches that do and do not consider culture . METHODS In a r and omized trial , 1227 lower-income African-American women from 10 urban public health centers were assigned to either a usual care control group , or to receive a series of six women 's health magazines with content tailored to each individual . By r and om assignment , these magazines were generated from either behavioral construct tailoring ( BCT ) , culturally relevant tailoring ( CRT ) or both ( BCT + CRT ) . The CRT magazines were based on four cultural constructs : religiosity , collectivism , racial pride , and time orientation . All tailored magazines sent to women ages 40 - 65 promoted use of mammography ; magazines sent to women ages 18 - 39 promoted fruit and vegetable ( FV ) intake . Analyses examined changes from baseline to 18-month follow-up in use of mammography and servings of FV consumed daily . RESULTS Women receiving BCT + CRT magazines were more likely than those in the BCT , CRT , and control groups to report getting a mammogram ( 76 % vs. 65 % vs. 64 % vs. 55 % , respectively ) , and had greater increases in FV servings consumed daily ( + 0.96 vs. + 0.43 vs. + 0.25 vs. + 0.59 ) . CONCLUSIONS Systematic ally integrating culture into tailored cancer prevention and control interventions may enhance their effectiveness in diverse population INTRODUCTION Health communication interventions have been modestly effective for increasing informed decision making for prostate cancer screening among African-American men ; however , knowledge and informed decision making is still question able even with screening . Church-based programs may be more effective if they are spiritually based in nature . OBJECTIVE The aims of the present study were to implement and provide an initial evaluation of a spiritually based prostate cancer screening informed decision making intervention for African-American men who attend church , and determine its efficacy for increasing informed decision making . DESIGN AND METHOD Churches were r and omized to receive either the spiritually based or the non-spiritual intervention . Trained community health advisors , who were African-American male church members , led an educational session and distributed educational print material s. Participants completed baseline and immediate follow-up surveys to assess the intervention impact on study outcomes . RESULTS The spiritually based intervention appeared to be more effective in areas such as knowledge , and men read more of their material s in the spiritually based group than in the non-spiritual group . CONCLUSIONS Further examination of the efficacy of the spiritually based approach to health communication is warranted BACKGROUND African Americans remain a critically underserved group for smoking cessation interventions . This study tested the effectiveness of a tailored , culturally sensitive intervention for African American smokers who called the NCI Cancer Information Service ( CIS ) for help to quit smoking . METHODS This paper presents results of a 2-year study of tailored counseling strategies among African American smokers ( n = 1,422 ) who called four regional CIS offices in response to a radio-based media campaign in 14 communities . Callers were r and omly assigned to receive either the st and ard CIS quit smoking counseling and guide ( Clearing the Air ) or counseling and a guide ( Pathways to Freedom ) tailored to the quitting needs and barriers of African American smokers . Callers were predominantly female ( 63.6 % ) . ages 20 - 49 ( 88 % ) , with a high school education or more ( 84 % ) . Median smoking history was 17 years ; median smoking rate was 20 cigarettes/day . St and ard ( n = 689 ) and Tailored ( n = 733 ) group subjects did not differ on most baseline measures . RESULTS On most measures , St and ard and Tailored counseling/guides received similar ratings , but the Tailored guide was rated as having more appealing photos ( P = 0.001 ) and as being more appropriate for family members ( P = 0.003 ) . Six-month follow-up with 893 subjects ( response rates were 63 % St and ard , 62 % Tailored , ns ) showed significantly more quit attempts ( P = 0.002 ) and greater use of prequitting strategies ( P < 0.05 ) among Tailored than among St and ard subjects , but no differences in self-reported 1-week abstinence ( 14.4 % St and ard , 16.2 % Tailored ) ( ns ) . An opportunistic 12-month follow-up of subjects recruited in the last year of the study ( n = 445 ) ( response rates were 57 % St and ard , 60 % Tailored , ns ) showed a significantly higher quit rate ( 15.4 % St and ard , 25.0 % Tailored ) for Tailored subjects ( P = 0.034 ) . CONCLUSIONS Results show promise for tailored approaches to boost quit attempts and success rates among African American smokers Studies comparing empirically supported substance abuse treatments versus their culturally accommo date d counterparts with participants from a specific ethnic minority group are lacking in the literature . To address this gap , this pilot study was conducted to compare the feasibility and relative efficacy of an empirically supported st and ard version of cognitive-behavioral substance abuse treatment ( S-CBT ) to a culturally accommo date d version ( A-CBT ) with a sample of Latino adolescents . This study was guided by a Cultural Accommodation Model for Substance Abuse Treatment ( CAM-SAT ) . Thirty-five Latino adolescents ( mean age = 15.49 ) were r and omly assigned to one of two 12-week group-based treatment conditions ( S-CBT = 18 ; A-CBT = 17 ) with assessment s conducted at pretreatment , posttreatment and 3-month follow-up . Results indicated similar retention and satisfaction rates for participants in both treatment conditions . In addition , participants in both conditions demonstrated significant decreases in substance use from pre- to posttreatment with slight increases at 3-month follow-up ; however , substance use outcomes were moderated by two cultural variables : ethnic identity and familism . Implication s of these findings within the context of conducting clinical trials with Latino adolescents are discussed . ( PsycINFO Data base Record ( c ) 2012 APA , all rights reserved ) Despite the many recommendations for specialized counseling for African-American men arrested for domestic violence , research has yet to document its effectiveness in improving program completion . This experimental clinical trial compared the program completion rates of culturally-focused counseling in all-African-American groups , conventional counseling in all-African-American groups , and conventional counseling in racially-mixed groups . The completion rate for the 16-week program was approximately 55 % across the three counseling options . Completion rates were slightly lower in the specialized counseling groups following stricter enforcement of dismissal policies . For men with high racial identification , the completion rate rose to between 63 % and 65 % in the culturally-focused and conventional all-African-American groups versus only 40 % in the racially-mixed groups . Programs might offer the option of culturally-focused counseling to African-American men to efficiently improve program completion . The influence of the program 's strong link to the criminal justice system and weaker link to the community warrants further consideration Obesity is a risk factor for a variety of chronic diseases . Although weight loss may reduce these risks , weight loss programs design ed for black women have yielded mixed results . Studies suggest that religion/spirituality is a prominent component of black culture . Given this , the inclusion of religion/spirituality as an active component of a weight loss program may enhance the benefits of the program . The role of religion/spirituality , however , has not been specifically tested as a mechanism that enhances the weight loss process . This paper presents the results of " Faith on the Move , " a r and omized pilot study of a faith-based weight loss program for black women . The goals of the study were to estimate the effects of a 12-week culturally tailored , faith-based weight loss intervention on weight loss , dietary fat consumption and physical activity . The culturally tailored , faith-based weight loss intervention was compared to a culturally tailored weight loss intervention with no active faith component . Fifty-nine overweight/obese black women were r and omized to one of the two interventions . Although the results were not statistically significant , the effect size suggests that the addition of the faith component improved results . These promising preliminary results will need to be tested in an adequately powered trial OBJECTIVE To examine whether tailored cancer communication for African American women can be enhanced by tailoring on 4 sociocultural constructs : religiosity , collectivism , racial pride , and time orientation . METHODS In a r and omized trial , participants ( n=1,227 ) received a women 's health magazine tailored using behavioral construct tailoring ( BCT ) , culturally relevant tailoring ( CRT ) , or both ( COMBINED ) . Two follow-up interviews assessed responses to the magazines . RESULTS Responses to all magazines were positive . The health focus of the magazines was initially obscured in the CRT condition , but this disappeared over time , and CRT magazines were better liked . CONCLUSIONS Implication s for developing and underst and ing effects of tailored cancer communication are discussed OBJECTIVE To evaluate the effect of a theory-based , culturally targeted intervention on adherence to follow-up among low-income and minority women who experience an abnormal Pap test . METHOD 5,049 women were enrolled and underwent Pap testing . Of these , 378 had an abnormal result and 341 ( 90 % ) were r and omized to one of three groups to receive their results : Intervention ( I ) : culturally targeted behavioral and normative beliefs + knowledge/skills + salience + environmental constraints/barriers counseling ; Active Control ( AC ) : nontargeted behavioral and normative beliefs + knowledge/skills + salience + environmental constraints/barriers counseling ; or St and ard Care Only ( SCO ) . The primary outcome was attendance at the initial follow-up appointment . Secondary outcomes included delay in care , completion of care at 18 months , state anxiety ( STAI Y-6 ) , depressive symptoms ( CES-D ) , and distress ( CDDQ ) . Anxiety was assessed at enrollment , notification of results , and 7 - 14 days later with the CDDQ and CES-D. RESULTS 299 women were included in intent-to-treat analyses . Adherence rates were 60 % ( I ) , 54 % ( AC ) , and 58 % ( SCO ) , p = .73 . Completion rates were 39 % ( I ) and 35 % in the AC and SCO groups , p = .77 . Delay in care ( in days ) was ( M ± SD ) : 58 ± 75 ( I ) , 69 ± 72 ( AC ) , and 54 ± 75 ( SCO ) , p = .75 . Adherence was associated with higher anxiety at notification , p < .01 and delay < 90 days ( vs. 90 + ) was associated with greater perceived personal responsibility , p < .05 . Women not completing their care ( vs. those who did ) had higher CES-D scores at enrollment , p < .05 . CONCLUSIONS A theory-based , culturally targeted message was not more effective than a nontargeted message or st and ard care in improving behavior OBJECTIVE This study examined the effects ( affective reactions , cognitive reactions and processing , perceived benefits and barriers and intent to screen ) of targeted peripheral+evidential ( PE ) and peripheral+evidential+socio-cultural ( PE+SC ) colorectal cancer communications . METHODS This study was a two-arm r and omized control study of cancer communication effects on affective , cognitive processing , and behavioral outcomes over a 22-week intervention . There were 771 African American participants , 45 - 75 years , participating in the baseline survey related to CRC screening . Three follow-up interviews that assessed intervention effects on affective response to the publications , cognitive processing , and intent to obtain CRC screening were completed . RESULTS There were no statistically significant differences between PE and PE+SC intervention groups for affect , cognitive processing or intent to screen . However , there were significant interactions effects on outcome variables . CONCLUSIONS The advantages and disadvantages of PE+SC targeted cancer communications and implication s of sex differences are considered . PRACTICE IMPLICATION S While there do not appear to be significant differences in behavioral outcomes when using PE and PE+SC strategies , there appear to be subtle differences in affective and cognitive processing outcomes related to medical suspicion and ethnic identity , particularly as it relates to gender OBJECTIVES Strategies are needed to improve medication management among vulnerable population s. We tested the effect of providing illustrated , plain- language medication lists on medication underst and ing , adherence , and satisfaction among Latino patients with diabetes in a safety net clinic . STUDY DESIGN R and omized controlled trial . METHODS Intervention patients received a PictureRx illustrated medication list that depicted the medication , indication , and dosing instructions , accompanied by plain language bilingual text . Usual care patients received a written list of their medications in their preferred language , with indication but no images . Outcomes were assessed by telephone approximately 1 week later . The Medication Underst and ing Question naire measured patients ' ability to report the indication , strength , dosing , and frequency for their medication regimen . Self-reported adherence and satisfaction were secondary outcomes . Analysis was performed by intention to treat . RESULTS Of 200 enrolled participants , 197 ( 98.5 % ) completed follow-up . Most ( 71 % ) had not graduated high school , and 59 % had low health literacy . Patients r and omized to illustrated medication instructions had better overall underst and ing of their medications ( P<.001 ) , including greater ability to report the drug indication ( P<.01 ) , strength ( P<.05 ) , dosing ( P<.01 ) , and frequency of administration ( P<.001 ) . Self-reported adherence did not differ significantly between study groups . Patients who received illustrated medication lists were very satisfied with them . CONCLUSIONS In this r and omized controlled trial , patients who received illustrated , plain- language medication lists demonstrated significantly greater underst and ing of their medication regimen . Such tools have the potential to improve medication use and chronic disease control , as well as reduce health disparities-although this requires further study BACKGROUND Methamphetamine-dependent gay and bisexual men ( GBM ) are at high risk for HIV transmission , largely due to drug-associated sexual risk behaviors . This project evaluated the efficacy of four behavioral drug abuse treatments for reducing methamphetamine use and sexual risk behaviors among this population . METHODS In this r and omized controlled trial , 162 methamphetamine-dependent ( SCID-verified ) GBM in Los Angeles County were r and omly assigned to one of four treatment conditions for 16 weeks : st and ard cognitive behavioral therapy ( CBT , n=40 ) , contingency management ( CM , n=42 ) , combined cognitive behavioral therapy and contingency management ( CBT+CM , n=40 ) , and a culturally tailored cognitive behavioral therapy ( GCBT , n=40 ) . Stimulant use was assessed thrice-weekly during treatment using urine drug screens ( 48 measures ) . Sexual risk behaviors were monitored monthly ( four measures ) . Follow-up assessment s were conducted at 6 ( 80.0 % ) and 12 months ( 79.9 % ) . RESULTS Statistically significant differences in retention ( F(3,158)=3.78 , p<.02 ) , in longest period of consecutive urine sample s negative for methamphetamine metabolites ( F(3,158)=11.80 , p<.001 ) , and in the Treatment Effectiveness Score were observed by condition during treatment ( F(3,158)=7.35 , p<.001 ) with post hoc analyses showing the CM and CBT+CM conditions to perform better than st and ard CBT . GEE modeling results showed GCBT significantly reduced unprotected receptive anal intercourse ( URAI ) during the first 4 weeks of treatment ( X2=6.75 , p<.01 ) . During treatment between-group differences disappeared at follow-up with overall reductions in outcomes sustained to 1-year . CONCLUSIONS Among high-risk methamphetamine-dependent GBM , drug abuse treatments produced significant reductions in methamphetamine use and sexual risk behaviors . Drug abuse treatments merit consideration as a primary HIV prevention strategy for this population Previous research has highlighted the importance of cultural relevance in health risk communications , including tobacco interventions . However , few studies have examined the active components of smoking cessation messages targeting low-income African American smokers . This study tested the influence of message content and culturally specific framing in a sample of adult smokers . In a 2 x 2 factorial experiment , 243 African American smokers ( M = 19 cigarettes/day ) recruited from the community ( 55 % women ; mean age = 43 years ) were r and omly assigned to 1 of 4 conditions : culturally specific smoking messages , st and ard smoking messages , culturally specific exercise/weight messages , or st and ard exercise/weight messages . The primary outcome measures were theoretical antecedents to behavior change , including risk perceptions ( general , personal , and culturally specific ) , readiness to quit smoking , and smoking-related knowledge . The results showed that the smoking messages produced greater culturally specific risk perceptions , readiness to quit smoking , and smoking-related knowledge . The culturally specific messages produced greater personal risk perceptions and intentions to quit . Culturally specific risk perceptions were most affected by culturally specific smoking messages . Findings support the roles of message content and culturally specific framing in the efficacy of brief written interventions for smoking cessation in this population . Future research is needed to examine the influence of these constructs on behavior change This pilot study sought to dismantle the efficacy of culturally specific print material s for smoking cessation . Two-hundred sixty-one African American smokers were r and omized into 1 of 2 conditions : st and ard booklet or culturally specific booklet . The content and length of the interventions were identical yet varied in their degree of cultural specificity . Three-month follow-up assessment s were completed by 70 % ( N = 183 ) of participants . Dependent variables included content evaluation , readiness to quit smoking , and actual behavior change . Evidence suggested that the culturally specific material was more effective at capturing attention , providing encouragement and gaining interest compared to st and ard material s ; however , greater credibility was found for st and ard material s. In addition , greater readiness to quit and more 24-hour quit attempts were found in the st and ard condition . No differences were found in abstinence rates . In conclusion , culturally specific interventions may be preferred over st and ard approaches among African American smokers . Culturally specific approaches , however , may not result in greater behavior change . Implication s for written interventions and cultural specificity are discussed A r and omized clinical trial of culturally adapted and unadapted motivational interviewing to reduce drinking and related problems among heavy drinking Latinos assessed 57 participants at baseline and at 2 ( 86 % retention ) and 6 months ( 84 % retention ) after treatment . Significant decreases across both treatments were found in heavy drinking days per month and drinking consequences ( p < .001 ) , with greater reductions for drinking consequences for culturally adapted motivational interviewing at 2 months ( p = .009 ) and continuing reductions in culturally adapted motivational interviewing at 6 months . Findings provide preliminary support for the value of cultural adaptation to enhance the efficacy of motivational interviewing with Latino heavy drinkers OBJECTIVE Test the impact of tailoring CRC screening messages for African Americans ( AAs ) using novel theoretical variables and to examine moderating effect of communication preferences . METHODS Participants were r and omized to receive two minimally tailored or two enhanced tailored print newsletters addressing CRC . The enhanced intervention was tailored on Self-Determination Theory and other novel psychological constructs . Minimal tailoring only used information available in the patient 's EHR . The primary outcome was CRC screening based on EHR . Participants were AA members aged 50 - 74 of an integrated health care delivery system not up to date on CRC screening . RESULTS We enrolled 881 participants . CRC screening participation rates at 1-year follow up were 20.5 % and 21.5 % in the minimally and enhanced tailored groups , respectively . Communication preferences moderated the impact of the intervention . Specifically , among those with an autonomous communication preference , screening rates in the minimally and enhanced tailored groups were 17.1 % and 25.9 % , respectively , while no intervention effect was evident among those with a directive preference . CONCLUSION Future research is needed to explore the impact of communication preference tailoring for other health behaviors and among other population s. PRACTICE IMPLICATION S Tailored communications should consider communication style preference to help guide the content and tone of messages |
10,590 | 17,176,480 | Most quality indicators evaluated processes of care . | Background Breast cancer in women is increasingly frequent , and care is complex , onerous and expensive , all of which lend urgency to improvements in care .
Quality measurement is essential to monitor effectiveness and to guide improvements in healthcare . | UNLABELLED Information on treatment outcome outside clinical trials is sparse . This is the first study that relates surgical and medical quality of care in daily practice with outcome . BACKGROUND In a previous study we showed , that the quality of chemotherapy as described by a guideline and given in daily practice to premenopausal primary breast cancer patients was suboptimal with only 68 % and 53 % of the patients receiving chemotherapy with a dose intensity ( DI ) and relative dose intensity ( RDI ) of > or = 85 % , respectively . Many invalid reasons for delay and dose reductions were identified . PATIENTS AND METHODS Premenopausal node-positive primary breast cancer patients treated from 1988 to 1992 were traced using two national registries . Relevant data were collected from their records . The following treatment-related variables were correlated with prognosis : type of surgery , number of investigated lymph nodes , radiotherapy , chemotherapy , interval between surgery and start of chemotherapy , DI , duration , delays and dose adjustments of chemotherapy and hospital size . RESULTS Twenty-four of the 254 traced patients did not receive any chemotherapy , 230 received the recommended schedule of cyclophosphamide ( C ) , methotrexate ( M ) and 5-fluorouracil ( F ) . The median time of follow-up was 6.7 ( range 0.9 - 10.2 ) years . The 5-year disease-free survival ( DFS ) and overall survival ( OS ) was 61 % and 77 % , respectively . In an univariate analysis DI < 65 % correlated with a worse DFS and OS ( p=0.05 and p=0.03 , respectively ) . The use of chemotherapy correlated with a better DFS ( p=0.03 ) than no use . In a multivariate analysis DI between 65 and 85 % result ed in a better DFS ( p=0.02 ) than DI > or = 85 % and DI < 65 % . CONCLUSION The prognosis of the breast cancer patients in this population was comparable with the results of r and omised trials using adjuvant CMF . The only treatment related variable of value for prognosis was DI . Unexpectedly DI between 65 % and 85 % result ed in the best prognosis in this population . The relevance of this observation remains unclear and warrants further investigation PURPOSE To investigate the effects of the Interactive Breast Cancer CDROM as a decision aid for breast cancer patients with a choice between breast conserving therapy ( BCT ) and mastectomy ( MT ) . PATIENTS AND METHODS Consecutive patients with stage I and II breast cancer were enrolled . A quasi-experimental , longitudinal , and pretest/posttest design was used . Follow-up was scheduled 3 and 9 months after discharge from the hospital . Control patients ( n = 88 ) received st and ard care ( oral information and brochures ) . The CDROM was provided to patients in the experimental condition ( n = 92 ) as a supplement to st and ard procedures . Outcome variables were treatment decision , satisfaction , and quality of life ( QoL ) . RESULTS No effect on treatment decision was found . CDROM patients expressed more general satisfaction with information at 3 and 9 months ( 95 % confidence interval for the difference ( d ) between the means ( d : 4.1 to 12.5 and 5.7 to 14.2 respectively ) . CDROM patients were also more satisfied with their treatment decision at 3 and at 9 months ( d : 0.1 to 0.4 ; 0.2 to 0.5 ) . Moreover , at 9 months , CDROM patients were more satisfied with breast cancer-specific information ( d : 0.9 to 16.5 ) , the decision-making process ( d : 0.1 to 0.4 ) , and communication ( d : 0.2 to 11.0 ) . At 3 and 9 months , a positive effect was found on general health ( d : 0.2 to 14.5 and 0.3 to 15.0 ) . Moreover , at 9 months , CDROM patients reported better physical functioning ( d : 5.1 to 19.8 ) , less pain ( d : -17.9 to -4.5 ) , and fewer arm symptoms ( d : -14.1 to -0.5 ) . CONCLUSION The Interactive Breast Cancer CDROM improved decision making in patients with early-stage breast cancer with a choice between BCT and MT , as evaluated in terms of patients ' satisfaction and BACKGROUND AND PURPOSE The International Breast Cancer Study Group ( IBCSG ) has developed and approach for assessing the impact of adjuvant therapy on quality of life ( QL ) within the framework of international , multilingual clinical trials . The major steps are summarized . Conceptual , method ological and practical issues are discussed with reference to results of two trials closed to accrual ( IBCSG VI , VII ) and one subsequent ongoing trial ( IBCSG IX ) . PATIENTS AND METHODS QL was assessed in pre- and post-menopausal patients with operable breast cancer . Various single-item linear analogue self- assessment ( LASA ) scales were used as indicators of components of QL , including global indicators of well-being , functioning and health perception , and specific indicators of symptoms of disease and treatment . In trials VI and VII , QL was assessed at baseline , during adjuvant treatment and follow-up , and at recurrence . Based on this experience , the QL form was revised for subsequent trials and further investigated in a sub sample of patients r and omized into trial IX . RESULTS In trials VI and VII , the QL indicators were responsive to the impact of biomedical factors at baseline , various adjuvant treatments , changes over the first 18 months , and recurrence . In trial IX , the revised QL form was well accepted by patients and staff . Completing this form did not exceed five minutes . QL differences between on and off cytotoxic treatment strengthen the cl aim that these measures are responsive . Correlations and logistic regression analyses show the expected relationship among the various global and specific indicators . CONCLUSION Results from two trials closed to accrual and an ongoing trial confirm the feasibility , validity and clinical relevance of the IBCSG approach for study ing the impact of adjuvant breast cancer therapy on QL in international clinical trials |
10,591 | 20,500,945 | Indiscriminate application of eSET in population s with less than optimal prognosis for live birth will result in a significant reduction in effectiveness compared with DET .
In women aged 38 years and over , eSET may result in a significant reduction in live birth rate compared with DET . | OBJECTIVE To review the effect of elective single embryo transfer ( eSET ) compared with double embryo transfer ( DET ) following in vitro fertilization ( IVF ) , and to provide guidelines on the use of eSET in order to optimize live birth rates and minimize twin pregnancies .
OPTIONS Rates of live birth , clinical pregnancy , and multiple pregnancy following eSET and DET are compared .
Given the high costs of treatment , uptake of eSET would be enhanced by public funding of IVF treatment . (
In order to maintain the reduction in the rate of multiples achieved by fresh eSET , eSET should be performed in subsequent frozen-thawed embryo transfer cycles . (
In women aged 36 to 37 years , eSET should be considered in good-prognosis patients with good quality embryos , particularly when blastocysts are available for transfer . (
In oocyte donor-recipient cycles when the donor has good prognosis and when good quality embryos are available , eSET should be performed . (
In order to achieve successful uptake of eSET , it is essential to provide patient and physician education regarding the risks of twin pregnancy and regarding the similar cumulative live birth rate following an eSET strategy and DET . ( | BACKGROUND Twin pregnancies after IVF are still frequent and are considered high-risk pregnancies leading to high costs . Transferring one embryo can reduce the twin pregnancy rate . We compared cost-effectiveness of one fresh cycle elective single embryo transfer ( eSET ) versus one fresh cycle double embryo transfer ( DET ) in an unselected patient population . METHODS Patients starting their first IVF cycle were r and omized between eSET and DET . Societal costs per couple were determined empirically , from hormonal stimulation up to 42 weeks after embryo transfer . An incremental cost-effectiveness ratio ( ICER ) was calculated , representing additional costs per successful pregnancy . RESULTS Successful pregnancy rates were 20.8 % for eSET and 39.6 % for DET . Societal costs per couple were significantly lower after eSET ( 7334 euro ) compared with DET ( 10,924 euro ) . The ICER of DET compared with eSET was 19,096 euro , meaning that each additional successful pregnancy in the DET group will cost 19,096 euro extra . CONCLUSIONS One cycle eSET was less expensive , but also less effective compared to one cycle DET . It depends on the society 's willingness to pay for one extra successful pregnancy , whether one cycle DET is preferred from a cost-effectiveness point of view OBJECTIVE To identify factors that influence patient decision making concerning embryo transfer . DESIGN Prospect i ve analysis . SETTING In vitro fertilization unit at a tertiary-care , university-affiliated teaching hospital . PATIENT(S ) Seventy-nine women and 53 men who were referred consecutively for IVF treatment . INTERVENTION(S ) Provision of risk information about complications of twin pregnancy . MAIN OUTCOME MEASURE(S ) Rated desirability of different transfer options and twin pregnancy , together with st and ardized measures of depression and infertility stress . RESULT ( S ) Women 's initial preference for two-embryo transfer ( 2ET ) was related to beliefs that the chance of pregnancy was higher with 2ET vs. elective single-embryo transfer and that the personal chance of twins was relatively likely with 2ET but was not related to a specific desire for twins . Providing risk information increased the desirability of elective single-embryo transfer and decreased the desirability of twin pregnancy among both men and women . CONCLUSION ( S ) Cautious patients , preferring transfer of fewer embryos , balance desires to maximize the chance of pregnancy with acceptance of risks associated with twins . Less-cautious patients may be motivated by beliefs about the influence of age , desires for , and likelihood of twin pregnancy . Information about risks may affect these groups differently and diverse patient motivations may require tailored information to ensure informed consent Survivors of the " vanishing " twin syndrome , which occurred in dichorionic twins only , and singletons that began as singletons , had similar mean gestational duration and birth weights , as well as similar frequencies of maternal and neonatal complications . This similarity persisted when conventional IVF and IVF plus ICSI cases were separately evaluated BACKGROUND Single embryo transfer ( SET ) after IVF/ICSI has been shown to result in an acceptable pregnancy rate in selected subjects . In our unit , SET is routinely carried out among women under the age of 36 in the first or second treatment cycle when a top- quality embryo is available . In order to define further the selection criteria for SET , we have analysed the outcome of elective SET ( eSET ) , including the cumulative pregnancy rate after frozen embryo transfers , performed in the years 2000 - 2002 in the Oulu Fertility Center . METHODS During the study period , a total of 1271 transfers were performed , and in 468 cycles SET ( 39 % of all transfers ) was carried out . Of the SET cycles , in 308 cases a top- quality embryo was transferred on day 2 and extra embryos were frozen . Of these eSET cycles , ICSI was carried out in 87 cycles ( 28 % ) . RESULTS The overall clinical pregnancy rate per transfer was 34.7 % in the eSET cycles . In the eSET ICSI cycles , the clinical pregnancy rate was significantly higher than in the corresponding IVF cycles ( 50.6 versus 28.5 % , P < 0.001 ) . The cumulative pregnancy rate per patient after fresh and frozen embryo transfers was also significantly higher after ICSI ( 71.2 versus 53.4 % , P < 0.01 ) . CONCLUSIONS A high cumulative pregnancy rate per oocyte retrieval can be achieved after eSET in daily clinical practice . The implantation rate of fresh top- quality embryos in the ICSI cycles was significantly higher than in the IVF cycles , possibly due to more successful selection of the embryo for embryo transfer on day 2 after ICSI . In addition , our data suggest that embryo quality is a more important determinant of outcome than the age of the woman BACKGROUND We analysed the difference in maternal , neonatal and total costs after single ( SET ) versus double day 3 embryo transfer ( DET ) . METHODS We performed a two-centre prospect i ve study of women in their first IVF/ICSI cycle choosing between SET or DET . Infertility treatment data were gathered from a data base ; maternal and neonatal outcome data from a case report form ( CRF ) ; health economic data from medical acts registered in the CRF for the outpatient part and from hospital bills . SET was performed in 206/367 ( 56.1 % ) and DET in 161/367 ( 43.9 % ) women . RESULTS In all , 367 transfers yielded 186 positive pregnancy tests , 148 ongoing pregnancies and 136 live deliveries ( 50.7 , 40.3 and 37.1 % per embryo transfer ) of which 15 ( 11.0 % ) were twins . Live birth rate was 37.4 % for SET , 36.6 % for DET . Intention-to-treat analysis showed differences for : duration of pregnancy ( SET : 39.0 + /- 1.4 versus DET : 38.3 + /- 2.2 weeks ; P = 0.055 ) , percentage prematurity ( 8.5 versus 23.8 % ; P = 0.033 ) , percentage of neonates hospitalized ( 5.7 versus 17.9 % ; P = 0.121 ) and duration of neonatal hospitalization ( 6.3 + /- 2.2 versus 10.3 + /- 10.1 days ; P = 0.01 ) . Total cost after DET was higher ( SET : 4700 + /- 3239 versus DET : 8613 + /- 10 105 ; P = 0.105 ) , due to significantly higher neonatal costs ( 451 + /- 957 versus 3453 + /- 8154 ; P < 0.001 ) and not to differences in maternal costs ( 4250 + /- 2882 versus 5160 + /- 4106 ; P = 0.152 ) . CONCLUSIONS This prospect i ve health economic study shows that transfer of a single top quality embryo is equally effective as , but substantially cheaper than , double embryo transfer in women < 38 years of age in their first IVF/ICSI cycle St and ard protocol s for in-vitro fertilization ( IVF ) include transfer of two or three embryos . Not surprisingly , the rate of twin pregnancy after IVF is high ( about 24 % of all pregnancies ) . Routine transfer of one , rather than two , embryos would be expected to result in a much lower rate of twin pregnancies at the cost of a lower take-home baby rate . The aim of this study was to compare hypothetical costs to society incurred by pregnancies achieved with IVF protocol s based on the transfer of one or two embryos . We compared actual ( for two-embryo transfers ) and hypothetical ( for one-embryo transfers ) take-home baby rates ; risks of twin pregnancies ; and costs of sick leave and hospitalization during pregnancy , deliveries , neonatal intensive care , and h and icap care after transfer of one or two embryos . The study showed that even when more treatments might be needed to achieve similar baby take-home rates after transfer of one compared with two embryos , the lower twin pregnancy rate of the former approach caused it to be more cost-efficient than the latter . In conclusion , IVF costs are the sum of fertilization treatment costs and the costs for health care of the pregnant women and their offspring . Considering the association of the latter costs with numbers of embryos transferred , studies of one-embryo transfer protocol s are urgently needed BACKGROUND Transfer of several embryos after IVF results in a high multiple birth rate associated with increased morbidity and high costs for the neonatal care . In a previous r and omized trial we demonstrated that a single embryo transfer ( SET ) strategy , including one fresh single embryo transfer and , if no live birth , one additional frozen-thawed SET , result ed in a live-birth rate that was not substantially lower than after double embryo transfer ( DET ) but markedly reduced the multiple birth rate . METHODS We compared costs for maternal health care and productivity losses and paediatric costs for the SET and DET strategies . In addition , maternal and paediatric outcomes between the two groups were compared . RESULTS The SET strategy result ed in lower average total costs from treatment until 6 months after delivery . There were a few more deliveries with at least one live-born child in the DET group . The incremental cost per extra delivery in the DET alternative was high , 71 940 . The rates of prematurely born and low birthweight children were significantly lower with the SET strategy . There were also markedly fewer maternal and paediatric complications in the SET group . CONCLUSIONS The SET strategy is superior to the DET strategy , when number of deliveries with at least one live-born child , incremental cost-effectiveness ratio and maternal and paediatric complications are taken into consideration . The findings do not support continuing transfers of two embryos in this group of patients Abstract Objective To compare neurological sequelae in twins born after assisted conception with singletons after assisted conception and naturally conceived twins and to assess neurological sequelae in children conceived after in vitro fertilisation ( IVF ) compared with intracytoplasmic sperm injection ( ICSI ) . Design Controlled , national register based , cohort study . Participants Twins ( n = 3393 ) and singletons ( n = 5130 ) conceived by using assisted reproductive technologies and naturally conceived twins ( n = 10 239 ) born in Denmark between 1995 and 2000 . The children 's age at time of follow up was 2 - 7 years . Data sources Children were identified by cross linkage of the national medical birth registry and the national registry for in vitro fertilisation . Neurological and psychiatric diagnoses were retrieved from the national patients ' registry and the Danish psychiatric central registry . Main outcome measures Neurological sequelae , defined as cerebral palsy , mental retardation , severe mental developmental disturbances , and retarded psychomotor development . Further we made separate analyses on the specific cerebral palsy diagnosis . Results The crude prevalence rates per 1000 of neurological sequelae in twins and singletons after assisted conception and in naturally conceived twins were 8.8 , 8.2 , and 9.6 , and of cerebral palsy 3.2 , 2.5 , and 4.0 , respectively . In twins after assisted conception compared with control twins , the odds ratios of neurological sequelae and specifically of cerebral palsy , adjusted for child sex and year of birth , were 0.9 ( 95 % confidence interval 0.6 to 1.4 ) and 0.8 ( 0.4 to 1.6 ) , respectively . The corresponding odds ratios for twins after assisted conception compared with singletons after assisted conception were 1.1 ( 0.7 to 1.7 ) for neurological sequelae and 1.3 ( 0.6 to 2.9 ) for cerebral palsy . The odds ratio of neurological sequelae in children conceived by ICSI was 0.9 ( 0.5 to 1.7 ) ν children conceived by IVF . Conclusions Twins from assisted conception have a similar risk of neurological sequelae as their naturally conceived peers and singletons from assisted conception . Children born after ICSI have the same risk of neurological sequelae as children born after IVF BACKGROUND Elective single embryo transfer ( eSET ) in a selected group of patients ( i.e. young patients with at least one good quality embryo ) reduces the number of multiple pregnancies in an IVF programme . However , the reduced overall multiple pregnancy rate ( PR ) is still unacceptably high . Therefore , a r and omized controlled trial ( RCT ) was conducted comparing eSET and double embryo transfer ( DET ) in an unselected group of patients ( i.e. irrespective of the woman 's age or embryo quality ) . METHODS Consenting unselected patients were r and omized between eSET ( RCT -eSET ) ( n = 154 ) or DET ( RCT -DET ) ( n = 154 ) . R and omization was performed just prior to the first embryo transfer , provided that at least two 2PN zygotes were available . Non- participants received our st and ard transfer policy [ SP-eSET in a selected group of patients ( n = 100 ) , otherwise SP-DET ( n = 122 ) ] . RESULTS The ongoing PR after RCT -eSET was significantly lower as compared with RCT -DET ( 21.4 versus 40.3 % ) and the twin PR was reduced from 21.0 % after RCT -DET to 0 % after RCT -eSET . The ongoing PRs after SP-eSET and SP-DET did not differ significantly ( 33.0 versus 30.3 % ) , with an overall twin PR of 12.9 % . CONCLUSION To avoid twin pregnancies result ing from an IVF treatment , eSET should be applied in all patients . The consequence would be a halving of the ongoing PR as compared with applying a DET policy in all patients . The transfer of one embryo in a selected group of good prognosis patients leads to a less drastic reduction in PR but maintains a twin PR of 12.9 % BACKGROUND The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies . The only strategy to avoid dizygotic twins is to transfer one embryo at a time . METHODS A total of 144 women , who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection ( ICSI ) and who had no more than one previous failed treatment cycle , were r and omized to have either one or two embryos transferred . The treatment outcomes including those after frozen embryo transfer were compared between these groups . RESULTS The clinical pregnancy rate per transfer was 32.4 % in the one embryo transfer group and 47.1 % in the two embryo transfer group , the difference being not significant . Eleven twin deliveries ( n = 39 ) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group . The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3 % in the one embryo transfer group and 58.6 % in the two embryo transfer group . CONCLUSIONS Our results indicate that among women who have good quality embryos in their first IVF/ICSI , good treatment results can be achieved . They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate , while dizygotic twins can be avoided BACKGROUND The possible interference of assisted reproduction techniques ( ART ) with epigenetic reprogramming during early embryo development has recently sparked renewed interest about the reported lower birth weight among infants born as a consequence of infertility treatments . However , the latter finding so far has relied on the comparison of the birth weight of infants conceived with ART to general population data . A more appropriate comparison group should involve pregnancies in infertile women after natural conception . Therefore , we compared neonatal birth weight data of infants born after various ART treatments , including intrauterine insemination ( IUI ) , with those of previously infertile women achieving pregnancy after sexual intercourse . METHODS Between August 1996 and March 2004 the data of all infertile women presenting in the infertility unit of the University Women 's Hospital of Basel , Switzerl and , were collected prospect ively , adding up to 995 intact pregnancies and deliveries . The birth weight of all infants result ing from 741 singleton pregnancies were analysed with regard to the patients ' characteristics , the occurrence of complications during pregnancy and the type of infertility treatment with which the pregnancies were achieved . RESULTS Comparison of duration of pregnancy and birth weight of infants born after infertility treatment confirms a shorter pregnancy span and a lower mean birth weight in infants born after IVF and ICSI . If women with pregnancies after ART deliver before term , neonatal birth weight is significantly lower . CONCLUSIONS There is a specific effect of ART , mainly IVF and ICSI , on both shortening the duration of pregnancy and lowering neonatal birth weight . Both these parameters seem to be interrelated consequences of some modification in the gestational process induced by the infertility treatment . Freezing and thawing of oocytes in the pronucleate stage had a lesser impact on pregnancy span and on neonatal birth weight BACKGROUND Recently , concern has risen about poor obstetrical and neonatal outcome of singletons after IVF/ICSI . Because the population of patients receiving single-embryo transfer ( SET ) result ing in singleton pregnancies is different from the one that would have become pregnant ( with a singleton ) before SET was introduced , we wanted to investigate whether the outcome of singleton pregnancies after SET differed from spontaneously conceived singletons . METHODS The obstetrical and early neonatal outcome of all pregnancies originating from SET after IVF/ICSI procedures between 1 January 1998 and 31 December 2003 , was prospect ively collected and analyzed . RESULTS Data from 251 singleton pregnancies and births after SET were analyzed and compared to data from 59,535 spontaneously conceived singletons retrieved from the Centre for Perinatal Epidemiology . The mean birthweight of the singletons after SET was 3322 g ( + /-538 SD ) versus 3330 g ( + /-531 SD ) for the spontaneously conceived singletons ( P = 0.82 ) . The mean gestational age was 38.7 weeks ( + /-1.9 SD ) for SET and 38.9 weeks ( + /-1.8 SD ) for spontaneously conceived singletons ( P = 0.06 ) . The proportion of very preterm birth ( < 32 weeks ) was 0.8 % in each group , and the proportion of preterm birth ( < 37 weeks ) was 10.0 % for SET singletons and 6.24 % for spontaneous singletons ( P = 0.03 ) . However , mean birthweight of very preterm , preterm and term SET singleton babies was similar to the mean birthweight in every category of gestational age in the spontaneous conceived control group . Stillbirth was 0.4 % for both population s ( P = 0.99 ) . CONCLUSIONS Good prognosis patients , in whom SET is applied , do not only have a higher chance of conception but do not have an unfavourable outcome of their singleton baby when compared to spontaneous singletons BACKGROUND With the aim of reducing the number of multiple pregnancies after IVF we investigated the effectiveness of two cycles with single embryo transfer ( SET ) and one cycle with double embryo transfer ( DET ) after IVF and calculated the cost-effectiveness of both strategies . METHODS A r and omized controlled trial was performed in 107 women , aged < 35 years , in their first IVF cycle , with at least one good quality embryo . They were r and omized to the SET ( n = 54 ) or DET ( n = 53 ) group using a computer-generated r and om block number table , stratified for primary or secondary infertility . RESULTS The cumulative live birth rates per woman r and omized of two consecutive cycles of SET [ 41 % ; 95 % confidence interval ( CI ) 27 - 54 ] versus one cycle of DET ( 36 % ; 95 % CI 23 - 49 ) were comparable , whereas the multiple pregnancy rate was significantly higher : 37 % ( 95 % CI 15 - 59 ) in the DET and 0 % in the in the SET group ( P = 0.002 ) . Combining the medical costs of the IVF treatments ( where 1.5 more SET cycles were required to achieve each live birth ) and of pregnancies up to 6 weeks after delivery , the total medical costs of DET per live birth were 13,680 and 13,438 for SET . CONCLUSIONS Two cycles with SET were equally effective as one cycle with DET , and the medical costs per live birth up to 6 weeks after delivery were the same . However , if lifetime costs for severe h and icaps are included , more than 7000 per live birth will be saved after implementing SET . Because of the high probability of multiple pregnancies in this group of IVF patients , only SET should be performed BACKGROUND Single-embryo transfer has been recommended to reduce the incidence of multiple gestations when in vitro fertilization is performed in women under 36 years of age . We design ed a prospect i ve , r and omized , controlled trial to determine whether there were any differences in the rates of pregnancy and delivery between women undergoing transfer of a single cleavage-stage ( day 3 ) embryo and those undergoing transfer of a single blastocyst-stage ( day 5 ) embryo . METHODS We studied 351 infertile women under 36 years of age who were r and omly assigned to undergo transfer of either a single cleavage-stage embryo ( 176 patients ) or a single blastocyst-stage embryo ( 175 patients ) . Multifollicular ovarian stimulation was performed with a gonadotropin-releasing hormone antagonist and recombinant follicle-stimulating hormone . RESULTS The study was terminated early after a prespecified interim analysis ( which included 50 percent of the planned number of patients ) found a higher rate of pregnancy among women undergoing transfer of a single blastocyst-stage embryo ( P=0.02 ) . The rate of delivery was also significantly higher in this group than in the group undergoing transfer of a single cleavage-stage embryo ( 32.0 percent vs. 21.6 percent ; relative risk , 1.48 ; 95 percent confidence interval , 1.04 to 2.11 ) . Two multiple births occurred , both of monozygotic twins , both of which were in the group undergoing transfer of a single cleavage-stage embryo . CONCLUSIONS These findings support the transfer of a single blastocyst-stage ( day 5 ) embryo in infertile women under 36 years of age BACKGROUND The purpose of this study was to assess the effect of alternative ways of providing information about the risks of twins on couples ' perceptions about elective single embryo transfer ( eSET ) . METHODS Couples undergoing IVF were r and omized into three groups . Group 1 received a st and ard information pack , group 2 an extra information leaflet about twin pregnancy , and group 3 an additional discussion session . The primary outcome measure was acceptability of a hypothetical policy of eSET . Data were collected by means of a question naire . RESULTS eSET was acceptable to 17 ( 27 % ) , 20 ( 30 % ) and 24 ( 32 % ) couples in groups 1 , 2 and 3 , if it meant a slight reduction in pregnancy rates , and to 51 ( 82 % ) , 55 ( 83 % ) and 53 ( 87 % ) couples , respectively , if pregnancy rates were unchanged . A fixed charge for all fresh and frozen embryo transfers following a single oocyte retrieval led to acceptability rates of 35 ( 57 % ) , 36 ( 55 % ) and 38 ( 65 % ) . CONCLUSIONS Additional information , involving an extra information leaflet and face to face discussion , did not changes couples ' attitudes towards eSET . Maintaining existing rates of pregnancy and offering a fixed charge for all embryo transfers result ing from an oocyte recovery may encourage more couples to consider eSET BACKGROUND In the context of mounting concern about the risks of twin pregnancies result ing from IVF , this study aim ed to assess staff and patients ' attitudes towards a proposed r and omized controlled trial ( RCT ) of elective single embryo transfer ( SET ) in a Scottish fertility centre . METHODS The views of 10 members of IVF clinic staff were assessed by means of a focus group and those of 12 couples by semi-structured interviews . RESULTS Staff were aware of the risks of twin pregnancies to mothers and babies and the need for evidence of success in SET , but had reservations about the proposed RCT . The need to subject patients to unpopular scientific procedures such as r and omization and blinding conflicted with their perceived caring role . They felt it would be hard to recruit and onerous to patients but nevertheless discussed how it could be successfully mounted if necessary . They debated how to ensure that consent was fully informed , and when , and how , to r and omize . Patients accepted the possibility of twins but were largely unaware of risks inherent in twin pregnancies . They saw no need for a trial and found the idea of r and omization unacceptable except in younger women . They would accept SET if it became unit policy and appeared unaffected by financial considerations . CONCLUSIONS Involving affected staff at the design stage may make it easier to conduct a SET trial in their clinics . IVF patients whose ultimate goal is pregnancy are less likely to support a trial which aims to minimize twin pregnancies OBJECTIVE To present a report on assisted reproductive technologies ( ART ) cycles performed in 2005 in Canada . This is the fifth annual report from the Canadian ART Register ( CARTR ) . DESIGN Prospect i ve cohort study . SETTING Twenty-five of 25 ART centers in Canada . PARTICIPANT(S ) Couples undergoing ART treatment in Canada during 2005 . INTERVENTION(S ) ART treatments , including IVF , intracytoplasmic sperm injection ( ICSI ) , and frozen ET ( FET ) . MAIN OUTCOME MEASURE(S ) Clinical pregnancy , live birth , and multiple birth rates . RESULT ( S ) A total of 11,414 ART cycles was reported to CARTR . In 8195 IVF/ICSI cycles using the women 's own oocytes , the clinical pregnancy rate per cycle started was 32.1 % ( 37.5 % per ET procedure ) , and the live birth rate was 25.6 % ; the multiple birth rate per delivery was 30.8 % , with a triplet birth rate of 1.4 % . IVF was performed in 40 % of cycles and ICSI in 60 % with similar pregnancy rates . One or two embryos