Unnamed: 0
int64 0
14.2k
| ReviewID
int64 2.14M
32.7M
| Target
stringlengths 12
3.68k
| Background
stringlengths 46
5.35k
⌀ | Abstract
stringlengths 263
730k
⌀ |
|---|---|---|---|---|
13,300 | 20,091,248 | More extensive changes were seen with longer duration of treatment .
Conclusions Substantial increases in fat and declines in lean mass were observed in prostate cancer patients treated with ADT .
Implication s for cancer survivorsProstate cancer survivors should be made aware of the side effect of treatment on body composition and further work is required to determine what interventions can minimize the impact of ADT on body composition and therefore what evidence based advice they should be provided with .
In general , though recommendation of a healthy diet and moderate exercise is reasonable | Introduction The use of and rogen deprivation therapy ( ADT ) in the treatment of prostate cancer is associated with changes in body composition including increased fat and decreased lean mass .
Limited information exists regarding the rate and extent of these changes .
This systematic review was conducted to determine the effects of ADT on body composition in prostate cancer patients . | BACKGROUND Little is known about the long-term impact of and rogen deprivation therapy ( ADT ) on body composition in men with prostate cancer . We compared body composition parameters in men with non-metastatic prostate cancer on or not on therapy with healthy , age-matched controls at baseline and monitored changes over a 2-year period . METHODS We measured body fat mass and lean body mass in 81 men with prostate cancer on no ADT , 43 men on acute ADT ( less than 6 months ) , 67 men on chronic ADT ( more than 6 months ) and 53 age-matched healthy controls . Measurements were performed every 6 months for 2 years . RESULTS Men with prostate cancer on acute ADT ( mean 3 months ) had significant gains in body fat mass [ 1499.56+/-322.28 g ( mean+/-S.E. ) after 12 months , 2167.15+/-676.45 g after 24 months , p<0.01 for both ] and losses in lean body mass ( 929.74+/-296.36 g after 12 months , 1785.81+/-501.31 g after 24 months , p<0.01 for both ) over 2 years . Men on chronic ADT ( mean 31 months ) had smaller but still significant body composition changes over 24 months . Changes in body composition in men on no ADT were small and healthy controls had no significant changes . CONCLUSIONS Men with prostate cancer on ADT have significant gains in body fat mass and losses lean body mass over 2 years . These changes are most pronounced with initiation of ADT BACKGROUND AND PURPOSE The ongoing Early Prostate Cancer ( EPC ) programme is assessing bicalutamide ( ' Casodex ' ) 150 mg , either alone or as adjuvant to treatment of curative intent , in patients with localised or locally advanced prostate cancer ( n=8113 ) . This paper presents an exploratory analysis of the subgroup of the EPC programme who received radiotherapy with curative intent ( n=1370 ) in order to determine the efficacy ( in terms of progression-free survival [ PFS ] ) and tolerability of bicalutamide 150 mg in this setting . PATIENTS AND METHODS 1370 patients with T1 - 4 , MO , any N prostate cancer received bicalutamide 150 mg or placebo adjuvant to radiotherapy of curative intent . This analysis was undertaken at median 5.3 years ' follow-up . RESULTS In patients with locally advanced disease ( n=305 ) , bicalutamide adjuvant to radiotherapy significantly increased PFS by 53 % ( event-time ratio 1.53 ; 95 % confidence intervals [ CI ] 1.16 , 2.02 ) compared with placebo and reduced the risk of disease progression by 42 % ( hazard ration [ HR ] 0.58 ; 95 % CI 0.41 , 0.84 ; P=0.00348 ) . In these patients , objective progression was experienced by 33.5 % of those r and omised to bicalutamide versus 48.6 % for those r and omised to placebo . The between-group difference in patients with localised disease ( n=1065 ) failed to reach statistical significance ( HR 0.80 ; 95 % CI 0.62 , 1.03 ; P=0.088 ) . The most common adverse events were breast pain ( 74.8 % ) and gynaecomastia ( 66.6 % ) , which were mild to moderate in > 90 % of cases . CONCLUSIONS Bicalutamide 150 mg/day given as adjuvant to radiotherapy significantly improved PFS in patients with locally advanced prostate cancer . For patients with localised disease , the results at this stage from the radiotherapy subgroup and the overall EPC programme suggest that adjuvant hormonal therapy is currently not appropriate . There were no unexpected tolerability findings CONTEXT GnRH agonists markedly increase fat mass in men with prostate cancer , but little is known about the effects of treatment on insulin sensitivity . OBJECTIVE The objective of the study was to assess the effects of short-term GnRH agonist treatment on insulin sensitivity . DESIGN This was a prospect i ve 12-wk study . SETTING The study was conducted at a general clinical research center . PATIENTS OR OTHER PARTICIPANTS We studied 25 men with locally advanced or recurrent prostate cancer , no radiographic evidence of metastases , no history of diabetes mellitus , and no evidence of diabetes mellitus at baseline visit . INTERVENTION Leuprolide depot and bicalutamide were used in the study . MAIN OUTCOME MEASURES Oral glucose tolerance tests and body composition assessment by dual-energy x-ray absorptiometry were performed at baseline and wk 12 . The primary study outcome was change in insulin sensitivity index . RESULTS Mean ( + /- se ) percentage fat body mass increased by 4.3 + /- 1.3 % from baseline to wk 12 ( P = 0.002 ) . Insulin sensitivity index decreased by 12.9 + /- 7.6 % ( P = 0.02 ) . Insulin sensitivity by homeostatic model assessment decreased by 12.8 + /- 5.9 % ( P = 0.02 ) . Fasting plasma insulin levels increased by 25.9 + /- 9.3 % ( P = 0.04 ) . Mean glycosylated hemoglobin also increased significantly ( P < 0.001 ) . CONCLUSIONS Short-term treatment with leuprolide and bicalutamide significantly increased fat mass and decreased insulin sensitivity in men with prostate cancer . These observations suggest that GnRH agonists may increase the risk of diabetes mellitus and cardiovascular disease in older men OBJECTIVE Casodex ( Zeneca ) is a new potent , long‐acting non‐steroidal anti‐ and rogen , which produces and rogen deprivation by blocking the and rogen receptor . We evaluated the endocrine effects of Casodex 150 mg daily given in monotherapy as primary treatment for patients with prostate cancer 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 PURPOSE Gonadotropin-releasing hormone agonists decrease bone mineral density , lean mass , and muscle size and increase fat mass in men with prostate cancer . Less is known about the effects of bicalutamide monotherapy on bone mineral density and body composition . PATIENTS AND METHODS In a 12-month , open-label study , we r and omly assigned 52 men with prostate cancer and no bone metastases to receive either leuprolide or bicalutamide ( 150 mg by mouth daily ) . Bone mineral density and body composition were measured by dual energy x-ray absorptiometry and quantitative computed tomography . RESULTS Mean ( + /- st and ard error ) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5 % + /- 0.5 % in the leuprolide group and increased by 2.5 + /- 0.5 in the bicalutamide group from baseline to 12 months ( P < .001 ) . Mean changes in bone mineral density of the total body , total hip , femoral neck , and trabecular bone of the lumbar spine also differed significantly between groups ( P < or = .003 for each comparison ) . Fat mass increased by 11.1 % + /- 1.3 % in the leuprolide group and by 6.4 % + /- 1.1 % in the bicalutamide group ( P = .01 ) . Changes in lean mass , muscle size , and muscle strength were similar between the groups . Breast tenderness and enlargement were more common in the bicalutamide group than in the leuprolide group . Fatigue , loss of sexual interest , and vasomotor flushing were less common in the bicalutamide group than in the leuprolide group . CONCLUSION In men with prostate cancer , bicalutamide monotherapy increases bone mineral density , lessens fat accumulation , and has fewer bothersome side effects than treatment with a gonadotropin-releasing hormone agonist PURPOSE We evaluated changes in bone mineral density ( BMD ) , fat-free mass ( FFM ) and serum lipid levels during bicalutamide 150 mg monotherapy compared with medical castration for 2 years . MATERIAL S AND METHODS A total of 103 men with localized or locally advanced prostate cancer ( T1-T4 , Nx , M0 ) for whom immediate and rogen deprivation was indicated were enrolled in this prospect i ve , multicenter , open-label , parallel group study . Patients were r and omized to bicalutamide 150 mg once daily ( 51 ) or medical castration with a luteinizing hormone releasing hormone analogue ( 52 ) for 96 weeks . Primary end points were mean percent change from baseline in lumbar spine BMD , hip BMD and FFM at 96 weeks . Mean changes in lipid parameters with time were also evaluated . RESULTS BMD was maintained during bicalutamide 150 mg monotherapy ( + 2.42 % for lumbar spine BMD and + 1.13 % for hip BMD at week 96 ) , while castration was associated with a progressive loss in BMD ( -5.40 % and -4.39 % at week 96 , respectively , both p < 0.0001 at week 96 ) . There was no significant difference between bicalutamide 150 mg and castration in mean percent change from baseline in FFM ( -1.56 % and -3.86 % , respectively , at week 96 , p = 0.31 ) , although there was a trend for greater progressive loss over time with castration . Mean changes in lipid parameters were small and similar in the 2 groups . CONCLUSIONS Bicalutamide 150 mg monotherapy may offer an important advantage compared to castration in terms of bone loss and body composition for patients who require long-term and rogen deprivation for localized or locally advanced prostate cancer PURPOSE Radiation Therapy Oncology Group protocol 85 - 31 was design ed to evaluate the effectiveness of adjuvant and rogen suppression , using goserelin , in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy ( RT ) . METHODS AND MATERIAL S Eligible patients were those with palpable primary tumor extending beyond the prostate ( clinical Stage T3 ) or those with regional lymphatic involvement . Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and /or seminal vesicle involvement was documented histologically . Stratification was based on histologic differentiation , nodal status , acid phosphatase status , and prior prostatectomy . The patients were r and omized to either RT and adjuvant goserelin ( Arm I ) or RT alone followed by observation and application of goserelin at relapse ( Arm II ) . In Arm I , the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression . RESULTS Between 1987 and 1992 , when the study was closed , 977 patients were entered : 488 to Arm I and 489 to Arm II . As of July 2003 , the median follow-up for all patients was 7.6 years and for living patients was 11 years . At 10 years , the absolute survival rate was significantly greater for the adjuvant arm than for the control arm : 49 % vs. 39 % , respectively ( p = 0.002 ) . The 10-year local failure rate for the adjuvant arm was 23 % vs. 38 % for the control arm ( p < 0.0001 ) . The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24 % vs. 39 % ( p < 0.001 ) and 16 % vs. 22 % ( p = 0.0052 ) , respectively , both in favor of the adjuvant arm . CONCLUSION In a population of patients with unfavorable prognosis carcinoma of the prostate , and rogen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival . The improvement in survival appeared preferentially in patients with a Gleason score of 7 - 10 Greater body mass index ( BMI ) is associated with shorter time to prostate‐specific antigen ( PSA ) failure following radical prostatectomy and radiation therapy ( RT ) . Whether BMI is associated with prostate cancer‐specific mortality ( PCSM ) was investigated in a large r and omized trial of men treated with RT and and rogen deprivation therapy ( ADT ) for locally advanced prostate cancer As men age , serum testosterone concentrations decrease , the percentage of body mass that is fat increases , the percentage of lean body mass decreases , and muscle strength decreases . Because these changes are similar to those that occur in hypogonadal men , we hypothesized that increasing the serum testosterone concentration of men over 65 yr of age to that in young men would decrease their fat mass , increase their lean mass , and increase their muscle strength . We r and omized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch in a double blind study for 36 months . We measured body composition by dual energy x-ray absorptiometry and muscle strength by dynamometer before and during treatment . Ninety-six men completed the entire 36-month protocol . Fat mass decreased ( -3.0+/-0.5 kg ) in the testosterone-treated men during the 36 months of treatment , which was significantly different ( P = 0.001 ) from the decrease ( -0.7+/-0.5 kg ) in the placebo-treated men . Lean mass increased ( 1.9+/-0.3 kg ) in the testosterone-treated men , which was significantly different ( P < 0.001 ) from that ( 0.2+/-0.2 kg ) in the placebo-treated men . The decrease in fat mass in the testosterone-treated men was principally in the arms ( -0.7+/-0.1 kg ; P < 0.001 compared to the placebo group ) and legs ( -1.1+/-0.2 kg ; P < 0.001 ) , and the increase in lean mass was principally in the trunk ( 1.9+/-0.3 kg ; P < 0.001 ) . The change in strength of knee extension and flexion at 60 degrees and 180 degrees angular velocity during treatment , however , was not significantly different between the two groups . We conclude that increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men decreased fat mass , principally in the arms and legs , and increased lean mass , principally in the trunk , but did not increase the strength of knee extension and flexion , as measured by dynamometer Objective . To evaluate body composition changes , specifically skeletal muscle mass , in men receiving and rogen deprivation with luteinizing-hormone releasing hormone-agonist ( LHRH-A ) for prostate cancer ( PCa ) in comparison with healthy controls . Design . Retrospective analysis of body composition changes in men with prostate cancer receiving LHRH-A therapy from 2 clinical trials compared to men without prostate cancer serving as a placebo-control in another clinical trial . Setting . Clinical Research Center in Connecticut . Participants . Thirty men ( > 60 years ) receiving 6 months of LHRH-A therapy for PCa were compared to a healthy group of 25 men without PCa . Measurements . Appendicular skeletal muscle/height2 ( ASM/ht2 ) , lean and fat mass were assessed by dual energy x-ray absorptiometry . Total testosterone levels were assessed by enzyme immunoassay . Results . At baseline , 12/30 ( 40 % ) of the treatment group and 7/25 ( 28 % ) of the control group ( p = 0.11 ) met criteria for sarcopenia . There were no differences between control groups in ASM/ht2 or lean mass . The LHRH-A group had a higher percent body fat than the control group , 29.8 ± 6.3 versus 26.3 ± 4.6 ( p = 0.02 ) . ASM/ht2 and lean mass decreased in the LHRH-A group from 7.5 ± 0.9 kg to 7.3 ± 0.9 kg ( −2.3 % ± 0.03 ; p ⩽ 0.001 ) and 53.5 ± 5.4 kg to 52.3 ± 5.3 kg ( −2.1 % ± 0.03 ; p ⩽ 0.001 ) , respectively . There was no muscle loss in the control group . At 6 months , the LHRH-A group had increased percent body fat from 29.8 ± 6.4 to 32.2 ± 5.8 ( 9.5 % ± 0.13 ; p ⩽ 0.001 ) , whereas the control group had decreased in percent body fat from 26.6 ± 4.6 to 25.3 ± 5.0 ( −3.8 % ± 0.08 ; p = 0.02 ) . Conclusions . Men undergoing LHRH-A treatment for PCa decreased appendicular skeletal muscle and lean tissue and increased body fat within 6 months of initiation of therapy . Lifestyle changes or medical interventions to minimize the effects of and rogen deprivation therapy for PCa deserve investigation OBJECTIVES To assess the effects of and rogen deprivation therapy on body composition in men with nonmetastatic prostate cancer . METHODS In a multicenter study , men with Stage M0 prostate cancer were prospect ively evaluated during initial and rogen deprivation therapy ( gonadotropin-releasing hormone agonist or bilateral orchiectomy ) . The main outcomes were changes in weight , percentage fat mass , and percentage lean mass from baseline to 12 months . RESULTS Seventy-nine subjects were assessed . Serum testosterone concentrations decreased by 79.7 % + /- 3.0 % ( P < 0.001 ) . Weight increased by 1.8 % + /- 0.5 % ( P < 0.001 ) . The percentage fat mass increased by 11.0 % + /- 1.7 % , and the percentage lean mass decreased by 3.8 % + /- 0.6 % ( P < 0.001 for each comparison ) . CONCLUSIONS And rogen deprivation therapy increased weight and fat mass and decreased lean mass in men with nonmetastatic prostate cancer The aim of this study was to determine the effects of initial treatment with a GnRH agonist on body composition in asymptomatic men with nonmetastatic prostate cancer . Forty men with locally advanced , node-positive or biochemically recurrent prostate cancer , no radiographic evidence of metastases , and no prior and rogen deprivation therapy were treated with leuprolide 3-month depot 22.5 mg i m every 12 wk for 48 wk . The main outcome measures were percentage changes in weight , percentage fat body mass , percentage lean body mass , fat distribution , and muscle size after 48 wk . Thirty-two subjects were evaluable . Serum T concentrations decreased by 96.3 % plus or minus 0.4 % ( P < 0.001 ) . Weight increased by 2.4 % plus or minus 0.8 % ( P = 0.005 ) . Percentage fat body mass increased by 9.4 % plus or minus 1.7 % ( P < 0.001 ) , and percentage lean body mass decreased by 2.7 % plus or minus 0.5 % ( P < 0.001 ) . Cross-sectional areas of the abdomen and abdominal sc fat increased by 3.9 % plus or minus 1.2 % ( P = 0.003 ) and 11.1 % plus or minus 3.4 % ( P = 0.003 ) , respectively . In contrast , the cross-sectional area of intraabdominal fat did not change significantly ( P = 0.94 ) . Cross-sectional paraspinal muscle area decreased by 3.2 % plus or minus 1.3 % ( P = 0.02 ) . GnRH agonists increase weight and percentage fat body mass and decrease percentage lean body mass and muscle size in men with nonmetastatic prostate cancer . Increased fatness result ed primarily from accumulation of sc rather than intraabdominal adipose tissue BACKGROUND We did a r and omised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone ( LHRH ) to investigate the added value of long-term and rogen suppression in locally advanced prostate cancer . METHODS Between 1987 and 1995 , 415 patients were r and omly assigned radiotherapy alone or radiotherapy plus immediate and rogen suppression . Eligible patients had T1 - 2 tumours of WHO grade 3 or T3 - 4 N0 - 1 M0 tumours ; the median age of participants was 71 years ( range 51 - 80 ) . In both treatment groups , 50 Gy radiation was delivered to the pelvis over 5 weeks , and 20 Gy over 2 weeks as a prostatic boost . Goserelin ( 3.6 mg subcutaneously every 4 weeks ) was started on the first day of irradiation and continued for 3 years ; cyproterone acetate ( 150 mg orally ) was given for 1 month starting 1 week before the first goserelin injection . The primary endpoint was clinical disease-free survival . Analyses were by intention to treat . FINDINGS 412 patients had evaluable data , with median follow-up of 66 months ( range 1 - 126 ) . 5-year clinical disease-free survival was 40 % ( 95 % CI 32 - 48 ) in the radiotherapy-alone group and 74 % ( 67 - 81 ) in the combined-treatment group ( p=0.0001 ) . 5-year overall survival was 62 % ( 52 - 72 ) and 78 % ( 72 - 84 ) , respectively ( p=0.0002 ) and 5-year specific survival 79 % ( 72 - 86 ) and 94 % ( 90 - 98 ) . INTERPRETATION Immediate and rogen suppression with an LHRH analogue given during and for 3 years after external irradiation improves disease-free and overall survival of patients with locally advanced prostate cancer PURPOSE To compare the efficacy of bicalutamide monotherapy to maximal and rogen blockade ( MAB ) in the treatment of advanced prostatic cancer . PATIENTS AND METHODS Previously untreated patients with histologically proven stage C or D disease ( American Urological Association Staging System ) were r and omly allocated to receive either bicalutamide or MAB . After disease progression , patients treated with bicalutamide were assigned to castration . The primary end point for this trial was overall survival . Secondary end points included response to treatment , disease progression , treatment safety , quality -of-life ( QOL ) , and sexual function . RESULTS A total of 108 patients received bicalutamide and 112 received MAB . There was no difference in the percentage of patients whose prostate-specific antigen returned to normal levels . At the time of the present analysis ( median follow-up time , 38 months ; range , 1 to 60 months ) , 129 patients progressed and 89 died . There was no difference in the duration of either progression-free survival or overall survival . However , a survival trend favored bicalutamide in stage C disease but MAB in stage D disease . Overall and subgroup trends were confirmed by multivariate analysis . Serious adverse events and treatment discontinuations were more common in patients receiving MAB ( P = .08 and P = .04 , respectively ) . Fewer patients in the bicalutamide group complained of loss of libido ( P = . 01 ) and of erectile dysfunction ( P = .002 ) . Significant trends favored bicalutamide-treated patients also with respect to their QOL , namely relative to social functioning , vitality , emotional well-being , and physical capacity . CONCLUSION Bicalutamide monotherapy yielded comparable results relative to st and ard treatment with MAB , induced fewer side effects , and produced a better QOL |
13,301 | 27,381,448 | Three studies reported health care utilisation data but overall results are inconclusive .
No optimal dispensing or supply procedures were identified .
Organisation devices may help unintentional medication non-adherence and could improve health outcomes . | Background Suboptimal medication adherence is a significant threat to public health and re sources .
Devices that organise weekly doses by time and day are commonly used to reduce unintentional non-adherence .
However , there is limited evidence to support their use .
This systematic review was conducted to evaluate current evidence for their efficacy , safety and costs . | An estimated 20 million Americans suffer from diabetes . Patients with non-insulin-dependent diabetes mellitus ( NIDDM ) comprise approximately 90 % of the diabetic population . An estimated 10 - 30 % of patients with NIDDM withdraw from their prescribed regimen within 1 year of diagnosis , and of the remainder , nearly 20 % administer insufficient medication to facilitate an adequate reduction in blood glucose . A r and omized trial was undertaken to discern the effect of pharmacy-based value-added utilities on prescription-refill compliance with sulfonylurea therapy and health service utilization . The subjects were 258 Medicaid beneficiaries from the state of South Carolina , previously untreated for NIDDM , prescribed 5 mg of the second-generation sulfonylurea glyburide twice daily , and monitored with regard to prescription-refill compliance and health service utilization for 1 year . Subjects provided informed consent and were r and omly assigned to one of four experimental groups : ( i ) the control cohort received st and ard pharmaceutical care with each dispensing of glyburide ; ( ii ) the second cohort received st and ard pharmaceutical care and was mailed a medication-refill reminder 10 days prior to each sequential refill date ; ( iii ) the third cohort received st and ard pharmaceutical care and was provided unit-of-use packaging with each prescription-refill request ; ( iv ) the fourth cohort received st and ard pharmaceutical care , mailed medication-refill reminders , and unit-of-use packaging . Analysis of variance ( ANOVA ) procedures revealed that patients receiving mailed prescription-refill reminders , unit-of-use packaging , or a combination of both interventions achieved a significant ( P < or = 0.05 ) increase in the Medication Possession Ratio ( MPR ) for sulfonylurea therapy relative to controls . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND : Concordance , which involves prescribing with rather than for patients , should result in less drug wastage ( non-use ) , but is proving hard to put into practice . One possible way of easing elderly people and prescribers toward concordance is to use a medicines organizer ( MO ) . OBJECTIVE : To document medication wastage , using a pharmacy-prepared reusable MO , and explore , using a qualitative approach , use of this information on communication of individuals ' drug regimens . METHODS : Sixty-two sheltered housing residents , aged ⩾60 years , participated in an exploratory controlled , matched study . The intervention group received medication in the MO , and the control group continued with st and ard packaging . Community pharmacists recorded details of wasted drugs returned during the 3-month study and , for the intervention group , 6 , 9 , and 12 months after the study . Medicines management data were collected from participants . Qualitative interviews were conducted with a sample of general practitioners ( GPs ) and community pharmacists to explore views on the role of the MO . RESULTS : Intervention group wastage was reduced from 18.1 % ( pre study ) to 1 % at 12 months . No data on wastage were collected for the control group after the pre study assessment . Sixty-one percent more prescription changes , including significant decreases in the number of prescribed drugs and dosages , were reported for the intervention group . GPs and pharmacists reported improvements in communication concerning medication-related dialog . CONCLUSIONS : This small exploratory study has shown that a pharmacy-prepared reusable MO provided visual , objective insights into medication wastage . This result ed in improved communication of drug needs and reduced wastage — the foundation for concordance This article reports a r and omized controlled trial design ed to test the effects of special packaging of antihypertensive medication on compliance and blood pressure control . One hundred eighty subjects who had exhibited elevated blood pressure greater than 90 mmHg in the two years prior to the study were recruited from patients receiving care at a community hospital-based family medicine practice . After completing preenrollment interviews and blood pressure measurements , subjects were r and omly assigned to receive their antihypertensive medications either in the usual vials or in special unit dose-reminder packaging . Follow-up interviews , pill counts , and blood pressure measurements were performed at three-month intervals . There were no statistically significant differences between the control and experimental groups with regard to age , sex , race , employment , education , marital status , insurance coverage , or blood pressure regimens . Prior to the intervention , the experimental group had slightly lower diastolic blood pressure and reported better compliance than the control group . Analyses performed on 165 subjects completing the first follow-up visit revealed no significant improvements in blood pressure control or compliance for patients receiving special medication packaging . While some patients found it easy to remember to take pills packaged using this format , they also found the packages somewhat more difficult and inconvenient to use . In contrast to previously reported work , this study did not demonstrate any significant improvement in compliance with special packaging of antihypertensive medications Adherence to prescribed antihypertensive agents is critical because control of elevated blood pressure is the single most important way to prevent stroke and other end organ damage . Unfortunately , nonadherence remains a significant problem . Previous interventions design ed to improve adherence have demonstrated only small benefits of strategies that target single facets such as underst and ing medication directions . The intervention described here is informed by prospect i ve memory theory and performance of older adults in laboratory-based paradigms and uses a comprehensive , multifaceted approach to improve adherence . It incorporates multiple strategies design ed to support key components of prospect i ve remembering involved in taking medication . The intervention is delivered by nurses in the home with an education control group for comparison . Differences between groups in overall adherence following the intervention and 6 months later will be tested . Systolic and diastolic blood pressure levels also will be examined between groups and as they relate to adherence . Intra-individual regression is planned to examine change in adherence over time and its predictors . Finally , we will examine the association between executive function/working memory and adherence , predicting that adherence will be related to executive/working memory in the control group but not in the intervention group Adherence to medications is an important issue in oncology due to the increasing number of anticancer agents , such as targeted therapies , formulated for oral dosing . A prospect i ve , crossover design was utilized in which patients on capecitabine were r and omly assigned to one of two packaging methods for one cycle , and then switched over to the alternate packaging method in the subsequent cycle . Twenty-five patients were accrued to this study . Adherence rates were similar when using the daily pill boxes ( 17/21 = 81 % ) and when using the conventional pill bottles ( 18/21 = 86 % ) . However , more patients were satisfied with the daily pill boxes ( 61 % versus 11 % , P = 0.027 ) , preferred the daily pill boxes ( 61 % versus 17 % , P = 0.061 ) , and thought the daily pill boxes were more helpful in reminding them to take their medications ( 50 % versus 11 % , P = 0.070 ) . In conclusion , this small pilot study did not demonstrate that the use of daily pill boxes improved patient adherence with capecitabine , but patient satisfaction and preference for this packaging method were greater than for the conventional pill bottles . Further exploration of this intervention in a larger study is warranted A r and omised trial was undertaken to discern the effect of pharmacy-based value-added utilities on prescription refill compliance with antihypertensive therapy and subsequent health care expenditures . The subjects were 304 Medicaid beneficiaries from the state of Florida , previously untreated for mild to moderate hypertension , prescribed 240 mg of calcium channel antagonist verapamil once daily and monitored regarding prescription refill compliance and health service utilisation for one year . Subjects provided informed consent and were r and omly assigned to one of four experimental groups : ( 1 ) the control cohort received st and ard pharmaceutical care with each dispensing of antihypertensive therapy , ( 2 ) the second cohort received st and ard pharmaceutical care and was mailed a medication-refill reminder ten days prior to each sequential refill date , ( 3 ) the third cohort received st and ard pharmaceutical care and was provided unit-of-use packaging with each prescription-refill request and ( 4 ) the fourth cohort received st and ard pharmaceutical care , mailed medication-refill reminders and unit-of-use packaging . Analysis of variance ( ANOVA ) procedures revealed that patients receiving mailed prescription-refill reminders , unit-of-use packaging or a combination of both interventions achieved a significant ( P < or = 0.05 ) increase in the Medication Possession Ratio ( MPR ) for antihypertensive therapy relative to controls . Receipt of both interventions result ed in a significant ( P < or = 0.05 ) improvement in the MPR for antihypertensive therapy relative to all other groups no significant difference was discerned between groups receiving either mailed prescription-refill reminders or unit-of-use packaging . ( ABSTRACT TRUNCATED AT 250 WORDS Inappropriate prescribing is particularly common in older patients and is associated with adverse drug events ( ADEs ) , hospitalization , and wasteful utilization of re sources . We r and omized 400 hospitalized patients aged ≥65 years to receive either the usual pharmaceutical care ( control ) or screening with STOPP/START criteria followed up with recommendations to their attending physicians ( intervention ) . The Medication Appropriateness Index ( MAI ) and Assessment of Underutilization ( AOU ) index were used to assess prescribing appropriateness , both at the time of discharge and for 6 months after discharge . Unnecessary polypharmacy , the use of drugs at incorrect doses , and potential drug – drug and drug – disease interactions were significantly lower in the intervention group at discharge ( absolute risk reduction 35.7 % , number needed to screen to yield improvement in MAI = 2.8 ( 95 % confidence interval 2.2–3.8 ) ) . Underutilization of clinical ly indicated medications was also reduced ( absolute risk reduction 21.2 % , number needed to screen to yield reduction in AOU = 4.7 ( 95 % confidence interval 3.4–7.5 ) ) . Significant improvements in prescribing appropriateness were sustained for 6 months after discharge A prospect i ve , controlled , crossover study on drug compliance was initiated in 22 elderly patients from a geriatric clinic . Half of the patients received their pills from a commercially prepared calendar mealtime blister-pak ; the remaining patients received their medication from st and ard pill bottles . At the end of three months the two groups were crossed over . Pill count and issuance of a new drug supply were done monthly to assess compliance . It was found that the average noncompliance index was significantly decreased ( 9.17 to 2.04 ) with the blister-pak packaging system . The relationship of age , Folstein mini-mental status , overcompliance , frequency of dosing interval , and living situation were also explored The impact of pill organizers on pill taking was determined in the Trial of Antioxidant Vitamins C and E ( TRACE ) Study , a factorial trial of vitamin C and vitamin E supplementation in 184 individuals . Participants were recruited in 1996 - 1997 and r and omized to one of two groups ( pill organizer or no organizer ) and to one of four supplement groups for 2 months . The pill count ( observed/expected X 100 % ) distribution was similar in the organizer and no organizer group for both vitamins . Mean differences in changes in serum vitamin levels between active and placebo groups did not differ by pill organizer use . The impact of pill organizers and blister packs was compared in another trial , the Vitamins , Teachers , and Longevity ( VITAL ) Study , in 297 individuals r and omized in 1993 - 1994 to receive study pills either in blister packs or in pill organizers and to take one of two supplements . Among those with lower adherence , the pill count distribution in the blister-pack group exceeded that in the organizer group . Mean differences in serum vitamin E levels between active and placebo groups did not differ by types of pill packaging . In summary , use of blister packs , but not pill organizers , improved adherence as measured by pill counts among those with lower adherence . Neither pill delivery system improved adherence as measured by serum vitamin levels OBJECTIVE To assess the impact of calendar blister pack ( CBP ) use on glycemic and blood pressure control . RESEARCH DESIGN AND METHODS We conducted an 8-month r and omized controlled double-blind study among diabetic patients with poor glucose control ( HbA1c > 9.0 % ) in an urban area of South Auckl and , New Zeal and , with a high proportion of Maori and Pacific Isl and s people . Subjects included 68 consecutive patients , of whom 50 % were prescribed three or more medications per day RESULTS HbA1c was reduced by 0.95+/-0.22 % in the CBP group and 0.15+/-0.25 % in the control group ( P = 0.026 ) . Diastolic blood pressure decreased 5.8+/-1.5 mm Hg in the CBP group and increased 0.1+/-1.9 mm Hg in the control group ( P = 0.0041 ) . Systolic blood pressure did not change significantly CONCLUSIONS CBPs should be considered among diabetic patients with poor glycemic control receiving multiple medications |
13,302 | 29,090,832 | Two types of assessment lead to opposite findings ; they do not evaluate sustained attention the same way .
Studies using overall assessment s of sustained attention ability tend to reveal a deficit , whereas studies using over time assessment s do not . | Impairments in sustained attention , that is , the ability to achieve and maintain the focus of cognitive activity on a given stimulation source or task , have been described as central to schizophrenia .
Today , sustained attention deficit is still considered as a hallmark of schizophrenia .
Nevertheless , current findings on this topic are not consistent . | Sustained attention abnormality in schizophrenia is usually refractory to available treatment . Nicotine can transiently improve sustained attention in schizophrenia patients , although its neural mechanisms are unknown . Underst and ing the neural basis of this effect may lead to new treatment strategies for this cognitive deficit . Twenty schizophrenia patients and 24 healthy comparison smokers participated in a double-blind , placebo-controlled , crossover , r and omized functional magnetic resonance imaging study comparing nicotine vs placebo patch on sustained attention , using the rapid visual information-processing task . Schizophrenia patients had impaired visual sustained attention accuracy and processing speed ( all P 's < .001 ) and showed significantly reduced activation in the frontal-parietal-cingulate-thalamic attention network compared with healthy comparison subjects . Nicotine administration enhanced accuracy and processing speed compared with placebo ( all P 's ≤.006 ) , with no drug × diagnosis interactions . However , schizophrenia patients ' task performance remained impaired during the nicotine condition , even when compared with healthy comparison subjects in the placebo condition ( all P 's ≤.01 ) . Nicotine exerted no significant reversal of the impaired attention network associated with schizophrenia . Activations in brain regions associated with nicotine-induced behavioral improvement were not significantly different between patients and comparison subjects . Thus , nicotine transiently enhanced sustained attention similarly in schizophrenia patients and in healthy comparison smokers . The neural mechanisms for this nicotinic effect in schizophrenia appear similar to those for healthy comparison subjects . However , nicotine , at least in a single sustained dose , does not normalize impaired sustained attention and its associated brain network in schizophrenia . These findings provide guidance for developing new treatment strategies for the sustained attention deficit in schizophrenia The goal of this study was to assess whether degree of information processing load differentially affects vigilance performance in patients with schizophrenia as compared to normal controls or patients with other attentional disorders . We contrasted the performance of clinical ly stable out patients with schizophrenia ( n = 18 ) , with that of normal controls ( n = 17 ) , and adults with developmental attentional/learning disorders ( n = 13 ) on simple and dem and ing versions of a visual continuous performance test ( CPT ) . Patients with schizophrenia were significantly impaired on both versions of the CPT compared to normal controls , and showed a significant decline in perceptual sensitivity and significantly more omission errors with increased processing dem and s. Compared to adults with developmental attentional/learning disorders , patients with schizophrenia manifested a tendency toward a decline in perceptual sensitivity . There were no significant differences between groups on a measure of response bias . The data support the hypothesis that patients with schizophrenia have insufficient information processing re sources to cope with higher processing dem and s on effortful attention tasks . Further study comparing schizophrenic patients with patients who have other neuropsychiatric disorders , controlling for severity of illness , is required to determine the specificity of this deficit in schizophrenia BACKGROUND Tobacco smoking , driven by the addictive properties of nicotine , is the most prevalent preventable cause of death in the Western world . Accumulated evidence suggests that nicotine may increase appetitive responding for nondrug incentives in the environment . METHODS To test this hypothesis , we conducted a r and omized , double-blind , placebo-controlled , crossover study of the effect of a single dose of transdermal nicotine on reward responsiveness in 30 psychiatrically healthy nonsmokers . A novel signal detection task in which correct responses were differentially rewarded in a 3:1 ratio was used to assess the extent to which participants modulated their behavior as a function of reward . RESULTS Despite expected adverse effects such as nausea , nicotine significantly increased response bias toward the more frequently rewarded condition , at the expense of accuracy , independent of effects on attention or overall vigilance . Additionally , response bias on placebo was greater in participants who received nicotine in the first session , indicating that an effect of nicotine on reward responsiveness or reward-based learning persisted for at least 1 week . CONCLUSIONS These findings suggest that a single dose of nicotine enhances response to non-drug-related rewards in the environment , with lasting effects . This effect may contribute to reinforcement of early smoking behavior and development of nicotine dependence Although continuous performance tasks ( CPTs ) are becoming more common in psychiatric research , it remains unclear which performance measures best differentiate psychiatric patient groups and along which psychological dimensions . To address this the authors examined sustained attention decrements in patients with bipolar disorder and schizophrenia using CPT measures of perceptual sensitivity , response bias , and psychomotor processing speed . Patients with bipolar disorder with psychotic features ( N=20 ) , schizophrenia ( N=20 ) , and healthy controls ( N=20 ) were evaluated using structured clinical interviews . These patients were rated with the Scale for the Assessment of Positive Symptoms and the Young Mania Rating Scale before completing a de grade d-stimulus version of the CPT . Psychomotor processing speed was the only measure that reliably differentiated the groups across the entire vigilance period and was the strongest predictor of group membership . These findings suggest that reaction time measures may be sensitive to differences in the sustained attention abilities of patients with bipolar disorder and schizophrenia . By incorporating reaction time measures into CPT assessment s , discriminant ability may be enhanced Abstract The Continuous Performance Test ( CPT ) is a widely used procedure for sustained attention/vigilance measurement . However , though the key index of vigilance impairment is the decrement of sensitivity over time during the test period , only few studies have examined whether schizophrenics show a larger drop in CPT performance than do healthy controls . 48 schizophrenic in patients and 48 controls were investigated with the Munich CPT ( 480 visual stimuli , 25 % target stimuli , one stimulus per second ) . Stimuli were de grade d by r and omly inverting 40 % , 41 % , 42 % , or 43 % of the pixels . Results were calculated separately for three consecutive trial sections . Additionally , PANSS ratings , medication , and other clinical data were documented . Schizophrenics show a vigilance decrement over time , controls show a vigilance increase . Differential vigilance changes were not related to the level of stimulus degradation . Schizophrenics performed worse than controls only at the lowest degradation level . While overall sensitivity correlated negatively with the dose of atypical neuroleptics and benzodiazepines , vigilance shifts over time correlated negatively with the dose of typical neuroleptics . Furthermore , sensitivity was related to the cognitive PANSS syndrome , number of admissions/ duration of illness . Differential sensitivity decrements of schizophrenics and controls can be shown if suited CPT procedures are used . The need for basic research on experimental conditions of the CPT as well as examination of the relationship between sustained attention/vigilance decrements and clinical features of schizophrenia is suggested Introduction . Although deficits in executive functioning in schizophrenia have been consistently reported , their precise relationship to symptomatology remains unclear . Recent approaches to executive functioning in nonschizophrenia studies have aim ed to “ fractionate ” the individual cognitive processes involved . In this study , we hypothesised that if these processes are fractionable , then particular symptom syndromes may be selectively related to executive deficits . In particular , it was hoped that this approach could clarify whether negative and positive symptoms of schizophrenia are differentially related to particular aspects of executive/attentional functions . Methods . A total of 32 patients with schizophrenia and 16 matched controls were assessed on a series of tasks design ed to tap the theoretically derived executive functions of Inhibition , Shifting set , Working memory , and Sustained attention . Results . Negative symptoms were significantly predicted by performance on an “ Inhibition ” task ( Stroop ) , and not by performance on any other task . Furthermore , for a subgroup of patients with predominantly negative symptoms variance in positive symptoms was only significantly predicted by performance on a set-shifting task ( Visual Elevator ) , and not by performance on other tasks , including inhibition . Conclusions . Our results support the contention that negative symptoms can , at least partly , be conceived of as cognitive behaviours expressing specific executive deficits . Specifically , we discuss the possibility that negative symptoms may , in part , express a failure in response monitoring . We further suggest that the disordered metacognition result ing in positive symptoms may be mediated by cognitive flexibility in patients with a predominantly negative symptom profile Perceptual sensitivity to a visual target presented in a r and om continuous sequence of targets and nontargets decreased rapidly over time when stimuli were highly de grade d visually but not when moderately de grade d or unde grade d. Large declines in sensitivity , independent of changes in response criterion , were found after only 5 minutes of observation . These rapid decrements of sensitivity to de grade d targets seem to result from dem and s on the limited capacity of visual attention Substantial gains have been made on the neurobiology of attention from systems neuroscience work in animal models and human cognitive neuroscience . However , the integration of rodent-based research on the specific neurotransmitter systems that subserve attention with the results from human behavioral and neuroimaging studies has been hampered by the lack of tasks that validly assess attention in both species . To address this issue , an operant sustained attention task that has been extensively used in research on the neurobiology of attention in rats was re design ed and vali date d for use in humans . Although humans showed better performance overall , the two species showed similar effects of several attention-related variables , including the introduction of distractor-related challenge . This task provides a useful tool for integrative , cross-species research and may help to determine how specific neurotransmitter systems contribute to the hemodynamic changes observed in human functional neuroimaging experiments Nicotine enhances attentional functions . Since chronic nicotine exposure through smoking induces neuroadaptive changes in the brain at a structural and molecular level , the present functional MRI ( fMRI ) study aim ed at investigating the neural mechanisms underlying visuospatial and sustained attention in smokers and non-smokers . Visuospatial attention was assessed with a location-cueing paradigm , while sustained attention was measured by changes in response speed over time . During invalid trials , neural activity within the basal forebrain was selectively enhanced in smokers and higher basal forebrain activity was associated with increased parietal cortex activation . Moreover , higher levels of expired carbon monoxide in smokers before scanning were associated with higher parietal cortex activation and faster responses to invalidly cued targets . Smokers showed a slowing of responses and additionally recruited an area within the right supramarginal gyrus with increasing time on task . Activity decreases over time were observed in visual areas in smokers . The data provide evidence for altered attentional functions in smokers as compared with non-smokers , which were partly modulated by residual nicotine levels and were observed at a behavioural level for sustained and at a neural level for spatial and sustained attention |
13,303 | 27,382,300 | Our findings demonstrate that the administration of v and etanib leads to a significantly increased risk of diarrhea , which varies in different carcinoma patients . | BACKGROUND AND PURPOSE V and etanib is a promising anticancer targeted agent for treating advanced carcinomas , such as non-small-cell lung cancer , small-cell lung cancer , breast cancer , malignant glioma , hepatocellular cancer , and unresectable , locally advanced , or metastatic medullary thyroid cancer .
However , diarrhea is a frequently reported adverse event .
The incidence of v and etanib-associated diarrhea varies extensively in different study population s and has not been carefully estimated .
This systematic review and meta- analysis of clinical trials aims to figure out the overall risks of all- grade and high- grade diarrhea during v and etanib treatment and get a better underst and ing of its prediction and management . | PURPOSE V and etanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor ( VEGFR ) and epidermal growth factor receptor ( EGFR ) signaling . In this two-part phase II study , the efficacy and safety of v and etanib was compared with that of gefitinib , an inhibitor of EGFR signaling . PATIENTS AND METHODS Patients ( N = 168 ) with locally advanced or metastatic ( stage IIIB/IV ) non-small-cell lung cancer ( NSCLC ) , after failure of first-line with or without second-line platinum-based chemotherapy , received once-daily v and etanib 300 mg ( n = 83 ) or gefitinib 250 mg ( n = 85 ) until disease progression or evidence of toxicity ( part A ) . After a 4-week washout period , eligible patients had the option to switch to the alternative treatment ( part B ) . Progression-free survival ( PFS ) was the primary efficacy assessment in part A , which was design ed to have a higher than 75 % power to detect a 33 % prolongation of PFS at a one-sided significance level of .2 . RESULTS In part A , v and etanib prolonged PFS compared with gefitinib ( hazard ratio = 0.69 ; 95 % CI , 0.50 to 0.96 ; one-sided P = .013 ) . Patients receiving v and etanib experienced adverse events that were manageable and generally consistent with inhibition of EGFR and VEGFR signaling , including diarrhea , rash , and hypertension . There were no unexpected safety findings with gefitinib . Overall survival , a secondary assessment , was not significantly different between patients initially r and omly assigned to either v and etanib or gefitinib . CONCLUSION The primary efficacy objective was achieved , with v and etanib demonstrating a significant prolongation of PFS versus gefitinib . V and etanib 300 mg/d is currently being evaluated as a monotherapy in two r and omized phase III studies in advanced NSCLC V and etanib is a once-daily multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 , epidermal growth factor receptor , and the rearranged-during-transfection oncogene . A phase I trial was conducted to describe the pharmacokinetics of v and etanib in patients with recurrent glioma on enzyme-inducing anti-epileptic drugs ( EIAEDs ) and to identify the maximum tolerated dose ( MTD ) in this population . A phase II trial evaluated the efficacy of v and etanib in patients with recurrent malignant glioma not on EIAEDs as measured by 6-month progression-free survival ( PFS6 ) . In the phase I trial , 15 patients were treated with v and etanib at doses of 300 , 400 , and 500 mg/day , in a st and ard dose-escalation design . The MTD in patients on EIAEDs was 400 mg/day , and steady-state levels were similar to those measured in patients not on EIAEDs . Dose-limiting toxicities were prolonged QTc and thromboembolism . Thirty-two patients with recurrent glioblastoma multiforme ( GBM ) and 32 patients with recurrent anaplastic gliomas ( AGs ) were treated in the phase II trial , at a dosage of 300 mg/day on 28-day cycles . Six patients ( 4 GBM , 2 AG ) had radiographic response . PFS6 was 6.5 % in the GBM arm and 7.0 % in the AG arm . Median overall survival was 6.3 months in the GBM arm and 7.6 months in the AG arm . Seizures were an unexpected toxicity of therapy . V and etanib did not have significant activity in unselected patients with recurrent malignant glioma PURPOSE This double-blind r and omized phase II trial examined whether v and etanib , an inhibitor of vascular endothelial and epidermal growth factor receptors , could prolong progression-free survival in responding patients with small-cell lung cancer . PATIENTS AND METHODS Eligible patients with complete response ( CR ) or partial response ( PR ) to combination chemotherapy ( + /- thoracic or prophylactic cranial radiation ) received oral v and etanib 300 mg/d or matched placebo . With 100 patients and 77 events , the study had 80 % power to detect an improvement in median progression-free survival from 4 to 6.5 months ( one-sided , 10%-level test ) . RESULTS Between May 2003 and March 2006 , 107 patients were accrued ; 46 had limited disease and 61 extensive disease . There were fewer patients with a performance status of 0 ( n = 11 v 20 ) , and fewer had CR to initial therapy ( n = 4 v 8) in the v and etanib arm . V and etanib patients had more toxicity and required more dose modifications for gastrointestinal toxicity and rash . Asymptomatic Corrected QT interval ( QTC ) prolongation was observed in eight v and etanib patients . Median progression-free survival for v and etanib and placebo was 2.7 and 2.8 months , respectively ( hazard ratio [ HR ] , 1.01 ; 80 % CI , 0.75 to 1.36 ; one-sided P = .51 ) . Overall survival for v and etanib was 10.6 versus 11.9 months for placebo ( HR , 1.43 ; 80 % CI , 1.00 to 2.05 ; one-sided P = 0.9 ) . In planned subgroup analyses , a significant interaction was noted ( P = .01 ) : limited-stage v and etanib patients had longer overall survival ( HR , 0.45 ; one-sided P = .07 ) and extensive-stage v and etanib patients shorter survival compared with placebo ( HR , 2.27 ; one-sided P = .996 ) . CONCLUSION V and etanib failed to demonstrate efficacy as maintenance therapy for small-cell lung cancer PURPOSE V and etanib is a once-daily , oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling . The antitumor activity of v and etanib monotherapy or v and etanib with paclitaxel and carboplatin ( VPC ) was compared with paclitaxel and carboplatin ( PC ) in previously untreated patients with non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded , placebo-controlled , r and omized phase II study . Patients were r and omly assigned 2:1:1 to receive v and etanib , VPC , or PC . Progression-free survival ( PFS ) was the primary end point , and the study was powered to detect a reduced risk of progression with VPC versus PC ( hazard ratio = 0.70 ; one-sided P < .2 ) and to demonstrate noninferiority for v and etanib versus PC . Overall survival was a secondary assessment . RESULTS The risk of progression was reduced for patients receiving VPC ( n = 56 ) versus PC ( n = 52 ; hazard ratio = 0.76 , one-sided P = .098 ) ; median PFS was 24 weeks ( VPC ) and 23 weeks ( PC ) . The v and etanib monotherapy arm ( n = 73 ) was discontinued after a planned interim PFS analysis met the criterion for discontinuation ( hazard ratio > 1.33 v PC ) . Overall survival was not significantly different between patients receiving VPC or PC . Rash , diarrhea , and hypertension were common adverse events ; no pulmonary or CNS hemorrhage events required intervention . CONCLUSION VPC could be safely administered to patients with NSCLC , including those with squamous cell histology and treated brain metastases . Compared with the PC control arm , patients receiving VPC had longer PFS , meeting the prespecified study end point , whereas those receiving v and etanib monotherapy had shorter PFS PURPOSE V and etanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling . This phase III study assessed the efficacy of v and etanib versus erlotinib in unselected patients with advanced non-small-cell lung cancer ( NSCLC ) after treatment failure with one to two prior cytotoxic chemotherapy regimens . PATIENTS AND METHODS One thous and two hundred forty patients were r and omly assigned to receive v and etanib 300 mg/d ( n = 623 ) or erlotinib 150 mg/d ( n = 617 ) . The primary objective was to show superiority in progression-free survival ( PFS ) for v and etanib versus erlotinib . If the difference did not reach statistical significance for superiority , a noninferiority analysis was conducted . RESULTS There was no significant improvement in PFS for patients treated with v and etanib versus erlotinib ( hazard ratio [ HR ] , 0.98 ; 95.22 % CI , 0.87 to 1.10 ; P = .721 ) ; median PFS was 2.6 months for v and etanib and 2.0 months for erlotinib . There was also no significant difference for the secondary end points of overall survival ( HR , 1.01 ; P = .830 ) , objective response rate ( both 12 % ) , and time to deterioration of symptoms for pain ( HR , 0.92 ; P = .289 ) , dyspnea ( HR , 1.07 ; P = .407 ) , and cough ( HR , 0.94 ; P = .455 ) . Both agents showed equivalent PFS and overall survival in a preplanned noninferiority analysis . Adverse events ( AEs ; any grade ) more frequent with v and etanib than erlotinib included diarrhea ( 50 % v 38 % , respectively ) and hypertension ( 16 % v 2 % , respectively ) ; rash was more frequent with erlotinib than v and etanib ( 38 % v 28 % , respectively ) . The overall incidence of grade ≥ 3 AEs was also higher with v and etanib than erlotinib ( 50 % v 40 % , respectively ) . CONCLUSION In patients with previously treated advanced NSCLC , v and etanib showed antitumor activity but did not demonstrate an efficacy advantage compared with erlotinib . There was a higher incidence of some AEs with v and etanib BACKGROUND & AIMS Inhibitors of vascular endothelial growth factor receptor ( VEGFR ) and epidermal growth factor receptor ( EGFR ) have shown anti-tumor activities in advanced hepatocellular carcinoma ( HCC ) . The present study evaluated the efficacy and safety of v and etanib , an oral inhibitor of both VEGFR and EGFR , in patients with unresectable advanced HCC . METHODS Eligible patients were r and omized 1:1:1 to receive v and etanib 300mg/day , v and etanib 100mg/day , or placebo . Upon disease progression , all patients had the option to receive open-label v and etanib 300mg/day . The primary objective was to evaluate tumor stabilization rate ( complete response+partial response+stable disease ⩾4months ) . Secondary assessment s included progression-free survival ( PFS ) , overall survival ( OS ) and safety . Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI ) . RESULTS Sixty-seven patients were r and omized to v and etanib 300 mg ( n=19 ) , v and etanib 100 mg ( n=25 ) or placebo ( n=23 ) groups . Twenty-nine patients entered open-label treatment . V and etanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels . In both v and etanib arms , tumor stabilization rate was not significantly different from placebo : 5.3 % ( v and etanib 300 mg ) , 16.0 % ( v and etanib 100 mg ) and 8.7 % ( placebo ) . DCE-MRI did not detect significant vascular change after v and etanib treatment . Although trends of improved PFS and OS after v and etanib treatment were found , they were statistically insignificant . The most common adverse events were diarrhea and rash , whose incidence did not differ significantly between treatment groups . CONCLUSIONS V and etanib has limited clinical activity in HCC . The safety profile was consistent with previous studies |
13,304 | 24,682,606 | Based on low- to moderate- quality evidence , acromioplasty , be it open or arthroscopic , is no more effective than exercises for the treatment of RC tendinopathy .