were transferred in 68 % of cycles ; transferring more embryos did not increase the pregnancy rate . In 301 IVF/ICSI cycles using donor oocytes , the clinical pregnancy rate was 46.5 % , and the live birth rate was 35.2 % ; the multiple birth rate was 33.3 % , with no triplet birth . In 2498 FET cycles using the woman 's own oocytes , the clinical pregnancy rate was 22.8 % , and the live birth rate was 17.4 % ; the multiple birth rate was 24.5 % , with a triplet birth rate of 1.6 % . Compared with singletons , babies from multiple births had higher risks for preterm birth , low birth weight , and perinatal death . CONCLUSION ( S ) For 2005 , CARTR achieved 100 % voluntary participation from Canadian ART centers for the third consecutive year . Clinical pregnancy and live birth rates continued to increase in 2005 compared with previous years BACKGROUND Elective single embryo transfer ( eSET ) , applied in the first or second IVF cycle in young patients with good quality embryos , has been demonstrated to lower the twin pregnancy rate , while the overall pregnancy rate is not compromised . It is as yet unclear whether eSET could be the preferred transfer policy in all treatment cycles , or that it should be restricted to the first or first two cycles . METHODS eSET policy ( when two or more embryos were available , at least one of them being of good quality ) was offered to patients younger than 38 years in the first three treatment cycles . Retrospectively , treatment cycle outcome was studied . RESULTS In 326 patients , 586 treatment cycles were performed ( 326 first , 168 second and 92 third treatment cycles ) . In 65 cycles ( 11 % ) , eSET could not be applied because there was either no fertilization , or only one embryo available . In the remaining 521 cycles , eSET was performed in 111 cycles ( 19 % ) , while in 410 cycles , no good quality embryo was available result ing in the transfer of two embryos ( double embryo transfer , DET ) . No significant differences in ongoing pregnancy rates after transfer of fresh embryos were observed between eSET and DET in the first ( both 33 % ) , second ( 36 and 23 % , respectively ) and third treatment cycles ( 20 and 24 % , respectively ) . In significantly more eSET cycles compared to DET cycles , could embryos be frozen . This result ed in a significantly higher cumulative pregnancy rate after eSET compared to DET . CONCLUSIONS In patients younger than 38 years with at least one top quality embryo , eSET can be the transfer policy of choice in at least the first three treatment cycles , since the pregnancy rates obtained in each treatment cycle are comparable to those after DET OBJECTIVE To reduce the twin rate in our IVF program . DESIGN A prospect i ve educational study of infertile couples ; a retrospective review of IVF outcomes before vs. after m and atory single embryo transfer ( mSBT ) policy change . SETTING University-based infertility center . PATIENT(S ) One hundred ten of 120 consecutive new infertile couples completed the educational study . Outcomes of all embryo transfers ( n = 693 ) performed 17 months before and 17 months after mSBT were evaluated . INTERVENTION(S ) A 1-page educational summary of comparative risks of twins vs. singletons to maternal and child health . MAIN OUTCOME MEASURE(S ) Knowledge of twin risks and desired number of embryos transferred before and after education . Pregnancy rates , number of embryos transferred , and multiple-gestation rates before and after mSBT policy . RESULT ( S ) After education , knowledge of twin risks improved and a significant number of subjects changed their desired outcome to a lower gestational number . There was no change in ongoing pregnancy rates with blastocyst transfer before and after mSBT ( 63 % vs. 58 % ; NS ) . Program-wide number of embryos transferred ( 2.1 + /- 0.6 vs. 1.9 + /- 0.7 ) and multiple-gestation rates ( 35 % vs. 19 % ) decreased significantly while pregnancy rates were maintained . CONCLUSION ( S ) Simple educational material s can improve knowledge of twin pregnancy risks and affect decision making . In high-risk patients , mSBT results in pregnancy rates similar to two-blastocyst transfer , with decreased twin rates OBJECTIVE To determine the extent to which embryo selection by blastulation and elective single blastocyst transfer , supported by efficient cryostorage of spare embryos , can reduce multiple pregnancies and maintain or improve on the live birth rate from IVF . DESIGN Prospect i ve , nonr and omized cohort study . SETTING Sydney IVF , a private clinic in Australia . PATIENT(S ) In vitro fertilization patients aged < 38 years with three or more usable blastocyst , recruited from April 2000 through December 2001 , with pregnancies followed up until August 2004 . INTERVENTION(S ) Blastocysts were cultured and cryostored with stage-specific culture medium and low oxygen conditions . MAIN OUTCOME MEASURE(S ) Fetal heart-positive twin pregnancy rate and accumulating " take-home baby " rate per retrieval leading to blastocyst transfer . RESULT ( S ) Among 121 women who elected single fresh blastocyst transfer ( but who could elect to have two frozen blastocysts transferred at once ) , 79 ( 65.3 % ) took home a baby , with a twin pregnancy rate of 7 % . Among 285 women who chose two blastocysts for fresh transfer , 184 ( 64.2 % ) took home at least one baby , with a twin pregnancy rate of 34 % and five perinatal deaths . CONCLUSION ( S ) With technically appropriate blastocyst culture and freezing , and elective single blastocyst transfer in the fresh cycle , the overall multiple pregnancy rate can be reduced by > 75 % , permitting in this series a slight increase in the chance of taking home a baby OBJECTIVE Our objective was to determine the incidence of spontaneous reduction in multiple pregnancies during the first 12 gestational weeks and determine the outcome of the surviving fetuses . STUDY DESIGN Analysis of prospect ively collected ultrasound and birth information on 709 multiple and 5962 singleton pregnancies conceived at a private infertility clinic . RESULTS Spontaneous reduction of one or more gestational sacs and or embryos occurred before the 12th week of gestation in 36 % of twin ( 95 % CI , 32%-40 % ) , 53 % of triplet ( 95 % CI , 44%-61 % ) , and 65 % of quadruplet ( 95 % CI , 46%-85 % ) pregnancies . Reduction was less frequent after ovulation induction than after spontaneous ovulation . In general , pregnancy duration and birth weight were inversely related to the initial gestational sac number irrespective of the final birth number . CONCLUSIONS More than 50 % of patients with 3 or more gestational sacs had spontaneous reduction before 12 weeks . The surviving fetuses weighed less and were born earlier than unreduced pregnancies with the same initial number of fetuses OBJECTIVE To examine psychosocial and obstetric outcomes at 1 year postpartum in first-time mothers who conceived after IVF . DESIGN Prospect i ve cohort study . SETTING University medical center in the United Kingdom . PATIENT(S ) One hundred twenty-nine mothers with a single naturally conceived birth , 95 mothers with a single IVF birth , and 36 mothers with a twin or triplet IVF birth . MAIN OUTCOME MEASURE(S ) General Health Question naire and Parenting Stress Index . RESULT ( S ) Twenty-two percent of mothers of multiples had Parenting Stress Index scores indicating severe parenting stress , compared with 5 % of mothers of IVF singletons ( odds ratio , 5.14 [ 95 % confidence interval ( CI ) , 1.55 - 16.99 ] ) and 9 % of mothers of naturally conceived singletons ( odds ratio , 2.76 [ 95 % CI , 1.03 - 7.4 ] ) . Mothers of multiple children conceived by IVF did not have poorer mental health but were less likely to be in paid employment at follow-up than were mothers of singletons conceived by IVF ( odds ratio , 0.3 [ 95 % CI , 0.13 - 0.67 ] ) or naturally ( odds ratio , 0.27 [ 95 % CI , 0.12 - 0.59 ] ) . Multiple births were more premature , had lower birth weights , and had more medical complications . They were more likely to have been admitted to special care than were singletons conceived by IVF ( odds ratio , 14.6 [ 95 % CI , 5.1 - 42.0 ) ] or those conceived naturally ( odds ratio , 10.59 [ 95 % CI , 3.67 - 30.57 ] ) CONCLUSION ( S ) Clinicians should ensure that couples making decisions about embryo transfer have considered the potential psychosocial burden of a multiple birth A prospect i ve r and omized study comparing single embryo transfer with double embryo transfer after in-vitro fertilization or intracytoplasmic sperm injection ( IVF/ICSI ) was carried out . First , top quality embryo characteristics were delineated by retrospectively analysing embryos result ing in ongoing twins after double embryo transfer . A top quality embryo was characterized by the presence of 4 or 5 blastomeres at day 2 and at least 7 blastomeres on day 3 after insemination , the absence of multinucleated blastomeres and < 20 % cellular fragments on day 2 and day 3 after fertilization . Using these criteria , a prospect i ve study was conducted in women < 34 years of age , who started their first IVF/ICSI cycle . Of 194 eligible patients , 110 agreed to participate of whom 53 produced at least two top quality embryos and were prospect ively r and omized . In all , 26 single embryo transfers result ed in 17 conceptions , 14 clinical and 10 ongoing pregnancies [ implantation rate ( IR ) = 42.3 % ; ongoing pregnancy rate ( OPR ) = 38.5 % ] with one monozygotic twin ; 27 double embryo transfers result ed in 20 ongoing conceptions with six ( 30 % ) twins ( IR = 48.1 % ; OPR = 74 % ) . We conclude that by using single embryo transfer and strict embryo criteria , an OPR similar to that in normal fertile couples can be achieved after IVF/ICSI , while limiting the dizygotic twin pregnancy rate to its natural incidence of < 1 % of all ongoing pregnancies High numbers of embryos transferred during assisted reproduction have become implicated as the cause of higher than normal twinning and multiple gestation rates following this form of therapy . However , reducing the number to a single embryo transferred has been shown to carry unfavourable results in the first cycle , but with similar cumulative live birth rates . This study tested the theory by performing a r and omized controlled trial of elective single embryo transfer ( SET ) versus double embryo transfer ( DET ) in young women , and follow them up for 1 year to determine the result of cryo-embryo transfer cycles in the two cohorts . The results showed that the probability of a live birth was not significantly different between the two groups , but with a higher rate of twins in the DET group . In addition , during the 1-year follow-up period , the live birth , clinical pregnancy and multiple pregnancy rates were also similar , and in line with the results of the r and omized trial . In conclusion , the results of this prospect i ve r and omized trial and 1-year follow-up show that in young women , elective SET should be the first line of choice . Even so , these results should be confirmed by larger r and omized studies OBJECTIVE To present the results of assisted reproductive technology ( ART ) cycles performed in 2004 in Canada . This is the fourth annual report of Canadian ART outcomes . DESIGN Prospect i ve cohort study . SETTING Twenty-six of 26 ART centers in Canada . PATIENT(S ) Couples undergoing ART treatment in Canada during 2004 . INTERVENTION(S ) Assisted reproductive technology treatments , including IVF , intracytoplasmic sperm injection ( ICSI ) , frozen embryo transfer , and oocyte donation . MAIN OUTCOME MEASURE(S ) Clinical pregnancy , live birth , and multiple birth rates . RESULT ( S ) A total of 11,068 ART cycles was reported to the Canadian ART Register . There were 7,874 IVF/ICSI cycles that used the woman 's own oocytes . Per cycle started , the clinical pregnancy rate was 31.7 % ( 37.8 % per embryo transfer procedure ) , and the live birth rate was 24.2 % ; the multiple birth rate per delivery was 27.8 % , with a triplet birth rate of 1.5 % . In vitro fertilization was performed in 42 % of cycles , and ICSI , in 58 % , with similar pregnancy rates . There were 365 IVF/ICSI cycles that used donor oocytes . The clinical pregnancy rate was 44.9 % , and the live birth rate was 33.7 % ; the multiple birth rate was 32.5 % , with a triplet birth rate of 4.3 % . There were 2,431 frozen embryo transfer cycles that used the woman 's own oocytes . The clinical pregnancy rate was 22.8 % and the live birth rate was 16.5 % ; the multiple birth rate was 26.0 % , with a triplet birth rate of 1.0 % . There were 398 cycles of various other ART types , including 87 cycles involving gestational carriers . CONCLUSION ( S ) For 2004 , the Canadian ART Register achieved 100 % voluntary participation from Canadian ART centers for the second consecutive year . Clinical pregnancy and live birth rates were higher and multiple birth rates were lower in 2004 than in previous years OBJECTIVE To determine the efficacy of single blastocyst transfer . DESIGN Prospect i ve r and omized trial . SETTING Private assisted reproductive technology unit . PATIENT(S ) Forty-eight women undergoing IVF-embryo transfer with day 3 FSH < or=10 mIU/mL and at least 10 follicles > 12 mm in diameter on day of hCG administration . INTERVENTION(S ) Embryo culture to the blastocyst stage in sequential media G1/G2 followed by transfer of either one or two blastocysts . MAIN OUTCOME MEASURE(S ) Implantation rate , ongoing pregnancy rate , and twinning . RESULT ( S ) The transfer of a single blastocyst result ed in an implantation and ongoing pregnancy rate of 60.9 % with no twins . The transfer of two blastocysts result ed in an implantation rate of 56 % , an ongoing pregnancy rate of 76 % with a 47.4 % incidence of twins . CONCLUSION ( S ) Single blastocyst transfer is an effective method of eliminating multiple births while maintaining high pregnancy rates in this selected group of patients OBJECTIVE To determine the proportion of infertile women who prefer a multiple birth over a singleton , patient characteristics associated with this desire , and patient knowledge about the risks of multiple births . DESIGN Prospect i ve analysis . SETTING Academic university hospital-based infertility center and private general gynecology clinic . PATIENT(S ) Four hundred sixty-four female patients with infertility who presented for their initial visit . MAIN OUTCOME MEASURE(S ) Demographic characteristics , infertility history , desire regarding multiple births , knowledge of the risks of multiple births , and goals of infertility evaluation and treatment were determined by using a 41- question survey . Univariate analysis was performed to assess patient characteristics associated with the desire for multiple births . Independent factors associated with this desire were assessed by multivariable logistic regression analysis . RESULT ( S ) 20.3 % of women desired multiples over a singleton gestation . Nulliparity , lower family income , younger patient age , prior evaluation for infertility , longer duration of infertility , and lack of knowledge regarding risks of twin gestations were associated with this desire . Only nulliparity and lower family income were independently associated . CONCLUSION ( S ) A sizable minority of infertility patients prefers a multiple birth as their treatment outcome . Patient education may be an effective strategy to reduce the incidence of twin and higher-order multiple pregnancies OBJECTIVE To present a report on assisted reproductive technologies ( ART ) cycles performed in 2006 in Canada and show trends in outcomes over time . This is the sixth annual report from the Canadian ART Register ( CARTR ) . DESIGN Prospect i ve cohort study . SETTING Twenty-five of 25 ART centers in Canada . PATIENT(S ) Couples undergoing ART treatment in Canada during 2006 . INTERVENTION(S ) ART treatments , including in vitro fertilization ( IVF ) , intracytoplasmic sperm injection ( ICSI ) , and frozen embryo transfer ( FET ) . MAIN OUTCOME MEASURE(S ) Clinical pregnancy , live birth , and multiple birth rates . RESULT ( S ) A total of 12,052 ART cycles was reported to CARTR . In 8278 IVF/ICSI cycles using the woman 's own oocytes , the clinical pregnancy rate per cycle started was 33.7 % ( 38.6 % per ET ) , and the live birth rate was 27.1 % ; the multiple birth rate per delivery was 30.3 % , with a high-order multiple birth rate of 1.5 % . In 64 % of cycles , ICSI was performed . One or two embryos were transferred in 67 % of cycles . In 350 IVF/ICSI cycles using donor oocytes , the clinical pregnancy rate was 42.3 % , and the live birth rate was 33.6 % ; the multiple birth rate was 37.3 % , with no triplet birth . In 2838 FET cycles using the woman 's own oocytes , the clinical pregnancy rate was 24.3 % , and the live birth rate was 18.6 % ; the multiple birth rate was 22.5 % , with a triplet birth rate of 0.6 % . Birth outcomes were unknown for 3.6 % of ongoing pregnancies . CONCLUSION ( S ) For 2006 , CARTR achieved 100 % voluntary participation from Canadian ART centers for the fourth consecutive year . Clinical pregnancy and live birth rates continued to increase in 2006 compared with previous years , but multiple birth rates decreased only slightly OBJECTIVE To establish the nature and extent of difficulties in parenting and child development in families with twins conceived by assisted reproduction . DESIGN Comparisons were carried out between a representative sample of 344 families with 2- to 5-year-old twins conceived by IVF/intracytoplasmic sperm injection ( ICSI ) and a matched comparison group of 344 families with singletons from IVF/ICSI . One twin was r and omly selected for data analysis to avoid the bias associated with nonindependence of measures . SETTING A general population sample of IVF/ICSI families . PATIENT(S ) Mothers and children . INTERVENTION(S ) Mothers completed a question naire booklet . MAIN OUTCOME MEASURE(S ) St and ardized measures of the mother 's psychological well-being ( parenting stress , depression , and quality of marriage ) and st and ardized measures of the child 's psychological development ( emotional/behavioral problems and cognitive development ) . RESULT ( S ) Mothers of twins showed significantly higher levels of parenting stress and depression than mothers of singletons and were significantly more likely to find parenting difficult and significantly less likely to obtain pleasure from their child . Regarding the children , there was no difference in the level of emotional or behavioral problems between twins and singletons . However , twins showed significantly lower levels of cognitive functioning . CONCLUSION ( S ) Greater difficulties in parenting and child development were experienced by IVF/ICSI families with twins than by IVF/ICSI families with singletons R and omized control trials have shown that single embryo transfer ( SET ) results in lower live birth rates than double embryo transfer ( DET ) , while observational , retrospective studies find no decrease in overall live birth rate when using a SET policy . The cumulative ( fresh transfer followed by frozen - thawed transfers of embryos from the same stimulated cycle ) live birth rate after the first and the second stimulated cycle of SET and DET respectively has been analysed . All couples who received their first fresh embryo transfer at Sahlgrenska University Hospital during 2003 and 2004 were included ( n = 689 ) . The live birth rates after DET versus SET in the first and second fresh cycles were 29.7 ( 47/158 ) versus 23.9 % ( 127/531 ) and 30.8 ( 41/133 ) versus 22.0 % ( 45/205 ) . The cumulative live birth rate per patient after the addition of frozen-thawed embryo transfers were similar : 33.5 ( 53/158 ) and 34.8 % ( 185/531 ) for DET and SET respectively after the first cycle and 32.3 ( 43/133 ) versus 32.2 % ( 66/205 ) after the second cycle . A logistic regression analysis showed no significant correlation for SET or DET with cumulative live birth . Thus , cumulative live birth rates are similar after SET and DET in a routine IVF programme with a majority of SET transfers , although a higher number of frozen-thawed cycles were needed in the SET group OBJECTIVE To determine if increased psychosocial risks are associated with each increase in birth multiplicity ( i.e. , singleton , twin , triplet ) result ing from assisted reproduction . DESIGN Stratified r and om sample ( n = 249 ) . SETTING An academic teaching hospital and private practice infertility center . PATIENT(S ) Mothers raising 1- to 4-year-old children ( n = 128 singletons , n = 111 twins , and n = 10 triplets ) conceived through assisted reproduction . INTERVENTION(S ) Self-administered , mailed survey . MAIN OUTCOME MEASURE(S ) Scales measuring material needs , quality of life , social stigma , depression , stress , and marital satisfaction . RESULT ( S ) Using multivariate logistic regression models , for each additional multiple birth child , the odds of having difficulty meeting basic material needs more than tripled and the odds of lower quality of life and increased social stigma more than doubled . Each increase in multiplicity was also associated with increased risks of maternal depression . CONCLUSION ( S ) To increase patients ' informed decision-making , assisted reproduction providers might consider incorporating a discussion of these risks with all patients before they begin fertility treatment , and holding the discussion again if the treatment results in a multiple gestation . These data may also help providers to identify appropriate counseling , depression screening , and supports for patients with multiple births |
10,592 | 28,035,491 | Further analyses examining clopidogrel showed no significant association with cancer event rate or malignancy-related death .
Conclusions Our results suggest that there is currently insufficient evidence to suggest that thienopyridine exposure is associated with an increased risk of cancer event rate or mortality | Introduction Thienopyridines are a class of antiplatelet drugs widely used in cardiovascular disease prevention and treatment .
A recent concern has come to light regarding the safety of thienopyridines because of the possible risk of malignancy .
We therefore performed a systematic review and meta- analysis to evaluate the association between thienopyridine exposure and malignancy . | AIMS In the dual antiplatelet therapy ( DAPT ) study , continued thienopyridine beyond 12 months after drug-eluting stent placement was associated with increased mortality compared with placebo . We sought to evaluate factors related to mortality in r and omized patients receiving either drug-eluting or bare metal stents in the DAPT study . METHODS AND RESULTS Patients were enrolled after coronary stenting , given thienopyridine and aspirin for 12 months , r and omly assigned to continued thienopyridine or placebo for an additional 18 months ( while taking aspirin ) , and subsequently treated with aspirin alone for another 3 months . A blinded independent adjudication committee evaluated deaths . Among 11 648 r and omized patients , rates of all-cause mortality rates were 1.9 vs. 1.5 % ( continued thienopyridine vs. placebo , P = 0.07 ) , cardiovascular mortality , 1.0 vs. 1.0 % ( P = 0.97 ) , and non-cardiovascular mortality , 0.9 vs. 0.5 % ( P = 0.01 ) over the r and omized period ( Months 12 - 30 ) . Rates of fatal bleeding were 0.2 vs. 0.1 % ( P = 0.81 ) , and deaths related to any prior bleeding were 0.3 vs. 0.2 % ( P = 0.36 ) , Months 12 - 33 ) . Cancer incidence did not differ ( 2.0 vs. 1.6 % , P = 0.12 ) . Cancer-related deaths occurred in 0.6 vs. 0.3 % ( P = 0.02 ) and were rarely related to bleeding ( 0.1 vs. 0 , P = 0.25 ) . After excluding those occurring in patients with cancer diagnosed before enrolment , rates were 0.4 vs. 0.3 % ( P = 0.16 ) . CONCLUSION Bleeding accounted for a minority of deaths among patients treated with continued thienopyridine . Cancer-related death in association with thienopyridine therapy was mainly not related to bleeding and may be a chance finding . Caution is warranted when considering extended thienopyridine in patients with advanced cancer . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00977938 Background — The impact of changing demographics on causes of long-term death after percutaneous coronary intervention ( PCI ) remains incompletely defined . Methods and Results — We evaluated trends in cause-specific long-term mortality after index PCI performed at a single center from 1991 to 2008 . Deaths were ascertained by scheduled prospect i ve surveillance . Cause was determined via telephone interviews , medical records , autopsy reports , and death certificates . Competing-risks analysis of cause-specific mortality was performed using 3 time periods of PCI ( 1991–1996 , 1997–2002 , and 2003–2008 ) . Final follow-up was December 31 , 2012 . A total of 19 077 patients survived index PCI hospitalization , of whom 6988 subsequently died ( 37 % , 4.48 per 100 person-years ) . Cause was determined in 6857 ( 98.1 % ) . Across 3 time periods , there was a 33 % decline in cardiac deaths at 5 years after PCI ( incidence : 9.8 % , 7.4 % , and 6.6 % ) but a 57 % increase in noncardiac deaths ( 7.1 % , 8.5 % , and 11.2 % ) . Only 36.8 % of deaths in the recent era were cardiac . Similar trends were observed regardless of age , extent of coronary disease , or PCI indication . After adjustment for baseline variables , there was a 50 % temporal decline in cardiac mortality but no change in noncardiac mortality . The decline in cardiac mortality was driven by fewer deaths from myocardial infa rct ion/sudden death ( P<0.001 ) but not heart failure ( P=0.85 ) . The increase in noncardiac mortality was primarily attributable to cancer and chronic diseases ( P<0.001 ) . Conclusions — This study found a marked temporal switch from predominantly cardiac to predominantly noncardiac causes of death after PCI over 2 decades . The decline in cardiac mortality was independent of changes in baseline clinical characteristics . These findings have implication s for patient care and clinical trial design OBJECTIVES : We evaluated the effect of the use of aspirin , nonsteroidal anti-inflammatory drugs ( NSAIDS ) , and anticoagulants on the performance of immunochemical fecal occult blood test ( I-FOBT ) . METHODS : A prospect i ve , cross-sectional study of 1,221 ambulatory patients having total colonoscopy after preparing three I-FOBTs . Information regarding the use of medications was collected from the health medical organization ( HMO ) data base . I-FOBT was analyzed with the OC-MICRO instrument using both ≥75 and 100 ngHb/ml of buffer thresholds to determine positivity . RESULTS : Colorectal cancer ( CRC ) was found in 17 and advanced adenomatous polyp ( AAP ) in 97 patients . A total of 212 patients were using aspirin/NSAIDS at the time of I-FOBT testing . Qualitative analysis for the detection of AAP/CRC reveals a trend for an increased sensitivity with aspirin/NSAIDS use . At the threshold 75 ng/ml for positivity , the sensitivity for the detection of AAP/CRC was 66.7 % for aspirin/NSAIDS use vs. 51.2 % for nondrug takers ( P=0.20 ) , and at the threshold of 100 ng/ml , the sensitivity was 66.7 vs. 46.5 % ( P=0.09 ) . The specificity , however , was not affected by the use of aspirin/NSAIDS . At the threshold of 75 ng/ml for positivity , the specificity for the detection of AAP/CRC was 89.5 % for aspirin/NSAIDS use vs. 91.2 % for nondrug takers ( P=0.47 ) , and at the threshold of 100 ng/ml , the specificity was 92.17 vs. 93.0 % ( P=0.69 ) . A total of 33 patients were using antithrombotics/coagulants at the time of I-FOBT testing . This group was small ; however , it appears that their use was also associated with a trend for increased sensitivity and no change in specificity . CONCLUSIONS : The use of aspirin/NSAIDS and anticoagulants was associated with a trend for increased sensitivity with no change in specificity for the detection of AAP/CRC . This study suggests that there is no need to stop these agents before I-FOBT testing BACKGROUND Despite current treatments , patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events . We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients . METHODS We r and omly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel ( 300 mg immediately , followed by 75 mg once daily ) ( 6259 patients ) or placebo ( 6303 patients ) in addition to aspirin for 3 to 12 months . RESULTS The first primary outcome --a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or stroke -- occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group ( relative risk with clopidogrel as compared with placebo , 0.80 ; 95 percent confidence interval , 0.72 to 0.90 ; P<0.001 ) . The second primary outcome --the first primary outcome or refractory ischemia -- occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group ( relative risk , 0.86 ; 95 percent confidence interval , 0.79 to 0.94 ; P<0.001 ) . The percentages of patients with in-hospital refractory or severe ischemia , heart failure , and revascularization procedures were also significantly lower with clopidogrel . There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group ( 3.7 percent vs. 2.7 percent ; relative risk , 1.38 ; P=0.001 ) , but there were not significantly more patients with episodes of life-threatening bleeding ( 2.2 percent [ corrected ] vs. 1.8 percent ; P=0.13 ) or hemorrhagic strokes ( 0.1 percent vs. 0.1 percent ) . CONCLUSIONS The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation . However , the risk of major bleeding is increased among patients treated with clopidogrel 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 ] . PURPOSE Concerns were raised about the safety of antiplatelet thienopyridine derivatives after a r and omized control trial reported increased risks of cancer and cancer deaths in prasugrel users . We investigate whether clopidogrel , a widely used thienopyridine derivative , was associated with increased risk of cancer-specific or all-cause mortality in cancer patients . METHODS Colorectal , breast and prostate cancer patients , newly diagnosed from 1998 to 2009 , were identified from the National Cancer Data Repository . Cohorts were linked to the UK Clinical Practice Research Data link , providing prescription records , and to the Office of National Statistics mortality data ( up to 2012 ) . Unadjusted and adjusted hazard ratios ( HRs ) for cancer-specific and all-cause mortality in post-diagnostic clopidogrel users were calculated using time-dependent Cox regression models . RESULTS The analysis included 10 359 colorectal , 17 889 breast and 13 155 prostate cancer patients . There was no evidence of an increase in cancer-specific mortality in clopidogrel users with colorectal ( HR = 0.98 95 % confidence interval ( CI ) 0.77 , 1.24 ) or prostate cancer ( HR = 1.03 95%CI 0.82 , 1.28 ) . There was limited evidence of an increase in breast cancer patients ( HR = 1.22 95%CI 0.90 , 1.65 ) ; however , this was attenuated when removing prescriptions in the year prior to death . CONCLUSIONS This novel study of large population -based cohorts of colorectal , breast and prostate cancer patients found no evidence of an increased risk of cancer-specific mortality among colorectal , breast and prostate cancer patients using clopidogrel |
10,593 | 27,433,856 | Compared to polyvinyl alcohol , tris-acryl gelatin microsphere showed a significant benefit in improving the overall quality of life and in reducing uterine volume at three and six months , in reducing overall symptom severity at 6 and 12 months , and furthermore in reducing treatment failure .
In addition , tris-acryl gelatin microsphere could significantly reduce leiomyoma volume and decrease < 90 % complete leiomyoma infa rct ion rate at three months .
There were no differences in pain severity , other post-procedural symptoms or medication use in the two groups .
Conclusions : A better effect of tris-acryl gelatin microsphere in leiomyoma embolization for patients with symptomatic leiomyoma | Abstract Objective : Use systematic review s and meta-analyses to assess the effect of polyvinyl alcohol and tris-acryl gelatin microsphere material s in leiomyoma embolization for symptomatic leiomyomas . | OBJECTIVE Patients with completely resected stages I-IV high grade uterine leiomyosarcoma are at high risk for recurrence . No adjuvant treatment has been shown to improve survival , although prospect i ve data are limited . We sought to determine whether adjuvant gemcitabine-docetaxel would yield a 2-year progression-free survival of at least 50 % in this leiomyosarcoma population . METHODS Eligible patients were treated with gemcitabine 900 mg/m(2 ) over 90 min days 1 and 8 plus docetaxel 75 mg/m(2 ) day 8 , every 3 weeks for 4 cycles . CT imaging was performed at baseline , after cycle 4 , and every 3 months . Progression was defined as evidence of new disease on CT . RESULTS Twenty-five patients ( median age 49 ; range , 37 - 73 ) enrolled ; 23 were evaluable ( 1-never treated , 1-ineligible ) . With median follow-up of 49 months for all patients , 10 ( 45 % ) of the 23 evaluable patients remained progression free at 2 years , with a median progression-free survival of 13 months . The median overall survival is not yet reached . Among the 18 patients with stages I or II uterine leiomyosarcoma , 59 % remain progression-free at 2 years , with a median progression-free survival of 39 months . Median overall survival for stages I and II patients is not yet reached with median follow-up duration of 49 months . Sites of first recurrence were : lung only - 3/23 ( 13 % ) ; pelvis only - 5/23 ( 22 % ) ; both - 5 ( 22 % ) . CONCLUSIONS Post-resection gemcitabine-docetaxel for stages I-IV high- grade uterine leiomyosarcoma yields 2-year progression-free survival rates that appear superior to historical rates . Gemcitabine-docetaxel merits further study as part of an adjuvant strategy for patients with completely resected , early-stage uterine leiomyosarcoma PURPOSE To determine the long-term outcome of uterine fibroid therapy ( UFE ) using tris-acryl gelatin microspheres ( TAGM ) . MATERIAL S This was a multicenter prospect i ve study of patients undergoing UFE with TAGM , and during this phase of the study , the clinical outcomes 3 years after treatment were assessed . Measures of outcome included the Ruta Menorrhagia Question naire , patient self- assessment s of symptoms and impact on activities , patient satisfaction and health-related quality of life as measured by the SF-12 . Long-term re-intervention rates were also assessed . The data were analyzed at each interval compared to baseline using appropriate statistical tests . RESULTS Of the 102 patients enrolled , 96 patients had complete baseline data and of these , 69 ( 72 % ) had known outcomes at 3 years after treatment . Sixty-one patients ( 64 % ) completed long-term follow-up without major intervention . An additional 8 patients ( 8.3 % ) underwent fibroid surgery ( 7 hysterectomies and 1 myomectomy ) . Among those without intervention , at 3 years after treatment , the mean Ruta Question naire Score was 19.3 , compared to 47.9 at baseline and 24.5 at 3 months ( P < .01 ) . At baseline , 57 % of patients had extremely heavy bleeding , while only 2 % had that complaint at 36 months . At 36 months , much or moderate improvement in pelvic pain occurred in 83 % of patients , pelvic discomfort in 83 % , and urinary problems in 69 % and 84 % were moderately or very satisfied with their outcome . CONCLUSIONS Over the long-term , UFE using TAGM is effective and safe , with high levels of durable symptom control , improved health-related quality of life and patient satisfaction AIM The purpose of this study was to compare the depth of vascular penetration of non-spherical polyvinyl alcohol ( PVA ) versus trisacryl gelatin microspheres ( MS ) in women undergoing uterine artery embolization ( UAE ) immediately before transabdominal myomectomy . MATERIAL S AND METHODS A total of 17 patients who had been referred for embolization before myomectomy underwent bilateral uterine artery embolization using either 355 - 500 microm PVA ( group A ) or 700 - 900 microm MS ( group B ) . The depth of penetration of the particles was assessed by identifying their presence and location in the resected specimen . RESULTS Of the 17 women enrolled in this study , 10 were in group A and 6 in group B. One woman underwent embolization using both types of particle and was excluded from the analysis . Embolic particles were significantly ( p = 0.048 ) more frequently located within the fibroid ( 4/6 , 67 % ) in Group B than Group A ( 1/10 , 10 % ) . Particles were also identified in the perifibroid tissues in 4/6 ( 67 % ) in Group B and 4/10 ( 40 % ) in Group A , with no statistical difference . There were no procedural complications . CONCLUSION MS particles ( 700 - 900 microm ) penetrate significantly deeper into leiomyomata compared with non-spherical PVA ( 355 - 500 microm ) . MS may therefore confer advantages in UAE , as they may more specifically target the fibroid , allowing an earlier end-point to embolization and minimizing ischaemic damage to normal myometrium and ovaries 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 PURPOSE To compare tris-acryl microspheres and polyvinyl alcohol ( PVA ) microspheres as embolic agents in uterine artery embolization ( UAE ) for uterine leiomyomas in terms of clinical outcome , inflammatory response , and adverse reactions . MATERIAL S AND METHODS A double-blinded r and omized controlled trial was performed , with 27 patients in the tris-acryl microsphere group and 29 in the PVA microsphere group . The primary endpoint was clinical success , defined as a 2-year freedom from subsequent surgery as a result of persistent or deteriorated symptoms . Secondary endpoints included ( i ) posttreatment leiomyoma enlargement , ( ii ) leiomyoma volume reduction at 3 and 9 months , ( iii ) significant residual intratumoral perfusion , ( iv ) increase in inflammatory and stress markers , ( v ) incidence of complications , and ( vi ) duration of hospital stay . RESULTS There was no statistically significant difference between the two groups in patient demographics , clinical presentation , initial tumor findings , change in inflammatory and stress markers after treatment , incidence of complications , and duration of hospital stay . Tris-acryl microspheres were associated with a higher rate of clinical success than PVA microspheres ( 96.3 % [ 26 of 27 ] vs 69 % [ 20 of 29 ] ; P = .012 ) , a lower incidence of posttreatment leiomyoma enlargement ( P = .030 ) , and a lower incidence of significant residual intratumoral perfusion ( P = .030 ) . CONCLUSIONS In the treatment of uterine leiomyomas , UAE with tris-acryl microspheres was associated with a higher clinical success rate , a lower incidence of tumor enlargement , and no significant differences in adverse reactions and inflammatory response compared with the use of PVA microspheres . Tris-acryl microspheres therefore represent the preferred agent for UAE of uterine leiomyomas Objective To evaluate the efficacy of acrylamido polyvinyl alcohol microspheres ( a-PVAM ) as an embolic agent for uterine artery embolization ( UAE ) compared with Tris-acryl gelatin microspheres ( TAGM ) . Design , Setting , Participants Prospect i ve r and omized double-blind noninferiority trial . Conducted at two sites both with regional UAE practice s. Forty-six women with symptomatic leiomyomas . InterventionUAE procedure was performed with either of the two embolic agents . Either 700–900-μm a-PVAM or 500–700-μm TAGM was used . Main Outcome Measures Changes in leiomyoma perfusion , overall uterine volume , and dominant leiomyomas volume measured by contrast-enhanced magnetic resonance imaging at 1 week , 3 months , and 6 months after UAE by a reader blinded to the embolic agent used . Changes in Uterine Fibroid Symptoms and Quality of Life question naire scores were measured at 3 , 6 , and 12 months after UAE . Results Forty-six patients were r and omized and treated under the study protocol ( a-PVAM n = 22 , TAGM n = 24 ) . There were no procedure-related complications . Two patients were excluded from analysis ( one technical failure of the procedure , one withdrawal from study ) . Successful ( > 90 % ) leiomyoma devascularization was observed in 81 % of subjects at 1 week after UAE , 97 % at 3 months after UAE , and 95 % at 6 months after UAE . No significant differences were observed in 14 of 15 outcome measurements , consistent with noninferiority . TAGM was slightly superior to a-PVAM on one comparison ( overall quality of life at 3 months after UAE ) Purpose This study was design ed to compare quality of life ( QoL ) outcomes after uterine artery embolization ( UAE ) or myomectomy . Methods Women with symptomatic fibroids diagnosed by ultrasound who wished to preserve their uterus were r and omized to myomectomy ( n = 81 ) or UAE ( n = 82 ) . Endpoints at 1 year were QoL measured by a vali date d question naire , hospital stay , rates of complications , and need for reintervention . Results UAE patients had shorter hospitalization ( 2 vs. 6 days , p < 0.001 ) . By 1 year postintervention , significant and equal improvements in QoL scores had occurred in both groups ( myomectomy n = 59 ; UAE n = 61 ) . There had been two ( 2.9 % ) major complications among UAE versus 6 ( 8 % ) among myomectomy patients ( not significant ) . By 2 years , among UAE patients ( n = 57 ) there were eight ( 14.0 % ) re interventions for inadequate symptom control compared with one ( 2.7 % ) among myomectomy patients ( n = 37 ) . Half of the women who required hysterectomy had concomitant adenomyosis missed by US . Conclusions UAE and myomectomy both result in significant and equal improvements in QoL. UAE allows a shorter hospital stay and fewer major complications but with a higher rate of reintervention Purpose To report 5-year contrast-enhanced magnetic resonance imaging findings of the REST trial recruits who underwent either uterine artery embolization ( UAE ) or myomectomy . Methods A total of 157 patients were r and omized to UAE or surgery ( hysterectomy or myomectomy ) . Ninety-nine patients who had UAE and eight patients who had myomectomy were analyzed . MRI scans at baseline , 6 months , and 5 years were independently interpreted by two radiologists . Dominant fibroid diameter , uterine volume , total fibroid infa rct ion ( complete 100 % , almost complete 90–99 % , partial < 90 % ) , and new fibroid formation were the main parameters assessed and related to the need for reintervention . Results In the UAE group , mean ± st and ard deviation uterine volume was 670 ± 503 , 422 ± 353 , and 292 ± 287 mL at baseline , 6 months , and 5 years , respectively . Mean dominant fibroid diameter was 7.6 ± 3.0 , 5.8 ± 2.9 , and 5 ± 2.9 cm at baseline , 6 months , and 5 years . Fibroid infa rct ion at 6 months was complete in 35 % of women , almost complete in 29 % , and partial in 36 % . Need for reintervention was 19 , 10 , and 33 % in these groups , respectively ( p = 0.123 ) . No myomectomy cases had further intervention . At 5 years , the prevalence of new fibroid was 60 % in the myomectomy group and 7 % in the UAE group ( p = 0.008 ) . Conclusion There is a further significant reduction in both uterine volume and dominant fibroid diameter between 6 months and 5 years after UAE . Complete fibroid infa rct ion does not translate into total freedom from a subsequent reintervention . New fibroid formation is significantly higher after myomectomy 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 PURPOSE To assess the efficacy of two embolic agents in the treatment of symptomatic uterine leiomyomas . MATERIAL S AND METHODS A r and omized , prospect i ve , single-center study enrolled 60 women with symptomatic uterine leiomyomas . Uterine artery embolization ( UAE ) with spherical polyvinyl alcohol ( SPVA ) microspheres ( n = 30 ; 700 - 900 μm and 900 - 1,200 μm ; near-stasis or stasis endpoint ) and tris-acryl gelatin ( TAG ) microspheres ( n = 30 ; 500 - 700 μm ; " pruned-tree " endpoint ) was performed . Infa rct ion rates were calculated for the dominant tumor and for small ( < 2 cm ) and large ( > 2 cm ) nondominant tumors . The primary endpoint was tumor infa rct ion at 24 hours measured by contrast-enhanced magnetic resonance imaging assessed by a blinded review er . RESULTS Baseline characteristics were similar between groups . The primary endpoint was similar in both treatments ( ≥ 91 % dominant tumor infa rct ion ; SPVA . 86.2 % ; TAG , 93.3 % , P = .35 ) . Complete infa rct ion ( 100 % ) was also similar between arms at 24 hours and 3 months . Symptom severity was reduced and quality of life improved equally at 3 and 12 months in each treatment group . Complications were minor in both groups . CONCLUSIONS Uterine leiomyoma infa rct ion at 24 hours and 3 months after treatment with SPVA or TAG microspheres was comparable when using near-stasis as a procedural endpoint with SPVA microspheres . Symptom relief was maintained for as long as 12 months for both embolic agents OBJECTIVE To compare the long-term evolution of uterine arteries after embolization with the two most commonly used embolic agents for fibroid embolization : nonspherical polyvinyl alcohol ( PVA ) particles and trisacryl gelatin microspheres ( TGMS ) . DESIGN Prospect i ve study . SETTING University-based interventional radiology , pathology , and reproductive physiology units . ANIMAL(S ) Two groups of 10 sheep embolized in the uterine artery . INTERVENTION(S ) Embolization of the uterine artery with either 600 - 1000 microm nonspherical polyvinyl alcohol ( PVA ) particles or with 700 - 900 microm trisacryl gelatin microspheres ( TGMS ) . Animals were synchronized and naturally inseminated . Animals were killed at 26 months . MAIN OUTCOME MEASURE(S ) Uteri were examined pathologically for vessel size , site of occlusion , recanalization rate of vessels , and particle location within the vascular wall . RESULT ( S ) The PVA particles were more numerous in the vessels ' lumen than the TGMS particles ( 13.3 + /- 20.8 vs. 2.5 + /- 2.7 ) , were located more proximally than TGMS ( 97 % vs. 68 % in the trunk and first branches of the uterine artery ) , and were found almost exclusively in the intima ( 99.2 % ) . In contrast , 54.4 % of the TGMS particles were found in the intima , and 45.6 % partially or totally excluded . The rate of recanalization was not statistically significantly different for PVA and TGMS ( 65.2 % vs. 60.6 % ) . CONCLUSION ( S ) The long-term evolution of uterine arteries was different after uterine artery embolization with PVA and TGMS because PVA particles formed large-sized aggregates that occluded proximal vessels and remained in the vessel intima . Microspheres occluded more distal vessels , and about 50 % of them were partially or totally excluded from the vessel PURPOSE To compare the efficacy of spherical polyvinyl alcohol ( PVA ) particles versus conventional PVA particles for uterine artery embolization ( UAE ) . MATERIAL S AND METHODS Of 149 patients with 1-year follow-up after UAE , 96 received conventional PVA particles and 53 received spherical PVA particles . Severity of symptoms was ranked on an 11-point numeric rating scale ( 0 - 10 ) . The changes in severity of symptoms after embolization , blood hemoglobin level , and the size of the dominant tumor depicted by ultrasonography were used to assess the efficacy of the two types of particles . The number of hysterectomies and myomectomies in each group was also recorded as evidence of UAE failure . RESULTS On 1-year follow-up , patients treated with conventional PVA showed average numeric rating scale score improvements of 4.6 in menorrhagia , 2.9 in dysmenorrhea , 3.7 in pressure sensation , and 3.4 in urinary frequency . With spherical PVA , the average improvements were 3.0 in menorrhagia , 2.4 in dysmenorrhea , 3.1 in pressure sensation , and 2.0 in urinary frequency . Except in dysmenorrhea , all differences were significant ( P < .001 ) . With conventional PVA , there was an 8-mg/mL increase in blood hemoglobin level versus a 3-mg/mL increase with spherical PVA ( P < .05 ) . With conventional PVA , there was a 28-mm ( 34 % ) average reduction in diameter of the dominant tumor versus a 15.7-mm ( 19 % ) reduction with spherical PVA ( P = .01 ) . Eight of 96 patients ( 8 % ) treated with conventional PVA underwent hysterectomy or myomectomy during the entire length of the study , versus six of 53 patients ( 11 % ) treated with spherical PVA ( P = .6 ) . No patient underwent multiple embolizations . CONCLUSIONS In comparison with conventional PVA particles , UAE with the use of spherical PVA particles result ed in less fibroid tumor shrinkage and less improvement in clinical symptoms UTERINE artery embolization ( UAE ) is an innovative treatment for symptomatic uterine leiomyomas , which are also called myomas or fibroids . Because the vascular supply of uterine leiomyoma is from the uterine arteries ( 1 ) , embolization of these vessels leads to necrosis of these benign tumors . Several investigators have reported the infa rct ion of leiomyoma alone , leaving the myometrium intact ( 2–4 ) . Ravina et al ( 5 ) reported the first study in the English literature . Subsequent published studies have described a clinical success rate of 85%–89 % ( 2,3,6–11 ) . However , these studies have been case series and , to date , there have been no prospect i ve comparative studies . Clinical success has been measured by the degree of improvement or resolution of the primary symptoms of pain , bleeding , and bulk-related symptoms ( 2,3,5–11 ) . Many published studies have evaluated patient outcome at follow-up office visits or with the use of symptom question naires . In most cases , these measures have not been vali date d. Objective evaluation for changes in uterine and leiomyoma size has been largely based on ultrasonographic ( US ) findings , which are subject to substantial interobserver variability . Similar problems limit the quality of the data supporting other treatments for leiomyoma , such as hysterectomy and myomectomy . For these reasons and others , as the evaluation of this treatment proceeds , better measures of symptom and imaging outcome need to be developed . This report is intended to serve as a guideline for investigators developing studies on UAE to improve the quality of the scientific data presented and published in the future . Study design , clinical definitions , imaging methods , and tools for measuring outcome will be review ed with the goal of improving the validity of conclusions derived from clinical studies of UAE PURPOSE To determine the degree of leiomyoma infa rct ion after uterine artery embolization ( UAE ) performed with tris-acryl gelatin microspheres or polyvinyl alcohol ( PVA ) microspheres . MATERIAL S AND METHODS Patients determined to be c and i date s and scheduled for UAE were r and omized prospect ively to receive tris-acryl gelatin microspheres or PVA microspheres . The manufacturers ' recommended technique was used for both products during the UAE procedures ( including the recently described refined protocol for PVA microspheres ) . All patients underwent magnetic resonance ( MR ) imaging of the pelvis with contrast agent enhancement before and after the UAE procedure . On the postprocedural MR study , the degree of tumor infa rct ion was assessed on postcontrast images . These findings were classified as follows : 100 % infa rct ion , 90%-99 % infa rct ion , 50%-89 % infa rct ion , and less than 50 % infa rct ion . Treatment failure was defined by enhancement of more than 10 % of a patient 's entire tumor burden . RESULTS A total of 53 patients were enrolled in this study . Twenty-seven ( mean age , 44.9 years ) received PVA microspheres and 26 ( mean age , 45.1 years ) received tris-acryl gelatin microspheres . There were no significant differences in the preprocedural uterine volume , dominant tumor volume , location of dominant tumor , and presenting symptoms between population s. In the PVA microsphere group , treatment failure was seen in eight patients ( 29.6 % ) . In the tris-acryl gelatin microsphere group , treatment failure was seen in one patient ( 3.8 % ) , which was a significant difference between groups ( P < or = .025 ) . CONCLUSIONS There was a significantly greater degree of tumor infa rct ion in patients treated with tris-acryl gelatin microspheres during UAE than in patients who received PVA microspheres administered in accordance with a newly refined protocol . Given the known risk of recurrence in patients with persistent tumor enhancement after UAE , it is concluded that tris-acryl gelatin microspheres should be the preferred agent for UAE at this time PURPOSE To compare the outcomes of uterine artery embolization ( UAE ) for leiomyomas with use of tris-acryl gelatin microspheres ( TAGM ) versus spherical polyvinyl alcohol ( PVA ) particles . MATERIAL S AND METHODS Patients undergoing UAE were r and omly assigned to receive TAGMs or PVA . Embolization was performed in a st and ardized manner . Outcome data were collected at 3 months after embolization , including assessment of clinical symptoms , scores from a fibroid tumor-specific symptom and quality of life ( QOL ) question naire , and findings on contrast material -enhanced magnetic resonance ( MR ) imaging , including the degree of tumor infa rct ion and volume reduction . Data were analyzed with use of t tests , the Mann-Whitney U test , and chi2 tests as appropriate . RESULTS Thirty-six patients were treated . There were no differences in the two treatment groups at baseline . Clinical follow-up was obtained in 35 patients . Among the clinical outcome measures , QOL score improvement was greater for UAE with TAGMs compared with PVA ( 49.0 vs 27.9 ; P = .02 ) , but no other differences were noted . Of the 25 patients in whom 3-month MR imaging follow-up was completed , those treated with TAGM were significantly more likely to have complete infa rct ion of all leiomyomas ( six patients vs one patient ; P = .02 ) , were more likely to have at least 90 % tumor infa rct ion ( eight patients vs four patients ; P = .03 ) , and had a lower mean percent of residual perfused fibroid tumor tissue ( 9.6 % vs 44.3 % ; P = .004 ) compared with patients treated with PVA . Based on these differences between the embolic agents , enrollment in this study was terminated . CONCLUSION The use of spherical PVA particles in the manner described herein results in an unacceptably high rate of failed tumor infa rct ion in UAE |
10,594 | 27,179,900 | We found no evidence for temporal changes in the incremental mortality risk associated with DM in the setting of MI .
The improvements in management of MI patients during the last decades have not been associated with a reduction of the gap between diabetic and non-diabetic patients | BACKGROUND / OBJECTIVES It is not well known whether the gap in outcomes after myocardial infa rct ion ( MI ) between patients with and without diabetes mellitus ( DM ) has changed over time .
We performed a systematic review and metaregression of temporal trends in the excess mortality associated with DM after MI . | Background The long-term prognosis of diabetic patients with acute myocardial infa rct ion ( AMI ) treated by acute revascularization is uncertain , and the optimal pharmacotherapy for such cases has not been fully evaluated . Methods To eluci date the long-term prognosis and prognostic factors in diabetic patients with AMI , a prospect i ve , cohort study involving 3021 consecutive AMI patients was conducted . All patients discharged alive from hospital were followed to monitor their prognosis every year . The primary endpoint of the study was all-cause mortality , and the secondary endpoint was the occurrence of major cardiovascular events . To eluci date the effect of various factors on the long-term prognosis of AMI patients with diabetes , the patients were divided into two groups matched by propensity scores and analyzed retrospectively . Results Diabetes was diagnosed in 1102 patients ( 36.5 % ) . During the index hospitalization , coronary angioplasty and coronary thrombolysis were performed in 58.1 % and 16.3 % of patients , respectively . In-hospital mortality of diabetic patients with AMI was comparable to that of non-diabetic AMI patients ( 9.2 % and 9.3 % , respectively ) . In total , 2736 patients ( 90.6 % ) were discharged alive and followed for a median of 4.2 years ( follow-up rate , 96.0 % ) . The long-term survival rate was worse in the diabetic group than in the non-diabetic group , but not significantly different ( hazard ratio , 1.20 [ 0.97 - 1.49 ] , p = 0.09 ) . On the other h and , AMI patients with diabetes showed a significantly higher incidence of cardiovascular events than the non-diabetic group ( 1.40 [ 1.20 - 1.64 ] , p < 0.0001 ) . Multivariate analysis revealed that three factors were significantly associated with favorable late outcomes in diabetic AMI patients : acute revascularization ( HR , 0.62 ) ; prescribing aspirin ( HR , 0.27 ) ; and prescribing renin-angiotensin system ( RAS ) inhibitors ( HR , 0.53 ) . There was no significant correlation between late outcome and prescription of beta-blockers ( HR , 0.97 ) or calcium channel blockers ( HR , 1.27 ) . Although st and ard Japanese-approved doses of statins were associated with favorable outcome in AMI patients with diabetes , this was not statistically significant ( 0.67 [ 0.39 - 1.06 ] , p = 0.11 ) . Conclusions Although diabetic patients with AMI have more frequent adverse events than non-diabetic patients with AMI , the present results suggest that acute revascularization and st and ard therapy with aspirin and RAS inhibitors may improve their prognosis BACKGROUND There are limited data describing the presenting characteristics , management , and outcomes of diabetic and nondiabetic patients with an acute coronary syndrome ( ACS ) . OBJECTIVE To examine differences in these factors , patients with ST-segment elevation acute myocardial infa rct ion , non-ST-segment elevation acute myocardial infa rct ion , and unstable angina were enrolled in a large multinational coronary disease registry . METHODS The Global Registry of Acute Coronary Events is a prospect i ve observational study of patients hospitalized with an ACS at 94 hospitals in 14 countries . The study sample consisted of 5403 patients with ST-segment elevation acute myocardial infa rct ion , 4725 with non-ST-segment elevation acute myocardial infa rct ion , and 5988 with unstable angina . RESULTS Approximately 1 in 4 patients presented to participating hospitals with a history of diabetes . Patients with diabetes were older , more often women , with a greater prevalence of comorbidities , and they were less likely to be treated with effective cardiac therapies than nondiabetic patients . Patients with diabetes who developed an ACS were at increased risk for each hospital outcome examined including heart failure , renal failure , cardiogenic shock , and death . These differences remained after adjustment for potentially confounding prognostic factors . CONCLUSIONS A considerable proportion of patients with an ACS has diabetes and is at increased risk for adverse outcomes compared with patients without diabetes . There are certain proven therapeutic strategies that remain underused in the diabetic population . A more widespread awareness of this increased risk and a more diligent use of proven cardiac treatment approaches are indicated for patients with diabetes who develop an ACS The objective of this report was to examine the effects of sex and diabetic status on in-hospital mortality and 12 year survival following hospital discharge among 4109 patients hospitalized between 1974 and 1986 with acute myocardial infa rct ion . Sixteen general hospitals in the Worcester , MA , st and ard metropolitan statistical area were included . The age-adjusted in-hospital case-fatality rate was significantly higher in diabetic women ( 23.3 % ) than in non-diabetic women ( 18.9 % ) ( p < 0.05 ) while no significant difference was noted among men . Over a 12 year follow-up period , the relative risk of dying among diabetic men was 1.56 times that for non-diabetic men ( 95 % CI , 1.43 , 1.68 ) . Diabetic women were 1.57 times as likely to die as non-diabetic women ( 95 % CI , 1.45 , 1.73 ) . Among non-diabetic subjects , men had a 17 % excess risk of death compared to women ( 95 % CI , 1.09 , 1.25 ) . No significant difference in long-term mortality was noted among diabetic persons . Thus , the " female advantage " observed in the non-diabetic population was eliminated among the diabetic patients . R and omized clinical trials are needed in the diabetic population to identify specific therapies to reduce their increased risk of death Background Diabetes mellitus and admission blood glucose are important risk factors for mortality in ST segment elevation myocardial infa rct ion patients , but their relative and individual role remains on debate . Objective To analyze the influence of diabetes mellitus and admission blood glucose on the mortality of ST segment elevation myocardial infa rct ion patients su bmi tted to primary coronary percutaneous intervention . Methods Prospect i ve cohort study including every ST segment elevation myocardial infa rct ion patient su bmi tted to primary coronary percutaneous intervention in a tertiary cardiology center from December 2010 to May 2012 . We collected clinical , angiographic and laboratory data during hospital stay , and performed a clinical follow-up 30 days after the ST segment elevation myocardial infa rct ion . We adjusted the multivariate analysis of the studied risk factors using the variables from the GRACE score . Results Among the 740 patients included , reported diabetes mellitus prevalence was 18 % . On the univariate analysis , both diabetes mellitus and admission blood glucose were predictors of death in 30 days . However , after adjusting for potential confounders in the multivariate analysis , the diabetes mellitus relative risk was no longer significant ( relative risk : 2.41 , 95 % confidence interval : 0.76 - 7.59 ; p-value : 0.13 ) , whereas admission blood glucose remained and independent predictor of death in 30 days ( relative risk : 1.05 , 95 % confidence interval : 1.02 - 1.09 ; p-value ≤ 0.01 ) . Conclusion In ST segment elevation myocardial infa rct ion patients su bmi tted to primary coronary percutaneous intervention , the admission blood glucose was a more accurate and robust independent predictor of death than the previous diagnosis of diabetes . This reinforces the important role of inflammation on the outcomes of this group of patients OBJECTIVES This study was design ed to study the influence of diabetes on the outcome of unstable coronary artery disease ( CAD ) . BACKGROUND Diabetes mellitus is a major contributor to CAD . Despite improvement in the management of patients with unstable coronary syndromes , this condition is still linked to a substantially increased mortality and morbidity among diabetic patients . Recent evidence advocates early revascularization in unstable coronary syndromes . Diabetic patients subjected to coronary interventions under stable conditions have a higher risk for complications and a more dismal prognosis than nondiabetic subjects . Accordingly , it is of considerable interest to obtain further information regarding the best possible management of diabetic patients with unstable CAD . METHODS A total of 2158 patients without and 299 with diabetes mellitus were r and omized to an early invasive or a noninvasive strategy . The severity of CAD was expressed as the number and extent of vessel involvement . RESULTS Three-vessel disease was diagnosed in 42 % of diabetic and 31 % of nondiabetic patients ( p = 0.006 ) . The percentages of patients with ST-depression and troponin-T > 0.03 microg/l at admission were comparable among diabetic and nondiabetic patients . Mortality and reinfa rct ion after 12 months were more frequent among diabetic than nondiabetic patients in both treatment groups . Diabetes remained a strong independent predictor for death and myocardial infa rct ion in multivariable analysis . The invasive strategy reduced event rate in nondiabetic patients from 12.0 % to 8.9 % ( odds ratio [ OR ] = 0.72 ; confidence interval [ CI ] 0.54 to 0.95 ; p = 0.019 ) and in diabetic patients from 29.9 % to 20.6 % ( OR 0.61 ; CI 0.36 to 1.04 ; p = 0.066 ) . In a multivariate analysis including the extent of CAD , diabetes remained a strong independent predictor of the combined end point ( relative risk [ RR ] 2.40 ; CI 1.47 to 3.91 ; p = 0.0001 ) and of mortality ( RR 5.43 ; CI 2.09 to 14.12 ; p = 0.001 ) . CONCLUSIONS An invasive strategy improved outcome for both diabetic and nondiabetic patients with unstable CAD . However , diabetes mellitus remained an independent and important risk factor for death and myocardial infa rct ion in the invasive group . Thus , factors beyond the extent of flow-limiting coronary lesions are of considerable importance for outcome in diabetic subjects with unstable coronary syndromes OBJECTIVES To determine whether type 2 diabetes mellitus and hyperglycemia on admission should be considered independent predictors of mortality in elderly adults with acute coronary syndrome ( ACS ) . DESIGN Prospect i ve cohort study . SETTING Twenty-three hospitals in Italy . PARTICIPANTS Individuals aged 75 and older with non-ST-elevation ACS ( NSTEACS ) ( mean age 82 , 47 % female ) ( N = 645 ) . MEASUREMENTS Diabetic status and blood glucose levels were assessed on admission . Hyperglycemia was defined as glucose greater than 140 mg/dL. Multivariable Cox proportional hazard regression was used to assess the potential confounding effect of major covariates on the association between diabetic status , admission glucose , and 1-year mortality . RESULTS A history of diabetes mellitus was found in 231 participants ( 35.8 % ) , whereas 257 ( 39.8 % ) had hyperglycemia . Hyperglycemia was found in 171 participants with diabetes mellitus ( 70 % ) and 86 ( 21 % ) without diabetes mellitus . Participants with diabetes mellitus were significantly ( P < .05 ) more likely to have had prior myocardial infa rct ion and stroke and had lower ejection fraction and blood hemoglobin . Hyperglycemia was associated with lower ( P < .05 ) ejection fraction and estimated glomerular filtration rate ( eGFR ) . Diabetic status and hyperglycemia were associated with greater 1-year mortality according to univariate analysis ( 54 participants with diabetes mellitus died ( 23.4 % ) , versus 66 ( 15.9 % ) without diabetes mellitus ( hazard ratio ( HR ) = 1.5 95 % confidence interval ( CI ) = 1.0 - 2.1 ) , and 60 participants with hyperglycemia died ( 23.3 % ) , versus 60 ( 15.5 % ) without hyperglycemia ( HR=1.6 ; 95 % CI = 1.1 - 2.2 ) , but this association was not statistically significant after adjustment for ejection fraction , age , blood hemoglobin , and eGFR . CONCLUSION In elderly adults with NSTEACS , diabetes mellitus and hyperglycemia on admission are associated with higher mortality , mostly because of preexisting cardiovascular and renal damage Background Although unstable coronary artery disease is the most common reason for admission to a coronary care unit , the long-term prognosis of patients with this diagnosis is unknown . This is particularly true for patients with diabetes mellitus , who are known to have a high morbidity and mortality after an acute myocardial infa rct ion . Methods and Results Prospect ively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes ( OASIS ) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non – Q-wave myocardial infa rct ion . Overall , 1718 of 8013 registry patients ( 21 % ) had diabetes . Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients ( 23 % versus 20 % , P < 0.001 ) but had similar rates of catheterization and angioplasty . Diabetes independently predicted mortality ( relative risk [ RR ] , 1.57 ; 95 % CI , 1.38 to 1.81;P < 0.001 ) , as well as cardiovascular death , new myocardial infa rct ion , stroke , and new congestive heart failure . Moreover , compared with their nondiabetic counterparts , women had a significantly higher risk than men ( RR , 1.98 ; 95 % CI , 1.60 to 2.44 ; and RR , 1.28 ; 95 % CI , 1.06 to 1.56 , respectively ) . Interestingly , diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease . Conclusions Hospitalization for unstable angina or non – Q-wave myocardial infa rct ion predicts a high 2-year morbidity and mortality ; this is especially evident for patients with diabetes . Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease OBJECTIVES To compare the use of evidence -based pharmacological and invasive treatments and 12-month mortality rates between patients with and without diabetes who present with acute myocardial infa rct ion ( MI ) , and to explore the relationship between these treatments and late clinical outcomes . DESIGN AND SETTING Prospect i ve , nationwide multicentre registry : the Acute Coronary Syndrome Prospect i ve Audit ( ACACIA ) . PATIENTS Patients presenting to 24 metropolitan and 15 non-metropolitan hospitals with acute coronary syndrome ( ACS ) and a final discharge diagnosis of acute MI between November 2005 and July 2007 . MAIN OUTCOME MEASURE All-cause mortality at 12 months . RESULTS Nearly a quarter of 1744 patients with a final diagnosis of acute MI had a history of diabetes on presentation . Patients with diabetes were older , with a greater prevalence of comorbidities than non-diabetic patients , and were less likely to be treated at discharge with evidence -based medications ( aspirin , clopidogrel , a statin and /or a beta-blocker ) or to receive early invasive procedures . After adjusting for baseline characteristics and therapeutic interventions , diabetes at presentation was independently associated with a higher mortality at 12 months after MI ( hazard ratio , 1.79 ; 95 % CI , 1.18 - 2.72 ; P=0.007 ) . Early invasive management and discharge prescription of guideline -recommended medications were associated with a significantly reduced hazard of mortality at 12 months . CONCLUSION Patients with diabetes have a higher risk than non-diabetic patients of late mortality following an acute MI , yet receive fewer guideline -recommended medications and early invasive procedures . Increased application of proven pharmacotherapies and an early invasive management strategy in patients with diabetes presenting with ACS might improve their outcomes . STUDY PROTOCOL NUMBER ( SANOFI-AVENTIS ) : PML-0051 Aim : The hypothesis that patients with hyperglycaemia during admission , regardless of previous diagnosis of diabetes , have worse prognosis than those with normal glucose values is controversial . The objective was to assess the role of hyperglycaemia on short-term mortality after myocardial infa rct ion ( MI ) . Methods and Results : A cohort study nested in a prospect i ve registry of MI patients in the reference hospital of Gerona , Spain was performed . All consecutive MI patients under 75 were registered between 1993 and 1996 . Patient and clinical characteristics , including previous diagnosis of diabetes , glycaemia on admission and in the next four days , were recorded . Patients with glycaemia on admission or four day mean glycaemia > 6.67 mmol/l were considered hyperglycaemic . The main outcome measure was mortality at 28 days . Of 662 patients with MI included , 195 ( 29.7 % ) had previously known diabetes mellitus , but 457 ( 69.0 % ) had glycaemia > 6.67 mmol/l on admission . Patients with hyperglycaemia on admission were older , more often female , more frequently had a previous diagnosis of diabetes , developed more complications , and had higher 28 day mortality . The effect of admission glycaemia > 6.67 mmol/l on 28 day mortality was independent of major confounding factors , particularly previous diagnosis of diabetes ( OR=4.20 , 95 % confidence intervals 1.18 to 14.96 ) . Conclusions : Higher 28 day mortality was observed among MI patients with glycaemia on admission > 6.67 mmol/l compared with patients with lower levels , independently of major confounding variables and , particularly , previous diagnosis of diabetes . This early , simple , and inexpensive marker of bad prognosis after MI should prompt the application of more aggressive treatment of MI and risk factors and , probably , of glycaemia during admission Background —A prior diagnosis of diabetes mellitus is associated with adverse outcomes after acute myocardial infa rct ion ( MI ) , but the risk associated with a new diagnosis of diabetes in this setting has not been well defined . Methods and Results —We assessed the risk of death and major cardiovascular events associated with previously known and newly diagnosed diabetes by study ing 14 703 patients with acute MI enrolled in the VALsartan In Acute myocardial iNfa rcT ion ( VALIANT ) trial . Patients were grouped by diabetic status : previously known diabetes ( insulin use or diagnosis of diabetes before MI , n=3400 , 23 % ) ; newly diagnosed diabetes ( use of diabetic therapy or diabetes diagnosed at r and omization [ median 4.9 d after infa rct ion ] , but no known diabetes at presentation , n=580 , 4 % ) ; or no diabetes ( n=10 719 ) . Patients with newly diagnosed diabetes were younger and had fewer comorbid conditions than did patients with previously known diabetes . At 1 year after enrollment , patients with previously known and newly diagnosed diabetes had similarly increased adjusted risks of mortality ( hazard ratio [ HR ] 1.43 ; 95 % confidence interval [ CI ] , 1.29 to 1.59 and HR , 1.50 ; 95 % CI , 1.21 to 1.85 , respectively ) and cardiovascular events ( HR , 1.37 ; 95 % CI , 1.27 to 1.48 and HR , 1.34 ; 95 % CI , 1.14 to 1.56 ) . Conclusions —Diabetes mellitus , whether newly diagnosed or previously known , is associated with poorer long-term outcomes after MI in high-risk patients . The poor prognosis of patients with newly diagnosed diabetes , despite having baseline characteristics similar to those of patients without diabetes , supports the idea that metabolic abnormalities contribute to their adverse outcomes Background Diabetes ( DM ) deteriorates the prognosis in patients with coronary heart disease . However , the prognostic value of different glucose abnormalities ( GA ) other than DM in subjects with acute myocardial infa rct ion ( AMI ) treated invasively remains unclear . Aims To assess the incidence and impact of GA on clinical outcomes in AMI patients treated with percutaneous coronary intervention ( PCI ) . Methods A single-center , prospect i ve registry encompassed 2733 consecutive AMI subjects treated with PCI . In all in-hospital survivors ( n = 2527 , 92.5 % ) without the history of DM diagnosed before or during index hospitalization st and ard oral glucose tolerance test ( OGTT ) was performed during stable condition before hospital discharge and interpreted according to WHO criteria . The mean follow-up period was 37.5 months . Results The incidence of GA was as follows : impaired fasting glycaemia - IFG ( n = 376 , 15 % ) ; impaired glucose tolerance - IGT ( n = 560 , 22 % ) ; DM ( n = 425 , 17 % ) ; new onset DM ( n = 384 , 15 % ) ; and normal glucose tolerance – NGT ( n = 782 , 31 % ) . During the long-term follow-up , death rate events for previously known DM , new onset DM and IGT were significantly more frequent than those for IFG and NGT ( 12.3 ; 9.6 and 9.4 vs. 5.6 and 6.4 % , respectively , P < 0.05 ) . The strongest and common independent predictors of death in GA patients were glomerular filtration rate < 60 ml/min/1,73 m^2 ( HR 2.0 and 2.8 ) and left ventricle ejection fraction < 35 % ( HR 2.5 and 1.8 , all P < 0.05 ) respectively . Conclusions Glucose abnormalities are very common in AMI patients . DM , new onset DM and IGT increase remote mortality . Impaired glucose tolerance bears similar long-term prognosis as diabetes Due to the lack of appropriately design ed r and omized trials , the definitive answer in regard to the prognostic role of in-hospital glucose values in patients with AMI is lacking . We prospect ively assessed the prognostic role of in-hospital peak glycemia ( ≤1.40 , 141–180 and > 180 g/l ) in 611 consecutive STEMI patients ( diabetic and without previously known diabetes ) su bmi tted to percutaneous coronary intervention . One hundred and fifteen ( 18.8 % ) were diabetic and the remaining 496 ( 81.2 % ) without previously known diabetes . At multivariable logistic regression analysis , peak glycemia was an independent predictor for in-ICCU death in the overall population and in patients without previously known diabetes . At follow-up , in the overall population ( as well as in diabetic and non-diabetic patients ) , patients with peak glycemia > 1.8 g/l showed the lowest survival rate , those with peak glycemia < 1.4 g/l the highest and patients with peak glycemia > 1.4 and < 1.8 g/l intermediate survival rates . In-hospital peak glycemia is an independent predictor for early death in patients without previously known diabetes , but not in diabetic STEMI patients . At follow-up , in-hospital peak glycemia is able to affect long-term survival in diabetic and non-diabetic patients . Our data underscore strongly suggest that different glucose targets and thresholds may be pursued in diabetic and non-diabetic STEMI patients BACKGROUND Mortality of diabetic patients with acute myocardial infa rct ion ( MI ) remains high despite recent improvement in their management . There is a need to evaluate efficacy and safety of novel treatments of MI in this high-risk population . We evaluated whether treatment with an ACE inhibitor begun within 24 hours from the onset of symptoms is able to decrease mortality and morbidity of diabetic patients with acute MI . METHODS AND RESULTS A retrospective analysis of the data of the GISSI-3 study in patients with and without a history of diabetes was performed . Patients with suspected acute MI were r and omized to treatment with lisinopril ( 2.5 to 5 up to 10 mg/d ) with or without nitroglycerin ( 5 to 20 microg I.V. then 10 mg/d ) begun within 24 hours and continued for 6 weeks . The main end point was mortality at 6 weeks , and the secondary end point was a combined evaluation of mortality and severe left ventricular dysfunction . Information on diabetic status was available for 18,131 patients ( approximately 94 % of the total population enrolled ) , of whom 2790 patients had a history of diabetes . Treatment with lisinopril was associated with a decreased 6-week mortality in diabetic patients ( 8.7 % versus 12.4 % ; OR , 0.68 ; 95 % CI , 0.53 to 0.86 ; 37+/-12 lives saved per 1000 treated patients ) , an effect that was significantly ( P<.025 ) higher than that observed in nondiabetic patients . The survival benefit in diabetics was mostly maintained at 6 months despite withdrawal from treatment at 6 weeks ( 12.9 % versus 16.1 % ; OR , 0.77 ; 95 % CI , 0.62 to 0.95 ) . CONCLUSIONS Early treatment with the ACE inhibitor lisinopril in diabetic patients with acute MI is associated with a decreased 6-week mortality . This beneficial effect supports a widespread and early use of ACE inhibitors in diabetic patients with acute MI . The burden of mortality plus morbidity for ventricular dysfunction in diabetics remains clinical ly important and warrants further testing of novel therapeutic approaches In a prospect i ve study among 5839 consecutive patients after acute myocardial infa rct ion ( AMI ) , the prognosis of men and women with diabetes was compared with that of patients without diabetes after AMI . The prevalence of insulin-treated diabetes or diabetes treated with oral hypoglycemic drugs was 2 % and 8 % among men and 6 % and 12 % among women respectively . After multiple regression analysis , the odds ratio for in-hospital mortality was 1.26 ( 95 % confidence interval [ CI ] 0.82 to 1.92 ) for non-insulin-treated men with diabetes and 2.24 ( 95 % CI 1.14 to 4.38 ) for those treated with insulin . Among women , these odds ratios were 1.46 ( 95 % CI 0.90 to 2.36 ) and 1.80 ( 0.93 to 3.51 ) , respectively . The 10-year relative risk for death was 1.32 ( 95 % CI 1.10 to 1.58 ) for men with non-insulin-treated diabetes and 1.75 ( 95 % CI 1.26 to 2.45 ) for men treated with insulin . For women , the respective relative risks for 10-year mortality were 1.41 ( 95 % CI 1.10 to 1.82 ) for those treated with oral hypoglycemic drugs and 2.59 ( 95 % CI 1.89 to 3.56 ) for diabetic women treated with insulin . We conclude that ( 1 ) diabetes requiring treatment emerged as an independent predictor of short- and longterm mortality after AMI ; ( 2 ) diabetic women had a worse long-term prognosis than diabetic men after AMI ; and ( 3 ) diabetic patients treated with insulin had the worst short- and long-term prognosis after AMI in both genders BACKGROUND Information about the occurrence of heart failure in the acute phase of myocardial infa rct ion ( MI ) in diabetic patients and its impact on prognosis are sparse . AIM The purpose of the present study was to describe how MI patients with diabetes mellitus ( DM ) differed from MI patients without DM with respect to the occurrence of heart failure and with respect to the influence of heart failure on mortality during follow-up 30 days extending to 15 years . METHODS The study is a retrospective long-term follow-up of prospect ively recorded data concerning 1954 consecutive cases of MI admitted to one coronary care unit ( CCU ) between 1979 and 1983 . DM was diagnosed in 10 % ( n=194 ) , with 17 % ( n=33 ) on insulin therapy . Patients with DM comprised of a higher proportion of women ( DM 36 % vs. no DM 26 % , P<0.001 ) compared with non-diabetic patients . Baseline risk factors were more prevalent in the patients with DM . The cumulative incidence of heart failure was higher among patients with than without DM ( DM 54 % vs. no DM 34 % , P<0.001 ) . The incidence of life-threatening arrhythmias were similar in both groups . Only 2 % of patients with DM and heart failure survived 10 years of follow-up compared with 15 % of the non-diabetic patients with heart failure ( P<0.001 ) . In multivariate analysis DM was not independently associated with 30 days mortality . During long-term follow-up DM was an important risk factor for mortality independent on the presence of heart failure . CONCLUSION DM disposes to the development of heart failure . In acute myocardial infa rct ion diabetic patients with heart failure have a worse prognosis than non-diabetic patients with heart failure AIMS The CAPTIM study r and omized patients managed within 6 h of acute ST-segment elevation myocardial infa rct ion to primary angioplasty or prehospital fibrinolysis ( rt-PA ) , with immediate transfer to a centre with interventional facilities . It found a similar incidence of the primary endpoint of death , recurrent MI , or stroke at 30 days with both strategies . We report here the outcome in the diabetic subgroup . METHODS AND RESULTS The relationship of diabetic status ( diabetics , n=103 , non-diabetics , n=731 ) and treatment strategy with the occurrence of the primary endpoint and of death was analysed . Compared with non-diabetics , diabetics had a higher baseline risk profile , a higher rate of the primary endpoint ( 14.6 vs. 5.6 % ; P=0.002 ) , and a high rate of mortality ( 8.7 vs. 3.1 % ; P=0.01 ) at 30 days . The incidence of the primary endpoint tended to be higher in diabetics r and omized to prehospital fibrinolysis compared with those r and omized to primary angioplasty [ 21.7 vs. 8.8 % ( 10/46 vs. 5/57 ) ; RR : 2.47 ( 0.91 - 6.74 ) ; P=0.09 ] . This difference was driven by the higher mortality in the fibrinolysis group [ 13.0 vs. 5.3 % ( 6/46 vs. 3/57 ) ; RR : 2.47 ( 0.7 - 9.4 ) ; P=0.29 ] . For non-diabetics , no such trend was observed . Compared with non-diabetics , diabetics had a much higher rate of rescue angioplasty ( 41.4 vs. 23.5 % ; P=0.01 ) and a higher mortality after rescue angioplasty [ 17.4 vs. 0 % ( 4/23 vs. 0/90 ) ; P=0.001 ] . CONCLUSION These results suggest that diabetic patients presenting within 6 h of an acute myocardial infa rct ion may derive particular benefit from a strategy of primary angioplasty . However , the small number of diabetic patients in this subgroup analysis does not allow a final conclusion and a specifically design ed study is warranted This study was design ed to evaluate how new treatment guidelines of acute coronary syndrome ( ACS ) without ST elevation have been implemented in clinical practice especially in diabetic patients . A prospect i ve follow-up was performed on 501 consecutive patients with suspected ACS without ST elevation admitted to nine hospitals in Finl and between 15 January and 11 March 2001 . The study group included 143 ( 29 % ) diabetic patients . Their risk profile was more severe than in non-diabetic patients ; ST-depression on admission electrocardiography 57 versus 38 % ; P<0.0001 , elevated troponin levels 66 versus 56 % ; P<0.05 . Six months composite incidence of death , new myocardial infa rct ion ( MI ) , refractory angina or readmission for unstable angina was 39 % in diabetic patients and 20 % in non-diabetic patients ( P<0.0001 ) . In spite of this more severe risk profile , glycoprotein ( GP ) IIb/IIIa receptor antagonists and statins were used with similar frequency in non-diabetic and diabetic patients ( 15 vs. 19 and 48 vs. 54 % , respectively ; P = NS for both ) . In diabetic patients mean delay for in hospital coronary angiography was longer ( 6.4 vs. 4.2 days , P<0.05 ) and it was performed less often ( 32 vs. 45 % P<0.05 ) . Our results show that diabetic patients with ACS have higher risk profile and worse outcome than non-diabetic patients . Despite their indisputable benefits in diabetic patients , statins , GP IIb/IIIa receptor antagonists and invasive strategy were underused or often neglected . Further education is needed to change attitudes and to better implement new guidelines into clinical practice We sought to determine the benefits of stent implantation and abciximab in patients with diabetes mellitus and acute myocardial infa rct ion ( AMI ) who underwent primary angioplasty . In a 2-by-2 factorial design , 2,082 patients with AMI were r and omly assigned to balloon angioplasty versus stenting , with or without abciximab . Diabetes was present in 346 patients ( 16.6 % ) . The primary end point was the composite incidence of death , disabling stroke , reinfa rct ion , and ischemic target vessel revascularization ( TVR ) . The primary end point at 1 year occurred significantly more frequently in diabetic than nondiabetic patients ( 21.9 % vs 16.8 % , p < 0.02 ) , driven by increased rates of death ( 6.1 % vs 3.9 % , p = 0.04 ) and TVR ( 16.4 % vs 12.7 % , p = 0.07 ) . Among patients with diabetes , TVR at 1 year was significantly reduced with routine stenting compared with balloon angioplasty ( 10.3 % vs 22.4 % , p = 0.004 ) , with no differences in death , reinfa rct ion , or stroke . Angiographic restenosis was also greatly reduced in diabetics r and omized to stenting ( 21.1 % vs 47.6 % , p = 0.009 ) . No beneficial effects were apparent with abciximab in diabetic patients at 1 year . Despite the improved outcomes with stenting in patients with diabetes , 1-year mortality remained increased in diabetic patients who received stents compared with nondiabetics ( 8.2 % vs 3.6 % , p = 0.005 ) . Thus , routine stent implantation in diabetic patients with AMI significantly reduces restenosis and enhances survival free from TVR , independent of abciximab use , although survival remains reduced compared with survival in nondiabetic patients regardless of reperfusion modality Aims /hypothesisWe sought to evaluate the impact of diabetes mellitus on long-term outcome in patients with unstable angina and non-ST-segment elevation myocardial infa rct ion treated with a very early invasive strategy . Methods We carried out a prospect i ve cohort study in 270 diabetic and 1163 non-diabetic patients with unstable angina and non-ST-segment elevation myocardial infa rct ion . All patients underwent coronary angiography and , if appropriate , subsequent revascularisation within 24 hours of admission . The primary endpoint was all-cause mortality during follow-up for up to 60 months . Results Diabetic patients had less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infa rct ion . Percutaneous coronary intervention was performed in 53 % of diabetic patients and 56 % of non-diabetic patients . Coronary artery bypass grafting was done in 21 % of diabetic patients and 12 % of non-diabetic patients . In-hospital mortality ( 4.1 % vs 1.3 % ; hazard ratio 3.47 ; 95 % CI : 1.57 to 7.64 ; p=0.002 ) and long-term mortality ( 9.7 % vs 4.9 % ; hazard ratio 2.11 ; 95 % CI : 1.33 to 3.36 ; p=0.002 ) were significantly higher in diabetic patients . After adjustment for differences in baseline characteristics , diabetes mellitus was no longer an independent predictor of long-term mortality ( hazard ratio 1.43 ; 95 % CI : 0.74 to 2.78 ; p=0.292 ) . Conclusions /interpretationDiabetic patients treated with a very early invasive strategy for unstable angina and non-ST-segment elevation myocardial infa rct ion have a higher in-hospital and long-term mortality that is largely explained by their less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infa rct ion OBJECTIVES This study was design ed to assess outcome in patients with diabetes who received thrombolytic therapy and to determine whether differences in angiographic characteristics may account for the worse outcome observed in diabetic patients . BACKGROUND Patients with diabetes are known to have a worse outcome after acute myocardial infa rct ion than that of patients without diabetes . METHODS Clinical and angiographic characteristics of the 148 patients with diabetes and the 923 patients without diabetes in the Thrombolysis and Angioplasty in Myocardial Infa rct ion ( TAMI ) trials were examined and analyzed . RESULTS Patients with diabetes tended to be older ( median age 59 vs. 56 years ) and to have a higher incidence of hypertension and hyperlipidemia and a lower incidence of cigarette smoking . Patients with diabetes had significantly more severe anatomic disease ( 66 % vs. 46 % had multivessel disease , p < 0.0001 ) , similar global left ventricular ejection fraction ( 49 % vs. 51 % ) and worse noninfa rct zone ventricular function ( -0.13 vs. 0.32 SD/chord , p = 0.02 ) than that of nondiabetic patients . Angiographic patency rates at 90 min after thrombolytic therapy were similar in patients with and without diabetes ( initial 90-min patency 71 % vs. 70 % ) . Diabetic patients had nearly twice the in-hospital mortality rate ( 11 % vs. 6 % , p < 0.02 ) and a higher incidence of pulmonary edema ( 11 % vs. 4 % , p = 0.001 ) . Diabetic women had an especially high in-hospital mortality rate ( 21 % ) . No retinal hemorrhages were observed . Although diabetes as an unadjusted variable was predictive of in-hospital ( p < 0.02 ) and long-term ( p = 0.003 ) mortality , after adjustment for baseline clinical and angiographic characteristics , diabetes was not found to have an independent influence on mortality . CONCLUSIONS Patients with diabetes after myocardial infa rct ion have a worse outcome than that of patients without diabetes despite similar rates of infa rct vessel patency . However , diabetes was not found to be an independent risk factor for increased mortality . These findings suggest that diabetes itself is not a major risk factor for poor early outcome after thrombolytic therapy for myocardial infa rct ion ; rather , the secondary effects such as more extensive coronary artery disease account for the worse outcome BACKGROUND Diabetes-related differences in treatment and clinical outcome of patients across the entire spectrum of acute coronary syndromes ( ACSs ) have potential clinical implication s but have not been well studied . METHODS The multicenter , prospect i ve , Canadian ACS Registry enrolled 4578 patients hospitalized for ACS between 1999 and 2001 across 9 provinces in Canada . We compared baseline characteristics , in-hospital and post-discharge treatments , and clinical outcome of diabetic and non-diabetic patients . The impact of diabetes on use of thrombolytic therapy and coronary revascularization ; and the independent association between diabetes , treatments , and diabetes-treatment interactions on outcome were examined . RESULTS Diabetic patients with ACS had more cardiovascular risk factors and higher-risk clinical presentation . They paradoxically received less evidence -based medications in-hospital , at discharge , and at 1-year . Although diabetes independently predicted higher 1-year mortality ( OR 1.47 , 95 % CI 1.15 - 1.87 ; P = .002 ) after adjustment for vali date d prognosticators , it was also an independent predictor of not receiving thrombolytic therapy ( OR 0.72 , 95 % CI 0.54 - 0.95 ; P = .021 ) and coronary revascularization ( OR 0.69 , 95 % CI 0.59 - 0.82 ; P < .001 ) . These underused therapies were all independently associated with reduced 1-year mortality , with no significant diabetes-related treatment- outcome heterogeneity . Importantly , diabetes remained an independent adverse prognosticator even after further adjustment for these differences in treatment . CONCLUSIONS Evidence -based therapies are underused in the contemporary management of diabetic patients with ACS , which partly explains their worse outcome . Diabetes should be considered a high-risk feature in ACS risk stratification that encourages more intensive treatments . Continued efforts to promote adherence to existing proven therapies and to develop novel treatment strategies targeting diabetes-specific cardiovascular pathophysiology are imperative to improve their adverse prognosis Aims The mechanisms underlying the higher risk of heart failure after myocardial infa rct ion ( MI ) in diabetic patients remain incompletely understood . Our aim was to investigate cardiac remodeling after MI according to diabetic status . Methods Data from 512 patients with a first anterior MI included in two prospect i ve cohorts on left-ventricular remodeling were analyzed . Echocardiographic studies were performed before discharge , at 3 months and at 1 year . Clinical follow-up was performed after 3 years . Results There were 60 ( 23 % ) diabetic patients in cohort 1 and 51 ( 21 % ) in cohort 2 . Therapeutic strategies , infa rct size and residual left-ventricular ejection fraction did not differ between diabetic and nondiabetic patients . In both cohorts , there was a significant increase in left-ventricular volumes and a recovery in left-ventricular systolic function from baseline to 1 year ; these parameters did not differ according to diabetic status at any of the three time points . Diastolic function was analyzed in cohort 2 : the E/Ea ratio was higher in diabetic patients at baseline and during follow-up . Diabetes mellitus was an independent predictor of cardiovascular death or rehospitalization for heart failure in cohort 1 [ relative risk ( RR ) 2.62 ( 1.35–5.11 ) ] and in cohort 2 [ RR 4.99 ( 2.06–12.21 ) ] . Conclusions In patients with a modern treatment of MI , diabetes mellitus remains a major and independent predictor of subsequent heart failure . This higher risk is not associated with a decreased left-ventricular systolic function or with increased left-ventricular remodeling . The evidence of higher left-ventricular filling pressures suggests left-ventricular diastolic dysfunction as a potential mechanism OBJECTIVES Short-term r and omised trials suggest that patients with diabetes mellitus ( DM ) , admitted with acute coronary syndromes ( ACS ) are at increased risk of subsequent adverse events . We tested whether this hypothesis was true for an unselected population of ACS patients with and without DM admitted with non-ST elevation MI or unstable angina , in a non-trial setting over a longer term of follow-up . METHODS Prospect i ve , central ly , coordinated multicenter registry involving 56 centers throughout the UK ( half having angiographic facilities ) . Consecutive patients admitted with ACS without ST elevation on the presenting ECG were followed up to 6 months . A sub-group of patients were flagged with the UK Office for National Statistics and followed-up for death over 4 years . RESULTS Data were collected on 1046 ACS patients of whom 170 ( 16 % ) had a prior diagnosis of DM . DM patients had higher baseline co-morbidities and unadjusted mortality rates at 6 months ( 11.8 % vs. 6.4 % , p=0.01 ) . After correcting for clinical variables such as age , gender , smoking status and chest pain/ischaemic ECG changes on admission , prior history of any of myocardial infa rct ion , heart failure , hypertension , hypercholesterolemia ( on treatment ) , stroke or coronary revascularisation ( PTCA or CABG ) , mortality rates for DM patients were no longer significantly raised ( hazard ratio 1.35 , 95 % CI : 0.79 - 2.30 ; p=0.27 at 6 months and 1.15 , 95 % CI 0.72 - 1.83 at 4 years ) . 