Low- grade evidence also suggests that arthroscopic acromioplasty may yield better results in the short-term for shoulder range of motion in flexion compared to open acromioplasty , but long-term results are comparable between the two types of surgery . | The objective of this study is to review r and omized controlled trials evaluating the efficacy of surgery for the treatment of rotator cuff ( RC ) tendinopathy . | Objective To investigate the efficacy of a programme of manual therapy and exercise treatment compared with placebo treatment delivered by physiotherapists for people with chronic rotator cuff disease . Design R and omised , participant and single assessor blinded , placebo controlled trial . Setting Metropolitan region of Melbourne , Victoria , Australia . Participants 120 participants with chronic ( > 3 months ) rotator cuff disease recruited through medical practitioners and from the community . Interventions The active treatment comprised a manual therapy and home exercise programme ; the placebo treatment comprised inactive ultrasound therapy and application of an inert gel . Participants in both groups received 10 sessions of individual st and ardised treatment over 10 weeks . For the following 12 weeks , the active group continued the home exercise programme and the placebo group received no treatment . Main outcome measures The primary outcomes were pain and function measured by the shoulder pain and disability index , average pain on movement measured on an 11 point numerical rating scale , and participants ’ perceived global rating of overall change . Results 112 ( 93 % ) participants completed the 22 week trial . At 11 weeks no difference was found between groups for change in shoulder pain and disability index ( 3.6 , 95 % confidence interval −2.1 to 9.4 ) or change in pain ( 0.7 , −0.1 to 1.5 ) ; both groups showed significant improvements . More participants in the active group reported a successful outcome ( defined as “ much better ” ) , although the difference was not statistically significant : 42 % ( 24/57 ) of active participants and 30 % ( 18/61 ) of placebo participants ( relative risk 1.43 , 0.87 to 2.34 ) . The active group showed a significantly greater improvement in shoulder pain and disability index than did the placebo group at 22 weeks ( between group difference 7.1 , 0.3 to 13.9 ) , although no significant difference existed between groups for change in pain ( 0.9 , −0.03 to 1.7 ) or for the percentage of participants reporting a successful treatment outcome ( relative risk 1.39 , 0.94 to 2.03 ) . Several secondary outcomes favoured the active group , including shoulder pain and disability index function score , muscle strength , interference with activity , and quality of life . Conclusion A st and ardised programme of manual therapy and home exercise did not confer additional immediate benefits for pain and function compared with a realistic placebo treatment that controlled for therapists ’ contact in middle aged to older adults with chronic rotator cuff disease . However , greater improvements were apparent at follow-up , particularly in shoulder function and strength , suggesting that benefits with active treatment take longer to manifest . Trial registration Clinical trials NCT00415441 BACKGROUND Controversy exists regarding the optimal technique for arthroscopic rotator cuff repair . The purpose of this multicenter , r and omized , double-blind controlled study was to compare the functional outcomes and healing rates after use of single-row and double-row suture techniques for repair of the rotator cuff . METHODS Ninety patients undergoing arthroscopic rotator cuff repair were r and omized to receive either a single-row or a double-row repair . The primary objective was to compare the Western Ontario rotator cuff index ( WORC ) score at twenty-four months . Secondary objectives included comparison of the constant and american shoulder and elbow surgeons ( ASES ) scores and strength between groups . Anatomical outcomes were assessed with magnetic resonance imaging ( MRI ) or ultrasonography to determine the postoperative healing rates . RESULTS Baseline demographic data including age ( p = 0.29 ) , sex ( p = 0.68 ) , affected side ( p = 0.39 ) , and rotator cuff tear size ( p = 0.28 ) did not differ between groups . The WORC score did not differ significantly between groups at any time point ( p = 0.48 at baseline , p = 0.089 at three months , p = 0.52 at six months , p = 0.83 at twelve months , and p = 0.60 at twenty-four months ) . The WORC score at each postoperative time point was significantly better than the baseline value . The Constant score , ASES score , and strength did not differ significantly between groups at any time point . Logistic regression analysis demonstrated that a smaller initial tear size and double-row fixation were associated with higher healing rates . CONCLUSIONS No significant differences in functional or quality -of-life outcomes were identified between single-row and double-row fixation techniques . A smaller initial tear size and a double-row fixation technique were associated with higher healing rates as assessed with ultrasonography or MRI . LEVEL OF EVIDENCE Therapeutic level I. See Instructions for Authors for a complete description of levels of evidence Purpose The purpose of this study was to compare arthroscopic rotator cuff repair with single-row and double-row techniques because research has demonstrated the superiority of double-row repair from a biological and mechanical point of view but there is no evidence of clinical superiority . Methods A total of 160 patients with a full-thickness rotator cuff tear underwent arthroscopic repair with suture anchors . They were r and omised into two groups of 80 patients according to the repair technique : single-row ( group 1 ) and double-row ( group 2 ) . Results were evaluated by use of the University of California , Los Angeles ( UCLA ) , American Shoulder and Elbow Surgeons ( ASES ) and Constant question naires , the Shoulder Strength Index ( SSI ) and range of motion . Follow-up time was two years . Magnetic resonance imaging ( MRI ) studies were performed on each shoulder preoperatively and two years after repair . Results One hundred per cent of the patients were followed up . All measurements showed significant improvement compared with the preoperative status . The UCLA score showed significant improvement in group 2 . In over 30-mm tears UCLA and ASES showed significant differences . SSI showed significant improvement in group 2 . Range of motion showed significant improvements in flexion and abduction in group 2 . In under 30-mm tears group 2 showed also significant improvement in internal and external rotation . In MRI studies there were no significant differences . Conclusions At two years follow-up the double-row repair technique showed a significant difference in clinical outcome compared with single-row repair and this was even more significative in over 30-mm tears . No MRI differences were observed PURPOSE This study aim ed to determine whether radiofrequency (RF)-based plasma microtenotomy ( microdebridement ) was effective for treating chronic supraspinatus tendinosis . METHODS The institutional ethics committee approved the study design , and all patients signed informed consent forms . Patients ( age range , 30 to 70 years ) were considered for enrollment if 6 months of active conservative treatment had failed and they had Neer stage II impingement syndrome , positive radiographic evidence of type II acromion , and magnetic resonance imaging or ultrasound evidence of supraspinatus tendinosis . Patients ( N = 60 ) were r and omly assigned to undergo arthroscopic subacromial decompression or RF-based plasma microtenotomy . For microtenotomy , a bipolar RF-based probe ( TOPAZ ; ArthroCare , Austin , TX ) was used to perform microdebridement in the supraspinatus tendon ; patients did not undergo acromioplasty . Outcomes evaluation consisted of self-reported pain via a visual analog scale , as well as functional assessment ( American Shoulder and Elbow Surgeons [ ASES ] survey , Constant score , and University of California , Los Angeles [ UCLA ] question naire ) . Statistical analyses were performed by use of factorial dependent- measures analysis of variance tests . RESULTS Age and baseline scores on the visual analog scale ( mean + /- SD ) were 52.0 + /- 6.7 and 53.2 + /- 6.6 years and 8.4 + /- 0.9 and 8.2 + /- 0.8 points in the microtenotomy and arthroscopic subacromial decompression groups , respectively . A significant reduction in pain ( P < .001 ) and improved function ( P < .001 for all measures ) were observed in both groups postoperatively . Both treatment groups had almost identical longitudinal recovery profiles for pain relief ( P = .416 ) and restoration of function ( P = .964 for ASES score , P = .978 for Constant score , and P = .794 for UCLA score ) . At 1 year , the median pain score was 1.0 , and all patients had ASES , Constant , and UCLA scores of greater than 90 , greater than 80 , and greater than 30 , respectively . CONCLUSIONS Both procedures were associated with significant improvement postoperatively , but the RF-based plasma microtenotomy procedure draws into question the need for a more extensive procedure such as subacromial decompression in this patient population . LEVEL OF EVIDENCE Level I , therapeutic r and omized controlled study OBJECTIVES To compare the effect of grade d physiotherapeutic training of the rotator cuff versus arthroscopic subacromial decompression in patients with subacromial impingement . METHODS R and omised controlled trial with 12 months ' follow up in a hospital setting . Ninety consecutive patients aged 18 to 55 years were enrolled . Symptom duration was between six months and three years . All fulfilled a set of diagnostic criteria for rotator cuff disease , including a positive impingement sign . Patients were r and omised either to arthroscopic subacromial decompression , or to physiotherapy with exercises aim ing at strengthening the stabilisers and decompressors of the shoulder . Outcome was shoulder function as measured by the Constant score and a pain and dysfunction score . " Intention to treat " analysis was used , with comparison of means and control of confounding variables by general equation estimation analysis . RESULTS Of 90 patients enrolled , 84 completed follow up ( 41 in the surgery group , 43 in the training group ) . The mean Constant score at baseline was 34.8 in the training group and 33.7 in the surgery group . After 12 months the mean scores improved to 57.0 and 52.7 , respectively , the difference being non-significant . No group differences in mean pain and dysfunction score improvement were found . CONCLUSIONS Surgical treatment of rotator cuff syndrome with subacromial impingement was not superior to physiotherapy with training . Further studies are needed to qualify treatment choice decisions , and it is recommended that sample s are stratified according to disability level In a r and omized prospect i ve study , we selected 15 patients for arthroscopic subacromial decompression ( ASD ) and 19 patients for open subacromial decompression ( OSD ) . All had impingement syndrome ( Neer grade II ) , and had been unsuccessfully treated without surgery for more than 6 months . The UCLA Shoulder Rating Scale , Visual Analogue Scales for pain and satisfaction , isokinetic dynamometer recordings and physical testing were assessed preoperatively and at 1 ( except isokinetic testing ) , 3 , 6 , and 12 months , and , finally , 8 years after surgery . We found essentially no differences in the clinical tests between the groups during this period . The use of ASD or OSD seems to be a matter of cosmesis and personal preference This prospect i ve study was design ed to measure the costs and benefits of using a laser rather than electrocautery for soft tissue resection during arthroscopic shoulder decompression . Forty-nine shoulders with refractory Neer stage II impingement ( persistent fibrosis and tendinitis ) were divided into 2 groups . The composition of the 2 groups was similar with regard to sex , worker 's compensation status , dominant arm involvement , duration of symptoms , and length of conservative treatment . In one group , electrocautery was used to ablate the bursa and periosteum , release the coracoacromial ligament , and maintain hemostasis . In the other group , a laser was used in place of electrocautery . Patients had been evaluated preoperatively with 2 functional scoring systems . The patients were reexamined at 1 week and at 1 , 2 , 3 , 6 , and 12 months after surgery . There were no differences between the groups with regard to functional outcome or satisfaction . There was also no difference in terms of estimated blood loss or operative time . However , there was a statistically significant difference in total hospital charges between groups , with the laser group having a 23 % higher hospital bill . On the basis of these results , it is concluded that there was no medical benefit to laser-assisted arthroscopic subacromial decompression but there was an increased monetary cost Objectives : To compare the prognosis of subacromial impingement ( SAI ) stage II treated conservatively or with subacromial decompression . Methods : A follow‐up study after 4–8 years in a r and omized controlled trial ( RCT ) with 90 adult cases with SAI treated in a Danish hospital from 1996 to 2000 with grade d physiotherapy and exercises or arthroscopic subacromial decompression . Outcomes were proportion of time per year with income transfers ( indexed 0–1 ) , including total transfers ( marginalization ) , sick leave and disability pension obtained from the registry at the Ministry of Work . Self‐reported function , working capability , employment status and global improvement were obtained by question naire in September 2004 . The main outcomes are given as differences in development from baseline . Results : Seventy‐nine ( 88 % ) responded to the question naire and registry data were obtained from 81 . After 1 year the marginalization index increased by 0.45 [ 95 % confidence interval ( CI ) 0.35–0.56 ] for surgery and 0.25 ( 0.16–0.34 ) for physiotherapy . Cases undergoing surgery also tended to have more sick payments during the first year , but the difference was not significant . Four years after inclusion , changes in indices did not differ between treatment groups . Self‐reported outcomes after 4–8 years did not differ between treatment groups . Conclusion : The results of surgical decompression were equal to those of conservative treatment , and the surgery group had more income transferrals during the first year of follow‐up We report a r and omised controlled trial to examine the effectiveness and cost-effectiveness of arthroscopic acromioplasty in the treatment of stage II shoulder impingement syndrome . A total of 140 patients were r and omly divided into two treatment groups : supervised exercise programme ( n = 70 , exercise group ) and arthroscopic acromioplasty followed by a similar exercise programme ( n = 70 , combined treatment group ) . The main outcome measure was self-reported pain on a visual analogue scale of 0 to 10 at 24 months , measured on the 134 patients ( 66 in the exercise group and 68 in the combined treatment group ) for whom endpoint data were available . An intention-to-treat analysis disclosed an improvement in both groups but without statistically significant difference in outcome between the groups ( p = 0.65 ) . The combined treatment was considerably more costly . Arthroscopic acromioplasty provides no clinical ly important effects over a structured and supervised exercise programme alone in terms of subjective outcome or cost-effectiveness when measured at 24 months . Structured exercise treatment should be the basis for treatment of shoulder impingement syndrome , with operative treatment offered judiciously until its true merit is proven Objective : First , to vali date an ultrasonographic measure of the acromio-humeral distance ( AHD ) ; second , to compare the AHD variation during active abduction in patients with shoulder impingement syndrome ( SIS ) and healthy subjects ; and third , to evaluate the relationship between functional status and AHD variations before and after rehabilitation in SIS subjects . Design : This study has 3 components : ( 1 ) a reliability study , ( 2 ) a case-control study , and ( 3 ) a preliminary pretreatment/posttreatment clinical trial . Setting : Primary care hospital setting . Participants : Seven SIS patients and 13 healthy subjects . Interventions : For the clinical trial , the SIS subjects participated in 12 sessions of a rehabilitation program over 4 weeks . Main Outcome Measures : First , intraclass correlation coefficient for interobserver reliability ; second , AHD measured at 0 ° , 45 ° , and 60 ° of active abduction ; and third , Western Ontario Rotator Cuff Index . Results : Intraclass correlation coefficient for interobserver reliability ranged from 0.86 to 0.92 for the 3 shoulder positions . A significant reduction of the AHD was found within groups between rest and active abduction ( P < 0.05 ) . Comparison of AHD between groups was not statistically different ( P = 0.06 ; β < 0.80 ) . In pre-post rehabilitation analysis , improvement of the Western Ontario Rotator Cuff Index score was positively correlated to the reduction of the AHD narrowing as the arm was abducted ( r = 0.86 ; P = 0.01 ) . Conclusions : The ultrasound measure of AHD is reliable and sensitive . Although a distinct pattern of AHD variation in SIS patients could not be confirmed , a strong positive relationship was found between the reduction of AHD narrowing and functional improvement following rehabilitation . Ultrasound measurement of AHD might help identify SIS patients who will benefit from rehabilitation Thirty-eight patients with chronic calcifying tendinopathy of the shoulder were r and omized prospect ively into two groups : 19 patients had endoscopic decompression and 19 had open decompression . Thirty-three patients ( 19 with open and 14 with endoscopic decompression ) were available for followup . Clinical and ultrasonographic investigations were done at followup . The purpose of the current study was to evaluate prospect ively the clinical and sonographic results after open decompression and after endoscopic decompression . Apportionment of age and gender was similar in both groups . The followup was 15.7 months for patients after open decompression and 17.1 months for patients after endoscopic decompression . The average Patte score was 84.5 points ( 84.4 for patients who had endoscopic decompression and 84.6 for patients who had open decompression ) . Corresponding results were found with a Constant and Murley score of 96.6 points ( 97.6 for patients who had endoscopic decompression and 95.8 for patients who had open decompression ) . In the endoscopic group physiotherapy was recommended for 5 weeks more than in the open surgery group . Similar results were seen for the incapacity to work in both groups with 4.6 weeks for the patients who had endoscopic surgery and 5 weeks for the patients who had open surgery . No nerve injuries , wound infections , or other postoperative complications were found . Comparison of both surgical methods showed good clinical and score results . Endoscopic and open surgery are equally effective in the treatment of chronic calcifying tendinopathy The purpose of this study was to compare early postoperative outcomes between arthroscopic and mini-open repair for rotator cuff tears smaller than 3 cm to determine whether arthroscopic repair causes less postoperative pain and allows for faster recovery of range of motion . Sixty patients scheduled for rotator cuff repair were r and omized to either an arthroscopic repair group ( 30 patients ) or a mini-open repair group ( 30 patients ) . Pain level , range of motion , shoulder stiffness , and complications were compared between the 2 groups from immediately postoperatively to 6 months postoperatively . Although no statistically significant difference was found in mean visual analog scale pain scores between the 2 groups during the 6 months postoperatively , mean visual analog scale pain score was significantly lower in the arthroscopic repair group compared with the mini-open repair group at postoperative days 1 and 2 ( P=.02 and P=.04 , respectively ) . No significant difference existed in postoperative range of motion , duration of rehabilitation , shoulder stiffness , or complications between the 2 groups ; however , the use of additional analgesics in the arthroscopic repair group was significantly lower than in the mini-open repair group ( P=.03 ) . Arthroscopic and mini-open repair had equivalent clinical outcomes in the early postoperative period . The hypothesis that arthroscopic repair would cause less postoperative pain and allow faster recovery of range of motion in the early postoperative period compared with mini-open repair was not supported In a prospect i ve , r and omised study on the repair of tears of the rotator cuff we compared the clinical results of two suture techniques for which different suture material s were used . We prospect ively r and omised 100 patients with tears of the rotator cuff into two groups . Group 1 had transosseous repair with No. 3 Ethibond using modified Mason-Allen sutures and group 2 had transosseous repair with 1.0 mm polydioxanone cord using modified Kessler sutures . After 24 to 30 months the patients were evaluated clinical ly using the Constant score and by ultrasonography . Of the 100 patients , 92 completed the study . No significant statistical difference was seen between the two groups : Constant score , 91 % vs 92 % ; rate of further tear , 18 % vs 22 % ; and revision , 4 % vs 4 % . In cases of further tear the outcome in group 2 did not differ from that for the intact repairs ( 91 % vs 91 % ) , but in group 1 it was significantly worse ( 94 % vs 77 % , p = 0.005 ) . Overall , seven patients had complications which required revision surgery , in four for pain ( two in each group ) and in three for infection ( two in group 1 and one in group 2 ) OBJECTIVE --To compare the effectiveness of arthroscopic surgery , a supervised exercise regimen , and placebo soft laser treatment in patients with rotator cuff disease ( stage II impingement syndrome ) . DESIGN --R and omised clinical trial . SETTING --Hospital departments of orthopaedics and of physical medicine and rehabilitation . PATIENTS --125 patients aged 18 - 66 who had had rotator cuff disease for at least three months and whose condition was resistant to treatment . INTERVENTIONS --Arthroscopic subacromial decompression performed by two experienced surgeons ; exercise regimen over three to six months supervised by one experienced physiotherapist ; or 12 sessions of detuned soft laser treatment over six weeks . MAIN OUTCOME MEASURES --Change in the overall Neer shoulder score ( pain during previous week and blinded evaluation of function and range of movement by one clinician ) after six months . RESULTS --No differences were found between the three groups in duration of sick leave and daily intake of analgesics . After six months the difference in improvement in overall Neer score between surgery and supervised exercises was 4.0 ( 95 % confidence interval -2 to 11 ) and 2.0 ( -1.4 to 5.4 ) after adjustment for sex . The condition improved significantly compared with placebo in both groups given the active treatments . Treatment costs were higher for those given surgery ( 720 pounds v 390 pounds ) . CONCLUSIONS --Surgery or a supervised exercise regimen significantly , and equally , improved rotator cuff disease compared with placebo We performed a prospect i ve , r and omized study to determine whether arthroscopic subacromial decompression changes the outcome of rotator cuff repair . We performed a power analysis to ensure statistical validity . Patients scheduled for arthroscopic rotator cuff repair were r and omized to cuff repair with arthroscopic subacromial decompression ( group 1 ) or without it ( group 2 ) . All other aspects of the surgical and postsurgical treatment were identical . We included patients with full-thickness tears limited to the supraspinatus tendon and a type 2 acromion . We excluded patients with prior surgery , those with larger tears involving two or more tendons , those with a type 1 or 3 acromion , those with workers ' compensation cl aims , and those who had concomitant procedures ( labral repair , acromioclavicular joint resection ) There were 47 patients in group 1 and 46 in group 2 . Minimum follow-up was 1 year ( mean , 15.6 + /- 3.3 months ) . We recorded the American Shoulder and Elbow Surgeons ( ASES ) shoulder scores preoperatively and postoperatively . There was no statistical difference in postoperative ASES scores between group 1 ( 91.5 + /- 10.3 ) and group 2 ( 89.2 + /- 15.1 ) ( P = .392 ) . The change in ASES score over time did not differ between the two groups ( 61.1 vs 60.2 , P = .363 ) . In conclusion , within the parameters described above , arthroscopic subacromial decompression does not appear to change the functional outcome after arthroscopic repair of the rotator cuff Forty-two patients with subacromial impingement syndrome entered a r and omized prospect i ve study comparing open anterior acromioplasty with a physiotherapy regime . The criterion for a successful outcome of treatment was a reduction of the initial pain score of more than 50 % using the visual analogue scale ( VAS ) technique . The evaluation was performed by an independent observer . At the 6-month follow-up , treatment in the surgical group had been successful in 12/21 ( 57 % ) patients versus 6/18 ( 33 % ) in the physiotherapy group . A one-year evaluation revealed 16/21 ( 76 % ) " successes " in the surgical group . A direct and unbiased comparison with the physiotherapy group was not possible at one year , since 13 patients chose surgery after initial physiotherapy . However , in " an intention to treat " analysis outcome at one year was significantly better in those r and omized to surgery . We found two st and ardized , composite , active movements -- the " Pour out of a Pot " manoeuvre requiring the emptying of a pot of water , and the " H and in Neck " manoeuvre -- to be of predictive value for the outcome of surgery . When combining three pain-related variables into a criterion for prediction of success , a sensitivity of 78 % ( p < 0.02 ) and a specificity of 90 % ( p < 0.03 ) were attained . We advance the hypothesis that pain in the impingement syndrome is mainly elicited by comparison of the subacromial bursa . In some patients a traction-responsive pain generator in the supraspinatus tendon may be present as well The results of open subacromial decompression ( OSD ) were compared with arthroscopic subacromial decompression ( ASD ) after 1 year in 32 subjects ( 4 bilateral ) , and the correlation between the two shoulder rating scales for impingement was documented . Patients were evaluated clinical ly on the modified University of California at Los Angeles ( UCLA ) shoulder rating scale , and Constant scale . Scapular position and rotation were evaluated as well as a rotation and abduction shoulder strength test using the Cybex II dynamometer . No parameters revealed significant differences between the groups , except for the UCLA score which indicated an advantage for the ASD group ( p = 0.046 ) . The OSD group scored 24.5 ( 5.45 ) on the UCLA scale and 73.8 ( 18.9 ) on the Constant scale , whereas the ASD group scored 28.3 ( 5.6 ) and 80.8 ( 16.4 ) . To study the correlation between both scales , the Pearson correlation product-moment coefficient was calculated and a high correlation ( r = 0.81 ) obtained . Less mobility was found in the operated arm for all parameters , with the exception of glenohumeral abduction in both groups and passive elevation in the OSD group . Only in the OSD group did the scapula in the operated extremity show more abduction of the inferior angle of the scapula . Weaker abduction strength in the operated side was found in the ASD group , whereas in the OSD group there was significantly less adduction and external rotation strength at 180 degrees/s en 240 degrees/s . We conclude that after one year the open group tends to catch up with the arthroscopic patients and that the main benefits after arthroscopic surgery as described in literature are more evident in the shorter period The effectiveness of arthroscopic surgery , supervised exercises , and placebo was compared in 125 patients with rotator cuff disease ( impingement syndrome stage II ) in a r and omized clinical trial . The median age was 48 years , and the median duration of complications was 1 to 2 years . The treatments were arthroscopic subacromial decompression performed by 2 experienced surgeons , an exercise regimen supervised for 3 to 6 months by 1 experienced physiotherapist , or 12 sessions of detuned soft laser ( placebo ) for 6 weeks . The criterion for success was a Neer shoulder score > 80 . Fifteen ( 50 % ) and 11 ( 22 % ) of the patients r and omized to placebo and exercises , respectively , had surgery during the 2 1/2-year follow-up period and were classified as having failure with the treatments . The success rate was higher ( P < .01 ) for patients r and omized to surgery ( 26 of 38 ) and exercises ( 27 of 44 ) compared with the placebo group ( 7 of 28 ) . The odds ratio for success after surgery compared with exercises was 1.5 ( 95 % confidence interval 0.6 to 3.7 ; P = .49 ) . Including all patients who underwent operation , the success rate in those not on sick leave ( 19 of 21 ) before surgery was higher compared with those on sick leave ( 18 of 36 ) ( adjusted odds ratio 5.6 [ 1.2 to 29.2 ] ) . Similar results were observed for patients not receiving versus those receiving regular pain medication before surgery ( adjusted odds ratio 4.2 [ 1.2 to 15.8 ] ) A r and om prospect i ve comparison was conducted of 20 patients who underwent arthroscopic subacromial decompression or open acromioplasty as treatment for impingement syndrome . The Neer anterior acromioplasty served as comparison in the evaluation to arthroscopic technique . The comparison shows more rapid rehabilitation and better range of motion in the arthroscopic group . Time of surgery is also shorter for arthroscopy than for the open technique . Arthroscopic subacromial decompression appears to be superior to open acromioplasty as a treatment for impingement syndrome In a prospect i ve study , 20 patients were r and omly selected for either open acromioplasty according to Neer or for arthroscopic subacromial decompression ( ASD ) . All suffered from shoulder impingement for which conservative treatment had been unsuccessful . Functional results after two years were assessed . All patients were assessed radiographically to visualize recurrence of subacromial osteophytes . Functional results in the arthroscopic group are good and similar to those after open surgery . Both methods seem to result in adequate subacromial decompression , including bone resection . The arthroscopic method also has in its favor less operating time , earlier restoration of active range of motion , and reduction in time away from work In a prospect i ve r and omised study we compared the results of arthroscopic subacromial bursectomy alone with debridement of the subacromial bursa followed by acromioplasty . A total of 57 patients with a mean age of 47 years ( 31 to 60 ) suffering from primary subacromial impingement without a rupture of the rotator cuff who had failed previous conservative treatment were entered into the trial . The type of acromion was classified according to Bigliani . Patients were assessed at follow-up using the Constant score , the simple shoulder test and visual analogue scores for pain and functional impairment . One patient was lost to follow-up . At a mean follow-up of 2.5 years ( 1 to 5 ) both bursectomy and acromioplasty gave good clinical results . No statistically significant differences were found between the two treatments . The type of acromion and severity of symptoms had a greater influence on the clinical outcome than the type of treatment . As a result , we believe that primary subacromial impingement syndrome is largely an intrinsic degenerative condition rather than an extrinsic mechanical disorder Between May 1988 and May 1990 , 44 patients with Stage II impingement were r and omized into open and arthroscopic treatment groups . Forty-one patients were available for final follow-up in May 1991 : 22 in the open group , 19 in the arthroscopic group . Comparisons of pain , function , motion , and strength were made preoperatively and at 2 , 6 , 12 , 26 , and 52 weeks postoperatively . Final analysis showed that the main benefits of arthroscopic acromioplasty were evident in the first 3 months postoperatively . Arthroscopic patients regained flexion and strength more rapidly than did open patients , had shorter hospitalizations , used less narcotics , and returned more quickly to both work and activities of daily living . By 3 months postoperatively , open patients tended to " catch up " with arthroscopic patients , and further recovery was equivalent . In both groups , full recovery took at least 1 year for the majority of patients and in both groups at 1 year > 90 % of patients achieved a satisfactory result . Because of its medical and economic advantages for both the patient and the health-care system , we conclude that arthroscopic acromioplasty should become the procedure of choice for patients with impingement syndrome refractory to conservative treatment The purpose of this study is to determine whether arthroscopic acromioplasty is equivalent or superior to open acromioplasty , in a prospect i ve , r and omized , controlled , blinded clinical trial . Seventy-one patients with a clinical diagnosis of impingement syndrome were r and omized to arthroscopic or open acromioplasty . Nine were excluded because of full-thickness rotator cuff tears diagnosed after r and omization . Sixty-two patients ( 49 men and 13 women ) with a minimum follow-up of 12 months ( mean , 25 months ) were included . The patient groups were virtually identical with regard to duration of symptoms , shoulder functional dem and s , age , sex , h and dominance , mechanism of onset , range of motion , strength , joint laxity , and the presence of a compensation cl aim . Patients were prospect ively r and omized to arthroscopic or open acromioplasty after stratification for age ( > 50 years),associated ligamentous laxity , and the presence of an ongoing compensation cl aim . The main outcome measure was visual analog scales for pain and function . Also recorded were UCLA shoulder scores and visual analog scales for postoperative improvement , patient satisfaction , and a variety of clinical measures . An independent blinded examiner assessed all patients . There was no significant difference between open and arthroscopic acromioplasty in visual analog scales for postoperative improvement ( P = .30 ) , patient satisfaction ( P = .94 ) , UCLA shoulder score ( P = .69 ) , or strength ( P = .62 ) ; however , open was superior to arthroscopic acromioplasty for pain and function ( P = .01 ) . Overall , 67 % of patients had a good or excellent result . This increased to 87 % when unsettled compensation cl aims were excluded . Repeat ( open ) acromioplasty was performed in 5 patients in the unsuccessful arthroscopic group without improvement . Open acromioplasty was equivalent to arthroscopic acromioplasty for UCLA scores and patient satisfaction . For pain and function , both gave significant improvement but the open technique may be superior . Unsettled compensation is a predictor of poor outcome STUDY OBJECTIVE To determine the amount of change in pain severity , as measured by a visual analog scale , that constitutes a minimum clinical ly significant difference . METHODS Patients 18 years of age or older who presented with acute pain result ing from trauma were enrolled in this prospect i ve , descriptive study . The setting was an urban county hospital emergency department with a Level 1 trauma center . In the course of a brief interview , patients were asked to indicate their current pain severity with a single mark through a st and ard 100-mm visual analog scale . At intervals of 20 minutes for the next 2 hours , patients were asked to repeat this measurement and , in addition , to contrast their present pain severity with that at the time of the previous measurement . They were to indicate whether they had " much less , " " a little less , " " about the same , " " a little more , " or " much more " pain . All contrasts were made without reference to prior visual analog scale measurements . A maximum of six measurements of pain change were recorded per patient . Measurements ended when the patient left the ED or when the patient reported a pain score of zero . The minimum clinical ly significant change in visual analog scale pain score was defined as the mean difference between current and preceding visual analog scale scores when the subject noted a little less or a little more pain . RESULTS Forty-eight subjects were enrolled , and 248 pain contrasts were recorded . Of these contrasts , 41 were rated as a little less and 39 as a little more pain . The mean difference between current and preceding visual analog scale scores in these 80 contrasts was 13 mm ( 95 % confidence interval , 10 to 17 mm ) . CONCLUSION The minimum clinical ly significant change in patient pain severity measured with a 100-mm visual analog scale was 13 mm . Studies of pain experience that report less than a 13-mm change in pain severity , although statistically significant , may have no clinical importance |
13,305 | 23,572,293 | The short-term adverse effects were mild as shown by the low rate of withdrawal due to adverse effects | Background UV-based therapies , which include narrow-b and ( NB ) UVB , broad-b and ( BB ) UVB , and psoralen and UVA ( PUVA ) , are well known treatment options for moderate to severe plaque psoriasis .
However , there are limited evidence -based review s on their efficacy , short-term safety , and tolerability .
Aim The aim of the study was to evaluate the efficacy , short-term safety , and tolerability of UV-based therapy in the treatment of adults with moderate to severe plaque psoriasis . | The synthetic compound MC 903 ( calcipotriol ) is a structural analogue of the naturally occurring , biologically active 1,25-dihydroxyvitamin D3 [ 1,25-(OH)2-D3 ] . MC 903 and 1,25-(OH)2-D3 show similar receptor binding and comparable effects on cell differentiation . However , MC 903 appears to be at least 100 times less potent in its effects on calcium metabolism . In previous double-blind placebo-controlled studies , topical MC 903 has been shown to have a therapeutic effect in psoriasis . The present open study involving 20 patients with psoriasis vulgaris was a right/left comparison of the efficacy and tolerability of MC 903 ointment ( 50 micrograms/g ) alone or with UVB radiation . After treatment for 8 weeks , topical MC 903 alone result ed in marked improvement in 66 % of the patients and in clearance in 17 % . Combination of topical MC 903 with UVB result ed in marked improvement in 50 % of the patients and in clearance in 39 % . These differences were not statistically significant . No significant change in serum calcium levels was detected . Two patients developed a facial dermatitis which disappeared spontaneously during continued treatment . These results show that the combination of topical MC 903 and UVB radiation is well tolerated . Larger-scale studies are warranted to answer the question whether UVB radiation induces a significant improvement of the antipsoriatic effect of topical MC 903 BACKGROUND Psoralen plus ultraviolet A ( PUVA ) for the treatment of psoriasis has never been evaluated using the Psoriasis Area Severity Index ( PASI ) in a r and omized , double-blind , placebo-controlled trial . The lack of such data limits our capacity to estimate PUVA 's efficacy relative to other treatment options that are available today . OBJECTIVES The purpose of this study was to evaluate the efficacy of PUVA therapy for patients with plaque-type psoriasis . METHODS This study involved 40 patients with psoriasis ; 30 received PUVA and 10 received UVA with placebo . PASI scores were assessed at baseline and every 4 weeks thereafter for 12 weeks . RESULTS By nonresponder imputation , 60 % ( 18 of 30 ) in the PUVA group achieved 75 % or more improvement in PASI score after 12 weeks of treatment compared with 0 % ( 0 of 10 ) in the UVA plus placebo group ( P < .0001 ) . Using intent to treat with last observation carried forward analysis , 63 % ( 19 of 30 ) in the PUVA group achieved 75 % or more improvement in PASI score compared with 0 % ( 0 of 10 ) in the UVA plus placebo group ( P < .0001 ) . By per protocol analysis , 86 % ( 18 of 21 ) in the PUVA group as compared with 0 % ( 0 of 7 ) in the UVA plus placebo group reached 75 % or more improvement in PASI score after 12 weeks ( P < .0001 ) . LIMITATIONS The study was relatively small with only 40 patients enrolled and 28 patients who completed the protocol . Further studies that involve head-to-head comparison of PUVA with other treatment modalities are needed . Nonresponder imputation , last observation carried forward with intent to treat , and per protocol analyses each have separate advantages and limitations when determining clinical significance . CONCLUSIONS This study supports the observation that PUVA is a highly efficacious treatment for chronic plaque psoriasis BACKGROUND Psoralen-UVA ( PUVA ) photochemotherapy is widely used for the treatment of psoriasis despite concerns of skin carcinogenesis from high cumulative UVA doses and number of treatments . OBJECTIVE We attempted to determine whether combined bath-PUVA with narrow-b and ( 311 nm ) phototherapy improves efficacy and reduces long-term toxicity . METHODS Twelve psoriatic patients underwent phototesting with 311 nm lamps and , after topical bath-water psoralen sensitization , with 311 nm , UVA , or both radiations . Patients were treated with bath-PUVA on one side of the body and with bath-PUVA plus 311 nm exposures ( bath-PUVA-311 nm ) on the other side . On both sides , four weekly treatments were delivered and UVA doses were increased once weekly whereas 311 nm doses were adjusted at each exposure . RESULTS Psoralen sensitization did not modify the erythematous threshold to 311 nm radiation . However , 311 nm exposures enhanced the phototoxic activity of bath-PUVA . Bath-PUVA-311 nm cleared psoriasis with fewer exposures and lower cumulative UVA doses under the same minimally erythemogenic conditions . CONCLUSION Combination with 311 nm exposures enhanced the phototoxic and therapeutic activities of bath-PUVA OBJECTIVE To determine whether the addition of 311-nm narrowb and UV-B ( NB UV-B ) phototherapy accelerates and improves the therapeutic efficacy of alefacept , a biological antipsoriatic drug approved for the treatment of moderate to severe psoriasis . DESIGN R and omized half-body comparison study . SETTING Ambulatory section of a university hospital photodermatology unit . PATIENTS Fourteen patients with moderate to severe psoriasis . INTERVENTIONS All patients were treated with 7.5 mg of intravenous alefacept once weekly for 12 weeks . Three times each week , a r and omly selected body half ( left or right ) was treated with NB UV-B light until complete remission , defined as a reduction in the Psoriasis Area Severity Index ( PASI ) to 3 or lower , was achieved on the irradiated body half . MAIN OUTCOME MEASURES Modified PASI , self-assessed visual analogue scale rating of skin lesions , and self-assessed therapeutic efficacy . RESULTS After 12 weeks of treatment , the mean PASIs on UV-irradiated and nonirradiated body halves were significantly reduced by 81 % and 62 % , respectively ( P < .001 ) . From week 3 to week 12 , the mean PASI was significantly lower on UV-irradiated body halves than on nonirradiated body halves ( P < .001 ) . At week 12 , PASI reductions of greater than 75 % had been achieved significantly more often on UV-irradiated body halves ( 86 % , 12 of 14 ) than on nonirradiated body halves ( 43 % , 6 of 14 ) , and complete remission had been achieved significantly more often on UV-irradiated body halves ( 43 % , 6 of 14 ) than on nonirradiated body halves ( 0 of 14 ) ( McNemar test P = .03 ) . CONCLUSIONS In this r and omized half-side comparison of alefacept with and without phototherapy for psoriasis , alefacept with NB UV-B phototherapy accelerated and improved the clearance of psoriasis . This suggests a promising future for this combination as antipsoriatic therapy Summary Background The optimum treatment frequency for narrowb and ( TL‐01 ) ultraviolet B ( NB‐UVB ) in psoriasis is not yet known . We have previously found three times weekly to be preferable to five times weekly treatment in our population A prospect i ve , r and omized , double-blind , placebo-controlled trial was performed to assess the effect of a potent topical corticosteroid cream used in conjunction with ultraviolet B ( UVB ) phototherapy on psoriasis with respect to time to clearing and duration of remission after clearing . Of the 53 out patients who received suberythemogenic UVB phototherapy three times per week , 24 applied the topical corticosteroid and 29 applied the placebo cream twice daily until clearing was achieved . Nine patients in each group failed to comply with the protocol . Although there was a trend toward a slightly more rapid response in the topical corticosteroid-treated group , there was no significant difference in patients ' early response to therapy , number of treatments , and UVB dose required to achieve clearing . Patients in the topical corticosteroid-treated group remained in remission longer than did patients in the control group ( 183 vs 116 days ) . Life-table analysis predicts that 62 % of emollient-treated patients flare within 6 months of clearing compared with only 42 % of topical corticosteroid-treated patients ( p less than 0.1 ) . For most patients with psoriasis who receive UVB therapy in an outpatient setting , the use of potent topical corticosteroids appears to produce , at most , a modest beneficial effect The efficacy of trimethylpsoralen bath PUVA and UVB TL01 were compared in chronic plaque psoriasis . Patients were r and omly assigned to receive UVB TL01 on one side and bath PUVA on the contra-lateral side . Altogether 17 patients received treatments and 15 completed the trial . The decrease in the PASI score was greater with UVB TL01 than PUVA . At the end of the treatment period , the difference was highly significant ( p < 0.001 ) . The difference was already significant at week 3 ( p = 0.014 ) . The relative median decrease in the PASI score was 77 % ( 24 - 100 % ) with UVB and 45 % ( 8 - 100 % ) with PUVA . The median cumulative UVB dose was 39.92 ( range 13.95 - 81.56 ) J/cm2 and the corresponding UVA dose was 8.06 ( range 3.31 - 12.51 ) J/cm2 . All patients relapsed within 4 months . Narrowb and UVB improved psoriasis clinical ly and statistically more efficiently than trimethylpsoralen bath PUVA , and UVB was better tolerated BACKGROUND Combination UVB phototherapeutic regimens were introduced to improve therapeutic results and reduce cumulative UVB doses . OBJECTIVE Broadb and UVB and UVB + bergamot oil ( UVBB ) therapies in the treatment of psoriasis were compared with regard to : efficacy , side effects , mean number of procedures , mean UVB dose , and duration of remissions . PATIENTS / METHODS One hundred and ninety three ( 193 ) patients r and omly divided into two groups were treated : Group I with UVB monotherapy and Group II with UVB and bergamot oil ( UVBB ) . RESULTS Overall assessment of the efficacy of the two treatment regimens demonstrated no statistically significant differences in either the post-therapy PASI values ( t = 0.27 , p = 0.786 ) or the duration of remissions ( t = 0.22 , p = 0.904 ) . However , significant differences in the number of procedures ( t = 2.3 , p = 0.04 ) and the cumulative UVB doses were established ( t = 3.4 , p = 0.004 ) . CONCLUSION UVBB phototherapy significantly reduces the UVB doses and the duration of treatment for psoriatic patients Thirty‐four patients with extensive psoriasis were treated in a double‐blind parallel fashion with either acitretin plus bath PUVA ( trimethylpsoralen bath + UVA ) or etretinate plus bath PUVA . Each group consisted of 17 patients . The dose of retinoid was 40 mg/day during the 2‐week monotherapy phase and subsequently 20 mg/day during the combination treatment . Bath PUVA was given three times a week starting with a UVA dose of 0.06 J/cm2 . Remission ( > 90 % improvement ) was achieved in all patients in 6–10 weeks . There were no significant differences in clinical response between the two groups ; the mean ±SD PASI score ( psoriasis area and severity index ) before treatment was 22.6±7.1 in the acitretin‐PUVA group and 19.4±7.8 in the etretinate‐PUVA group . The corresponding figures after treatment were 0.6±0.6 and 1.0±0.5 , respectively . Side‐effects related to retinoid treatment were frequent in both groups but they were usually mild and well‐tolerated . There was only one case of diffuse alopecia after 8 weeks in the etretinate‐PUVA group . Scaling of the palms and soles was seen in six patients in the acitretin‐group but only in two patients in the etretinate‐group . Triglycerides were elevated in about half of the patients in both groups . The present study shows that acitretin is as effective as etretinate in the combination with bath PUVA Ro 10 - 9359 is a retinoic acid derivative , selected for study because of a better tolerance than retinoic acid , shown in animal experiments . Doses of 25 mg b.i.d . , 25 mg t.i.d . and 50 mg b.i.d . were administered orally to 27 patients suffering from severe chronic generalized psoriasis . The clinical efficacy was evaluated by means of a new index , psoriasis area and severity index ( PASI ) based on severity and area of psoriatic lesions . At doses of 25 mg t.i.d . or 50 mg b.i.d . Ro 10 - -9359 proved to be an extremely potent antipsoriatic drug . A more than 90 % reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4 - 8 weeks of treatment . This good effect lasted about 5 weeks after treatment . Side effects were frequent , but mostly mild and completely reversible after termination of treatment BACKGROUND : The addition of calcipotriol ointment to PUVA therapy for psoriasis vulgaris results in a lower total UVA dose and a faster onset of response . The addition of calcipotriol cream to PUVA , however , has not been studied . OBJECTIVE : To investigate whether combining calcipotriol cream with PUVA therapy has a UVA sparing effect . METHODS : We performed a r and omized , multicentre , vehicle‐controlled , double‐blind , 12‐week comparative study including 120 patients with psoriasis covering 20–50 % body surface area . The study consisted of a washout phase followed by a 10‐week treatment phase . PUVA therapy three times weekly was added within 1 week after r and omization . Efficacy was assessed by the Psoriasis Area and Severity Index ( PASI ) . RESULTS : At baseline the mean PASI scores were 17.5 and 19.2 in the calcipotriol and vehicle ( placebo ) groups , respectively . At the end of treatment , the mean PASI scores were 2.65 and 7.03 ( p<0.01 ) , respectively . A reduction in PASI score > 90 % was observed in 69 % of the patients in the calcipotriol‐treated group and in 36.4 % of the patients in the vehicle group ( p<0.01 ) . CONCLUSION : Calcipotriol cream plus PUVA clearly reduces the cumulative dose of UVA and improves the response of psoriasis vulgaris to PUVA BACKGROUND Although PUVA treatment of psoriasis is more effective than conventional or broad-b and UVB phototherapy , two small studies have suggested that narrow-b and or TL-01 phototherapy may have a therapeutic effect equal to PUVA . If confirmed , this would be of considerable importance as TL-01 therapy is likely to be considerably safer in the long term than PUVA . OBJECTIVE The purpose of this study was to compare PUVA with narrow-b and ( TL-01 ) phototherapy in psoriasis . METHODS We studied 100 patients with plaque-type psoriasis who were r and omly allocated to twice-weekly treatment with PUVA or narrow-b and UVB . RESULTS Clearance of psoriasis was achieved in a significantly greater proportion of patients treated with PUVA ( 84 % ) than with TL-01 ( 63 % ) ( P = .018 ) , and with significantly fewer treatments ( median number of treatments for clearance with PUVA , 16.7 ; with TL-01 , 25.3 ; P = .001 ) . Only 12 % of those treated with TL-01 were clear of psoriasis 6 months after finishing treatment compared with 35 % for PUVA ( P = .002 ) . CONCLUSION When given twice weekly , PUVA is more effective for psoriasis than narrow-b and UVB phototherapy BACKGROUND Combining phototherapy with topical and oral agents allows clinicians to treat recalcitrant psoriasis with reduced number of treatments and cumulative UV exposures . OBJECTIVE This study was design ed to determine the number of treatments necessary to clear plaque-type psoriasis when narrowb and ( NB ) UVB is administered with methotrexate ( MTX ) or placebo in a r and omized , controlled fashion . METHODS MTX ( 15 mg/wk ) or placebo was administered 3 weeks before st and ard NB UVB phototherapy was started . Treatments with the oral agent and phototherapy were continued until Psoriasis Area and Severity Index scores were reduced to less than 10 % of the original scores or 24 weeks . Follow-up was performed until lesional scores returned to 50 % of the original ones . RESULTS A total of 24 patients were enrolled and 19 patients completed the study . Kaplan-Meier analysis revealed that the median time to clear psoriasis in the MTX/NB UVB group was 4 weeks , which was significantly less than that for the placebo/NB UVB group . LIMITATIONS Our sample size was relatively small ( 24 patients ) with 5 dropouts . In addition , the study was conducted in skin types III to IV , Asian patients . Follow-up was limited to 4 to 6 months after completion of phototherapy . CONCLUSION MTX pretreatment allows physicians to clear psoriasis in fewer phototherapy sessions than when phototherapy is administered alone BACKGROUND Bath-psoralen plus ultraviolet A ( PUVA ) radiation therapy is increasingly replacing oral PUVA because of its superior short- and long-term safety profile . Several investigations in recent years have led to a refinement of the bath-PUVA protocol ; however , the optimal therapeutic concentration of methoxsalen in the bath water has as yet not been delineated . OBJECTIVES The therapeutic efficacy and tolerability of bath-PUVA by using two different dilutions of methoxsalen ( 1 mg/L vs 5 mg/L or 0.0001 % vs 0.0005 % ) were compared in 46 patients with chronic plaque-type psoriasis in a prospect i ve , r and omized , double-blind study . METHODS Scores of the Psoriasis Area and Severity Index excluding psoriasis of the head ( PASI(TUL ) ) and the Plaque Severity Index ( PSI ) were assessed at baseline and at biweekly intervals thereafter until (near)complete clearance or maximal improvement . In addition , methoxsalen plasma levels were determined immediately after the psoralen bath during the first week of treatment and treatment-related side effects were recorded throughout the entire study period . RESULTS The median baseline PASI(TUL ) score decreased from 11.7 ( 7.5 - 32.8 ) to 3.3 ( 0.6 - 1.2 ) ( -72 % ) in the 1 mg/L methoxsalen group and from 10.8 ( 6.6 - 20.7 ) to 1.4 ( 03.2 ) ( -87 % ) in the 5 mg/L methoxsalen group ( P < .01 ) . The median baseline PSI score decreased from 9 ( 6 - 12 ) to 3.1 ( 0.6 - 10 ) ( -66 % ) in the 1 mg/L methoxsalen group and from 9.3 ( 7.3 - 12 ) to 1.6 ( 0 - 3.6 ) ( -83 % ) in the 5 mg/L methoxsalen group ( P < .01 ) . The median cumulative UVA exposure dose was 25.4 ( 5.3 - 81.5 ) J/cm2 for 5 mg/L methoxsalen and 71.9 ( 20.7 - 587.3 ) J/cm2 for 1 mg/L methoxsalen ( P = .001 ) . The number of exposures ( 22 [ 11 - 29 ] vs 23 [ 11 - 34 ] ) and treatment duration ( 43 [ 19 - 68 ] vs 44 [ 23 - 66 ] days ) was comparable for both methoxsalen dilutions ( P = .97 ) . Median psoralen plasma levels were 0 ( 0 - 26 ) ng/mL after the 1 mg/L and 30 ( 0 - 64 ) ng/mL after the 5 mg/L methoxsalen immersion ( P = .001 ) . Mild to moderate adverse events were more common in the 5 mg/L methoxsalen group . LIMITATIONS The conclusions of this r and omized controlled study are limited by the relatively small sample size . CONCLUSIONS Our data indicate that in bath-PUVA treatment the use of a high ( 5 mg/L ) methoxsalen concentration is substantially more effective in clearing chronic plaque-type psoriasis than a low ( 1 mg/L ) concentration OBJECTIVE To compare the efficacy of oral psoralen-UV-A ( PUVA ) therapy with that of narrowb and UV-B ( NB-UVB ) therapy in patients with chronic plaque psoriasis . DESIGN Double-blind r and omized study . SETTING Phototherapy unit in a university hospital . Patients Ninety-three patients with chronic plaque psoriasis . Interventions Twice-weekly NB-UVB or PUVA therapy , starting at 70 % of the minimum phototoxic or erythema dose , with 20 % incremental increases . Patients were treated until clearance , up to a maximum of 30 sessions ; those with clearance were followed up until relapse or for 12 months . MAIN OUTCOME MEASURES Proportion of patients achieving clearance , number of treatments to clearance , and , among those with clearance , the proportion remaining in remission at 6 months . RESULTS Patients with skin types V and VI had a lower rate of clearance than those with skin types I through IV ( 24 % vs 75 % ; P = .001 ) . In patients with skin types I through IV , PUVA was significantly more effective than NB-UVB at achieving clearance ( 84 % vs 65 % ; P = .02 ) . The median number of treatments to clearance was significantly lower in the PUVA group ( 17.0 vs 28.5 ; P<.001 ) . More patients treated with PUVA vs NB-UVB were reported to have erythema at some stage during treatment ( 49 % vs 22 % ; P = .004 ) , although this difference may have been due to ascertainment bias . Six months after the cessation of therapy , 68 % of PUVA-treated patients were still in remission vs 35 % of NB-UVB-treated patients . Conclusion Compared with NB-UVB , PUVA achieves clearance in more patients with fewer treatment sessions and results in longer remissions BACKGROUND Psoriasis is a chronic , recurring inflammatory disease affecting the skin , joints and nails that has a significant negative impact on the quality of life . Efficacy of combination of methotrexate/narrowb and ultraviolet B ( NBUVB ) phototherapy in the treatment of psoriasis has been rarely assessed . OBJECTIVES To compare the efficacy of methotrexate/NBUVB phototherapy combination vs. NBUVB phototherapy in the treatment of chronic plaque psoriasis . METHODS Forty patients with chronic plaque-type psoriasis ( body surface area involvement > 10 % ) were r and omized to receive either methotrexate/NBUVB phototherapy ( group A ) or placebo/NBUVB phototherapy ( group B ) . End point of treatment was 75 % reduction in Psoriasis Area and Severity Index ( PASI ) Score or upto 6 months , whichever was earlier . Patients were then followed up for a period of 12 weeks for assessment of relapse . RESULTS Of 40 patients , 37 completed the treatment period and 29 both the treatment period and follow-up . PASI 75 was achieved in 19/20 patients in group A and 14/20 patients in group B ( P < 0.04 ) . The mean number of weeks(P = 0.001 ) , the mean cumulative dose of NBUVB ( P = 0.001 ) and the mean number of phototherapy sessions ( P = 0.0001 ) required to achieve PASI 75 were significantly less in group A compared with group B. There was no significant difference in the number of patients who relapsed during the follow-up period ( P = 0.68 ) . CONCLUSION Combination of methotrexate and NBUVB phototherapy provides more rapid clinical improvement compared with NBUVB monotherapy in the treatment for chronic plaque-type psoriasis BACKGROUND Treatment with the tumor necrosis factor-alpha antibody adalimumab for 12 - 16 weeks produces a satisfactory response [ i.e. , 75 % reduction in psoriasis area and severity index ( PASI ) ] in a majority ( 70 - 80 % ) of patients with psoriasis . We asked whether 311 nm ultraviolet B ( UVB ) can improve therapeutic response of psoriatic lesions to adalimumab . METHODS Four patients ( age range , 49 - 67 years ) with moderate to severe plaque-type psoriasis were treated with st and ard dosage of adalimumab . During adalimumab therapy , a r and omly selected body half ( left or right , excluding the head ) was irradiated with 311 nm UVB three times weekly for 6 weeks . Treatment response was monitored weekly in terms of half-body PASI . RESULTS 311 nm UVB significantly accelerated the therapeutic response during adalimumab treatment . At the start of 311 nm UVB therapy , the mean PASI was 14.8 . After 6 weeks of 311 nm UVB therapy , the mean PASI was 2.0 on UV-irradiated body halves and 6.9 on non-irradiated body halves ( difference , 4.9 ; 95 % confidence interval , 0.4 - 9.4 ; P=0.041 ; 2-tailed paired t-test ) . This corresponded to an overall mean PASI reduction from baseline ( i.e. , adalimumab start ) of 86 % on UV-irradiated body halves vs. 53 % on non-irradiated body halves . CONCLUSION 311 nm UVB may accelerate and improve the clearance of psoriatic lesions in adalimumab-treated patients A r and omized double-blind study was design ed with 65 patients in order to clarify two points : ( 1 ) does addition of a retinoid to psoralen-ultra violet A photochemotherapy ( PUVA ) of severe psoriasis decrease the UVA energy required to achieve remission , and ( 2 ) is there a difference between two retinoids , i.e. etretinate and acitretin . Acitretin-PUVA treatment was significantly superior to placebo-PUVA with respect to several items ( decrease in lesional scores after 6 weeks of therapy , number of PUVA exposures , and total dose of UVA until remission ) . There were also differences between the etretinate-PUVA and placebo-PUVA groups , but only the decrease in lesional scores reached statistical significance Summary Two ultraviolet A ( UVA ) regimens for oral S‐methoxypsoralen ( 8‐MOP ) photochemotherapy ( PUVA ) for moderate/severe chronic plaque psoriasis using a half body study technique were compared . Each patient received both regimens . A higher‐dose regimen based on minimal phototoxic dose ( MPD ) within percentage incremental increases was given to one‐half of the body . The other half received a lower dose regimen based on skin type with fixed incremental UVA increases . Patients were treated twice weekly . Symmetrical plaques were scored to determine the rate of resolution with each regimen . In addition , the number of treatments , cumulative UVA dose and number of days in treatment to achieve overall clearance were recorded . Patients were review ed monthly for 1 year to record remission data . Thirty‐three patients completed the study . Both regimens were effective and well tolerated . With the MPD‐based approach , the number of exposures was significantly less for patients with skin types I and II but not III . Although the cumulative UVA dose was higher with the MPU regimen for all skin types studied , the reduced number of exposures required for clearance for skin types I and II but not III , combined with thesecurity of individualized MPD testing , has practical attractions . MPD testing also identified live patients who required an increased psoralen dose and six patients who required a reduction of the initial UVA dose with the skin type regimen . Forty‐two per cent were still clear 1 year after treatment and there was no significant difference in the number of days in remission between the regimens for those whose psoriasis had recurred . The reduction in the number of exposures required lor clearance with the MPD‐based regimen may be safer and more cost effective in the long term Background : Calcipotriol has been combined with a number of systemic antipsoriatric treatments , improving efficacy or reducing the systemic treatment required . Although studies on calcipotriol and UVB have also been performed , there are no data on the UVB-saving effect of calcipotriol combined with broad-b and UVB to reduce overall UVB exposure , while maintaining efficacy . Objectives : To assess the efficacy and safety of calcipotriol cream ( 50 μg/g ) combined with twice weekly broad-b and UVB and to determine if this treatment would require fewer UVB treatments and lower cumulative UVB irradiance when compared to a st and ard 3 times weekly broad-b and UVB regime in patients with extensive psoriasis . Methods : This multicentre , prospect i ve , r and omised , parallel-group , vehicle-controlled , single-blind ( investigator ) study consisted of a 1-week wash-out phase , 12-week treatment phase and 12-week follow-up phase . Broad-b and UVB equipment was st and ardised and calibrated prior to the study . The UVB starting dose was based on the patient ’s minimal erythema dose . Assessment s included PASI , extent , severity and investigator and patient ’s overall assessment s of the psoriasis . Results : Fewer exposures ( 12 vs. 19 ) and less cumulative UVB irradiance ( 1,570 vs. 5,430 mJ/cm2 ) were required by the calcipotriol + twice weekly UVB group to achieve 80 % reduction in PASI ( p < 0.001 ) . Similarly , fewer exposures ( 22 vs. 25 ) and less cumulative UVB irradiance ( 4,147 vs. 9,670 mJ/cm2 ) were required by this group to achieve total clearance ( p < 0.001 ) . There was no difference in the PASI , patient ’s and investigator ’s overall assessment s and number of adverse events recorded by either group for both the treatment and follow-up phases . Conclusion : Calcipotriol cream + twice weekly broad-b and UVB phototherapy is an effective and safe antipsoriatric treatment , result ing in fewer UVB exposures , lower cumulative irradiance and a saving of time OBJECTIVE To compare the efficacy of narrowb and UV-B ( TL-01 ) phototherapy with oral 8-methoxypsoralen photochemotherapy ( 8-MOP psoralen-UV-A [ PUVA ] ) in patients with chronic plaque psoriasis ( CPP ) . DESIGN Open , r and omized , controlled study . SETTING Phototherapy unit in a dermatology hospital . PATIENTS Fifty-four patients with CCP . INTERVENTIONS Patients received whole-body threshold erythemogenic dose of either 3-times weekly TL-01 or twice-weekly oral 8-MOP PUVA , based on minimal erythema or phototoxic doses . Patients were treated until completely clear . OUTCOME MEASURES Number of treatments to clear , number of days in treatment , number of days in remission , and adverse effects of both therapies were assessed . RESULTS Forty-five patients completed the study . Those in the PUVA group required significantly fewer treatments to clear ( P = .03 ) . There was no significant difference in the number of days to clear or number of days in remission . A similar percentage of patients in the TL-01 and PUVA groups developed minimal perceptible erythema , showing that the regimens were equally erythemogenic . Asymptomatic , well-defined erythema occurred only in the PUVA group . Pruritus and polymorphic light eruption occurred equally in both groups , but only patients in the PUVA group developed nausea . CONCLUSION Narrowb and UV-B phototherapy , used 3 times weekly , is as effective for the treatment of CPP as oral 8-MOP PUVA used twice weekly BACKGROUND Narrow-b and UVB ( 311 nm ) phototherapy offering an emission spectrum closely conforming to the peak of the action spectrum for clearing psoriasis has significantly improved phototherapy for psoriasis . Because the majority of the commonly used topical therapies in treatment of psoriasis have limitations , a need for new topical agents remains . Tazarotene has been shown to be efficacious in plaque-type psoriasis . Combination of narrow-b and UVB with topical agents has been shown to enhance efficacy of both treatment modalities . OBJECTIVE We attempted to evaluate the efficacy of narrow-b and UVB phototherapy in combination with topical tazarotene . METHODS Ten patients with stable plaque psoriasis were treated with narrow-b and UVB . In addition , topical tazarotene 0.05 % was applied once daily to one side of the body . The follow-up period was 4 weeks . Efficacy was assessed separately for both body halves by means of a modified Psoriasis Area and Severity Index ( PASI ) . RESULTS Both treatment modalities notably reduced the PASI scores with values being significantly lower in skin areas treated with narrow-b and UVB phototherapy in combination with topical tazarotene . CONCLUSION The addition of tazarotene to narrow-b and UVB phototherapy promotes more effective , faster clearing of psoriasis compared with UVB ( 311 nm ) monotherapy BACKGROUND Alefacept , a fully human LFA-3/IgG(1 ) fusion protein , is a selective biological agent approved in the United States for the treatment of chronic plaque psoriasis . In phase 3 trials , clinical improvement and prolonged off-treatment remission of psoriasis correlated with reductions in circulating memory T cells . Reductions in pathogenic epidermal T cells in psoriatic lesions also have been noted following phototherapy with ultraviolet B ( UVB ) light . Because alefacept and UVB target T cells in different ways , combination therapy with these two agents may lead to greater efficacy . OBJECTIVES To determine the safety , tolerability , and efficacy trends of combination therapy with alefacept plus UVB light in patients with chronic plaque psoriasis . METHODS In an open-label , parallel-group study conducted at two sites , one in France and one in the United States , patients with chronic plaque psoriasis who were c and i date s for phototherapy received 12-weekly intramuscular injections of alefacept , 15 mg . In addition , patients were r and omized to one of three treatment arms : no UVB treatment , 6-week UVB treatment , and 12-week UVB treatment . UVB treatment consisted of narrowb and ( NB ) UVB at the site in France and broadb and ( BB ) UVB at the site in the United States . The 12-week treatment period was followed by a 12-week follow-up period . Clinic visits occurred weekly during treatment and every 2 - 4 weeks during follow-up . RESULTS A total of 60 patients ( n = 30/site ) were enrolled in the study . Alefacept was well tolerated when administered in combination with UVB treatment and as monotherapy . There was no evidence of increased phototoxicity or photosensitivity with the combination . At each study site , alefacept/UVB provided a higher overall response rate and led to a more rapid onset of response compared with alefacept monotherapy . Of patients who achieved > or = 50 % reduction from baseline Psoriasis Area Severity Index ( PASI 50 ) at 2 weeks after the last dose of alefacept , 75 - 100 % in the combination therapy groups maintained this response throughout follow-up in the absence of further psoriasis therapy . CONCLUSIONS In patients with chronic plaque psoriasis , combination therapy with alefacept plus short-term ( 6 - 12 weeks ) UVB treatment is well tolerated with a trend toward greater and more rapid efficacy than alefacept alone BACKGROUND Psoralen UV-A ( PUVA ) is an established therapy for psoriasis , but there is a well-documenated risk of melanoma and nonmelanoma skin cancer . Narrow-b and Ultraviolet-B ( NBUVB ) therapy has a lower carcinogenic risk , has equal therapeutic potential and is considerably safe in the long term than PUVA . AIM The aim of present study was to compare the efficacy and side-effects of PUVA and NBUVB in chronic plaque psoriasis . METHODS Sixty patients of chronic plaque psoriasis were taken up for the study and were r and omly divided into two groups of 30 each . They were well matched in terms of age , sex , psoriasis extent and pretreatment psoriasis area severity index ( PASI ) scoring . One group was treated with twice-weekly narrow-b and UV-B ( TL-01 ) phototherapy and the other group received twice-weekly oral 8-Methoxsalen PUVA for a period of 3 months . RESULTS Both the groups achieved > 75 % reduction in the PASI score or complete clearance at the end of 3 months , but PUVA group patients required significantly fewer number of treatment sessions and fewer number of days to clear the psoriasis as compared to the NBUVB group , while the mean cumulative clearance dose and adverse effects were significantly lower in the NBUVB group . CONCLUSION We concluded that PUVA group patients achieved a faster clearance , but the adverse effects were significantly lower in the NBUVB group Eighty ambulatory adult patients with severe psoriasis were included in our 14‐week study to compare the clinical effects of treatment with an aromatic retinoid ( Tigason ) , combination treatment with aromatic retinoid plus PUVA ( RePUVA ) , and PUVA alone . RePUVA was given by two different modifications : either 4 weeks of pretreatment with retinoid followed by 6 weeks of PUVA treatment , or 10 weeks of retinoid treatment with concomitant PUVA treatment during the last 6 weeks . The latter modification of RePUVA proved to be significantly more effective than the other treatments ( P<0.01 ) as regards complete remission . With respect to the number of patients with good or excellent improvement ( 75–100 % improvement ) there was no marked difference between RePUVA and PUVA treatments . Retinoid alone proved to be the least effective , showing , however , a good to excellent result in 65 % of patients . Besides the increase in efficacy , another advantage achieved by RePUVA was a highly significant ( P<0.001 ) reduction of total UVA doses to about one third as compared to PUVA therapy BACKGROUND Oral psoralen , when combined with UVB , shows an increased response in psoriasis . In this study , conventional psoralen-UVA ( PUVA ) therapy was compared with psoralen-UVB ( PUVB ) therapy in plaque-type psoriasis in patients with Fitzpatrick skin type IV . PATIENTS AND METHODS Equal numbers of patients with stable , plaque-type psoriasis were treated with either PUVA ( n = 22 ) or PUVB ( n = 22 ) , three times weekly until 90 % clearance was achieved . A final evaluation was made 3 months later . RESULTS The two groups showed no significant differences in terms of clearance of disease , mean number of exposures , or the average duration of therapy ; however , the cumulative dose of UVB required for clearance was significantly lower than that of UVA . Both groups had a similar acute side-effects ' profile . CONCLUSIONS PUVB therapy is as effective as conventional PUVA in the treatment of stable , plaque-type psoriasis in patients with Fitzpatrick skin type IV . A significantly lower dose of UVB is required for clearance as compared with UVA UVB is widely used to treat psoriasis . Conventional broadb and UVB lamps are less effective than narrowb and UVB lamps , which have an emission peak at 311 nm . The long-term safety of narrowb and UVB phototherapy is uncertain . " Selective " broadb and UVB lamps , which have little emission < 290 nm , are also available , but have not been adequately compared to narrowb and UVB lamps . We performed a r and omized comparison of narrowb and UVB ( TL-01 lamps ) and selective broadb and UVB ( UV6 lamps ) in 100 patients with psoriasis . The median number of exposures for clearance was 28.4 for TL-01 and 30.4 for UV6 ( ratio of the medians 0.93 ; 95 % confidence interval ( CI ) 0.80 , 1.09 ; P=0.39 ) . No significant difference was found in the proportion of patients achieving clearance : TL-01 56 % , UV6 40 % ( odds ratio for clearance with TL-01 relative to UV6 was 2.00 ( 95 % CI 0.87 , 4.62 ) , P=0.10 ) . Side effects , including the development of erythema during phototherapy , were similar for the two lamp types . Risk estimates based on the human photocarcinogenesis action spectrum predict that narrowb and UVB lamps will be 50 % more carcinogenic for equal erythemal doses than selective broadb and lamps ( UV6 ) . As these two lamp types appear to be of similar efficacy , phototherapy using a selective broadb and source may be a safer option than use of narrowb and UVB Three and five times weekly narrow‐b and TL‐01 ( 311–313 nm ) ultraviolet ( UV ) B phototherapy regimens for chronic plaque psoriasis were compared in a r and omized , observer‐blinded , half‐body , within‐patient paired study . Twenty‐one patients [ 13 men , eight women , age range 21–68 years , skin phototypes I ( two patients ) , II ( 14 ) and III ( five ) ] entered the study . Sixteen reached clearance or minimal residual activity ( MRA ) on both sides . Of the other five , three withdrew because they did not reach clearance or MRA on the 5 × weekly side by a maximum of 30 treatments , one when he was satisfied with moderate improvement and one because of repeated failure to attend . Those who completed treatment reached clearance or MRA after a median of 35 days with 5 × weekly treatment compared with 40 days with 3 × weekly treatment ( P = 0.007 ) , but required a median of 23.5 compared with 17 UVB exposures ( P = 0.001 ) and 94 minimal erythema dose multiples ( MEDs ) compared with 64 MEDs ( P = 0.01 ) . Fifteen ( of 16 ) developed at least one episode of well‐demarcated erythema during 5 × weekly treatment compared with just three of 16 treated 3 × weekly ( P < 0.001 ) . There was no significant difference between regimens in duration of remission . For this skin phototype I – III population , the more rapid clearance of psoriasis with 5 × weekly phototherapy is not , for the majority of patients , sufficient to justify the extra exposures and higher UVB dose . We no longer use 5 × weekly phototherapy for psoriasis BACKGROUND PUVA treatment of psoriasis is usually given with broad-b and fluorescent UVA lamps . Narrow-b and UVB exposure after oral methoxsalen has been shown to achieve a greater therapeutic response in psoriasis than identical UVB exposure given without psoralen . OBJECTIVE The purpose of this study was to compare conventional PUVA with psoralen-UVB therapy in psoriasis . METHODS We studied 100 patients with plaque-type psoriasis who were r and omly selected to receive either conventional psoralen-UVA or psoralen-UVB treatment . RESULTS No significant difference was found between the two treatments in the proportion of patients whose skin cleared during treatment or in the number of exposures required for clearance of psoriasis . As expected , the cumulative UV dose for clearance was smaller in the group treated with UVB compared with those receiving UVA . Side effects and disease status at 3 months after the end of treatment were similar for the two groups . CONCLUSION Psoralen-UVB treatment of psoriasis is as effective as conventional PUVA . The mechanism of psoralen-311 nm UVB action on psoriasis requires study to predict the long-term safety of this treatment Summary Background In 1991 , consensus guidelines recommended psoralen plus ultraviolet A photochemotherapy ( PUVA ) for those requiring second‐line therapy for psoriasis . Narrowb and ( TL‐01 ) UVB has since become more widely available , replacing the less effective broadb and sources OBJECTIVE To evaluate whether low concentrated saline spa water baths followed by ultraviolet B ( LC-SSW-UVB ) are superior to UVB alone in moderate to severe psoriasis . BACKGROUND There is a lack of sufficiently large r and omized controlled clinical trial evaluating the additional benefit of saltwater baths followed by UVB compared to UVB only in psoriasis . STUDY DESIGN Partly evaluator blind , multicentre , pragmatic , r and omized controlled trial . SETTING Five German spa centres . SUBJECTS One hundred and forty-three adults with stable psoriasis during the last month and a Psoriasis Area and Severity Index ( PASI ) of > 10 and /or an affected body surface area of > 15 % . INTERVENTIONS LC-SSW-UVB or UVB thrice a week until remission ( PASI < 5 ) or for a maximum of 6 weeks . Sodium chloride concentrations of natural springs varied between 4.5 % and 12 % . Conventional UVB ( broadb and UVB or selective UVB phototherapy ) was used as irradiation source . MAIN OUTCOME Reduction of PASI and /or affected body surface area of 50 % at the end of the intervention period ( PASI-50 ) . Only participants receiving at least one intervention were included in the primary analysis . RESULTS Patients allocated to LC-SSP-UVB attained a statistically significantly higher rate of PASI-50 at the end of the intervention period than patients allocated to UVB [ 58/79 ( 73 % ) vs. 32/64 ( 50 % ) ; P = 0.01 ; NNT , 4.3 , 95 % CI , 2.4 - 18.1 ] . Benefit persisted until 3 months only for one of two secondary outcomes considered . CONCLUSIONS In routine clinical practice balneophototherapy using conventional UVB is superior to conventional UVB only at the end of a 6-week treatment course BACKGROUND Broad-b and UVB phototherapy has appeared to be effective in clearing psoriatic lesions . After the advent of calcipotriol ointment , promising results have been obtained by combining these two therapeutic modalities . Also , an additional effect of narrow-b and UVB phototherapy on treatment with calcipotriol ointment has been demonstrated . OBJECTIVE Our purpose was to compare treatment with low-dose narrow-b and UVB phototherapy both with and without calcipotriol ointment . METHODS We included 53 patients suffering from plaque-type psoriasis . All patients underwent low-dose narrow-b and UVB phototherapy . Nearly half of the patients were r and omized to apply calcipotriol ointment ( 50 microg/g ) twice daily on the affected skin . The Psoriasis Area and Severity Index ( PASI ) was used to evaluate psoriatic lesions . RESULTS In this study we showed that low-dose narrow-b and UVB phototherapy is effective in the treatment of psoriasis and that calcipotriol ointment does not improve treatment outcome . CONCLUSION Calcipotriol ointment does not improve treatment with low-dose narrow-b and UVB phototherapy Forty-four patients with chronic plaque psoriasis were r and omly allocated to treatment with bath-water-delivered 8-methoxypsoralen ( bath 8-MOP ) or oral 8-methoxypsoralen ( oral 8-MOP ) PUVA therapy . There was a significant reduction in extent of the lesions and psoriasis area and severity index ( PASI ) after 20 treatments with each modality . There was a fourfold reduction in cumulative ultraviolet A ( UVA ) dose in the bath group . Side-effects of erythema and nausea were less with bath therapy The ideal psoralen‐ultraviolet A ( PUVA ) regimen for chronic plaque psoriasis has yet to be established . There are four components to a PUVA regimen : the dose of psoralen , the starting dose of UVA , the frequency of treatment and the incremental UVA dose protocol . Recent studies have been directed at trying to optimize the efficacy of PUVA while minimizing acute side‐effects and the risk of cutaneous carcinogenesis , believed to be independently related to the cumulative dose of UVA and the total number of treatments . The British Photodermatology Group recommends two twice‐weekly PUVA regimens : one starts with 50 % of the minimal phototoxic dose ( MPD ) and uses weekly increments of 40 % , 30 % , 25 % , 20 % , 15 % , 10 % and 5 % of the previous dose to a maximum of 14.5 J/cm2 ; the other starts with a fixed dose based on skin type and uses weekly dose increments of 40 % , decreasing to 20 % once erythema develops . We undertook a prospect i ve r and omized controlled trial comparing these regimens in 85 Irish patients . The clearance rate with the MPD regimen was lower than with the skin type regimen , 67.5 % vs. 95 % ( P < 0.05 ) . The reasons for treatment failure were grade 3 erythema and severe PUVA itch . There was a trend suggesting that patients with skin types I and II , but not skin type III , required a higher cumulative UVA dose and fewer exposures to clear with the MPD regimen than the skin type regimen , although this did not reach statistical significance . Grade s 2 or 3 erythema were very common in both treatment groups ( 52.5 % of the skin type group and 45 % of the MPD group ) . This is the third study to suggest that patients with skin types I and II receive a higher total UVA dose when the starting dose is 50–70 % of the MPD ( rather than 0.5 J/cm2 for skin type I and 1.0 J/cm2 for skin type II ) and when large dose increments are used . We suggest that smaller dose increments should be used in patients with skin types I and II BACKGROUND / PURPOSE The successful use of narrow-b and ultraviolet B ( UVB ) phototherapy for the management of psoriasis has prompted the examination of various combination treatments with narrow-b and UVB . However , there have been contradictory reports on the effect of the calcipotriol-narrow-b and UVB combination . This study was performed to compare the clinical efficacy of the calcipotriol-narrow-b and UVB combination with narrow-b and UVB alone . METHODS Of the 28 psoriasis patients , 10 were treated with the calcipotriol-narrow-b and UVB and 18 with narrow-b and UVB alone . Phototherapy was done once daily three times a week and the dose was gradually increased in a stepwise fashion by 0.05 J/cm2 . At the end of therapy , overall efficacy was classified according to the chosen grading system . RESULTS On assessing the therapeutic results using the criteria selected , 90.0 % patients ( n = 9 ) in the calcipotriol-narrow-b and UVB group and 61.1 % patients ( n = 11 ) in the narrow-b and UVB group showed grade IV at the end of therapy . The calcipotriol-narrow-b and UVB group showed more rapid improvement at the early stage . The final and total UVB dose were slightly lower in the calcipotriol-narrow-b and UVB group but no significant difference was observed with respect to the total number of irradiations , duration of treatment , final UVB dose or total cumulative UVB dose required to reach grade IV in both groups ( P > 0.05 ) . The pattern of adverse effects was similar in both groups with a slightly higher frequency in the calcipotriol-narrow-b and UVB group . CONCLUSION Our results demonstrated that the total cumulative UVB dose required to reach grade IV was not significantly different in both groups , although it was slightly lower in the calcipotriol-narrow-b and UVB group . However , a higher percentage of patients attained grade IV at the end of therapy in the combination group and this therapy was more effective in reducing the Psoriasis Area and Severity Index early in treatment . More studies are warranted to confirm these results The combination of retinoids with phototherapy enhances the efficacy of phototherapy and reduces the cumulative ultraviolet dose and duration of the therapy needed to treat chronic plaque psoriasis . Although TL-01 phototherapy has been used widely , there are few data about the effectiveness of the combination of acitretin with TL-01 in treatment of the disease . The aim of this study was to compare acitretin-narrow-b and TL-01 phototherapy with acitretin-psoralen plus ultraviolet A ( acitretin-PUVA ) in psoriasis . We studied 60 patients with moderate to severe plaque psoriasis who were r and omly allocated to three times weekly treatment acitretin-narrow-b and TL-01 or acitretin-PUVA . The efficacy of treatments was assessed using the Psoriasis Area and Severity Index by a blinded observer . Clearance of psoriasis was achieved in 56.6 % of patients treated with acitretin-narrow-b and TL-01 and in 63.3 % of those treated with acitretin-PUVA . All of these patients remained clear of psoriasis 3 months after finishing the treatments . Mucocutaneous side-effects , such as dry lips and mouth , were the most common complaints in both groups . In conclusion , acitretin-narrow-b and TL-01 is an effective and well-tolerated treatment for moderate to severe plaque psoriasis , with a therapeutic effect equal to that of acitretin-PUVA |
13,306 | 28,362,665 | Hence , compared with fibrinolysis , PPCI is expected to be the preferred method of revascularization in patients with AMI , especially in PCI-capable centers | Objectives We aim ed to improve the limitations encountered in previously published studies and then compare mortality in patients with acute myocardial infa rct ion ( AMI ) who were treated with either fibrinolysis or a primary percutaneous coronary intervention ( PPCI ) . | Background — The Danish Acute Myocardial Infa rct ion 2 ( DANAMI-2 ) study found that primary angioplasty ( primary percutaneous coronary intervention [ pPCI ] ) compared with fibrinolysis reduced 30-day adverse events in patients with ST-segment elevation myocardial infa rct ion . The present study investigated whether the benefit of pPCI was maintained at a long-term follow-up . Methods and Results — We r and omly assigned 1572 patients with ST-segment elevation myocardial infa rct ion—1129 patients at referral hospitals and 443 patients at invasive hospitals — to pPCI or fibrinolysis . Median time from r and omization to arrival in the catheterization laboratory for patients admitted to referral hospitals was 67 minutes , with 96 % of patients arriving in the catheterization laboratory within 120 minutes . The primary study end point was a composite of death or reinfa rct ion . Median follow-up time was 7.8 years . For the primary end point , 8-year cumulative incidence ( 1-Kaplan – Meier ) was 34.8 % in the pPCI group and 41.3 % in the fibrinolysis group ( hazard ratio , 0.78 ; 95 % confidence interval , 0.66 to 0.92 ) . Reinfa rct ion rates were reduced in the pPCI group ( 11.7 % versus 18.5 % ; hazard ratio , 0.60 ; 95 % confidence interval , 0.46 to 0.77 ) . Among patients r and omized at referral hospitals , pPCI reduced reinfa rct ion ( 13 % versus 18.5 % ; hazard ratio , 0.66 ; 95 % confidence interval , 0.49 to 0.89 ) and mortality ( 26.7 % versus 33.3 % ; hazard ratio , 0.78 ; 95 % confidence interval , 0.63 to 0.97 ) . Conclusions — The benefit of pPCI over fibrinolysis was maintained at a long-term follow-up . pPCI reduced the risk of reinfa rct ion in the overall cohort and reduced reinfa rct ion and mortality among patients r and omized at referral hospitals . This result reinforces that pPCI should be offered to ST-segment elevation myocardial infa rct ion patients when interhospital transport to an invasive hospital can be completed within 120 minutes BACKGROUND Prevention of myocardial damage is the main goal of all reperfusion therapies in patients with acute myocardial infa rct ion . The relative efficacy of various reperfusion strategies is under intensive investigation . We assessed whether coronary stenting combined with the blockade of platelet glycoprotein IIb/IIIa receptors produces a greater degree of myocardial salvage than fibrinolysis with an accelerated infusion of alteplase , a tissue plasminogen activator , in patients with acute myocardial infa rct ion . METHODS A total of 140 patients were enrolled in the r and omized trial ; 71 were assigned to receive a stent plus abciximab , and 69 to receive intravenous alteplase . The primary end point was the degree of myocardial salvage , determined by means of serial scintigraphic studies with technetium Tc 99 m sestamibi . The secondary end point was a composite of death , reinfa rct ion , and stroke within six months after r and omization . RESULTS In the group that received a stent plus abciximab , the median size of the final infa rct was 14.3 percent of the left ventricle ( 25th and 75th percentiles , 6.8 and 24.5 percent ) , as compared with a median of 19.4 percent ( 25th and 75th percentiles , 7.9 and 34.2 percent ) in the alteplase group ( P=0.02 ) . This difference was due to the larger salvage index ( the percentage of the left ventricle that was salvaged , divided by the percentage that was compromised by the initial perfusion defect ) in the stent group : 0.57 ( 25th and 75th percentiles , 0.35 and 0.69 ) , as compared with 0.26 ( 25th and 75th percentiles , 0.09 and 0.61 ; P<0.001 ) . The cumulative incidence of death , reinfa rct ion , or stroke at six months was lower in the stent group than in the alteplase group ( 8.5 vs. 23.2 percent . P=0.02 ; relative risk , 0.34 ; 95 percent confidence interval , 0.13 to 0.88 ) . CONCLUSIONS In patients with acute myocardial infa rct ion , coronary stenting plus abciximab leads to a greater degree of myocardial salvage and a better clinical outcome than does fibrinolysis with a tissue plasminogen activator OBJECTIVES The purpose of this study was to examine the incidence and implication s of recurrent ischemia after different reperfusion strategies in acute myocardial infa rct ion . BACKGROUND The rates and effects of recurrent ischemia after reperfusion with thrombolytic therapy and with primary percutaneous transluminal coronary angioplasty have not been compared . METHODS At 12 centers 395 patients presenting within 12 h of the onset of acute myocardial infa rct ion were prospect ively r and omized to receive recombinant tissue-type plasminogen activator ( rt-PA ) or primary coronary angioplasty . Sixteen clinical variables were examined by using univariate and multiple logistic regression analysis to identify the predictors of recurrent ischemia . The relation of recurrent ischemic events to patient outcome was analyzed . RESULTS Recurrent ischemia developed in 76 patients ( 19.2 % ) before hospital discharge , result ing in reinfa rct ion in 18 patients ( 4.6 % ) and death in 5 ( 2.6 % ) . Recurrent ischemia occurred in 56 patients ( 28.0 % ) after rt-PA but in only 20 patients ( 10.3 % ) after coronary angioplasty ( p < 0.0001 ) , directly contributing to a higher rate of death or reinfa rct ion ( 7.5 % vs. 3.1 % , p = 0.05 ) , catheterization and revascularization procedures and prolonged hospital stay after thrombolysis . By multivariate analysis , treatment with coronary angioplasty rather than rt-PA was the strongest predictor of freedom from recurrent ischemia . Although the incidence of recurrent ischemia after angioplasty and after rt-PA was similar within the 1st 2 days of admission ( 9.2 % vs. 14.5 % , p = 0.11 ) , after hospital day 2 recurrent ischemia occurred in only 2 patients who received primary angioplasty compared with 27 patients who received rt-PA ( 1.1 % vs. 13.5 % , p < 0.0001 ) . CONCLUSIONS The development of recurrent ischemia adversely affects patient outcome , increasing morbidity , mortality and re source utilization . The much lower rate of recurrent ischemia after primary coronary angioplasty than after rt-PA results in improved survival without reinfa rct ion and allows a shorter , less complicated hospital stay . Given the extremely low rate of recurrent ischemia after hospital day 2 , safe early discharge on day 3 after primary coronary angioplasty should be feasible in selected patients with acute myocardial infa rct ion BACKGROUND Although both prehospital fibrinolysis and primary angioplasty provide a clinical benefit over in-hospital fibrinolysis in acute myocardial infa rct ion , they have not been directly compared . Our aim was to find out whether primary angioplasty was better than prehospital fibrinolysis . METHODS We did a r and omised multicentre trial of 840 patients ( of 1200 planned ) who presented within 6 h of acute myocardial infa rct ion with ST-segment elevation , initially managed by mobile emergency-care units . We assigned patients to prehospital fibrinolysis ( n=419 ) with accelerated alteplase or primary angioplasty ( n=421 ) , and transferred all to a centre with access to emergency angioplasty . Our primary endpoint was a composite of death , non-fatal reinfa rct ion , and non-fatal disabling stroke at 30 days . Analyses were by intention to treat . FINDINGS The median delay between onset of symptoms and treatment was 130 min in the prehospital-fibrinolysis group and 190 min ( time to first balloon inflation ) in the primary -angioplasty group . Rescue angioplasty was done in 26 % of the patients in the fibrinolysis group . The rate of the primary endpoint was 8.2 % ( 34 patients ) in the prehospital-fibrinolysis group and 6.2 % ( 26 patients ) in the primary -angioplasty group ( risk difference 1.96 , 95 % CI -1.53 to 5.46 ) . 16 ( 3.8 % ) patients assigned prehospital fibrinolysis and 20 ( 4.8 % ) assigned primary angioplasty died ( p=0.61 ) . INTERPRETATION A strategy of primary angioplasty was not better than a strategy of prehospital fibrinolysis ( with transfer to an interventional facility for possible rescue angioplasty ) in patients presenting with early myocardial infa rct ion OBJECTIVES The Air Primary Angioplasty in Myocardial Infa rct ion ( PAMI ) study was design ed to determine the best reperfusion strategy for patients with high-risk acute myocardial infa rct ion ( AMI ) at hospitals without percutaneous transluminal coronary angioplasty ( PTCA ) capability . BACKGROUND Previous studies have suggested that high-risk patients have better outcomes with primary PTCA than with thrombolytic therapy . It is unknown whether this advantage would be lost if the patient had to be transferred for PTCA , and reperfusion was delayed . METHODS Patients with high-risk AMI ( age > 70 years , anterior MI , Killip class II/III , heart rate > 100 beats/min or systolic BP < 100 mm Hg ) who were eligible for thrombolytic therapy were r and omized to either transfer for primary PTCA or on-site thrombolysis . RESULTS One hundred thirty-eight patients were r and omized before the study ended ( 71 to transfer for PTCA and 67 to thrombolysis ) . The time from arrival to treatment was delayed in the transfer group ( 155 vs. 51 min , p < 0.0001 ) , largely due to the initiation of transfer ( 43 min ) and transport time ( 26 min ) . Patients r and omized to transfer had a reduced hospital stay ( 6.1 + /- 4.3 vs. 7.5 + /- 4.3 days , p = 0.015 ) and less ischemia ( 12.7 % vs. 31.8 % , p = 0.007 ) . At 30 days , a 38 % reduction in major adverse cardiac events was observed for the transfer group ; however , because of the inability to recruit the necessary sample size , this did not achieve statistical significance ( 8.4 % vs. 13.6 % , p = 0.331 ) . CONCLUSIONS Patients with high-risk AMI at hospitals without a catheterization laboratory may have an improved outcome when transferred for primary PTCA versus on-site thrombolysis ; however , this will require further study . The marked delay in the transfer process suggests a role for triaging patients directly to specialized heart-attack centers OBJECTIVE To assess the safety and feasibility of acute transport followed by rescue percutaneous transluminal coronary angioplasty ( PTCA ) or primary PTCA in patients with acute myocardial infa rct ion initially admitted to a hospital without PTCA facilities . DESIGN In a multicentre r and omised open trial , three regimens of treatment of acute large myocardial infa rct ion were compared for patients admitted to hospitals without angioplasty facilities : thrombolytic treatment with alteplase ( 75 patients ) , alteplase followed by transfer to the PTCA centre and ( if indicated ) rescue PTCA ( 74 patients ) , or transfer for primary PTCA ( 75 patients ) . RESULTS Between 1995 and 1997 224 patients were included . Baseline characteristics were distributed evenly . Transport to the PTCA centre was without severe complications in all patients . Mean ( SD ) delay from onset of symptoms to r and omisation was 130 ( 75 ) minutes and from r and omisation to angiography 90 ( 25 ) minutes . Death or recurrent infa rct ion within 42 days occurred in 12 patients in the thrombolysis group , in 10 patients in the rescue PTCA group , and in six patients in the primary PTCA group . These differences were not significant . CONCLUSIONS Acute transfer for rescue PTCA or primary PTCA in patients with extensive myocardial infa rct ion is feasible and safe . Efficacy of rescue PTCA or primary PTCA in this setting will have to be tested in larger series before this approach can be implemented as “ routine treatment ” for patients with extensive myocardial infa rct ion AIMS Our study aim ed to compare two reperfusion strategies in patients with ST-elevation myocardial infa rct ion ( STEMI ) admitted initially to a community hospital without catheterization facilities . METHODS AND RESULTS Four hundred and one patients with STEMI admitted to community hospital ( 13 hospitals , radius 20 - 150 km from cath-lab ) were r and omized to on-site thrombolysis or to transport with tirofiban ( 10 microg/kg bolus i.v . + i.v . infusion 0.1 microg/kg/min ) for primary PCI in single invasive centre . Primary endpoints were total mortality , recurrent MI ( re-AMI ) , and stroke during 1 year follow-up . Delay to reperfusion defined as interval between admission and start of fibrinolysis or primary PCI was 35 and 145 min ( P < 0.0001 ) . Mean time of tirofiban administration to PCI in transfer group was : 122.3 + /- 35.7 min . Mortality was not different during hospitalization and at 30th-day , with trend towards lower mortality at 1 year in transport group ( 12.5 vs. 7.0 % , P = 0.061 ) . There were no differences in the rate of re-AMI and stroke , with trend towards lower incidence of re-AMI in transfer group at 1 year ( 7.5 vs. 3.5 % , P = 0.073 ) . Composite of death/re-AMI/stroke was higher in on-site group during follow-up ( 15.5 vs. 8.0 % , P = 0.019 ; 21.5 vs. 11.4 % , P = 0.006 , respectively , at 30th-day and 1 year ) . CONCLUSION Outcomes at 1 year follow-up suggest that transportation with adjunctive therapy with GP IIb/IIIa inhibitor tirofiban for primary PCI is superior to on-site thrombolysis for patient with STEMI presenting to hospital without catheterization facilities To determine the role of tissue-type plasminogen activator ( t-PA ) and immediate percutaneous transluminal coronary angioplasty ( PTCA ) in treating patients with evolving transmural myocardial infa rct ion , 50 patients received t-PA ( 1.25 mg/kg iv over 3 hrs ) or placebo according to 3:1 double-blind r and omization 3.8 + /- 1.1 hr after onset of symptoms . At emergency coronary arteriography , patency of the infa rct -related vessel was demonstrated in 32 of 38 ( 84 % ) patients receiving t-PA vs two of 12 ( 17 % ) receiving placebo ( p less than .001 ) . Of the 32 patients with recanalization after t-PA , 28 had a residual stenosis of at least 50 % and underwent r and omization a second time to immediate ( n = 15 ) or no PTCA ( n = 13 ) . Immediate PTCA of the infa rct -related vessel was successful in all 15 patients , with reduction of the residual diameter stenosis from 80.8 + /- 8.2 % to 32.5 + /- 15.6 % ( p less than .001 ) . The incidence of postinfa rct ion angina ( greater than or equal to 20 min of chest discomfort and reversible electrocardiographic changes ) and reinfa rct ion ( documented by recurrent creatine kinase isoenzyme elevation ) was reduced in the patients receiving t-PA and PTCA ( 2/15 ) compared with that in patients receiving t-PA alone ( 7/13 ; p = .006 ) . At 1 week there was no difference in patency of the infa rct -related vessel ( 12/15 t-PA and PTCA vs 9/13 t-PA only ) or in global ventricular functional change between the two groups ( 0.5 + /- 10.4 SD/chord for t-PA and PTCA vs -2.1 + /- 8.2 SD/chord for t-PA only ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Results from a number of studies indicate that primary percutaneous coronary intervention ( PCI ) is superior to fibrinolysis for treatment of acute ST-elevation myocardial infa rct ion . Modern adjunctive antithrombotic treatment with systematic use of low-molecular-weight heparins , fibrin-specific thrombolysis , and glycoprotein IIb/IIIa receptor inhibitors may improve the outcome compared with what was achieved in previous studies . METHODS Patients with ST-elevation myocardial infa rct ion were r and omized to receive enoxaparin followed by reteplase ( group A ; n = 104 ) or enoxaparin followed by abciximab and transfer to invasive center for optional PCI ( group B ; n = 101 ) . Primary end points were ST-segment resolution 120 minutes and TIMI flow at coronary angiography 5 to 7 days after r and omization . RESULTS Forty-two percent of the patients started therapy in the prehospital phase . Time from symptom to treatment was 114 minutes in group A and 202 minutes in group B. Baseline characteristics were similar in the 2 groups . Sixty-four percent in group A and 68 % in group B had ST resolution of > 50 % at 120 minutes ( not significant ) . At control angiography , 54 % in the fibrinolytic group and 71 % in the invasive group had TIMI 3 flow ( P = .04 ) . At 30 days , the composite of death , stroke , or reinfa rct ion occurred in 8 % in the fibrinolytic group compared with 3 % in the invasive group ( not significant ) . CONCLUSIONS Despite much shorter time delay to start of fibrinolysis than PCI , this did not result in signs of superior myocardial reperfusion . Epicardial flow in the infa rct -related artery was better after invasive therapy , and there was a trend toward better clinical outcome after this treatment compared with after fibrinolysis OBJECTIVES The aim of the study was to compare r and omly assigned primary angioplasty and accelerated recombinant tissue plasminogen activator ( rt-PA ) , in patients with " high-risk " inferior acute myocardial infa rct ion ( ST-segment elevation in the inferior leads and ST-segment depression in the precordial leads ) . BACKGROUND The ST-segment depression in the precordial leads is a marker of severe prognosis in patients with inferior myocardial infa rct ion . The comparative outcome of treatment with primary angioplasty or lysis with accelerated rt-PA has not been investigated . METHODS One hundred and ten patients within 6 h of symptoms were r and omized to either treatment . To assess the in-hospital and 1-year outcome of both treatments the following results were compared : death or nonfatal infa rct ion , recurrence of angina , left ventricular ejection fraction ( LVEF ) , and the need for repeat target vessel revascularization ( TVR ) . RESULTS In patients treated with angioplasty ( 55 ) and rt-PA ( 55 ) the rate of in-hospital mortality and reinfa rct ion was 3.6 % versus 9.1 % ( p=0.4 ) . Recurrence of angina was 1.8 % versus 20 % ( p=0.002 ) , new TVR was used in 3.6 % versus 29.1 % ( p=0.0003 ) , and the LVEF ( % ) at discharge was 55.2+/-9.5 versus 48.2+/-9.9 ( p=0.0001 ) . There were no hemorrhagic strokes , no emergency coronary artery bypass graft ( CABG ) and identical ( 5.5 % ) need for blood transfusions . At 1 year , the incidence of death , reinfa rct ion or repeat TVR was 11 % in the percutaneous transluminal coronary angioplasty ( PTCA ) group versus 52.7 % in the rt-PA group ( log-rank 22.38 , p < 0.0001 ) . CONCLUSIONS Primary angioplasty is superior to accelerated rt-PA in terms of both myocardial preservation and reduction of in-hospital complications in patients with inferior myocardial infa rct ion and precordial ST-segment depression . Primary angioplasty also yields a better long-term event-free survival BACKGROUND For the treatment of myocardial infa rct ion with ST-segment elevation , primary angioplasty is considered superior to fibrinolysis for patients who are admitted to hospitals with angioplasty facilities . Whether this benefit is maintained for patients who require transportation from a community hospital to a center where invasive treatment is available is uncertain . METHODS We r and omly assigned 1572 patients with acute myocardial infa rct ion to treatment with angioplasty or accelerated treatment with intravenous alteplase ; 1129 patients were enrolled at 24 referral hospitals and 443 patients at 5 invasive-treatment centers . The primary study end point was a composite of death , clinical evidence of reinfa rct ion , or disabling stroke at 30 days . RESULTS Among patients who underwent r and omization at referral hospitals , the primary end point was reached in 8.5 percent of the patients in the angioplasty group , as compared with 14.2 percent of those in the fibrinolysis group ( P=0.002 ) . The results were similar among patients who were enrolled at invasive-treatment centers : 6.7 percent of the patients in the angioplasty group reached the primary end point , as compared with 12.3 percent in the fibrinolysis group ( P=0.05 ) . Among all patients , the better outcome after angioplasty was driven primarily by a reduction in the rate of reinfa rct ion ( 1.6 percent in the angioplasty group vs. 6.3 percent in the fibrinolysis group , P<0.001 ) ; no significant differences were observed in the rate of death ( 6.6 percent vs. 7.8 percent , P=0.35 ) or the rate of stroke ( 1.1 percent vs. 2.0 percent , P=0.15 ) . Ninety-six percent of patients were transferred from referral hospitals to an invasive-treatment center within two hours . CONCLUSIONS A strategy for reperfusion involving the transfer of patients to an invasive-treatment center for primary angioplasty is superior to on-site fibrinolysis , provided that the transfer takes two hours or less BACKGROUND The DANAMI-2 trial showed that in patients with ST-elevation myocardial infa rct ion ( STEMI ) , a strategy of inter-hospital transfer for primary angioplasty was superior to on-site fibrinolysis at 30 days follow-up . This paper reports on the pre-specified long-term composite endpoint at 3 years follow-up in DANAMI-2 . METHODS AND RESULTS We r and omized 1572 patients with STEMI to primary angioplasty or intravenous alteplase ; 1129 patients were enrolled at 24 referral hospitals and 443 patients at 5 angioplasty centres . Ninety-six percent of inter-hospital transfers for angioplasty were completed within 2 h. No patients were lost to follow-up . The composite endpoint ( death , clinical re-infa rct ion , or disabling stroke ) was reduced by angioplasty when compared with fibrinolysis at 3 years ( 19.6 vs. 25.2 % , P = 0.006 ) . For patients transferred to angioplasty compared with those receiving on-site fibrinolysis , the composite endpoint occurred in 20.1 vs. 26.7 % ( P = 0.007 ) , death in 13.6 vs. 16.4 % ( P = 0.18 ) , clinical re-infa rct ion in 8.9 vs. 12.3 % ( P = 0.05 ) , and disabling stroke in 3.2 vs. 4.7 % ( P = 0.23 ) . CONCLUSION The benefit of transfer for primary angioplasty based on the composite endpoint was sustained after 3 years . For patients with characteristics as those in DANAMI-2 , primary angioplasty should be the preferred treatment strategy when inter-hospital transfer can be completed within 2 CONTEXT Trials comparing primary percutaneous coronary intervention ( PCI ) and thrombolytic therapy for treatment of acute myocardial infa rct ion ( MI ) suggest primary PCI is the superior therapy , although they differ with respect to the durability of benefit . Because PCI is often limited to hospitals that have on-site cardiac surgery programs , most acute MI patients do not have access to this therapy . OBJECTIVE To determine whether treatment of acute MI with primary PCI is superior to thrombolytic therapy at hospitals without on-site cardiac surgery and , if so , whether superiority is durable . DESIGN The Atlantic Cardiovascular Patient Outcomes Research Team ( C-PORT ) trial , a prospect i ve , r and omized trial conducted from July 1996 through December 1999 . SETTING Eleven community hospitals in Massachusetts and Maryl and without on-site cardiac surgery or extant PCI programs . PATIENTS Four hundred fifty-one thrombolytic-eligible patients with acute MI of less than 12 hours ' duration associated with ST-segment elevation on electrocardiogram . INTERVENTIONS After a formal primary PCI development program was completed at all sites , patients were r and omly assigned to receive primary PCI ( n = 225 ) or accelerated tissue plasminogen activator ( bolus dose of 15 mg and an infusion of 0.75 mg/kg for 30 minutes followed by 0.5 mg/kg for 60 minutes ; n = 226 ) . After initiation of assigned treatment , all care was determined by treating physicians . MAIN OUTCOME MEASURES Six-month composite incidence of death , recurrent MI , and stroke ; median hospital length of stay . RESULTS The incidence of the composite end point was reduced in the primary PCI group at 6 weeks ( 10.7 % vs 17.7 % ; P = .03 ) and 6 months ( 12.4 % vs 19.9 % ; P = .03 ) after index MI . Six-month rates for individual outcomes were 6.2 % vs 7.1 % for death ( P = .72 ) , 5.3 % vs 10.6 % for recurrent MI ( P = .04 ) , and 2.2 % vs 4.0 % for stroke ( P = .28 ) for primary PCI vs thrombolytic therapy , respectively . Median length of stay was also reduced in the primary PCI group ( 4.5 vs 6.0 days ; P = .02 ) . CONCLUSIONS Compared with thrombolytic therapy , treatment of patients with primary PCI at hospitals without on-site cardiac surgery is associated with better clinical outcomes for 6 months after index MI and a shorter hospital stay 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 BACKGROUND Primary percutaneous coronary intervention ( PCI ) has become an alternative to thrombolytic therapy as a reperfusion strategy for ST-elevation acute myocardial infa rct ion ( AMI ) . METHODS The main goal of this study was to determine whether PCI and thrombolytic therapy achieve comparable reperfusion rates , as evidence d by ST-segment resolution . Secondary end points included infa rct vessel patency rates before hospital discharge and short- and long-term outcomes . Patients with ischemic chest pain with duration < or = 12 hours and no contraindication for thrombolytic therapy were included . RESULTS Between October 1993 and August 1995 , 58 patients were r and omly assigned to streptokinase ( SK ) and 54 patients to primary PCI . Baseline clinical characteristics and infa rct location were well balanced in both groups . Median age ( interquartile range ) was 68 ( 58 , 75 ) years , 29 % were women , and 78 % of the patients met at least one criterion for " not low risk " AMI ( anterior location , age > 70 years old , previous MI , systolic blood pressure < 100 mm Hg , and /or heart rate > 100 bpm ) . The median time from symptom onset to r and om assignment was 217 ( 139 , 335 ) minutes in the PCI group and 210 ( 145 , 334 ) minutes in the SK group . Median r and om assignment to balloon time was 82 ( 55 , 100 ) minutes , and median r and om assignment to needle time was 15 ( 10 , 26 ) minutes ( P < .0001 ) . TIMI grade 3 flow after primary PCI was obtained in 85 % of patients . The proportion of patients with ST-segment resolution > or = 50 % at 120 minutes was 80 % in the PCI group and 50 % in the SK group ( P = .001 ) . The predischarge angiogram showed the presence of TIMI 3 flow in 96 % of patients who received PCI and 65 % of patients who received SK ( P < .001 ) . A composite of in-hospital death , reinfa rct ion , severe heart failure , stroke , and major bleeding occurred in 15 % of patients who received PCI and 21 % of patients who received SK ( P = .4 ) . At 3 years , freedom from the composite end point of AMI , postdischarge revascularization , and death was 61 % in the PCI group and 40 % in the SK group ( P = .025 ) . CONCLUSIONS Our study shows that primary PCI , as compared with SK , is associated with more effective ST-segment resolution , higher patency rates in the infa rct vessel at 7 days , and more favorable clinical outcomes at 3 years of follow-up Objectives : To study the clinical significance of infa rct location during long term follow up in a trial comparing thrombolysis with primary angioplasty . Design : Retrospective longitudinal cohort analysis of prospect ively entered data . Setting : Patients with acute ST elevation myocardial infa rct ion ( STEMI ) treated with primary percutaneous coronary intervention ( PCI ) . Patients : In the Zwolle trial 395 patients with acute STEMI were r and omly assigned to intravenous streptokinase or PCI . Main outcome measures : Survival according to infa rct location and treatment after 8 ( 2 ) years of follow up . Results : 105 patients died : 63 patients in the streptokinase group and 42 patients in the primary PCI group ( relative risk ( RR ) 1.6 , 95 % confidence interval ( CI ) 1.0 to 2.6 ; p = 0.03 ) . In patients with non-anterior STEMI there was no difference in mortality between streptokinase and PCI treated patients ( RR 1.1 , 95 % CI 0.6 to 2.1 ; p = 0.68 ) but the streptokinase group had significantly more major adverse cardiac events ( MACE ) than the PCI group ( RR 2.1 , 95 % CI 1.2 to 3.6 ) . The number needed to treat to prevent one MACE was four . In patients with anterior STEMI , mortality was higher in the streptokinase group than in the PCI group ( RR 2.7 , 95 % CI 1.4 to 5.5 ; p = 0.004 ) . The number needed to treat to prevent one death was five . Kaplan-Meier analysis confirmed the benefits of primary angioplasty in the first year and showed additional benefit of PCI compared with streptokinase between 1–8 years after the acute event . Conclusions : Patients with anterior STEMI have better long term survival when treated with PCI than with streptokinase . In patients alive one year after the acute event , PCI confers a significant additional survival benefit , probably due to better preserved residual left ventricular function BACKGROUND As compared with thrombolytic therapy , primary coronary angioplasty results in a higher rate of patency of the infa rct -related coronary artery , lower rates of stroke and reinfa rct ion , and higher in-hospital or 30-day survival rates . However , the comparative long-term efficacy of these two approaches has not been carefully studied . METHODS We r and omly assigned a total of 395 patients with acute myocardial infa rct ion to treatment with angioplasty or intravenous streptokinase . Clinical information was collected for a mean ( + /-SD ) of 5+/-2 years , and medical charges associated with the two treatments were compared . RESULTS A total of 194 patients were assigned to undergo primary angioplasty , and 201 to receive streptokinase . Mortality was 13 percent in the angioplasty group , as compared with 24 percent in the streptokinase group ( relative risk , 0.54 ; 95 percent confidence interval , 0.36 to 0.87 ) . Nonfatal reinfa rct ion occurred in 6 percent and 22 percent of the two groups , respectively ( relative risk , 0.27 ; 95 percent confidence interval , 0.15 to 0.52 ) . The combined incidence of death and nonfatal reinfa rct ion was also lower among patients assigned to angioplasty than among those assigned to streptokinase , with a relative risk of 0.13 ( 95 percent confidence interval , 0.05 to 0.37 ) for early events ( within the first 30 days ) and a relative risk of 0.62 ( 95 percent confidence interval , 0.43 to 0.91 ) for late events ( after 30 days ) . The rates of readmission for heart failure and ischemia were also lower among patients in the angioplasty group