30 % of diabetics were dead after 4 years of follow-up . Patients with DM were more likely to have been revascularised at 6 months and were more likely to receive ACE inhibitors . Based on the rate of recruitment and the population covered in the study , about 21,000 patients with DM will be admitted with non-ST elevation ACS each year in the UK . CONCLUSIONS DM is common amongst patients admitted with ACS without ST elevation and is associated with significant morbidity and mortality : approximately 1 in 8 will not survive up to 6 months and 1 in 3 to 4 years . DM patients should be managed aggressively to reduce their risk of future complications Background Women with acute myocardial infa rct ion ( AMI ) exhibit greater hospital mortality than do men . In general , diabetes mellitus is one of the major factors influencing the outcome of patients with AMI . The aim of this study was to analyze the interaction between diabetes and gender , specifically with regard to the higher hospital mortality of female AMI patients aged ≤ 75 years . Methods We prospect ively collected data from 3,715 patients aged ≤ 75 ( 2,794 men , 921 women ) with acute myocardial infa rct ion who were treated in 25 hospitals in Berlin , Germany , from 1999 to 2002 . In a multivariate analysis , we specifically studied the interaction between the factors diabetes mellitus and gender in their effects on hospital mortality . Results After adjustment in multivariate analysis , the interaction between gender and diabetes was statistically significant , and the estimated odds ratios were as follows : female diabetic patients compared with male diabetic patients , odds ratio ( OR ) = 2.28 ( 95 % confidence interval [ CI ] 1.42 - 3.68 ) ; female diabetic patients compared with male nondiabetic patients , OR = 2.90 ( 95 % CI 1.90 - 4.42 ) ; and female diabetic patients compared with female nondiabetic patients , OR = 2.92 ( 95 % CI 1.75 - 4.87 ) . There was no statistically significant difference between the risk of dying for female nondiabetic patients or for male diabetic patients when compared with male nondiabetic patients . Conclusions In AMI patients aged ≤ 75 years , female gender alone is not an independent predictor of hospital mortality . Detailed , multivariate analysis reveals that specifically diabetic women demonstrate higher hospital mortality than do men . Special attention should be provided to these female diabetic patients OBJECTIVES We studied the outcome of diabetics enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries ( GUSTO ) V trial to assess whether the combination of half-dose reteplase and abciximab provides any propitious benefits over st and ard fibrinolytic therapy in diabetic patients . BACKGROUND Diabetics with acute ST-segment elevation myocardial infa rct ion ( MI ) have a worse outcome compared with nondiabetics . Higher-risk patients are usually more likely to benefit from advances in medical therapy . METHODS We analyzed diabetic patients enrolled in the GUSTO V trial to assess the outcome of those r and omized to the combination of half-dose reteplase and abciximab versus those r and omized to reteplase . We also evaluated whether any differences existed in presentation and outcome of MI among the diabetics versus the nondiabetics enrolled in the study . RESULTS The trial enrolled 13782 nondiabetics and 2633 diabetics . Compared to nondiabetics , diabetics had a significantly higher mortality at 30 days ( 8.5 % vs. 5.1 % , p < 0.001 ) and at 1 year ( 12.7 % vs. 7.5 % , p < 0.001 ) . Among the diabetic subset , no significant difference existed in the incidence of 30-day ( 8.8 % vs. 8.2 % , p = 0.52 ) or 1-year mortality ( 13.0 % vs. 12.4 % , p = 0.62 ) among patients r and omized to reteplase compared to those receiving combination of abciximab and reteplase . The incidence of reinfa rct ion ( 2.5 % vs. 4.3 % , p = 0.013 ) , recurrent ischemia ( 11.8 % vs. 14.9 % , p = 0.017 ) , and urgent revascularization ( 10.9 % vs. 13.3 % , p = 0.055 ) at seven days was lower in diabetics treated with the combination therapy . CONCLUSIONS Compared to nondiabetics , diabetics continue to have a worse outcome with MI . Although combination therapy did not provide a survival benefit , nonfatal ischemic outcomes , including reinfa rct ion , recurrent ischemia , and urgent revascularization , were substantially reduced Hyperglycemia in the context of acute coronary syndrome ( ACS ) is a common observation , and existing data suggest that high glucose levels are associated with increased in-hospital mortality . We assessed the relation between r and om glucose and long-term mortality in 9,020 patients with ACS who were enrolled in the OPUS-TIMI 16 trial . A significant relation between glucose level and 10-month mortality was observed ( 2.7 % in quartile 1 vs 7.0 % in quartile 4 , p < 0.0001 ) . After multivariable adjustment for co-morbidity , which included history of diabetes , this relation remained significant ( quartile 4 vs 1 , hazard ratio 1.70 , 95 % confidence interval 1.16 to 2.50 , p = 0.006 ) . These observations were similar in the TACTICS-TIMI 18 trial . In addition , we observed that B-type natriuretic peptide and troponin I levels increased across glucose quartiles in the OPUS-TIMI 16 trial ( p values for trend = 0.002 and 0.0001 , respectively ) and the TACTICS-TIMI 18 trial ( p values for trend = 0.006 and 0.0001 , respectively ) . High blood glucose during ACS is an independent predictor of long-term mortality and is significantly correlated with prognostic biomarkers . Glucose levels during ACS may be an important addition to the risk stratification of patients with ACS and a potentially important target for therapy AIMS To study clinical presentation , in-hospital course and short-term prognosis in men and women with diabetes mellitus and acute coronary syndromes ( ACS ) . METHODS Men ( n = 6488 , 21.2 % with diabetes ) and 2809 women ( 28.7 % with diabetes ) < or = 80 years old , with a discharge diagnosis of ACS were prospect ively enrolled in the Euro Heart Survey of ACS . RESULTS Women with diabetes were more likely to present with ST elevation than non-diabetic women , a difference that became more marked after adjustment for differences in smoking , hypertension , obesity , medication and prior disease [ adjusted odds ratio ( OR ) 1.46 ( 1.20 , 1.78 ) ] , whereas there was little difference between diabetic and non-diabetic men [ adjusted OR 0.99 ( 0.86 , 1.14 ) ] . In addition , women with diabetes were more likely to develop Q-wave myocardial infa rct ion ( MI ) than non-diabetic women [ adjusted OR 1.61 ( 1.30 , 1.99 ) ] , while there was no difference between men with and without diabetes [ adjusted OR 0.99 ( 0.85 , 1.15 ) ] . There were significant interactions between sex , diabetes and presenting with ST-elevation ACS ( P < 0.001 ) , and Q-wave MI ( P < 0.001 ) , respectively . Of the women with diabetes , 7.4 % died in hospital , compared with 3.6 % of non-diabetic women [ adjusted OR 2.13 ( 1.39 , 3.26 ) ] , whereas corresponding mortality rates in men with and without diabetes were 4.1 % and 3.3 % , respectively [ OR 1.13 ( 0.76 , 1.67 ) ] ( P for diabetes-sex interaction 0.021 ) . CONCLUSION In women with ACS , diabetes is associated with higher risk of presenting with ST-elevation ACS , developing Q-wave MI , and of in-hospital mortality , whereas in men with ACS diabetes is not significantly associated with increased risk of either . These findings suggest a differential effect of diabetes on the pathophysiology of ACS based on the patient 's sex In 787 patients with acute myocardial infa rct ion originally participating in the Göteborg Metoprolol Trial , mortality and morbidity during 5 years ' follow-up were assessed and related to whether patients had diabetes mellitus . Diabetes occurred in 78 patients ( 10 % ) . Patients with diabetes had a different risk factor pattern , including higher age , higher occurrence of angina pectoris and hypertension , whereas smoking habits did not differ . In the early phase ( hospitalization ) , patients with diabetes had a higher mortality ( 12 % versus 8 % ) , required more treatment for heart failure and stayed longer in hospital . Other morbidity aspects , such as severity of pain , occurrence of severe supraventricular and ventricular arrhythmias , high-degree AV-block and infa rct size did not differ . During 5 years ' follow-up mortality rate in patients with diabetes mellitus was 55 % as compared with 30 % among patients with no diabetes ( p less than 0.001 ) . Reinfa rct ion rate during 5 years was 42 % in diabetics versus 25 % in non-diabetics ( p less than 0.001 ) . In a multivariate analysis , taking into account the differences in risk factor pattern , diabetes turned out to be an independent determinant for long-term mortality and reinfa rct ion ( p less than 0.001 ) . We conclude that patients with diabetes mellitus , developing acute myocardial infa rct ion , is a group with particularly high risk of death and reinfa rct ion . Interventions aim ing at its reduction have priority BACKGROUND The determinants of a worse outcome in diabetic patients after an acute myocardial infa rct ion ( AMI ) are controversial . They include delayed hospital admission , worse clinical presentation and lesser efficacy of accepted therapeutic interventions . Therefore , to improve our knowledge , we aim ed to describe the clinical characteristics , treatment options and short-term outcomes of diabetic patients in a survey of consecutive AMI subjects admitted to the Italian coronary care unit ( CCU ) network in the current era of reperfusion . METHODS The BLITZ study prospect ively enrolled patients with AMI , within 48 hours of symptom onset , admitted to 296 out of the 341 existing Italian CCUs from October 15 to 29 , 2001 . Diabetic status was recorded by collecting clinical history . In-hospital and post-discharge management and outcomes were collected up to 30 days from admission . RESULTS Overall , 434 of 1959 enrolled patients ( 22 % ) had a clinical diagnosis of diabetes . Diabetic patients were older , more frequently women , had a worse coronary risk profile , and an unfavorable clinical presentation compared to non-diabetics . Among 1275 patients with ST-elevation AMI , diabetics ( 20 % ) received a similar proportion of any reperfusion therapy ( 61 vs 66 % , p = 0.10 ) , but significantly less primary percutaneous coronary angioplasty ( 9 vs 16 % , p = 0.003 ) . Diabetic patients were treated less often with oral beta-blockers than non-diabetics both during hospitalization ( 56 vs 64 % , p = 0.003 ) and at discharge ( 54 vs 61 % , p = 0.01 ) . In contrast , in-hospital use of angiotensin-converting enzyme inhibitors ( 76 vs 67 % , p = 0.0003 ) , digitalis ( 10 vs 5 % , p = 0.0005 ) , and diuretics ( 54 vs 36 % , p < 0.0001 ) was more frequent among diabetics . During their index admission , subjects with diabetes had higher in-hospital mortality ( 11 vs 6 % , p = 0.0004 ) , as well as higher rates of reinfa rct ion ( 6 vs 2 % , p = 0.0003 ) , new congestive heart failure ( 28 vs 14 % , p < 0.0001 ) , cardiogenic shock ( 10 vs 5 % , p = 0.0005 ) or recurrent angina ( 22 vs 16 % , p = 0.0034 ) . A similar pattern was observed at 30-day follow-up . At multivariate analysis , diabetic status was not confirmed to be an independent predictor of 30-day mortality . CONCLUSIONS Although diabetic patients with AMI admitted to the Italian CCU network have a higher in-hospital and 30-day morbidity and mortality rates compared to non-diabetics , a clinical diagnosis of diabetes has no independent predictive value on short-term outcome OBJECTIVES To compare management and short-term outcome of diabetic and non-diabetic patients hospitalized for acute myocardial infa rct ion . METHODS This was a prospect i ve epidemiological survey . All patients admitted in coronary care units in France in November 2000 for confirmed acute myocardial infa rct ion were eligible to enter the study . RESULTS Of the 2320 patients recruited from 369 centers , 487 were diabetic ( 21 % ) . Compared to non-diabetic patients , diabetic patients were 5 years older , more often female , obese and hypertensive ; they had more often a history of cardiovascular disease ; they had a lower ejection fraction and worse Killip class . Reperfusion therapy was less frequent among diabetic patients ( 39 % versus 51 % ; p=0.0001 ) , as was the use of beta-blockers ( 61 % versus 72 % ; p=0.0001 ) , aspirin ( 83 % versus 89 % ; p=0.0001 ) and statins ( 52 % versus 60 % ; p=0.001 ) during hospitalization . Conversely , the use of ACE-inhibitors was more frequent ( 54 % versus 44 % ; p=0.0001 ) . 58 % of diabetic patients received insulin during hospitalization . Twenty-eight-day mortality was 13.1 % in diabetic patients and 7.0 % in non-diabetic patients ( risk ratio : 1.87 ; p=0.001 ) . Diabetes remained associated with increased mortality after adjustment for relevant risk factors including age and ejection fraction ( risk ratio : 1.51 ; p=0.07 ) . In patients treated with antidiabetic drugs ( chiefly sulfonylureas ) before admission , 28-day mortality was 10.4 % compared with 19.9 % in diabetic patients on diet alone or untreated ( p=0.005 ) . CONCLUSION Despite higher cardiovascular risk and worse prognosis , in-hospital management of diabetic patients with acute myocardial infa rct ion remains sub-optimal . Patients previously treated with antidiabetic drugs including sulfonylureas had a better prognosis than untreated diabetic patients Hypertension ( HT ) and diabetes mellitus ( DM ) lead to structural and functional cardiac impairment and worsen the prognosis after myocardial infa rct ion ( MI ) . However , the prognosis of male or female patients with the coexistence of HT and DM after MI has not been clearly demonstrated . The study sample comprised 4317 consecutive patients with an acute MI from a prospect i ve nationwide survey conducted in 1992 , 1994 and 1996 in all 25 coronary care units operating in Israel . The in-hospital , 30-day and 1-year outcome of diabetic hypertensive patients ( n=546 ) was compared with that of diabetic normotensive patients ( n=547 ) and with that of nondiabetic hypertensive patients ( n=1192 ) and nondiabetic normotensive subjects ( n=2032 ) . The crude in-hospital , 30-day and 1-year mortality rates of diabetic hypertensive patients ( 11.7 , 16.5 and 27.6 % , respectively ) were significantly higher than those of the diabetic normotensive patients ( 9.5 , 15.4 and 22.9 % , respectively ) and nondiabetic hypertensive patients ( 7.1 , 11.6 and 17.6 % , respectively ) . Kaplan – Meier survival curves showed increased mortality rates during the 1-year follow-up in diabetic hypertensive patients . Adjusted risk for 1-year mortality was increased in diabetic patients . However , the risk was similar in diabetic hypertensive and normotensive patients ( hazard ratio ( HR ) 1.55 , 95 % confidence interval ( CI ) 1.25–1.93 , and 1.62 , 95 % CI 1.29–2.04 , respectively ) . Adjusted Kaplan – Meier survival curves of diabetic hypertensive patients converged with those of the diabetic normotensives . The existence of DM increases the 1-year mortality after MI by about 60 % . However , controlled hypertension did not worsen the outcome of diabetic male or female patients after MI Objective — There is an excess mortality after myocardial infa rct ion in diabetics , but also documented significant differences in the characteristics of MI and in management between diabetics and non-diabetics . The aim of this prospect i ve study in a large unselected patient cohort in a single French region was to determine if baseline characteristics , management , or in-hospital and one-year mortality differed in diabetic and non-diabetic patients with myocardial infa rct ion . Methods and results — Data were prospect ively collected in consecutive patients with myocardial infa rct ion admitted to all hospitals in three departments in the Rhône-Alpes region between September 1 , 1993 and January 31,1995 . Among the 2,297 patients , 410 patients ( 17.8 % ) were diabetic . Although diabetics were older than non-diabetics ( 70.3 vs. 67.8 years ; p < 0.0004 ) , and less likely to receive thrombolysis ( 31 % vs. 36 % ; p = 0.043 ) , in-hospital mortality was not significantly higher ( 17.3 % vs. 14.7 % ) than in non-diabetics . In multivariate analysis , diabetes was a significant predictor of one-year mortality ( relative risk : 1.41 ; 95 % CI = 1.10 – 1.79 ; p = 0.0063 ) but not of in-hospital mortality ( relative risk : 1.2 ; 95 % CI = 0.9 – 1.7 ; p = 0.25 ) . Multivariate predictors of in-hospital and one-year mortality in diabetics were age and Killip class at admission . Conclusions — In this large unselected French cohort , diabetes mellitus was a significant predictor of one-year but not of in-hospital mortality after myocardial infa rct ion in a French region . This negative effect of diabetes on mortality was not related to differences in baseline characteristics , or in initial or post-discharge management between diabetics and non-diabetics OBJECTIVES This study was conducted to determine the role of insulin-dependent and noninsulin-dependent diabetes in the prognosis of patients after myocardial infa rct ion and treatment with fibrinolytic agents . BACKGROUND Several studies have shown that diabetic patients have a high mortality rate after acute myocardial infa rct ion . However , the impact of diabetes on survival in patients treated with fibrinolytic agents is still undefined . It is also not known whether the type of diabetes or gender affects prognosis . METHODS We analyzed prevalence and prognostic significance of a history of diabetes in patients enrolled in the GISSI-2 study , all of whom received fibrinolytic agents . The incidence of deaths in the hospital and at 6 months after study entry was computed for patients without diabetes and for insulin-dependent and noninsulin-dependent diabetic patients ; relative risks were evaluated by univariate and multivariate analysis . RESULTS Information on diabetic status was available for 11,667 patients , 94.2 % of those r and omized in the GISSI-2 study . The prevalence of diabetes was higher in women than in men ( 8.75 % vs. 1.85 % , p < 0.01 for insulin-dependent and 23.7 % vs. 13.8 % , p < 0.01 for noninsulin-dependent diabetic patients ) . The type of fibrinolytic agent did not affect mortality rates ; the increase in in-hospital mortality of diabetic patients was moderate and similar for men with insulin- and noninsulin-dependent diabetes ( 8.7 % and 10.1 % , respectively , vs. 5.8 % in nondiabetic patients ) ; in women , mortality was markedly higher for insulin-dependent and only slightly higher for noninsulin-dependent diabetic patients ( 24.0 % and 15.8 % , respectively , vs. 13.9 % for nondiabetic patients ) . The adjusted relative risks were 1.9 ( 95 % confidence interval 1.2 to 2.9 ) for insulin-dependent diabetic women and 1.4 ( 95 % confidence interval 1.1 to 1.8 ) for noninsulin-dependent diabetic men . The mortality rate after discharge showed a similar gender difference , and in insulin-dependent diabetic women , prognosis was ominous even in the absence of left ventricular damage before discharge . CONCLUSIONS A history of diabetes is associated with a worse prognosis after myocardial infa rct ion , even in patients treated with fibrinolytic agents . Gender and type of diabetes appear to be critical in affecting survival . In men , both insulin-dependent and noninsulin-dependent diabetes are associated with a moderately higher mortality rate ; in women , insulin-dependent diabetes is , in itself , a strong risk factor for death after myocardial infa rct ion BACKGROUND Patients with diabetes mellitus ( DM ) are at higher risk for complications after ST-elevation myocardial infa rct ion ( STEMI ) than patients without DM . Potent antithrombotic therapies may offer particular benefit for these high-risk patients and must be balanced against the potential for increased bleeding . METHODS We performed a prospect ively planned analysis of efficacy and safety in patients with DM among 20,479 patients with STEMI treated with fibrinolysis and r and omized to a strategy of enoxaparin ( up to 8 days ) or unfractionated heparin ( UFH ) ( 48 hours ) in ExTRACT-TIMI 25 . RESULTS Patients with DM ( n = 3060 ) were older and more likely to be women and to present with heart failure ( P < .0001 for each ) than those without DM . After adjustment for the TIMI Risk Score , sex , and renal function , patients with DM were at 30 % higher risk for death or myocardial infa rct ion ( MI ) by 30 days ( OR(adj ) 1.29 , 95 % CI 1.14 - 1.46 ) . Among patients with DM , the enoxaparin strategy reduced mortality ( 9.5 % vs 11.8 % , relative risk [ RR ] 0.81 , 95 % CI 0.66 - 0.99 ) , death/MI ( 13.6 % vs 17.1 % , RR 0.80 ; 95 % CI 0.67 - 0.94 ) , and death/MI/urgent revascularization ( 16.0 % vs 19.7 % , RR 0.81 , 95 % CI 0.70 - 0.94 ) . The enoxaparin strategy was associated with a trend toward higher major bleeding ( 2.6 % vs 1.6 % , RR 1.63 , 95 % CI 0.99 - 2.69 ) . Taking efficacy and safety into account , the enoxaparin strategy offered superior net clinical benefit ( death/MI/major bleed , 14.8 % vs 18.0 % , RR 0.83 , 95 % CI 0.70 - 0.97 ) compared with UFH in patients with DM . CONCLUSIONS In a subgroup analysis , a reperfusion strategy including enoxaparin significantly improved outcomes compared with UFH among high-risk STEMI patients with DM undergoing fibrinolysis Objective The purpose of this study was to document trends in the prevalence of diabetes among men and women hospitalized for myocardial infa rct ion ( MI ) and to determine the effect of diabetes on in-hospital case fatality rates and long-term survival . Research Design and Methods : The Minnesota Heart Survey is a population -based surveillance system that has monitored trends in coronary heart disease morbidity since 1970 . As part of this effort , a 50 % r and om sample of acute Ml discharge records in Minneapolis-St . Paul metropolitan area hospitals was abstract ed in 1970,1980 , and 1985 . Research Design and Methods The Minnesota Heart Survey is a population -based surveillance system that has monitored trends in coronary heart disease morbidity since 1970 . As part of this effort , a 50 % r and om sample of acute MI discharge records in Minneapolis-St . Paul metropolitan area hospitals was abstract ed in 1970 , 1980 , and 1985 . Results The prevalence of diabetes among MI patients was compared over time , and the data indicated a significant increase between 1970 and 1985 in both men ( 8.2 vs. 16.8 % , P = 0.001 ) and women ( 16.0 vs. 25.8 % , P = 0.01 ) . Diabetic individuals had an odds ratio of in-hospital death after an MI 1.5 times that of nondiabetic individuals ( P < 0.01 ) after controlling for the effects of sex , age , and year of MI . Among discharged MI survivors , the risk of death was 40 % higher ( P < 0.01 ) in diabetic individuals than nondiabetic individuals after 6 yr of follow-up . Compared with nondiabetic individuals , diabetic individuals appeared more likely to have cardiac ( pump ) failure with acute MI . Conclusions Our findings suggest that the risk of coronary heart disease morbidity and mortality attributable to diabetes may be increasing over time . Therefore , clinicians need to take extra care in the management of MIs in diabetic individuals , and public health efforts to reduce diabetes prevalence are warranted |
10,595 | 24,709,690 | There was also no evidence of irinotecan dose , regimen or line of therapy having an impact on this association | To date , studies of irinotecan pharmacogenetics have mostly focused on the effect of the UGT1A1 * 28 allele on irinotecan-related toxicity .
However , the clinical utility of routine UGT1A1 * 28 genotyping to pre-emptively adjust irinotecan dosage is dependent upon whether UGT1A1 * 28 also affects patient survival following irinotecan therapy .
Previous observational studies evaluating the influence of UGT1A1 * 28 on survival have shown contradictory results . | Purpose : Inherited variations in drug metabolizing enzymes may influence drug efficacy . This phase II study assesses the impact of second-line weekly irinotecan (CPT-11)/docetaxel in non-small cell lung cancer ( NSCLC ) patients , and gauges the uridine diphosphate glucuronosyl transferase ( UGT1A1 ) polymorphism influence in toxicity and antitumor activity . Experimental Design : Fifty-one patients with NSCLC treated with at least one prior chemotherapy regimen were enrolled . Patients received irinotecan 70 mg/m2 followed by docetaxel 25 mg/m2 . Both drugs were given on days 1 , 8 , and 15 every 28 days . UGT1A1 polymorphism were analyzed in blood sample s of 47 patients . The UGT1A1 polymorphism are classified according to the number of TA repeats in the promoter region of this gene . Results : Three patients ( 6 % ) achieved a partial response and nineteen patients ( 37 % ) had stable disease . Median survival was 8 months ( 95 % CI : 4.8–11.2 ) and 1-year survival 30 % . Grade 3–4 hematologic toxicity was low ( less than 10 % of patients ) ; 15 % of patients had grade 3 asthenia and 25 % of patients had grade 3/4 diarrhea . The frequency of UGT1A1 genotypes was as follows : 6/6 49 % , 6/7 36 % , and 7/7 15 % . No differences in toxicity were observed according to UGT1A1 polymorphism . A nonsignificant improvement in time to progression ( 4 vs. 3 months ) and median survival ( 11 vs. 8 months ) was detected in patients with the variant alleles ( 6/7 and 7/7 ) . Conclusions : This weekly irinotecan/docetaxel regimen has shown an acceptable toxicity profile while encouraging median and 1-year survival in heavily pretreated NSCLC patients . The tendency to better prognosis in patients carrying the variant genotypes 6/7 and 7/7 of UGT1A1 gene requires further validation Background : The impact of thymidylate synthase ( TYMS ) and UDP-glucoronosyltransferase 1A ( UGT1A ) germline polymorphisms on the outcome of colorectal cancer ( CRC ) patients treated with irinotecan plus 5-fluorouracil ( irinotecan/5FU ) is still controversial . Our objective was to define a genetic-based algorithm to select patients to be treated with irinotecan/5FU . Methods : Genotyping of TYMS ( 5′TRP and 3′UTR ) , UGT1A1 * 28 , UGT1A9 * 22 and UGT1A7 * 3 was performed in 149 metastatic CRC patients treated with irinotecan/5FU as first-line chemotherapy enrolled in a r and omised phase 3 study . Their association with response , toxicity and survival was investigated by univariate and multivariate statistical analysis . Results : TYMS 3TRP/3TRP genotype was the only independent predictor of tumour response ( OR=5.87 , 95 % confidence interval (CI)=1.68–20.45 ; P=0.005 ) . UGT1A1 * 28/*28 was predictive for haematologic toxicity ( OR=6.27 , 95 % CI=1.09–36.12 ; P=0.04 ) , specifically for neutropenia alone ( OR=6.40 , 95 % CI=1.11–37.03 ; P=0.038 ) or together with diarrhoea ( OR=18.87 , 95 % CI=2.14–166.67 ; P=0.008 ) . UGT1A9 * 1/*1 was associated with non-haematologic toxicity ( OR=2.70 , 95 % CI=1.07–6.82 ; P=0.035 ) . Haplotype VII ( all non-favourable alleles ) was associated with non-haematologic toxicity ( OR=2.11 , 95 % CI=1.12–3.98 ; P=0.02 ) . Conclusion : TYMS and UGT1A polymorphisms influence on tumour response and toxicities derived from irinotecan/5FU treatment in CRC patients . A genetic-based algorithm to optimise treatment individualisation is proposed Oxaliplatin and irinotecan have proven effective in the treatment of gastric cancer . We attempted to determine whether single nucleotide polymorphisms in ERCC1 , GST , TS and UGT1A1 predicted overall survival in gastric cancer patients receiving FOLFOX and /or FOLFIRI chemotherapy . Total genomic DNA was extracted from the whole blood of patients . The PCR-restriction fragment length polymorphism technique was applied in order to detect the known variant sites of ERCC1 , GST , TS and UGT1A1 . The response rate of FOLFOX ( N=75 ) was 24 % . Grade 3 - 4 neutropenia and neurotoxicity were observed at frequencies of 34.7 and 16 % , respectively . TTP and OS of first-line administration of FOLFOX ( N=35 ) were 3.1 months ( 95 % CI , 0.1 - 6.1 months ) and 13.9 months ( 95 % CI , 12.2 - 15.6 months ) , respectively . Only the GSTM1 positive genotype exhibited a significantly better time to progression ( P=0.023 ) . However , significant genotypic variation of TS , GST and ERCC1 , which was assumed to affect the activity of oxaliplatin , was not observed to affect RR , toxicity and overall survival . The response rate of FOLFIRI ( N=74 ) was 23 % . Grade 3 - 4 neutropenia and diarrhea were observed in 55.4 and 9.5 % of cases , respectively . TTP and OS of first-line administration of FOLFIRI ( N=33 ) was 4.9 months ( 95 % CI , 3.5 - 6.4 months ) and 19.0 months ( 95 % CI , 8.5 - 29.5 months ) . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia . However , significant genotypic variation of UGT1A1 , which was assumed to affect irinotecan toxicity , was not observed to affect RR , toxicity or survival . In this study , the GSTM1 positive genotype evidence d a significantly better time to progression in cases of advanced gastric cancer being treated with FOLFOX . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia in cases of advanced gastric cancer treated with FOLFIRI PURPOSE Irinotecan plus cisplatin ( IP ) improved survival over etoposide plus cisplatin ( EP ) in Japanese patients with extensive-stage small-cell lung cancer ( E-SCLC ) . To confirm those results and discern the potential role of population -related pharmacogenomics ( PG ) in outcomes , we conducted a large r and omized trial of identical design to the Japanese trial in North American patients with E-SCLC . PATIENTS AND METHODS Patients were r and omly assigned to IP ( irinotecan 60 mg/m(2 ) on days 1 , 8 , and 15 ; cisplatin 60 mg/m(2 ) day 1 , every 4 weeks ) or EP ( etoposide 100 mg/m(2 ) on days 1 through 3 ; cisplatin 80 mg/m(2 ) day 1 , every 3 weeks ) . Blood specimens for genomic DNA analysis were collected before r and om assignment in 169 patients . RESULTS Of 671 patients , 651 were eligible ( 324 and 327 patients in the IP and EP arms , respectively ) . Response rates with IP and EP were 60 % and 57 % , respectively ( P = .56 ) . Median progression-free survival for IP and EP was 5.8 and 5.2 months , respectively ( P = .07 ) . Median overall survival for IP and EP was 9.9 and 9.1 months , respectively ( P = .71 ) . Severe diarrhea was more common with IP ( 19 % v 3 % ) ; severe neutropenia and thrombocytopenia were higher with EP versus IP ( 68 % v 33 % and 15 % v 4 % , respectively ) . PG analysis showed that ABCB1 (C3435T)T/T ( membrane transport ) was associated with IP-related diarrhea ; UGT1A1 (G-3156A)A/A ( drug metabolism ) was associated with IP-related neutropenia . CONCLUSION This large North American trial failed to confirm the previously reported survival benefit observed with IP in Japanese patients . Both regimens produced comparable efficacy , with less hematologic and greater gastrointestinal toxicity with IP . These results emphasize the potential importance of PG in interpreting trials of cancer therapy BACKGROUND The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined . Our aim was to investigate whether combination treatment is better than the sequential administration of the same drugs in patients with advanced colorectal cancer . METHODS In this open-label , r and omised , phase 3 trial , we r and omly assigned patients ( 1:1 ratio ) with advanced , measurable , non-resectable colorectal cancer and WHO performance status 0 - 2 to receive either first-line treatment with bolus ( 400 mg/m(2 ) ) and infusional ( 2400 mg/m(2 ) ) fluorouracil plus leucovorin ( 400 mg/m(2 ) ) ( simplified LV5FU2 regimen ) , second-line LV5FU2 plus oxaliplatin ( 100 mg/m(2 ) ) ( FOLFOX6 ) , and third-line LV5FU2 plus irinotecan ( 180 mg/m(2 ) ) ( FOLFIRI ) or first-line FOLFOX6 and second-line FOLFIRI . Chemotherapy was administered every 2 weeks . R and omisation was done central ly using minimisation ( minimisation factors were WHO performance status , previous adjuvant chemotherapy , number of disease sites , and centre ) . The primary endpoint was progression-free survival after two lines of treatment . Analyses were by intention-to-treat . This trial is registered at Clinical Trials.gov , NCT00126256 . FINDINGS 205 patients were r and omly assigned to the sequential group and 205 to the combination group . 161 ( 79 % ) patients in the sequential group and 161 ( 79 % ) in the combination group died during the study . Median progression-free survival after two lines was 10·5 months ( 95 % CI 9·6 - 11·5 ) in the sequential group and 10·3 months ( 9·0 - 11·9 ) in the combination group ( hazard ratio 0·95 , 95 % CI 0·77 - 1·16 ; p=0·61 ) . All six deaths caused by toxic effects of treatment occurred in the combination group . During first-line chemotherapy , significantly fewer severe ( grade 3 - 4 ) haematological adverse events ( 12 events in 203 patients in sequential group vs 83 events in 203 patients in combination group ; p<0·0001 ) and non-haematological adverse events ( 26 events vs 186 events ; p<0·0001 ) occurred in the sequential group than in the combination group . INTERPRETATION Upfront combination chemotherapy is more toxic and is not more effective than the sequential use of the same cytotoxic drugs in patients with advanced , non-resectable colorectal cancer . FUNDING Sanofi-Aventis France The primary end point of the study was the analysis of associations between polymorphisms with putative influence on 5-fluorouracil/irinotecan activity and progression-free survival ( PFS ) of patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy . Peripheral blood sample s from 146 prospect ively enrolled patients were used for genotyping polymorphisms in thymidylate synthase ( TS ) , methylenetetrahydrofolate reductase ( MTHFR ) , excision repair cross-complementation group-1 ( ERCC 1 ) xeroderma pigmentosum group-D ( XPD ) , X-ray cross-complementing-1 ( XRCC 1 ) , X-ray cross-complementing-3 ( XRCC 3 ) and uridine diphosphate-glucuronosyltransferases-A1 ( UGT1 A1 ) . TS 3′-UTR 6+/6 + and XRCC3 - 241 C/C genotypes were associated with adverse PFS . Hazard ratio for PFS achieved 2.89 ( 95 % confidence interval=1.56–5.80 ; P=0.002 ) in 30 patients ( 20 % ) with both risk genotypes . Risk for Grade III – IV neutropenia was significantly associated with UGT1A1 * 28 7/7 genotype . These promising findings deserve further investigations and their validation in independent prospect i ve studies PURPOSE C and i date predictive biomarkers for irinotecan and oxaliplatin were assessed in 1,628 patients in Fluorouracil , Oxaliplatin , CPT-11 : Use and Sequencing ( FOCUS ) , a large r and omized trial of fluorouracil alone compared with fluorouracil and irinotecan and compared with fluorouracil and oxaliplatin in advanced colorectal cancer . METHODS The c and i date biomarkers were : tumor immunohistochemistry for MLH1/MSH2 , p53 , topoisomerase-1 ( Topo1 ) , excision repair cross-complementing gene 1 ( ERCC1 ) , O-6-methylguanine-DNA-methyltranserase ( MGMT ) , and cyclooxygenase 2 ( COX2 ) ; germline DNA polymorphisms in GSTP1 , ABCB1 , XRCC1 , ERCC2 , and UGT1A1 . These were screened in more than 750 patients for interaction with benefit from irinotecan or oxaliplatin ; two markers ( Topo1 and MLH1/MSH2 ) met criteria to be taken forward for analysis in the full population . Primary end points were progression-free survival ( PFS ) and overall survival . RESULTS One thous and three hundred thirteen patients ( 81 % ) were assessable for Topo1 immunohistochemistry ( low , < 10 % ; moderate , 10 % to 50 % ; or high , > 50 % tumor nuclei ) . In patients with low Topo1 , PFS was not improved by the addition of either irinotecan ( hazard ratio [ HR ] , 0.98 ; 95 % CI , 0.78 to 1.22 ) or oxaliplatin ( HR , 0.85 ; 95 % CI , 0.68 to 1.07 ) ; conversely , patients with moderate/high Topo1 benefited from the addition of either drug ( HR , 0.48 to 0.70 in all categories ; interaction P = .005 ; overall , P = .001 for irinotecan ; P = .05 for oxaliplatin ) . High Topo1 was associated with a major overall survival benefit with first-line combination chemotherapy ( HR , 0.60 ; median benefit , 5.3 months ) ; patients with moderate or low Topo1 did not benefit ( HR , 0.92 and 1.09 , respectively ; interaction P = .005 ) . MLH1/MSH2 did not show significant interaction with treatment , although the low rate of loss ( 4.4 % ) limits the power of the study for this biomarker . CONCLUSION Topo1 immunohistochemistry identified sub population s that did or did not benefit from irinotecan , and possibly also from oxaliplatin . If verified independently , this information will contribute to the individualization of treatment for colorectal cancer Hypothesis : Irinotecan-containing regimens are known to be active and tolerable in patients with non-small cell lung cancer ( NSCLC ) . A r and omized phase II trial was conducted to evaluate the efficacy of irinotecan plus paclitaxel or gemcitabine for previously untreated stage IIIB or stage IV NSCLC . Patients and Methods : Previously untreated patients with adequate organ function who gave written informed consent were r and omly assigned to receive irinotecan ( 50 mg/m2 on days 1 , 8 , and 15 ) plus paclitaxel ( 180 mg/m2 on day 1 ) every 4 weeks ( IP group ) or irinotecan ( 100 mg/m2 on days 1 and 8) plus gemcitabine ( 1000 mg/m2 on days 1 and 8) every 3 weeks ( IG group ) . The primary endpoint was the response rate . We also evaluated the relationship of response and toxicity to polymorphisms of the uridine diphosphate glucuronosyltransferase ( UGT ) gene . Results : Eighty patients were enrolled , and 78 patients were eligible ( 38 in the IP group and 40 in the IG group ) . The response rate was 31.6 % ( 95 % confidence interval : 17.5–48.7 % ) in the IP group and 20.0 % ( 9.1–35.6 % ) in the IG group . The median progression-free survival time was 86 days and 145 days , respectively . Both regimens were well tolerated . The most common severe adverse event was grade 4 neutropenia ( 36.8 % and 10.0 % , respectively ) , which was associated with UGT1A1 * 6 and UGT1A1 * 27 . UGT polymorphisms did not correlate with response . Conclusions : Irinotecan plus paclitaxel may be more active against NSCLC than irinotecan plus gemcitabine . The UGT1A1 * 6 and UGT1A1 * 27 genotypes might be useful predictors of grade 4 neutropenia in patients who receive irinotecan-based chemotherapy PURPOSE Severe toxicity is commonly observed in cancer patients receiving irinotecan . UDP-glucuronosyltransferase 1A1 ( UGT1A1 ) catalyzes the glucuronidation of the active metabolite SN-38 . This study prospect ively evaluated the association between the prevalence of severe toxicity and UGT1A1 genetic variation . PATIENTS AND METHODS Sixty-six cancer patients with advanced disease refractory to other treatments received irinotecan 350 mg/m(2 ) every 3 weeks . Toxicity and pharmacokinetic data were measured during cycle 1 . UGT1A1 variants ( -3279G > T , -3156G > A , promoter TA indel , 211G > A , 686C > A ) were genotyped . RESULTS The prevalence of grade 4 neutropenia was 9.5 % . Grade 4 neutropenia was much more common in patients with the TA indel 7/7 genotype ( 3 of 6 patients ; 50 % ) compared with 6/7 ( 3 of 24 patients ; 12.5 % ) and 6/6 ( 0 of 29 patients ; 0 % ) ( P = .001 ) . The TA indel genotype was significantly associated with the absolute neutrophil count nadir ( 7/7 < 6/7 < 6/6 , P = .02 ) . The relative risk of grade 4 neutropenia was 9.3 ( 95 % CI , 2.4 to 36.4 ) for the 7/7 patients versus the rest of the patients . Pretreatment total bilirubin levels ( mean + /- st and ard deviation ) were significantly higher in patients with grade 4 neutropenia ( 0.83 + /- 0.08 mg/dL ) compared to those without grade 4 neutropenia ( 0.47 + /- 0.03 mg/dL ; P < .001 ) . The -3156G > A variant seemed to distinguish different phenotypes of total bilirubin within the TA indel genotypes . The -3156 genotype and the SN-38 area under the concentration versus time curve were significant predictors of ln(absolute neutrophil count nadir ; r(2 ) = 0.51 ) . CONCLUSION UGT1A1 genotype and total bilirubin levels are strongly associated with severe neutropenia , and could be used to identify cancer patients predisposed to the severe toxicity of irinotecan . The hypothesis that the -3156G > A variant is a better predictor of UGT1A1 status than the previously reported TA indel requires further testing |
10,596 | 14,526,862 | Runners can reduce risk of injury by using established training programs that gradually increase distance or time of running and provide appropriate rest .
Orthoses and heel lifts can correct malalignments of the leg .
Prevention addresses factors proven to cause running injuries . | OBJECTIVE To present a practical approach for preventing running injuries .
QUALITY OF EVIDENCE Much of the research on running injuries is in the form of expert opinion and comparison trials .
Recent systematic review s have summarized research in orthotics , stretching before running , and interventions to prevent soft tissue injuries .
MAIN MESSAGE The most common factors implicated in running injuries are errors in training methods , inappropriate training surfaces and running shoes , malalignment of the leg , and muscle weakness and inflexibility . | Eighty-seven male inmates from a state prison and 70 inmates from a county jail volunteered as subjects . The subjects , age 20 to 35 yrs , were assigned r and omly into a control or exercise group . Their Vo2max and treadmill performance values were determined before and after a 20 week jogging program . Training intensity was between 85 and 90 percent of maximum heart rate and involved workouts 3 days/week for 15 , 30 , or 45-min duration at the state prison and for 30-min 1 , 3 , or 5 days/week at the country jail . Cardiorespiratory fitness improved in direct proportion to frequency and duration of training . Injury , occurred in 22 % , 24 % and 54 % of the 15 , 30 , and 45-min duration groups and in 0 % , 12 % , and 39 % of the 1 , 3 , and 5-day/week groups , respectively . Attrition result ing from injury occurred in 0 % , 0 % , and 17 % and in 0 % , 4 % , and 6 % of the same respective groups . Attrition due to lack of interest was similar for all training groups ( 25 % ) , but was significantly lower in the control groups ( 10 % ) . Although the results showed a greater increase in cardiorespiratory fitness for the 45-min duration and 5-day/week groups , these programs are not recommened for beginning joggers because of the significantly greater percent of injuries Three hundred fifty male recruits were r and omly allocated to either the st and ard recruit training program ( N = 180 ) or substituted a weighted-march activity for all formal run periods ( N = 170 ) in the physical training program . All injuries were seen at a single medical facility , and the cause , location , and severity of injury were recorded in the medical documents . Lower-limb injuries constituted 79.8 % of all Run injuries and 61.1 % of all Walk injuries . Foot ( 18.9 % ) , knee ( 16.7 % ) , ankle ( 13.3 % ) , and shoulder ( 8.9 % ) were the most common sites of injury in the Walk group . In the Run group , the most common sites were knee ( 32.1 % ) , ankle ( 18.3 % ) , foot ( 11.9 % ) , and shin ( 7.3 % ) . There were two stress fractures ( tibial ) in the Run group and none in the Walk group , giving the Run group an incidence of 1.1 % . There were 10 medical discharges in the Walk group and 16 in the Run group . Ten ( 62.5 % ) of the Run and 2 ( 20 % ) of the Walk discharges were due to lower-limb causes . Of these , only 1 ( 10 % ) of the Walk and 4 ( 25 % ) of the Run injuries were not considered to be pre-existing conditions . Marching ( 30.0 % ) , physical training ( 25.5 % ) , and the obstacle course ( 11.1 % ) were the most frequent causes of injury in the Walk group . In the Run group , the leading causes were running ( 36.6 % ) , physical training ( 19.2 % ) , and the obstacle course ( 14.6 % ) . Running was the major cause of knee injury in the Run group ( 17/35 ) , whereas physical training was the major cause of knee injury in the Walk group ( 5/15 ) . Running was also the major cause of other lower-limb injuries in the Run group ( 19/58 ) , whereas marching was the major cause in the Walk group ( 19/50 ) . Lower-limb injuries were more frequent in the Run group , with running cited as the major cause of these injuries Three hundred fifty male recruits were r and omly allocated to either the st and ard recruit training program ( N = 180 ) or substituted a weighted march activity for all running periods in the physical training program ( N = 170 ) . There were no other differences in the formal training program . The incidence of injury was 37.6 and 46.6 % in the walk and run groups , respectively . The rate of injury was 52.9/100 recruits in the walk group and 61.7/100 in the run group . The exposure incidence was 12.8/1,000 hours of physical training in the walk group and 14.9/1,000 hours in the run group . There was no statistically significantly difference in the total number of injured recruits in the two groups ( 64 vs. 85 , chi(2 ) = 2.90 , p = 0.09 , relative risk [ RR ] = 1.24 ) . There were , however , significantly more lower-limb ( 43 vs. 75 , chi(2 ) = 9.77 , p = 0.0018 , RR = 1.65 ) and knee injuries ( 15 vs. 35 , chi(2 ) = 6.54 , p = 0.011 , RR = 2.14 ) in the Run group . Lower-limb injuries constituted 79.8 % of all Run injuries and 61.1 % of all Walk injuries . Injuries in the Run group produced more morbidity , with nearly double the number of days of restriction , hospitalization , and not fit for duty . St and ardized morbidity rates showed an average of 5.4 days of restriction per injury in the Run group and 3.96 days of restriction per injury in the Walk group . Reduction of running distance in the physical training program result ed in significant reductions in both the incidence of lower-limb injury and the overall severity of injury Objective : To determine if measurable lower extremity alignment is a risk factor for overuse running injuries . Design : Prospect i ve cohort study . Setting : Thirty-two week marathon training program . Patients or Participants : Three hundred fifty-five volunteers from the marathon training program began the study ; 255 finished the study . Interventions : None . Main Outcome Measures : Past training and injury history was determined by question naire , and five lower extremity alignment measures were performed at the beginning of the training program : arch index ( AI ) , heel valgus ( HV ) , knee tubercle-sulcus angle ( TSA ) , knee varus ( KV ) , and leg-length difference ( LLD ) . Overuse injuries , incurred by the runners and categorized by anatomic parts , were recorded during the training period . Results : Ninety subjects experienced overuse injuries . Multivariate analyses with stepwise Poisson regression showed few consistent relationships between alignment and overuse injury rates . Higher AI was protective against overall injuries and knee injuries ; higher HV was protective against knee and foot injuries ; higher TSA was associated with shin injuries ; higher KV was associated with shin injuries ; and low LLD was associated with more overall injuries . Conclusions : Minor variations in lower extremity alignment do not appear conclusively to be major risk factors for overuse injuries in runners . Because of the study limitations and the likely multifactorial nature of running injuries , further study is suggested , perhaps in more novice runners The purpose of this intervention study was to prove that increasing flexibility of the hamstring musculotendinous unit would decrease the number of lower extremity overuse injuries that occur in military infantry basic trainees . Two different companies going through basic training at the same time were used . Hamstring flexibility was checked at the beginning and at the end of the 13-week infantry basic training course . The control company ( N 148 ) proceeded through normal basic training . The intervention company ( N 150 ) followed the same program but added three hamstring stretching sessions to their already scheduled fitness program . All subsequent lower extremity overuse injuries were recorded through the troop medical clinic . Hamstring flexibility increased significantly in the intervention group compared with the control group . The number of injuries was also significantly lower in the intervention group . Forty-three injuries occurred in the control group for an incidence rate of 29.1 % , compared with 25 injuries in the intervention group for an incidence rate of 16.7 % . Thus , in this study , the number of lower extremity overuse injuries was significantly lower in infantry basic trainees with increased hamstring flexibility Sedentary individuals , particularly new military recruits , who start a physical training program have a substantial risk of developing an overuse injury of the lower limb . In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training . The experimental group consisted of 237 r and omly selected new recruits , while 1151 recruits were the control group . Insoles were given to the experimental group and compliance was monitored . A panel of doctors documented and classi fied all injuries occurring during the 9 week period . A total of 54 ( 22.8 % ) and 237 ( 31.9 % ) injuries were reported in the experimental and control groups , re spectively . In both groups , the majority of injuries were overuse ( experimental group , 90.7 % ; control group , 86.4 % ) . The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower ( P < 0.05 ) in the experimental group . The mean incidence of stress fractures was lower in the experimental group but not significantly so ( 0.05 < P < 0.1 ) . This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles The purpose of this study was to evaluate the effect of a health education intervention on running injuries . The intervention consisted of information on , and the sub sequent performance of , st and ardized warm-up , cool- down , and stretching exercises . Four hundred twenty- one male recreational runners were matched for age , weekly running distance , and general knowledge of preventing sports injuries . They were r and omly split into an intervention and a control group : 167 control and 159 intervention subjects participated throughout the study . During the 16-week study , both groups kept a daily diary on their running distance and time , and reported all injuries . In addition , the intervention group was asked to note compliance with the st and ardized program . At the end of the study period , knowledge and attitude were again measured . There were 23 injuries in the control group and 26 in the intervention group . Injury incidence for control and intervention sub jects was 4.9 and 5.5 running injuries per 1000 hours , respectively . The intervention was not effective in re ducing the number of running injuries ; it proved signifi cantly effective ( P < 0.05 ) in improving specific knowl edge of warm-up and cool-down techniques in the intervention group . This positive change can perhaps be regarded as a first step on the way to a change of behavior , which may eventually lead to a reduction of running injuries As the number of runners has increased dramatically , so has the incidence of running-related injuries . In order to determine what training factors are associated with running-related injuries , as well as what percentage of injured runners seeks professional medical attention , a r and om sample of entrants to a 10 kilometer race was asked to complete a question naire . There were 451 respondents , 355 men and 96 women , with a nonre sponse rate of 12.7 % . Nonrespondents did not differ from respondents with regard to age or sex . Forty- seven percent of respondents indicated that they had sustained a running-related injury in the last 2 years . Injured runners differed significantly from noninjured runners in that they were more likely to have ( 1 ) run more miles per week , ( 2 ) run more days per week , ( 3 ) run a faster pace , ( 4 ) run more races in the last year , ( 5 ) stretched before running , and ( 6 ) not participated regularly in other sports . Associated with injury , but not statistically significant , were those who had run mara thons and had done muscle-strengthening exercises . No association was found with regard to the length of time running , running surfaces , part of the foot first contacting the ground , or running intervals , sprints , or hills . Seventy percent of those injured sought profes sional medical care , with 76 % of these having a good or excellent recovery from their injuries . Compliance with medical advice correlated well with treatment suc cess This prospect i ve study of 583 habitual runners used baseline information to examine the relationship of several suspected risk factors to the occurrence of running-related injuries of the lower extremities that were severe enough to affect running habits , cause a visit to a health professional , or require use of medication . During the 12-month follow-up period , 252 men ( 52 % ) and 48 women ( 49 % ) reported at least one such injury . The multiple logistic regression results identified that running 64.0 km ( 40 miles ) or more per week was the most important predictor of injury for men during the follow-up period ( odds ratio = 2.9 ) . Risk also was associated with having had a previous injury in the past year ( odds ratio = 2.7 ) and with having been a runner for less than 3 years ( odds ratio = 2.2 ) . These results suggest that the incidence of lower-extremity injuries is high for habitual runners , and that for those new to running or those who have been previously injured , reducing weekly distance is a reasonable preventive behavior In a prospect i ve study , quantitative measures of the structure of the longitudinal arch of the foot were established and related to the incidence of stress fractures in the bones of the lower limbs of military recruits . In addition , the role of a semirigid orthotic device ( Langer military stress orthotic ) in preventing stress fractures was evaluated as a function of the structure of the longitudinal arch . Femoral and tibial stress fractures were found to be more prevalent in the presence of feet with high arches , whereas the incidence of metatarsal fractures was higher in feet with low arches . The use of an orthotic device reduced the incidence of femoral stress fractures only in the presence of feet with high arches and the incidence of metatarsal fractures only among feet with low arches . The findings suggest that the normal foot with a low arch acts as a better shock absorber than the normal foot with a high arch , and that an orthotic device may improve the shock absorbing capacity of the arch Three hundred fifty male recruits were divided into two groups : Walk ( N = 170 ) and Run ( N = 180 ) . A physical screen was performed before the commencement of recruit training consisting of a visual assessment of the feet looking for pes planus , pes cavus , and deformities of the toes . Each recruit was also asked if he had sustained any injury in the preceding 2 years . The visual findings and history of prior injury were noted and compared with actual injuries sustained during the 12-week training course . Fifty-three subjects in the Walk group and 54 in the Run group were identified as being at risk as a consequence of the screen . The sensitivity of the screen for predicting the subsequent injury was 34.4 % in the Walk group and 31.8 % in the Run group . The specificity was 72.6 and 77.4 % in the Walk and Run groups , respectively . The predictive value of the test was 44.9 % in the Walk group and 50.9 % in the Run group . When reinjury was examined , the sensitivities fell to 9.4 % ( Walk ) and 4.7 % ( Run ) and the specificities to 57.5 % ( Walk ) and 50.5 % ( Run ) . The screen correctly identified only 1 of 10 medical discharges in the Walk group and 2 of 16 in the Run group . The screening examination had poor sensitivity , specificity , and predictive value , and more than half of those thought to be at risk did not subsequently sustain an injury . Anecdotal beliefs that improvements in medical screening would reduce recruit wastage were not borne out . Abnormalities of the foot ( pes planus , pes cavus , hallux valgus ) were not significant factors in the development of injury during recruit training This study investigated effects of ankle dorsiflexion range and pre-exercise calf muscle stretching on relative risk of selected injuries in 1093 male Army recruits undertaking 12 weeks of intensive training . Prior to training , ankle dorsiflexion range was measured and recruits were allocated to stretch and control groups using a quasi-r and om procedure . The stretch group stretched calf muscles under supervision prior to all intense exercise . The control group stretched upper limb muscles instead . Forty-eight injuries were recorded . Survival analysis indicated that ankle dorsiflexion range was a strong predictor of injury ( p = 0.03 ) . Definitive evidence of an effect of stretching on injury risk was not found ( p = 0.76 ) , but the sample size may have been insufficient to detect such an effect PURPOSE This study investigated the effect of muscle stretching during warm-up on the risk of exercise-related injury . METHODS 1538 male army recruits were r and omly allocated to stretch or control groups . During the ensuing 12 wk of training , both groups performed active warm-up exercises before physical training sessions . In addition , the stretch group performed one 20-s static stretch under supervision for each of six major leg muscle groups during every warm-up . The control group did not stretch . RESULTS 333 lower-limb injuries were recorded during the training period , including 214 soft-tissue injuries . There were 158 injuries in the stretch group and 175 in the control group . There was no significant effect of preexercise stretching on all-injuries risk ( hazard ratio [ HR ] = 0.95 , 95 % CI 0.77 - 1.18 ) , soft-tissue injury risk ( HR = 0.83 , 95 % CI 0.63 - 1.09 ) , or bone injury risk ( HR = 1.22 , 95 % CI 0.86 - 1.76 ) . Fitness ( 20-m progressive shuttle run test score ) , age , and enlistment date all significantly predicted injury risk ( P < 0.01 for each ) , but height , weight , and body mass index did not . CONCLUSION A typical muscle stretching protocol performed during preexercise warm-ups does not produce clinical ly meaningful reductions in risk of exercise-related injury in army recruits . Fitness may be an important , modifiable risk factor |
10,597 | 29,855,423 | Both DRS-targeted and general QI interventions were effective , particularly when baseline attendance levels were low .
All commonly used QI components and BCTs were associated with significant improvements , particularly in those with poor attendance .
However , BCTs targeting emotional factors around DRS were under-represented .
Cost-effectiveness increased when DRS attendance was lower and with longer screening intervals .
R and omised controlled trial evidence indicates that QI interventions incorporating specific BCT components are associated with meaningful improvements in DRS attendance compared with usual care .
Interventions generally used appropriate BCTs that target important barriers to screening attendance , with a high probability of being cost-effective . | BACKGROUND Diabetic retinopathy screening ( DRS ) is effective but uptake is suboptimal .
OBJECTIVES To determine the effectiveness of quality improvement ( QI ) interventions for DRS attendance ; describe the interventions in terms of QI components and behaviour change techniques ( BCTs ) ; identify theoretical determinants of attendance ; investigate coherence between BCTs identified in interventions and determinants of attendance ; and determine the cost-effectiveness of QI components and BCTs for improving DRS . | OBJECTIVE To evaluate the impact of systematic patient evaluation and patient and provider feedback on the processes and intermediate outcomes of diabetes care in Independent Practice Association model internal medicine practice s. RESEARCH DESIGN AND METHODS Nine practice s providing care to managed care patients were r and omly assigned as intervention or comparison sites . Intervention-site subjects had Annual Diabetes Assessment Program ( ADAP ) assessment s ( HbA(1c ) , blood pressure , lipids , smoking , retinal photos , urine microalbumin , and foot examination ) at years 1 and 2 . Comparison-site subjects had ADAP assessment s at year 2 . At Intervention sites , year 1 ADAP results were review ed with subjects , mailed to providers , and incorporated into electronic medical records with guideline -generated suggestions for treatment and follow-up . Medical records were evaluated for both groups for the year before both the year 1 and year 2 ADAP assessment s. Processes and intermediate outcomes were compared using linear and logistic mixed hierarchical models . RESULTS Of 284 eligible subjects , 103 of 173 ( 60 % ) at the Intervention sites and 71 of 111 ( 64 % ) at the comparison sites participated ; 83 of 103 ( 81 % ) of the intervention-site subjects returned for follow-up at year 2 . Performance of the six recommended assessment s improved in intervention-site subjects at year 2 compared with year 1 ( 5.8 vs. 4.3 , P = 0.0001 ) and compared with comparison-site subjects at year 2 ( 4.2 , P = 0.014 ) . No significant changes were noted in intermediate outcomes . CONCLUSIONS The ADAP significantly improved processes of care but not intermediate outcomes . Additional interventions are needed to improve intermediate outcomes BACKGROUND In the Medicare Modernization Act of 2003 , Congress required the Centers for Medicare and Medicaid Services to test the commercial disease-management model in the Medicare fee-for-service program . METHODS The Medicare Health Support Pilot Program was a large , r and omized study of eight commercial programs for disease management that used nurse-based call centers . We r and omly assigned patients with heart failure , diabetes , or both to the intervention or to usual care ( control ) and compared them with the use of a difference-in-differences method to evaluate the effects of the commercial programs on the quality of clinical care , acute care utilization , and Medicare expenditures for Medicare fee-for-service beneficiaries . RESULTS The study included 242,417 patients ( 163,107 in the intervention group and 79,310 in the control group ) . The eight commercial disease-management programs did not reduce hospital admissions or emergency room visits , as compared with usual care . We observed only 14 significant improvements in process-of-care measures out of 40 comparisons . These modest improvements came at substantial cost to the Medicare program in fees paid to the disease-management companies ( $ 400 million ) , with no demonstrable savings in Medicare expenditures . CONCLUSIONS In this large study , commercial disease-management programs using nurse-based call centers achieved only modest improvements in quality -of-care measures , with no demonstrable reduction in the utilization of acute care or the costs of care Background and objectives Many clinical management guidelines for chronic diseases have been published , but they have not been put into practice by busy clinicians at primary care levels . This study evaluates the implementation of national guidelines incorporated within a structured diabetes and hypertension clinical record ( SR ) in Cape Town in a r and omised controlled trial ( RCT ) . Methods Eighteen public sector community health centres ( CHC ) were r and omly selected and allocated as intervention or control CHC . At each clinic , 25 patients with diabetes and 35 patients with hypertension were enrolled at baseline . Question naires were completed , blood sample s were collected , blood pressure ( BP ) and anthropometric measures were taken and patient records were audited . SR with clinical guideline prompts were introduced at the intervention clinics after training doctors in their use and suggestions to incorporate them in regular patient records . Contact was maintained during the year of intervention with the clinic staff . A follow-up survey was conducted 1 year later to assess BP and HbA1c , and the patient records were examined to ascertain the extent of use of the SR in the intervention clinics . In-depth interviews were conducted with doctors and nurses to record their response to the intervention . Results The intervention evaluated in this RCT had no impact on either diabetes or hypertension control . In the intervention clinics , less than 60 % of the patient folders contained the SR and when present was seldom used . Although the staff were well disposed to the research team , their workload prohibited them from undertaking a true evaluation of the SR , and overall they did not perceive the SR as supporting their current process of patient care . Conclusions No benefit to diabetes of hypertension care by introducing and availability of the staff in the use of the SR was shown in this RCT . The process measures suggest that the SR was not widely used by the healthcare provided in the primary care clinics OBJECTIVE —The purpose of this study was to determine whether implementation of a multicomponent organizational intervention can produce significant change in diabetes care and outcomes in community primary care practice s. RESEARCH DESIGN AND METHODS —This was a group-r and omized , controlled clinical trial evaluating the practical effectiveness of a multicomponent intervention ( TRANSLATE ) in 24 practice s. The intervention included implementation of an electronic diabetes registry , visit reminders , and patient-specific physician alerts . A site coordinator facilitated previsit planning and a monthly review of performance with a local physician champion . The principle outcomes were the percentage of patients achieving target values for the composite of systolic blood pressure ( SBP ) < 130 mmHg , LDL cholesterol < 100 mg/dl , and A1C < 7.0 % at baseline and 12 months . Six process measures were also followed . RESULTS —Over 24 months , 69,965 visits from 8,405 adult patients with type 2 diabetes were recorded from 238 health care providers in 24 practice s from 17 health systems . Diabetes process measures increased significantly more in intervention than in control practice s , giving net increases as follows : foot examinations 35.0 % ( P < 0.0.001 ) ; annual eye examinations 25.9 % ( P < 0.001 ) ; renal testing 28.5 % ( P < 0.001 ) ; A1C testing 8.1%(P < 0.001 ) ; blood pressure monitoring 3.5 % ( P = 0.05 ) ; and LDL testing 8.6 % ( P < 0.001 ) . Mean A1C adjusted for age , sex , and comorbidity decreased significantly in intervention practice s ( P < 0.02 ) . At 12 months , intervention practice s had significantly greater improvement in achieving recommended clinical values for SBP , A1C , and LDL than control clinics ( P = 0.002 ) . CONCLUSIONS — Introduction of a multicomponent organizational intervention in the primary care setting significantly increases the percentage of type 2 diabetic patients achieving recommended clinical outcomes Technology and improved care coordination models can help diabetes educators and providers meet national care st and ards and provide culturally sensitive diabetes education that may improve diabetes outcomes . The purpose of the study was to evaluate the clinical usefulness of a nurse-led diabetes care program ( Comprehensive Diabetes Management Program , CDMP ) for poorly controlled Hispanic type 2 diabetes ( T2DM ) patients in an urban community health center setting . Patients were r and omized to the intervention condition ( IC ; n = 21 ) or an attention control condition ( AC ; n = 18 ) . IC and AC conditions were compared on rates of adherence to national clinical practice guidelines ( blood glucose , blood pressure , foot exam , eye exam ) , and levels of diabetes distress , depression , and treatment satisfaction . IC patients had a significant improvement in A1C from baseline to 12-month follow-up compared with AC ( −1.6 % ± 1.4 % versus −0.6 % ± 1.1 % ; P = .01 ) . The proportion of IC patients meeting clinical goals at follow-up tended to be higher than AC for A1c ( IC = 45 % ; AC = 28 % ) , systolic blood pressure ( IC = 55 % ; AC = 28 % ) , eye screening ( IC = 91 % ; AC = 78 % ) , and foot screening , ( IC = 86 % ; AC = 72 % ) . Diabetes distress and treatment satisfaction also showed greater improvement for IC than AC ( P = .05 and P = .06 , respectively ) , with no differences for depression . The CDMP intervention was more effective than an attention control condition in helping patients meet evidence -based guidelines for diabetes care Abstract Objective . To study the effectiveness of a comprehensive diabetes programme in general practice that integrates patient-centred lifestyle counselling into structured diabetes care . Design and setting . Cluster r and omised trial in general practice s. Intervention . Nurse-led structured diabetes care with a protocol , record keeping , reminders , and feedback , plus training in motivational interviewing and agenda setting . Subjects . Primary care nurses in 58 general practice s and their 940 type 2 diabetes patients with an HbA1c concentration above 7 % , and a body mass index ( BMI ) above 25 kg/m2 . Main outcome measures . HbA1c , diet , and physical activity ( medical records and patient question naires ) . Results . Multilevel linear and logistic regression analyses adjusted for baseline outcomes showed that despite active nurse participation in the intervention , the comprehensive programme was no more effective than usual care after 14 months , as shown by HbA1c levels ( difference between groups = 0.13 ; CI 20.8–0.35 ) and diet ( fat ( difference between groups = 0.19 ; CI 20.82–1.21 ) ; vegetables ( difference between groups = 0.10 ; CI-0.21–0.41 ) ; fruit ( difference between groups = 20.02 ; CI 20.26–0.22 ) ) , and physical activity ( difference between groups = 21.15 ; CI 212.26–9.97 ) , or any of the other measures of clinical parameters , patient 's readiness to change , or quality of life . Conclusion . A comprehensive programme that integrated lifestyle counselling based on motivational interviewing principles integrated into structured diabetes care did not alter HbA1c or the lifestyle related to diet and physical activity . We thus question the impact of motivational interviewing in terms of its ability to improve routine diabetes care in general practice The objective of this study was to identify the baseline frequency of eye examinations for Medicare beneficiaries with diabetes in Montana and to determine whether a direct mail reminder increased eye examinations . Using Medicare Part A and Medicare Part B cl aims data , a cohort of Medicare beneficiaries with diabetes was defined . Eye examination cl aims were identified using billing codes specific for retinal examinations , as well as visits to ophthalmologists and optometrists during which retinal exams were likely to have been performed . A r and om sample of the identified beneficiaries with diabetes received a letter encouraging regular annual retinal examinations . In the first 3-month period after the mailing , the billed eye examination rate for those to whom letters were sent was 2.2 percentage points greater than the rate for those to whom letters were not sent ( 19.4 % vs 17.2 % ; relative risk , 1.13 ; 95 % confidence interval , 1.01 - 1.26 ) . However , 6 months after the letters were sent , there was no longer a significant difference in the rates for these 2 groups ( 32.9 % vs 32.4 % ; relative risk , 1.02 ; 95 % confidence interval , 0.94 - 1.10 ) . In this study , direct mail outreach initially influenced the proportion of Medicare beneficiaries receiving an eye examination , but this pattern was not sustained over the 6-month follow-up period OBJECTIVE To evaluate the effect of adding pharmacists to primary care teams on the management of hypertension and other cardiovascular risk factors in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We conducted a r and omized controlled trial with blinded ascertainment of outcomes within primary care clinics in Edmonton , Canada . Pharmacists performed medication assessment s and limited history and physical examinations and provided guideline -concordant recommendations to optimize medication management . Follow-up contact was completed as necessary . Control patients received usual care . The primary outcome was a ≥10 % decrease in systolic blood pressure at 1 year . RESULTS A total of 260 patients were enrolled , 57 % were women , the mean age was 59 years , diabetes duration was 6 years , and blood pressure was 129/74 mmHg . Forty-eight of 131 ( 37 % ) intervention patients and 30 of 129 ( 23 % ) control patients achieved the primary outcome ( odds ratio 1.9 [ 95 % CI 1.1–3.3 ] ; P = 0.02 ) . Among 153 patients with inadequately controlled hypertension at baseline , intervention patients ( n = 82 ) were significantly more likely than control patients ( n = 71 ) to achieve the primary outcome ( 41 [ 50 % ] vs. 20 [ 28 % ] ; 2.6 [ 1.3–5.0 ] ; P = 0.007 ) and recommended blood pressure targets ( 44 [ 54 % ] vs. 21 [ 30 % ] ; 2.8 [ 1.4–5.4 ] ; P = 0.003 ) . The 10-year risk of cardiovascular disease , based on changes to the UK Prospect i ve Diabetes Study Risk Engine , were predicted to decrease by 3 % for intervention patients and 1 % for control patients ( P = 0.005 ) . CONCLUSIONS Significantly more patients with type 2 diabetes achieved better blood pressure control when pharmacists were added to primary care teams , which suggests that pharmacists can make important contributions to the primary care of these patients OBJECTIVES To compare the effects of a tailored ( individualized ) and targeted ( design ed for a subgroup ) print intervention in promoting dilated fundus examinations ( DFEs ) in older African Americans and to determine whether other factors ( eg , demographics , preventive health practice s , health literacy score , behavioral intentions , and DFE rates ) are associated with getting a DFE . METHODS African Americans aged 65 years or older who had not had a DFE in at least 2 years were recruited from community setting s. Participants were r and omized to receive either a tailored or targeted newsletter . Telephone follow-up was conducted at 1 , 3 , and 6 months to ascertain eye examination status . All participant-reported DFEs were confirmed by contacting their eye doctor ( optometrist or ophthalmologist ) by telephone . Main Outcome Measure Eye doctor-confirmed DFE at 6 months . RESULTS Of the 329 participants enrolled , 128 ( 38.9 % ) had an eye doctor-confirmed DFE . No significant difference was noted in this measure by intervention group ( relative risk , 1.07 ; 95 % confidence interval , 0.82 - 1.40 ) , with 66 participants in the tailored group ( 40.2 % ) and 62 participants in the targeted group ( 37.6 % ) having an eye doctor-confirmed DFE . Based on logistic regression analysis , reading the newsletter ( odds ratio , 1.76 ; 95 % confidence interval , 1.08 - 2.87 ) and planning to make an appointment for a DFE ( odds ratio , 2.46 ; 95 % confidence interval , 1.42 - 4.26 ) were significant predictors for DFE . CONCLUSIONS The tailored and targeted interventions were equally effective in promoting eye doctor-confirmed DFEs at 6 months . Given the increased cost and effort associated with tailoring , our results suggest that well- design ed targeted print messages can motivate older African Americans to get DFEs . Trial Registration clinical trials.gov Identifier : NCT00649766 PURPOSE To evaluate the effects of a collaborative case management intervention for patients with poorly controlled type 2 diabetes on glycemic control , intermediate cardiovascular outcomes , satisfaction with care , and re source utilization . METHODS We conducted a r and omized controlled trial at two Department of Veterans Affairs Medical Centers involving 246 veterans with diabetes and baseline hemoglobin A(1C ) ( HbA(1C ) ) levels > or=7.5 % . Two nurse practitioner case managers worked with patients and their primary care providers , monitoring and coordinating care for the intervention group for 18 months through the use of telephone contacts , collaborative goal setting , and treatment algorithms . Control patients received educational material s and usual care from their primary care providers . RESULTS At the conclusion of the study , both case management and control patients remained under poor glycemic control and there was little difference between groups in mean exit HbA(1C ) level ( 9.3 % vs. 9.2 % ; difference = 0.1 % ; 95 % confidence interval : -0.4 % to 0.7 % ; P = 0.65 ) . There was also no evidence that the intervention result ed in improvements in low-density lipoprotein cholesterol level or blood pressure control or greater intensification in medication therapy . However , intervention patients were substantially more satisfied with their diabetes care , with 82 % rating their providers as better than average compared with 64 % of patients in the control group ( P = 0.04 ) . CONCLUSION An intervention of collaborative case management did not improve key physiologic outcomes for high-risk patients with type 2 diabetes . The type of patients targeted for intervention , organizational factors , and program structure are likely critical determinants of the effectiveness of case management . Health systems must underst and the potential limitations before expending substantial re sources on case management , as the expected improvements in outcomes and downstream cost savings may not always be realized OBJECTIVE To conduct a 1-year r and omized clinical trial to evaluate a remote comprehensive diabetes self-management education ( DSME ) intervention , Diabetes TeleCare , administered by a dietitian and nurse/certified diabetes educator ( CDE ) in the setting of a federally qualified health center ( FQHC ) in rural South Carolina . RESEARCH DESIGN AND METHODS Participants were recruited from three member health centers of an FQHC and were r and omized to either Diabetes TeleCare , a 12-month , 13-session curriculum delivered using telehealth strategies , or usual care . RESULTS Mixed linear regression model results for repeated measures showed a significant reduction in glycated hemoglobin ( GHb ) in the Diabetes TeleCare group from baseline to 6 and 12 months ( 9.4 ± 0.3 , 8.3 ± 0.3 , and 8.2 ± 0.4 , respectively ) compared with usual care ( 8.8 ± 0.3 , 8.6 ± 0.3 , and 8.6 ± 0.3 , respectively ) . LDL cholesterol was reduced at 12 months in the Diabetes TeleCare group compared with usual care . Although not part of the original study design , GHb was reduced from baseline to 12 and 24 months in the Diabetes TeleCare group ( 9.2 ± 0.4 , 7.4 ± 0.5 , and 7.6 ± 0.5 , respectively ) compared with usual care ( 8.7 ± 0.4 , 8.1 ± 0.4 , and 8.1 ± 0.5 , respectively ) in a post hoc analysis of a subset of the r and omized sample who completed a 24-month follow-up visit . CONCLUSIONS Telehealth effectively created access to successfully conduct a 1-year remote DSME by a nurse CDE and dietitian that improved metabolic control and reduced cardiovascular risk in an ethnically diverse and rural population Abstract Background Following the introduction of a computerised diabetes register in part of the northeast of Engl and , care initially improved but then plateaued . We therefore enhanced the existing diabetes register to address these problems . The aim of the trial was to evaluate the effectiveness and efficiency of an area wide ' extended , ' computerised diabetes register incorporating a full structured recall and management system , including individualised patient management prompts to primary care clinicians based on locally-adapted , evidence -based guidelines . Methods The study design was a pragmatic , cluster r and omised controlled trial , with the general practice as the unit of r and omisation . Set in 58 general practice s in three Primary Care Trusts in the northeast of Engl and , the study outcomes were the clinical process and outcome variables held on the diabetes register , patient-reported outcomes , and service and patient costs . The effect of the intervention was estimated using generalised linear models with an appropriate error structure . To allow for the clustering of patients within practice s , population averaged models were estimated using generalized estimating equations . Results Patients in intervention practice s were more likely to have at least one diabetes appointment recorded ( OR 2.00 , 95 % CI 1.02 , 3.91 ) , to have a recording of a foot check ( OR 1.87 , 95 % CI 1.09 , 3.21 ) , have a recording of receiving dietary advice ( OR 2.77 , 95 % CI 1.22 , 6.29 ) , and have a recording of blood pressure ( BP ) ( OR 2.14 , 95 % CI 1.06 , 4.36 ) . There was no difference in mean HbA1c or BP levels , but the mean cholesterol level in patients from intervention practice s was significantly lower ( -0.15 mmol/l , 95 % CI -0.25 , -0.06 ) . There were no differences in patient-reported outcomes or in patient-reported use of drugs , or uptake of health services . The average cost per patient was not significantly different between the intervention and control groups . Costs incurred in administering the system at the register and in general practice were in addition to these . Conclusion This study has shown benefits from an area-wide , computerised diabetes register incorporating a full structured recall and individualised patient management system . However , these benefits were achieved at a cost . In future , these costs may fall as electronic data exchange becomes a reliable reality . Trial registration : International St and ard R and omised Controlled Trial Number ( IS RCT N ) Register , IS RCT N32042030 OBJECTIVE To assess the impact of a quality improvement ( QI ) intervention on the quality of diabetes care at primary care clinics . RESEARCH DESIGN AND METHODS Twelve primary care medical practice s were matched by size and location and r and omized to intervention or control conditions . Intervention clinic staff were trained in a seven-step QI change process to improve diabetes care . Surveys and medical record review s of 754 patients , surveys of 329 clinic staff , interviews with clinic leaders , and analysis of training session videotapes evaluated compliance with and impact of the intervention . Mixed-model nested analyses compared differences in the quality of diabetes care before and after intervention . RESULTS All intervention clinics completed at least six steps of the seven-step QI change process in an 18-month period and , compared with control clinics , had broader staff participation in QI activities ( P = 0.04 ) , used patient registries more often ( P = 0.03 ) , and had better test rates for HbA(1c ) ( A1C ) , LDL , and blood pressure ( P = 0.02 ) . Other processes of diabetes care were unchanged . The intervention did not improve A1C ( P = 0.54 ) , LDL ( P = 0.46 ) , or blood pressure ( P = 0.69 ) levels or a composite of these outcomes ( P = 0.35 ) . CONCLUSIONS This QI change process was successfully implemented but failed to improve A1C , LDL , or blood pressure levels . Data suggest that to be successful , such a QI change process should direct more attention to specific clinical actions , such as drug intensification and patient activation OBJECTIVE To test effects of a web-based decision support tool , the diabetes Disease Management Application ( DMA ) , developed to improve evidence -based management of type 2 diabetes . RESEARCH DESIGN AND METHODS We conducted a group r and omized controlled trial of 12 intervention and 14 control staff providers and 307 intervention and 291 control patients with type 2 diabetes in a hospital-based internal medicine clinic . Providers were r and omly assigned from May 1998 through April 1999 to have access to the DMA ( intervention ) or not to have access ( control ) . The DMA displays interactive patient-specific clinical data , treatment advice , and links to other web-based care re sources . We compared patients in the intervention and control groups for changes in processes and outcomes of care from the year preceding the study through the year of the study by intention-to-treat analysis . RESULTS The DMA was used for 42 % of scheduled patient visits . The number of HbA(1c ) tests obtained per year increased significantly in the intervention group ( + 0.3 tests/year ) compared with the control group ( -0.04 tests/year , P = 0.008 ) , as did the number of LDL cholesterol tests ( intervention , + 0.2 tests/year ; control , + 0.01 tests/year ; P = 0.02 ) and the proportions of patients undergoing at least one foot examination per year ( intervention , + 9.8 % ; control , -0.7 % ; P = 0.003 ) . Levels of HbA(1c ) decreased by 0.2 in the intervention group and increased by 0.1 in the control group ( P = 0.09 ) ; proportions of patients with LDL cholesterol levels < 130 mg/dl increased by 20.3 % in the intervention group and 10.5 % in the control group ( P = 0.5 ) . CONCLUSIONS Web-based patient-specific decision support has the potential to improve evidence -based parameters of diabetes care BACKGROUND Diabetes mellitus continues to result in substantial morbidity and mortality despite receiving much attention from health care providers . Automated clinician reminder systems have been developed to improve adherence to diabetes care guidelines , but these reminder systems do not always provide actionable information and may be unable to detect relevant , subjective patient information that affects clinical decision making . Face-to-face visits with pharmacists , who have knowledge of care guidelines and medication management strategies , may assist in improving diabetes care . It is unknown if the combination of pharmacist chart review and clinician reminders could improve diabetes care without requiring face-to-face visits . OBJECTIVE To assess the effects of a comprehensive , pharmacistdelivered , primary care , physician-focused intervention in a large hospital based primary care practice to improve the quality of care for patients with diabetes including rates of semiannual hemoglobin A1c testing and other biomarker and process measures . METHODS This was a prospect i ve , r and omized , controlled study conducted in a hospital-based , primary care practice , composed of 37 faculty primary care physicians ( PCPs ) and 95 internal medicine residents . The initial sample included 346 patients with diabetes and 72 PCPs caring for them . PCPs were r and omized to receive either a personalized letter from a practicing pharmacist containing treatment recommendations for patients with upcoming primary care visits ( intervention , n = 33 ) or to usual care without the letters ( control , n = 39 ) . The letter included patient-specific recommendations regarding overdue testing as well as drug therapy to achieve diabetes-related treatment targets . The intervention included addition of the letter to the electronic medical record ( EMR ) and presentation of the letter to the PCP at the time of the index primary care visit that occurred between November 2003 and August 2004 . Follow-up chart review was performed after the primary care visit to determine changes in 5 process and 3 biomarker outcome measures of diabetes care within 30 days of the index visit . The primary study outcome was a process measure , change in rates of semiannual A1c testing from baseline to 30-day follow-up . Baseline differences were tested for statistical significance using Pearson chisquare . The statistical significance of the intervention 's effect was tested using logistic regression models predicting achievement of each study outcome , with r and omization status ( intervention vs. control ) as the predictor variable of interest , controlling for baseline performance for each measure . RESULTS 171 patients were in the 4 medical clinic suites with 33 PCPs who received the intervention , and 175 patients were in the 4 suites with 39 PCPs in usual care . 