than among patients in the streptokinase group . Total medical charges per patient were lower in the angioplasty group ( 16,090 dollars ) than in the streptokinase group ( 16,813 dollars , P=0.05 ) . CONCLUSIONS During five years of follow-up , primary coronary angioplasty for acute myocardial infa rct ion was associated with lower rates of early and late death and nonfatal reinfa rct ion , fewer hospital readmissions for ischemia or heart failure , and lower total medical charges than treatment with intravenous streptokinase OBJECTIVES This study compares the efficacy of primary angioplasty and systemic thrombolysis with t-PA in reducing the in-hospital mortality of patients with anterior AMI . BACKGROUND Controversy still exists about the relative benefit of primary angioplasty over thrombolysis as treatment for AMI . METHODS Two-hundred and twenty patients with anterior AMI were r and omly assigned in our institution to primary angioplasty ( 109 patients ) or systemic thrombolysis with accelerated t-PA ( 111 patients ) within the first five hours from the onset of symptoms . RESULTS Baseline characteristics were similar in both groups . Primary angioplasty was independently associated with a lower in-hospital mortality ( 2.8 % vs. 10.8 % , p = 0.02 , adjusted odds ratio 0.23 , 95 % confidence interval 0.06 to 0.85 ) . During hospitalization , patients treated by angioplasty had a lower frequency of postinfa rct ion angina or positive stress test ( 11.9 % vs. 25.2 % , p = 0.01 ) and less frequently underwent percutaneous or surgical revascularization after the initial treatment ( 22.0 % vs. 47.7 % , p < 0.001 ) than did patients treated by t-PA . At six month follow-up , patients treated by angioplasty had a lower cumulative rate of death ( 4.6 % vs. 11.7 % , p = 0.05 ) and revascularization ( 31.2 % vs. 55.9 % , p < 0.001 ) than those treated by t-PA . CONCLUSIONS In centers with an experienced and readily available interventional team , primary angioplasty is superior to t-PA for the treatment of anterior AMI OBJECTIVES We sought to compare primary coronary angioplasty and thrombolysis as treatment for low risk patients with an acute myocardial infa rct ion . BACKGROUND Primary coronary angioplasty is the most effective reperfusion therapy for patients with acute myocardial infa rct ion ; however , intravenous thrombolysis is easier to apply , more widely available and possibly more appropriate in low risk patients . METHODS We stratified 240 patients with acute myocardial infa rct ion at admission according to risk . Low risk patients ( n = 95 ) were r and omized to primary angioplasty or thrombolytic therapy . The primary end point was death , nonfatal stroke or reinfa rct ion during 6 months of follow-up . Left ventricular ejection fraction and medical charges were secondary end points . High risk patients ( n = 145 ) were treated with primary angioplasty . RESULTS In low risk patients , the incidence of the primary clinical end point ( 4 % vs. 20 % , p < 0.02 ) was lower in the group with primary coronary angioplasty than in the group with thrombolysis , because of a higher rate of reinfa rct ion in the latter group . Mortality and stroke rates were low in both treatment groups . There were no differences in left ventricular ejection fraction or total medical charges . High risk patients had a 14 % incidence rate of the primary clinical end point . CONCLUSIONS Simple clinical data can be used to risk-stratify patients during the initial admission for myocardial infa rct ion . Even in low risk patients , primary coronary angioplasty results in a better clinical outcome at 6 months than does thrombolysis and does not increase total medical charges OBJECTIVES The purpose of the present study was to compare intravenous streptokinase therapy with immediate coronary angioplasty without antecedent thrombolytic therapy with regard to left ventricular function and hospital mortality and reinfa rct ion . BACKGROUND Despite the widespread use of intravenous thrombolytic therapy and immediate percutaneous transluminal coronary angioplasty , these two strategies to treat patients with an acute myocardial infa rct ion have only recently been compared in r and omized trials . Coronary angioplasty has been shown to result in a higher patency rate of the infa rct -related coronary artery , with a less severe residual stenotic lesion , compared with streptokinase therapy , but whether this more favorable coronary anatomy results in clinical benefit remains to be established . METHODS We studied 301 patients with acute myocardial infa rct ion r and omly assigned to undergo immediate coronary angioplasty without antecedent thrombolytic therapy or to receive intravenous streptokinase therapy . Before discharge left ventricular ejection fraction was measured by radionuclide scanning . RESULTS The in-hospital mortality rate in the streptokinase group was 7 % ( 11 of 149 patients ) compared with 2 % ( 3 of 152 patients ) in the angioplasty group ( p = 0.024 ) . In the streptokinase group recurrent myocardial infa rct ion occurred in 15 patients ( 10 % ) versus in 2 ( 1 % ) in the angioplasty group ( p < 0.001 ) . Either death or nonfatal reinfa rct ion occurred in 23 patients ( 15 % ) in the streptokinase group and in 5 patients ( 3 % ) in the angioplasty group ( p = 0.001 ) . Left ventricular ejection fraction was 44 + /- 11 % ( mean + /- SD ) in the streptokinase group versus 50 + /- 11 % in the angioplasty group ( p < 0.001 ) . CONCLUSIONS These findings indicate that immediate coronary angioplasty without antecedent thrombolytic therapy results in better left ventricular function and lower risk of death and recurrent myocardial infa rct ion than treatment with intravenous streptokinase BACKGROUND Several relatively small r and omized trials have shown that primary angioplasty results in a better short-term outcome than thrombolytic therapy in patients with acute myocardial infa rct ion . These results , however , have not been duplicated other than in investigational trials . METHODS We compared mortality during hospitalization and long-term mortality , as well as the use of re sources , among 1050 patients in a primary -angioplasty group and 2095 patients in a thrombolytic-therapy group . Patients were selected from the Myocardial Infa rct ion Triage and Intervention Project Registry cohort of 12,331 consecutive patients admitted with acute myocardial infa rct ion to 19 Seattle hospitals between 1988 and 1994 . Because of the potential for selection bias , several subgroup analyses were performed that included patients eligible for thrombolysis , high-risk patients , and patients in the primary -angioplasty group who were treated at hospitals with high volumes of angioplasty . RESULTS There was no significant difference in mortality during hospitalization or long-term follow-up between patients in the thrombolytic-therapy group and those in the primary -angioplasty group ( mortality during hospitalization , 5.6 percent and 5.5 percent , respectively ; P=0.93 ; adjusted hazard ratio for the risk of death within three years after primary angioplasty , 0.95 ; 95 percent confidence interval , 0.8 to 1.2 ) . There was also no significant difference in mortality between high-risk subgroups of patients in the two treatment groups . The rates of procedures and costs were lower among patients in the thrombolytic-therapy group both at the time of hospital discharge and after three years of follow-up ( 30 percent fewer coronary angiograms , 15 percent fewer coronary angioplasties , and 13 percent lower costs after three years of follow-up ) . CONCLUSIONS In a community setting , we observed no benefit in terms of either mortality or the use of re sources with a strategy of primary angioplasty rather than thrombolytic therapy in a large cohort of patients with acute myocardial infa rct ion BACKGROUND Patients with acute myocardial infa rct ion might benefit from the addition of glycoprotein IIb/IIIa inhibitors to fibrinolytic or mechanical reperfusion strategies . We compared two strategies , stenting and fibrinolysis , both combined with abciximab , in terms of their ability to salvage myocardium in patients with acute myocardial infa rct ion . METHODS We enrolled 162 patients with acute myocardial infa rct ion within 12 h of onset of symptoms , assigning 81 stenting plus abciximab and 81 alteplase plus abciximab . Technetium-99 m sestamibi scintigraphy was done at admission and after a median of 11 days to calculate initial perfusion defect , final infa rct size , and degree of myocardial salvage . The primary endpoint was the salvage index ( the ratio of the degree of myocardial salvage to the initial perfusion defect ) . Major adverse clinical events within 6 months from r and omisation were also compared between the two treatments . FINDINGS Paired scintigraphic measurements were available for 70 patients in the stent group and 71 in the alteplase group . Stenting was associated with greater myocardial salvage than alteplase ( median 13.6 % [ IQR 5.9 - 23.9 ] vs 8.0 % [ 2.5 - 16.0 ] of the left ventricle ; p=0.007 ) . Salvage index was greater in the stent group than in the alteplase group ( median 0.60 [ 0.37 - 0.82 ] vs 0.41 [ 0.13 - 0.58 ] ; p=0.001 ) . The 6-month mortality rate was 5 % ( four deaths ) in the stent group and 9 % ( seven deaths ) in the alteplase group ( relative risk 0.56 [ 95 % CI 0.17 - 1.88 ] ; p=0.35 ) . INTERPRETATION In patients with acute myocardial infa rct ion , a reperfusion strategy based on stenting with abciximab produced more myocardial salvage than the combination of fibrinolysis plus abciximab . Larger studies are needed to assess whether these effects translate into clinical benefit BACKGROUND The success of thrombolytic therapy for acute myocardial infa rct ion is limited by bleeding complications , the impossibility of reperfusing all occluded coronary arteries , recurrent myocardial ischemia , and the relatively small number of patients who are appropriate c and i date s for this therapy . We hypothesized that these problems could be overcome by the use of immediate percutaneous transluminal coronary angioplasty ( PTCA ) , without previous thrombolytic therapy . METHODS At 12 clinical centers , 395 patients who presented within 12 hours of the onset of myocardial infa rct ion were treated with intravenous heparin and aspirin and then r and omly assigned to undergo immediate PTCA ( without previous thrombolytic therapy , 195 patients ) or to receive intravenous tissue plasminogen activator ( t-PA , 200 patients ) followed by conservative care . Radionuclide ventriculography was performed to assess ventricular function within 24 hours and at six weeks . RESULTS Among the patients r and omly assigned to PTCA , 90 percent underwent the procedure ; the success rate was 97 percent , and no patient required emergency coronary-artery bypass surgery . The in-hospital mortality rates in the t-PA and PTCA groups were 6.5 and 2.6 percent , respectively ( P = 0.06 ) . In a post hoc analysis , the mortality rates in the subgroups classified as " not low risk " were 10.4 and 2.0 percent , respectively ( P = 0.01 ) . Reinfa rct ion or death in the hospital occurred in 12.0 percent of the patients treated with t-PA and 5.1 percent of those treated with PTCA ( P = 0.02 ) . Intracranial bleeding occurred more frequently among patients who received t-PA than among those who underwent PTCA ( 2.0 vs. 0 percent , P = 0.05 ) . The mean ( + /- SD ) ejection fractions at rest ( 53 + /- 13 vs. 53 + /- 13 percent ) and during exercise ( 56 + /- 13 vs. 56 + /- 14 percent ) were similar in the t-PA and PTCA groups at six weeks . By six months , reinfa rct ion or death had occurred in 32 patients who received t-PA ( 16.8 percent ) and 16 treated with PTCA ( 8.5 percent , P = 0.02 ) . CONCLUSIONS As compared with t-PA therapy for acute myocardial infa rct ion , immediate PTCA reduced the combined occurrence of nonfatal reinfa rct ion or death , was associated with a lower rate of intracranial hemorrhage , and result ed in similar left ventricular systolic function OBJECTIVES The study evaluated the efficacy and safety of a short-acting reduced-dose fibrinolytic regimen to promote early infa rct -related artery ( IRA ) patency during the inherent delay experienced by infa rct patients referred for angioplasty as the principal recanalization modality . BACKGROUND Previous approaches using long-acting , full-dose thrombolytic infusions rarely showed benefit , but they did increase adverse event rates . METHODS Following aspirin and heparin , 606 patients were r and omized to a 50-mg bolus of recombinant tissue-type plasminogen activator ( rt-PA ) ( alpha half-life 4.5 min ) or to placebo followed by immediate angiography with angioplasty if needed . The end points included patency rates on catheterization laboratory ( cath lab ) arrival , technical results when PTCA ( percutaneous transluminal coronary angioplasty ) was performed , complication rates , and left ventricular ( LV ) function by treatment assignment and time to restored patency following angioplasty . RESULTS Patency on cath lab arrival was 61 % with rt-PA ( 28 % Thrombolysis in Myocardial Infa rct ion trial [TIMI]-2 , 33 % TIMI-3 ) , and 34 % with placebo ( 19 % TIMI-2 , 15 % TIMI-3 ) ( p = 0.001 ) . Rescue and primary PTCA restored TIMI-3 in closed arteries equally ( 77 % , 79 % ) . No differences were observed in stroke or major bleeding . Left ventricular function was similar in both treatment groups , but convalescent ejection fraction ( EF ) was highest with a patent IRA ( TIMI-3 ) on cath lab arrival ( 62.4 % ) or when produced by angioplasty within an hour of bolus ( 62.5 % ) . However , in 88 % of angioplasties , the delay exceeded 1 h : convalescent EF 57.3 % . CONCLUSIONS Tailored thrombolytic regimens compatible with subsequent interventions lead to more frequent early recanalization ( before cath arrival ) , which facilitates greater LV function preservation with no augmentation of adverse events OBJECTIVES The objective of this study was to obtain preliminary data on the relative clinical utility of direct coronary angioplasty compared with that of intravenous thrombolytic therapy for patients with acute myocardial infa rct ion . BACKGROUND The relative merits of intravenous thrombolytic therapy and direct coronary angioplasty as treatment for acute myocardial infa rct ion are incompletely understood , and r and omized trials of these treatments have been extremely limited . METHODS One hundred patients with ST segment elevation presenting to a single high volume interventional center within 6 h of the onset of chest pain were r and omized to receive either streptokinase ( 1.2 million U intravenously over 1 h ) or immediate catheterization and direct coronary angioplasty . Patients were excluded for age > or = 75 years , prior bypass surgery , Q wave infa rct ion in the region of ischemia or excessive risk of bleeding . All patients were then treated with aspirin ( 325 mg orally/day ) and heparin ( 1,000 U intravenously/h ) for 48 h until catheterization was performed to determine the primary study end point , namely , infa rct -related artery patency at 48 h. Secondary end points were in-hospital death , left ventricular ejection fraction at 48 h and time to treatment . RESULTS There was no difference in the baseline characteristics of the two treatment groups . Overall patient age was 56 + /- 10 years , 83 % of patients were male , 11 % had prior infa rct ion , 40 % had anterior infa rct ion and 97 % were in Killip class I or II . Although time to treatment was delayed in the angioplasty group ( 238 + /- 112 vs. 179 + /- 98 min , p = 0.005 ) , there was no difference in 48-h infa rct -related artery patency or left ventricular ejection fraction ( patency 74 % vs. 80 % ; ejection fraction 59 + /- 13 % vs. 57 + /- 13 % ; angioplasty vs. streptokinase , p = NS for both ) . There were no major bleeding events , and the mortality rate with angioplasty ( 6 % ) and streptokinase ( 2 % ) did not differ ( p = NS ) . CONCLUSIONS These results suggest that intravenous thrombolytic therapy might be preferred over coronary angioplasty for most patients because of the often shorter time to treatment BACKGROUND Immediate angioplasty and the administration of a thrombolytic agent followed by conservative treatment are two approaches to the management of acute myocardial infa rct ion , but these methods have not been compared prospect ively . METHODS We enrolled 108 patients with acute myocardial infa rct ion in a r and omized trial design ed to test the hypothesis that immediate angioplasty ( without previous thrombolytic therapy ) may result in greater myocardial salvage than the administration of a thrombolytic agent followed by conservative treatment . The primary end point was the change in the size of the perfusion defect as assessed at admission and discharge by tomographic imaging with technetium-99 m sestamibi , a myocardial perfusion agent that can measure myocardium at risk and final infa rct size . RESULTS End-point data were available for 56 patients r and omly assigned to receive tissue plasminogen activator ( mean [ + /- SD ] time to start of infusion , 232 + /- 174 minutes after the onset of chest pain ) and 47 patients r and omly assigned to receive angioplasty ( first balloon inflation at 277 + /- 144 minutes ) . In the case of anterior infa rct ion , myocardial salvage as assessed by imaging with technetium-99 m sestamibi was 27 + /- 21 percent of the left ventricle for 22 patients in the thrombolysis group , as compared with 31 + /- 21 percent for 15 patients in the angioplasty group . For infa rcts in all other locations , myocardial salvage was 7 + /- 13 percent for 34 patients in the thrombolysis group and 5 + /- 10 percent for 32 patients in the angioplasty group . After adjustment for infa rct location , the difference in mean salvage between groups was 0 ( P = 0.98 ) , with a 95 percent confidence interval of + /- 6 percent of the left ventricle . CONCLUSIONS In patients with acute myocardial infa rct ion , immediate angioplasty does not appear to result in greater myocardial salvage than the administration of a thrombolytic agent followed by conservative treatment , although a small difference between these two therapeutic approaches can not be excluded We r and omly assigned 56 patients who presented within 12 hours of their first symptoms of acute myocardial infa rct ion to treatment with either intracoronary streptokinase or coronary angioplasty . The mean ( + /- SD ) duration of symptoms ( 3.0 + /- 1.2 hours in the group treated with angioplasty vs. 3.6 + /- 1.8 in the group treated with streptokinase ; P not significant ) and time to recanalization ( 4.1 + /- 1.4 hours vs. 4.8 + /- 1.7 hours ; P not significant ) were similar in both groups . Coronary recanalization was achieved in 83 percent of the patients treated with angioplasty and in 85 percent of those treated with streptokinase ( P not significant ) . Residual luminal stenosis in the coronary artery was significantly decreased after angioplasty , as compared with streptokinase therapy ( 43 + /- 31 percent of patients vs. 83 + /- 17 ; P less than 0.001 ) . Residual stenosis of 70 percent or more was present in 4 percent of the angioplasty-treated patients and in 83 percent of the streptokinase-treated patients ( P less than 0.01 ) . Ventricular function after therapy was assessed by serial contrast ventriculograms . Increases in both global ejection fraction ( 8 + /- 7 percent vs. 1 + /- 6 ; P less than 0.001 ) and regional wall motion ( + 1.32 + /- 1.32 SD vs. + 0.59 + /- 0.79 SD ; P less than 0.05 ) were greater for the angioplasty group . We conclude that angioplasty and streptokinase produce similar rates of early coronary reperfusion during evolving transmural myocardial infa rct ion . However , angioplasty is significantly more effective in alleviating the underlying coronary stenoses , and this may result in more effective preservation of ventricular function after therapy BACKGROUND Despite the widespread use of intravenous thrombolytic therapy and of immediate percutaneous transluminal coronary angioplasty for the treatment of acute myocardial infa rct ion , r and omized comparisons of the two approaches to reperfusion are lacking . We report the results of a prospect i ve , r and omized trial comparing immediate coronary angioplasty ( without previous thrombolytic therapy ) with intravenous streptokinase treatment . METHODS A total of 142 patients with acute myocardial infa rct ion were r and omly assigned to receive one of the two treatments . The left ventricular ejection fraction was measured by radionuclide scanning before hospital discharge . Quantitative coronary angiography was performed to assess the degree of residual stenosis in the infa rct -related arteries . RESULTS A total of 72 patients were assigned to receive streptokinase and 70 patients to undergo immediate angioplasty . Angioplasty was technically successful in 64 of the 65 patients who underwent the procedure . Infa rct ion recurred in nine patients assigned to receive streptokinase , but in none of those assigned to receive angioplasty ( P = 0.003 ) . Fourteen patients in the streptokinase group had unstable angina after their infa rct ion , but only four in the angioplasty group ( P = 0.02 ) . The mean ( + /- SD ) left ventricular ejection fraction as measured before discharge was 45 + /- 12 percent in the streptokinase group and 51 + /- 11 percent in the angioplasty group ( P = 0.004 ) . The infa rct -related artery was patent in 68 percent of the patients in the streptokinase group and 91 percent of those in the angioplasty group ( P = 0.001 ) . Quantitative coronary angiography revealed stenosis of 36 + /- 20 percent of the luminal diameter in the angioplasty group , as compared with 76 + /- 19 percent in the streptokinase group ( P < 0.001 ) . CONCLUSIONS Immediate angioplasty after acute myocardial infa rct ion was associated with a higher rate of patency of the infa rct -related artery , a less severe residual stenotic lesion , better left ventricular function , and less recurrent myocardial ischemia and infa rct ion than was intravenous streptokinase BACKGROUND Primary coronary angioplasty is an effective reperfusion strategy in acute myocardial infa rct ion . However , its availability is limited , and transporting patients to an angioplasty centre in the acute phase of myocardial infa rct ion has not yet been proved safe . METHODS The PRAGUE study ( PRimary Angioplasty in patients transferred from General community hospitals to specialized PTCA Units with or without Emergency thrombolysis ) compared three reperfusion strategies in patients with acute myocardial infa rct ion , presenting within 6 h of symptom onset at community hospitals without a catheterization laboratory : group A - thrombolytic therapy in community hospitals ( n=99 ) , group B - thrombolytic therapy during transportation to angioplasty ( n=100 ) , group C - immediate transportation for primary angioplasty without pre-treatment with thrombolysis ( n=101 ) . RESULTS No complications occurred during transportation in group C. Two ventricular fibrillations occurred during transportation in group B. Median admission-reperfusion time in transported patients ( group B 106 min , group C 96 min ) compared favourably with the anticipated > 90 min in group A. The combined primary end-point ( death/reinfa rct ion/stroke at 30 days ) was less frequent in group C ( 8 % ) compared to groups B ( 15 % ) and A ( 23 % , P<0 . 02 ) . The incidence of reinfa rct ion was markedly reduced by transport to primary angioplasty ( 1 % in group C vs 7 % in group B vs 10 % in group A , P<0.03 ) . CONCLUSIONS Transferring patients from community hospitals to a tertiary angioplasty centre in the acute phase of myocardial infa rct ion is feasible and safe . This strategy is associated with a significant reduction in the incidence of reinfa rct ion and the combined clinical end-point of death/reinfa rct ion/stroke at 30 days when compared to st and ard thrombolytic therapy at the community hospital BACKGROUND It is not known whether prehospital fibrinolysis , coupled with timely coronary angiography , provides a clinical outcome similar to that with primary percutaneous coronary intervention ( PCI ) early after acute ST-segment elevation myocardial infa rct ion ( STEMI ) . METHODS Among 1892 patients with STEMI who presented within 3 hours after symptom onset and who were unable to undergo primary PCI within 1 hour , patients were r and omly assigned to undergo either primary PCI or fibrinolytic therapy with bolus tenecteplase ( amended to half dose in patients ≥75 years of age ) , clopidogrel , and enoxaparin before transport to a PCI-capable hospital . Emergency coronary angiography was performed if fibrinolysis failed ; otherwise , angiography was performed 6 to 24 hours after r and omization . The primary end point was a composite of death , shock , congestive heart failure , or reinfa rct ion up to 30 days . RESULTS The primary end point occurred in 116 of 939 patients ( 12.4 % ) in the fibrinolysis group and in 135 of 943 patients ( 14.3 % ) in the primary PCI group ( relative risk in the fibrinolysis group , 0.86 ; 95 % confidence interval , 0.68 to 1.09 ; P=0.21 ) . Emergency angiography was required in 36.3 % of patients in the fibrinolysis group , whereas the remainder of patients underwent angiography at a median of 17 hours after r and omization . More intracranial hemorrhages occurred in the fibrinolysis group than in the primary PCI group ( 1.0 % vs. 0.2 % , P=0.04 ; after protocol amendment , 0.5 % vs. 0.3 % , P=0.45 ) . The rates of nonintracranial bleeding were similar in the two groups . CONCLUSIONS Prehospital fibrinolysis with timely coronary angiography result ed in effective reperfusion in patients with early STEMI who could not undergo primary PCI within 1 hour after the first medical contact . However , fibrinolysis was associated with a slightly increased risk of intracranial bleeding . ( Funded by Boehringer Ingelheim ; Clinical Trials.gov number , NCT00623623 . ) |
13,307 | 27,500,435 | Time to radiographic fracture union was the most common primary outcome measure evaluated .
The most reduction in time to radiographic union by LIPUS treatment was seen in fractures with a long natural healing tendency .
LIPUS treatment effectively reduces the time to radiographic fracture union , but this does not directly result in a beneficial effect of accelerated functional recovery or the prevention of delayed union or nonunion .
The increase in bone formation as a result of LIPUS treatment may provide a valuable tool in fracture repair , but it does not always lead to healing . | BACKGROUND Low-intensity pulsed ultrasound ( LIPUS ) is frequently used to enhance or to accelerate fracture-healing , but its clinical role and effectiveness as a treatment modality remain uncertain .
We performed a systematic review and meta- analysis of r and omized controlled trials to determine the efficiency of LIPUS on bone-healing and /or fracture union , as well as on functional recovery . | BACKGROUND Several r and omised trials have been published on the effect of low-intensity pulsed ultrasound ( LIPUS ) on fracture healing in both distal radius and tibia fractures . Most studies showed a positive effect on time to clinical and radiological healing . We hypothesised that LIPUS has a beneficial effect on the healing of fresh clavicle fractures as well and studied its effect in non-operatively treated shaft fractures . METHODS We conducted a r and omised double blind , placebo-controlled multi-centre trial in 101 adult patients with a non-operatively treated fresh clavicle shaft fracture . Of these patients , 49 used a placebo transducer and 52 patients had an active transducer with ultrasound stimulation ( Exogen 2000 ) . Data were analysed on intention to treat basis . Baseline parameters of both groups were not significantly different . RESULTS There were no differences in time to subjective clinical fracture healing , resumption of daily activities , sports or professional work , Visual Analogue pain Scores ( VAS ) and use of pain medication . CONCLUSION Our findings did not confirm that LIPUS accelerates clinical healing time of fresh clavicle shaft fractures . LEVEL OF EVIDENCE Level 1 evidence that low-intensity pulsed ultrasound does not accelerate clinical fracture healing in non-operatively treated fresh midshaft clavicle fractures INTRODUCTION Osteogenic cell proliferation and differentiation play an important role in adequate fracture healing , and is target for osteoinductive therapies in delayed fracture healing . The aim of this study was to investigate whether low-intensity pulsed ultrasound enhances fracture healing at the tissue level in patients with a delayed union of the osteotomized fibula through an effect on the presence of RUNX2 immunopositive osteogenic cells . The effect was studied in both atrophic and hypertrophic delayed unions . MATERIAL S AND METHODS Biopsies were obtained from 6 female and 1 male patient ( age 43 - 63 ) with a delayed union of the osteotomized fibula after a high tibial osteotomy treated for 2 - 4 months with or without low-intensity pulsed ultrasound in a r and omized prospect i ve double-blind placebo-controlled trial . Immunolocalization of RUNX2 protein was performed to identify osteogenic cells . Histomorphometrical analysis was performed to determine the number of cells expressing RUNX2 located within and around the newly formed woven bone at the fracture end ( area of new bone formation ) , and up to 3 mm distant from the fracture end . RESULTS Cells expressing RUNX2 were present in all histological sections of control and low-intensity pulsed ultrasound-treated bone evaluated . Within the area of new bone formation , RUNX2 immunopositive cells were found in the undifferentiated soft connective tissue , at the bone surface ( presumably osteoblasts ) , and within the newly formed woven bone . Low-intensity pulsed ultrasound treatment of fibula delayed unions significantly reduced the number of RUNX2 immunopositive cells within the soft connective tissue at the fracture ends , whereas the number of RUNX2 immunopositive cells at the bone surface was not affected . The number of RUNX2 immunopositive cells was similar for the atrophic and hypertrophic delayed unions . CONCLUSIONS Immunolocalization of RUNX2 positive cells in delayed unions of the fibula reveals that delayed clinical fracture healing does not result in impairment of osteogenic cell proliferation and /or differentiation at the tissue level , even if delayed unions are clinical ly regarded as atrophic . Reduced number of osteogenic RUNX2 immunopositive cells within the soft connective tissue , and unchanged number of RUNX2 immunopositive cells at the bone surface , implicate that low-intensity pulsed ultrasound does not increase osteogenic cell presence , but likely affects osteogenic cell differentiation Background The role of low-intensity pulsed ultrasound ( LIPUS ) in the management of fractures remains controversial . The purpose of this study was to assess the feasibility of a definitive trial to determine the effect of LIPUS on functional and clinical outcomes in tibial fractures managed operatively . Methods We conducted a multicenter , concealed , blinded r and omized trial of 51 skeletally mature adults with operatively managed tibial fractures who were treated with either LIPUS or a sham device . All participating centers were located in Canada and site investigators were orthopedic surgeons specializing in trauma surgery . The goals of our pilot study were to determine recruitment rates in individual centers , investigators ’ ability to adhere to study protocol and data collection procedures , our ability to achieve close to 100 % follow-up rates , and the degree to which patients were compliant with treatment . Patients were followed for one year and a committee ( blinded to allocation ) adjudicated all outcomes . The committee adjudicators were experienced ( 10 or more years in practice ) orthopedic surgeons with formal research training , specializing in trauma surgery . Results Our overall rate of recruitment was approximately 0.8 patients per center per month and site investigators successfully adhered to the study protocol and procedures . Our rate of follow-up at one year was 84 % . Patient compliance , measured by an internal timer in the study devices , revealed that 39 ( 76 % ) of the patients were fully compliant and 12 ( 24 % ) demonstrated a greater than 50 % compliance . Based on patient feedback regarding excessive question naire burden , we conducted an analysis using data from another tibial fracture trial that revealed the Short Musculoskeletal Function Assessment ( SMFA ) dysfunction index offered no important advantages over the SF-36 Physical Component Summary ( PCS ) score . No device-related adverse events were reported . Conclusions Our pilot study identified key issues that might have rendered a definitive trial unfeasible . By modifying our protocol to address these challenges we have enhanced the feasibility of a definitive trial to explore the effect of LIPUS on tibial fracture healing . Trial registration The TRUST definitive trial was registered at Clinical Trials.gov on 21 April 2008 ( identifier : NCT00667849 ) OBJECTIVE To determine whether stimulation with low-intensity ultrasound will reduce the radiologic healing time of fresh tibial shaft fractures fixed with a reamed and statically locked intramedullary rod . DESIGN Prospect i ve , r and omized , double blinded , and placebo controlled . PATIENTS AND METHODS Thirty-two adult patients were included , fifteen in the active ultrasound group and seventeen in the placebo group . They all used an ultrasound device twenty minutes daily for seventy-five days without knowing whether it was active or inactive . St and ardized radiographs were taken every third week until healing and at six and twelve months . All radiographs were assessed blinded and independently by a radiologist and an orthopaedic surgeon . The codes were not broken until all fractures had healed and all radiographs had been evaluated . RESULTS The time until the first visible callus averaged 40+/-3 days for the active group and 37+/-3 days for the placebo ( p=0.44 ) . The healing time , defined as radiologic bridging of three cortices , was on average 155+/-22 days ( median 113 days ) for the active treatment group and 125+/-11 days ( median 112 days ) for the placebo group ( p=0.76 ) as assessed by the radiologist and 128+/-13 days for the active group and 114+/-9 days for the placebo group ( p=0.40 ) as evaluated by the orthopaedic surgeon . CONCLUSION We conclude that low-intensity ultrasound treatment did not shorten healing time in fresh tibial fractures treated with a reamed and statically locked intramedullary nail . Our results are not in accordance with previous findings reporting reduced healing time in nonoperatively treated tibial shaft fractures when subjected to ultrasound The use of pedicled vascularised bone grafts from the distal radius makes it possible to transfer bone with a preserved circulation and viable osteoclasts and osteoblasts . Experiments performed at the basic science level has provided substantial evidence that low-intensity ultrasound can accelerate and augment the fracture healing process . Only an adequate double-blind trial comparing treatment by ultrasound stimulation in patients treated by similar surgical techniques can provide evidence of the true effect of ultrasound . This paper describes the results of such a trial . From 1999 to 2004 , 21 fractures of the scaphoid with established non-union treated with vascularised pedicle bone graft were selected for inclusion in a double-blind trial . All patients were males , with an average age of 26.7 years ( range 17–42 years ) and an average interval between injury and surgery of 38.4 months ( range 3 months–10 years ) . Low-intensity ultrasound was delivered using a TheraMed 101-B bone-growth stimulator ( 30 mW/cm2 , 20 min/day ) , which was modified to accomplish double-blinding . These modifications did not affect the design ated active units . The placebo units were adjusted to give no ultrasound signal output across the transducer . Externally , all units appeared identical but were marked with individual code numbers . Patients were r and omly allocated to either an active or placebo stimulation . Follow-up averaged 2.3 years ( range 1–4 years ) . All patients achieved fracture union ( active and placebo groups ) , but compared with the placebo device ( 11 patients ) , the active device ( ten patients ) accelerated healing by 38 days ( 56±3.2 days compared with 94±4.8 days , p<0.0001 , analysis of variance).RésuméL’utilisation de greffes pediculées de l’extrémité distale du radius est possible . Elles peuvent être utilisées comme transferts osseux pourvu que l’on préserve la vascularisation garant d’une bonne circulation avec des osteoclastes et osteoblates bienvivants . De nombreuses expérimentations ont également montré que l’utilisation d’ultrasons de basse intensité peut accélérer et augmenter le processus de consolidation osseuse . Seule une étude en double aveugle stimulant l’ostéogènèse par ultrasons sur des patients opérés avec des techniques identiques peut mettre en évidence le véritable effet de ceux-ci . Le but decetravail est de décrire les résultats d’un tel essai . Entre 1999 et 2004 21 fractures du scaphoide avec pseudarthrose ont été traitées par une greffe pédiculée et sélectionnée pour cet essai en double aveugle . Tous les patients étaient de sexe masculin , l’âge moyen était de 26 ans ( 17 à 42 ans ) et le temps moyen entre le traumatisme et l’intervention chirurgicale a été de 38,4 mois ( 3 mois à 10 ans ) . Des ultrasons de basse intensité ont été utilisés avec un stimulateur de type TheraMed 101-B ( 30 mW/cm2 , 20 minutes par jour ) en double aveugle . Un appareil de type placébo a été également utilisé . L’apparence externe des deux appareils était absolument identique . Les patients ont été r and omisés entre ceux recevant la stimulation placébo et ceux recevant une stimulation active d’ultrason . Après un suivi moyen de 2,3 ans ( de 1 à 4 ans ) , tous les patients ont consolidé , aussi bien dans la série avec ultrasons que dans la série placébo . Si l’on compare la série avec appareil de type placébo ( 11 patients ) à la série utilisant un appareil délivrant des ultrasons ( 10 patients ) , la guérison a été plus rapide dans cette dernière série de 38 jours ( 56±3,2 jours , versus 94±4,8 jours ; p<0.0001 en analyse devariance ) Since pulsed low-intensity ultrasound ( frequency : 1.5 MHz , pulsed by 1 kHz , signal burst width : 200 microseconds , intensity : 30 mW/cm2 ) has been proven to stimulate fracture healing both clinical ly and experimentally , our question was whether this therapy also accelerates healing of fresh stable scaphoid fractures . Addressing this question , we did the following prospect i ve r and omized clinical trial . Regarding the results of former clinical fresh fracture studies by Heckman and Kristiansen , we postulated that low intensity ultrasound accelerates healing by about 30 % . Based on this thesis , we calculated that 30 patients divided into two groups would be necessary to show significant differences between the st and ard treatment ( treated by casting ) and an adjunctive ultrasound treatment ( treated by casting and additional daily 20 minutes ultrasound treatment ) if present . Diagnosis and healing was assessed by CT scans every two weeks . CT 's were analyzed by two independent radiologists and one h and surgeon . Furthermore , areas of cancellous bone bridging in correlation to the diameter of the scaphoid was measured in each CT scan . The results showed ultrasounded fractures healing in 43.2 + /- 10.9 days versus 62 + /- 19.2 days in the control group ( p < 0.01 ) . Trabecular bridging six weeks after injury showed 81.2 % + /- 10.4 % healed in the ultrasound-stimulated fractures versus 54.6 % + /- 29 % in the control ( p < 0.05 ) . Our study results confirm those of Heckman and Kristiansen and show a similar acceleration of bone healing . Low intensity ultrasound is successful in accelerating the healing of fresh scaphoid fractures Background We compared the healing response of tibial delayed unions between subjects treated with low-intensity pulsed ultrasound ( LIPUS ) ( n = 51 ) and subjects treated with a sham device ( n = 50 ) . Fracture age was ≥ 4 months in all cases . Study personnel and participants were blinded to r and om treatment assignment throughout the study . Methods This multi-center r and omized sham-controlled trial was undertaken at six hospitals in Germany . Adult patients who had sustained a tibial shaft fracture that subsequently showed inadequate progress toward healing ( i.e. , delayed union ) were enrolled and r and omized to receive either LIPUS ( Exogen 2000/2000 + , Smith & Nephew GmbH , Schenefeld , Germany ) or an identical nonoperative sham device . The daily treatment duration was 20 minutes , for a period of 16 weeks . Subjects r and omly assigned to active treatment had the ultrasound pressure wave signal set at the following parameters : 1.5 MHz frequency , 1 kHz repetition rate , 200 μs pulse duration , 30 mW/cm2 spatial intensity . Progress toward healing was estimated from changes in bone mineral density ( BMD ) and gap area as determined from computed tomography scans . Intention-to-treat analysis was conducted using a multiple imputation methodology . Results Based on log-transformed data , mean improvement in BMD was 1.34 ( 90 % confidence interval ( CI ) 1.14 to 1.57 ) times greater for LIPUS-treated subjects compared to sham ( p = 0.002 ) . A mean reduction in bone gap area also favored LIPUS treatment ( p = 0.014 ) . Conclusions These findings demonstrate significantly greater progress toward bone healing after LIPUS treatment compared to no LIPUS treatment in subjects with established delayed unions of the tibia Introduction There are no previous reports of low intensity pulsed ultrasound therapy in connection with bioabsorbable fracture fixation . In this r and omised , prospect i ve , double-blind and placebo-controlled study , the effects of ultrasound on bone mineral density and bone healing were examined in lateral malleolar fractures fixed with a bioabsorbable self-reinforced poly-L-lactide screw ( SR-PLLA ) . Material s and methods Thirty adult patients with SR-PLLA screw-fixed lateral malleolar fracture underwent ultrasound therapy 20 min daily for 6 weeks . Half of the patients were provided r and omly with a sham ultrasound device . Bone mineral density and bone healing were assessed by dual-energy X-ray absorptiometry ( DXA ) and by radiographs . Results Bone mineral density of the fractured lateral malleolus tended to increase slightly during 12 weeks of follow-up . The increase was symmetrical and statistically non-significant between the ultrasound and non-ultrasound group . All the fractures healed uneventfully . The biocompatibility of the bioabsorbable SR-PLLA fixation device and low intensity pulsed ultrasound was good . Despite the slight tendency for more frequent callus formation in the ultrasound group , no statistically significant effect of low intensity pulsed ultrasound on lateral malleolar fracture healing could be observed . Conclusion It was not possible to observe any statistically significant effect of low intensity pulsed ultrasound on lateral malleolar fracture healing in this study . Further studies are needed to examine the role of ultrasound therapy in the healing of fractures treated with bioabsorbable fixation devices A low intensity ultrasound device was investigated as an accelerator of cortical and cancellous bone fracture healing in smokers and non-smokers . Statistically significant reductions in healing time for smokers and nonsmokers were observed for tibial and distal radius fractures treated with an active ultrasound device compared with a placebo control device . The healing time for a tibial fracture was reduced 41 % in smokers and 26 % in nonsmokers with the active ultrasound device . Similarly , distal radius fracture healing time was reduced by 51 % in smokers and 34 % in nonsmokers with the active device . Treatment with the active ultrasound device also substantially reduced the incidence of tibial delayed unions in smokers and nonsmokers . The use of the active ultrasound device accelerates cortical and cancellous bone fracture healing , substantially mitigates the delayed healing effects of smoking , speeds the return to normal activity , and reduces the long-term complication of delayed union BACKGROUND Low-intensity pulsed ultrasound ( LIPUS ) was proven to have a positive impact on bone healing in animal and clinical studies . METHODS In this prospect i ve , r and omized controlled trial the effect of LIPUS during distraction osteogenesis was investigated . Thirty-six patients who underwent distraction osteogenesis ( > 2 cm ) were enrolled . Sixteen patients in the treatment group received LIPUS , and 20 patients as control group did not . Ultrasound treatment device was transcutaneously applied at the distraction gap for 20 minutes daily ( frequency 1.5 MHz , signal burst with 200 μs , signal repetition frequency 1.0 kHz , intensity 30 mW/cm(2 ) ) . Evaluation of patients was performed by st and ard radiographs every 3 weeks to 4 weeks . RESULTS Average transport distance was 7.0 cm in the ultrasound group and 6.3 cm in the control group . Mean Paley index for the ultrasound group was 1.09 mo/cm and 1.49 mo/cm for the control group . Mean distraction consolidation index for the ultrasound group was 32.8 d/cm and 44.6 d/cm for the control group . The calculated indices indicated no significant statistical difference between the two groups ( p < 0.116 ) but the fixator gestation period could be decreased for 43.6 days in the treatment group . CONCLUSIONS Therapeutic application of LIPUS during callus distraction constitutes a useful adjuvant treatment during distraction osteogenesis and has a positive effect on healing time with no negative effects PURPOSE To test the hypothesis that low-intensity pulsed ultrasound ( LIPUS ) may accelerate healing at osteotomy sites after forearm bone shortening osteotomies . METHODS In this prospect i ve study , we enrolled 27 patients who underwent ulnar shortening osteotomy for ulnar impaction syndrome or radial shortening osteotomy for Kienböck disease . We r and omized limbs to be treated with LIPUS ( 14 osteotomies , LIPUS group ) or without LIPUS ( 13 osteotomies , control group ) . At 1 week postoperatively , patients in the LIPUS group received once-daily 20-minute LIPUS treatments that continued until at least 12 weeks postoperatively . At 2 , 4 , 6 , 8 , 12 , 16 , and 24 weeks postoperatively , we assessed union of the osteotomy site to determine the time to union using 4 projections of x-rays . RESULTS In this study , all osteotomies achieved complete union . The mean times to complete cortical union were 57 days in the LIPUS group and 76 days in the control group . Regarding endosteal union , the mean times were 121 days in the LIPUS group and 148 days in the control group . The LIPUS group had significantly reduced times for both types of union . CONCLUSIONS Application of LIPUS shortened the time to cortical union by 27 % , and to endosteal union by 18 % . Our results indicate that LIPUS accelerated bone healing after we performed forearm bone shortening osteotomies . This may provide earlier return to activity and work for patients undergoing forearm osteotomies Serum levels of bone markers were measured prospect ively for 1 year in 30 adult patients with an intramedullary fixed tibial fracture . In a double blinded design , half of the patients received low intensity ultrasound . All fractures healed , although in seven of 30 the healing was delayed more than 6 months . There was no significant difference in radiologic healing time between the ultrasound group ( median , 113 days ) and the placebo group ( median , 112 days ) . The marker for bone resorption , crosslinked telopeptide , peaked at 1 to 4 weeks , whereas markers for bone formation peaked at 10 to 16 weeks for bone specific alkaline phosphatase and osteocalcin . Crosslinked telopeptide was lower at 1 week in patients treated with ultrasound than in those receiving placebo . Patients with delayed healing did not differ in crosslinked telopeptide compared with patients with normal healing . There were no differences in bone formation markers between patients who received ultrasound or placebo . Patients with delayed healing had lower levels of bone specific alkaline phosphatase between 4 and 7 weeks than did patients with normal healing , although no such differences were seen for osteocalcin . The results indicate that low intensity ultrasound might slow bone resorption , although there is no visible effect on bone formation . Patients with delayed healing had adequate bone resorption but slower early bone formation than did patients with normal healing Background and Aims : The present study was initiated to evaluate the long-term effects of low-intensity ultrasound therapy on bioabsorbable screw-fixed lateral malleolar fractures , which has not been studied earlier . Patients and Methods : The study design was prospect i ve , r and omized , double-blinded , and placebo-controlled . Sixteen dislocated lateral malleolar fractures were fixed with one bioabsorbable self-reinforced poly-L-lactide screw . The patients used an ultrasound device 20 minutes daily for six weeks without knowing it was active ( eight patients ) or inactive ( eight patients ) . The follow-up time was 18 months . The radiological bone morphology was assessed by multidetector computed tomography ( MDCT ) scans , the bone mineral density by dual-energy X-ray absorptiometry scans , and the clinical outcome by Olerud-Mol and er scoring and clinical examination of the ankle . Results : The MDCT scans revealed that all fractures were fully healed , and no differences were observed in radiological bone morphology at the fracture site . The bone mineral density of the fractured lateral malleolus tended to increase slightly during the 18-month follow-up , the increase being symmetrical in both groups . No differences were observed in the clinical outcome or Olerud-Mol and er scores . Conclusions : The six-week low-intensity ultrasound therapy had no effect on radiological bone morphology , bone mineral density or clinical outcome in bioabsorbable screw-fixed lateral malleolar fractures 18 months after the injury Chevron osteotomy is a widely accepted method for correction of symptomatic hallux valgus deformity . Full weight bearing in regular shoes is not recommended before 6 weeks after surgery . Low intensity pulsed ultrasound is known to stimulate bone formation leading to more stable callus and faster bony fusion . We performed a r and omized , placebo-controlled , double-blinded study on 44 participants ( 52 feet ) who underwent chevron osteotomy to evaluate the influence of daily transcutaneous low intensity pulsed ultrasound ( LIPUS ) treatment at the site of osteotomy . Follow-up at 6 weeks and 1 year included plain dorsoplantar radiographs , hallux-metatarsophalangeal-interphalangeal scale and a question naire on patient satisfaction . There was no statistical difference in any pre- or postoperative clinical features , patient satisfaction or radiographic measurements ( hallux valgus angle , intermetatarsal angle , sesamoid index and metatarsal index ) except for the first distal metatarsal articular angle ( DMAA ) . The DMAA showed statistically significant ( p = 0.046 ) relapse in the placebo group upon comparison of intraoperative radiographs after correction and fixation ( 5.2 degrees ) and at the 6-week follow-up ( 10.6 degrees ) . Despite potential impact of LIPUS on bone formation , we found no evidence of an influence on outcome 6 weeks and 1 year after chevron osteotomy for correction of hallux valgus deformity INTRODUCTION Low-intensity pulsed ultrasound ( LIPUS ) accelerates impaired fracture healing , but the exact mechanism is unknown . The aim of this study was to investigate how LIPUS affects bone healing at the tissue level in patients with a delayed union of the osteotomized fibula , by using histology and histomorphometric analysis to determine bone formation and bone resorption parameters . MATERIAL S AND METHODS Biopsies were obtained from 13 patients ( 9 female , 4 male ; age 42 - 63 ) with a delayed union of the osteotomized fibula after a high tibial osteotomy , treated for 2 - 4 months with or without LIPUS in a r and omized prospect i ve double-blind placebo-controlled trial . In the histological sections of the delayed union biopsies , 3 areas of interest were distinguished , i.e. 1 ) area of new bone formation at the fracture ends , 2 ) area of cancellous bone , and 3 ) area of cortical bone . Histomorphometrical analysis was performed to determine bone formation and bone resorption parameters ( as well as angiogenesis ) . RESULTS In LIPUS-treated delayed unions , endosteal callus formation by direct bone formation without a cartilage intermediate as well as indirect bone formation was observed , while in untreated controls only indirect bone formation was observed . In the area of new bone formation , LIPUS significantly increased osteoid thickness by 47 % , mineral apposition rate by 27 % , and bone volume by 33 % . No increase in the number of blood vessels was seen in the newly formed bony callus . In the area of cancellous bone , bone volume was significantly increased by 17 % whereas no effect on osteoid thickness and mineral apposition rate was seen . LIPUS did not affect osteoid volume , osteoid maturation time , number of osteocytes , osteocyte lacunae , or osteoclast-like cells in any of the areas of interest . CONCLUSIONS Our results suggest that LIPUS accelerates clinical fracture healing of delayed unions of the fibula by increasing osteoid thickness , mineral apposition rate , and bone volume , indicating increased osteoblast activity , at the front of new bony callus formation . Improved stability and /or increased blood flow , but probably not increased angiogenesis , might explain the differences in ossification modes between LIPUS-treated delayed unions and untreated controls Purpose Low-intensity pulsed ultrasound ( LIPUS ) has been used successfully to accelerate healing of fresh fractures and non-unions . It also improved callus maturation with distraction osteogenesis in animal trials . However , only few clinical studies are available to support its widespread use for the latter indication in humans . Methods Twenty-one patients undergoing callus distraction for posttraumatic tibial defects were r and omized into two groups : the trial group ( 12 men ; mean age 32 years ) which received 20 minutes LIPUS daily during treatment and the control group ( six men and three women ; mean age 29 years ) without LIPUS treatment . The Ilizarov ring fixator was used in all cases . Results were examined clinical ly and radiologically , analysing callus maturation with a computer-assisted measurement . Results Patients in the LIPUS group needed a mean of 33 days to consoli date every 1 cm of new bone in comparison to 45 days in the control group . The healing index was therefore shortened by 12 days/cm in the LIPUS group . This means that callus maturation was 27 % faster in the LIPUS group . The fixator time was shortened by 95 days in the LIPUS group . The overall daily increase in radiographic callus density was 33 % more in the LIPUS group than in the control group . Conclusions LIPUS treatment is an effective non-invasive adjuvant method to enhance callus maturation in distraction osteogenesis . With the help of this treatment , the healing time and the duration of external fixation can be reliably shortened OBJECTIVE In a double blind r and omised clinical pilot trial , it was investigated whether low intensity pulsed ultrasound therapy stimulates early bone formation in a distraction gap created in a severely resorbed m and ible . DESIGN Eight patients underwent a m and ibular vertical distraction over an average distance of 6.6+/-1.1 mm . Ultrasound self-therapy or placebo therapy was started on the first day of distraction and continued daily until the implants were inserted . After 31+/-3.8 days of consolidation , the distraction device was removed , a transm and ibular biopsy was taken , and two endosseous implants were inserted . RESULTS All patients complied well with ultrasound therapy . During an average of 30.1+/-4.1 months follow-up , no complications did occur . Microradiographic examination of the biopsies revealed a comparable mean area of mineralised tissue in the distraction gap of 1.9+/-1.7mm(2 ) in the ultrasound treatment group and 1.9+/-1.3mm(2 ) in the placebo treatment group . Histological examination indicated that active woven bone was present within the distraction gap just adjacent to the osteotomy plane , with no apparent differences between the treatment groups . The lamellar bone formation outside the distraction gap appeared to have started as well . CONCLUSION During a 31-day consolidation period , ultrasound treatment does not appear to stimulate bone formation in the severely resorbed vertical distracted m and ible and it seems that this period is too short to evaluate properly if there is an effect . Therefore , a longer consolidation period has to be studied BACKGROUND Opening-wedge high tibial osteotomy by hemicallotasis for osteoarthritis in the medial compartment of the knee requires external fixation for a long time , until callus maturation is complete . The aim of this study was to determine if low-intensity pulsed ultrasound would accelerate callus maturation when applied after distraction to limbs treated with opening-wedge high tibial osteotomy by hemicallotasis . METHODS Twenty-one patients with symmetric grade s of osteoarthritis and similar degrees of varus deformity in the two knees underwent bilateral one-stage opening-wedge high tibial osteotomy by hemicallotasis . After completion of distraction , the bone mineral density of the distraction callus was measured . Then , one r and omly selected limb was subjected to ultrasound treatment for twenty minutes daily until removal of the external fixator . The contralateral limb was left untreated to serve as the control . After four weeks of treatment , bone mineral density was measured again . RESULTS During the four-week treatment period , the mean increase in callus bone mineral density was significantly greater in the ultrasound-treated tibiae ( 0.20 + /- 0.12 g/cm(2 ) ) than in the control tibiae ( 0.13 + /- 0.10 g/cm(2 ) ) ( p = 0.02 , unpaired t test ) . In eighteen patients the increase in the bone mineral density was greater in the ultrasound-treated limb than in the control limb , whereas in three patients the increase was greater in the control limb . CONCLUSIONS We found that low-intensity pulsed ultrasound applied during the consolidation phase of distraction osteogenesis accelerates callus maturation after opening-wedge high tibial osteotomy by hemicallotasis in elderly patients Sixty-seven closed or grade -I open fractures of the tibial shaft were examined in