30-day outcomes were analyzed for 301 patients ( 87.0 % ) who attended their scheduled index primary care visit . Of these 301 patients , 44.5 % were black , 65.8 % were female , and the mean age was 63 years . At baseline , there were no significant differences between the intervention group ( n = 150 ) and the usual care ( control ) group ( n = 151 ) in the 3 biomarker measures ( proportion with A1c less than 7 % , proportion with low-density lipoprotein cholesterol [ LDL-C ] less than 100 milligrams per deciliter [ mg per dL ] , or blood pressure less than 130/80 millimeters mercury [ mm Hg ] ) . There were no significant baseline differences in 4 of the 5 process measures ; however , the rate of annual LDL-C testing was significantly higher for the intervention than for the control group at baseline ( 86.0 % vs. 74.8 % , respectively , P = 0.015 ) . In logistic regression analysis , rates of semiannual A1c testing were not significantly different between the intervention and control groups , increasing from baseline to follow-up by 16 % in the intervention group and 9 % in the control group ( P = 0.146 ) . The proportion of patients with A1c less than 7 % at follow-up was 43.3 % in the intervention group versus 37.7 % in the control group ( intervention effect P = 0.099 ) . The only statistically significant difference between the 2 groups in the 8 outcome measures was a higher proportion with an annual eye exam at follow-up in the intervention group ( 60.0 % ) versus the usual care group ( 50.3 % , intervention effect P = 0.017 ) . CONCLUSIONS Pharmacist-generated recommendations delivered by letter to PCPs in an academic medical practice were not associated with statistically significant improvements in most quality measures for diabetes care assessed at 30 days following the intervention . Further research is needed with more patients and a longer follow-up time to determine how best to improve the quality of care of patients with diabetes using focused recommendations for therapy changes and reminder notices to clinicians OBJECTIVE The study 's objective was to assess the effects of automated telephone outreach with speech recognition ( ATO-SR ) on diabetes-related testing . RESEARCH DESIGN AND METHODS We identified 1,200 health plan members who were overdue for diabetes-related testing and r and omly allocated 600 to ATO-SR and 600 to usual care ( no intervention ) . The intervention included three interactive calls encouraging recommended testing . The primary outcome was retinopathy testing , since this was the health plan 's principal goal . Tests for glycemia , hyperlipidemia , and nephropathy were secondary outcomes . RESULTS In total , 232 participants ( 39 % ) verbally responded to the calls . There was no difference between the intervention and the usual care groups in the primary outcome ( adjusted hazard ratio 0.93 [ 95 % CI 0.71–1.22 ] ) and no effect of the intervention on any of the secondary outcomes . CONCLUSIONS Fewer than 40 % of the patients r and omized to ATO-SR interacted verbally with the system . The intervention had no effect on the study 's outcomes Background Disease management programmes ( DMPs ) are costly and impose additional work load on general practitioners ( GPs ) . Data on their effectiveness are inconclusive . We therefore conducted a cluster-r and omised controlled trial to evaluate the effectiveness of the Austrian DMP for diabetes mellitus type 2 on HbA1c and quality of care for adult patients in primary care . Methods All GPs of Salzburg-province were invited to participate . After cluster-r and omisation by district , all patients with diabetes type 2 were recruited consecutively from 7 - 11/2007 . The DMP , consisting mainly of physician and patient education , st and ardised documentation and agreement on therapeutic goals , was implemented in the intervention group while the control group received usual care . We aim ed to show superiority of the intervention regarding metabolic control and process quality . The primary outcome measure was a change in HbA1c after one year . Secondary outcomes were days in the hospital , blood pressure , lipids , body mass index ( BMI ) , enrolment in patient education and regular guideline -adherent examination . Blinding was not possible . Results 92 physicians recruited 1489 patients ( 649 intervention , 840 control ) . After 401 ± 47 days , 590 intervention- patients and 754 controls had complete data . In the intention to treat analysis ( ITT ) of all 1489 patients , HbA1c decreased 0.41 % in the intervention group and 0.28 % in controls . The difference of -0.13 % ( 95 % CI -0.24 ; -0.02 ) was significant at p = 0.026 . Significance was lost in mixed models adjusted for baseline value and cluster-effects ( adjusted mean difference -0.03 ( 95 % CI -0.15 ; 0.09 , p = 0.607 ) . Of the secondary outcome measures , BMI and cholesterol were significantly reduced in the intervention group compared to controls in ITT after adjustments ( -0.53 kg/m² ; 95 % CI -1.03;-0.02 ; p = 0.014 and -0.10 mmol/l ; 95 % CI -0.21 ; -0.003 ; p = 0.043 ) . Additionally , more patients received patient education ( 49.5 % vs. 20.1 % , p < 0.0001 ) , eye- ( 71.0 % vs. 51.2 % , p < 0.0001 ) , foot examinations ( 73.8 % vs. 45.1 % , p < 0.0001 ) , and regular HbA1c checks ( 44.1 % vs. 36.0 % , p < 0.01 ) in the intervention group . Conclusion The Austrian DMP implemented by statutory health insurance improves process quality and enhances weight reduction , but does not significantly improve metabolic control for patients with type 2 diabetes mellitus . Whether the small benefit seen in secondary outcome measures leads to better patient outcomes , remains unclear . Trial Registration Current Controlled trials Ltd. , IS RCT N27414162 OBJECTIVE --To evaluate the effectiveness and acceptability of central ly organised prompting for coordinating community care of non-insulin dependent diabetic patients . DESIGN --R and omised single centre trial . Patients allocated to prompted care in the community or to continued attendance at hospital diabetic clinic ( controls ) . Median follow up two years . SETTING --Two hospital outpatient clinics , 38 general practice s , and 11 optometrists in the catchment area of a district general hospital in Islington . PATIENTS --181 patients attending hospital outpatient clinics . NULL HYPOTHESIS -- There is no difference in process of medical care measures and medical outcome between prompted community care and hospital clinic care . RESULTS --14 hospital patients failed to receive a single review in the clinic as compared with three patients in the prompted group ( chi 2 = 6.1 , df = 1 ; p = 0.013 ) . Follow up for retinal screening was better in prompted patients than in controls ; two prompted patients defaulted as against 12 controls ( chi 2 = 6.9 , df = 1 ; p = 0.008 ) . Three measures per patient yearly were more frequent in prompted patients : tests for albuminuria ( median 3.0 v 2.3 ; p = 0.03 ) , plasma glucose estimations ( 3.1 v 2.5 ; p = 0.003 ) , and glycated haemoglobin estimations ( 2.4 v 0.9 ; p < 0.001 ) . Continuity of care was better in the prompted group ( 3.2 v 2.2 review s by each doctor seen ; p < 0.001 ) . The study ended with no significant differences between the groups in last recorded r and om plasma glucose concentration , glycated haemoglobin value , numbers admitted to hospital for a diabetes related reason , and number of deaths . Question naires revealed a high level of patient , general practitioner , and optometrist satisfaction . CONCLUSIONS --Six monthly prompting of non-insulin treated diabetic patients for care by inner city general practitioners and by optometrists is effective and acceptable Background Theory-based process evaluations conducted alongside r and omized controlled trials provide the opportunity to investigate hypothesized mechanisms of action of interventions , helping to build a cumulative knowledge base and to inform the interpretation of individual trial outcomes . Our objective was to identify the underlying causal mechanisms in a cluster r and omized trial of the effectiveness of printed educational material s ( PEMs ) to increase referral for diabetic retinopathy screening . We hypothesized that the PEMs would increase physicians ’ intention to refer patients for retinal screening by strengthening their attitude and subjective norm , but not their perceived behavioral control . Methods Design : A theory based process evaluation alongside the Ontario Printed Educational Material ( OPEM ) cluster r and omized trial . Postal surveys based on the Theory of Planned Behavior were sent to a r and om sample of trial participants two months before and six months after they received the intervention . Setting : Family physicians in Ontario , Canada . Participants : 1,512 family physicians ( 252 per intervention group ) from the OPEM trial were invited to participate , and 31.3 % ( 473/1512 ) responded at time one and time two . The final sample comprised 437 family physicians fully completing question naires at both time points . Main outcome measures : Primary : behavioral intention related to referring patient for retinopathy screening ; secondary : attitude , subjective norm , perceived behavioral control . Results At baseline , family physicians reported positive intention , attitude , subjective norm , and perceived behavioral control to advise patients about retinopathy screening suggesting limited opportunities for improvement in these constructs . There were no significant differences on intention , attitude , subjective norm , and perceived behavioral control following the intervention . Respondents also reported additional physician- and patient-related factors perceived to influence whether patients received retinopathy screening . Conclusions Lack of change in the primary and secondary theory-based outcomes provides an explanation for the lack of observed effect of the main OPEM trial . High baseline levels of intention to advise patients to attend retinopathy screening suggest that post-intentional and other factors may explain gaps in care . Process evaluations based on behavioral theory can provide replicable and generalizable insights to aid interpretation of r and omized controlled trials of complex interventions to change health professional behavior . Trial registration IS RCT N72772651 OBJECTIVE To evaluate the impact of primary care group visits ( chronic care clinics ) on the process and outcome of care for diabetic patients . RESEARCH DESIGN AND METHODS We evaluated the intervention in primary care practice s r and omized to intervention and control groups in a large-staff model health maintenance organization ( HMO ) . Patients included diabetic patients > or = 30 years of age in each participating primary care practice , selected at r and om from an automated diabetes registry . Primary care practice s were r and omized within clinics to either a chronic care clinic ( intervention ) group or a usual care ( control ) group . The intervention group conducted periodic one-half day chronic care clinics for groups of approximately 8 diabetic patients in their respective doctor 's practice . Chronic care clinics consisted of st and ardized assessment s ; visits with the primary care physician , nurse , and clinical pharmacist ; and a group education/peer support meeting . We collected self-report question naires from patients and data from administrative systems . The question naires were mailed , and telephoned interviews were conducted for nonrespondents , at baseline and at 12 and 24 months ; we queried the process of care received , the satisfaction with care , and the health status of each patient . Serum cholesterol and HbA1c levels and health care use and cost data was collected from HMO administrative systems . RESULTS In an intention-to-treat analysis at 24 months , the intervention group had received significantly more recommended preventive procedures and helpful patient education . Of five primary health status indicators examined , two ( SF-36 general health and bed disability days ) were significantly better in the intervention group . Compared with control patients , intervention patients had slightly more primary care visits , but significantly fewer specialty and emergency room visits . Among intervention participants , we found consistently positive associations between the number of chronic care clinics attended and a number of outcomes , including patient satisfaction and HbA1c levels . CONCLUSIONS Periodic primary care sessions organized to meet the complex needs of diabetic patients imrproved the process of diabetes care and were associated with better outcomes Theory-based intervention programmes to support health-related behaviour change aim to increase health impact and improve underst and ing of mechanisms of behaviour change . However , the science of intervention development remains at an early stage . We present a causal modelling approach to developing complex interventions for evaluation in r and omized trials . In this approach a generic model links behavioural determinants , causally through behaviour , to physiological and biochemical variables , and health outcomes . It is tailored to context , target population , behaviours and health outcomes . The development of a specific causal model based on theory and evidence is illustrated by the ProActive programme , supporting increased physical activity among individuals at risk of Type 2 diabetes . The model provides a rational guide to appropriate measures , intervention points and intervention techniques , and can be tested quantitatively . Causal modelling is critically compared to other approaches to intervention development and evaluation , and research directions are indicated OBJECTIVE To test whether the implementation of elements of the Chronic Care Model ( CCM ) via a specially trained practice nurse leads to an improved cardiovascular risk profile among type 2 diabetes patients . RESEARCH DESIGN AND METHODS This cluster r and omized controlled trial with primary care physicians as the unit of r and omization was conducted in the German part of Switzerl and . Three hundred twenty-six type 2 diabetes patients ( age > 18 years ; at least one glycosylated hemoglobin [ HbA1c ] level of ≥7.0 % [ 53 mmol/mol ] in the preceding year ) from 30 primary care practice s participated . The intervention included implementation of CCM elements and involvement of practice nurses in the care of type 2 diabetes patients . Primary outcome was HbA1c levels . The secondary outcomes were blood pressure ( BP ) , LDL cholesterol , accordance with CCM ( assessed by Patient Assessment of Chronic Illness Care [ PACIC ] question naire ) , and quality of life ( assessed by the 36-item short-form health survey [ SF-36 ] ) . RESULTS After 1 year , HbA1c levels decreased significantly in both groups with no significant difference between groups ( −0.05 % [ −0.60 mmol/mol ] ; P = 0.708 ) . Among intervention group patients , systolic BP ( −3.63 ; P = 0.050 ) , diastolic BP ( −4.01 ; P < 0.001 ) , LDL cholesterol ( −0.21 ; P = 0.033 ) , and PACIC subscores ( P < 0.001 to 0.048 ) significantly improved compared with control group patients . No differences between groups were shown in the SF-36 subscales . CONCLUSIONS A chronic care approach according to the CCM and involving practice nurses in diabetes care improved the cardiovascular risk profile and is experienced by patients as a better structured care . Our study showed that care according to the CCM can be implemented even in small primary care practice s , which still represent the usual structure in most European health care systems Background Behavioural theory can be used to better underst and the effects of behaviour change interventions targeting healthcare professional behaviour to improve quality of care . However , the explicit use of theory is rarely reported despite interventions inevitably involving at least an implicit idea of what factors to target to implement change . There is a quality of care gap in the post-fracture investigation ( bone mineral density ( BMD ) scanning ) and management ( bisphosphonate prescription ) of patients at risk of osteoporosis . We aim ed to use the Theoretical Domains Framework ( TDF ) within a systematic review of interventions to improve quality of care in post-fracture investigation . Our objectives were to explore which theoretical factors the interventions in the review may have been targeting and how this might be related to the size of the effect on rates of BMD scanning and osteoporosis treatment with bisphosphonate medication . Methods A behavioural scientist and a clinician independently coded TDF domains in intervention and control groups . Quantitative analyses explored the relationship between intervention effect size and total number of domains targeted , and as number of different domains targeted . Results Nine r and omised controlled trials ( RCTs ) ( 10 interventions ) were analysed . The five theoretical domains most frequently coded as being targeted by the interventions in the review included “ memory , attention and decision processes ” , “ knowledge ” , “ environmental context and re sources ” , “ social influences ” and “ beliefs about consequences ” . Each intervention targeted a combination of at least four of these five domains . Analyses identified an inverse relationship between both number of times and number of different domains coded and the effect size for BMD scanning but not for bisphosphonate prescription , suggesting that the more domains the intervention targeted , the lower the observed effect size . Conclusions When explicit use of theory to inform interventions is absent , it is possible to retrospectively identify the likely targeted factors using theoretical frameworks such as the TDF . In osteoporosis management , this suggested that several likely determinants of healthcare professional behaviour appear not yet to have been considered in implementation interventions . This approach may serve as a useful basis for using theory-based frameworks such as the TDF to retrospectively identify targeted factors within systematic review s of implementation interventions in other implementation context OBJECTIVE We evaluated automated telephone disease management ( ATDM ) with telephone nurse follow-up as a strategy for improving diabetes treatment processes and outcomes in Department of Veterans Affairs ( VA ) clinics . We also compared the results with those of a prior ATDM trial conducted in a county health care system . RESEARCH DESIGN AND METHODS A total of 272 VA patients with diabetes using hypoglycemic medications were r and omized . During the 1-year study period , intervention patients received biweekly ATDM health assessment and self-care education calls , and a nurse educator followed up with patients based on their ATDM assessment reports . Telephone surveys were used to measure patients ' self-care , symptoms , and satisfaction with care . Outpatient service use was evaluated using electronic data bases and self-reports , and glycemic control was measured by HbA1c and serum glucose testing . RESULTS At 12 months , intervention patients reported more frequent glucose self-monitoring and foot inspections than patients receiving usual care and were more likely to be seen in podiatry and diabetes specialty clinics . Intervention patients also were more likely than control patients to have had a cholesterol test . Among patients with baseline HbA1c levels > or = 8 % , mean end-point values were lower among intervention patients than control patients ( 8.7 vs. 9.2 % , respectively ; P = 0.04 ) . Among intervention and control patients with baseline values > or = 9 % , mean end-point values were 9.1 and 10.2 % , respectively ( P = 0.04 ) . At follow-up , intervention patients reported fewer symptoms of poor glycemic control than control patients and greater satisfaction with their health care . CONCLUSIONS This intervention improved the quality of VA diabetes care . Intervention effects for most end points replicated findings from the prior county clinic trial , although intervention-control differences in the current study were smaller because of the relatively good self-care and health status among the current study 's enrollees Background Method ological guidelines for intervention reporting emphasise describing intervention content in detail . Despite this , systematic review s of quality improvement ( QI ) implementation interventions continue to be limited by a lack of clarity and detail regarding the intervention content being evaluated . We aim ed to apply the recently developed Behaviour Change Techniques Taxonomy version 1 ( BCTTv1 ) to trials of implementation interventions for managing diabetes to assess the capacity and utility of this taxonomy for characterising active ingredients . Methods Three psychologists independently coded a r and om sample of 23 trials of healthcare system , provider- and /or patient-focused implementation interventions from a systematic review that included 142 such studies . Intervention content was coded using the BCTTv1 , which describes 93 behaviour change techniques ( BCTs ) grouped within 16 categories . We supplemented the generic coding instructions within the BCTTv1 with decision rules and examples from this literature . Results Less than a quarter of possible BCTs within the BCTTv1 were identified . For implementation interventions targeting providers , the most commonly identified BCTs included the following : adding objects to the environment , prompts/cues , instruction on how to perform the behaviour , credible source , goal setting ( outcome ) , feedback on outcome of behaviour , and social support ( practical ) . For implementation interventions also targeting patients , the most commonly identified BCTs included the following : prompts/cues , instruction on how to perform the behaviour , information about health consequences , restructuring the social environment , adding objects to the environment , social support ( practical ) , and goal setting ( behaviour ) . The BCTTv1 mapped well onto implementation interventions directly targeting clinicians and patients and could also be used to examine the impact of system-level interventions on clinician and patient behaviour . Conclusions The BCTTv1 can be used to characterise the active ingredients in trials of implementation interventions and provides specificity of content beyond what is given by broader intervention labels . Identification of BCTs may provide a more helpful means of accumulating knowledge on the content used in trials of implementation interventions , which may help to better inform replication efforts . In addition , prospect i ve use of a behaviour change techniques taxonomy for developing and reporting intervention content would further aid in building a cumulative science of effective implementation interventions OBJECTIVE Despite the increased shifting of health care costs to consumers , little is known about the impact of financial barriers on health care utilization . This study investigated the effect of out-of-pocket expenditures on the utilization of recommended diabetes preventive services . RESEARCH DESIGN AND METHODS This was a survey-based observational study ( 2000 - 2001 ) in 10 managed care health plans and 68 provider groups across the U.S. serving approximately 180,000 patients with diabetes . From 11,922 diabetic survey respondents , we studied the occurrence of self-reported annual dilated eye exams and diabetes health education and among insulin users , daily self-monitoring of blood glucose ( SMBG ) . Conditional probabilities were estimated for outcomes at each level of self-reported out-of-pocket expenditure by using hierarchical logistic regression models with r and om intercepts . RESULTS Conditional probabilities of utilization ( 95 % CI ) varied by expenditure for dilated eye exam [ no cost 78 % ( 75 - 82 ) , copay 79 % ( 75 - 82 ) , and full price 70 % ( 64 - 75 ) ; P < 0.0001 ] ; diabetes health education [ no cost 29 % ( 23 - 36 ) , copay 29 % ( 23 - 36 ) , and full price 19 % ( 14 - 25 ) ; P < 0.0001 ] ; and daily SMBG [ no cost 75 % ( 68 - 81 ) , copay 68 % ( 60 - 75 ) , and full price 59 % ( 49 - 68 ) ; P < 0.0001 ] . Extensive adjustment for patient factors had no discernible effect on the estimates or their significance , and cost-utilization relationships were similar across income levels and other patient characteristics . CONCLUSIONS Benefit packages structured to derive greater fiscal contribution from the health plan membership result in suboptimal use of diabetes preventive services and may thus lead to poorer clinical outcomes , greater future costs , and lower health plan quality ratings Background Diabetes is an increasing public health problem in the UK and globally . Diabetic retinopathy is a microvascular complication of diabetes , and is one of the leading causes of blindness in the UK working age population . The diabetic eye screening programme in Engl and aims to invite all people with diabetes aged 12 or over for retinal photography to screen for the presence of diabetic retinopathy . However , attendance rates are only 81 % , leaving many people at risk of preventable sight loss . Methods This is a three arm r and omized controlled trial to investigate the impact of different types of financial incentives ( based on principles from behavioral economics ) on increasing attendance at diabetic eye screening appointments in London . Eligible participants will be aged 16 or over , and are those who have been invited to screening appointments annually , but who have not attended , or telephoned to rearrange an appointment , within the last 24 months . Eligible participants will be r and omized to one of three conditions:1.Control condition ( usual invitation letter)2.Fixed incentive condition ( usual invitation letter , including a voucher for £ 10 if they attend their appointment)3.Probabilistic incentive condition ( invitation letter , including a voucher for a 1 in 100 chance of winning £ 1000 if they attend their appointment ) . Participants will be sent invitation letters , and the primary outcome will be whether or not they attend their appointment . One thous and participants will be included in total , r and omized with a ratio of 1.4:1:1 . In order to test whether the incentive scheme has a differential impact on patients from different demographic or socio-economic groups , information will be recorded on age , gender , distance from screening center , socio-economic status and length of time since they were last screened . A cost-effectiveness analysis will also be performed . Discussion This study will be the first trial of financial incentives for improving uptake of diabetic eye screening . If effective , the intervention may suggest a cost-effective way to increase screening rates , thus reducing unnecessary blindness . Trial registration IS RCT N14896403 , 25 February Abstract Aims To evaluate the effect of multifaceted interventions using the Achievable Benchmark of Care ( ABC ) method for improving the technical quality of diabetes care in primary care setting s. Methods We conducted a 1‐year cluster r and omized controlled trial in 22 regions divided into an intervention group ( IG ) or control group ( CG ) . Physicians in the IG received a monthly report of their care quality , with the top 10 % quality of diabetes care scores for all physicians being the achievable benchmark . The change in quality ‐of‐care scores between the IG and CG during follow‐up was analysed using a generalized linear model considering clustering . Results A total of 2199 patients were included . Their mean ( sd ) age was 56.5 ± 5.9 years and the mean ( sd ) HbA1c level was 56.4 ± 13.3 mmol/mol ( 7.4 ± 1.2 % ) . The quality ‐of‐care score in the CG changed from 50.2%‐point at baseline to 51%‐point at 12 months , whereas the IG score changed from 49.9%‐point to 69.6%‐point , with statistically significant differences between the two groups during follow‐up [ the effect of intervention was 19.0%‐point ( 95 % confidence interval 16.7%‐ to 21.3%‐point ; P < 0.001 ) ] . Conclusions Multifaceted intervention , measuring quality ‐of‐care indicators and providing feedback regarding the quality of diabetes care to physicians with ABC , was effective for improving the technical quality of care in patients with Type 2 diabetes in primary care setting s. ( Trial Registration : umin.ac.jp/ctr as UMIN000002186 We studied whether nonmydriatic digital retinal imaging with remote interpretation ( teleretinal imaging ) in the ambulatory care setting affected adherence to annual dilated eye examinations among patients with diabetes . We r and omly assigned 448 patients to a teleretinal imaging group or a control group . We measured the number of patients who had dilated eye examinations within 12 months of group assignment and the agreement for level of diabetic retinopathy between teleretinal imaging and the eye examinations . The teleretinal imaging group ( n = 223 ) had significantly more dilated eye examinations than the control group ( n = 225 ) . Teleretinal imaging and eye examination results showed significant correlation and moderate agreement . Cataract and smaller pupil size were significantly associated with ungradable retinal images . Two-thirds of patients with ungradable images had other ocular findings . Patients reported high satisfaction with nonmydriatic teleretinal imaging . Nonmydriatic teleretinal imaging improves diabetic retinopathy assessment rates BACKGROUND Current diabetes management guidelines offer blueprints for providers , yet type 2 diabetes control is often poor in disadvantaged population s. The group visit is a new treatment modality originating in managed care for efficient service delivery to patients with chronic health problems . Group visits offer promise for delivering care to diabetic patients , as visits are lengthier and can be more frequent , more organized , and more educational . OBJECTIVE To evaluate the effect of group visits on clinical outcomes , concordance with 10 American Diabetes Association ( ADA ) guidelines [ American Diabetes Association , Diabetes Care , 28:S4–36 , 2004 ] and 3 United States Preventive Services Task Force ( USPSTF ) cancer screens [ U.S. Preventive Services Task Force , http://www.ahrq.gov/clinic/uspstf/re source .htm , 2003 ] . RESEARCH DESIGN AND METHODS A 12-month r and omized controlled trial of 186 diabetic patients comparing care in group visits with care in the traditional patient – physician dyad . Clinical outcomes ( HbA1c , blood pressure [ BP ] , lipid profiles ) were assessed at 6 and 12 months and quality of care measures ( adherence to 10 ADA guidelines and 3 USPSTF cancer screens ) at 12 months . RESULTS At both measurement points , HbA1c , BP , and lipid levels did not differ significantly for patients attending group visits versus those in usual care . At 12 months , however , patients receiving care in group visits exhibited greater concordance with ADA process-of-care indicators ( p < .0001 ) and higher screening rates for cancers of the breast ( 80 vs. 68 % , p = .006 ) and cervix ( 80 vs 68 % , p = .019 ) . CONCLUSIONS Group visits can improve the quality of care for diabetic patients , but modifications to the content and style of group visits may be necessary to achieve improved clinical outcomes AIM To investigate whether a comprehensive strategy involving both patients and professionals , with the introduction of a diabetes passport as a key component , improves diabetes care . METHODS The first 150 consecutive patients who visited their internist for a diabetes check up at the internal medicine outpatient departments at each of nine Dutch general hospitals were included in this 1 year clustered , r and omised , controlled trial . Health care professionals attended an educational meeting about the use and dissemination of the diabetes passport which is a patient held record . They also received aggregated feedback on baseline data and personal feedback . Educational meetings were also organised for patients . Patient files were used in conjunction with question naires to determine adherence rates . Data were analysed using multilevel regression analysis . RESULTS Small but significant changes were found in mean HbA1c levels . In the intervention group , positive health changes for patients were found ( -0.3 % ) when compared to those in the control group ( + 0.2 % ) . Diastolic blood pressure improved slightly , but no changes were found in systolic blood pressure or cholesterol . Improvements were found with regard to levels of examination of patients ' feet and in patient education . CONCLUSIONS Efforts to improve professional practice involving both professionals and patients led to small improvements in HbA1c and diastolic blood pressure levels . Further study is needed to establish whether a better structured health care delivery , operating in a more supportive environment can enhance these effects OBJECTIVE To evaluate the effect of case management by a clinical pharmacist on glycemic control and preventive measures in patients with type 2 diabetes mellitus . STUDY DESIGN R and omized controlled trial in a university-affiliated primary care internal medicine clinic . METHODS We recruited 80 patients with poorly controlled type 2 diabetes mellitus . A clinical pharmacist provided evaluation and modification of pharmacotherapy , self-management diabetes education , and reinforcement of diabetes complications screening processes through clinic visits and telephone follow-up . The main clinical outcome was hemoglobin A1C ( HbA1C ) level ; process measures included HbA1C and low-density lipoprotein measurement , retinal examination , urine microalbumin testing ( or use of angiotensin-converting enzyme inhibitors ) , and monofilament screening for diabetic neuropathy . RESULTS Patients in the intervention and control groups were similar in age , sex , mean HbA1C levels ( 10.1 % and 10.2 % , respectively ; P = .65 ) , and current treatment regimens at baseline . Patients who received case management by the clinical pharmacist achieved greater reduction in HbA1C levels than those in the control group ( 2.1 % vs 0.9 % , P = .03 ) . Three of the 5 process measures were conducted more frequently in the intervention group than the control group , including low-density lipoprotein measurement ( 100.0 % vs 85.7 % , P = .02 ) , retinal examination ( 97.3 % vs 74.3 % ) , and monofilament foot screening ( 92.3 % vs 62.9 % ) . CONCLUSIONS Proactive diabetes case management by a pharmacist substantially improved glycemic control and diabetes process-of-care measures . This approach , integrated with and based in the primary care setting , was an effective and efficient approach to improving care , especially for those with poor glycemic control at baseline We studied the impact of nurse case management ( NCM ) on blood pressure ( BP ) , hemoglobin A1C , lipids , and diabetes complication screening . A 1-year r and omized-controlled trial was conducted in two primary care clinics of the Penn State Hershey Medical Center . Diabetes patients were r and omized to control group ( CG ) ( n=182 ) who received usual care by their primary care provider and intervention group ( IG ) ( n=150 ) who received additional NCM care , including self-management education , and implementation of diabetes guidelines . Primary outcomes included BP , A1C , lipid , process measures , and secondary outcome was diabetes-related emotional distress as assessed by Problem Areas in Diabetes ( PAID ) . BP significantly decreased from 137/77 to 129/72 in IG as compared to an increase from 136/77 to 138/79 in CG after 1 year . PAID scores improved significantly in IG ( from 23 to 10 ) due to reduced emotional stress . A1C ( 7.4 ) and LDL ( 105 ) were unaffected . Complications screening significantly improved in IG compared to CG : opthalmologic exam 26 to 68 % , foot exam 47 to 64 % , and nephropathy screening 34 to 72 % . NCM improved BP , diabetes-related emotional distress , and process measures in primary care . Unchanged A1C and lipids might be due to a threshold effect . Intervention based upon initial risk assessment may prove more cost-effective BACKGROUND / OBJECTIVES Glycosylated hemoglobin ( HbA1C ) measurements in patients with diabetes mellitus contribute to glycemic control , and , therefore to lower diabetic complication rates . Determine if an intervention that includes cl aims -based feedback about patterns of HbA1C measurement results in more frequent monitoring of HbA1C in diabetic Medicare beneficiaries . SUBJECTS Primary care physicians in a single Southern state treating Medicare beneficiaries with diabetes mellitus . METHODS A group-r and omized evaluation of an intervention that included cl aims -based feedback about patterns of HbA1C measurement , educational material s , and practice aids . RESULTS Rates for each quality indicator increased from 1996 to 1998 for both the intervention and comparison groups , although increases were larger for intervention counties . HbA1C testing rates increased in intervention counties 16.8 % compared to 13.0 % in the comparison counties , an absolute difference of 4.0 % ( 95 % CI , 0.7 to 7.3 ) . Differences for other indicators were small , although positive and favoring the intervention , and lacked statistical significance . CONCLUSIONS Physician interventions that included practice -level feedback about monitoring of glycemic control successfully led to improved care of diabetic Medicare beneficiaries IMPORTANCE Minimal information exists regarding the long-term comparative effectiveness of telemedicine to provide diabetic retinopathy screening examinations . OBJECTIVE To compare telemedicine to traditional eye examinations in their ability to provide diabetic retinopathy screening examinations . DESIGN , SETTING , AND PARTICIPANTS From August 1 , 2006 , through September 31 , 2009 , 567 participants with diabetes were r and omized and followed up to 5 years of follow-up ( last date of patient follow-up occurred on August 6 , 2012 ) as part of a multicenter r and omized clinical trial with an intent to treat analysis . We assigned participants to telemedicine with a nonmydriatic camera in a primary care medical clinic ( n = 296 ) or traditional surveillance with an eye care professional ( n = 271 ) . Two years after enrollment , we offered telemedicine to all participants . MAIN OUTCOMES AND MEASURES Percentage of participants receiving annual diabetic retinopathy screening examinations , percentage of eyes with worsening diabetic retinopathy during the follow-up period using a vali date d scale from stage 0 ( none ) to stage 4 ( proliferative diabetic retinopathy ) , and percentage of telemedicine participants who would require referral to an eye care professional for follow-up care using a cutoff of moderate diabetic retinopathy or worse , the presence of macular edema , or an unable-to-determine result for retinopathy or macular edema . RESULTS The telemedicine group was more likely to receive a diabetic retinopathy screening examination when compared with the traditional surveillance group during the 6-month or less ( 94.6 % [ 280/296 ] vs 43.9 % [ 119/271 ] ; 95 % CI , 46.6%-54.8 % ; P < .001 ) and greater than 6-month through 18-month ( 53.0 % [ 157/296 ] vs 33.2 % [ 90/271 ] ; 95 % CI , 16.5%-23.1 % ; P < .001 ) time bins . After we offered telemedicine to both groups , we could not identify a difference between the groups in the percentage of diabetic retinopathy screening examinations . Diabetic retinopathy worsened by 2 stages or more in 35 ( 8.6 % ) of 409 participants ( 95 % CI , 5.8%-11.2 % ) and improved by 2 stages or more in 5 ( 1.2 % ) of 409 participants ( 95 % CI , 0.1%-2.3 % ) during the 4-year period . The percent of telemedicine participants requiring referral ranged from 19.2 % ( 52/271 ) to 27.9 % ( 58/208 ) . CONCLUSIONS AND RELEVANCE Telemedicine increased the percentage of diabetic retinopathy screening examinations , most participants did not require referral to an eye care professional , and diabetic retinopathy levels were generally stable during the study period . This finding suggests that primary care clinics can use telemedicine to screen for diabetic retinopathy and monitor for disease worsening over a long period . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01364129 OBJECTIVE To evaluate the effectiveness of using personalized follow-up , as compared to reminder letters , in increasing return rates at urban eye disease screening clinics for African Americans with diabetes , and to identify factors predictive of the patient 's likelihood of returning for annual follow-up exams . RESEARCH DESIGN AND METHODS All patients attending free community-based retinopathy screening clinics who were advised to return in one year for another diabetes eye evaluation ( DEE ) were r and omized to st and ard or personalized follow-up interventions . Patients in the st and ard follow-up group received reminder letters a month before it was time to return for their next annual DEE . Patients in the intensive personalized intervention also received the letters , but those patients who did not call for an appointment within 10 days received a phone call from project staff , encouraging them to return for a DEE . RESULTS One hundred thirty-two African Americans with diabetes were r and omized to one of the 2 treatments . The return rate for the intensive , personalized follow-up group was 66 % , significantly ( P=.001 ) higher than the 35 % return rate for the st and ard follow-up group . CONCLUSION This study demonstrated the efficacy of personal contact by telephone in improving return rates for annual DEEs in this population of patients . This finding is consistent with one of the key design principles of the project , which was to establish credible personal relationships with community leaders and patients as a means to maximize the utilization of the eye screening clinics Increasing dem and to deliver and document therapeutic and preventive care sharpens the need for disease management strategies that accomplish these goals efficiently while preserving quality of care . The purpose of this study was to compare selected outcomes for a new chronic disease management program involving a nurse practitioner - physician team with those of an existing model of care . One hundred fifty-seven patients with hypertension and diabetes mellitus were r and omly assigned to their primary care physician and a nurse practitioner or their primary care physician alone . Costs for personnel directly involved in patient management , calculated from hourly rates and encounter time with patients , and pre- and post- study glycosylated hemoglobin ( HbA1c ) , high-density lipoprotein cholesterol ( HDL-c ) , satisfaction with care and health-related quality of life ( HRQoL ) were assessed . Although 1-year costs for personnel were higher in the team-treated group , participants experienced significant improvements in mean HbA1c ( − 0.7 % , p = 0.02 ) and HDL-c ( + 2.6 mg dL − 1 , p = 0.02 ) . Additionally , satisfaction with care improved significantly for team-treated subjects in several sub-scales whereas the mean change over time in HRQoL did not differ significantly between groups . This study demonstrates the value of a complementary team approach to chronic disease management in improving patient-derived and clinical outcomes at modest incremental costs Background : Sub-Saharan Africa faces an epidemic of diabetes with its attendant complications . Early treatment of diabetic retinopathy prevents visual impairment and blindness . However , very little has been done to establish diabetic retinopathy screening in Africa . We aim ed to measure current use of the eye department by diabetics and the increase in eye examinations following education about diabetic eye disease by a dedicated nurse counselor and the offer of a free eye examination . Methods : In a prospect i ve study over 6 months we enrolled all diabetics over the age of 18 attending the diabetic clinic at KCMC . Data was collected on whether patients had had a previous dilated eye exam and whether they knew this was necessary . Education on diabetic eye disease and a referral form to the eye clinic for a free examination were given to the patient . Findings : Three-hundred sixteen patients were enrolled in the study . 187 ( 59.1 % ) of the patients reported that they had undergone dilated fundus exam at some point since their diagnosis . 91 ( 28.8 % ) had undergone fundus examination within the past 12 months . Of the 316 patients , 114 ( 36 % ) came to the eye clinic with the referral form . 106 had not been examined in the last year . 65 of these had never been examined before . A logistic regression model demonstrated that knowledge that diabetes damages the eye ( OR = 7.34 , 95%CI = 4.66–11.57 ) and age ( OR = 1.02 , 95%CI = 1.01–1.03 ) but not duration of diabetes were independently associated with ever having had a dilated fundus exam and with having had an exam in the past year . Interpretation : Only 29 % of diabetics had had an eye examination in the previous year . After the intervention this increased to 47 % of those who had not been examined . In the short term we achieved a reasonable , albeit less than optimal , increase in use of eye care services among diabetic patients . It is essential that we continue to strive to find ways to improve eye care for diabetic patients in Africa to avoid an increase in visual impairment BACKGROUND The aim of the present study was to determine whether the addition of nurse case managers ( NCMs ) trained in motivational interviewing ( MI ) to usual care would result in improved outcomes in high-risk type 2 diabetes patients . METHODS A 2-year r and omized controlled pragmatic trial r and omized 545 patients to usual care control ( n=313 ) or those who received the intervention ( n=232 ) with additional practice -embedded NCM care , including MI-guided behavior change counseling . The NCMs received intensive MI training with ongoing fidelity assessment . RESULTS Systolic blood pressure ( SBP ) was better in the intervention than usual care group ( 131 ± 15 vs. 135 ± 18 mmHg , respectively ; P<0.05 ) . Improvements were seen in both the control and intervention groups in terms of HbA1c ( from 9.1 % to 8.0 % and from 8.8 % to 7.8 % , respectively ) , low-density lipoprotein ( LDL ; from 127 to 100 mg/dL and from 128 to 102 mg/dL , respectively ) , and diastolic blood pressure ( from 78 to 74 mmHg and from 80 to 74 mmHg , respectively ) . Depression symptom scores were better in the intervention group . The reduction in diabetes-related distress approached statistical significance . CONCLUSIONS The NCMs and MI improved SBP and complications screening . The large decrease in HbA1C and LDL in the control group may have obscured any further intervention effect . Although nurses prompted providers for medication titration , strategies to reduce provider clinical inertia may also be needed Nurses with advanced training — diabetes re source nurses (DRNs)—can improve care for people with diabetes in capitated payment setting s. Their effectiveness in fee-for-service setting s has not been investigated . We conducted a 12-month practice -r and omized trial involving 22 practice s in a fee-for-service metropolitan network with 92 primary care physicians caring for 1891 Medicare patients ≥65 years with diabetes mellitus . Each practice was r and omized to one of three intervention groups : physician feedback on process measures using Medicare cl aims data ; Medicare cl aims feedback plus feedback on clinical measures from medical record ( MR ) abstract ion ; or both types of feedback plus a practice -based DRN . The primary endpoint investigated was hemoglobin A1c level . Other measures were low-density lipoprotein ( LDL ) cholesterol level , blood pressure , annual hemoglobin A1c testing , annual LDL screening , annual eye exam , annual foot exam , and annual renal assessment . Data were collected from medical chart abstract ion and Medicare cl aims . The number of patients with hemoglobin A1c < 9 % increased by 4 ( 0.9 % ) in the Cl aims group ; 9 ( 2.1 % ) in the Cl aims + MR group ( comparison with Cl aims : P = 0.97 ) ; and 16 ( 3.8 % ) in the DRN group ( comparison with Cl aims : P = 0.31 ) . Results were similar for the other clinical outcomes , with no differences significant at P = 0.10 . For process of care measures , decreases were seen in all groups , with no significant differences in change scores . Quality improvement strategies must be evaluated in the appropriate setting . Initiatives that have been effective in capitated systems may not be effective in fee-for-service environments PURPOSE We investigated 3 approaches for implementing the Chronic Care Model to improve diabetes care : ( 1 ) practice facilitation over 6 months using a reflective adaptive process ( RAP ) approach ; ( 2 ) practice facilitation for up to 18 months using a continuous quality improvement ( CQI ) approach ; and ( 3 ) providing self-directed ( SD ) practice s with model information and re sources , without facilitation . METHODS We conducted a cluster-r and omized trial , called Enhancing Practice , Improving Care ( EPIC ) , that compared these approaches among 40 small to midsized primary care practice s. At baseline and 9 months and 18 months after enrollment , we assessed practice diabetes quality measures from chart audits and Practice Culture Assessment scores from clinician and staff surveys . RESULTS Although measures of the quality of diabetes care improved in all 3 groups ( all P < .05 ) , improvement was greater in CQI practice s compared with both SD practice s ( P < .0001 ) and RAP practice s ( P < .0001 ) ; additionally , improvement was greater in SD practice s compared with RAP practice s ( P < .05 ) . In RAP practice s , Change Culture scores showed a trend toward improvement at 9 months ( P = .07 ) but decreased below baseline at 18 months ( P < .05 ) , while Work Culture scores decreased from 9 to 18 months ( P < .05 ) . Both scores were stable over time in SD and CQI practice s. CONCLUSIONS Traditional CQI interventions are effective at improving measures of the quality of diabetes care , but may not improve practice change and work culture . Short-term practice facilitation based on RAP principles produced less improvement in quality measures than CQI or SD interventions and also did not produce sustained improvements in practice culture BACKGROUND : Although mailed reminders have been used for prevention among general population s , few studies have evaluated their effectiveness among chronically ill population s. OBJECTIVE : We evaluated the effectiveness of mailed reminders for improving diabetes management . The reminder included a letter from the individual ’s primary care physician ( PCP ) , a self-care h and book , a preventive care checklist , and specific recommendations regarding receipt of routine monitoring and screening . METHODS : Of 195 PCPs practicing with a large group practice , 111 agreed to have their adult patients with diabetes r and omized to receive the reminder ( n=1,641 ) or usual care ( n=1,668 ) . Using data from automated data bases , we fit generalized estimating equations to evaluate the effect of reminder receipt on fasting lipid profile and glycated hemoglobin testing , dilated retinal exam receipt , and visit frequency during the 6 and 12 months following r and omization , and glycated hemoglobin and cholesterol levels in the year following r and omization . RESULTS : Reminder and usual care recipients did not differ in sociodemographic , clinical , or prior testing characteristics . In the 6 months following r and omization , reminder recipients were more likely to receive a retinal exam ( odds ratio [ OR ] , 1.29 ; 95 % confidence interval [ 95 % CI ] , 1.12 to 1.49 ) and diabetes visit ( OR , 1.28 ; 95 % CI , 1.12 to 1.47 ) . In the 12 months following r and omization , reminder recipients were more likely to receive a glycated hemoglobin test ( OR , 1.21 ; 95 % CI , 1.03 to 1.43 ) , retinal exam ( OR , 1.23 ; 95 % CI , 1.07 to 1.41 ) , and diabetes visit ( OR , 1.25 ; 95 % CI , 1.09 to 1.29 ) . In the follow-up year , reminder recipients also tended to have a glycated hemoglobin test that did not reflect poor control ( < 9.5 % ) . CONCLUSIONS : We found small but significant improvements in the management of patients with diabetes receiving a computerized mailed reminder Background and Aims Little is known about the extent and nature of publication bias in economic evaluations . Our objective was to determine whether economic evaluations are subject to publication bias by considering whether economic data are as likely to be reported , and reported as promptly , as effectiveness data . Methods Trials that intended to conduct an economic analysis and ended before 2008 were identified in the International St and ard R and omised Controlled Trial Number ( IS RCT N ) register ; a r and om sample of 100 trials was retrieved . Fifty comparator trials were r and omly drawn from those not identified as intending to conduct an economic study . The trial start and end date s , estimated sample size and funder type were extracted . For trials planning economic evaluations , effectiveness and economic publications were sought ; publication date s and journal impact factors were extracted . Effectiveness abstract s were assessed for whether they reached a firm conclusion that one intervention was most effective . Primary investigators were contacted about reasons for non-publication of results , or reasons for differential publication strategies for effectiveness and economic results . Results Trials planning an economic study were more likely to be funded by government ( p = 0.01 ) and larger ( p = 0.003 ) than other trials . The trials planning an economic evaluation had a mean of 6.5 ( range 2.7–13.2 ) years since the trial end in which to publish their results . Effectiveness results were reported by 70 % , while only 43 % published economic evaluations ( p < 0.001 ) . Reasons for non-publication of economic results included the intervention being ineffective , and staffing issues . Funding source , time since trial end and length of study were not associated with a higher probability of publishing the economic evaluation . However , studies that were small or of unknown size were significantly less likely to publish economic evaluations than large studies ( p < 0.001 ) . The authors ’ confidence in labelling one intervention clearly most effective did not affect the probability of publication . The mean time to publication was 0.7 years longer for cost-effectiveness data than for effectiveness data where both were published ( p = 0.001 ) . The median journal impact factor was 1.6 points higher for effectiveness publications than for the corresponding economic publications ( p = 0.01 ) . Reasons for publishing in different journals included editorial decision making and the additional time that economic evaluation takes to conduct . Conclusions Trials that intend to conduct an economic analysis are less likely to report economic data than effectiveness data . Where economic results do appear , they are published later , and in journals with lower impact factors . These results suggest that economic output may be more susceptible than effectiveness data to publication bias . Funders , grant review ers and trialists themselves should ensure economic evaluations are prioritized and adequately staffed to avoid potential problems with bias AIMS To evaluate the effectiveness of a multifaceted intervention to improve the clinical decision making of general practitioners ( GPs ) for patients with diabetes . To identify practice characteristics which predict success . METHODS Cluster r and omized controlled trial with 124 practice s and 185 GPs in The Netherl and s. The intervention group received feedback reports and support from a facilitator ; the control group received no special attention . Outcome measures were the compliance rates with evidence -based recommendations pertaining to discussion of body weight control , discussion of problems with medication , blood pressure measurement , foot examination , eye examination , initiating anti-diabetic medication or increasing the dosage in cases of uncontrolled blood glucose , and scheduling a follow-up appointment . RESULTS The GPs reported on their clinical decision making in 1410 consultations with Type 2 diabetic patients at baseline and 1449 consultations after the intervention period . The intervention result ed in statistically significant improvement for two of the seven outcome measures : foot examination ( odds ratio 1.68 ; 95 % confidence interval 1.19 - 2.39 ) and eye examination ( 1.52 ; 1.07 - 2.16 ) . Discussion of problems with medication showed a near significant trend towards increased benefit for the intervention group ( 1.52 ; 0.99 - 2.32 ) . Practice characteristics were not found to be related to the success of the intervention . CONCLUSIONS Feedback reports with support from facilitators appear to increase rates of foot examination and eye examination in general practice . Alternative interventions should be explored to improve the pursuit of metabolic control by GPs BACKGROUND Improving the quality and efficiency of chronic disease care is an important goal . OBJECTIVE To test whether patients with chronic disease working with lay " care guides " would achieve more evidence -based goals than those receiving usual care . DESIGN Parallel-group r and omized trial , stratified by clinic and conducted from July 2010 to April 2012 . Patients were assigned in a 2:1 ratio to a care guide or usual care . Patients , providers , and persons assessing outcomes were not blinded to treatment assignment . ( Clinical Trials.gov : NCT01156974 ) . SETTING 6 primary care clinics in Minnesota . PATIENTS Adults with hypertension , diabetes , or heart failure . INTERVENTION 2135 patients were given disease-specific information about st and ard care goals and asked to work toward goals for 1 year , with or without the help of a care guide . Care guides were 12 laypersons who received brief training about these diseases and behavior change . MEASUREMENTS The primary end point for each patient was change in percentage of goals met 1 year after enrollment . RESULTS The percentage of goals met increased in both the care guide and usual care groups ( changes from baseline , 10.0 % and 3.9 % , respectively ) . Patients with care guides achieved more goals than usual care patients ( 82.6 % vs. 79.1 % ; odds ratio , 1.31 [ 95 % CI , 1.16 to 1.47 ] ; P < 0.001 ) ; reduced unmet goals by 30.1 % compared with 12.6 % for usual care patients ; and improved more than usual care patients in meeting several individual goals , including not using tobacco . Estimated cost was $ 286 per patient per year . LIMITATIONS Providers ' usual care may have been influenced by contact with care guides . Last available data in the electronic health record were used to assess end points . CONCLUSION Adding care guides to the primary care team can improve care for some patients with chronic disease at low cost OBJECTIVE To evaluate whether a new documentation-based clinical decision support system ( CDSS ) is effective in addressing deficiencies in the care of patients with coronary artery disease ( CAD ) and diabetes mellitus ( DM ) . STUDY DESIGN Controlled trial r and omized by physician . METHODS We assigned primary care physicians ( PCPs ) in 10 ambulatory practice s to usual care or the CAD/DM Smart Form for 9 months . The primary outcome was the proportion of deficiencies in care that were addressed within 30 days after a patient visit . RESULTS The Smart Form was used for 5.6 % of eligible patients . In the intention-to-treat analysis , patients of intervention PCPs had a greater proportion of deficiencies addressed within 30 days of a visit compared with controls ( 11.4 % vs 10.1 % , adjusted and clustered odds ratio = 1.14 ; 95 % confidence interval , 1.02 - 1.28 ; P = .02 ) . Differences were more pronounced in the " on-treatment " analysis : 17.0 % of deficiencies were addressed after visits in which the Smart Form was used compared with 10.6 % of deficiencies after visits in which it was not used ( P < .001 ) . Measures that improved included documentation of smoking status and prescription of antiplatelet agents when appropriate . CONCLUSIONS Overall use of the CAD/DM Smart Form was low , and improvements in management were modest . When used , documentation-based decision support shows promise , and future studies should focus on refining such tools , integrating them into current electronic health record platforms , and promoting their use , perhaps through organizational changes to primary care practice Diabetes-related ophthalmic complications are the leading cause of newly diagnosed blindness among adults . These eye complications are often asymptomatic in the early stages , yet the majority of diabetes patients are not screened yearly . To develop a health promotion intervention to increase the rate of screening for diabetic retinopathy by dilated fundus exam ( DFE ) , we assessed the knowledge and health beliefs related to preventing diabetic eye complications among a sample of African-Americans with diabetes . The study design was cross-sectional , using a telephone interview to collect data . From a r and om sample of 104 African-Americans with diabetes , 67 ( 64 % ) were completed : 54 women ; mean age of 58 years . The telephone interview schedule contained items grouped into subscales for Perceived Incentives , Perceived Barriers to getting a DFE , Causes of Eye Problems , Risk of Eye Problems , and Effective Treatments for Eye Problems . Descriptive statistics were used to analyze the quantitative data . Transcribed qualitative responses to the open-ended questions were analyzed for themes . The incentives " having eye problems " and " doctor said it was important to go " each had 91 % responding it was an incentive to go for a DFE . Only about one-third agreed that any particular item was a barrier to receiving a DFE ( e.g. , economic factors ) . In the subscale for Risk of Eye Problems , " retinopathy " had the lowest level of perceived risk ( 30 % ) . Only 21 % of the sample reported there were effective treatments for retinopathy . Eighty-seven percent reported the faulty belief that " diabetic eye problems have symptoms . " Only 36 % of the sample said they had heard of retinopathy and of those , only 8 % could describe it correctly . Among general response themes were : fear , spirituality ( faith and hope ) , priorities , economic or logistical factors , and external/internal motivation . Perceived incentives for receiving a DFE were acknowledged at far greater rates than perceived barriers . Having a yearly DFE in the absence of symptoms must be emphasized in health promotion material s. There are effective , early treatments for diabetic eye problems , and this information should be used to counter the fear of a dreaded diagnosis with the hope of treatment and cure . Ways of coping with fear of having the exam should be included in health education . DFEs must become a routine yearly exam and not just a reaction to recognized problems . Health education must address the specific needs of high-risk minority population Objective Diabetic retinopathy is one of the leading causes of vision impairment among adults in the USA . While it is suggested that diabetics receive annual dilated fundus examinations ( DFE ) , many patients do not adhere to these recommendations . This paper investigates the outcomes and costs of an educational and telephone intervention on DFE follow-up adherence in patients with diabetes . Methods In a prospect i ve trial , 356 diabetic patients due for a DFE at an urban eye clinic were r and omly assigned to usual care ( UC ; reference case ) , mailed intervention ( MI ) , or telephone intervention ( TI ) . UC patients ( n = 119 ) received a st and ard form letter . MI patients ( n = 117 ) received a personalized letter encouraging scheduling of an eye examination with an educational brochure about diabetic eye disease . TI patients ( n = 120 ) received personal calls ( up to three attempts ) to schedule a follow-up with st and ard form letter . The primary outcome was obtaining a DFE within 90 days of suggested return . Costs ( US$ 2013 ) included time costs for staff , phone charges , supplies , and postage . Since TI involved greater cost components compared to MI , univariate sensitivity analysis examined the impact of reducing phone costs . Results Patients were mostly female ( 66 % ) and African American ( 70 % ) with a mean age of 61 years . TI patients were more likely to schedule DFE [ 65 vs. 42 % ; relative risk ( RR ) 1.54 ; CI 1.20–1.96 ; P < 0.001 ] versus UC patients . Obtaining a DFE within 90 days of suggested return was also significantly higher among TI patients compared to UC patients ( 51 vs. 36 % , RR 1.41 ; CI 1.05–1.89 ; P = 0.024 ) . MI patients were slightly less likely to schedule DFE versus UC patients ( 38 vs. 42 % , RR 0.90 ; CI 0.66–1.22 ; P = NSS ) and obtain a DFE ( 32 vs. 36 % ; RR 0.90 ; CI 0.63–1.28 ; P = NSS ) . The total cost of TI was US$ 798.28 or US$ 6.65/patient and the cost/follow-up DFE was US$ 26.05 . Sensitivity analyses revealed that the cost/follow-up can be greatly reduced but remains greater compared to UC ( US$ 2.76 if US$ 0.25/call , US$ 11.13 if $ 1/call ; US$ 22.29 if US$ 2/call ) . Conclusions Personal phone assistance in scheduling DFE follow-up is more effective but also more costly . Follow-up research has been initiated to determine whether automated phone reminders can achieve similar effectiveness at a lower cost Background Evidence of the effectiveness of printed educational messages in narrowing the gap between guideline recommendations and practice is contradictory . Failure to screen for retinopathy exposes primary care patients with diabetes to risk of eye complications . Screening is initiated by referral from family practitioners but adherence to guidelines is suboptimal . We aim ed to evaluate the ability of printed educational messages aim ed at family doctors to increase retinal screening of primary care patients with diabetes . Methods Design : Pragmatic 2 × 3 factorial cluster trial r and omized by physician practice , involving 5,048 general practitioners ( with 179,833 patients with diabetes ) . Setting : Ontario family practitioners . Interventions : Reminders ( that retinal screening helps prevent diabetes-related vision loss and is covered by provincial health insurance for patients with diabetes ) with prompts to encourage screening were mailed to each physician in conjunction with a widely-read professional newsletter . Alternative printed material s formats were an ‘ outsert ’ ( short , directive message stapled to the outside of the newsletter ) , and /or a two-page , evidence -based article ( ‘ insert ’ ) and a pre-printed sticky note reminder for patients . Main outcome measure : A successful outcome was an eye examination ( which includes retinal screening ) provided to a patient with diabetes , not screened in the previous 12 months , within 90 days after visiting a family practitioner . Analysis accounted for clustering of doctors within practice groups . Results No intervention effect was detected ( eye exam rates were 31.6 % for patients of control physicians , 31.3 % for the insert , 32.8 % for the outsert , 32.3 % for those who received both , and 31.2 % for those who received both plus the patient reminder with the largest 95 % confidence interval around any effect extending from −1.3 % to 1.1 % ) . Conclusions This large trial conclusively failed to demonstrate any impact of printed educational messages on screening uptake . Despite their low cost , printed educational messages should not be routinely used in attempting to close evidence - practice gaps relating to diabetic retinopathy screening . Trial registration IS RCT OBJECTIVE There is a well-documented gap between diabetes care guidelines and the services received by patients in most health care setting s. This report presents 12-month follow-up results from a computer-assisted , patient-centered intervention to improve the level of recommended services patients received from a variety of primary care setting s. RESEARCH DESIGN AND METHODS A total of 886 patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program . Physicians were stratified and r and omized to intervention or control conditions and evaluated on two primary outcomes : number of recommended laboratory screenings and recommended patient-centered care activities completed from the National Committee on Quality Assurance/American Diabetes Association Provider Recognition Program ( PRP ) . Secondary outcomes were evaluated using the Problem Areas in Diabetes 2 quality of life scale , lipid and HbA1c levels , and the Patient Health Question naire-9 depression scale . RESULTS The program was well implemented and significantly improved both the number of laboratory assays and patient-centered aspects of diabetes care patients received compared with those in the control condition . There was overall improvement on secondary outcomes of lipids , HbA1c , quality of life , and depression scores ; between-condition differences were not significant . CONCLUSIONS Staff in small , mixed-payer primary care offices can consistently implement a patient-centered intervention to improve PRP measures of quality of diabetes care . Alternative explanations for why these process improvements did not lead to improved outcomes , and suggested directions for future research are discussed OBJECTIVE To assess the feasibility and effectiveness of shared medical appointments ( SMAs ) among Hispanic patients with diabetes mellitus attending a family medicine residency clinic . STUDY DESIGN Exploratory and descriptive study . METHODS Hispanic patients having diabetes with poor glycemic control ( glycated hemoglobin level , > 7 % ) attending a family medicine residency clinic were r and omized to an SMA group ( n = 50 ) or a control group ( n = 53).The main outcome was glycated hemoglobin level . Secondary outcomes were quality of life and diabetes knowledge . RESULTS When comparing pre-post measures , there were mean decreases in glycated hemoglobin level of 1.19 % for the SMA group ( P < .01 ) and 0.67 % for the control group ( P = .02).In the SMA group , quality -of-life and diabetes knowledge scores increased by 5 and 1.5 points , respectively ( P < .01 ) . CONCLUSIONS Implementing SMAs is feasible and effective among Hispanic patients with diabetes attending a family medicine residency clinic . Health plan managers and policy makers can work with family medicine residents to encourage the use of this model as an alternative approach or in addition to conventional one-on-one interactions with patients The objective of this study was to evaluate the value of an intensive telephone follow-up as an additional component of a diabetes disease management program already shown to be effective in improving glycemic control , adherence with American Diabetes Association ( ADA ) st and ards of care , and health-related quality of life ( HRQOL ) . The study involved a r and omized controlled trial . The intervention group received a series of 12 weekly phone calls reinforcing base education and self-management skills . Five hundred and seven consenting patients , age 18 years or older , with type 1 or type 2 diabetes mellitus referred to the hospital- based disease management program who had telephones and were able to complete surveys in English or Spanish were enrolled . Outcomes were evaluated at 3 and 12 months follow- up . Adherence to ADA st and ards of care , specifically annual eye exams , physician foot exams , foot self-exams , and pneumonia vaccination were significantly better with the added telephone intervention , but there were no differences between the groups on glycemic control , HRQOL , or patient satisfaction . The effectiveness of the disease management program was replicated with sustained improvement in glycemic control , HRQOL , and adherence to ADA st and ards . The additional telephone intervention further improved adherence to ADA guidelines for self-care and medical care but did not affect glycemic control or HRQOL OBJECTIVE This study evaluated the efficacy of a nurse-care management system design ed to improve outcomes in patients with complicated diabetes . RESEARCH DESIGN AND METHODS In this r and omized controlled trial that took place at Kaiser Permanente Medical Center in Santa Clara , CA , 169 patients with longst and ing diabetes , one or more major medical comorbid conditions , and HbA(lc ) > 10 % received a special intervention ( n = 84 ) or usual medical care ( n = 85 ) for 1 year . Patients met with a nurse-care manager to establish individual outcome goals , attended group sessions once a week for up to 4 weeks , and received telephone calls to manage medications and self-care activities . HbA(lc ) , LDL , HDL , and total cholesterol , triglycerides , fasting glucose , systolic and diastolic blood pressure , BMI , and psychosocial factors were measured at baseline and 1 year later . Annualized physician visits were determined for the year before and during the study . RESULTS At 1 year , the mean reductions in HbA(lc ) , total cholesterol , and LDL cholesterol were significantly greater for the intervention group compared with the usual care group . Significantly more patients in the intervention group met the goals for HbA(1c ) ( < 7.5 % ) than patients in usual care ( 42.6 vs. 24.6 % , P < 0.03 , chi(2 ) ) . There were no significant differences in any of the psychosocial variables or in physician visits . CONCLUSIONS A nurse-care management program can significantly improve some medical outcomes in patients with complicated diabetes without increasing physician visits OBJECTIVES ( 1 ) To describe baseline patterns of adherence to American Diabetes Association and American Academy of Ophthalmology vision care guidelines for diabetes in the Diabetic Retinopathy Awareness Program , and ( 2 ) to evaluate factors associated with nonadherence . This paper describes the baseline characteristics of a population enrolled in a prospect i ve , r and omized clinical trial . DESIGN Cross-sectional study . PARTICIPANTS Between October 1993 and May 1994 , the study identified 2308 persons with diabetes , 18 years of age or older , who were residents of Suffolk County , New York , via a multimedia community-wide recruitment campaign . INTERVENTION AND METHODS Eligibility for the trial was determined during a 20-minute phone interview , which included questions about vision care practice s ; diabetes management ; and knowledge , attitudes , and beliefs about diabetes , vision , and diabetic retinopathy . This paper describes these patient characteristics at baseline . Eligible patients would be r and omized subsequently to a 2-year diabetes educational intervention arm , which included mailed packets and newsletters focused on vision care , or to a control nonintervention arm . MAIN OUTCOME MEASURE Nonadherence to guidelines at baseline was defined as the absence of a dilated eye examination during the year before recruitment into the study . RESULTS Of the 2308 persons interviewed , 813 ( 35 % ) did not follow the vision care guidelines ; two thirds of this group reported no eye examination in the year before the interview , and one third had an undilated examination . Ophthalmologists performed 49 % of the examinations in the nonadherent group , versus 86 % in the adherent group . In logistic regression analyses , factors related to nonadherence were : younger age ( odds ratio [ OR ] = 0.97 ) , type 2 diabetes with or without insulin use ( OR = 1.62 and 1.99 , respectively ) , shorter diabetes duration ( OR = 0.97 ) , last eye examination performed by an optometrist ( OR = 5.32 ) or other nonophthalmologist ( OR = 4.29 ) , less practical knowledge about diabetes ( OR = 1.57 ) , and no prior formal diabetes education ( OR = 1.30 ) . CONCLUSIONS Within this population , more than one third of participants had not been following vision care guidelines . Nonadherence was linked to several potentially modifiable factors ; changes in these factors could enhance the early detection of diabetic retinopathy BACKGROUND Failure to achieve treatment targets is common among people with type 2 diabetes . Cost-effective treatments are required to delay the onset and slow the progression of diabetes-related complications . AIMS This study aim ed to measure the effect of a 6-month telephone coaching intervention on glycaemic control , risk factor status and adherence to diabetes management practice s at the intervention 's conclusion ( 6 months ) and at 12 months . METHOD This r and omised controlled trial recruited 94 adults with type 2 diabetes and an HbA1C > 7 % from the Diabetes Clinic of St Vincent 's Hospital Melbourne . People who were non-English speaking , cognitively impaired , severely hearing impaired or without telephone access were excluded . Participants were r and omised to receive usual care plus 6 months of telephone coaching focusing on achieving treatment targets and complication screening , or usual care only . The primary outcome was HbA1C at 6 months ; secondary outcomes included other physiological and monitoring measures . RESULTS Significant interaction effects were observed between group and time at 6 months , demonstrating improvement in HbA1C , fasting glucose , diastolic blood pressure and physical activity . The intervention 's effect on these parameters was not sustained at 12 months . Intervention group participants also improved compliance with foot examinations and pneumococcal vaccination by 6 months and retinal screening by 12 months . CONCLUSIONS Telephone coaching improved glycaemic control and adherence to complication screening in people with type 2 diabetes , for the duration of its delivery , but these effects were not maintained on withdrawal of the intervention . Strategies that assist patients to sustain these benefits are required Attendance at diabetic retinopathy screening in minority ethnic groups , including the South Asian population , is known to be poor . We describe a cluster r and omised controlled trial conducted in 10 general practitioner ( GP ) surgeries in Coventry , UK , during 2007 which aim ed to evaluate the use of a Link Worker – delivered intervention to improve attendance . The intervention consisted of a simple telephone reminder with the main outcome measure being attendance at diabetic retinopathy screening . We found a statistically significant difference between mean attendance proportions for intervention ( 0.89 ) and control ( 0.74 ) practice s : difference ( 95 % confidence interval ( CI ) ) 0.15 ( 0.04–0.27 ) , t = 3.03 , p = 0.0162 ; this difference remained significant when adjusted for previous year ’s proportions . In this proof-of-concept study , in inner city Coventry , we demonstrated increased attendance at diabetic retinopathy screening by use of a simple Link Worker – implemented telephone call intervention . The use of Link Worker phone calls may be a useful tool to increase attendance for diabetic retinopathy screening in a group with high did-not-attend ( DNA ) rates and a high prevalence of diabetic retinopathy and visual impairment Introduction : Formal didactic continuing medical education ( CME ) is relatively ineffective for changing physician behaviur . Diabetes mellitus is an increasingly prevalent disease , and interventions to improve adherence to clinical practice guidelines ( CPGs ) are needed . Methods : A stratified , cluster‐r and omized , controlled trial design was used to evaluate the effects of a teleconferenced educational detailing ( TED ) CME on glycemic control ( hemoglobin [ Hb ] A1c ) and family physician adherence to national diabetes guidelines . TED employed sequential , small‐group , case‐based education using CPGs delivered by a diabetes specialist . Medical record audit data from baseline through the end of a 12‐month postintervention period were compared for the control and intervention groups . Satisfaction with the intervention was evaluated . Results : Sixty‐one physicians provided 660 medical records . The intervention did not affect mean Hb A1c levels but did significantly ( p = .04 ) alter the distribution of patients by category of glycemic control , with fewer in the intervention group in inadequate control ( 15.8 % versus 23.9 % ) . More patients took insulin ( alone or with oral agents ) in the intervention group ( 21.2 % versus 12.0 % , p = .03 ) , and more took oral agents only in the control group ( 89.0 % versus 82.9 % , p = .005 ) . More patients in the intervention group had documentation of body mass index ( 7.8 % versus 1.9 % , p < .02 ) , eye exam ( 12.1 % versus 5.1 % , p = .02 ) , and treatment plan ( 43.5 % versus 23.6 % , p = .01 ) and used a flow sheet ( 14.6 % versus 7.7 % , p < .03 ) . Although there was general satisfaction with the teleconferencing format , specialist educators found the format more challenging than the family physicians . Discussion : CME delivered by teleconference was feasible , well attended , well received by participants , and improved some key diabetes management practice s and outcomes BACKGROUND Participation in diabetic retinopathy screening is suboptimal . The Vision is Precious study ( 2001 - 2005 ) tested the hypothesis that a tailored telephone intervention in urban minority diabetes population s , offered in English or Spanish , would result in greater screening for retinopathy than a st and ard print intervention . DESIGN R and omized controlled trial SETTING / PARTICIPANTS Subjects ( N=598 ) were adults with diabetes without a dilated fundus examination ( DFE ) in > 1 year from three healthcare centers in Bronx NY . INTERVENTION A tailored telephone intervention to promote retinopathy screening compared to a st and ard print intervention over a 6-month period . MAIN OUTCOME MEASURES Documentation of a DFE within 6 months was the main outcome . Data on risk perceptions using the Risk Perception Survey for Diabetes were collected pre- and post-intervention . Electronic data bases were used to obtain hemoglobin A1c information . RESULTS Subjects were 40 % men , mean age 57 years ; 39 % reported household incomes as < $ 15 K ; 45 % reported their race as black , and 42 % reported ethnicity as Hispanic/Latino ; 23 % chose Spanish as their preferred language . Data were analyzed in 2006 . There was a 74 % increase in retinopathy screening in the telephone versus print group ( p<0.0005 ) , with no differences by intervention language or by gender . Predictors of undergoing a DFE included : telephone intervention , baseline risk-perception scores indicating less worry and more realism about diabetes complications , and the interaction of self-reported worry and being in the telephone intervention . Subjects who had poor diabetes control responded with greater success to telephone interventions . CONCLUSIONS A limited telephone intervention can improve significantly participation in retinopathy screening in a minority , low-income population . This intervention influenced risk perceptions about diabetes complications . Further research is needed to develop effective risk communications to prevent the complications of diabetes OBJECTIVES To demonstrate that pharmacists working with physicians and other providers in an ambulatory care setting can improve glucose , blood pressure , and lipid control for patients with type 2 diabetes and to report patient adherence to screening and general preventive measures . DESIGN Prospect i ve , r and omized , clinical practice study . SETTING Burlington , MA , between January 2001 and August 2003 . PATIENTS 164 patients patients with type 2 diabetes older than 18 years with glycosylated hemoglobin ( A1C ) greater than 8 % . INTERVENTION Pharmacist-patient clinic visits included obtaining a comprehensive medication review ; performing targeted physical assessment ; ordering laboratory tests ; review ing , modifying , and monitoring patients ' medication therapy and providing detailed counseling on all therapies ; facilitating self-monitoring of blood glucose ; and providing reinforcement of dietary guidelines and exercise . MAIN OUTCOME MEASURE Effect of clinical pharmacists working with physicians in an ambulatory setting on health measures ( e.g. , A1C , blood pressure , cholesterol ) of patients with diabetes . RESULTS Baseline characteristics were similar between the two groups . After 1 year , significant improvements occurred for A1C and low-density lipoprotein ( LDL ) cholesterol in the intervention group compared with the control group ( A1C , 7.7 % vs. 8.4 % ; LDL , 93.7 vs. 105.1 mg/dL ; P < 0.05 ) . Systolic blood pressure improved for all study patients without a difference between the two groups . Diastolic blood pressure improved significantly in the intervention group compared with the control group ( 73.4 mm Hg vs. 77.6 mm Hg , P < 0.05 ) . Significantly more intervention patients were screened for retinopathy , neuropathy , and microalbuminuria than control patients ( P < 0.05 ) . CONCLUSION For all indices measured , this study demonstrated that collaborative diabetes management with a clinical pharmacist can improve overall care OBJECTIVE Although an active role of the patient is often stressed in diabetes care , it is not easily implemented in daily practice . The aim of the study was to measure the effects of introducing a diabetes passport to patients after embedding the passport in the organization of care . DESIGN R and omized controlled trial . SETTING Forty general practice in The Netherl and s. PARTICIPANTS Pre- and post-intervention data were obtained from 993 patients with type 2 diabetes mellitus . Patients treated in secondary care and patients over 80 years of age were excluded . INTERVENTION The intervention consisted of clarifying the diabetes care tasks for all practice staff and embedding the diabetes passports in the structured care . Main outcome measure . Self-reported use of the diabetes passport . RESULTS Diabetes passports were issued to 87 % of the patients . After 15 months , 76 % of the patients reported that the passport was being used during clinic visits . The process indicators of care improved by 10 % on average in the intervention group . However , there were no changes in the outcome measures . CONCLUSION Diabetes passports can be introduced successfully in structured primary care and they lead to improved effect measures for medical behaviour UNLABELLED The prevalence of diabetes in Mexico among those 20 - 64 years of age has increased from 7.2 % in 1993 to 10.7 % in 2000 . National population -based surveys in Mexico demonstrated that 50 % of the total population with diabetes had blood glucose levels of 200mg/dl or higher . Thus , diabetes care has become one of the most important public health challenges in this country . The aim of the study was to improve the quality of diabetes care in primary health care centers using the chronic care model and the breakthrough series ( BTS ) collaborative methodology . METHODS Ten public health centers in the cities of Xalapa and Veracruz were r and omly selected to participate in the project . Five of the health centers were r and omly assigned to receive the intervention ( intervention group ) and the other five followed usual care ( usual care group ) . The intervention was evaluated by A1c test before and after the intervention in both groups of patients . Patients were followed for 18 months from November 2002 to May 2004 . Results were adjusted for the clustering of patients within practice s and baseline measure . RESULTS The proportion of people with good glycemic control ( A1c<7 % ) among those in the intervention group increased from 28 % before the intervention to 39 % after the intervention . The proportion of patients achieving three or more quality improvement goals increased from 16.6 % to 69.7 % ( p<0.001 ) among the intervention group while the usual care group experienced a non-significant decrease from 12.4 % to 5.9 % ( p=0.118 ) . The focus on the primary care team and the participation of people with diabetes were strategic elements incorporated into the methodology , expected to ensure sustainability of continued improvement of health outcomes . CONCLUSIONS The intervention introduced modifications to solve problems identified by health teams in their practice and improved process and outcome measures of quality diabetes care . Most of the actions were directed at four components of the chronic care model : self-management support , decision support , delivery system design , and clinical information systems OBJECTIVE To evaluate a system for improving diabetes care in remote Indigenous communities . DESIGN R and omised , unblinded cluster trial over one year ( 1 March to 29 February 2000 ) . PARTICIPANTS AND SETTING Primary healthcare staff in 21 primary healthcare centres in the Torres Strait and Northern Peninsula Area ( NPA ) Health Service District , north Queensl and , and 678 people with diabetes , mostly Torres Strait Isl and ers . INTERVENTION Diabetes recall system established at eight of the 21 sites , as well as staff training in basic diabetes care , regular phone calls from the project officer , a two-monthly newsletter and a mid-project workshop . MAIN OUTCOME MEASURES Regular checks of weight , blood pressure , eye and foot care , serum lipid levels and glucose monitoring and control , urinary albumin to creatinine ratio and serum creatinine levels , and administration of recommended vaccines ; hospitalisation in the previous 12 months . RESULTS There was improvement in most measures at most sites , except for blood pressure monitoring and control , and vaccination status . Intervention sites showed greater improvement in most indicators than control sites ( combined relative risk [ RR ] , 1.21 ; 95 % CI , 1.03 - 1.43 ) . The intervention group showed a 32 % reduction in hospital admissions for diabetes-related conditions over the study period ( P=0.012 ) . At follow-up , patients in intervention sites were 40 % less likely to be hospitalised for a diabetes-related condition than those in control sites ( RR , 0.60 ; 95 % CI , 0.41 - 0.86 ; P=0.007 ) . CONCLUSION A simple recall system , managed by local healthcare workers and supported by a diabetes outreach service , achieved significant improvements in diabetes care and reduced hospitalisations in a high-risk population OBJECTIVES This study evaluated a multicomponent educational intervention to increase ophthalmic examination rates among African Americans with diabetes . METHODS A r and omized trial was conducted with 280 African Americans with diabetes , enrolled from outpatient departments of 5 medical centers in the New York City metropolitan area , who had not had a dilated retinal examination within 14 months of r and omization ( 65.7 % female , mean age = 54.7 years [ SD = 12.8 years ] ) . RESULTS After site differences were controlled , the odds ratio for receiving a retinal examination associated with the intervention was 4.3 ( 95 % confidence interval = 2.4 , 7.8 ) . The examination rate pooled across sites was 54.7 % in the intervention group and 27.3 % in the control group . CONCLUSIONS The intervention was associated with a rate of ophthalmic examination double the rate achieved with routine medical care IMPORTANCE African American individuals are at high risk of diabetes mellitus and diabetic retinopathy but have suboptimal rates of dilated fundus examinations ( DFEs ) . Early intervention is crucial for the prevention of diabetic retinopathy in this high-risk population . OBJECTIVE To test the efficacy of behavioral activation for diabetic retinopathy prevention on rates of DFEs in older African American individuals with diabetes mellitus . DESIGN , SETTING , AND PARTICIPANTS Masked r and omized clinical trial at 2 urban medical centers from October 1 , 2010 , to May 31 , 2014 . Participants included 206 African American individuals 65 years and older with diabetes mellitus who had not obtained a DFE in the preceding 12 months . INTERVENTIONS Participants were r and omized to either behavioral activation for diabetic retinopathy prevention , a behavioral intervention design ed to provide education , facilitate identifying and addressing health care barriers , and promote goal setting to improve rates of DFEs , or supportive therapy , a control condition . MAIN OUTCOMES AND MEASURES The primary outcome was medical documentation of a DFE at 6 months ' follow-up . Secondary outcomes included the Risk Perceptions and Risk Knowledge Survey of Diabetes Mellitus , Diabetes Self-Care Inventory , Patient Health Question naire 9 , and National Eye Institute Vision Function Question naire 25 scores and hemoglobin A1c levels . RESULTS More participants in the behavioral activation for diabetic retinopathy prevention group ( 87.9 % ) obtained a DFE compared with those in the supportive therapy group ( 34.1 % ) by the 6-month follow-up assessment ( P < .001 ) . Overall , participants in the behavioral activation for diabetic retinopathy prevention group were 2.5 times more likely to obtain a DFE compared with those in the supportive therapy group ( risk ratio = 2.58 ; 95 % CI , 1.91 - 3.48 ; P < .001 ) . The intervention had no short-term effect on secondary outcomes of hemoglobin A1c levels , depression , or the Risk Perceptions and Risk Knowledge Survey of Diabetes Mellitus or National Eye Institute Vision Function Question naire 25 composite scores ; however , both groups had improved adherence to diabetes mellitus self-care behaviors from baseline to 6-month follow-up . CONCLUSIONS AND RELEVANCE Behavioral activation for diabetic retinopathy prevention significantly increased rates of DFEs in older African American individuals with diabetes mellitus . Behavioral interventions may have the potential to positively affect screening for diabetic retinopathy in at-risk population s. TRIAL REGISTRATION clinical trials.gov Identifier : NCT01179555 AIM To evaluate the effect of an educational intervention among primary care physicians on several indicators of good clinical practice in diabetes care . METHODS Two groups of physicians were r and omly assigned to the intervention or control group ( IG and CG ) . Every physician r and omly selected two sample s of patients from all type 2 diabetic patients aged 40 years and above and diagnosed more than a year ago . Baseline and final information were collected cross-sectionally 12 months apart , in two independent sample s of 30 patients per physician . The educational intervention comprised : distribution of educational material s and physicians ' specific bench-marking information , an on-line course and three on-site educational workshops on diabetes . External observers collected information directly from the physicians and from the medical records of the patients on personal and family history of disease and on the evolution and treatment of their disease . Baseline information was collected retrospectively in the control group . RESULTS Intervention group comprised 53 physicians who included a total of 3018 patients in the baseline and final evaluations . CG comprised 50 physicians who included 2868 patients in the same evaluations . Measurement of micro-albuminuria in the last 12 months ( OR = 1.6 , 95 % CI : 1.1 - 2.4 ) and foot examination in the last year ( OR = 2.0 , 95 % CI : 1.1 - 3.6 ) were the indicators for which greater improvement was found in the IG . No other indicator considered showed statistically significant improvement between groups . CONCLUSIONS The identification of indicators with very low level of compliance and the implementation of a simple intervention in physicians to correct them is effective in improving the quality of care of diabetic patients The objective of this article is to quantify quality improvement using data from a r and omized controlled trial that tested the effectiveness of a community health worker in the primary role of diabetes educator in a clinic serving uninsured Mexican Americans . The intervention group received 7 hours of diabetes education/case management in excess of usual medical care . Of 16 process and outcome measures evaluated , the intervention group was significantly more likely to have received a dilated retinal examination , and 53 % achieved a hemoglobin A1c below 7 % compared with 38 % of the control group participants . Composite quality measures were similar in magnitude with published practice -based benchmarks at study conclusion . This suggests that the overall diabetes care delivered in this clinic serving uninsured patients was comparable to the levels of excellence achieved in other primary care setting s. Quantitative measurements of quality improvement can inform health policy regarding the relative effectiveness of diabetes interventions OBJECTIVE To determine whether multiple mailed patient reminders can produce an increase in the rate of diabetic retinal examinations ( DRE ) over that seen with a single reminder . RESEARCH DESIGN AND METHODS All diabetic members > or = 18 years who were enrolled in a large network-based health maintenance organization ( HMO ) in California from August 1996 to July 1997 were identified using cl aims and pharmacy data bases . Members who had no record of DRE in the HMO 's cl aims data base were then r and omized into two groups . Both groups received mailed educational material s and a reminder to obtain the examination . Their physician groups also received a letter explaining the program , current guidelines for DRE , and a list of their diabetes patients with their DRE status . The single intervention group received no additional reminders . The multiple intervention group received additional reminders at 3 , 6 , and 9 months after baseline if they continued with no record of service , as determined from the cl aims data base . RESULTS The study cohort comprised 19,523 diabetic members , which were r and omized into single ( n = 9,614 ) and multiple ( n = 9,909 ) intervention groups . There was an increase in monthly DRE rates after the intervention in August 1996 for both intervention groups . After the second reminder was sent to the multiple intervention group , the percentage of diabetic members receiving DRE was higher than the single intervention group . Rates before and after the third intervention were not significantly different , nor were monthly differences found . There was a significant difference in overall annual DRE rates between the groups ( P = 0.023 ) . CONCLUSIONS Multiple patient reminders are more effective than single reminders in improving DRE rates in a managed care setting . However , the improvement noted was clinical ly small and appeared only after the second reminder ; no incremental improvement was seen with additional reminders . Re sources used for multiple reminders aim ed at diabetic retinopathy might better be spent on other approaches to reducing complications of diabetes Background The diabetes of many patients is managed in general practice ; healthcare providers aim to promote healthful behaviors , such as healthful diet , adequate physical activity , and smoking cessation . These measures may decrease insulin resistance , improve glycemic control , lipid abnormalities , and hypertension . They may also prevent cardiovascular disease and complications of diabetes . However , professionals do not adhere optimally to guidelines for lifestyle counseling . Motivational interviewing to change the lifestyle of patients with type 2 diabetes is intended to improve diabetes care in accordance with the national guidelines for lifestyle counseling . Primary care nurses will be trained in motivational interviewing embedded in structured care in general practice . The aim of this paper is to describe the design and methods of a study evaluating the effects of the nurses ' training on patient outcomes . Methods / Design A cluster , r and omized , controlled trial involving 70 general practice s ( 35 practice s in the intervention arm and 35 in the control arm ) starting in March 2007 . A total of 700 patients with type 2 diabetes will be recruited . The patients in the intervention arm will receive care from the primary care nurse , who will receive training in an implementation strategy with motivational interviewing as the core component . Other components of this strategy will be adaptation of the diabetes protocol to local circumstances , introduction of a social map for lifestyle support , and educational and supportive tools for sustaining motivational interviewing . The control arm will be encouraged to maintain usual care . The effect measures will be the care process , metabolic parameters ( glycosylated hemoglobin , blood pressure and lipids ) , lifestyle ( diet , physical activity , smoking , and alcohol ) , health-related quality of life , and patients ' willingness to change behaviors . The measurements will take place at baseline and after 14 months . Discussion Applying motivational interviewing for patients with diabetes in primary care has been studied , but to our knowledge , no other study has yet evaluated the implementation and sustainability of motivating and involving patients in day-to-day diabetes care in general practice . If this intervention proves to be effective and cost-effective , large-scale implementation of this nurse-oriented intervention will be considered and anticipated . Trial registration Current Controlled Trials IS RCT N68707773 |