a prospect i ve , r and omized , double-blind evaluation of use of a new ultrasound stimulating device as an adjunct to conventional treatment with a cast . Thirty-three fractures were treated with the active device and thirty-four , with a placebo control device . At the end of the treatment , there was a statistically significant decrease in the time to clinical healing ( 86 + /- 5.8 days in the active-treatment group compared with 114 + /- 10.4 days in the control group ) ( p = 0.01 ) and also a significant decrease in the time to over-all ( clinical and radiographic ) healing ( 96 + /- 4.9 days in the active-treatment group compared with 154 + /- 13.7 days in the control group ) ( p = 0.0001 ) . The patients ' compliance with the use of the device was excellent , and there were no serious complications related to its use . This study confirms earlier animal and clinical studies that demonstrated the efficacy of low-intensity ultrasound stimulation in the acceleration of the normal fracture-repair process Tibial stress fractures commonly occur in athletes and military recruits . This prospect i ve , r and omized , double-blind clinical study sought to determine whether pulsed ultrasound reduces tibial stress fracture healing time . Twenty-six midshipmen ( 43 tibial stress fractures ) were r and omized to pulsed ultrasound or placebo treatment . Twenty-minute daily treatments continued until patients were asymptomatic with signs of healing on plain radiographs . The groups were not significantly different in demographics , delay from symptom onset to diagnosis , missed treatment days , total number of treatments , or time to return to duty . Pulsed ultrasound did not significantly reduce the healing time for tibial stress fractures BACKGROUND Low-intensity ultrasound has demonstrated an acceleration of bone healing and more profound callus formation in animal and human clinical experiments . In this study , the effect of pulsed , low-intensity ultrasound was determined in established nonunion cases . METHODS The enrolled cases were review ed for the time from their last surgical procedure and evidence of no healing or progression of healing during the 3 or more months before the start of low-intensity ultrasound therapy to determine whether the cases were established nonunions . Twenty-nine cases , located in the tibia , femur , radius/ulna , scaphoid , humerus , metatarsal , and clavicle , met the criteria for established nonunions . On average , the postfracture period before the start of ultrasound treatment was 61 weeks . Initial fracture treatment was conservative in 8 cases and operative in 21 cases . Additional treatments including bone grafting , reosteo synthesis , and other surgical procedures were performed an average of 52 weeks before the start of ultrasound treatment . Daily , 20-minute applications of low-intensity ultrasound at the site of the nonunion were performed by the patients at home . RESULTS Twenty-five of the 29 nonunion cases ( 86 % ) healed in an average treatment time of 22 weeks ( median , 17 weeks ) . Stratification of the healed and failed outcome for age , gender , concomitant disease , bone location , fracture age , prior last surgery interval , nonunion type , smoking habits , and fixation before and during treatment showed a significant difference only in the smoking habit strata . CONCLUSION Noninvasive ultrasound therapy can be useful in the treatment of challenging , established nonunions Background We investigated the effect of low-intensity ultrasound on bone healing in bioabsorbable self-reinforced poly-l-lactic acid ( SR-PLLA ) screw-fixed lateral malleolar fractures . The study design was prospect i ve , r and omized , double-blind , and placebo-controlled . Methods A total of 22 fractures were fixed with one SR-PLLA screw . All the patients were instructed to use an ultrasound device 20 min daily for 42 days without knowing whether it was active or inactive . Eleven patients had active and eleven sham ultrasound devices . The causes of error during treatment with head module placement and attachment to the convex surface of the lateral distal fibula were minimized by careful targeting and using coupling gel . Radiological fracture healing was assessed by radiographs and multidetector computed tomography ( CT ) scans in a blinded manner by a radiologist and orthopedic surgeons . Results The overall compliance to the daily ultrasound treatments was good . All wounds healed uneventfully , and no foreign body reactions were observed . No difference was observed between the groups regarding either fracture line visualization or callus formation assessed by plain radiographs . In the CT images at 9 weeks , the share of the endosteal united fracture line compared to the non-united fracture line was slightly higher in the active ultrasound device group than in the sham ultrasound device group , but the difference was not statistically significant . Conclusion The study indicates that the biocompatibility of ultrasound therapy and bioabsorbable SR-PLLA screw fixation is good . There was no obvious effect of low-intensity ultrasound on lateral malleolar fracture healing . However , the relatively small number of patients must be kept in mind when interpreting our results . It is also important to limit any conclusions based on the present study to malleolar fractures fixed with the SR-PLLA screw A clinical study was conducted to investigate the effect of low-intensity pulsed ultrasound ( US ) stimulation ( LIPUS ) on the healing of complex tibial fractures . Thirty complex tibial fractures were r and omly assigned to the treatment with LIPUS ( n = 16 ) or by a dummy machine ( sham-exposed : n = 14 ) . The fractures were immobilized by either internal or external fixations according to the clinical indications . LIPUS was given 20 min/day for 90 days . Fracture healing was monitored by clinical , radiological , densitometric and biochemical assessment s. The LIPUS-treated group showed statistically significantly better healing , as demonstrated by all assessment s. Complications were minimal in the LIPUS group . There were two cases of delayed union , with one in each group . There were two cases of infection in the control group . The delayed-union cases were subsequently treated by LIPUS and the infection cases were treated with st and ard protocol . Fracture healing in these patients was again treated by LIPUS Objective : To evaluate the effectiveness of low-intensity pulsed ultrasound ( LIPUS ) for the improvement of lower limb bone stress injuries in a civilian population . Design : A prospect i ve , r and omized , double-blinded , placebo-controlled trial to compare LIPUS with placebo . Setting : Civilian private practice population in Sydney , Australia . Participants : Subjects were recruited if a grade II-IV bone stress injury was diagnosed on magnetic resonance imaging ( MRI ) of either the postero-medial tibia , fibula or second , third , or fourth metatarsal . Subjects of all levels of sporting activity were included . Thirty subjects were initially recruited , and 23 subjects were included in the final analysis . Interventions : Subjects were r and omized into either the treatment or placebo arm and matched to the site of injury ( tibia , fibula , or metatarsal ) . Subjects in both arms used either treatment or placebo devices for 20 minutes daily for 4 weeks . Main Outcome Measures : Six clinical parameters ( night pain , pain at rest , pain on walking , pain with running , tenderness , and pain with single leg hop ) were compared before and after intervention . The changes in MRI grade and bone marrow edema size were also compared . Results : There were no significant differences between the treatment and placebo conditions for changes in MRI grading ( 2.2 vs 2.4 , P = 0.776 ) or bone marrow edema size ( 3 vs 4.1 , P = 0.271 ) . There were no significant differences between the treatment and placebo conditions for the 6 clinical parameters . Conclusions : Low-intensity pulsed ultrasound was found not to be an effective treatment for the healing of lower limb bone stress injuries in this study . However , this was measured over a relatively short duration of 4 weeks in a small , mostly female population . Clinical Relevance : This double-blinded , r and omized , placebo-controlled trial has shown that LIPUS is not an effective treatment for lower limb bone stress injuries PURPOSE To investigate the accelerating effects of low-intensity pulse ultrasound stimulation ( LIPUS ) on the fracture healing of distal radius . METHODS A total of 81 patients with distal radius fracture were r and omly divided into two groups : the ultrasound treatment group and the control group . Patients in the ultrasound treatment group were immobilized in a below-elbow cast and received LIPUS treatment 15 min/day , while the control group were immobilized by a plaster support and cast . The patients were followed up every week and took X-ray films . The initial and healed X-ray films and the gray value of fracture site were analyzed by Photoshop software . The effect of reposition was evaluated based upon Steward recommended by Dienst , combining with Aro 's measuring method . RESULTS Clinical fracture healing time in ultrasound group was significantly shorter than that in the control group ( 32.04 ± 2.58d vs. 40.75 ± 5.12d , p < 0.01 ) . In addition , the grey value changes of fracture sites of the ultrasound group were much higher than that of the control group . The reposition effects of fracture healing had no difference between the two groups ( p > 0.05 ) . CONCLUSION Low-intensity pulse ultrasound stimulation could accelerate fracture healing of the distal radius and promote local bone formation A multicenter , prospect i ve , r and omized , double-blind , placebo-controlled clinical trial was conducted to test the efficacy of a specifically programmed , low-intensity , non-thermal , pulsed ultrasound medical device for shortening the time to radiographic healing of dorsally angulated fractures ( negative volar angulation ) of the distal aspect of the radius that had been treated with manipulation and a cast . Sixty patients ( sixty-one fractures ) were enrolled in the study within seven days after the fracture . The patients used either an active ultrasound device ( thirty fractures ) or a placebo device ( thirty-one fractures ) daily for twenty minutes at home for ten weeks . The two types of devices were identical except that the placebo devices emitted no ultrasound energy . Clinical examination was performed and radiographs were made at one , two , three , four , five , six , eight , ten , twelve , and sixteen weeks after the fracture by each site investigator . The time to union was significantly shorter for the fractures that were treated with ultrasound than it was for those that were treated with the placebo ( mean [ and st and ard error ] , 61 ± 3 days compared with 98 ± 5 days ; p < 0.0001 ) . Each radiographic stage of healing also was significantly accelerated in the group that was treated with ultrasound as compared with that treated with the placebo . Compared with treatment with the placebo , treatment with ultrasound was associated with a significantly smaller loss of reduction ( 20 ± 6 per cent compared with 43 ± 8 per cent ; p < 0.01 ) , as determined by the degree of volar angulation , as well as with a significant decrease in the mean time until the loss of reduction ceased ( 12 ± 4 days compared with 25 ± 4 days ; p < 0.04 ) . We concluded that this specific ultrasound signal accelerates the healing of fractures of the distal radial metaphysis and decreases the loss of reduction during fracture-healing |
13,308 | 24,228,084 | Overall , hysteroscopic sterilization is associated with lower pregnancy rates and lower complication rates compared to tubal ligation .
No deaths have been reported for hysteroscopic sterilization .
This review indicates that hysteroscopic tubal sterilization is associated with : lower pregnancy rates compared to tubal ligation ; lower complication rates compared to tubal ligation ; no significant improvement in patient satisfaction compared to tubal ligation . | BACKGROUND Hysteroscopic tubal sterilization is a minimally invasive alternative to laparoscopic tubal ligation for women who want permanent contraception .
The procedures involves non-surgical placement of permanent microinserts into both fallopian tubes .
Patients must use alternative contraception for at least 3 months postprocedure until tubal occlusion is confirmed .
Compared to tubal ligation , potential advantages of the hysteroscopic procedure are that it can be performed in 10 minutes in an office setting without the use of general or even local anesthesia .
OBJECTIVE The objective of this analysis was to determine the effectiveness and safety of hysteroscopic tubal sterilization compared with tubal ligation for permanent female sterilization .
Both approaches involve closing off the fallopian tubes , preventing the egg from moving down the tube and the sperm from reaching the egg .
Tubal ligation is a surgical procedure to tie or seal the fallopian tubes , and it usually requires general anesthesia . | BACKGROUND The aim of this study was to assess the diagnostic accuracy of three-dimensional ultrasound ( 3D-US ) for determining the position of Essure microinserts and the success of sterilization by the Essure method . METHODS This retrospective observational study examined the case records of 311 women who underwent hysteroscopic sterilization from October 2002 through October 2008 . Imaging with 3D-US or pelvic X-radiography or both was performed 3 months after the procedure to verify device position . Hysterosalpingography ( HSG ) was performed when a bilateral procedure was not completed because of a history of salpingectomy or blocked tube , when doubt persisted after 3D-US or pelvic radiography , or for comparative purpose s in a prospect i ve study . The positions seen on 3D-US were classified in four categories according to a specific scale we devised . RESULTS The insertion procedure was completed in 94.2 % patients . Only 90.5 % underwent imaging verification of the device 3 months afterwards . In all , 227 3D-US , 175 pelvic radiography and 64 HSG imaging procedures were performed . Visualization of the device was possible in 99.6 % of the 3D-US images . According to our classification , 3D-US was appropriate for assessing device position for 195 ( 85.9 % ) patients . The need for HSG confirmation was significantly lower with 3D-US than radiographic imaging ( 14.1 versus 26.8 % , P = 0.001 ) . 3D-US examinations , compared with the results of HSG as the reference test , had a sensitivity of 100 % and a specificity of 76.6 % . Neither pregnancy nor early expulsion occurred when 3D-US found that the devices were correctly placed . CONCLUSIONS 3D-US is a simple technique for assessing the position of Essure ( ® ) microinserts , even after concomitant endometrial surgery . The 3D-US classification presented here appears to make it possible to use HSG for back-up confirmation only when the microinsert is found in a very distal position on 3D-US and thus to protect the majority of women from the negative effects of pelvic radiography and HSG Objective To compare patient satisfaction , discomfort , procedure time , success rate and adverse events of hysteroscopic ( ESSURE , Conceptus Inc , San Carlos , USA ) versus laparoscopic sterilisation OBJECTIVE To assess the safety , effectiveness , and reliability of a tubal occlusion microinsert for permanent contraception , as well as to document patient recovery from the placement procedure and overall patient satisfaction . METHODS A cohort of 518 previously fertile women seeking sterilization participated in this prospect i ve , phase III , international , multicenter trial . Microinsert placement was attempted in 507 women . Microinserts were placed bilaterally into the proximal fallopian tube lumens under hysteroscopic visualization in outpatient procedures . RESULTS Bilateral placement of the microinsert was achieved in 464 ( 92 % ) of 507 women . The most common reasons for failure to achieve satisfactory placement were tubal obstruction and stenosis or difficult access to the proximal tubal lumen . More than half of the women rated the average pain during the procedure as either mild or none , and 88 % rated tolerance of device placement procedure as good to excellent . Average time to discharge was 80 minutes . Sixty percent of women returned to normal function within 1 day or less , and 92 % missed 1 day or less of work . Three months after placement , correct microinsert placement and tubal occlusion were confirmed in 96 % and 92 % of cases , respectively . Comfort was rated as good to excellent by 99 % of women at all follow-up visits . Ultimately , 449 of 518 women ( 87 % ) could rely on the microinsert for permanent contraception . After 9620 woman-months of exposure to intercourse , no pregnancies have been recorded . CONCLUSION This study demonstrates that hysteroscopic interval tubal sterilization with microinserts is well tolerated and results in rapid recovery , high patient satisfaction , and effective permanent contraception STUDY OBJECTIVES To evaluate the efficacy of performing the Essure hysteroscopic sterilization in an office-based setting . DESIGN Prospect i ve , longitudinal analysis ( Canadian Task Force classification II-3 ) . SETTING University out-patient office . PATIENTS All patients undergoing permanent sterilization in our outpatient office who opted for hysteroscopic sterilization were included . INTERVENTIONS Hysteroscopic placement of the Essure device in an office-based setting with only non-steroidal antiinflammatory drugs and paracervical block . MEASUREMENTS AND MAIN RESULTS Multiple data points were collected on each patient including demographic data , specific procedural information , and 12-week hysterosalpingogram data . Most of our patients were Hispanic and had an average body mass index of 30.3 . Average time to perform the procedure was 12.4 minutes , with the steepest improvement in the first 13 cases . Bilateral placement of the device was successful in 98 ( 96 % ) of 102 patients . Of these patients 92 have 12-week hysterosalpingography results ( 6 patients were lost to follow-up ) , with 90 ( 98 % ) showing bilateral tubal occlusion . There were no intraprocedural or postprocedural complications . CONCLUSION In our institution and in our experience , office-hysteroscopic placement of the Essure device is a feasible and effective approach for permanent sterilization BACKGROUND Unlike laparoscopic surgery for interval tubal sterilization , a hysteroscopic approach obviates surgical incision and requires only local anaesthesia or intravenous sedation . The safety , tolerability and efficacy of an hysteroscopically placed micro-insert device was evaluated . METHODS A cohort of 227 previously fertile women participated in this prospect i ve international multicentre trial . Micro-inserts were placed bilaterally into the proximal Fallopian tube lumens under hysteroscopic visualization in outpatient procedures . RESULTS Successful bilateral micro-insert placement was achieved in 88 % of women . The majority of women reported that intraprocedural pain was less than or equal to that expected , and 90 % rated tolerance of the device placement procedure as good to excellent . Most women could be discharged in an ambulatory state within 1 - 2 h. Adverse events occurred in 7 % of the women , but none was serious . Correct device placement was confirmed in 97 % of cases at 3 months . Over 24 months follow-up , 98 % of study participants rated their tolerance of the micro-insert as very good to excellent . After 6015 woman-months of exposure to intercourse , no pregnancies have been recorded . CONCLUSIONS Hysteroscopic sterilization result ed in rapid patient recovery without unacceptable post-procedure pain , as well as high long-term patient tolerability , satisfaction and effective permanent contraception OBJECTIVE To evaluate women 's satisfaction and tolerance of hysteroscopic sterilization . DESIGN Prospect i ve analysis of case series . SETTING Gynecology department in a teaching hospital . PATIENT(S ) A total of 1,630 women who underwent hysteroscopic sterilization by placement of Essure microinserts ( Conceptus , Inc. , Mountain View , CA ) from January 2003 to June 2006 . INTERVENTION(S ) Transvaginal ultrasound examination , pelvic x-ray examination , and hysterosalpingography 3 months after sterilization with Essure microinserts . Satisfaction was assessed by a visual analog scale . Adverse effects and tolerance also were recorded . MAIN OUTCOME MEASURE(S ) Transvaginal ultrasound and pelvic x-ray confirmation of correct localization of microinserts and patient 's satisfaction and tolerance after a 3-month follow-up . RESULT ( S ) The rate of successful insertion was 99 % . Most of women returned to their daily activities on the same day of insertion , and 86.5 % considered the procedure painless or scarcely painful . All the patients were highly satisfied after hysteroscopic sterilization : 91 % of subjects by visual analog scale ( on a 0 to 10 scale ) rated the method at 10 ( high satisfaction degree ) , and none of the subjects rated it under 8 . For patients , the most valuable aspects of the procedure were absence of surgery room ( 52.7 % ) , method 's quickness and comfort ( 19.9 % ) , and permanent sterilization ( 18.2 % ) . More than 97 % of the patients said that they would recommend the procedure to others . CONCLUSION ( S ) This study provides evidence that Essure microinserts can be placed in a usual gynecologic consultation room in st and ard conditions without any type of anesthesia or sedation and are associated with great overall patient satisfaction . Women also have high tolerance for the procedure and describe minor postoperative pain STUDY OBJECTIVE To compare hysteroscopic female sterilization procedures performed in-office versus a hospital operating room ( OR ) among newly trained physicians . DESIGN Multisite hospital operating rooms and physician offices . PATIENTS Women desiring permanent hysteroscopic sterilization . INTERVENTION Hysteroscopic female sterilization with the Essure system . MEASUREMENTS AND MAIN RESULTS Procedure time ( scope in/scope out time ) , device placement rates , and incidence of complications and adverse events were compared . There was no significant difference in scope time between the 2 setting s. There was no significant difference in placement rates , although the placement rate was somewhat higher in-office ( 91 % vs 88 % ) . There were no complications among any of the procedures , and the incidence of minor adverse events was extremely low in both setting s ( OR=2 % , in-office=1 % ) . CONCLUSION There is no clear advantage to performing hysteroscopic sterilization in a hospital OR . Hysteroscopic sterilization can be performed safely and efficiently in an office setting OBJECTIVES Hysteroscopic flexible micro-insert ( Essure ) is an ambulatory improvement of fallopian tube sterilization , which is a deliberated suppression of fertility . The aim of this study was an evaluation of feasibility ( learning curve ) and the first year outcome of this method . PATIENTS AND METHODS This prospect i ve study , carried out between February 2002 and March 2003 , included patients who were matching with manufacturer recommendations . One surgeon only realized all the device placements . RESULTS Fifty patients were included ( one year follow-up ) . Mean age was 41 ( + /-3.3 ) , mean parity was 2.7 ( + /-0.8 ) . Mean time needed for device placement was 26 minutes ( + /-6.5 ) and was reduced with increased experience . Six failures of placement ( 12 % ) were related , because of submucus leiomyomas , proximal tubal stenotic disease or too retroverted uterus . Only 5 patients ( 11,4 % ) described intensive pelvic pain during the placement . The only case of device expulsion benefited from a successful second placement . The one-year follow-up showed no significant difference of body weight increasing , duration or quantity of menstruation , neither significant pelvic pain nor vaginal bleeding . Tolerance was rated at least at " somewhat satisfied " . There have been no pregnancies reported in 670 woman-months of effectiveness . DISCUSSION AND CONCLUSION Our results agree in any point with those of larger studies . We think that hysteroscopy micro-insert placement is not only reserved to specialized centers but also to any gynecologist who is used to performing hysteroscopy because of its feasibility STUDY OBJECTIVE To assess the safety and placement effectiveness of a new delivery catheter for the Essure micro-insert hysteroscopic sterilization system . DESIGN Prospect i ve , multicenter , single-arm clinical study . ( Canadian Task Force classification II-3 ) . SETTING Hospital-based clinical research centers . PATIENTS One hundred two women of reproductive age and proven fertility . INTERVENTION A new coil catheter delivery system was used for micro-insert placement . MEASUREMENTS AND MAIN RESULTS The bilateral placement of micro-inserts using the coil catheter delivery system occurred in 100 women out of 102 attempts ( 98 % ) . The two women who did not have successful micro-insert placement were subsequently shown to have proximal tubal stenotic disease . CONCLUSION These findings indicate that the introduction of the coil catheter delivery system for Essure hysteroscopic sterilization improves the micro-insert bilateral placement rate when compared with previous studies . It is hypothesized that the coil catheter has superior navigational properties , particularly within tortuous or narrowed tubal lumens Objective To estimate the risk of intraoperative or postoperative complications for interval laparoscopic tubal sterilizations . Methods We used a prospect i ve , multicenter cohort study of 9475 women who had interval laparoscopic tubal sterilization to calculate the rates of intraoperative or postoperative complications . The relative safety of various methods was assessed by calculating overall complication rates for each major method of tubal occlusion . Method -related complication rates also were calculated and included only complications attributable to a method of occlusion . We used logistic regression to identify independent predictors of one or more complications . Results When we used a more restrictive definition of unintended major surgery , the overall rate of complications went from 1.6 to 0.9 per 100 procedures . There was one life-threatening event and there were no deaths . Complications rates for each of the four major methods of tubal occlusion ranged from 1.17 to 1.95 , with no significant differences between them . When complication rates were calculated , the spring clip method had the lowest method -related complication rate ( 0.47 per 100 procedures ) , although it was not significantly different from the others . In adjusted analysis , diabetes mellitus ( adjusted odds ratio [ OR ] 4.5 ; 95 % confidence interval [ CI ] 2.3 , 8.8 ) , general anesthesia ( OR 3.2 ; CI 1.6 , 6.6 ) , previous abdominal or pelvic surgery ( OR 2.0 ; CI 1.4 , 2.9 ) , and obesity ( OR 1.7 ; CI 1.2 , 2.6 ) were independent predictors of one or more complications . Conclusion Interval laparoscopic sterilization generally is a safe procedure ; serious morbidity is rare OBJECTIVE : To describe the pregnancy rates among women whose husb and s underwent vasectomy . METHODS : Between 1985 and 1987 , 573 women aged 18–44 years whose husb and s underwent vasectomy in medical centers in 5 U.S. cities were enrolled in the U.S. Collaborative Review of Sterilization , a prospect i ve cohort study of male and female sterilization . Women were interviewed by telephone at 1 , 2 , 3 , and 5 years after their husb and s underwent vasectomy . RESULTS : Among the 540 eligible women at risk for pregnancy , there were 6 pregnancies occurring from 6 to 72 weeks after vasectomy . The cumulative probability of failure per 1,000 procedures ( 95 % confidence interval ) was 9.4 ( 1.2 , 17.5 ) 1 year after vasectomy and 11.3 ( 2.3 , 20.3 ) at years 2 , 3 , and 5 . CONCLUSION : Couples considering vasectomy should be counseled about the small , but real , risk of pregnancy following the procedure and that men are not sterile immediately after vasectomy . LEVEL OF EVIDENCE : Background : Current methods of female surgical sterilisation require incisional surgery , general anaesthesia and a prolonged recovery time . We studied the safety and effectiveness of Essure pbc , a minimally invasive , transcervically placed micro‐insert that occludes the Fallopian tubes , result ing in permanent female contraception BACKGROUND Hysteroscopic permanent tubal sterilization has recently been introduced , result ing in a non-invasive , safe and effective technique . The aim of this study was to assess the feasibility of outpatient hysteroscopic tubal sterilization using a nitinol-dacron intratubal device without anaesthesia and to assess patient procedure compliance . MATERIAL S AND METHODS We untertook a prospect i ve study of 36 consecutive cases of outpatient hysteroscopic tubal sterilization using a nitinol-dacron intratubal device without anaesthesia . Tubal sterilization was performed by placing the device with the aid of a 5.2-mm continuous-flow operative hysteroscope . At the end of the procedure women were asked to rate the pain experienced on a visual analogue scale ( VAS ) ( 0 , no discomfort to 100 , severe discomfort ) . Successful device placement was assessed after 3 months by hysterosalpingography and diagnostic hysteroscopy . RESULTS Successful bilateral placement was obtained in 32 patients ( 88.9 % ) ; in one ( 2.8 % ) the placement was monolateral ; and in three ( 8.3 % ) the procedure failed . Mean operating time was 8.6 + /- 5.3 min . A mean VAS of 36.1 + /- 23.9 was recorded . CONCLUSIONS The nitinol-dacron intratubal device is safe , appears to be effective long-term , is non-invasive and can be used in the outpatient setting without anaesthesia . Low-level discomfort was experienced by the patients . Limitations of its use include that it is not effective immediately , it is irreversible , it requires special equipment and training , and it is difficult to use in cases of uterine anomalies . We conclude that this method may be offered to all woman asking for permanent tubal sterilization , particularly those who refuse or have contraindications for anaesthesia OBJECTIVE To assess pain and patient satisfaction with office-based hysteroscopic sterilization . DESIGN This prospect i ve , observational study was design ed to assess patient pain perception and satisfaction with office-based hysteroscopic sterilization using the Essure device ( Conceptus , Mountain View , CA ) . SETTING Faculty practice office at an inner-city urban medical center . PATIENT(S ) Women seeking hysteroscopic sterilization . INTERVENTION(S ) Office hysteroscopic sterilization under local anesthesia . MAIN OUTCOME MEASURE(S ) Pain assessed at the time of the procedure by a 0 - 10 visual scale and satisfaction by a 1 - 5 scale . RESULT ( S ) From June 2003 to June 2006 , 209 patients were recruited . The mean scores for average procedural pain , most procedural pain , and average menstrual pain were 2.6+/-2.1 , 3.3+/-2.5 , and 3.6+/-2.6 , respectively . St and ardized pain scores revealed that 149 subjects ( 70 % ) experienced average pain that was less than or equal to the pain experienced with their menses . Mean satisfaction rating for the procedure was 4.7+/-0.71 . CONCLUSION ( S ) Office-based hysteroscopic sterilization performed with local anesthesia alone is well tolerated , and patients are satisfied with this method for permanent sterilization |
13,309 | 22,821,333 | Proprioceptive exercises are efficacious in the treatment of knee OA .
There is some evidence to indicate the effectiveness of proprioceptive exercises compared to general strengthening exercises in functional outcomes | Osteoarthritis ( OA ) is a leading cause of functional impairment and pain .
Proprioceptive defects may be associated with the onset and progression of OA of the knee .
The purpose of this study was to determine the effectiveness of proprioceptive exercises for knee OA using meta- analysis . | Background Impairment-based exercise programs have yielded only small to moderate benefits in reducing pain and improving function in people with knee osteoarthritis ( OA ) . It has previously been proposed that adding agility and perturbation training to exercise programs for people with knee OA may improve treatment effects for pain and function . Objective The purpose of this study was to examine the effectiveness of adding agility and perturbation techniques to st and ard exercise therapy compared with the st and ard exercise program alone for people with knee OA . Design This was a single-blinded r and omized controlled trial . Setting The study was conducted in the outpatient physical therapy clinic of a large , university-based health center . Participants One hundred eighty-three people with knee OA ( 122 women , 61 men ) participated . Interventions Participants were r and omly assigned to either a group that received agility and perturbation training with st and ard exercise therapy or a group that received only the st and ard exercise program . Measurements The outcome measures were self-reported knee pain and function , self-reported knee instability , a performance-based measure of function , and global rating of change . Results Although both groups exhibited improvement in self-reported function and in the global rating of change at the 2- , 6- , and 12-month follow-up periods , there were no differences between groups on these outcomes . There was no reduction in knee pain or improvement in performance-based function in either group . Limitations It is possible that more-intense application of the interventions or application of the interventions to participants with knee OA who were at greater risk for falling may have yielded additive effects of the agility and perturbation training approach . Conclusions Both intervention groups exhibited improvement in self-reported function and the global rating of change . Our results , however , did not support an additive effect of agility and perturbation training with st and ard exercise therapy in our sample of individuals with knee OA . Further study is needed to determine whether there are subgroups of individuals who might achieve an added benefit with this approach STUDY OBJECTIVES To underst and reasons for compliance and non-compliance with a home based exercise regimen by patients with osteoarthritis of the knee . DESIGN A qualitative study , nested within a r and omised controlled trial , examining the effectiveness of physiotherapy in reducing pain and increasing mobility in knee osteoarthritis . In the intervention arm , participants undertook a series of simple exercises and repositioning of the kneecap using tape . In depth interviews were conducted with a subset of participants in the intervention arm using open ended questions , guided by a topic schedule , to encourage patients to describe their experiences and reflect on why they did or did not comply with the physiotherapy . Interviews were audiotaped , fully transcribed and analysed thematically according to the method of constant comparison . A model explaining factors influencing compliance was developed . SETTING Patients were interviewed at home . The study was nested within a pragmatic r and omised controlled trial . PARTICIPANTS Twenty participants in the intervention arm of the r and omised trial were interviewed three months after they had completed the physiotherapy programme . Eight were interviewed again one year later . MAIN RESULTS Initial compliance was high because of loyalty to the physiotherapist . Reasoning underpinning continued compliance was more complex , involving willingness and ability to accommo date exercises within everyday life , the perceived severity of symptoms , attitudes towards arthritis and comorbidity and previous experiences of osteoarthritis . A necessary precondition for continued compliance was the perception that the physiotherapy was effective in ameliorating unpleasant symptoms . CONCLUSIONS Non-compliance with physiotherapy , as with drug therapies , is common . From the patient 's perspective , decisions about whether or not to comply are rational but often can not be predicted by therapists or research ers . Ultimately , this study suggests that health professionals need to underst and reasons for non-compliance if they are to provide supportive care and trialists should include qualitative research within trials whenever levels of compliance may have an impact on the effectiveness of the intervention In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials Background : In patients with knee osteoarthritis ( OA ) , there is a prominent loss in proprioception and kinesthesia sensation compared with control subjects of the same age and gender . Objectives : The aim of this study is the investigation of short-term clinical effects of kinesthesia and balance exercises in patients with knee OA . Methods : This 8-week study was conducted on 66 female patients with knee OA who were r and omized into 2 groups . The first group received kinesthesia and balance exercises ( such as retrowalking , walking on their toes , leaning to the sides , balance board exercises , minitrampoline exercises , plyometric exercises , and so on ) in addition to strengthening exercises . The second group received only strengthening exercises . Results : Statistically significant improvements were observed postexercise for both groups with respect to baseline for WOMAC , SF-36 Form , times for performing activities of daily living , isokinetic quadriceps muscle strength , and proprioceptive sensation levels . In the first group with kinesthesia training , compared with the second group , significantly greater improvements were obtained in all the subparameters that measure functional status ( WOMAC – physical function value , SF-36 Form [ physical function , role limitations –physical and vitality – energy or fatigue variables ] , 10 stairs climbing , and 10-m walking times ) and in isokinetic muscle strength at high angular velocities ( P < 0.05 ) . The absolute angular error percentage ( to assess proprioceptive accuracy ) was significantly improved postexercise in both groups . There were no differences between the groups . Conclusions : Additive positive effects of kinesthesia and balance exercises in knee OA have been demonstrated . Used in clinical applications , they should be able to increase the functional capacities of patients . Long-term studies about efficacy and cost-effectivity of these exercises are needed QUESTION Is four weeks of home-based balance training more effective than four weeks of home-based strength training at decreasing pain in patients with knee osteoarthritis ? DESIGN R and omised trial with concealed allocation and assessor blinding . PARTICIPANTS 48 community volunteers with knee osteoarthritis . INTERVENTION Two groups undertook home-based exercise programs : one group performed balance training and the other performed strength training . Participants performed 30 repetitions/leg/day , 5 days/week for four weeks . OUTCOME MEASURES The Knee injury and Osteoarthritis Outcome Score was used to evaluate pain , which was the primary outcome . Secondary outcomes were the other subscales of the Knee injury and Osteoarthritis Outcome Score ( other symptoms , function in daily living , function in sport and recreation , knee-related quality of life ) , strength , and mobility . RESULTS There was no significant difference between groups for pain ( mean difference -3 points out of 100 , 95 % CI -10 to 5 ) . The only between-group difference in the Knee injury and Osteoarthritis Outcome Score was in knee-related quality of life , where the strength group improved 17 points out of 100 ( 95 % CI 5 to 28 ) more than the balance group . There was no significant difference between groups for strength . The only between-group difference in mobility was in the time taken to walk downstairs , where the strength group improved by 2 s ( 95 % CI 0 to 3 ) more than the balance group . CONCLUSION There was no difference in pain between home-based strength training and home-based balance training in patients with knee osteoarthritis . TRIAL REGISTRATION NCT 00687726 Abstract Background Self-management has become increasingly popular in the management of chronic diseases . There are many different self-management models . Meta analyses of arthritis self-management have concluded that it is difficult to recommend any one program in preference to another due to inconsistencies in the study design s used to evaluate different programs . The Stanford Arthritis Self-Management Program ( ASMP ) , most commonly delivered by trained lay leaders , is a generic program widely used for people with rheumatological disorders . We have developed a more specific program expressly for people with osteoarthritis of the knee ( OAKP ) . It includes information design ed to be delivered by health professionals and results in improvements in pain , function and quality of life . Aim : To determine whether , for people with osteoarthritis ( OA ) of the knee , the OAKP implemented in a primary health care setting can achieve and maintain clinical ly meaningful improvements in more participants than ASMP delivered in the same environment . Methods / Design The effectiveness of the programs will be compared in a single-blind r and omized study . Participants : 146 participants with established OA knee will be recruited . Volunteers with coexistent inflammatory joint disease or serious co-morbidities will be excluded . Interventions : Participants will be r and omised into either OAKP or ASMP groups and followed for 6 months . Measurements : Assessment s will be immediately before and after the intervention and at 6 months . Primary outcome measures will be WOMAC and SF-36 question naires and a VAS for pain . Secondary outcomes will include balance , tested using a timed single leg balance test and a timed step test and self-efficacy . Data will be analysed using repeated measures ANOVA . Discussion With an aging population the health care costs for people with arthritis are ever increasing . Although cost analysis is beyond the scope of this study , it is reasonable to expect that costs will be greater when health professionals deliver self-management programs as opposed to lay leaders . Consequently it is critical to examine the relative effectiveness of the primary care management strategies available for OA.Trial Registration This study is registered with the Australian New Zeal and Clinical Trials Registry : Objective : To investigate whether alleviation of knee pain influences quadriceps function , proprioceptive acuity , and postural stability in patients with knee osteoarthritis ( OA ) . Methods : A crossover , within-subject , double blind study design involving 68 subjects with painful knee OA . Each subject received an intra-articular injection into one or both knees ( both if symptomatic ) of either 5 ml 0.5 % bupivacaine or 5 ml 0.9 % saline . Two weeks later they received an injection of the alternative agent . Subjects and observer were unaware of the order of injection , which was r and omly assigned . Knee pain ( 100 mm visual analogue scale ) , static postural sway , knee proprioceptive acuity , maximum voluntary contraction ( MVC ) , and percentage activation of the quadriceps were assessed immediately before and one hour after each injection . Results : Significant pain reduction was achieved one hour post-bupivacaine ( mean difference as a percentage change 56.85 , 95 % CI 31.01 to 73.65 ; p<0.001 ) and post-saline ( mean difference as a percentage change 41.94 , 95 % CI 11.57 to 76.66 ; p < 0.001 ) , with no significant difference between the two . Both MVC and activation increased significantly post-bupivacaine ( mean percentage differences 18.83 , 95 % CI −31.79 to −0.26 , and −11.90 , 95 % CI −39.53 to 2.97 , respectively ; both p<0.001 ) and post-saline ( mean percentage differences −7.64 , 95 % CI −21.96 to 4.73 , and −10.71 , 95 % CI −25.19 to 2.60 respectively ; both p<0.001 ) . Proprioception worsened after bupivacaine ( mean percentage difference −28.15 % , 95 % CI −83.47 to 19.74 ; p=0.009 ) , but there was no effect on postural sway ; saline injection had no effects . There was no order effect , and comparison of median percentage changes showed no significant differences between injections for change in MVC , activation , proprioception , or sway . Conclusion : Reduction in knee pain through either peripheral ( local anaesthetic ) or central ( placebo ) mechanisms result ed in increased MVC . This increase , however , did not result in improvements in proprioception or static postural stability , suggesting that other mechanisms play a part in these functions , at least in this acute model INTRODUCTION Physiotherapy is one of the most important components of therapy for osteoarthritis of the knee . The objective of this prospect i ve case series was to assess the efficiency of a guidance manual for patients with osteoarthritis of the knee in relation to pain , range of movement , muscle strength and function , active goniometry , manual strength test and function . METHODS Thirty-eight adults with osteoarthritis of the knee ( > or= 45 years old ) who were referred to the physiotherapy service at the university hospital ( Santa Casa de Misericórdia de São Paulo ) were studied . Patients received guidance for the practice of specific physical exercises and a manual with instructions on how to perform the exercises at home . They were evaluated for pain , range of movement , muscle strength and function . These evaluations were performed before they received the manual and three months later . Patients were seen monthly regarding improvements in their exercising abilities . RESULTS The program was effective for improving muscle strength , controlling pain , maintaining range of movement of the knee joint , and reducing functional incapacity . DISCUSSION A review of the literature showed that there are numerous clinical benefits to the regular practice of physical therapy exercises by patients with osteoarthritis of the knee(s ) in a program with appropriate guidance . This study shows that this guidance can be attained at home with the use of a proper manual . CONCLUSIONS Even when performed at home without constant supervision , the use of the printed manual for orientation makes the exercises for osteoarthritis of the knee beneficial Abstract . Osteoarthritis ( OA ) of the knee is a very common rheumatological disease , and there are various treatment modalities for it . The aim of this study was to investigate the effects of home-based exercise and walking programs in the treatment of OA . A total of 90 patients with knee osteoarthritis were included . Their ages ranged between 48 and 71 years . The patients were separated into three groups . None of them had practice d a daily simple exercise program during the previous year . Group 1 ( n=30 ) was given a home-based exercise program . Group 2 ( n=30 ) had regular a walking program three times per week , starting with 10-min duration . Group 3 ( n=30 ) was accepted as the control group . Patients were assessed according to pain , functional capacity , and quality of life parameters . Pain was evaluated by the Western Ontario McMaster osteoarthritis index ( WOMAC ) of pain score and visual analogue scale ( VAS ) . Functional capacity was measured by WOMAC physical function index . Quality of life was assessed by the Nottingham Health Profile question naire ( NHP ) . All groups continued the program for 3 months . At the end of the therapy , the patients were called and 81 were accepted to come to the hospital . Although WOMAC pain and physical functional scores and VAS scores were statistically lower in both groups than in the control group ( P<0.001 ) , the difference between groups 1 and 2 was not statistically significant ( P>0.05 ) . But the result of the NHP showed a statistically significant improvement in the walking group when compared to the home-based exercise and control groups ( P<0.001 ) . As a result , we conclude that a simple home-based exercise therapy and a regular walking program are effective in treating the symptoms of OA OBJECTIVES This study aim ed to establish the effects of hospital- and home-based proprioceptive and strengthening exercise programs on proprioception , pain , and functional status in patients with knee osteoarthritis ( OA ) . METHODS Sixty patients with bilateral knee OA were r and omly allocated into either a home-based or hospital-based exercise program . Hospital-based exercise group ( n=30 , mean age 50.23±9.07 years ) received functional training program with proprioceptive ability , ice , and home exercises . Home-based exercise group ( n=30 , mean age 54.4±7.9 years ) had a program of ice and home exercises . Treatment programs was conducted 5 days per week for 6 weeks ( 30 sessions ) . Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , Monitorized Functional Squat System-Proprioceptive Test ( MFSS ) , timed performance test ( TUG ) , and visual analogue scale ( VAS ) for the intensity of pain were used to quantify the variables . RESULTS Both groups demonstrated significant improvement when pre- and post-treatment results were compared for pain intensity , WOMAC , and TUG test scores ( p<0.05 ) . No statistically significant improvement was found in proprioception of the home-based group ( p>0.05 ) . Hospital-based group demonstrated significantly greater improvement in MFSS , TUG test , and VAS in activity when compared with the home-based group ( p<0.05 ) . CONCLUSION Both hospital- and home-based exercise programs decreased joint symptoms and improved function in patients with knee OA In 30 healthy volunteers with clinical ly inconspicuous knee joints and nine patients with posttraumatic recurrent patella dislocation , the proprioceptive abilities of the knee joint were evaluated by an angle reproduction test . The results of the control goup showed no gender-or dominant-specific difference . The patient group showed a significant deterioration of proprioceptive capability in the injured knee joint . Even in the contralateral , uninjured knee joint , the angle reproduction test result was significantly reduced compared with the control group . After applying an elastic knee b and age , the control group and the patients with patella dislocation showed a significant improvement of the proprioceptive capability Within the context of a double blind r and omized controlled parallel trial of 2 nonsteroidal antiinflammatory drugs , we vali date d WOMAC , a new multidimensional , self-administered health status instrument for patients with osteoarthritis of the hip or knee . The pain , stiffness and physical function subscales fulfil conventional criteria for face , content and construct validity , reliability , responsiveness and relative efficiency . WOMAC is a disease-specific purpose built high performance instrument for evaluative research in osteoarthritis clinical trials Objective : To investigate the effects of a sensorimotor training programme in osteoarthritic patients . Design : R and omized , single-blind , controlled trial . Setting : Kinesiology laboratory at School of Physical Therapy . Participants : A total of 60 patients were r and omly assigned to the training group and the control group . Only 29 patients ( training group , 15 ; control group , 14 ) completed the study . Intervention : The training group underwent a sensorimotor training programme using a sling suspension system complemented by a routine physical therapy . The control group underwent a routine physical therapy . Main measures : Active joint repositioning , functional testings , and self-reported function with the Western Ontario & McMaster Universities Arthritis Index before and after the eight-week intervention . Results : There were significant differences between the two groups with respect to the improvement in proprioception as measured by active joint repositioning ( the changes in the absolute error were 1.9± 1.7 ° , training group versus 0.1 ± 2.8 ° , control group ( P<0.05 ) , and in self-reported functional difficulty ( 33.2 ±35.1 , training group versus 8.0± 10.2 , control group ; P<0.05 ) ) . There was no significant difference between the two groups in other outcomes . Conclusion : A sensorimotor training using a sling suspension system improved the patients ' proprioception in the knee joints and their self-reported function . Thus , these exercises may serve as an exercise programme for patients with knee osteoarthritis STUDY DESIGN R and omized clinical trial . OBJECTIVE To investigate the clinical and functional efficacy of 2 different non-weight-bearing exercise regimens , proprioceptive training ( PrT ) versus strength training ( ST ) , for patients with knee osteoarthritis ( OA ) . BACKGROUND Both strength and proprioceptive training are important interventions for individuals with knee OA . The benefits of weight-bearing exercises are generally recognized in the clinical setting . However , exercising in a st and ing or weight-bearing position may aggravate symptoms in patients with knee OA . METHODS AND MEASURES One hundred eight patients were r and omly assigned to the PrT , ST , or no exercise ( control ) group for an 8-week intervention . Both the PrT and ST interventions consisted of non-weight-bearing exercises . Western Ontario and McMaster Universities Osteoarthritis Index-pain ( WOMAC-pain ) and -function scores , walking time on 3 different terrains , knee strength , and absolute knee reposition error were assessed before and after intervention . Data were analyzed using mixed-model ANOVAs . RESULTS Both PrT and ST significantly improved WOMAC-pain and -function score after intervention ( P<.008 ) . The improvement secondary to ST in the WOMAC-function scores ( 17.2 points ) and for knee extension strength ( 10.3 - 14.9 Nm ) was greater than the minimally clinical ly important difference for these measurements . The PrT group demonstrated greater improvement in walking time on a spongy surface and knee reposition error than the other 2 groups . No improvements were apparent in the control group . CONCLUSION Both types of non-weight-bearing exercises ( PrT and ST ) significantly improved outcomes in this study . PrT led to greater improvements in proprioceptive function , while ST result ed in a greater increase in knee extensor muscle strength Hazneci B , Yildiz Y , Sekir U , Aydin T , Kalyon TA : Efficacy of isokinetic exercise on joint position sense and muscle strength in patellofemoral pain syndrome . Am J Phys Med Rehabil 2005;84:521–527 . Objective : The objective of this study was to demonstrate the impairment of knee joint position sense in individuals with patellofemoral pain syndrome and investigate the effects of isokinetic exercise on knee joint position sense and muscle strength . Design : A total of 24 male patients complaining of anterior knee pain caused by overexertion and 24 male healthy individuals without symptoms were included for this investigation . Isokinetic exercise protocol was carried out at angular velocities of 60 degrees/sec and 180 degrees/sec . These sessions were repeated three times per week and lasted for 6 wks . At the beginning and after 6 wks of knee passive joint position sense , quadriceps and hamstring muscle strength and pain assessment s were performed . Results : After the isokinetic exercise , flexion peak torque ( P < 0.05 ) , extension peak torque ( P < 0.01 ) , flexion total work ( P < 0.001 ) , extension total work ( P < 0.001 ) , passive reproduction of knee joint position sense for 40 degrees of flexion ( P < 0.05 ) and 50 degrees of extension ( P < 0.01 ) , and pain score ( P < 0.001 ) improved significantly in the patellofemoral pain syndrome group . Conclusion : Isokinetic exercises have positive effects on passive position sense of knee joints , increasing the muscular strength and work capacity . These findings show that using the present isokinetic exercise in rehabilitation protocol s of patients with patellofemoral pain syndrome not only improves the knee joint stabilization but also the proprioceptive acuity 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 . Quantification of dynamic balance is often necessary to assess a patient 's level of injury or ability to function in order to initiate an appropriate plan of care . Some therapists use the star-excursion test in an attempt to quantify dynamic balance . This test requires the patient to balance on one leg while reaching with the other leg . For the purpose of this study , the reach was performed in four directions . No previous research ers have attempted to evaluate the reliability of this test . Twenty healthy subjects between the ages of 18 and 35 years participated in this study . During two testing sessions , each subject was required to perform five reaching trials in four directions . Reliability estimates , calculated using the intraclass correlation coefficient ( 2 , 1 ) , ranged from 0.67 to 0.87 . Six duplicate practice sessions were suggested to increase this range above 0.86 . Task complexity may account for the moderate reliability estimates . Subjects should engage in a learning period before being evaluated on the star-excursion test OBJECTIVE To investigate whether weight-bearing ( WB ) exercise enhances functional capacity to a greater extent than nonweight-bearing ( NWB ) exercise in participants with knee osteoarthritis . DESIGN R and omized controlled trial . SETTING Kinesiology laboratory . PARTICIPANTS Participants ( N=106 ) were r and omly assigned to WB exercise , NWB exercise , or a control group ( no exercise ) . INTERVENTION WB exercise and NWB exercise groups underwent an 8-week knee extension-flexion exercise program . MAIN OUTCOME MEASURES Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) function scale , walking speed , muscle torque , and knee reposition error were assessed before and after intervention . RESULTS Equally significant improvements were apparent for all outcomes after WB exercise and NWB exercise , except for reposition error , for which improvement was greater in the WB exercise group . In contrast , there were no improvements in the control group . CONCLUSIONS Simple knee flexion and extension exercises ( WB and NWB ) performed over 8 weeks result ed in significant improvement in the WOMAC function scale and knee strength compared with the control group . NWB exercise alone may be sufficient enough to improve function and muscle strength . The additional benefit of WB exercise was improved position sense , which may enhance complex walking tasks ( walking on figure of 8 route and spongy surface ) |
13,310 | 23,134,885 | Protein supplementation increases muscle mass and strength gains during prolonged resistance-type exercise training in both younger and older subjects | BACKGROUND Protein ingestion after a single bout of resistance-type exercise stimulates net muscle protein accretion during acute postexercise recovery .
Consequently , it is generally accepted that protein supplementation is required to maximize the adaptive response of the skeletal muscle to prolonged resistance-type exercise training . | To assess age and gender differences in muscle strength , isometric , concentric ( Con ) , and eccentric ( Ecc ) peak torque was measured in the knee extensors at a slow ( 0.52 rad/s ) and fast ( 3.14 rad/s ) velocity in 654 subjects ( 346 men and 308 women , aged 20 - 93 yr ) from the Baltimore Longitudinal Study of Aging . Regression analysis revealed significant ( P < 0.001 ) age-related reductions in Con and Ecc peak torque for men and women at both velocities , but no differences were observed between the gender groups or velocities . Age explained losses in Con better than Ecc peak torque , accounting for 30 % ( Con ) vs. 19 % ( Ecc ) of the variance in men and 28 % ( Con ) vs. 11 % ( Ecc ) in women . To assess age and gender differences in the ability to store and utilize elastic energy , the stretch-shortening cycle was determined in a subset of subjects ( n = 47 ) . The older women ( mean age = 70 yr ) showed a significantly greater enhancement in the stretch-shortening cycle , compared with men of similar age ( P < 0.01 ) and compared with younger men and women ( each P < 0.05 ) . Both men and women showed significant declines in muscle quality for Con peak torque ( P < 0.01 ) , but no gender differences were observed . Only the men showed a significant decline in muscle quality ( P < 0.001 ) for Ecc peak torque . Thus both men and women experience age-related losses in isometric , Con , and Ecc knee extensor peak torque ; however , age accounted for less of the variance in Ecc peak torque in women , and women tend to better preserve muscle quality with age for Ecc peak torque . In addition , older women have an enhanced capacity to store and utilize elastic energy compared with similarly aged men as well as with younger women and men We recently showed that resistance exercise and ingestion of essential amino acids with carbohydrate ( EAA+CHO ) can independently stimulate mammalian target of rapamycin ( mTOR ) signaling and muscle protein synthesis in humans . Providing an EAA+CHO solution postexercise can further increase muscle protein synthesis . Therefore , we hypothesized that enhanced mTOR signaling might be responsible for the greater muscle protein synthesis when leucine-enriched EAA+CHOs are ingested during postexercise recovery . Sixteen male subjects were r and omized to one of two groups ( control or EAA+CHO ) . The EAA+CHO group ingested the nutrient solution 1 h after resistance exercise . mTOR signaling was assessed by immunoblotting from repeated muscle biopsy sample s. Mixed muscle fractional synthetic rate ( FSR ) was measured using stable isotope techniques . Muscle protein synthesis and 4E-BP1 phosphorylation during exercise were significantly reduced ( P < 0.05 ) . Postexercise FSR was elevated above baseline in both groups at 1 h but was even further elevated in the EAA+CHO group at 2 h postexercise ( P < 0.05 ) . Increased FSR was associated with enhanced phosphorylation of mTOR and S6K1 ( P < 0.05 ) . Akt phosphorylation was elevated at 1 h and returned to baseline by 2 h in the control group , but it remained elevated in the EAA+CHO group ( P < 0.05 ) . 4E-BP1 phosphorylation returned to baseline during recovery in control but became elevated when EAA+CHO was ingested ( P < 0.05 ) . eEF2 phosphorylation decreased at 1 and 2 h postexercise to a similar extent in both groups ( P < 0.05 ) . Our data suggest that enhanced activation of the mTOR signaling pathway is playing a role in the greater synthesis of muscle proteins when resistance exercise is followed by EAA+CHO ingestion Systematic review s ( SRs ) are an increasingly popular evidence -based tool and are often used to answer complex research questions across many different research domains . Early SR methodology was advanced by social scientists , and the term meta- analysis was coined by a social scientist who also conducted research in psychology . SRs have recently become popular in healthcare and are likely to be beneficial in any field . The aim of this report is to highlight issues in SR conduct with a focus on the field of nutrition and to make recommendations on improving SR conduct in this area . Development of the research question is probably the most important step in conducting an SR . The 4 main components of an answerable question are 1 ) the patient , population , or problem ; 2 ) the intervention , independent variable , or exposure ; 3 ) the comparators ; and 4 ) the dependent variables or outcomes of interest . The question will be used to determine the optimal methods for conducting the SR . SRs often include study design s beyond r and omized trials and do not always include a meta- analysis of the results . Other topics explored include underst and ing and interpreting discordant review s and the importance of reporting tools [ eg , QUality Of Reporting Of Meta-analyses ( QUOROM Statement ) or CONsoli date d St and ards Of Reporting of Trials ( CONSORT Statement ) ] . Recommendations are then provided , such as developing a capacity-building program , search ing the primary literature for research gaps , and extending reporting tools such as the QUOROM Statement to the field of nutrition We examined the response of net muscle protein synthesis to ingestion of amino acids after a bout of resistance exercise . A primed , constant infusion ofl- [ ring-2H5]phenylalanine was used to measure net muscle protein balance in three male and three female volunteers on three occasions . Subjects consumed in r and om order 1 liter of 1 ) a mixed amino acid ( 40 g ) solution ( MAA ) , 2 ) an essential amino acid ( 40 g ) solution ( EAA ) , and 3 ) a placebo solution ( PLA ) . Arterial amino acid concentrations increased ∼150 - 640 % above baseline during ingestion of MAA and EAA . Net muscle protein balance was significantly increased from negative during PLA ingestion ( -50 ± 23 nmol ⋅ min-1 ⋅ 100 ml leg volume-1 ) to positive during MAA ingestion ( 17 ± 13 nmol ⋅ min-1 ⋅ 100 ml leg volume-1 ) and EAA ( 29 ± 14 nmol ⋅ min-1 ⋅ 100 ml leg volume-1 ; P < 0.05 ) . Because net balance was similar for MAA and EAA , it does not appear necessary to include nonessential amino acids in a formulation design ed to elicit an anabolic response from muscle after exercise . We concluded that ingestion of oral essential amino acids results in a change from net muscle protein degradation to net muscle protein synthesis after heavy resistance exercise in humans similar to that seen when the amino acids were infused BACKGROUND The anabolic effect of resistance exercise is enhanced by the provision of dietary protein . OBJECTIVES We aim ed to determine the ingested protein dose response of muscle ( MPS ) and albumin protein synthesis ( APS ) after resistance exercise . In addition , we measured the phosphorylation of c and i date signaling proteins thought to regulate acute changes in MPS . DESIGN Six healthy young men reported to the laboratory on 5 separate occasions to perform an intense bout of leg-based resistance exercise . After exercise , participants consumed , in a r and omized order , drinks containing 0 , 5 , 10 , 20 , or 40 g whole egg protein . Protein synthesis and whole-body leucine oxidation were measured over 4 h after exercise by a primed constant infusion of [1-(13)C]leucine . RESULTS MPS displayed a dose response to dietary protein ingestion and was maximally stimulated at 20 g. The phosphorylation of ribosomal protein S6 kinase ( Thr(389 ) ) , ribosomal protein S6 ( Ser(240/244 ) ) , and the epsilon-subunit of eukaryotic initiation factor 2B ( Ser(539 ) ) were unaffected by protein ingestion . APS increased in a dose-dependent manner and also reached a plateau at 20 g ingested protein . Leucine oxidation was significantly increased after 20 and 40 g protein were ingested . CONCLUSIONS Ingestion of 20 g intact protein is sufficient to maximally stimulate MPS and APS after resistance exercise . Phosphorylation of c and i date signaling proteins was not enhanced with any dose of protein ingested , which suggested that the stimulation of MPS after resistance exercise may be related to amino acid availability . Finally , dietary protein consumed after exercise in excess of the rate at which it can be incorporated into tissue protein stimulates irreversible oxidation Our purpose was to assess muscular adaptations during 6 weeks of resistance training in 36 males r and omly assigned to supplementation with whey protein ( W ; 1.2 g/kg/day ) , whey protein and creatine monohydrate ( WC ; 0.1 g/kg/day ) , or placebo ( P ; 1.2 g/kg/day maltodextrin ) . Measures included lean tissue mass by dual energy x-ray absorptiometry , bench press and squat strength ( 1-repetition maximum ) , and knee extension/flexion peak torque . Lean tissue mass increased to a greater extent with training in WC compared to the other groups , and in the W compared to the P group ( p < .05 ) . Bench press strength increased to a greater extent for WC compared to W and P ( p < .05 ) . Knee extension peak torque increased with training for WC and W ( p < .05 ) , but not for P. All other measures increased to a similar extent across groups . Continued training without supplementation for an additional 6 weeks result ed in maintenance of strength and lean tissue mass in all groups . Males that supplemented with whey protein while resistance training demonstrated greater improvement in knee extension peak torque and lean tissue mass than males engaged in training alone . Males that supplemented with a combination of whey protein and creatine had greater increases in lean tissue mass and bench press than those who supplemented with only whey protein or placebo . However , not all strength measures were improved with supplementation , since subjects who supplemented with creatine and /or whey protein had similar increases in squat strength and knee flexion peak torque compared to subjects who received placebo The purpose of this study was to determine the effects of 6 wk of essential amino acid ( EAA ) supplementation on body composition and exercise performance in untrained women ( n = 21 ) . Subjects were r and omly assigned to a placebo ( cellulose ) or an EAA ( average daily dose of 18.3 g of EAAs in pill form ) group . Each subject participated in aerobic and heavy-resistance training three times per week . Body composition was assessed via dual x-ray absorptiometry analysis . Muscular endurance was determined via treadmill time to exhaustion , and strength was assessed by the total amount of weight lifted for one set to exhaustion at an estimated 12 repetitions maximum . No changes occurred in either group for body weight , lean body mass , fat mass , or bone mineral content . Treadmill time to exhaustion ( TTE ) improved significantly ( P < 0.05 ) in the EAA group ( mean + /- SD ; pre-TTE = 13.15 + /- 3.67 min , post-TTE = 14 . 73 + /- 4.26 min ) , whereas the placebo group did not change significantly . The total weight lifted at the subject 's maximum 12 repetitions did not significantly change in either group . In previously untrained individuals , the ingestion of EAAs combined with aerobic and heavy-resistance training for 6 wk did not have a significant effect on body composition or muscular strength ; however , aerobic muscular endurance increased significantly This study was design ed to determine the response of muscle protein to the bolus ingestion of a drink containing essential amino acids and carbohydrate after resistance exercise . Six subjects ( 3 men , 3 women ) r and omly consumed a treatment drink ( 6 g essential amino acids , 35 g sucrose ) or a flavored placebo drink 1 h or 3 h after a bout of resistance exercise on two separate occasions . We used a three-compartment model for determination of leg muscle protein kinetics . The model involves the infusion of ring-(2)H(5)-phenylalanine , femoral arterial and venous blood sampling , and muscle biopsies . Phenylalanine net balance and muscle protein synthesis were significantly increased above the predrink and corresponding placebo value ( P < 0.05 ) when the drink was taken 1 or 3 h after exercise but not when the placebo was ingested at 1 or 3 h. The response to the amino acid-carbohydrate drink produced similar anabolic responses at 1 and 3 h. Muscle protein breakdown did not change in response to the drink . We conclude that essential amino acids with carbohydrates stimulate muscle protein anabolism by increasing muscle protein synthesis when ingested 1 or 3 h after resistance exercise The purpose of this study was to examine the effects of a drink containing creatine , amino acids , and protein vs. a carbohydrate placebo on body composition , strength , muscular endurance , and anaerobic performance before and after 10 weeks of resistance training . Fifty-one men ( mean ± SD ; age : 21.8 ± 2.9 years ) were r and omly assigned to either the test drink ( TEST ; n = 23 ) or the placebo ( PLAC ; n = 28 ) and performed two 30-second Win-gate Anaerobic Tests for determination of peak power ( PP ) and mean power ( MP ) , were weighed underwater for percent body fat ( % fat ) and fat-free mass ( FFM ) , and were tested for 1 repetition maximum ( 1RM ) dynamic constant external resistance strength and muscular endurance ( END ; number of repetitions performed with 80 % of 1RM ) on the bilateral leg extension ( LE ) and free-weight bench press ( BP ) exercises . The testing was conducted before ( PRE ) and after ( POST ) 10 weeks of resistance training ( 3 sets of 10 repetitions with 80 % of the subject 's 1RM performed 3 times per week ) on the LE and BP exercises . Body weight , FFM , LE 1RM , LE END , BP 1RM , and BP END increased ( p < 0.05 ) , whereas % fat decreased ( p < 0.05 ) from PRE to POST for both the TEST and PLAC groups . Peak power and MP , however , increased for the TEST group , but not for the PLAC group . These results suggested that the creatine- , amino acid– , and protein-containing drink provided no additional benefits when compared with carbohydrates alone for eliciting changes in body composition , strength , and muscular endurance after a 10-week resistance training period . The TEST drink was , however , more effective than carbohydrates alone for improving anaerobic power production PURPOSE We aim ed to determine whether women consuming fat-free milk versus isoenergetic carbohydrate after resistance exercise would see augmented gains in lean mass and reductions in fat mass similar to what we observed in young men . METHODS Young women were r and omized to drink either fat-free milk ( MILK : n = 10 ; age ( mean + /- SD ) = 23.2 + /- 2.8 yr ; BMI = 26.2 + /- 4.2 kg x m(-2 ) ) or isoenergetic carbohydrate ( CON : n = 10 ; age = 22.4 + /- 2.4 yr ; BMI = 25.2 + /- 3.8 kg x m(-2 ) ) immediately after and 1 h after exercise ( 2 x 500 mL ) . Subjects exercised 5 d x wk(-1 ) for 12 wk . Body composition changes were measured by dual-energy x-ray absorptiometry , and subjects ' strength and fasting blood were measured before and after training . RESULTS CON gained weight after training ( CON : + 0.86 + /- 0.4 kg , P < 0.05 ; MILK : + 0.50 + /- 0.4 kg , P = 0.29 ) . Lean mass increased with training in both groups ( P < 0.01 ) , with a greater net gain in MILK versus CON ( 1.9 + /- 0.2 vs 1.1 + /- 0.2 kg , respectively , P < 0.01 ) . Fat mass decreased with training in MILK only ( -1.6 + /- 0.4 kg , P < 0.01 ; CON : -0.3 + /- 0.3 kg , P = 0.41 ) . Isotonic strength increased more in MILK than CON ( P < 0.05 ) for some exercises . Serum 25-hydroxyvitamin D increased in both groups but to a greater extent in MILK than CON ( + 6.5 + /- 1.1 vs + 2.8 + /- 1.3 nM , respectively , P < 0.05 ) , and parathyroid hormone decreased only in MILK ( -1.2 + /- 0.2 pM , P < 0.01 ) . CONCLUSIONS Heavy , whole-body resistance exercise with the consumption of milk versus carbohydrate in the early postexercise period result ed in greater muscle mass accretion , strength gains , fat mass loss , and a possible reduction in bone turnover in women after 12 wk . Our results , similar to those in men , highlight that milk is an effective drink to support favorable body composition changes in women with resistance training Summary .This study examined 10 wks of resistance training and the ingestion of supplemental protein and amino acids on muscle performance and markers of muscle anabolism . Nineteen untrained males were r and omly assigned to supplement groups containing either 20 g protein ( 14 g whey and casein protein , 6 g free amino acids ) or 20 g dextrose placebo ingested 1 h before and after exercise for a total of 40 g/d . Participants exercised 4 times/wk using 3 sets of 6–8 repetitions at 85–90 % of the one repetition maximum . Data were analyzed with two-way ANOVA ( p < 0.05 ) . The protein supplement result ed in greater increases in total body mass , fat-free mass , thigh mass , muscle strength , serum IGF-1 , IGF-1 mRNA , MHC I and IIa expression , and myofibrillar protein . Ten-wks of resistance training with 20 g protein and amino acids ingested 1 h before and after exercise is more effective than carbohydrate placebo in up-regulating markers of muscle protein synthesis and anabolism along with subsequent improvements in muscle performance Objectives Creatine and protein supplementation can enhance the training outcomes of young subjects , but it is not clear if there are benefits for older individuals . Therefore , the purpose of this study was to determine the effects of creatine and protein supplementation on strength gains following a traditional resistance training program for middle-aged and older men . Design , Setting , Participants This study assessed changes in strength of men aged 48–72 years following 14 weeks of resistance training supplemented with creatine and /or protein . A double-blind , r and omized , placebo-controlled design placed 42 males into one of four groups : Resistance Trained Placebo ( RTP , n=10 ) ; Resistance Trained Creatine ( RTCr , 5 g Cr , n=10 ) ; Resistance Trained Protein ( RTPr , 35 g whey Pr , n=11 ) ; or Resistance Trained Creatine and Protein ( RTCrPr , 5 g Cr and 35 g Pr , n=11).InterventionAll groups trained 3 days per week for 14 weeks . The resistance training program was based on progressive overload . Training loads corresponded to 80 % 1RM ( one repetition maximum strength ) , 3 sets of 8 repetitions for the following exercises : knee extension/knee flexion ; bicep curl/tricep extension ; military press ; lat pull down ; seated leg press ; and bench press . Measurements 1 RM for each exercise and measures of lean body mass were assessed prior to and following the 14 week program . Results Each group significantly ( p<0.05 ) increased strength and lean body mass , however , there were no significant group effects or group X trial interactions . Conclusion Resistance training in middle-aged and older men significantly increased muscular strength and added muscle mass with no additional benefits from creatine and /or protein supplementation The purpose of this study was to examine the effects of whey protein supplementation on body composition , muscular strength , muscular endurance , and anaerobic capacity during 10 weeks of resistance training . Thirty-six resistance-trained males ( 31.0 ± 8.0 years , 179.1 ± 8.0 cm , 84.0 ± 12.9 kg , 17.8 ± 6.6 % ) followed a 4 days-per-week split body part resistance training program for 10 weeks . Three groups of supplements were r and omly assigned , prior to the beginning of the exercise program , in a double-blind manner to all subjects : 48 g per day ( g·d−1 ) carbohydrate placebo ( P ) , 40 g·d−1 of whey protein + 8 g·d−1 of casein ( WC ) , or 40 g·d−1 of whey protein + 3 g·d−1 branched-chain amino acids + 5 g·d−1 L-glutamine ( WBG ) . At 0 , 5 , and 10 weeks , subjects were tested for fasting blood sample s , body mass , body composition using dual-energy x-ray absorptiometry ( DEXA ) , 1 repetition maximum ( 1RM ) bench and leg press , 80 % 1RM maximal repetitions to fatigue for bench press and leg press , and 30-second Wingate anaerobic capacity tests . No changes ( p > 0.05 ) were noted in all groups for energy in-take , training volume , blood parameters , and anaerobic capacity . WC experienced the greatest increases in DEXA lean mass ( P = 0.0 ± 0.9 ; WC = 1.9 ± 0.6 ; WBG = -0.1 ± 0.3 kg , p < 0.05 ) and DEXA fat-free mass ( P = 0.1 ± 1.0 ; WC = 1.8 ± 0.6 ; WBG = −0.1 ± 0.2 kg , p < 0.05 ) . Significant increases in 1RM bench press and leg press were observed in all groups after 10 weeks . In this study , the combination of whey and casein protein promoted the greatest increases in fat-free mass after 10 weeks of heavy resistance training . Athletes , coaches , and nutritionists can use these findings to increase fat-free mass and to improve body composition during resistance training The effect of protein supplementation on athletic performance and hormonal changes was examined in 21 experienced collegiate strength/power athletes participating in a 12-week resistance training program . Subjects were r and omly assigned to either a protein supplement ( PR ; n = 11 ) or a placebo ( PL ; n = 10 ) group . During each testing session subjects were assessed for strength ( one repetition maximum [ 1-RM ] bench press and squat ) , power ( Wingate anaerobic power test ) and body composition . Resting blood sample s were analyzed at weeks 0 ( PRE ) , 6 ( MID ) and 12 ( POST ) for total testosterone , cortisol , growth hormone , and IGF-1 . No difference was seen in energy intake between PR and PL ( 3034 ± 209 kcal and 3130 ± 266 kcal , respectively ) , but a significant difference in daily protein intake was seen between PR ( 2.00 g·kg body mass[BM](-1)·d(-1 ) ) and PL ( 1.24 g·kgBM(-1)·d(-1 ) ) . A greater change ( p < 0.05 ) in the ∆ 1-RM squat was seen in PR ( 23.5 ± 13.6 kg ) compared to PL ( 9.1 ± 11.9 kg ) . No other significant strength or power differences were seen between the groups . Cortisol concentrations were significantly lower at MID for PL and this difference was significantly different than PR . No significant changes were noted in resting growth hormone or IGF-1 concentrations in either group . Although protein supplementation appeared to augment lower body strength development , similar upper body strength , anaerobic power and lean tissue changes do not provide clear evidence supporting the efficacy of a 12-week protein supplementation period in experienced resistance trained athletes . Key pointsCollegiate strength/power athletes may not meet daily recommended energy or protein needs . When athletes are provided a protein supplement they appear to meet the recommended daily protein intake for strength/power athletes . Protein supplementation did augment lower body strength development in experienced strength/power athletes . Results of upper body strength , anaerobic power and lean tissue changes did not support the efficacy of a 12-week protein supplementation period in experienced resistance trained athletes Signaling pathways sense local and systemic signals and regulate muscle hypertrophy . The effects of whey protein ingestion on acute and long-term signaling responses of resistance exercise are not well known . Previously untrained young men were r and omized into protein ( n = 9 ) , placebo ( n = 9 ) , and control ( n = 11 ) groups . Vastus lateralis ( VL ) muscle biopsies were taken before and 1 h and 48 h after a leg press of 5 x 10 repetitions [ resistance exercise ( RE ) ] and after 21 wk ( 2 times per week ) of resistance training ( RT ) . Protein ( 15 g of whey ) or nonenergetic placebo was ingested before and after a single RE bout and each RE workout throughout the RT . The protein group increased its body mass and VL muscle thickness ( measured by ultrasonography ) already at week 10.5 ( P < 0.05 ) . At week 21 , the protein and placebo groups had similarly increased their myofiber size . No changes were observed in the nonexercised controls . However , the phosphorylation of p70(S6 K ) and ribosomal protein S6 ( rpS6 ) were increased at 1 h post-RE measured by Western blotting , the former being the greatest with protein ingestion . Mammalian target of rapamycin ( mTOR ) phosphorylation was increased after the RE bout and RT only in the protein group , whereas the protein ingestion prevented the post-RE decrease in phosphorylated eukaryotic initiation factor 4E binding protein 1 ( p-4E-BP1 ) . Akt phosphorylation decreased after RT , whereas no change was observed in phosphorylated eukaryotic elongation factor 2 . A post-RE decrease in muscle myostatin protein occurred only in the placebo group . The results indicate that resistance exercise rapidly increases mTOR signaling and may decrease myostatin protein expression in muscle and that whey protein increases and prolongs the mTOR signaling response Limited data have suggested that the consumption of fluid milk after resistance training ( RT ) may promote skeletal muscle hypertrophy . The aim of this study was to assess whether a milk-based nutritional supplement could enhance the effects of RT on muscle mass , size , strength , and function in middle-aged and older men . This was an 18-mo factorial design ( r and omized control trial ) in which 180 healthy men aged 50 - 79 yr were allocated to the following groups : 1 ) exercise + fortified milk , 2 ) exercise , 3 ) fortified milk , or 4 ) control . Exercise consisted of progressive RT with weight-bearing impact exercise . Men assigned to the fortified milk consumed 400 ml/day of low-fat milk , providing an additional 836 kJ , 1000 mg calcium , 800 IU vitamin D(3 ) , and 13.2 g protein per day . Total body lean mass ( LM ) and fat mass ( FM ) ( dual-energy X-ray absorptiometry ) , midfemur muscle cross-sectional area ( CSA ) ( quantitative computed tomography ) , muscle strength , and physical function were assessed . After 18 mo , there was no significant exercise by fortified milk interaction for total body LM , muscle CSA , or any functional measure . However , main effect analyses revealed that exercise significantly improved muscle strength ( approximately 20 - 52 % , P < 0.001 ) , LM ( 0.6 kg , P < 0.05 ) , FM ( -1.1 kg , P < 0.001 ) , muscle CSA ( 1.8 % , P < 0.001 ) , and gait speed ( 11 % , P < 0.05 ) relative to no exercise . There were no effects of the fortified milk on muscle size , strength , or function . In conclusion , the daily consumption of low-fat fortified milk does not enhance the effects of RT on skeletal muscle size , strength , or function in healthy middle-aged and older men with adequate energy and nutrient intakes The purpose was to compare changes in lean tissue mass , strength , and myofibrillar protein catabolism result ing from combining whey protein or soy protein with resistance training . Twenty-seven untrained healthy subjects ( 18 female , 9 male ) age 18 to 35 y were r and omly assigned ( double blind ) to supplement with whey protein ( W ; 1.2 g/kg body mass whey protein + 0.3 g/kg body mass sucrose power , N = 9 : 6 female , 3 male ) , soy protein ( S ; 1.2 g/kg body mass soy protein + 0.3 g/kg body mass sucrose powder , N= 9 : 6 female , 3 male ) or placebo ( P ; 1.2 g/kg body mass maltodextrine + 0.3 g/kg body mass sucrose powder , N = 9 : 6 female , 3 male ) for 6 wk . Before and after training , measurements were taken for lean tissue mass ( dual energy X-ray absorptiometry ) , strength ( 1-RM for bench press and hack squat ) , and an indicator of myofibrillar protein catabolism ( urinary 3-methylhistidine ) . Results showed that protein supplementation during resistance training , independent of source , increased lean tissue mass and strength over isocaloric placebo and resistance training ( P < 0.05 ) . We conclude that young adults who supplement with protein during a structured resistance training program experience minimal beneficial effects in lean tissue mass and strength The effect of 10 wk of protein-supplement timing on strength , power , and body composition was examined in 33 resistance-trained men . Participants were r and omly assigned to a protein supplement either provided in the morning and evening ( n = 13 ) or provided immediately before and immediately after workouts ( n = 13 ) . In addition , 7 participants agreed to serve as a control group and did not use any protein or other nutritional supplement . During each testing session participants were assessed for strength ( one-repetition-maximum [ 1RM ] bench press and squat ) , power ( 5 repetitions performed at 80 % of 1RM in both the bench press and the squat ) , and body composition . A significant main effect for all 3 groups in strength improvement was seen in 1RM bench press ( 120.6 + /- 20.5 kg vs. 125.4 + /- 16.7 at Week 0 and Week 10 testing , respectively ) and 1RM squat ( 154.5 + /- 28.4 kg vs. 169.0 + /- 25.5 at Week 0 and Week 10 testing , respectively ) . However , no significant between-groups interactions were seen in 1RM squat or 1RM bench press . Significant main effects were also seen in both upper and lower body peak and mean power , but no significant differences were seen between groups . No changes in body mass or percent body fat were seen in any of the groups . Results indicate that the time of protein-supplement ingestion in resistance-trained athletes during a 10-wk training program does not provide any added benefit to strength , power , or body-composition changes PURPOSE The intent of this investigation was to examine the effects of a daily oral provision consisting of amino acids ( L-lysine , L-leucine , L-valine , L-phenylalanine , L-threonine , L-histidine , L-isoleucine , and L-methionine ) in combination with carbohydrates ( dextrose , sucrose , and fructose ) on whole muscle strength and size characteristics during a 12-wk progressive knee extensor resistance training ( PRT ) program in older men ( > 65 yr ) . METHODS Seventeen older men were r and omly assigned to either the experimental ( EX ) or control ( CN ) groups . The EX ( N = 8) and CN ( N = 9 ) groups had the following characteristics-EX : 70.8 + /- 1.5 yr , 91.0 + /- 4.9 kg , and 177.0 + /- 3.9 cm ; CN : 72.1 + /- 1.9 yr , 75.4 + /- 4.7 kg , and 176.1 + /- 3.0 . Pre and post PRT maximal unilateral isometric torque ( N.m ) , isokinetic torque ( 1.05 , 1.57 , 2.09 , 3.14 , 4.19 , and 5.24 rad.s-1 ) , work capacity ( 30 consecutive reps at 3.14 rad.s-1 ) torque , one repetition maximum ( 1RM ) bilateral isotonic strength , and whole muscle cross-sectional area ( CSA ) of the mid-thigh were performed by computed tomography on each subject . RESULTS All variables showed an improvement with training ( P < 0.05 ) ; however , there were no differences between the groups . Both groups increased in isometric strength by 21 % , and isokinetic torque by 24 % to 11 % with the varying velocities ( 1.05 - 5.24 rad.s-1 ) . Whole muscle 1RM strength and thigh CSA increased 50 % and 6.5 % , respectively . Additionally , voluntary torque/CSA increased 12 % in both the EX and CN groups ( P < 0.05 ) . CONCLUSIONS In conclusion , these data suggest that whole muscle strength and size are not enhanced with a postexercise daily provision of an oral amino-acid complex during 12 wk of PRT in older men OBJECTIVE We investigated whether postexercise consumption of a supplement containing whey protein , amino acids , creatine , and carbohydrate combined with a strength training program promotes greater gains in fat-free mass ( FFM ) , muscle strength and endurance , and anaerobic performance compared with an isocaloric , carbohydrate-only control drink combined with strength training . METHODS The study was double blind and r and omized , and the experimental supplement was compared with a carbohydrate-only control . Forty-one males ( n = 20 in control group , n = 21 in the supplement group ; mean age , 22.2 y ) participated in a 4 d/wk , 10-wk periodized strength training program . Subjects had to complete at least 70 % of the workouts . Before and after 10 wk of strength training , subjects were tested for body composition by using hydrostatic weighing and skinfold thicknesses , one repetition maximum strength and muscular endurance for the bench press and 45-degree leg press , and anaerobic performance using a 30-s Wingate test . Thirty-three subjects ( 80.5 % ) completed the training program ( n = 15 in control group , n = 18 in the supplement ) ; these 33 subjects also completed all post-training test procedures . Data were analyzed with two-way analysis of variance with repeated measures on time . P < = = 0.05 was set as statistically significant . All statistical analyses , including calculation of effect size and power , were completed with SPSS 11.0 . RESULTS Across groups , FFM increased during 10 wk of strength training . Although there was no statistically significant time x group interaction for FFM , there was a trend toward a greater increase in FFM for the supplement group ( + 3.4 kg ) compared with the control group ( + 1.5 kg ; P = 0.077 ) . The effect size ( eta(2 ) = 0.100 ) was moderately large . Percentage of body fat declined and fat mass was unchanged ; there were no differences between groups . One repetition maximum strength for the bench press and 45-degree leg press increased , but there were no differences between groups . Muscular endurance expressed as the number of repetitions completed with 85 % of the one repetition maximum was unchanged ; external work , which was estimated as repetitions completed x resistance used , increased for the 45-degree leg press but not for the bench press over the 10-wk training period ; there were no time x group interactions for either measurement . Anaerobic power and capacity improved , but there were no differences between groups for these variables or for fatigue rate . CONCLUSIONS Consumption of a recovery drink after strength training workouts did not promote greater gains in FFM compared with consumption of a carbohydrate-only drink ; however , a trend toward a greater increase in FFM in the supplement group suggests the need for longer-term studies . Performance variables such as muscle strength and endurance and anaerobic performance were not improved when compared with the carbohydrate-only group This r and omized double-blind cross-over study assessed protein ( PRO ) requirements during the early stages of intensive bodybuilding training and determined whether supplemental PRO intake ( PROIN ) enhanced muscle mass/strength gains . Twelve men [ 22.4 + /- 2.4 ( SD ) yr ] received an isoenergetic PRO ( total PROIN 2.62 g.kg-1.day-1 ) or carbohydrate ( CHO ; total PROIN 1.35 g.kg-1.day-1 ) supplement for 1 mo each during intensive ( 1.5 h/day , 6 days/wk ) weight training . On the basis of 3-day nitrogen balance ( NBAL ) measurements after 3.5 wk on each treatment ( 8.9 + /- 4.2 and -3.4 + /- 1.9 g N/day , respectively ) , the PROIN necessary for zero NBAL ( requirement ) was 1.4 - 1.5 g.kg-1.day-1 . The recommended intake ( requirement + 2 SD ) was 1.6 - 1.7 g.kg-1.day-1 . However , strength ( voluntary and electrically evoked ) and muscle mass [ density , creatinine excretion , muscle area ( computer axial tomography scan ) , and biceps N content ] gains were not different between diet treatments . These data indicate that , during the early stages of intensive bodybuilding training , PRO needs are approximately 100 % greater than current recommendations but that PROIN increases from 1.35 to 2.62 g.kg-1.day-1 do not enhance muscle mass/strength gains , at least during the 1st mo of training . Whether differential gains would occur with longer training remains to be determined We determined the effects of protein supplementation immediately before ( PRO-B ) and after ( PRO-A ) resistance training ( RT ; 12 weeks ) in older men ( 59–76 years ) , and whether this reduces deficits in muscle mass and strength compared to younger men ( 18–40 years ) . Older men were r and omized to PRO-B ( 0.3 g/kg protein before RT + placebo after RT , n=9 ) , PRO-A ( placebo before + protein after RT , n=10 ) , or PLA ( placebo before and after RT , n=10 ) . Lean tissue mass , muscle thickness of the elbow , knee , and ankle flexors and extensors , and leg and bench press strength were measured before and after RT and compared to data bases of younger subjects ( n=22–60 ) . Myofibrillar protein degradation ( 3-methylhistidine ) and bone resorption ( cross-linked N-telopeptides ) were also measured before and after RT . Lean tissue mass , muscle thickness ( except ankle dorsi flexors ) , and strength increased with training ( P<0.05 ) , with little difference between groups . There were no changes in 3-methylhistidine or cross-linked N-telopeptides . Before RT , all measures were lower in the older compared to younger groups ( P<0.05 ) , except for elbow extensor muscle thickness . Following training , muscle thickness of the elbow flexors and ankle dorsi flexors and leg press strength were no longer different than the young , and elbow extensor muscle thickness was greater in the old men ( P<0.05 ) . Supplementation with protein before or after training has no effect on muscle mass and strength in older men . RT was sufficient to overcome deficits in muscle size of the elbow flexors and ankle dorsi flexors and leg press strength in older compared to younger men BACKGROUND Skeletal loading and proper nutrition are necessary for optimal bone health . The appropriate amount of dietary protein to maximize skeletal health , however , is under constant debate . OBJECTIVE To determine if 6 months of protein supplementation in conjunction with a strength and conditioning training program improves areal and volumetric bone mineral density ( BMD ) . DESIGN Fifty-two apparently healthy males and females ages 18 - 25 years were r and omized to protein supplement ( PRO , Myoplex , EAS , Inc. Golden CO ) containing 280 kcal , 42 g protein , 21 g carbohydrate , and 1.5 g fat ) or calorically equivalent carbohydrate control ( CS ) . All subjects participated in a 5 sessions/week strength and conditioning program . Volumetric and areal BMD measurements were made by peripheral quantitative computed tomography ( pQCT ) of the tibia and whole body DXA . pSSI a measure of torsional bone strength , based on structural and material properties was obtained by pQCT . RESULTS Measurements at the 20 % tibia by pQCT revealed that overall there were significant increases in cortical vBMD ( 4.3 + /- 1.3 mg/cm(3 ) ) , cortical area ( 1.9 + /- 0.6 cm(2 ) ) , cortical thickness ( 0.05 + /- 0.02 mm ) and pSSI ( 67 + /- 24 mm(3 ) ) , and a decrease in endosteal circumference ( - 0.5 + /- 0.2 mm ) over the intervention period ( all , P < 0.05 ) . None of the changes in DXA measures were found to differ by group or sex , there was a trend for a greater increase in whole body BMC among the carbohydrate compared to protein supplemented group and a greater increase among males ( 16 + /- 8 g ) compared to females ( -9 + /- 9 g ) ( P = 0.06 ) . CONCLUSIONS The results of this study indicate that the consumption of additional protein does not improve measurements of vBMD or bone size during a 6-month strength and conditioning program . Longer duration studies may be necessary to determine the influence of increased dietary protein on bone in young adults . Males and females may have different bone responses to increased protein intake while participating in a strength and conditioning program The effects of timed ingestion of high- quality protein before and after resistance exercise are not well known . In this study , young men were r and omized to protein ( n = 11 ) , placebo ( n = 10 ) and control ( n = 10 ) groups . Muscle cross-sectional area by MRI and muscle forces were analyzed before and after 21 weeks of either heavy resistance training ( RT ) or control period . Muscle biopsies were taken before , and 1 and 48 h after 5 × 10 repetition leg press exercise ( RE ) as well as 21 weeks after RT . Protein ( 15 g of whey both before and after exercise ) or non-energetic placebo were provided to subjects in the context of both single RE bout ( acute responses ) as well as each RE workout twice a week throughout the 21-week-RT . Protein intake increased ( P ≤ 0.05 ) RT-induced muscle cross-sectional area enlargement and cell-cycle kinase cdk2 mRNA expression in the vastus lateralis muscle suggesting higher proliferating cell activation response with protein supplementation . Moreover , protein intake seemed to prevent 1 h post-RE decrease in myostatin and myogenin mRNA expression but did not affect activin receptor IIb , p21 , FLRG , MAFbx or MyoD expression . In conclusion , protein intake close to resistance exercise workout may alter mRNA expression in a manner advantageous for muscle hypertrophy BACKGROUND Seventy-three healthy , male subjects r and omly divided into 3 groups participated in a study to determine the effects of 2 high-calorie nutritional supplements on body composition , body segment circumferences , and muscular strength following a resistance-training ( RT ) program . METHODS In addition to their normal diets group 1 ( CHO/PRO ; n=26 ) consumed a 8.4 Mj x day(-1 ) ( 2010 kcal ) high calorie , high protein supplement containing 356 g carbohydrate and 106 g protein . Group 2 ( CHO ; n=25 ) consumed a carbohydrate supplement that was isocaloric with CHO/PRO . Group 3 ( CTRL ; n=22 ) received no supplement and served as a control . All subjects were placed on a 4-day x week(-1 ) RT program for 8 weeks . RESULTS Dietary analysis revealed no significant differences in total energy consumption or nutrients at any time in the non-supplemented diets of the 3 groups . Significant ( p= or < 0.05 ) increases in body mass ( BM ) and fat-free mass ( FFM ) were observed in CHO/PRO and CHO compared to CTRL . Mean ( + /- SD ) increases in BM were 3.1+/-3.1 kg and 3.1+/-2.2 kg , respectively . Fat-free mass significantly ( p= or < 0.05 ) increased 2.9+/-3.4 kg in CHO/PRO and 3.4+/-2.5 kg in CHO . Muscular strength , as measured by a one-repetition maximum in the bench press , leg press , and lat-pull down increased significantly ( p= or < 0.05 ) in all groups . No significant differences in strength measures were observed among groups following training . CONCLUSIONS Results indicate that high-calorie supplements are effective in increasing BM and FFM when combined with RT . However , once individual protein requirements are met , energy content of the diet has the largest effect on body composition OBJECTIVE To assess how dietary change affects gain in strength and muscle mass during heavy resistance training of elderly men . DESIGN R and omized controlled trial . INTERVENTION During 12 weeks of resistance training of knee extensors and flexors , a daily supplement of 560 + /- 16 kcal/day ( 17 % energy from protein , 43 % from carbohydrate , 40 % from fat ) was r and omly assigned to six men ( S ) while five men ( U ) received no supplement . Food intake , strength , whole body composition , and midthigh composition by CT scan were assessed before training and at 6 and 12 weeks . SETTING The men were out patients but lived in a Metabolic Research Unit during the three assessment s. PARTICIPANTS Eleven healthy men aged 61 to 72 years . RESULTS Densitometry showed no change over time in fat or fat-free mass . However , the S men increased ( P less than 0.05 ) weight , skinfold thickness at six sites , subcutaneous midthigh fat , and creatinine excretion ; in all men , changes in these values and in midthigh muscle were proportional to changes in reported energy intake ( P less than 0.05 ) . There was midthigh muscle hypertrophy in both groups , but it was greater in S than U ( P less than 0.01 ) . Both groups gained strength ( P less than 0.001 ) with no effect of diet . CONCLUSIONS During physical rehabilitation of the elderly , dietary intake may influence the increase in lean as well as adipose tissue without altering strength gain . These preliminary findings should be confirmed by a larger study with sedentary controls Objective : Athletes are interested in nutritional manipulations that may enhance lean tissue gains stimulated by resistance training . Some research demonstrates that acute consumption of food containing protein causes superior muscle protein synthesis compared to isoenergetic foods without protein . This benefit has not been verified in longer-term training studies . We compared body composition and muscle function responses to resistance training in males who consumed a carbohydrate or a multi-macronutrient beverage following each training session . Methods : Nineteen , untrained men ( 18–25 years ) consumed either a milk ( MILK ) or a carbohydrate-electrolyte ( CHO ) drink immediately following each workout during a 10 week resistance training program . Muscle strength ( 1RM for seven exercises ) , body composition ( DXA scan ) , fasted , resting concentrations of serum total and free testosterone , cortisol , IGF-1 , and resting energy expenditure ( REE ) were measured prior to and at the end of training . Results : Resistance training caused an increase ( 44 ± 4 % , p < 0.001 ) in muscular strength for all subjects . The training program reduced percent body fat ( 8 % , p < 0.05 , −0.9 ± 0.5 kg ) and increased fat-free soft tissue ( FFST ) mass ( 2 % , 1.2 ± 0.3 kg , p < 0.01 ) . MILK tended to increase body weight and FFST mass ( p=0.10 and p=0.13 , respectively ) compared to CHO . Resting total and free testosterone concentrations decreased from baseline values in all subjects ( 16.7 % , 11 % , respectively , p < 0.05 ) . Significant changes in fasting IGF-1 , cortisol , and REE across training were not observed for either group . Conclusion : Post-resistance exercise consumption of MILK and CHO caused similar adaptations to resistance training . It is possible that a more prolonged training with supplementation period would exp and the trend for greater FFST gains in MILK PURPOSE The purpose of this study was to examine the effect of creatine supplementation in conjunction with resistance training on physiological adaptations including muscle fiber hypertrophy and muscle creatine accumulation . METHODS Nineteen healthy resistance-trained men were matched and then r and omly assigned in a double-blind fashion to either a creatine ( N = 10 ) or placebo ( N = 9 ) group . Periodized heavy resistance training was performed for 12 wk . Creatine or placebo capsules were consumed ( 25 g x d(-1 ) ) for 1 wk followed by a maintenance dose ( 5 g x d(-1 ) ) for the remainder of the training . RESULTS After 12 wk , significant ( P < or = 0.05 ) increases in body mass and fat-free mass were greater in creatine ( 6.3 % and 6.3 % , respectively ) than placebo ( 3.6 % and 3.1 % , respectively ) subjects . After 12 wk , increases in bench press and squat were greater in creatine ( 24 % and 32 % , respectively ) than placebo ( 16 % and 24 % , respectively ) subjects . Compared with placebo subjects , creatine subjects demonstrated significantly greater increases in Type I ( 35 % vs 11 % ) , IIA ( 36 % vs 15 % ) , and IIAB ( 35 % vs 6 % ) muscle fiber cross-sectional areas . Muscle total creatine concentrations were unchanged in placebo subjects . Muscle creatine was significantly elevated after 1 wk in creatine subjects ( 22 % ) , and values remained significantly greater than placebo subjects after 12 wk . Average volume lifted in the bench press during training was significantly greater in creatine subjects during weeks 5 - 8 . No negative side effects to the supplementation were reported . CONCLUSION Creatine supplementation enhanced fat-free mass , physical performance , and muscle morphology in response to heavy resistance training , presumably mediated via higher quality training sessions PURPOSE Studies attributing gains in strength and lean body mass ( LBM ) to creatine monohydrate ( CrM ) during resistance exercise ( RE ) training have not assessed these changes alongside cellular and subcellular adaptations . Additionally , CrM-treated groups have seldom been compared with a group receiving a placebo similar in nitrogen and energy . The purpose of this study was to examine the effects of a CrM-containing protein-carbohydrate ( PRO-CHO ) supplement in comparison with a supplement containing a similar amount of nitrogen and energy on body composition , muscle strength , fiber-specific hypertrophy , and contractile protein accrual during RE training . METHODS In a double-blind , r and omized protocol , resistance-trained males were matched for strength and placed into one of three groups : protein ( PRO ) , PRO-CHO , or the same PRO-CHO supplement ( 1.5 g x kg(-1 ) body weight x d(-1 ) ) containing CrM ( Cr-PRO-CHO ) ( 0.1 g x kg(-1 ) body weight x d(-1 ) ) . Assessment s were completed the week before and after a 10-wk structured , supervised RE program : strength ( 1RM , three exercises ) , body composition ( DEXA ) , and vastus lateralis muscle biopsies for determination of muscle fiber type ( I , IIa , IIx ) , cross-sectional area ( CSA ) , contractile protein , and creatine content . RESULTS Cr-PRO-CHO provided greater improvements in 1RM strength . At least 40 % of the strength improvements could be attributed to hypertrophy of muscle involved in this exercise . Cr-PRO-CHO also result ed in greater increases in LBM , fiber CSA , and contractile protein compared with PRO and PRO-CHO . CONCLUSIONS In RE-trained participants , supplementation with Cr-PRO-CHO provided greater muscle hypertrophy than an equivalent dose of PRO-CHO , and this response was apparent at three levels of physiology ( LBM , fiber CSA , and contractile protein content ) Acute muscle protein metabolism is modulated not only by resistance exercise but also by amino acids . However , less is known about the long-term hypertrophic effect of protein supplementation in combination with resistance training . The present study was design ed to compare the effect of 14 weeks of resistance training combined with timed ingestion of isoenergetic protein vs carbohydrate supplementation on muscle fiber hypertrophy and mechanical muscle performance . Supplementation was administered before and immediately after each training bout and , in addition , in the morning on nontraining days . Muscle biopsy specimens were obtained from the vastus lateralis muscle and analyzed for muscle fiber cross-sectional area . Squat jump and countermovement jump were performed on a force platform to determine vertical jump height . Peak torque during slow ( 30 degrees s-1 ) and fast ( 240 degrees s-1 ) concentric and eccentric contractions of the knee extensor muscle was measured in an isokinetic dynamometer . After 14 weeks of resistance training , the protein group showed hypertrophy of type I ( 18 % + /- 5 % ; P < .01 ) and type II ( 26 % + /- 5 % ; P < .01 ) muscle fibers , whereas no change above baseline occurred in the carbohydrate group . Squat jump height increased only in the protein group , whereas countermovement jump height and peak torque during slow isokinetic muscle contraction increased similarly in both groups . In conclusion , a minor advantage of protein supplementation over carbohydrate supplementation during resistance training on mechanical muscle function was found . However , the present results may have relevance for individuals who are particularly interested in gaining muscle size We evaluated the response of various muscle and bone adaptation parameters with 24 wk of strength training in healthy , early postmenopausal women when a nutrient supplement ( protein , carbohydrate , calcium , and vitamin D ) or a placebo supplement ( a minimum of energy ) was ingested immediately following each training session . At inclusion , each woman was r and omly and double-blindedly assigned to a nutrient group or a placebo ( control ) group . Muscle hypertrophy was evaluated from biopsies , MRI , and dual-energy X-ray absorptiometry ( DEXA ) scans , and muscle strength was determined in a dynamometer . Bone mineral density ( BMD ) was measured using DEXA scans , and bone turnover was determined from serum osteocalcin and collagen type I cross-linked carboxyl terminal peptide . The nutrient group improved concentric and isokinetic ( 60 degrees /s ) muscle strength from 6 to 24 wk by 9 + /- 3 % ( P < 0.01 ) , whereas controls showed no change ( 1 + /- 2 % , P > 0.05 ) . Only the nutrient group improved lean body mass ( P < 0.05 ) over the 24 wk . BMD responded similarly at the lumbar spine but changed differently in the two groups at the femoral neck ( P < 0.05 ) [ control : 0.943 + /- 0.028 to 0.930 + /- 0.024 g/mm(3 ) ( -1.0 + /- 1.4 % ) ; nutrient group : 0.953 + /- 0.051 to 0.978 + /- 0.043 g/mm(3 ) ( 3.8 + /- 3.4 % ) ] when adjusted for age , body mass index , and BMD at inclusion . Bone formation displayed an interaction ( P < 0.05 ) , mainly caused by increased osteocalcin at 24 wk in the nutrient group . In conclusion , we report that nutrient supplementation results in superior improvements in muscle mass , muscle strength , femoral neck BMD , and bone formation during 24 wk of strength training . The observed differences following such a short intervention emphasize the significance of postexercise nutrient supply on musculoskeletal maintenance |
13,311 | 27,636,406 | None of the treatments conferred any medium-term or long-term survival benefits in the present study .