10,598 | 30,632,926 | Despite the limitations , this study provides additional support for CBT-E as a successful treatment across the range of EDs | ABSTRACT Enhanced cognitive behaviour therapy ( CBT-E ) has recently generated interest as a potentially useful treatment for eating disorders ( ED ) . | OBJECTIVE A subset of individuals with bulimia nervosa ( BN ) have borderline personality disorder ( BPD ) symptoms , including chronic negative affect and interpersonal problems . These symptoms predict poor BN treatment outcome in some studies . The broad version of Enhanced Cognitive Behavior Therapy ( CBT-E ) was developed to address co-occurring problems that interfere with treatment response . The current study investigated the relative effects , predictors , and moderators of CBT-E for BN with BPD and co-occurring mood/anxiety disorders . METHOD Fifty patients with BN and threshold or sub-threshold BPD and current or recent Axis I mood or anxiety disorders were r and omly assigned to receive focused CBT-E ( CBT-Ef ) or broad CBT-E ( CBT-Eb ) specifically including an interpersonal module and additional attention to mood intolerance . RESULTS Forty-two percent of the sample reported remission from binge eating and purging at termination . Significant changes across symptom domains were observed at termination and at 6-month follow-up . Though CBT-Ef predicted good outcomes in multivariate models , the severity of affective/interpersonal problems moderated treatment effects : participants with higher severity showed better ED outcomes in CBT-Eb , whereas those with lower severity showed better outcomes in CBT-Ef . Severity of affective/interpersonal BPD symptoms at baseline predicted negative outcomes overall . Follow-up BPD affective/interpersonal problems were predicted by baseline affective/interpersonal problems and by termination EDE score . DISCUSSION This study supports the utility of CBT-E for patients with BN and complex comorbidity . CBT-Ef appears to be more efficacious for patients with relatively less severe BPD symptoms , whereas CBT-Eb appears to be more efficacious for patients with more severe BPD symptoms Eating disorders may be viewed from a transdiagnostic perspective and there is evidence supporting a transdiagnostic form of cognitive behaviour therapy ( CBT-E ) . The aim of the present study was to compare CBT-E with interpersonal psychotherapy ( IPT ) , a leading alternative treatment for adults with an eating disorder . One hundred and thirty patients with any form of eating disorder ( body mass index > 17.5 to < 40.0 ) were r and omized to either CBT-E or IPT . Both treatments involved 20 sessions over 20 weeks followed by a 60-week closed follow-up period . Outcome was measured by independent blinded assessors . Twenty-nine participants ( 22.3 % ) did not complete treatment or were withdrawn . At post-treatment 65.5 % of the CBT-E participants met criteria for remission compared with 33.3 % of the IPT participants ( p < 0.001 ) . Over follow-up the proportion of participants meeting criteria for remission increased , particularly in the IPT condition , but the CBT-E remission rate remained higher ( CBT-E 69.4 % , IPT 49.0 % ; p = 0.028 ) . The response to CBT-E was very similar to that observed in an earlier study . The findings indicate that CBT-E is potent treatment for the majority of out patients with an eating disorder . IPT remains an alternative to CBT-E , but the response is less pronounced and slower to be expressed . Current controlled trials IS RCT N 15562271 What kinds of evidence reliably support predictions of effectiveness for health and social care interventions ? There is increasing reliance , not only for health care policy and practice but also for more general social and economic policy deliberation , on evidence that comes from studies whose basic logic is that of JS Mill 's method of difference . These include r and omized controlled trials , case-control studies , cohort studies , and some uses of causal Bayes nets and counterfactual-licensing models like ones commonly developed in econometrics . The topic of this paper is the ' external validity ' of causal conclusions from these kinds of studies . We shall argue two cl aims . Cl aim , negative : external validity is the wrong idea ; cl aim , positive : ' capacities ' are almost always the right idea , if there is a right idea to be had . If we are right about these cl aims , it makes big problems for policy decisions . Many advice guides for grading policy predictions give top grade s to a proposed policy if it has two good Mill's- method -of difference studies that support it . But if capacities are to serve as the conduit for support from a method -of-difference study to an effectiveness prediction , much more evidence , and much different in kind , is required . We will illustrate the complexities involved with the case of multisystemic therapy , an internationally adopted intervention to try to diminish antisocial behaviour in young people Consistent predictors , and more especially moderators , of response to psychological treatments for eating disorders have not been identified . The present exploratory study examined predictors and moderators of outcome in adult patients who took part in a r and omised clinical trial comparing two leading treatments for these disorders , enhanced cognitive behavioural therapy ( CBT-E ) and interpersonal psychotherapy ( IPT ) . Four potentially important findings emerged . Firstly , patients with a longer duration of disorder were less likely to benefit from either treatment . Second , across the two treatments the presence , at baseline , of higher levels of over-evaluation of the importance of shape predicted a less good treatment outcome . Third DSM-IV diagnosis did not predict treatment outcome . Fourth , with the exception of patients with baseline low self-esteem who achieved a better outcome with CBT-E , it was generally not possible to identify a subgroup of patients who would differentially benefit from one or other treatment OBJECTIVE The aim of this study was to compare two cognitive-behavioral treatments for out patients with eating disorders , one focusing solely on eating disorder features and the other a more complex treatment that also addresses mood intolerance , clinical perfectionism , low self-esteem , or interpersonal difficulties . METHOD A total of 154 patients who had a DSM-IV eating disorder but were not markedly underweight ( body mass index over 17.5 ) , were enrolled in a two-site r and omized controlled trial involving 20 weeks of treatment and a 60-week closed period of follow-up . The control condition was an 8-week waiting list period preceding treatment . Outcomes were measured by independent assessors who were blind to treatment condition . RESULTS Patients in the waiting list control condition exhibited little change in symptom severity , whereas those in the two treatment conditions exhibited substantial and equivalent change , which was well maintained during follow-up . At the 60-week follow-up assessment , 51.3 % of the sample had a level of eating disorder features less than one st and ard deviation above the community mean . Treatment outcome did not depend on eating disorder diagnosis . Patients with marked mood intolerance , clinical perfectionism , low self-esteem , or interpersonal difficulties appeared to respond better to the more complex treatment , with the reverse pattern evident among the remaining patients . CONCLUSIONS These two transdiagnostic treatments appear to be suitable for the majority of out patients with an eating disorder . The simpler treatment may best be viewed as the default version , with the more complex treatment reserved for patients with marked additional psychopathology of the type targeted by the treatment Anorexia nervosa is difficult to treat and no treatment is supported by robust evidence . As it is uncommon , it has been recommended that new treatments should undergo extensive preliminary testing before being evaluated in r and omized controlled trials . The aim of the present study was to establish the immediate and longer-term outcome following “ enhanced ” cognitive behaviour therapy ( CBT-E ) . Ninety-nine adult patients with marked anorexia nervosa ( body mass index ≤ 17.5 ) were recruited from consecutive referrals to clinics in the UK and Italy . Each was offered 40 sessions of CBT-E over 40 weeks with no concurrent treatment . Sixty-four percent of the patients were able to complete this outpatient treatment and in these patients there was a substantial increase in weight ( 7.47 kg , SD 4.93 ) and BMI ( 2.77 , SD 1.81 ) . Eating disorder features also improved markedly . Over the 60-week follow-up period there was little deterioration despite minimal additional treatment . These findings provide strong preliminary support for this use of CBT-E and justify its further evaluation in r and omized controlled trials . As CBT-E has already been established as a treatment for bulimia nervosa and eating disorder not otherwise specified , the findings also confirm that CBT-E is transdiagnostic in its scope OBJECTIVE This r and omized control trial is an evaluation of the effectiveness of enhanced cognitive behavioral treatment ( CBT-E ) for eating disorders adapted for a group setting . The study aim ed to examine the effects of group CBT-E on eating disorder psychopathology and additional maintaining pathology . METHOD A transdiagnostic sample of individuals with eating disorders with a BMI ≥ 18 kg/m2 ( N = 40 ) were r and omized to an immediate-start or delayed-start condition so as to compare therapeutic effects of group CBT-E with a waitlist control . Global Eating Disorder Examination Question naire ( EDE-Q ) scores , BMI , and measures of Clinical Perfectionism , Self-Esteem , Interpersonal Difficulties , and Mood Intolerance were measured across the 8-week control period , throughout the group treatment and at 3-months post-treatment . RESULTS Over 70 % of those who entered the trial completed treatment . The first eight weeks of group CBT-E were more effective at reducing Global EDE-Q scores than no treatment ( waitlist control ) . By post-treatment , good outcome ( a Global EDE-Q within 1 SD of Australian community norms plus BMI ≥ 18.5 ) was achieved by 67.9 % of treatment completers and 66.7 % of the total sample . Symptom abstinence within the previous month was reported by 14.3 % of treatment completers and 10.3 % of the total sample . Significant reductions in Clinical Perfectionism , Self-Esteem , Interpersonal Difficulties , and Mood Intolerance were also observed . DISCUSSION This study demonstrated that a group version of CBT-E can be effective at reducing eating disorder psychopathology in a transdiagnostic sample of individuals with eating disorders . Group CBT-E could provide a means of increasing availability of evidence -based treatment for eating disorders BACKGROUND There are no evidence -based treatments for severe and enduring anorexia nervosa ( SE-AN ) . This study evaluated the relative efficacy of cognitive behavioral therapy ( CBT-AN ) and specialist supportive clinical management ( SSCM ) for adults with SE-AN . METHOD Sixty-three participants with a diagnosis of AN , who had at least a 7-year illness history , were treated in a multi-site r and omized controlled trial ( RCT ) . During 30 out-patient visits spread over 8 months , they received either CBT-AN or SSCM , both modified for SE-AN . Participants were assessed at baseline , end of treatment ( EOT ) , and at 6- and 12-month post-treatment follow-ups . The main outcome measures were quality of life , mood disorder symptoms and social adjustment . Weight , eating disorder ( ED ) psychopathology , motivation for change and health-care burden were secondary outcomes . RESULTS Thirty-one participants were r and omized to CBT-AN and 32 to SSCM with a retention rate of 85 % achieved at the end of the study . At EOT and follow-up , both groups showed significant improvement . There were no differences between treatment groups at EOT . At the 6-month follow-up , CBT-AN participants had higher scores on the Weissman Social Adjustment Scale ( WSAS ; p = 0.038 ) and at 12 months they had lower Eating Disorder Examination ( EDE ) global scores ( p = 0.004 ) and higher readiness for recovery ( p = 0.013 ) compared to SSCM . CONCLUSIONS Patients with SE-AN can make meaningful improvements with both therapies . Both treatments were acceptable and high retention rates at follow-up were achieved . Between-group differences at follow-up were consistent with the nature of the treatments given BACKGROUND Anorexia nervosa ( AN ) is a serious illness leading to substantial morbidity and mortality . The treatment of AN very often is protracted ; repeated hospitalizations and lost productivity generate substantial economic costs in the health care system . Therefore , this study aim ed to determine the differential cost-effectiveness of out-patient focal psychodynamic psychotherapy ( FPT ) , enhanced cognitive-behavioural therapy ( CBT-E ) , and optimized treatment as usual ( TAU-O ) in the treatment of adult women with AN . METHOD The analysis was conducted alongside the r and omized controlled Anorexia Nervosa Treatment of Out Patients ( ANTOP ) study . Cost-effectiveness was determined using direct costs per recovery at 22 months post-r and omization ( n = 156 ) . Unadjusted incremental cost-effectiveness ratios ( ICERs ) were calculated . To derive cost-effectiveness acceptability curves ( CEACs ) adjusted net-benefit regressions were applied assuming different values for the maximum willingness to pay ( WTP ) per additional recovery . Cost-utility and assumptions underlying the base case were investigated in exploratory analyses . RESULTS Costs of in-patient treatment and the percentage of patients who required in-patient treatment were considerably lower in both intervention groups . The unadjusted ICERs indicated FPT and CBT-E to be dominant compared with TAU-O. Moreover , FPT was dominant compared with CBT-E. CEACs showed that the probability for cost-effectiveness of FTP compared with TAU-O and CBT-E was ⩾95 % if the WTP per recovery was ⩾€9825 and ⩾€24 550 , respectively . Comparing CBT-E with TAU-O , the probability of being cost-effective remained < 90 % for all WTPs . The exploratory analyses showed similar but less pronounced trends . CONCLUSIONS Depending on the WTP , FPT proved cost-effective in the treatment of adult AN BACKGROUND The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa ( BN ) , integrative cognitive-affective therapy ( ICAT ) , with an established treatment , ' enhanced ' cognitive-behavioral therapy ( CBT-E ) . METHOD Eighty adults with symptoms of BN were r and omized to ICAT or CBT-E for 21 sessions over 19 weeks . Bulimic symptoms , measured by the Eating Disorder Examination ( EDE ) , were assessed at baseline , at the end of treatment ( EOT ) and at the 4-month follow-up . Treatment outcome , measured by binge eating frequency , purging frequency , global eating disorder severity , emotion regulation , self-oriented cognition , depression , anxiety and self-esteem , was determined using generalized estimating equations ( GEEs ) , logistic regression and a general linear model ( intent-to-treat ) . RESULTS Both treatments were associated with significant improvement in bulimic symptoms and in all measures of outcome , and no statistically significant differences were observed between the two conditions at EOT or follow-up . Intent-to-treat abstinence rates for ICAT ( 37.5 % at EOT , 32.5 % at follow-up ) and CBT-E ( 22.5 % at both EOT and follow-up ) were not significantly different . CONCLUSIONS ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial r and omized controlled trial of a new individual psychotherapy for BN suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study BACKGROUND There is a lack of evidence pointing to the efficacy of any specific psychotherapy for adults with anorexia nervosa ( AN ) . The aim of this study was to compare three psychological treatments for AN : Specialist Supportive Clinical Management , Maudsley Model Anorexia Nervosa Treatment for Adults and Enhanced Cognitive Behavioural Therapy . METHOD A multi-centre r and omised controlled trial was conducted with outcomes assessed at pre- , mid- and post-treatment , and 6- and 12-month follow-up by research ers blind to treatment allocation . All analyses were intention-to-treat . One hundred and twenty individuals meeting diagnostic criteria for AN were recruited from outpatient treatment setting s in three Australian cities and offered 25 - 40 sessions over a 10-month period . Primary outcomes were body mass index ( BMI ) and eating disorder psychopathology . Secondary outcomes included depression , anxiety , stress and psychosocial impairment . RESULTS Treatment was completed by 60 % of participants and 52.5 % of the total sample completed 12-month follow-up . Completion rates did not differ between treatments . There were no significant differences between treatments on continuous outcomes ; all result ed in clinical ly significant improvements in BMI , eating disorder psychopathology , general psychopathology and psychosocial impairment that were maintained over follow-up . There were no significant differences between treatments with regard to the achievement of a healthy weight ( mean = 50 % ) or remission ( mean = 28.3 % ) at 12-month follow-up . CONCLUSION The findings add to the evidence base for these three psychological treatments for adults with AN , but the results underscore the need for continued efforts to improve outpatient treatments for this disorder . Trial Registration Australian New Zeal and Clinical Trials Registry ( ACTRN 12611000725965 ) The aim of this study was to examine the effectiveness of Enhanced Cognitive Behaviour Therapy ( CBT-E ) for eating disorders in an open trial for adults with the full range of eating disorders found in the community . The only previously published trial of CBT-E for eating disorders was a r and omised controlled trial ( RCT ) conducted in the U.K. for patients with a BMI ≥ 17.5 . The current study represents the first published trial of CBT-E to include patients with a BMI < 17.5 . The study involved 125 patients referred to a public outpatient clinic in Perth , Western Australia . Patients attended , on average , 20 - 40 individual sessions with a clinical psychologist . Of those who entered the trial , 53 % completed treatment . Longer waiting time for treatment was significantly associated with drop out . By the end of treatment full remission ( cessation of all key eating disorder behaviours , BMI ≥ 18.5 kg/m(2 ) , not meeting DSM-IV criteria for an eating disorder ) or partial remission ( meeting at least 2 these criteria ) was achieved by two thirds of the patients who completed treatment and 40 % of the total sample . The results compared favourably to those reported in the previous RCT of CBT-E , with one exception being the higher drop-out rate in the current study . Overall , the findings indicated that CBT-E results in significant improvements , in both eating and more general psychopathology , in patients with all eating disorders attending an outpatient clinic BACKGROUND Psychotherapy is the treatment of choice for patients with anorexia nervosa , although evidence of efficacy is weak . The Anorexia Nervosa Treatment of Out Patients ( ANTOP ) study aim ed to assess the efficacy and safety of two manual-based outpatient treatments for anorexia nervosa -- focal psychodynamic therapy and enhanced cognitive behaviour therapy -- versus optimised treatment as usual . METHODS The ANTOP study is a multicentre , r and omised controlled efficacy trial in adults with anorexia nervosa . We recruited patients from ten university hospitals in Germany . Participants were r and omly allocated to 10 months of treatment with either focal psychodynamic therapy , enhanced cognitive behaviour therapy , or optimised treatment as usual ( including outpatient psychotherapy and structured care from a family doctor ) . The primary outcome was weight gain , measured as increased body-mass index ( BMI ) at the end of treatment . A key secondary outcome was rate of recovery ( based on a combination of weight gain and eating disorder-specific psychopathology ) . Analysis was by intention to treat . This trial is registered at http://is rct n.org , number IS RCT N72809357 . FINDINGS Of 727 adults screened for inclusion , 242 underwent r and omisation : 80 to focal psychodynamic therapy , 80 to enhanced cognitive behaviour therapy , and 82 to optimised treatment as usual . At the end of treatment , 54 patients ( 22 % ) were lost to follow-up , and at 12-month follow-up a total of 73 ( 30 % ) had dropped out . At the end of treatment , BMI had increased in all study groups ( focal psychodynamic therapy 0·73 kg/m(2 ) , enhanced cognitive behaviour therapy 0·93 kg/m(2 ) , optimised treatment as usual 0·69 kg/m(2 ) ) ; no differences were noted between groups ( mean difference between focal psychodynamic therapy and enhanced cognitive behaviour therapy -0·45 , 95 % CI -0·96 to 0·07 ; focal psychodynamic therapy vs optimised treatment as usual -0·14 , -0·68 to 0·39 ; enhanced cognitive behaviour therapy vs optimised treatment as usual -0·30 , -0·22 to 0·83 ) . At 12-month follow-up , the mean gain in BMI had risen further ( 1·64 kg/m(2 ) , 1·30 kg/m(2 ) , and 1·22 kg/m(2 ) , respectively ) , but no differences between groups were recorded ( 0·10 , -0·56 to 0·76 ; 0·25 , -0·45 to 0·95 ; 0·15 , -0·54 to 0·83 , respectively ) . No serious adverse events attributable to weight loss or trial participation were recorded . INTERPRETATION Optimised treatment as usual , combining psychotherapy and structured care from a family doctor , should be regarded as solid baseline treatment for adult out patients with anorexia nervosa . Focal psychodynamic therapy proved advantageous in terms of recovery at 12-month follow-up , and enhanced cognitive behaviour therapy was more effective with respect to speed of weight gain and improvements in eating disorder psychopathology . Long-term outcome data will be helpful to further adapt and improve these novel manual-based treatment approaches . FUNDING German Federal Ministry of Education and Research ( Bundesministerium für Bildung und Forschung , BMBF ) , German Eating Disorders Diagnostic and Treatment Network ( EDNET ) OBJECTIVE To evaluate the effectiveness of a motivation-focused intervention prior to individual cognitive behavioural eating disorder treatment . METHOD Enhanced cognitive-behavioural therapy ( CBT-E ) in its usual form was compared with CBT-E preceded by four sessions of motivation-focused therapy ( MFT ) ( MFT + CBT-E ) . Participants were adult out patients seen at a specialist eating disorder clinic in Western Australia , who met criteria for a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition eating disorder . A sequential trial of CBT-E as usual ( n = 43 ) and MFT + CBT-E ( n = 52 ) was conducted over a 40-month period . RESULTS The MFT phase was associated with significant increases in readiness to change . There were no significant between-group differences in treatment completion rates , and treatment completers in both conditions reported comparable reductions in eating disorder symptoms over time . CONCLUSION In this sample , MFT + CBT-E was not associated with superior treatment outcome when compared with CBT-E as usual Clinical response and relapse following a regimen of osteopathic manual treatment ( OMT ) were assessed in patients with chronic low back pain ( LBP ) within the OSTEOPATHIC Trial , a r and omized , double-blind , sham-controlled study . Initial clinical response and subsequent stability of response , including final response and relapse status at week 12 , were determined in 186 patients with high baseline pain severity ( ≥50 mm on a 100-mm visual analogue scale ) . Substantial improvement in LBP , defined as 50 % or greater pain reduction relative to baseline , was used to assess clinical response at weeks 1 , 2 , 4 , 6 , 8 , and 12 . Sixty-two ( 65 % ) patients in the OMT group attained an initial clinical response vs. 41 ( 45 % ) patients in the sham OMT group ( risk ratio [ RR ] , 1.45 ; 95 % confidence interval [ CI ] , 1.11 - 1.90 ) . The median time to initial clinical response to OMT in these patients was 4 weeks . Among patients with an initial clinical response prior to week 12 , 13 ( 24 % ) patients in the OMT group vs. 18 ( 51 % ) patients in the sham OMT group relapsed ( RR , 0.47 ; 95 % CI , 0.26 - 0.83 ) . Overall , 49 ( 52 % ) patients in the OMT group attained or maintained a clinical response at week 12 vs. 23 ( 25 % ) patients in the sham OMT group ( RR , 2.04 ; 95 % CI , 1.36 - 3.05 ) . The large effect size for short-term efficacy of OMT was driven by stable responders who did not relapse |
10,599 | 31,110,933 | Interventions that incorporated these factors were associated with effectiveness .
Education about how to reduce future risk of Type 2 diabetes and using pedometers in interventions were not associated with intervention effectiveness .
Other factors that future interventions should address consist of ' putting others before yourself ' ; ' putting off lifestyle change ' ; ' lack of support from healthcare professionals ' and ' being a healthy role model for families ' .
Conclusion Combining the results of qualitative and quantitative studies can provide a nuanced underst and ing of the effectiveness of physical activity and lifestyle interventions | Women with previous Gestational Diabetes Mellitus ( GDM ) have seven times the risk of Type 2 diabetes later in life compared to women without GDM .
Physical activity can reduce this risk and most women with previous GDM are not physically active .
Aims To explore : ( 1 ) effectiveness of physical activity interventions for women with previous GDM ; ( 2 ) factors that women with previous GDM perceive influence their physical activity ; ( 3 ) how these factors are addressed by the interventions . | OBJECTIVE To pilot , among women with gestational diabetes mellitus ( GDM ) , the feasibility of a prenatal/postpartum intervention to modify diet and physical activity similar to the Diabetes Prevention Program . The intervention was delivered by telephone , and support for breastfeeding was addressed . RESEARCH DESIGN AND METHODS The goal was to help women return to their prepregnancy weight , if it was normal , or achieve a 5 % reduction from prepregnancy weight if overweight . Eligible participants were identified shortly after a GDM diagnosis ; 83.8 % consented to be r and omly assigned to intervention or usual medical care ( 96 and 101 women , respectively ) . The retention was 85.2 % at 12 months postpartum . RESULTS The proportion of women who reached the postpartum weight goal was higher , although not statistically significant , in the intervention condition than among usual care ( 37.5 vs. 21.4 % , absolute difference 16.1 % , P = 0.07 ) . The intervention was more effective among women who did not exceed the recommended gestational weight gain ( difference in the proportion of women meeting the weight goals : 22.5 % , P = 0.04 ) . The intervention condition decreased dietary fat intake more than the usual care ( condition difference in the mean change in percent of calories from fat : −3.6 % , P = 0.002 ) and increased breastfeeding , although not significantly ( condition difference in proportion : 15.0 % , P = 0.09 ) . No differences in postpartum physical activity were observed between conditions . CONCLUSIONS This study suggests that a lifestyle intervention that starts during pregnancy and continues postpartum is feasible and may prevent pregnancy weight retention and help overweight women lose weight . Strategies to help postpartum women overcome barriers to increasing physical activity are needed OBJECTIVE There is increasing evidence about the importance of factors that impact health beyond health care and individual behavior , yet there is little public and policy discourse about these things in the United States . We surveyed Wisconsin adults to see what they think are the most important factors that affect health . We also examined which interventions they believe would improve health , and whether government should prioritize such interventions . METHODS A phone survey of a r and om sample of 1459 Wisconsin adults was conducted between September 2006 and February 2007 . RESULTS The Wisconsin public believes that health practice s , access to health care , and health insurance are the most important factors affecting health , and that health insurance is a high government priority . Other broader social and economic determinants of health , such as employment , social support , income , housing , and neighborhood factors are seen as less important to health . Although respondents believe that health practice s are important to health , they are less likely to suggest that government prioritize improving individual health practice s. Although the public believes the government should prioritize access to health care and health insurance , they are not as likely to support government implementing social or economic policies in order to improve health . CONCLUSION In light of research demonstrating the importance of social and economic determinants of health , and of ongoing public forums meant to raise awareness of these determinants of health , it will be important to track whether public opinion of Wisconsin adults changes over time to increase attention to the social and economic determinants of health and related policy initiatives Background Women with gestational diabetes ( GDM ) are at high risk of developing diabetes later in life . After a GDM diagnosis , women receive prenatal care to control their blood glucose levels via diet , physical activity and medications . Continuing such lifestyle skills into early motherhood may reduce the risk of diabetes in this high risk population . In the Gestational Diabetes ’ Effects on Moms ( GEM ) study , we are evaluating the comparative effectiveness of diabetes prevention strategies for weight management design ed for pregnant/postpartum women with GDM and delivered at the health system level . Methods / Design The GEM study is a pragmatic cluster r and omized clinical trial of 44 medical facilities at Kaiser Permanente Northern California r and omly assigned to either the intervention or usual care conditions , that includes 2,320 women with a GDM diagnosis between March 27 , 2011 and March 30 , 2012 . A Diabetes Prevention Program-derived print/telephone lifestyle intervention of 13 telephonic sessions tailored to pregnant/postpartum women was developed . The effectiveness of this intervention added to usual care is to be compared to usual care practice s alone , which includes two pages of printed lifestyle recommendations sent to postpartum women via mail . Primary outcomes include the proportion of women who reach a postpartum weight goal and total weight change . Secondary outcomes include postpartum glycemia , blood pressure , depression , percent of calories from fat , total caloric intake and physical activity levels . Data were collected through electronic medical records and surveys at baseline ( soon after GDM diagnosis ) , 6 weeks ( range 2 to 11 weeks ) , 6 months ( range 12 to 34 weeks ) and 12 months postpartum ( range 35 to 64 weeks ) . Discussion There is a need for evidence regarding the effectiveness of lifestyle modification for the prevention of diabetes in women with GDM , as well as confirmation that a diabetes prevention program delivered at the health system level is able to successfully reach this population . Given the use of a telephonic case management model , our Diabetes Prevention Program-derived print/telephone intervention has the potential to be adopted in other setting s and to inform policies to promote the prevention of diabetes among women with GDM.Trial registration Clinical Trials.gov number , NCT01344278 Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results AIMS To report the weight loss findings after the first year of a lifestyle intervention trial among women with gestational diabetes mellitus ( GDM ) . METHODS A total of 1180 women with GDM were r and omly assigned ( 1:1 ) to receive a 4-year lifestyle intervention ( intervention group , n = 586 ) or st and ard care ( control group , n = 594 ) between August 2009 and July 2011 . Major elements of the intervention included 6 face-to-face sessions with study dieticians and two telephone calls in the first year , and two individual sessions and two telephone calls in each subsequent year . RESULTS Among 79 % of participants who completed the year 1 trial , mean weight loss was 0.82 kg ( 1.12 % of initial weight ) in the intervention group and 0.09 kg ( 0.03 % of initial weight ) in the control group ( P = .001 ) . In a prespecified subgroup analysis of people who completed the trial , weight loss was more pronounced in women who were overweight ( body mass index ≥24 kg/m2 ) at baseline : mean weight loss 2.01 kg ( 2.87 % of initial weight ) in the intervention group and 0.44 kg ( 0.52 % of initial weight ) in the control group ( P < .001 ) . Compared with those in the control group , women in the intervention group had a greater decrease in waist circumference ( 1.76 cm vs 0.73 cm ; P = .003 ) and body fat ( 0.50 % vs 0.05 % increase ; P = .001 ) . CONCLUSION The 1-year lifestyle intervention led to significant weight losses after delivery in women who had GDM , and the effect was more pronounced in women who were overweight at baseline The YMCA ’s Diabetes Prevention Program gives you the skills you need and the support you deserve to make lasting healthy lifestyle changes . WHAT IS PREDIABETES ? Prediabetes occurs when blood sugar levels are higher than normal but not high enough for a type 2 diabetes diagnosis . Risk for developing type 2 diabetes may be reduced or eliminated by weight loss , healthier eating and increased physical activity AIMS To explore factors influencing post-natal health behaviours following the experience of gestational diabetes , and to elicit women 's views about the feasibility of lifestyle intervention to prevent diabetes during the first 2 years after childbirth . METHODS Qualitative study using semi-structured interviews with women who had gestational diabetes . In phase 1 ( 31 women ) , interviews explored the experience of gestational diabetes , ideas about future risk of diabetes and factors influencing post-natal health-related behaviours . Statements were developed summarizing women 's views of lifestyle change to prevent diabetes . In phase 2 ( 14 women ) , interviews explored how the passage of time had contributed to changes in health behaviour , and the statements were used to develop views about diabetes interventions . RESULTS Women were aware of their risk of developing diabetes , but did not always act on such knowledge . Pregnancy motivated behaviour changes to benefit the unborn child , but after delivery these changes were often not maintained . Tiredness , maternal attachment and childcare dem and s were prominent barriers in the early post-natal months . Later , work , family and child development became more significant barriers . Many women became more receptive to healthy eating messages around the time of weaning . Women were positive about long-term support for self-management to reduce their diabetes risk . CONCLUSIONS There is potential to reduce the risk of Type 2 diabetes post-natally among women with gestational diabetes . Interventions need to be developed that take into account context ual factors and competing dem and s , are flexible and respond to women 's individual circumstances . R and omized trials of such interventions are warranted OBJECTIVE In this study , we examined patterns of postpartum physical activity among women with recent gestational diabetes mellitus ( GDM ) and psychosocial factors related to this behavior that could be addressed in diabetes prevention interventions . RESEARCH DESIGN AND METHODS A r and om sample of women who had attended diabetes clinics in Sydney , Australia , in the past 6 - 24 months for treatment of GDM were surveyed by telephone . Variables measured included physical activity behaviors , self-efficacy , social support , and barriers to participation . RESULTS Of 226 women who completed the survey ( mean age 33.4 years ) , 26.5 % were classified as sedentary , and only 33.6 % reported sufficient physical activity as recommended by health authorities . Walking was the most popular physical activity , and most women reported no other moderate- or vigorous-intensity activity . Lack of assistance with child care ( 49.1 % ) and insufficient time ( 37.6 % ) were the most common barriers to physical activity . The type of social support most often reported was verbal encouragement ( 39.1 % ) , with more than half of the women never receiving assistance with housework or others exercising with them . Self-efficacy for physical activity was lowest when women were under time pressure or tired . Multivariate analyses showed that sufficient physical activity was associated with high social support ( odds ratio 2.5 [ 95 % CI 1.21 - 3.79 ] ) and high self-efficacy ( 2.09 [ 1.06 - 3.20 ] ) . CONCLUSIONS The prevalence of sufficient physical activity was found to be low and strongly related to social support and self-efficacy . This is an important group to whom diabetes prevention strategies can be targeted Optimal strategies to prevent progression towards overt diabetes in women with recent gestational diabetes remain ill defined . We report a pilot study of a convenient , home based exercise program with telephone support , suited to the early post-partum period . Twenty eight women with recent gestational diabetes were enrolled at six weeks post-partum into a 12 week r and omised controlled trial of Usual Care ( n = 13 ) versus Supported Care ( individualised exercise program with regular telephone support ; n = 15 ) . Baseline characteristics ( Mean ± SD ) were : Age 33 ± 4 years ; Weight 80 ± 20 kg and Body Mass Index ( BMI ) 30.0 ± 9.7 kg/m2 . The primary outcome , planned physical activity { Median ( Range ) } , increased by 60 ( 0–540 ) mins/week in the SC group versus 0 ( 0–580 ) mins/week in the UC group ( P = 0.234 ) . Walking was the predominant physical activity . Body weight , BMI , waist circumference , % body fat , fasting glucose and insulin did not change significantly over time in either group . This intervention design ed to increase physical activity in post-partum women with previous gestational diabetes proved feasible . However , no measurable improvement in metabolic or biometric parameters was observed over a three month period OBJECTIVE To compare the effectiveness of diabetes prevention strategies addressing postpartum weight retention for women with gestational diabetes mellitus ( GDM ) delivered at the health system level : mailed recommendations ( usual care ) versus usual care plus a Diabetes Prevention Program (DPP)–derived lifestyle intervention . RESEARCH DESIGN AND METHODS This study was a cluster r and omized controlled trial of 44 medical facilities ( including 2,280 women with GDM ) r and omized to intervention or usual care . The intervention included mailed gestational weight gain recommendations plus 13 telephone sessions between 6 weeks and 6 months postpartum . Primary outcomes included the following : proportion meeting the postpartum goals of 1 ) reaching pregravid weight if pregravid BMI < 25.0 kg/m2 or 2 ) losing 5 % of pregravid weight if BMI ≥25.0 kg/m2 ; and pregravid to postpartum weight change . RESULTS On average , over the 12-month postpartum period , women in the intervention had significantly higher odds of meeting weight goals than women in usual care ( odds ratio [ OR ] 1.28 [ 95 % CI 1.10 , 1.47 ] ) . The proportion meeting weight goals was significantly higher in the intervention than usual care at 6 weeks ( 25.5 vs. 22.4 % ; OR 1.17 [ 1.01 , 1.36 ] ) and 6 months ( 30.6 vs. 23.9 % ; OR 1.45 [ 1.14 , 1.83 ] ) . Condition differences were reduced at 12 months ( 33.0 vs. 28.0 % ; OR 1.25 [ 0.96 , 1.62 ] ) . At 6 months , women in the intervention retained significantly less weight than women in usual care ( mean 0.39 kg [ SD 5.5 ] vs. 0.95 kg [ 5.5 ] ; mean condition difference −0.64 kg [ 95 % CI −1.13 , −0.14 ] ) and had greater increases in vigorous-intensity physical activity ( mean condition difference 15.4 min/week [ 4.9 , 25.8 ] ) . CONCLUSIONS A DPP-derived lifestyle intervention modestly reduced postpartum weight retention and increased vigorous-intensity physical activity AIMS Women with remote histories of gestational diabetes mellitus can reduce their diabetes risk through lifestyle changes , but the effectiveness of interventions in women with more recent histories of gestational diabetes has not been reported . Therefore , we conducted a pilot study of a low-intensity web-based pedometer programme targeting glucose intolerance among women with recent gestational diabetes . METHODS Women with a gestational diabetes delivery within the past 3 years were r and omized to a 13-week intervention consisting of a structured web-based pedometer programme which gave personalized steps-per-week goals , pedometers and education regarding lifestyle modification , or to a letter about diabetes risk reduction and screening after delivery for gestational diabetes ( control condition ) . The main outcome measures were change in fasting plasma glucose and 2-h glucose levels on a 75-g oral glucose tolerance test between baseline and 13-week follow-up . Weight was a secondary outcome and behavioural constructs ( self-efficacy , social support , risk perception ) were also assessed . RESULTS Forty-nine women were enrolled . At 13-week follow-up , women r and omized to the intervention did not have significant changes in behavioural constructs , physical activity or anthropometrics compared with women in the control group . Changes in fasting plasma glucose ( -0.046 mmol/l vs. 0.038 mmol/l , P = 0.65 ) , 2-h glucose values ( -0.48 mmol/l vs. -0.42 mmol/l , P = 0.91 ) and weight ( -0.14 kg vs. -1.5 kg , P = 0.13 ) were similar between the control and intervention groups , respectively . CONCLUSIONS Structured web-based education utilizing pedometers is feasible although uptake may be low . Such programmes may need to be supplemented with additional measures in order to be effective for reduction of diabetes risk Background We recently demonstrated that a gestational diabetes history in mothers is associated with higher postpartum incident diabetes not only in mothers but also in fathers . In the present study , we examined changes in health behaviours and cardiometabolic profiles in both mothers and partners who participated in a diabetes prevention program within 5 years of a gestational diabetes pregnancy . Methods Couples were enrolled into a 13-week program that included 5 half-day group sessions and web/telephone-based support between sessions . It was design ed in consultation with patients and previously studied in mothers . We computed mean changes from baseline ( 95 % CI ) for physical activity , eating , and sleep measures , and cardiometabolic parameters ( fasting and 2-h post glucose load plasma glucose , BMI , blood pressure ) in both partners and mothers . Results Among 59 couples enrolled , 45 partners ( 76 % ) and 47 mothers ( 80 % ) completed final evaluations . Baseline cardiometabolic measures averaged within normal limits . Similar to mothers , partners increased physical activity ( + 1645 steps/day , 95%CI 730 , 2561 ; accelerometer assessed moderate-to-vigorous physical activity + 36.4 min/week , 95 % CI 1.4 , 71.4 ) and sleep duration ( + 0.5 h/night , 95 % CI 0.1 , 0.9 ) and reduced the sodium-to-potassium ratio of food intake ( − 0.09 95 % CI -0.19 , − 0.001 ) . No conclusive changes were observed in glucose measures or insulin resistance ; in analyses combining mothers and partners , systolic blood pressure decreased ( − 2.7 mmHg , 95 % CI -4.4 , − 1.0 ) . Conclusions Partners and mothers demonstrated improved physical activity , sleep , and dietary quality . Baseline cardiometabolic profiles averaged at normal values and there were no changes in glucose or insulin resistance ; some blood pressure impact was observed . While strategies need to be developed to attract participants at higher cardiometabolic risk , this study demonstrates that partners of women within 5 years of a gestational diabetes diagnosis can be recruited and do achieve health behaviour change . Trial registration Clinical Trials.gov : NCT02343354 ( date of registration : January 22 , 2015 ) Aims . To develop a program to support behaviour changes for women with a history of Gestational Diabetes Mellitus ( GDM ) and a Body Mass Index ( BMI ) > 25 kg/m2 to delay or prevent Type 2 Diabetes Mellitus . Methods . Women diagnosed with GDM in the previous 6 to 24 months and BMI > 25 kg/m2 were r and omized to an intervention ( I ) ( n = 16 ) or a control ( C ) ( n = 15 ) group . The intervention was a pedometer program combined with nutrition coaching , with the primary outcome increased weight loss in the intervention group . Secondary outcomes included decreased waist and hip measurements , improved insulin sensitivity and body composition , increased physical activity , and improved self-efficacy in eating behaviours . Results . Median ( IQR ) results were as follows : weight : I −2.5 ( 2.3 ) kg versus C + 0.2 ( 1.6 ) kg ( P = 0.009 ) , waist : I −3.6 ( 4.5 ) cm versus C −0.1 ( 3.6 ) cm ( P = 0.07 ) , and hip : I −5.0 ( 3.3 ) cm versus C −0.2 ( 2.6 ) cm ( P = 0.002 ) . There was clinical improvement in physical activity and eating behaviours and no significant changes in glucose metabolism or body composition . Conclusion . A pedometer program and nutrition coaching proved effective in supporting weight loss , waist circumference , physical activity , and eating behaviours in women with previous GDM OBJECTIVE : To test the feasibility and effectiveness of a Web-based lifestyle intervention based on the Diabetes Prevention Program modified for women with recent gestational diabetes mellitus to reduce postpartum weight retention . METHODS : We r and omly allocated 75 women with recent gestational diabetes mellitus to either a Web-based lifestyle program ( Balance after Baby ) delivered over the first postpartum year or to a control group . Primary outcomes were change in body weight at 12 months from 1 ) first postpartum measured weight ; and 2 ) self-reported prepregnancy weight . RESULTS : There were no significant differences in baseline characteristics between groups including age , body mass index , race , and income status . Women assigned to the Balance after Baby program ( n=36 , three lost to follow-up ) lost a mean of 2.8 kg ( 95 % confidence interval –4.8 to −0.7 ) from 6 weeks to 12 months postpartum , whereas the control group ( n=39 , one lost to follow-up ) gained a mean of 0.5 kg ( −1.4 to + 2.4 ) ( P=.022 ) . Women in the intervention were closer to prepregnancy weight at 12 months postpartum ( mean change −0.7 kg ; −3.5 to + 2.2 ) compared with women in the control arm ( + 4.0 kg ; + 1.3 to + 6.8 ) ( P=.035 ) . CONCLUSION : A Web-based lifestyle modification program for women with recent gestational diabetes mellitus decreased postpartum weight retention . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT01158131 . LEVEL OF EVIDENCE : Background Women with gestational diabetes history are at increased risk for type 2 diabetes . They face specific challenges for behavioural changes , including childcare responsibilities . The aim of this study is to test a tailored type 2 diabetes prevention intervention in women within 5 years of a pregnancy with gestational diabetes , in terms of effects on weight and cardiometabolic risk factors . Methods The 13-week intervention , design ed based on focus group discussion s , included four group sessions , two with spousal participation and all with on-site childcare . Web/telephone-based support was provided between sessions . We computed mean percentage change from baseline ( 95 % confidence intervals , CI ) for anthropometric measures , glucose tolerance ( 75 g Oral glucose tolerance test ) , insulin resistance/sensitivity , blood pressure , physical activity , dietary intake , and other cardiometabolic risk factors . Results Among the 36 enrolled , 27 completed final evaluations . Most attended ≥ 3 sessions ( 74 % ) , used on-site childcare ( 88 % ) , and logged onto the website ( 85 % ) . Steps/day ( 733 steps , 95 % CI 85 , 1391 ) and fruit/vegetable intake ( 1.5 servings/day , 95 % CI 0.3 , 2.8 ) increased . Proportions decreased for convenience meal consumption ( −30 % , 95 % CI −50 , −9 ) and eating out ( −22 % , 95 % CI −44 , −0 ) ≥ 3 times/month . Body mass index and body composition were unchanged . Fasting ( −4.9 % , 95 % CI −9.5 , −0.3 ) and 2-hour postchallenge ( −8.0 % , 95 % CI −15.6 , −0.5 ) glucose declined . Insulin sensitivity increased ( ISI 0,120 23.7 % , 95 % CI 9.1 , 38.4 ; Matsuda index 37.5 % , 95 % CI 3.5 , 72.4 ) . Insulin resistance ( HOMA-IR −9.4 % , 95 % CI −18.6 , −0.1 ) and systolic blood pressure ( −3.3 % , 95 % CI −5.8 , −0.8 ) decreased . Conclusions A tailored group intervention appears to lead to improvements in health behaviours and cardiometabolic risk factors despite unchanged body mass index and body composition . This approach merits further study . Clinical trial registration Clinical Trials.gov ( NCT01814995 ) Background Gestational diabetes mellitus ( GDM ) is an increasingly prevalent risk factor for type 2 diabetes . We evaluated the effectiveness of a group-based lifestyle modification program in mothers with prior GDM within their first postnatal year . Methods and Findings In this study , 573 women were r and omised to either the intervention ( n = 284 ) or usual care ( n = 289 ) . At baseline , 10 % had impaired glucose tolerance and 2 % impaired fasting glucose . The diabetes prevention intervention comprised one individual session , five group sessions , and two telephone sessions . Primary outcomes were changes in diabetes risk factors ( weight , waist circumference , and fasting blood glucose ) , and secondary outcomes included achievement of lifestyle modification goals and changes in depression score and cardiovascular disease risk factors . The mean changes ( intention-to-treat [ ITT ] analysis ) over 12 mo were as follows : −0.23 kg body weight in intervention group ( 95 % CI −0.89 , 0.43 ) compared with + 0.72 kg in usual care group ( 95 % CI 0.09 , 1.35 ) ( change difference −0.95 kg , 95 % CI −1.87 , −0.04 ; group by treatment interaction p = 0.04 ) ; −2.24 cm waist measurement in intervention group ( 95 % CI −3.01 , −1.42 ) compared with −1.74 cm in usual care group ( 95 % CI −2.52 , −0.96 ) ( change difference −0.50 cm , 95 % CI −1.63 , 0.63 ; group by treatment interaction p = 0.389 ) ; and + 0.18 mmol/l fasting blood glucose in intervention group ( 95 % CI 0.11 , 0.24 ) compared with + 0.22 mmol/l in usual care group ( 95 % CI 0.16 , 0.29 ) ( change difference −0.05 mmol/l , 95 % CI −0.14 , 0.05 ; group by treatment interaction p = 0.331 ) . Only 10 % of women attended all sessions , 53 % attended one individual and at least one group session , and 34 % attended no sessions . Loss to follow-up was 27 % and 21 % for the intervention and control groups , respectively , primarily due to subsequent pregnancies . Study limitations include low exposure to the full intervention and glucose metabolism profiles being near normal at baseline . Conclusions Although a 1-kg weight difference has the potential to be significant for reducing diabetes risk , the level of engagement during the first postnatal year was low . Further research is needed to improve engagement , including participant involvement in study design ; it is potentially more effective to implement annual diabetes screening until women develop prediabetes before offering an intervention . Trial Registration Australian New Zeal and Clinical Trials Registry Fifty-nine women with recent gestational diabetes participated in a r and omized controlled trial to assess the feasibility and efficacy of a pragmatic diabetes risk reduction intervention . Intervention participants achieved improvements in energy , total and saturated fats , and carbohydrate intake , but no change in physical activity . Recruitment was challenging and below expectations CONTEXT Gestational diabetes ( GDM ) confers a high risk of type 2 diabetes . In the Diabetes Prevention Program ( DPP ) , intensive lifestyle ( ILS ) and metformin prevented or delayed diabetes in women with a history of GDM . OBJECTIVE The objective of the study was to evaluate the impact of ILS and metformin intervention over 10 years in women with and without a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study . DESIGN This was a r and omized controlled clinical trial with an observational follow-up . SETTING The study was conducted at 27 clinical centers . PARTICIPANTS Three hundred fifty women with a history of GDM and 1416 women with previous live births but no history of GDM participated in the study . The participants had an elevated body mass index and fasting glucose and impaired glucose tolerance at study entry . INTERVENTIONS Interventions included placebo , ILS , or metformin . OUTCOMES MEASURE Outcomes measure was diabetes mellitus . RESULTS Over 10 years , women with a history of GDM assigned to placebo had a 48 % higher risk of developing diabetes compared with women without a history of GDM . In women with a history of GDM , ILS and metformin reduced progression to diabetes compared with placebo by 35 % and 40 % , respectively . Among women without a history of GDM , ILS reduced the progression to diabetes by 30 % , and metformin did not reduce the progression to diabetes . CONCLUSIONS Women with a history of GDM are at an increased risk of developing diabetes . In women with a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study , both lifestyle and metformin were highly effective in reducing progression to diabetes during a 10-year follow-up period . Among women without a history of GDM , lifestyle but not metformin reduced progression to diabetes Forty-three women were recruited into a 1-year r and omised controlled trial to test the feasibility of a structured behavioural intervention to increase physical activity after gestational diabetes . Increases in achievement of physical activity targets were not attained . Recruitment and subject retention were identified as major challenges This systematic overview summarizes the relevant evidence from multiple systematic review s of the benefits of nonpharmacological interventions for preventing type 2 diabetes mellitus ( T2MD ) in women diagnosed with gestational diabetes mellitus ( GDM ) . A comprehensive search using the Cochrane Library , CINAHL , EMBASE and MEDLINE via Ovid SP , and PubMed data bases was completed on 18 November 2015 . Any systematic review s that evaluated r and omized controlled trials ( RCTs ) with defined nonpharmacological interventions for preventing T2DM in women diagnosed with GDM were eligible for inclusion . The authors independently performed critical appraisal s and quality assessment s of the included review s using the AMSTAR tool , and extracted data were converted to coherent values for tabular summarization . Six eligible review s of diet and /or exercise , breastfeeding , and reminder interventions were identified ; however , the method ologies of the review s varied greatly , and the majority of the evidence suggested unclear bias . We found inconsistent reporting on the rates at which diet and exercise interventions reduced the risk of T2DM progression , but these interventions were found to be effective at reducing glycemic load . Combined diet , exercise , and breastfeeding interventions proved to be effective at returning women to their postpartum weight . Neither diet alone nor exercise alone proved to be effective at lowering the risk of T2DM . Overall , there was no robust evidence to support the hypothesis that nonpharmacological interventions are effective at lowering the risk of T2DM in women diagnosed with GDM , and there was no consistent evidence showing that these interventions improved the predictor outcomes of T2DM , such as glycemic load or anthropometric changes BACKGROUND & AIMS Women with prior gestational diabetes mellitus ( GDM ) have a high risk of developing type 2 diabetes mellitus ( DM2 ) in later life . The study aim was to evaluate the efficacy of a lifestyle intervention for the prevention of glucose disorders ( impaired fasting glucose , impaired glucose tolerance or DM2 ) in women with prior GDM . METHODS A total of 260 women with prior GDM who presented with normal fasting plasma glucose at six to twelve weeks postpartum were r and omized into two groups : a Mediterranean lifestyle intervention group ( n = 130 ) who underwent an educational program on nutrition and a monitored physical activity program and a control group ( n = 130 ) with a conventional follow-up . A total of 237 women completed the three-year follow-up ( 126 in the intervention group and 111 in the control group ) . Their glucose disorders rates , clinical and metabolic changes and rates of adherence to the Mediterranean lifestyle were analyzed . RESULTS Less women in the intervention group ( 42.8 % ) developed glucose disorders at the end of the three-year follow-up period compared with the control group ( 56.75 % ) , p < 0.05 . The multivariate analysis indicated a reduction in the rate of glucose disorders with a BMI of less than 27 kg/m(2 ) ( OR 0.28 ; 0.12 - 0.65 ; p < 0.003 ) , low fat intake pattern ( OR 0.30 ; 0.13 - 0.70 ; p < 0.005 ) , low saturated fat pattern ( OR 0.30 ; 0.13 - 0.69 ; p < 0.005 ) and healthy fat pattern ( OR 0.34 ; 0.12 - 0.94 ; p < 0.04 ) . CONCLUSIONS Lifestyle intervention was effective for the prevention of glucose disorders in women with prior GDM . Body weight gain and an unhealthy fat intake pattern were found to be the most predictive factors for the development of glucose disorders . Current Controlled trials : IS RCT N24165302 . http://www.controlled-trials.com/is rct n/pf/24165302 |
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