Conclusions : Dual therapy was not inferior to corticosteroid monotherapy and could reduce the incidence of hepatorenal syndrome or acute kidney injury and risk of infection .
Therefore , dual therapy might be considered in treatment of patients with severe alcoholic hepatitis | Background and Aims : Although both corticosteroids and pentoxifylline are currently recommended drugs for the treatment of patients with severe alcoholic hepatitis , their effectiveness in reducing mortality remains unclear .
In this systematic review , we aim ed to evaluate the therapeutic and adverse effects of corticosteroids , pentoxifylline , and combination by using Cochrane methodology and therefore determine optimal treatment for severe alcoholic hepatitis . | BACKGROUND & AIMS An earlier pilot study from our liver unit suggested benefit from treatment with pentoxifylline ( PTX ) , an inhibitor of tumor necrosis factor ( TNF ) , in severe acute alcoholic hepatitis . The aim of the present study was to evaluate this treatment in a larger cohort of patients . METHODS One hundred one patients with severe alcoholic hepatitis ( Maddrey discriminant factor > or = 32 ) entered a 4-week double-blind r and omized trial of PTX ( 400 mg orally 3 times daily ) vs. placebo . Primary endpoints of the study were the effect of PTX on ( 1 ) short-term survival and ( 2 ) progression to hepatorenal syndrome . On r and omization , there were no differences in demographic and clinical characteristics or laboratory values ( including TNF ) between the 2 groups . RESULTS Twelve ( 24.5 % ) of the 49 patients who received PTX and 24 ( 46.1 % ) of the 52 patients who received placebo died during the index hospitalization ( P = 0.037 ; relative risk , 0.59 ; 95 % confidence interval , 0.35 - 0.97 ) . Hepatorenal syndrome was the cause of death in 6 ( 50 % ) and 22 ( 91.7 % ) patients ( P = 0.009 ; relative risk , 0.29 ; 95 % confidence interval , 0.13 - 0.65 ) . Three variables ( age , creatinine level on r and omization , and treatment with PTX ) were independently associated with survival . TNF values on r and omization were not predictive of survival ; however , during the study period they increased markedly in nonsurvivors compared with survivors in both groups . CONCLUSIONS Treatment with PTX improves short-term survival in patients with severe alcoholic hepatitis . The benefit appears to be related to a significant decrease in the risk of developing hepatorenal syndrome . Increasing TNF levels during the hospital course are associated with an increase in mortality rate IMPORTANCE Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis , a life-threatening disease . The benefit of their combination is unknown . OBJECTIVE To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone . DESIGN , SETTING , AND PARTICIPANTS Multicenter , r and omized , double-blind clinical trial conducted between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven alcoholic hepatitis , as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32 . Duration of follow-up was 6 months . The last included patient completed the study in October 2010 . None of the patients were lost to follow-up for the main outcome . INTERVENTION Patients were r and omly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day ( n=133 ) for 28 days , or 40 mg of prednisolone and matching placebo ( n=137 ) for 28 days . MAIN OUTCOMES AND MEASURES Six-month survival , with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model , which defines treatment nonresponders after 7 days of initiation of treatment . RESULTS In intention-to-treat analysis , 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups ( 69.9 % [ 95 % CI , 62.1%-77.7 % ] vs 69.2 % [ 95 % CI ; 61.4%-76.9 % ] , P = .91 ) , corresponding to 40 vs 42 deaths , respectively . In multivariable analysis , only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival . At 7 days , response to therapy assessed by the Lille model was not significantly different between the 2 groups ( Lille model score , 0.41 [ 95 % CI , 0.36 - 0.46 ] vs 0.40 [ 95 % CI , 0.35 - 0.45 ] , P = .80 ) . The probability of being a responder was not different in both groups ( 62.6 % [ 95 % CI , 53.9%-71.3 % ] vs 61.9 % [ 95 % CI , 53.7%-70.3 % ] , P = .91 ) . The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone and the placebo-prednisolone groups ( 8.4 % [ 95 % CI , 4.8%-14.8 % ] vs 15.3 % [ 95 % CI , 10.3%-22.7 % ] , P = .07 ) . CONCLUSION AND RELEVANCE In patients with alcoholic hepatitis , 4-week treatment with pentoxifylline and prednisolone , compared with prednisolone alone , did not result in improved 6-month survival . The study may have been underpowered to detect a significant difference in incidence of hepatorenal syndrome , which was less frequent in the group receiving pentoxifylline . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01214226 AIM To compare the efficacy of pentoxifylline and prednisolone in the treatment of severe alcoholic hepatitis , and to evaluate the role of different liver function scores in predicting prognosis . METHODS Sixty-eight patients with severe alcoholic hepatitis ( Maddrey score > or = 32 ) received pentoxifylline ( n = 34 , group I ) or prednisolone ( n = 34 , group II ) for 28 d in a r and omized double-blind controlled study , and subsequently in an open study ( with a tapering dose of prednisolone ) for a total of 3 mo , and were followed up over a period of 12 mo . RESULTS Twelve patients in group II died at the end of 3 mo in contrast to five patients in group I. The probability of dying at the end of 3 mo was higher in group II as compared to group I ( 35.29 % vs 14.71 % , P = 0.04 ; log rank test ) . Six patients in group II developed hepatorenal syndrome as compared to none in group I. Pentoxifylline was associated with a significantly lower model for end-stage liver disease ( MELD ) score at the end of 28 d of therapy ( 15.53 + /- 3.63 vs 17.78 + /- 4.56 , P = 0.04 ) . Higher baseline Maddrey score was associated with increased mortality . CONCLUSION Reduced mortality , improved risk-benefit profile and renoprotective effects of pentoxifylline compared with prednisolone suggest that pentoxifylline is superior to prednisolone for treatment of severe alcoholic hepatitis BACKGROUND Role of corticosteroids in treatment of severe alcoholic hepatitis ( SAH ) is controversial . Pentoxifylline ( PTX ) , an inhibitor of TNF , has also been shown to decrease short term mortality in SAH . Aim of this study was to evaluate the effect of PTX on short term mortality , renal and hepatic functions in patients with SAH . METHODS Fifty patients with SAH { Maddrey 's Discriminant Function ( DF ) > or = 32 } were prospect ively enrolled . Twenty five patients received PTX ( 400 mg orally , three times a day ) , and 25 received placebo for 4 weeks . Serum tumor necrosis factor ( TNF ) was measured in both groups . RESULTS Baseline characteristics of the two groups were similar . At 4 weeks , mortality in PTX group was lower than that in controls { 20 % ( 5/25 ) versus 40 % ( 10/25 ) respectively ; p = 0.216 ; RR 0.5 ; 95 % CI 0.19 - 1.25}. Renal failure was the cause of mortality in 20 % ( 1/5 ) patients in PTX group , and 70 % ( 7/10 ) in controls ( p = 0.11 ) . Significant reduction in urea , creatinine , DF and TNF was noted in PTX group . Reduction in TNF did not correlate with reduction in creatinine or DF . CONCLUSIONS In patients with SAH , PTX leads to a significant improvement in renal and hepatic functions , and a trend towards decreased short term mortality BACKGROUND / AIMS In severe alcoholic hepatitis ( AH ) , 40 % of patients will obtain no benefit from corticosteroids . Improvement in management of non-responders is warranted and only pentoxifylline can be considered an alternative . A two-step strategy was evaluated consisting of early withdrawal of corticosteroids and a switch to pentoxifylline for 28 additional days in non-responders identified using early change in bilirubin level . METHODS One hundred and twenty-one patients with AH were treated prospect ively with corticosteroids , and the two-step strategy was proposed to 29 non-responders treated according to a two-step strategy who were compared to 58 matched non-responders treated with corticosteroids only . RESULTS Clinical and biological features of the two groups were similar . There was no survival improvement at 2 months in patients treated with the two-step strategy compared to controls : 35.5+/-6.3 % vs 31+/-8.6 % . After 21 days , biological evolution was similar for prothrombin time ( -0.25s vs + 0.2s ) , bilirubin ( 0.8 mg/dl vs 2.03 mg/dl ) and creatinine ( + 0.16 mg/dl vs -0.7 mg/dl ) . In multivariate analysis , only age , evolution of bilirubin during the first week , creatinine and DF were associated with 2-month survival . CONCLUSIONS Non-responders to corticosteroids do not obtain any benefit from an early switch to pentoxifylline . Thus , the issue of management of non-responders remains unresolved BACKGROUND & AIMS Pentoxifylline , an inhibitor of tumor necrosis factor-alpha , is given to patients with liver diseases , but its effects in patients with advanced cirrhosis are unknown . We performed a r and omized , placebo-controlled , double-blind trial of its effects in patients with cirrhosis . METHODS A total of 335 patients with cirrhosis ( Child-Pugh class C ) were assigned to groups given either pentoxifylline ( 400 mg , orally , 3 times daily ; n = 164 ) or placebo ( n = 171 ) for 6 months . The primary end point was mortality at 2 months . Secondary end points were mortality at 6 months and development of liver-related complications . RESULTS By 2 months , 28 patients in the pentoxifylline group ( 16.5 % ) and 31 in the placebo group ( 18.2 % ) had died ( P = .84 ) . At 6 months , 50 patients in the pentoxifylline group ( 30.0 % ) and 54 in the placebo group ( 31.5 % ) had died ( P = .75 ) . The proportions of patients without complications ( eg , bacterial infection , renal insufficiency , hepatic encephalopathy , or gastrointestinal hemorrhage ) were higher in the pentoxifylline group than in the placebo group at 2 months ( 78.6 % vs 63.4 % ; P = .006 ) and 6 months ( 66.8 % vs 49.7 % ; P = .002 ) . The probability of survival without complications was higher in the pentoxifylline group than in the placebo group at 2 and 6 months ( P = .04 ) . In multivariate analysis , the factors associated with death were age , the Model for End-Stage Liver Disease score , and presence of early-stage carcinoma . Treatment with pentoxifylline was the only factor associated with liver-related complications . CONCLUSIONS Although pentoxifylline does not decrease short-term mortality in patients with advanced cirrhosis , it does reduce the risk of complications Background : Prednisolone and pentoxifylline ( PTX ) have been shown to be individually useful in severe alcoholic hepatitis with Maddrey discriminant function ( MDF ) score ≥32 . Previous report suggests that PTX is probably superior to prednisolone alone . However the efficacy of PTX and prednisolone combination over PTX alone in the management of acute alcoholic hepatitis ( MDF score ≥32 ) is yet unrevealed . Aim : The present study was initiated to find out the efficacy of combined pentoxifylline and prednisolone versus PTX alone in acute alcoholic hepatitis in respect of short and intermediate term outcomes . Subjects and Methods : A total of 124 patients with severe alcoholic hepatitis ( MDF score ≥ 32 ) initially were evaluated . 62 patients who fulfilled the inclusion and exclusion criteria were r and omized and divided into 2 groups . Group 1 received PTX only , whereas Group 2 received PTX plus Prednisolone . The total duration of follow-up was 12 months . Student′s t-test , Chi-square test , the Kaplan-Meier methods were used for statistical analysis . Results : A total of 60 patients , 30 in each group were available for final analysis . In Group-1 , 6 patients expired at the end of 1 year ( 5 within 3 months and another after 3 months ) . In Group 2 , 10 patients expired at the end of 1 year ( 9 within 3 months and another after 3 months ) . Though survival probability is higher among Group 1 patients but the difference is not statistically significant . Conclusion : The combination of PTX plus Prednisolone yields no additional benefit in terms of mortality and morbidity from that of PTX monotherapy The efficacy of methylprednisolone ( 1 g daily or three days ) , which is effective in reversing transplant rejection , was assessed in a r and omised controlled trial of 55 patients with severe acute alcoholic hepatitis , 34 of whom had encephalopathy . The clinical progress , frequency of bleeding and sepsis , and cause of death were similar in the treatment ( 27 patients ) and control groups ( 28 patients ) . There was no significant difference in mortality rate between the two groups : 57 % of the control group and 63 % of the treatment group died during the study . Patients ' survival depended on the presence of absence of the following features : encephalopathy , serum bilirubin concentration more than 340 micromol/l , serum creatinine concentration more than 250 micromol/l , and histological evidence of cirrhosis as well as severe acute alcoholic hepatitis STUDY OBJECTIVE To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe alcoholic hepatitis . DESIGN R and omized , double-blind , placebo-controlled multicenter trial . SETTING Four university teaching hospitals . PATIENTS We enrolled 66 patients with alcoholic hepatitis and either spontaneous hepatic encephalopathy or a discriminant function value greater than 32 , calculated using the formula : 4.6 ( prothrombin time - control time ) + serum bilirubin [ in mumol/L]/17.1 . Fifty-nine patients ( 89 % ) completed the study . Two patients withdrew from the trial . The other 64 patients were hospitalized for the duration of the trial ; however , treatment was discontinued in 5 patients because of potential drug toxicity . INTERVENTIONS Patients were r and omly assigned to receive either methylprednisolone ( 32 mg ) or placebo within 7 days of admission . Treatment was given for 28 days . The doses were then tapered over 2 weeks and discontinued . MEASUREMENTS AND MAIN RESULTS The endpoint of the study was death . Of the 31 recipients of placebo , 11 ( 35 % ) died within 28 days of r and omization compared with 2 ( 6 % ) of the 35 patients given methylprednisolone ( P = 0.006 ) . The 95 % CI for the difference in mortality was 12 % to 70 % . In the patients with spontaneous hepatic encephalopathy at entry , 9 of 19 recipients of placebo died ( 47 % ) compared with 1 ( 7 % ) of the 14 patients given methylprednisolone ( P = 0.02 ) . The 95 % CI for the difference in mortality was 14 % to 66 % . The Cox proportional hazards regression model showed the advantage of methylprednisolone over placebo after adjustment for other potentially important prognostic variables ( P = 0.004 ) . CONCLUSIONS Methylprednisolone therapy decreases short-term mortality in patients with severe alcoholic hepatitis manifested either by spontaneous hepatic encephalopathy or a markedly elevated discriminant function value BACKGROUND & AIMS Corticosteroids have been shown to significantly decrease short-term mortality in patients with severe alcoholic hepatitis . However , independent factors associated with a favorable outcome and long-term survival are unknown . The aim of this study was to examine prognostic factors and long-term survival in patients with biopsy-proven severe alcoholic hepatitis . METHODS Of 183 patients studied , 61 had been r and omized in a previous trial ; 32 of them were treated with prednisolone ( group I ) and 29 were not treated ( group II ) ; 61 were treated from the end of this r and omized trial ( group III ) ; and 61 were simulated ( group IV ) . RESULTS At 1 year , survival in group I ( 69 % ; confidence interval [ CI ] , 57%-81 % ) and group III ( 71 % ; CI , 55%-87 % ) was better than in the nontreated groups ( group II , 41 % ; CI , 23%-59 % ; P = 0.01 ) ( group IV , 50 % ; CI , 37%-63 % ; P = 0.05 ) . At 2 years , survival was not significantly different . Treated patients with marked liver polymorphonuclear infiltrate had better 1-year survival ( 76 % ; CI , 64%-88 % ) than the others ( 53 % ; CI , 35%-71 % ; P = 0.05 ) . Treated patients with polymorphonuclear counts of > 5500/mm3 had better 1-year survival ( 77 % ; CI , 65%-89 % ) than the others ( 40 % ; CI , 14%-66 % ; P = 0.003 ) . In the 93 treated patients , liver polymorphonuclear infiltrate ( P < 0.03 ) and polymorphonuclear count ( P < 0.001 ) were independently correlated with 1-year survival . CONCLUSIONS Prednisolone reduced mortality by at least 1 year . Liver polymorphonuclear infiltrate and polymorphonuclear count were independent prognostic factors In a prospect i ve double-blind study , 27 patients with alcoholic hepatitis were r and omized for 6-methylprednisolone ( 12 patients ) or placebo treatment ( 15 patients ) . The mortality was 50 % among steroid treated patients and 47 % in the control group ( P less than .05 ) . The role of liver biopsy feasibility at selection is emphasized since the mortality in this group was 10 % as opposed to 71 % when the procedure was contraindicated ( P less than .01 ) . Complications in the steroid-treated subjects were similar quantitatively and qualitatively to those observed in the control series Abstract A prospect i ve , double-blind controlled pilot study in 20 subjects of the efficacy of glucocorticosteroids in the treatment of severe , life-threatening , alcoholic hepatitis failed to demons BACKGROUND & AIMS The Acute Kidney Injury Network ( AKIN ) criteria are widely used in nephrology , but information on cirrhosis is limited . We aim ed at evaluating the AKIN criteria and their relationship with the cause of kidney impairment and survival . METHODS We performed a prospect i ve study of 375 consecutive patients hospitalized for complications of cirrhosis . One-hundred and seventy-seven ( 47 % ) patients fulfilled the criteria of Acute Kidney Injury ( AKI ) during hospitalization , the causes being hypovolemia , infections , hepatorenal syndrome ( HRS ) , nephrotoxicity , and miscellaneous ( 62 , 54 , 32 , 8 , and 21 cases , respectively ) . RESULTS At diagnosis , most patients had AKI stage 1 ( 77 % ) . Both the occurrence of AKI and its stage were associated with 3-month survival . However , survival difference between stages 2 and 3 was not statistically significant . Moreover , if stage 1 patients were categorized into 2 groups according to the level of serum creatinine used in the classical definition of kidney impairment ( 1.5mg/dl ) , the two groups had a significantly different outcome . Combining AKIN criteria and maximum serum creatinine , 3 risk groups were identified : ( A ) patients with AKI stage 1 with peak creatinine ≤ 1.5mg/dl ; ( B ) patients with stage 1 with peak creatinine > 1.5mg/dl ; and ( C ) patients with stages 2 - 3 ( survival 84 % , 68 % , and 36 % , respectively ; p<0.001 ) . Survival was independently related to the cause of kidney impairment , patients with HRS or infection-related having the worst prognosis . CONCLUSIONS A classification that combines the AKIN criteria and classical criteria of kidney failure in cirrhosis provides a better risk stratification than AKIN criteria alone . The cause of impairment in kidney function is key in assessing prognosis in cirrhosis A cooperative study was conducted to determine the efficacy of 30 days of treatment with either a glucocorticosteroid ( prednisolone ) or an anabolic steroid ( ox and rolone ) in moderate or severe alcoholic hepatitis . One hundred thirty-two patients with moderate disease and 131 with severe disease were r and omly assigned to one of three treatments : prednisolone , ox and rolone , or placebo . During the 30 days , mortality in the groups receiving steroid therapy was not significantly different from mortality in the placebo group . Thirteen per cent of the moderately ill patients and 29 per cent of the severely ill patients died . Although neither steroid improved short-term survival , ox and rolone therapy was associated with a beneficial effect on long-term survival . This was especially true in patients with moderate disease : among those who survived for one or two months after the start of treatment the conditional six-month death rate was 3.5 per cent after ox and rolone and 19 to 20 per cent after placebo ( P = 0.02 ) . No consistent long-term effect was associated with prednisolone therapy BACKGROUND & AIMS Both corticosteroid and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis . However , few studies have directly compared the efficacy of pentoxifylline and corticosteroid in patients with this condition . METHODS In this multicentre , open-labelled , r and omised non-inferiority trial , we assigned 121 patients with severe alcoholic hepatitis ( Maddrey 's discriminant function ⩾32 ) to receive either pentoxifylline ( 400 mg , 3 times daily , in 62 subjects ) or prednisolone ( 40 mg daily , in 59 subjects ) . The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone . RESULTS The 1-month survival rate of patients receiving pentoxifylline was 75.8 % ( 15 deaths ) compared with 88.1 % ( 7 deaths ) in those , taking prednisolone , for a treatment difference of 12.3 % ( 95 % confidence interval , -4.2 % to 28.7 % ; p = 0.08 ) . The 95 % confidence interval for the observed difference exceeded the predefined margin of non-inferiority ( Δ15 % ) and included zero . The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups ( 64.5 % vs. 72.9 % ; p = 0.23 ) . At 7 days , the response to therapy assessed by the Lille model was significantly lower in the prednisolone group ( n = 58 ) than in the pentoxifylline group ( n = 5 9 ) : 0.35 vs. 0.50 ( p = 0.012 ) . Hepatitis complications , including hepatorenal syndrome and side effects , such as infection and gastrointestinal bleeding , were similar in the two groups . CONCLUSIONS The findings demonstrate that the efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone , supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis |
13,312 | 27,841,440 | Findings from the other trials , all being of low to very low quality , suggest that applying a leave-on product ( moisturiser , skin protectant , or a combination ) might be more effective than not applying a leave-on product .
AUTHORS ' CONCLUSIONS Little evidence , of very low to moderate quality , exists on the effects of interventions for preventing and treating IAD in adults .
Soap and water performed poorly in the prevention and treatment of IAD .
Application of leave-on products ( moisturisers , skin protectants , or a combination ) and avoiding soap seems to be more effective than withholding these products .
The performance of leave-on products depends on the combination of ingredients , the overall formulation and the usage ( e.g. amount applied ) . | BACKGROUND Incontinence-associated dermatitis ( IAD ) is one of the most common skin problems in adults who are incontinent for urine , stool , or both .
In practice , products and procedures are the same for both prevention and treatment of IAD .
OBJECTIVES The objective of this review was to assess the effectiveness of various products and procedures to prevent and treat incontinence-associated dermatitis in adults . | Aim In a r and omized double‐blind study the therapeutic effect of a novel zinc – aluminium ointment was compared with placebo in patients with faecal incontinence OBJECTIVES To examine skin health outcomes of an exercise and incontinence intervention . DESIGN R and omized controlled trial with blinded assessment s of outcomes at three points over 8 months . SETTING Four nursing homes ( NHs ) . PARTICIPANTS One hundred ninety incontinent NH residents . INTERVENTION In the intervention group , research staff provided exercise and incontinence care every 2 hours from 8:00 a.m. to 4:30 p.m. ( total of four daily care episodes ) 5 days a week for 32 weeks . The control group received usual care from NH staff . MEASUREMENTS Perineal skin wetness and skin health outcomes ( primarily blanchable erythema and pressure ulcers ) as measured by direct assessment s by research staff , urinary and fecal incontinence frequency , and percentage of behavioral observations with resident engaged in st and ing or walking . RESULTS Intervention subjects were significantly better in urinary and fecal incontinence , physical activity , and skin wetness outcome measures than the control group . However , despite these improvements , differences in skin health measures were limited to the back distal perineal area , which included the sacral and trochanter regions . There was no difference between groups in the incidence rate of pressure ulcers as measured by research staff , even though those residents who improved the most on fecal incontinence showed improvement in pressure ulcers in one area . CONCLUSION A multifaceted intervention improved four risk factors related to skin health but did not translate into significant improvements in most measures of skin health . Even if they had adequate staffing re sources , NHs might not be able to improve skin health quality indicators significantly if they attempt to implement preventive interventions on all residents who are judged at risk because of their incontinence status Context Previous studies report that pressure ulcer classification and differentiation from incontinence associated dermatitis are difficult . Incorrect classification and differentiation result in incorrect prevention and treatment . Education is important to spread evidence -based insights about this topic and to improve classification skills . Aim To assess the effectiveness of the Pressure Ulcer Classification ( PUCLAS ) education tool . PUCLAS was developed by the PUCLAS Workgroup of the European Pressure Ulcer Advisory Panel . Design R and omised controlled trial . Setting and participants A convenience sample of 1217 Belgian , Dutch , British and Portuguese nurses . Outcome measure Correct classification of pressure ulcer photographs and differentiation from photographs of incontinence-associated dermatitis . Results Baseline , 44.5 % of the photographs were classified correctly . In the post-test , the results in the intervention group were significantly higher ( 63.2 % ) compared with the control group ( 53.1 % ; p<0.001 ) . The percentage of correct assessment s of incontinence associated dermatitis ( IAD ) was 70.7 % in the intervention group and 35.6 % in the control group ( p<0.001 ) . The skill to differentiate IAD from pressure ulcers was significantly associated with the experimental intervention ( OR 4.07 , 95 % CI 3.21 to 5.15 , p<0.001 ) . Conclusion The PUCLAS tool improved pressure ulcer classification and IAD differentiation significantly Background Most older adults with urinary incontinence use absorbent pads . Because of exposure to moisture and chemical irritating substances in urine , the perineal skin region is always at risk for development of incontinence-associated dermatitis ( IAD ) . The aim of this study was to examine the efficacy of an improved absorbent pad against IAD . Methods A cluster r and omized controlled design was used to compare the efficacy of two absorbent pads . Female in patients aged ≥65 years who had IAD and used an absorbent pad or diaper all day were enrolled . Healing rate of IAD and variables of skin barrier function such as skin pH and skin moisture were compared between the usual absorbent pad group ( n = 30 ) and the test absorbent pad group ( n = 30 ) . Results Thirteen patients ( 43.3 % ) from the test absorbent pad group and 4 patients ( 13.3 % ) from the usual absorbent pad group recovered completely from IAD . Moreover , the test absorbent pad group healed significantly faster than the usual absorbent pad group ( p = 0.009 ) . On the other h and , there were no significant differences between the two groups in skin barrier function . Conclusion The test absorbent pad for older adults with urinary incontinence might be more efficacious against IAD than usual absorbent pad . Trial registration UMIN-CTR : Soap and water and a no-rinse cleanser , with and without a moisture barrier , were examined for their effects as cleansing regimens on the perineal skin of 10 older female residents of an extended care facility . Each cleansing regimen was used for 3 weeks , with two weekly measurements obtained for erythema , pH , and transepidermal water loss . Results indicated that soap and water was the least efficacious regimen unless used with a moisture barrier . The no-rinse cleanser was better than soap and water in terms of skin effects and cost savings . The findings suggest that a no-rinse cleanser in conjunction with a moisture barrier is a more skin-preserving and cost-effective incontinence care cleansing regimen than soap and water for older female nursing home residents with incontinence PURPOSE : The purpose of this study was to measure the effect of a structured skin care regimen for critically ill patients with fecal incontinence . DESIGN : A nonr and omized , quasi-experimental research design ( comparison cohort ) was used for data collection . SUBJECTS AND SETTING : Seventy-six patients with fecal incontinence , Bristol stool form 5 , 6 , and 7 , and Braden Scale score of 16 or less in the intensive care units ( ICUs ) at Samsung Medical Center in Seoul , South Korea , participated in the study . METHODS : Of the 76 subjects enrolled , 38 were assigned to the experimental group and 38 to the control group . Participants in the active intervention group were being cared for in an ICU ; participants in the comparison group were cared for on cardiac , thoracic surgery , general surgery , and neurosurgical ICUs . A structured skin care regimen was developed and implemented , which included the regular use of a no-rinse skin cleanser , application of a skin protectant , and an indwelling fecal drainage system when indicated . Stool consistency was evaluated via the Bristol stool chart . Nurses trained in data collection determined Incontinence-Associated Dermatitis and its Severity ( IADS ) scores and assessed the perianal and sacral skin for occurrence of pressure ulcers daily over a 7-day period . RESULTS : Patients in the intervention group had significantly lower IADS scores ( t = 4.836 , P < .001 ) than subjects in the control group and were less likely to develop a pressure ulcer than were patients in the control group ( 5 vs 19 , & khgr;2 = 11.936 , P = .001 ) . Patients with higher IADS scores were significantly more likely to develop a pressure ulcer ( OR = 1.168 , 95%CI = 1.074–1.271 ) . CONCLUSION : A structured skin care regimen decreased IADS scores and occurrence of pressure ulcers . Higher IADS scores were associated with an increased risk for development of pressure ulcers Maintaining healthy , intact perineal skin in nursing home residents with incontinence is a challenge . Their condition puts them at risk for developing incontinence dermatitis , possibly predisposing them to develop pressure ulcers . To examine the cost-effectiveness of three perineal skin barriers ( a polymer-based barrier film and two petrolatum ointments ) used to prevent incontinence dermatitis , a 6-month descriptive study was conducted among residents ( N = 250 ) from four long-term care facilities ( nursing homes ) in the upper Midwestern US . All residents were incontinent and had intact perineal skin when they enrolled in the study . An economic analysis was performed using time-motion data from a convenience sample of enrolled residents and their caregivers . Residents had an average of 4.1 ( + /-2.307 ) incontinent episodes per day , the occurrence of incontinence dermatitis was 3.3 % and not significantly different between the different protocol s of care ( P = 0.4448 ) . Results of the economic analysis showed that daily barrier application costs ranged from $ 0.17 for the barrier film to $ 0.76 for the ointments evaluated . With labor included in the analysis , costs were also lower for the barrier film that required the least frequent application ( $ 0.26 ) compared to ointments that required more frequent application ( $ 1.40 ) . Results of this study suggest that the daily or three times weekly barrier film protocol s are affordable alternatives to using petrolatum ointments in the prevention of incontinence dermatitis PURPOSE : The purpose of this study was to compare 3 methods of bowel management to control fecal incontinence in adult critical care patients and their effect on incontinence-associated dermatitis , pressure ulcer prevalence , and clinician satisfaction . SUBJECTS AND SETTING : Fifty-nine adult patients in critical care with liquid fecal incontinence were recruited from 6 critical care units in a large Midwest healthcare system . METHODS : Subjects were r and omly assigned to 1 of 3 groups : bowel management system catheter , rectal/nasopharyngeal trumpet , or usual care . Subjects were assessed daily for incontinence-associated dermatitis , pressure ulcer prevalence , and other clinical data . Direct care nurse satisfaction with each method was evaluated by self-administered survey . RESULTS : Incontinence-associated dermatitis severity and pressure ulcer prevalence did not differ across groups at baseline . Over time , the change in incontinence-associated dermatitis severity score was significantly different across groups ( P < .001 ) . There were no significant differences in proportion of patients experiencing pressure ulcers during the study among groups . Clinicians reported significantly greater satisfaction with the bowel management system ( P = .007 ) and rectal trumpet ( P = .001 ) as compared to usual care . In addition , economic and safety benefits were identified with use of internal fecal devices . Specifically , an economic savings of $ 3100 to $ 3400 per 29 days of care was identified . Subjects experienced no adverse side effects when internal devices were used . CONCLUSION : Results of this r and omized controlled trial provide new information for the care of patients with fecal incontinence in the critical care setting . Incontinence-associated dermatitis severity scores differed across groups over time , pressure ulcer prevalence did not differ across groups over time , use of an internal device or bowel management system improved clinician satisfaction , and the use of internal fecal methods was more cost-effective than usual care Purpose To determine the cost and efficacy of 4 different regimens of incontinence-associated dermatitis ( IAD ) prevention in nursing home residents . Methods A multi-site open-label quasi-experimental study was conducted in 16 nursing homes stratified by location in 1 of 4 regions of the United States and r and omly selected . In 3 of the 4 regimens , a moisture barrier ointment or cream of different compositions was applied after each episode of incontinence , and in 1 regimen , a polymer-based barrier film was applied 3 times per week . All regimens used a pH-balanced moisturizing cleanser . Time and motion measures were documented for the amount of skin care products used ; the number , type , and time of caregivers performing IAD prevention care ; and the number and type of supplies used . Rates of incontinence in each nursing home were determined during a 3-day surveillance period . Results A total of 1,918 nursing home residents were screened , and 51 % ( n = 981 ) qualified for prospect i ve surveillance of incontinence dermatitis ; the majority were female ( 80.1 % ) and elderly ( 96 % ≥ 65 years old ) . A total of 78.6 % ( 771/981 ) of the participants were incontinent of both urine and feces . Compared to the 3 regimens in which a barrier was applied after each episode of incontinence , the use of a regimen in which a barrier film was applied 3 times weekly had significantly lower costs for the barrier product , labor associated with barrier application , and total cost , which included products , labor , and supplies . There were also savings in total product ( cleanser and barrier ) and total labor costs . Conclusions The use of a defined skin care regimen that includes a cleanser and a moisture barrier is associated with a low rate of IAD in nursing home residents who are incontinent . Use of a polymer skin barrier film 3 times weekly is effective for preventing incontinence-associated skin breakdown and can provide significant cost savings BACKGROUND No-rinse disposable wash gloves are increasingly implemented in health care to replace traditional soap and water bed baths without proper evaluation of ( cost ) effectiveness . OBJECTIVES To compare bed baths for effects on skin integrity and resistance against bathing and costs . DESIGN Cluster r and omized trial . SETTING Fifty six nursing home wards in the Netherl and s. Participants : Five hundred adult care-dependent residents and 275 nurses from nursing home wards . METHODS The experimental condition ' washing without water ' consists of a bed bath with disposable wash gloves made of non-woven waffled fibers , saturated with a no-rinse , quickly vaporizing skin cleaning and caring lotion . The control condition is a traditional bed bath using soap , water , washcloths and towels . Both conditions were continued for 6 weeks . Outcome measures were prevalence of skin damage distinguished in two levels of severity : any skin abnormality/lesion and significant skin lesions . Additional outcomes : resistance during bed baths , costs . RESULTS Any skin abnormalities/lesions over time decreased slightly in the experimental group , and increased slightly in the control group , result ing in 72.7 % vs 77.6 % of residents having any skin abnormalities/lesions after 6 weeks , respectively ( p=0.04 ) . There were no differences in significant skin lesions or resistance after 6 weeks . Mean costs for bed baths during 6 weeks per resident were estimated at € 218.30 ( 95%CI 150.52 - 286.08 ) in the experimental group and € 232.20 ( 95%CI : 203.80 - 260.60 ) in the control group ( difference € 13.90 ( 95%CI : -25.61 - 53.42 ) . CONCLUSION Washing without water mildly protects from skin abnormalities/lesions , costs for preparing and performing bed baths do not differ from costs for traditional bed bathing . Thus , washing without water can be considered the more efficient alternative Elderly patients with acute neurological impairment are prone to severe disability , fecal incontinence ( FI ) , and result ant complications . A suspension positioning system ( SPS ) , based on the orthopedic suspension traction system commonly used for conservative treatment of pediatric femoral fracture and uncomplicated adult pelvic fracture , was developed to facilitate FI management in patients immobilized secondary to an acute neurological condition . To evaluate the effectiveness and safety of the system , a prospect i ve , r and omized , controlled study was conducted between October 2009 and July 2012 . Two hundred ( 200 ) elderly , bedridden , hospitalized patients with acute , nonchronic neurological impairment were r and omly assigned to receive routine FI nursing care ( ie , individualized dietary modification , psychological support , health education , and social support for caregivers and family members [ control group ] ) or routine incontinence care plus the SPS ( experimental group ) during the day . Rates of perianal fecal contamination , skin breakdown , incontinence associated dermatitis , pressure ulcer development , and lower urinary tract infection ( LUTI ) were significantly lower in the SPS than in the control group ( P < 0.05 ) . Length of hospitalization and costs of care were also lower in the SPS group ( P < 0.05 ) . Patient quality -of-life ( QoL ) and FI QoL scores were similar at baseline but significantly higher ( better ) at the 6-month follow-up interview in the SPS than in the control group ( P < 0.05 ) . In this study , the rate of FI-associated morbidities was lower and 6-month patient QoL scores were higher in the SPS than in the control group . No adverse events were observed , and all patients completed the study . Further clinical studies are needed to examine the long-term effects of SPS use among neurologically impaired FI patients Background : Incontinence-associated dermatitis ( IAD ) is a potentially serious skin injury that can lead to pressure ulcers ( PUs ) . Multiple studies have indicated the need for evidence to find the most effective skin care protocol to reduce the incidence and severity of IAD in critically ill patients . Objective : To compare the incidence and severity of IAD in two groups on a progressive care unit ( PCU ) using a defined skin care protocol : cleaning with a gentle cleanser and moisturizer , then applying a skin protectant/barrier . The control group received the skin care protocol every 12 hours and the interventional group received the protocol every 6 hours ; both groups also received it as needed . Methods : A 9-month r and omized prospect i ve study was conducted on 99 patients ( N = 55 in the intervention group and N = 44 in the control group ) who were incontinent of urine , stool , or both , or had a fecal diversion device or urinary catheter for more than 2 days . Results : The dermatitis score in the intervention group on discharge was significantly less ( 7.1 % ; P ⩽ 0.001 ) in the moderate IAD group than in the control group ( 10.9 % ) . The dermatitis score means and P values of each group were compared using a paired t test . Conclusion : The research ers studied a defined skin care protocol using a cleanser with aloe vera and a cleansing lotion , followed by application of either a moisture barrier with silicone or skin protectant with zinc oxide and menthol , undertaken at two different frequencies . Data revealed the incidence of moderate IAD was decreased in the experimental group ( receiving the skin protocol every 6 hours and p.r.n . ) The authors wanted to compare the performance and skin environment provided by a recently introduced reusable underpad ( Test Group underpad ) to an underpad already well established in the absorbent products market ( Reference Group underpad ) . A controlled , prospect i ve , r and omized multi-centered clinical trial was conducted in 18 facilities ( 6 hospitals , 7 home health agencies , and 5 skilled nursing facilities ) and completed by 107 patients . The majority of the patients had a Braden score near 13 , were 70 to 80 years of age , and weighed 130 to 138 lbs . The Test Group underpad ranked more favorably overall and in all eight categories of daily assessment . These differences were statistically significant ( p < 0.05 ) in the Total Score and in four of the eight individual categories : Keeping Skin Dry , Keeping Clothing Dry , No Pooling of Fluid , and Patient Comfort . The Test Group underpad also ranked more favorably with statistical significance ( p < 0.05 ) in three of the assessment categories at the conclusion of the study : Pad Absorbency , Pad 's Ability to Wick Moisture , and Pad 's Ability to Keep Skin Dry . Investigators also noted that 57 patients ( 53 % ) exhibited some measure of improvement by the end of the study . Of these , 45 ( 79 % ) had been assigned to the Test Group . The Test Group underpad demonstrated better absorbency , kept patients ' skin , clothing and bed linens drier , exhibited less pooling of fluid and result ed in higher patient comfort . As a result , it may have contributed to a more beneficial skin environment , allowing for prevention of preexisting skin integrity problems and enhancement of healing A double blind controlled trial was carried out to measure the efficacy of Sudocrem , compared with zinc cream BP , in the treatment and prevention of incontinence-associated dermatitis in an elderly inpatient population . Three objective measures of skin condition were used to assess efficacy . Sudocrem was shown to be superior to zinc cream BP in the treatment of dermatitis , with no significant difference shown in terms of prophylaxis . The objective measures of skin health seemed to be a promising advance on earlier , subjective methods , and their further development is recommended . There was some indication that the normal skin of an incontinent patient does not deteriorate when managed with Sudocrem or zinc cream It is estimated that 30 % of nursing home residents may be faecally incontinent , with those figures rising to 60 % for patients in long-stay hospitals ( Royal College of Physicians , 1995 ) . Maintaining skin integrity for these patients can be complex . With little clinical information to support carers , choosing a skin care regime that maintains skin integrity for this high-risk group can be difficult . This study aims to compare two recognized skin care regimes , used in the cleansing of patients ' skin following an episode of incontinence , and their impact on patients ' skin integrity . A total of 93 patients were recruited to the trial from five care of the elderly or dependent service providers . The subjects were r and omly allocated to either group A ( soap and water ; n = 49 ) , or group B ( Clinisan ( Vernacare ) ; n = 44 ) . Initially , 33 patients in both groups started with healthy skin . However , the results of the final assessment identified only 17 subjects in group A remaining healthy , compared with 27 in group Perineal protection products were compared for their efficacy in preventing skin breakdown in the hospitalized patient with urinary and /or fecal incontinence . Each product was used for the duration of the hospital stay with daily observations for perineal skin condition . Results indicated the spray product and wipe product were comparable in rate of skin breakdown prevention . Findings suggest the wipe product is more cost-effective for use during hospitalization , and the spray product preserves skin integrity over a longer period of time , beyond average hospitalization duration OBJECTIVE This study compares the total cost of treatment , skin-condition management and prevention of skin breakdown of perianal/buttock skin in incontinent patients receiving 3 M Cavilon No Sting Barrier Film ( Cavilon NSBF ) and zinc oxide oil . METHOD This single-centre open-label prospect i ve r and omised study involved 40 patients with at least moderate skin damage result ing from incontinence . Patients were r and omised to receive either zinc oxide oil or Cavilon NSBF and were treated for 14 days . The study products and other treatment-related products used were recorded , as was the time needed to cleanse the application site and apply the product . RESULTS Use of both products result ed in an improvement in skin condition after 14 days , but this was significantly better with Cavilon NSBF than zinc oxide oil . Cavilon NSBF was more cost-effective as fewer applications were required , less time was spent applying the skin barrier product and faster healing rates were achieved . The cost-effectiveness ratio per treatment group showed an improvement of one point in the total score of the skin- assessment scale costs : 28.36 Euro for Cavilon NSBF versus 98.06 Euro for zinc oxide oil . CONCLUSION Both products result ed in an improvement in skin condition after 14 days , but Cavilon NSBF was found to be more cost-effective . DECLARATION OF INTEREST This study was supported by an educational grant from 3 M A report of a study that investigated the effect of a combined cleanser and barrier cream on the incidence of pressure sores in patients who were OBJECTIVE To determine whether low airloss hydrotherapy reduces the incidence of new skin lesions associated with incontinence in hospitalized patients and results in more rapid healing of existing pressure sores compared with st and ard care . To assess subjectively patient and nursing satisfaction related to using low airloss hydrotherapy beds . DESIGN R and omized , prospect i ve , unblinded study . SETTING Acute and chronic hospital wards . PARTICIPANTS A total of 116 newly admitted , incontinent , hospitalized patients with and without existing pressure sores . INTERVENTION Low airloss hydrotherapy compared with treatment on hospital beds and mattresses ordered by the patient 's attending physician . MEASUREMENTS Incidence rates of new skin lesion development , e.g. , pressure sores , c and idiasis , and chemical irritation ; improvement in existing pressure sore size , volume , and status ; subjective assessment of patient and nursing satisfaction . RESULTS Possible hypothermia was identified in two patients during the first week of the study , and patient and nursing dissatisfaction with low airloss hydrotherapy remained high throughout the first months of the study . Therefore , two major modifications in the initial protocol were made : ( 1 ) increased patient temperature monitoring for hypothermia was initiated in Week 2 of the study and ( 2 ) increased staff re sources for in-service training on bed use began in Week 18 of the study . After the latter change , 58 subjects were r and omized to low airloss hydrotherapy and 58 to st and ard care . Subjects were old ( median age > or = 80 years ) , and almost all were bedbound or nonambulatory . The median ( range ) length of follow-up for subjects in the treatment group was significantly shorter than for those in the control group ( 4 ( 1 - 60 ) days versus 6 ( 1 - 62 ) days , respectively , P = .017 ) because there were more dropouts from the treatment group ( 24 ( 36 % ) of 58 versus 2 ( 3 % ) of 58 , P = .0001 ) . The major reasons dropout occurred were patient or family dissatisfaction ( 12 ( 21 % ) ) , new or worsened skin lesions thought to be related to bed use ( 4 ( 7 % ) ) , and hypothermia < 97 degrees F ( 4 ( 7 % ) ) . The total cumulative incidence of new truncal skin lesions within 9 days of enrollment was greater in the treatment than in the control group ( 48 % versus 14 % , respectively , P < 0.01 ) . Too few patients with existing pressure sores were treated for too short a period of time to assess the effect of low airloss hydrotherapy on pressure sore healing . Because only 10 patients treated on low airloss hydrotherapy beds were able to complete satisfaction surveys meaningfully , interpretation of these data is difficult . Only nine ( 21 % ) of 44 nurses subjectively reported overall satisfaction using the low airloss hydrotherapy bed . CONCLUSIONS This study shows the value of a rigorously design ed clinical ly based evaluation of a new product developed for older patients . The results of the study led to re-engineering of the prototype low airloss hydrotherapy bed as well as a change in marketing strategy . Studies of products targeted to the prevention and treatment of pressure sores in older patients should be undertaken before generalized marketing begins Evidence -based practice drives nursing procedures and st and ards of care . Supporting practice with valid research can be a challenge . After identifying a knowledge- and problem-focused trigger , a group of WOC nurses began a research journey . Our purpose was to determine the effectiveness of the rectal trumpet compared to the fecal collector in maintaining skin integrity in patients with fecal incontinence . The methodology included a convenience sample of 100 patients r and omized to rectal trumpet or fecal collector versus st and ard care . Data were collected on signs of increased skin breakdown or healing , stool leakage around device , dislodgement , and discomfort from device . This article will reveal our journey in conducting this clinical research . After many challenges , the study was terminated , but the experiences and lessons learned during our efforts were invaluable . Even well-planned studies can encounter problems that prevent completion . It is important to evaluate these problems so that lessons can be learned and shared . This is our roller coaster ride in the research world PURPOSE : We compared the effectiveness of a 3-in-1 perineal care washcloth versus st and ard of care ( water and pH neutral soap ) to prevent and treat incontinence-associated dermatitis ( IAD ) . The product under study was a soft , premoistened washcloth , including a 3 % dimethicone formula , with cleansing , moisturizing , and barrier protection properties . DESIGN : R and omized , controlled clinical trial . SUBJECTS AND SETTING : The study sample comprised a r and om sample of 11 nursing home wards ( 6 experimental and 5 control ) in a convenience sample of 4 nursing homes in Belgium . The sample included nursing home residents at risk for and /or affected by IAD defined as incontinent of urine , feces , urine/feces , and /or having erythema of the perineal skin ( not caused by pressure/shear ) , and /or having an edematous skin in the genital area . METHODS : Participants in the experimental group were treated according to a st and ardized protocol , including the use of a 3-in-1 perineal care washcloth impregnated with a 3 % dimethicone skin protectant . Participants in the control group received perineal skin care with water and pH neutral soap , the st and ard of care in Belgian nursing homes . The study period was 120 days . Data were collected between February and May 2010 . Incontinence-associated dermatitis prevalence and severity were assessed using the IAD Skin Condition Assessment Tool . The surface ( cm2 ) , redness , and depth of the perineal lesion were assessed daily by the nurses . This tool generates a cumulative severity score ( maximum score = 10 ) based on area of skin affected , degree of redness , and depth of erosion . RESULTS : Four hundred sixty-four nursing home residents were assessed and 32.9 % ( n = 141 ) met the criteria for inclusion , including 73 subjects in the experimental group and 68 in the control group . Baseline IAD prevalence was comparable in both groups ( experimental : 22.3 % vs control : 22.8 % , P = .76 ) . Baseline IAD severity was 6.9/10 in the experimental group and 7.3/10 in the control group . A significant intervention effect on IAD prevalence was found ( experimental : 8.1 % vs control : 27.1 % , F = 3.1 , P = .003 ) . A nonsignificant effect on IAD severity could be determined ( experimental : 3.8/10 vs control : 6.9/10 , F = 0.8 , P = .06 ) . CONCLUSION : The use of a 3-in-1 washcloth , impregnated with a 3 % dimethicone formula , result ed in a significantly reduced prevalence of IAD and a trend toward less severe lesions . These findings provide indicative evidence for the use of 3-in-1 perineal care washcloth as an effective intervention against the use of water and a pH neutral soap to prevent and /or treat IAD OBJECTIVE The use of non-rinse skin cleansers in the care of patients who are at risk of tissue breakdown is not new within the National Health Service ( NHS ) . Back to the Floor Continence Care Rounds ( introduced in 2012 to facilitate bedside continence care education ) at University Hospitals Birmingham had identified that in the current climate of austerity and efficiency savings , the use of non-rinse cleanser was being r and omly rationed . Our objective was to determine whether the introduction of a smaller tube of non-rinse cleanser with targeted education would improve usage and ultimately improve the skin of incontinent patients . METHOD There were five clinical areas r and omised into two groups . In group 1 three clinical areas were provided with targeted education and new sizes of tubes of non-rinse skin cleanser . In group 2 , the two remaining clinical areas acted as control groups , one receiving targeted education only and the remaining had no education or new sized tubes . The incidence of incontinence associated moisture lesions from each clinical area was monitored for 13 weeks pre and post study period . RESULTS The in-depth study undertaken at University Hospitals Birmingham , over a 6-month period , confirmed a trend in staff committing to the ethos of prudency , and in turn compromising the use of the most effective treatment and prevention of incontinence associated moisture lesions . The ability of the Trust staff to recognise and respond to a change in practice and the responsiveness of a commercial provider to the proposed new methodology has result ed in a significant reduction in incontinence associated moisture lesions across the trust . The clinical areas included in the study demonstrated a 70 - 76.9 % reduction in moisture lesion incidence compared to an 8.3 - 13.6 % reduction in the control groups . CONCLUSION The results strongly suggest that a reduction in incontinence associated moisture lesions can be achieved by a simple change in nursing regime . The combination of solid education provision , alongside a more appropriate size of product , has demonstrated significant patient benefit , greater adherence in practice and a reduction in waste . The integrity of the patients ' tissue was preserved and staff were satisfied with their input and the patients ' progress . The outcomes of this study will have an impact on patient benefit and on the efficiency for trusts result ing in greater patient satisfaction and a more appropriate use of limited re sources . DECLARATION OF INTEREST SCA provided 20ml tubes of TENA Wash Cream free of charge and the TENA Nurse Advisor for support during the education provision element of the study Caring for the skin of patients with incontinence is an essential activity in long-term care . A prospect i ve descriptive study to compare the effect of two skin care protocol s on skin condition , pain , and caregiver time was conducted . Thirty-two ( 32 ) skilled nursing facility residents with incontinence participated in the 3-week study . Patients were r and omly assigned to a st and ard care regimen ( soap and water cleansing after each incontinence episode , followed by application of a moisturizing lotion ) or study care protocol ( no-rinse skin cleanser after each episode and application of a barrier cream with durable properties after the first incontinence episode of each shift ) . Number and type of incontinence episodes , skin condition , pain , and caregiver time spent were assessed . Skin integrity was maintained in the majority of control ( 69 % ) and study group ( 72 % ) patients and improvement occurred in 8 % of control and 17 % of the study group ( NS ) . Study protocol procedures took less time to complete than control procedures ( a savings of 79 minutes/patient/day ) . A positive correlation between pain intensity and level of skin impairment was observed ( r = 0.88 ) . The results of this study suggest that at this facility , use of soap , water , and a moisturizer may be less effective and more time-consuming than using a no-rinse cleanser and a durable barrier product AIMS AND OBJECTIVES The aims of this study were to measure skin moisture and transepidermal water loss after application of uncoated paper and to compare skin moisture and transepidermal water loss after use of uncoated paper and disposable underpads . STUDY DESIGN The study was a cross-over , prospect i ve , open-labeled , r and omized trial . SAMPLE AND SETTING Bedridden patients aged≥18 years at a medical center in Korea were included . Treatment order was r and omly assigned using block r and omization , with a block size of 4 and an assignment rate of one-by-one . METHODS Skin moisture was measured using a Corneometer 825 and transepidermal water loss was measured using a Tewameter 300 . RESULTS Skin moisture after application of an uncoated paper was significantly lower than observed after application of a disposable underpad ( mean 40.6 and SD 13.1 vs. mean 64.6 and SD 23.7 , p<0.001 ) . Transepidermal water loss also showed greater health scores after using uncoated paper ( mean 11.1 and SD 5.7 g/m2/hour ) than after applying a disposable underpad ( mean 23.2 and SD 11.1 g/m2 /hour , p<0.001 ) . There were no statistical between-group differences in room temperature , relative humidity , and body temperature . CONCLUSION We found that uncoated paper was helpful in avoiding excessive moisture without adverse effects . RELEVANCE TO CLINICAL PRACTICE As indicated by the results of this study , uncoated paper can be applied to bed-ridden patients who required incontinence care . Nurses may consider using uncoated paper as one of nursing methods in the routine care of bed-ridden patients for moisture control Absorbent pads are the main method of managing urinary incontinence in residential setting s for older people . Improvements in technology have result ed in highly absorbent products which may be worn all night , but the effects of prolonged pad wearing on aged skin are unknown . The aim of this study was to examine the effects of two different pad changing regimes on skin health . A cross-over design was used . Subjects from residential setting s were r and omly allocated to one of two pad changing regimes : a frequent pad changing regime or a less frequent pad changing regime . Each regime lasted 4 weeks and was followed by the alternative regime . Skin measurements were taken twice during each regime using ( i ) the Diastron Erythema meter , ( ii ) a visual grading scale , ( iii ) the Servomed evaporimeter , and ( iv ) a pH meter . The primary outcome variable was the Diastron Erythema meter index . Eighty-one subjects completed the study . No significant differences were found in the severity of erythema , or skin pH , between regimes . Measurements of trans-epidermal water loss were significantly higher in the less frequent pad changing regime indicating that skin was ' wetter ' ( P = 0.01 ; 95 % CI : 2.89 - 21.39 ) . Five subjects developed grade 2 pressure ulcers ( abrasions ) during the less frequent pad changing regime , but none in the frequent pad changing regime ; this result was not significant ( P = 0.1 ; 95 % CI : 0 - 1.09 ) . No evidence was found that a less frequent pad changing regime has an effect on skin erythema or pH. There is evidence that skin is wetter which may make it more vulnerable to friction and abrasion . The statistically non-significant finding of greater incidence of grade 2 pressure ulcers is a cause for concern and merits further investigation because of the clinical significance of loss of skin integrity A preliminary investigation was conducted to determine the efficacy of a structured skin care regimen to prevent perineal dermatitis in incontinent geriatric psychiatry patients . A 10-week , prospect i ve , clinical trial was conducted ( n = 15 ) . Four weeks ( weeks 2 to 5 ) were devoted to monitoring the unstructured pretreatment nursing skin care practice and to determining the incidence of perineal dermatitis in incontinent patients . Four weeks ( weeks 7 to 10 ) were also spent implementing and observing the structured nursing skin care regimen . The study revealed that 33 % ( three ) of the subjects in the unstructured skin care group and 33 % ( two ) of the subjects in the structured skin care group had perineal dermatitis . In subjects with a combination of urine and stool incontinence perineal dermatitis developed within 2 days . The findings suggest that perineal dermatitis occurs quickly in the presence of urine and stool incontinence . Further research is needed to vali date the efficacy of a structured skin care regimen to prevent perineal dermatitis PURPOSE : We compared the effects of 2 devices used to contain fecal incontinence — a perianal pouch and adult containment brief — on the incidence of incontinence-associated dermatitis ( IAD ) . DESIGN : R and omized controlled trial . SUBJECTS AND SETTING : The sample was drawn from patients hospitalized in the neurology and neurosurgery wards of a large university hospital in Turkey . Thirty bedridden subjects with fecal incontinence and indwelling urinary catheters participated in the study . Subjects were r and omly allocated to treatment with a perianal pouch ( n = 15 ) or adult containment brief ( n = 15 ) . METHODS : Routine hygiene was completed once daily and repeated whenever the perineal area was found to be soiled . Perineal skin integrity was evaluated daily during skin care . Data were collected using a Patient Identification Form , a Patient Observation Form , and a Perineal Skin Integrity Assessment Form . RESULTS : The mean number of products used on a daily basis by patients with a perianal pouch was 5.80 , as compared to 5.46 by patients with adult incontinence briefs . IAD occurred in 66.7 % of patients in the perianal pouch group and in 100 % of subjects managed by containment briefs , a statistically significant difference ( & khgr;2 = 6.0 , P = 0.04 ) . The onset of IAD occurred later in subjects allocated to management with a perianal pouch than in patients using adult containment briefs ( U = 30.500 , P = 0.011 ) . IAD involved an average of 1.8 areas among patients managed with a perianal pouch , as compared to 2.3 areas in patients managed with adult containment briefs ( P = NS ) . CONCLUSION : Management of bedridden patients with fecal incontinence with a perianal pouch reduced the incidence of IAD and delayed to time to onset when compared to management with adult containment briefs . We recommend use of perianal pouches for prevention of IAD in bedridden patients with fecal incontinence |
13,313 | 26,131,301 | Continuous passive motion did not improve ultimate motion .
Early weightbearing decreases patellofemoral pain .
Postoperative rehabilitative bracing did not improve swelling , pain range of motion , or safety .
Open chain quadriceps activity can begin at 6 weeks . | Context : Anterior cruciate ligament ( ACL ) reconstruction rehabilitation has evolved over the past 20 years .
This evolution has been driven by a variety of level 1 and level 2 studies .
Evidence Acquisition : The MOON Group is a collection of orthopaedic surgeons who have developed a prospect i ve longitudinal cohort of the ACL reconstruction patients .
To st and ardize the management of these patients , we developed , in conjunction with our physical therapy committee , an evidence -based rehabilitation guideline . | STUDY DESIGN R and omized clinical trial , single-masked . OBJECTIVES To determine the effectiveness of using a modified neuromuscular electrical stimulation ( NMES ) training program as an adjunct treatment for improving quadriceps strength and physical function in rehabilitation following anterior cruciate ligament reconstruction ( ACLR ) . BACKGROUND NMES training for quadriceps strengthening has previously been shown to be an effective adjunct treatment following ACLR when performed against isometric resistance using a dynamometer with the knee positioned in flexion . We developed a modified version of published NMES protocol because some patients have difficulty tolerating the existing protocol and many clinics may not have instrumented dynamometers . There is a need to determine the effectiveness of this modified protocol . METHODS AND MEASURES Forty-three subjects who had undergone ACLR were r and omly assigned to either a group that received ( NMES group ) or did not receive ( comparison group ) the NMES treatment in conjunction with their rehabilitation . Group means for quadriceps strength and self-reported measures of knee function were compared after 12 and 16 weeks of rehabilitation . The proportion of subjects in each group achieving clinical criteria to initiate ambulation without crutches , treadmill running , and agility training at selected times during rehabilitation were also compared . RESULTS The NMES group demonstrated moderately greater quadriceps strength at 12 weeks ( effect size , 0.48 ) , and moderately higher levels of self-reported knee function at both 12 ( effect size , 0.72 ) and 16 ( effect size , 0.65 ) weeks of rehabilitation compared to the comparison group . A greater proportion of subjects in the NMES group achieved clinical criteria for advancing to agility training at 16 weeks . CONCLUSIONS The modified NMES quadriceps training protocol can be a useful adjunct to ACLR rehabilitation programs , but the treatment effect is smaller than what has been reported in previous studies Pre- clinical studies have shown that treatment by pulsed electromagnetic fields ( PEMFs ) can limit the catabolic effects of pro-inflammatory cytokines on articular cartilage and favour the anabolic activity of the chondrocytes . Anterior cruciate ligament ( ACL ) reconstruction is usually performed by arthroscopic procedure that , even if minimally invasive , may elicit an inflammatory joint reaction detrimental to articular cartilage . In this study the effect of I-ONE PEMFs treatment in patients undergoing ACL reconstruction was investigated . The study end-points were ( 1 ) evaluation of patients ’ functional recovery by International Knee Documentation Committee ( IKDC ) Form ; ( 2 ) use of non-steroidal anti-inflammatory drugs ( NSAIDs ) , necessary to control joint pain and inflammation . The study design was prospect i ve , r and omized and double blind . Sixty-nine patients were included in the study at baseline . Follow-up visits were scheduled at 30 , 60 and 180 days , followed by 2-year follow-up interview . Patients were evaluated by IKDC Form and were asked to report on the use of NSAIDs . Patients were r and omized to active or placebo treatments ; active device generated a magnetic field of 1.5 mT at 75 Hz . Patients were instructed to use the stimulator ( I-ONE ) for 4 h per day for 60 days . All patients underwent ACL reconstruction with use of quadruple hamstrings semitendinosus and gracilis technique . At baseline there were no differences in the IKDC scores between the two groups . At follow-up visits the SF-36 Health Survey score showed a statistically significant faster recovery in the group of patients treated with I-ONE stimulator ( P < 0.05 ) . NSAIDs use was less frequent among active patients than controls ( P < 0.05 ) . Joint swelling resolution and return to normal range of motion occurred faster in the active treated group ( P < 0.05 ) too . The 2-year follow-up did not shown statistically significant difference between the two groups . Furthermore for longitudinal analysis the generalized linear mixed effects model was applied to calculate the group × time interaction coefficient ; this interaction showed a significant difference ( P < 0.0001 ) between the active and placebo groups for all investigated variables : SF-36 Health Survey , IKDC Subjective Knee Evaluation and VAS . Twenty-nine patients ( 15 in the active group ; 14 in the placebo group ) underwent both ACL reconstruction and meniscectomy ; when they were analysed separately the differences in SF-36 Health Survey scores between the two groups were larger then what observed in the whole study group ( P < 0.05 ) . The results of this study show that patient ’s functional recovery occurs earlier in the active group . No side effects were observed and the treatment was well tolerated . The use of I-ONE should always be considered after ACL reconstruction , particularly in professional athletes , to shorten the recovery time , to limit joint inflammatory reaction and its catabolic effects on articular cartilage and ultimately for joint preservation Immediately after reconstruction of the anterior cruciate ligament , 110 patients were r and omly assigned to treatment with high-intensity neuromuscular electrical stimulation ( thirty-one patients ) , high-level volitional exercise ( thirty-four patients ) , low-intensity neuromuscular electrical stimulation ( twenty-five patients ) , or combined high and low-intensity neuromuscular electrical stimulation ( twenty patients ) . All treatment was performed isometrically with the knee in 65 degrees of flexion . All of the patients participated in an intensive program of closed-kinetic-chain exercise . After four weeks of treatment , the strength of the quadriceps femoris muscle and the kinematics of the knee during stance phase were measured . Quadriceps strength averaged 70 per cent or more of the strength on the uninvolved side in the two groups that were treated with high-intensity electrical stimulation ( either alone or combined with low-intensity electrical stimulation ) , 57 per cent in the group that was treated with high-level volitional exercise , and 51 per cent in the group that was treated with low-intensity electrical stimulation . The kinematics of the knee joint were directly and significantly ( p < 0.05 ) correlated with the strength of the quadriceps . There was a clinical ly and statistically significant ( p < 0.05 ) difference in the recovery of the quadriceps and the gait parameters according to the type of operation that had been performed : the patients who had had reconstruction of the anterior cruciate ligament with use of an autologous patellar-ligament graft did poorly compared with the other patients Background This study will attempt to evaluate the efficacy of knee immobilization on patient pain levels after an anterior cruciate ligament reconstruction . Hypothesis There is no difference in visual analog scale pain scores 2 days after anterior cruciate ligament reconstruction between patients who wear a knee immobilizer and those who do not wear a knee immobilizer . Study Design R and omized clinical trial ; Level of evidence , 1 . Methods Patients aged 18 to 40 years who met study inclusion criteria were eligible . Patients meeting intraoperative inclusion critiera were r and omized ( immobilizer or no immobilizer ) after wound closure . The immobilizer used was a soft , unhinged brace with Velcro ® straps . Preoperative , intraoperative , and postoperative protocol s were st and ardized . The primary outcome was patient self-assessed pain using a 0-to-100-mm visual analog scale at day 2 after surgery . Secondary outcomes included pain and analgesic use in the first 14 days after surgery , complications , and range of motion ( approximately 3 weeks postoperatively ) . A sample size estimate was calculated and result ed in the need for 44 patients per group . Results A total of 102 patients were enrolled ; 88 patients were r and omized , and 14 were excluded intraoperatively . There was no difference in mean visual analog scale pain scores at 2 days after surgery between immobilized and nonimmobilized patients ( 32.6 and 35.2 , respectively ; P = .59 ; difference , —2.6 ; 95 % confidence interval , —12.2 to 6.9 ) . There were no differences between groups in medication consumed , range of motion , or complications . Pain and analgesic use were the same for both groups at 7 and 14 days postoperatively . Conclusion No differences in pain or any of the secondary outcomes were detected between immobilized and nonimmobilized patients at any point during the first 14 days after anterior cruciate ligament reconstruction A prospect i ve , blinded , r and omised controlled trial investigated the effectiveness of quadriceps exercises following anterior cruciate ligament reconstruction . A treatment group ( Quadriceps exercise group ) performed straight leg raises and isometric quadriceps contractions throughout the first two postoperative weeks , and a second group ( No quadriceps exercise group ) did not . A battery of outcome measures assessed subjects postoperatively at day one , two weeks , and one , three and six months . A total of 103 patients ( Quadriceps exercise n = 48 , No quadriceps exercise n = 55 ) commenced the study with 91 subjects available at final follow up ( Quadriceps exercise n = 47 , No quadriceps exercise n = 44 ) . Performance of quadriceps exercises significantly improved a number of knee flexion and extension range of motion measurements ( p = 0.01 to 0.04 ) . No significant differences were found between the two groups at any postoperative period for quadriceps lag ( p = 0.36 ) , functional hop testing ( p = 0.49 to 0.51 ) , isokinetic quadriceps strength ( p = 0.70 to 0.72 ) , the majority of numerical analogue scores ( p = 0.1 to 0.94 ) and Cincinnati scores ( p = 0.10 to 0.84 ) . Subjects performing quadriceps exercises reported significantly higher pain scores with exercise on the first postoperative day ( p = 0.02 ) . At six months postoperatively , the Quadriceps exercise subjects reported significantly more favourable Cincinnati scores for symptoms ( p = 0.005 ) and problems with sport ( p = 0.05 ) . While average knee laxity was not significantly different between treatment groups over time ( p = 0.27 to 0.94 ) , quadriceps exercise performance was associated with a significantly lower incidence of abnormal knee laxity . Isometric quadriceps exercises and straight leg raises can be safely prescribed during the first two postoperative weeks and confer advantages for faster recovery of knee range of motion and stability . It remains to be proven whether the magnitude of differences between groups is clinical ly significant The aim of the present study is to compare the effect of electrical muscle stimulation combined with voluntary muscle contractions with a program only with voluntary muscle contractions during immobilization in casts after anterior cruciate ligament surgery . Twenty-three patients , 7 women and 16 men with a mean age of 28 yr , were r and omized into two groups : an experimental group ( 13 patients ) and a control group ( 10 patients ) . Post-operatively , the patients were immobilized for 3 wk in a full leg cast with the knee flexed at an angle of 20 degrees to 30 degrees and then in a knee cast for another 3 wk . All patients had a st and ard program with quadriceps muscle contractions . In addition , the experimental group received electrical stimulation of the quadriceps muscle 4 X 10 min , 3 times.wk-1 , at a frequency of 30 Hz . During each stimulation , the patients were requested to contract the quadriceps muscle voluntarily as well . When pre-operative measurements were compared with those at the end of the immobilization period ( 6 wk after the operation ) , a significantly larger reduction in the knee extension isometric muscle strength was found for the control group than for the experimental group . In comparisons of the data of the male subjects only , this difference was still seen to be significant . The cross-sectional area of the quadriceps muscle measured with computed tomography was significantly less reduced during the immobilization period in the experimental group than in the control group . ( ABSTRACT TRUNCATED AT 250 WORDS To evaluate the effects of a rehabilitation brace locked in extension for the first week on the recovery of full extension after ACL reconstruction we compared two groups of subjects who underwent ACL bone-patellar tendon-bone reconstruction . The brace was unlocked twice a day for assisted physiotherapy . In Group A , 18 male subjects wore a post-operative brace locked from 0 ° to 90 ° . In Group B , 18 male subjects wore the same post-op brace locked in full extension for the first week . In both groups the brace was unlocked ( 0 ° -120 ° ) at the beginning of the second postoperative week , and then removed at the beginning of the third week . All the subjects followed the same rigorous , accelerated rehabilitation protocol . Each subject was evaluated pre and post-operatively ( at second , fourth and eighth week ) with bubble-level heel height difference ( HHD ) measurements and KT 1000 arthrometric assessment at the fourth postoperative month . Preoperative bubble-level HHD measurements of the two groups were statistically similar ( Group A 0.6 cm , Group B 1 cm ; not significant , n.s . ) . At the fourth week ( Group A 2.2 cm , Group B 0.6 cm ) and eighth week ( Group A 1.6 cm , Group B 0.1 cm ) follow-ups , bubble-level HHD measurements showed that the extension of the operated knees of Group B was significantly greater than in Group A. KT 1000 arthrometric scores showed no difference between the two groups ( Group A 1.8 mm , Group B 1.5 ; n.s . ) If permission of full active and passive extension immediately after an anterior cruciate ligament ( ACL ) reconstruction will increase the post-operative laxity of the knee has been a subject of discussion . We investigated whether a post-operative rehabilitation protocol including active and passive extension without any restrictions in extension immediately after an ACL reconstruction would increase the post-operative anterior – posterior knee laxity ( A – P laxity ) . Our hypothesis was that full active and passive extension immediately after an ACL reconstruction would have no effect on the A – P laxity and clinical results up to 2 years after the operation . Twenty-two consecutive patients ( 14 men , 8 women , median age 21 years , range 17–41 ) were included . All the patients had a unilateral ACL rupture and no other ligament injuries or any other history of previous knee injuries . The surgical procedure was identical in all patients and one experienced surgeon operated on all the patients , using the bone-patellar tendon-bone autograft . The post-operative rehabilitation programme was identical in both groups , except for extension training during the first 4 weeks post-operatively . The patients were r and omly allocated to post-operative rehabilitation programmes either allowing ( Group A , n=11 ) or not allowing [ Group B ( 30 to −10 ° ) , n=11 ] full active and passive extension immediately after the operation . They were evaluated pre-operatively and at 6 months and 2 years after the reconstruction . To evaluate the A – P knee laxity , radiostereometric analysis ( RSA ) and KT-1000 arthrometer ( KT-1000 ) measurements were used , range of motion , Lysholm score , Tegner activity level , the International Knee Documentation Committee ( IKDC ) evaluation system and one-leg-hop test quotient were used . Pre-operatively , the RSA measurements revealed side-to-side differences in Group A of 8.6 mm ( 2.3–15.4 ) , median ( range ) and in Group B of 7.2 mm ( 2.2–17.4 ) ( n.s . ) . The corresponding KT-1000 values were for Group A , 2.0 mm ( 0–8.0 ) and Group B , 4.0 mm ( 0–10.0 ) ( n.s . ) . At 2 years , the differences between the two groups were minimal , regardless of the method that had been used . The RSA measurements in Group A were 2.7 mm ( 0–10.7 ) and in Group B 2.8 ( −1.8 to 9.5 ) . The KT-1000 values were for Group A , 1.0 mm ( −1.5 to 3.5 ) , and for Group B , 0.5 mm ( −1.0 to 4.0 ) , without any significant differences between the groups . Nor did the Lysholm score , Tegner activity level , IKDC or one-leg-hop test differ . Early active and passive extension training , without any restrictions in extension , immediately after an ACL reconstruction using bone-patellar tendon-bone graft did not increase post-operative knee laxity up to 2 years after the ACL reconstruction Seventy-five patients undergoing arthroscopically-as sisted anterior cruciate ligament reconstruction by the same surgeon were divided into three r and om subgroups . All of the anterior cruciate ligament recon structions used the middle third of the ipsilateral patellar tendon autograft . Patients undergoing meniscal repair , extraarticular procedures , or repair of other ligaments were excluded . The 75 patients were divided into subgroups to assess the benefits or disadvantages of early active motion ( 25 patients ) , continuous passive motion ( 25 patients ) , and a combination of both ( 25 patients ) during the first 30 days after surgery . All patients were evaluated at specific intervals for 6 months after surgery . Data recorded included drain output , medication usage , tourniquet time , leg involved , hospital stay length , KT-1000 testing ( before surgery in the anesthetized patient , after the procedure was com pleted , and 2 and 6 months after surgery ) , and range of motion . Radiographs and the International Knee Evaluation Form were also used to evaluate the results . No statistically significant differences were found be tween the three groups . Side-to-side anterior-posterior differences , stability , and restoration of full range of motion were similar in each subgroup at each evaluated interval . In this prospect i ve study of motion , started immediately after anterior cruciate ligament reconstruc tion , passive and active methods were shown to have identical results . A supervised active and passive mo tion program during the 1 st month had the same results as either one used individually The use of continuous passive motion ( CPM ) following anterior cruciate ligament ( ACL ) reconstruction has become common . The duration of use of CPM for maximal therapeutic benefit is not known . This study compared 4-day CPM use with 14-day CPM use following arthroscopic ACL reconstruction using a bone-patellar tendon-bone autograft prospect ively in 20 patients . The patients were r and omly allocated to the CPM 4-day group [ 6 h daily CPM for 4 days in hospital followed by intermittent passive motion ( IPM ) at home ] or to the CPM 14-day group ( 6 h daily CPM for 14 days ) . The objective parameters measured were girth measurements at four lower limb locations for joint swelling and muscle atrophy ; range of motion of the knee , measured goniometrically ; and KT-1000 arthrometry measurements for joint laxity . The measurements were made prior to surgery , and on days 2 , 7 , 14 , and 42 , postoperatively . There were no statistically significant differences ( p greater than 0.05 ) at 42 days postoperatively between groups in all parameters measured with the exception of KT-1000 laxity at 42 days The purpose of this study was to compare the effects of two protocol s of electrical stimulation combined with voluntary contractions on the recovery of thigh muscles after anterior cruciate ligament ( ACL ) surgery . Ten sportsmen with a mean age of 26 yrs were r and omly assigned into two groups : a 80 Hz stimulated group ( 5 patients ) and a 20 Hz stimulated group ( 5 patients ) . All patients received electrical stimulation of the quadriceps femoris , five days a week , for 12 weeks , and had a st and ard program of voluntary contractions . Muscle and fat volumes of the thigh were assessed using MRI before surgery and after 12 weeks of rehabilitation . Quadriceps and hamstring muscle strength were evaluated by isokinetic measurements . Twelve weeks after surgery , the quadriceps peak torque deficit in the operated limb with respect to the non operated limb at 180 degrees /s and 240 degrees /s was significantly ( p < 0.05 ) less in the 20 Hz group than in the 80 Hz group . This difference was not confirmed when comparing the pre-surgery quadriceps peak torque of the operated limb with the post-surgery one . Subcutaneous fat volume was increased for the two groups at the post-surgery test . This increase was significantly ( p < 0.05 ) greater for the 80 Hz group . Thigh muscle volume deficit was not significantly different between the two groups Background and Purpose The purpose of this study was to determine the effect of a 6-month neuromuscular training ( NT ) program versus a traditional strength training ( ST ) program following anterior cruciate ligament ( ACL ) reconstruction . Subjects Seventy-four subjects with ACL reconstruction participated in the study . Methods The study was a r and omized , single-blinded , controlled trial . The NT and ST groups were tested preoperatively and at 3 and 6 months . The main outcome measure was the Cincinnati Knee Score . Secondary outcome measures were visual analog scales ( VASs ) for pain and function , the 36-Item Short-Form Health Survey ( SF-36 ) , hop tests , isokinetic muscle strength , proprioception , and static and dynamic balance tests . Results The NT group demonstrated significantly improved Cincinnati Knee Scores and VAS scores for global knee function compared with the ST group at the 6-month follow-up . There were no significant differences between the groups for the other outcome measures ( ie , hop , balance , proprioception , and muscle strength tests ) . Discussion and Conclusion The results of this study suggest that exercises included in the NT program should be part of the rehabilitation program following ACL reconstruction BACKGROUND AND PURPOSE Nondistally fixated ( ie , what is often referred to as " open kinetic chain " [ OKC ] ) knee extensor resistance training appears to have lost favor for some forms of rehabilitation due partly to concerns that this exercise will irritate the extensor mechanism . In this r and omized , single-blind clinical trial , nondistally fixated versus distally fixated ( ie , often called " closed kinetic chain " [ CKC ] ) leg extensor training were compared for their effects on knee pain . SUBJECTS Forty-three patients recovering from anterior cruciate ligament ( ACL ) reconstruction surgery ( 34 male , 9 female ; mean age=29 years , SD=7.9 , range=16 - 54 ) . METHODS Knee pain was measured at 2 and 6 weeks after ACL reconstruction surgery using visual analog scales in a self- assessment question naire and during maximal isometric contractions of the knee extensors . Between test sessions , subjects trained 3 times per week using either OKC or CKC resistance of their knee and hip extensors as part of their physical therapy . RESULTS No differences in knee pain were found between the treatment groups . DISCUSSION AND CONCLUSION Open kinetic chain and CKC leg extensor training in the early period after ACL reconstruction surgery do not differ in their immediate effects on anterior knee pain . Based on these findings , further studies are needed using different exercise dosages and patient groups Abstract In a prospect i ve study 60 patients were r and omized to brace and no-brace groups after bone-tendon-bone anterior cruciate ligament reconstruction . The brace group wore a rehabilitation orthosis for 12 weeks postoperatively , while the no-brace group was mobilized immediately , and crutches were discarded 2 weeks postoperatively . The groups were comparable with respect to age , gender , time from injury to surgery , knee score ( Lysholm ) , activity level ( Tegner ) , degree of laxity and isokinetic muscle torque . Although compared with the preoperative situation patients in both groups had significantly improved , there were no differences between the groups 1 and 2 years postoperatively in terms of functional outcome ( Lysholm and Tegner scores ) , stability of the knee or isokinetic muscle torque Data from large prospect ively collected anterior cruciate ligament ( ACL ) cohorts are being utilized to address clinical questions regarding ACL injury demographics and outcomes of ACL reconstruction . These data are affected by patient and injury factors as well as surgical factors associated with the site of data collection . The aim of this article is to compare primary ACL reconstruction data from patient cohorts in the United States and Norway , demonstrating the similarities and differences between two large cohorts . Primary ACL reconstruction data from the Multicenter Orthopaedic Outcomes Network ( MOON ) in the United States and the Norwegian National Knee Ligament Registry ( NKLR ) were compared to identify similarities and differences in patient demographics , activity at injury , preoperative Knee injury and Osteoarthritis Outcome Score ( KOOS ) , time to reconstruction , intraarticular pathology , and graft choice . Seven hundred and thirteen patients from the MOON cohort were compared with 4,928 patients from the NKLR . A higher percentage of males ( NKLR 57 % , MOON 52 % ; P < 0.01 ) and increased patient age ( NKLR 27 years , MOON 23 years ; P < 0.001 ) were noted in the NKLR population . The most common sports associated with injury in the MOON cohort were basketball ( 20 % ) , soccer ( 17 % ) , and American football ( 14 % ) ; while soccer ( 42 % ) , h and ball ( 26 % ) , and downhill skiing ( 10 % ) were most common in the NKLR . Median time to reconstruction was 2.4 ( Interquartile range [ IQR ] 1.2–7.2 ) months in the MOON cohort and 7.9 ( IQR 4.2–17.8 ) months in the NKLR cohort ( P < 0.001 ) . Both meniscal tears ( MOON 65 % , NKLR 48 % ; P < 0.001 ) and articular cartilage defects ( MOON 46 % , NKLR 26 % ; P < 0.001 ) were more common in the MOON cohort . Hamstring autografts ( MOON 44 % , NKLR 63 % ) and patellar tendon autografts ( MOON 42 % , NKLR 37 % ) were commonly utilized in both cohorts . Allografts were much more frequently utilized in the MOON cohort ( MOON 13 % , NKLR 0.04 % ; P < 0.001 ) . Significant diversity in patient , injury , and surgical factors exist among large prospect i ve cohorts collected in different locations . Surgeons should investigate and consider the characteristics of these cohorts when applying knowledge gleaned from these groups to their own patient population Objective : To compare the effect of a whole body vibration training ( WBVT ) programme with a conventional training ( CT ) programme on knee proprioception and postural stability after anterior cruciate ligament ( ACL ) reconstruction . Methods : Twenty athletes with unilateral ACL reconstruction were r and omly assigned to the WBVT or CT group ; all participants received 12 sessions of WBVT or conventional training . Absolute error in joint repositioning for two target angles ( 30 ° and 60 ° ) was measured with the Biodex dynamometer ; bilateral dynamic postural stability ( anteroposterior , mediolateral and overall stability indices ) was measured with the Biodex Stability System pre-intervention and post-intervention . Results : The improvement in postural stability in the WBVT group was significantly greater than that in the CT group ( p⩽0.05 ) . The p values of the changing scores of open overall , open anteroposterior , open mediolateral , closed overall , closed anteroposterior and closed mediolateral stability indices were 0.002 , 0.010 , 0.0001 , 0.001 , 0.0001 and 0.046 , respectively . In addition , there were significant differences in all averages of absolute angular error at 60 ° and 30 ° between the WBVT and CT groups in both knees ( p = 0.001 in healthy knees and p = 0.001 and p = 0.0001 in reconstructed knees ) , apart from the healthy knees at the 30 ° target position , which was not significant ( p = 0.131 ) . Conclusions : Whole body vibration training improved proprioception and balance in athletes with reconstructed ACL Neuromuscular electrical stimulation and voluntary muscle contraction are two exercise modes widely used in rehabilitation to strengthen skeletal muscle . Since there is no debate as to which mode is most effective , we compared electrical stimulation with voluntary contraction performed at matched intensities following reconstructive surgery of the anterior cruciate ligament . Forty men and women , aged 15 - 44 , were r and omly assigned to either an electrical stimulation or a voluntary contraction group . None of the subjects had a previous history of neuromuscular injury . The subjects received treatment for 30 minutes a day , 5 days a week , for 4 weeks . Knee extension torque was monitored during treatment to try to match the absolute muscular tensions ( quantified as " activity " ) achieved during therapy . To match the activity of the subjects in the electrical stimulation group , who were treated at the highest stimulation intensity they could tolerate , the subjects in the voluntary contraction group were paced at progressively increasing intensities corresponding to 15 , 25 , 35 , and 45 % of the injured limb 's maximum voluntary torque during weeks 1 , 2 , 3 , and 4 , respectively . We found no significant difference between the groups in terms of maximum voluntary knee extension torque throughout the study period . In addition , 1 year after surgery , there was still no significant difference between groups with regard to knee extension torque ( p > 0.4 ) . These data suggest that neuromuscular electrical stimulation and voluntary muscle contraction treatments , when performed at the same intensity , are equally effective in strengthening skeletal muscle that has been weakened by surgical repair of the anterior cruciate ligament A r and omised controlled trial ( 29 participants ) was used to compare a 6-week proprioceptive and balance exercise program with a 6-week strengthening program in the early phases of rehabilitation after anterior cruciate ligament ( ACL ) reconstruction . Measurements of functional activity were taken by a blinded assessor before the intervention and at the end of the 6 weeks . Results demonstrated that there were no significant differences between groups on hop testing at 6 weeks . For several items in the Cincinnati knee rating system and the patient specific functional scale however , the strengthening group improved more than the proprioceptive and balance group ( p < .05 ) . The hypothesis that proprioceptive and balance training would improve functional activity more than strengthening exercises was not supported . There was either no difference between the two forms of exercise or strength training may be more beneficial than proprioceptive and balance training in the early phase of rehabilitation after ACL reconstructive surgery STUDY DESIGN R and omized clinical trial . OBJECTIVES Determine effective interventions for improving readiness to return to sports postoperatively in patients with complete , unilateral , anterior cruciate ligament ( ACL ) rupture who do not compensate well after the injury ( noncopers ) . Specifically , we compared the effects of 2 preoperative interventions on quadriceps strength and functional outcomes . BACKGROUND The percentage of athletes who return to sports after ACL reconstruction varies considerably , possibly due to differential responses after acute ACL rupture and different management . Prognostic data for noncopers following ACL reconstruction is absent in the literature . METHODS Forty noncopers were r and omly assigned to receive either progressive quadriceps strength-training exercises ( STR group ) or perturbation training in conjunction with strength-training exercises ( PERT group ) for 10 preoperative rehabilitation sessions . Postoperative rehabilitation was similar between groups . Data on quadriceps strength indices [ ( involved limb/uninvolved limb force ) x 100 ] , 4 hop score indices , and 2 self-report question naires were collected preoperatively and 3 , 6 , and 12 months postoperatively . Mann-Whitney U tests were used to compare functional differences between the groups . Chi-square tests were used to compare frequencies of passing functional criteria and reasons for differences in performance between groups postoperatively . RESULTS Functional outcomes were not different between groups , except a greater number of patients in the PERT group achieved global rating scores ( current knee function expressed as a percentage of overall knee function prior to injury ) necessary to pass return-to-sports criteria 6 and 12 months after surgery . Mean scores for each functional outcome met return-to-sports criteria 6 and 12 months postoperatively . Frequency counts of individual data , however , indicated that 5 % of noncopers passed RTS criteria at 3 , 48 % at 6 , and 78 % at 12 months after surgery . CONCLUSION Functional outcomes suggest that a subgroup of noncopers require additional supervised rehabilitation to pass stringent criteria to return to sports . LEVEL OF EVIDENCE Therapy , level 2b . Note : If watching the first video , we recommend downloading and referring to the accompanying PowerPoint slides for any text that is not readable In a prospect i ve , r and omized study , 34 patients ( 25 male , 9 female ; mean age 27±8 years ) with unilateral anterior cruciate ligament ruptures and arthroscopic reconstruction with patellar tendon grafts were allocated at r and om to either early active motion only ( AM;n=17 ) or active motion in combination with continuous passive motion ( CPM;n=17 ) . Range of motion was measured with a goniometer and joint swelling with a tape measure , preoperatively and at 6 weeks postoperatively . Neither associated injuries nor the age of the aptients differed in the two groups . There was no difference in the range of motion between the two groups at 6 weeks ' follow-up . Joint swelling was more pronounced in the AM group both preoperatively and at 6 weeks ' follow-up . In this investigation the range of motion was not improved by CPM . The difference in joint swelling between the two groups may be explained by a persistent preoperative variation in joint effusion due to an imbalanced distribution of acute and chronic cases STUDY DESIGN Two-group repeated measures design using a sample of convenience of subjects with anterior cruciate ligament ( ACL ) reconstructive surgery . OBJECTIVES To determine the effect of incorporating one specific weight-bearing exercise ( lateral slide exercise using a slide board ) into an ACL reconstruction home exercise program . BACKGROUND Reduced clinic visits have increased the importance of home exercise programs in knee ligament reconstruction rehabilitation . Few studies have been conducted to test the efficacy of specific exercises as part of a home-based treatment program on subjects who have undergone ACL reconstruction . METHODS AND MEASURES Fourteen subjects who underwent patella tendon autograft reconstruction on one of their ACLs were studied . Testing consisted of the following 4 measurements : peak isometric knee extension torque , peak isometric knee flexion torque , maximum lateral step height , and lateral step-up repetitions to fatigue . Subjects were pretested at 8 weeks after surgery and were r and omly placed into either a control or experimental group . The postsurgical rehabilitation was similar for both groups , except the experimental group incorporated lateral slide exercise into their home exercise program . All subjects were re-evaluated 14 weeks after surgery . RESULTS A 2-way repeated measure ANOVA ( group by test session ) , and posthoc testing revealed significant improvements in the slide group for quadricep strength ( 101.9 + /- 31.3 N m to 140.5 + /- 31.3 N m of torque ) , while the control group showed no significant increase ( 125.1 + /- 61.7 N m to 125.8 + /- 45.1 N m of torque ) . Lateral step height also improved in the slide group ( from 22.9 + /- 5.3 cm to 28.7 + /- 5.6 cm ) , while the control group showed no increase ( 20.0 + /- 4.5 cm to 20.7 + /- 3.4 cm ) . Both groups increased in lateral step-up repetitions to fatigue . CONCLUSION Including lateral slide exercise in a home exercise program after ACL reconstruction appears to improve knee extension strength The purpose of this prospect i ve , r and omized , clinical trial was to evaluate the effect of knee bracing after anterior cruciate ligament reconstruction . Sixty patients were r and omized into one of two groups : Patients in the braced group wore rehabilitative braces for 2 weeks , followed by functional braces for 10 weeks , and patients in the nonbraced group did not wear braces . Data were recorded preoperatively , and postoperatively after 6 weeks , 3 and 6 months , and 1 and 2 years . The following outcome measures were used : KT-1000 arthrometry , the Cincinnati knee score , goniometry to record range of motion , computed tomography to determine thigh atrophy , Cybex 6000 isokinetic testing to evaluate muscle strength , three functional knee tests , and a visual analog scale to evaluate pain . At all follow-up times there were no significant differences between the two groups with regard to knee joint laxity , range of motion , muscle strength , functional knee tests , or pain . However , the Cincinnati knee score showed that patients in the braced group had significantly improved knee function compared with patients in the nonbraced group at the 3-month follow-up , even though the braced group showed significantly increased thigh atrophy compared with the nonbraced group at 3 months Abstract Despite changes in rehabilitation protocol s , an extension deficit remains an important potential cause of significant morbidity following anterior cruciate ligament ( ACL ) reconstruction . An extension-assisting brace was design ed using a limited motion brace and an elastic strap across a fulcrum on the anterior aspect of the knee joint . The effects of the brace were investigated in 40 patients undergoing primary ACL reconstruction using an autogenous central third patellar tendon graft . The patients were r and omized either to use the brace in the first 6 weeks postoperatively or to undertake the same accelerated rehabilitation programme but without any brace , and they were review ed at 4 months postoperatively . The following data were recorded : passive and active extension and flexion deficits compared with the non-operated limb , KT-1000 assessment of anterior laxity and isometric quadriceps and hamstring strength . There was no difference between the two groups for any of the recorded variables . This was largely attributed to satisfactory tunnel placement and emphasis on the restoration of extension and quadriceps function during the early postoperative rehabilitation Sixteen patients participated in a prospect i ve r and omized trial in which a st and ard cylinder cast was compared with a mobile cast brace . Both were worn for 4 weeks , beginning at 1 week after reconstruction of the anterior cruciate ligament . The athletes that had used a cast brace could return to sports activities in about one-half the time it took for the athletes with a st and ard cast . The patients with a st and ard cast showed a significant atrophy of Type I ( slow twitch ) muscle fibers in the vastus lateralis . The cast brace patients did not show any significant changes in cross-sectional areas of Type I or Type II ( fast twitch ) muscle fibers . The st and ard cast patients had a significant reduction of succinate dehydrogenase ( SDH ) activity in the vastus lateralis whereas the patients with the cast brace did not show any significant changes . No difference in surgical end result was found . A cast brace with a limited range of motion between 20 and 60 ° of flexion is recommended as the st and ard postopera tive treatment after knee ligament surgery BACKGROUND AND PURPOSE Electrical stimulation has been shown to be effective in aiding the recovery of quadriceps femoris muscle force production after anterior cruciate ligament reconstruction . The actual dosage of stimulation ( training intensity ) has not been well described . The purpose of this investigation was to establish a dose-response curve for electrical stimulation regimens design ed to improve quadriceps femoris muscle recovery in patients after anterior cruciate ligament reconstruction . SUBJECTS AND METHODS We analyzed data from a sub sample ( n = 52 ) of patients receiving electrical stimulation ( N = 110 ) who were involved in a large , multicenter r and omized clinical trial investigating treatment strategies design ed to enhance quadriceps femoris muscle recovery . Fifty-two subjects ( 40 male , 12 female ) , with an age range of 15 to 43 years ( mean = 25 , SD = 7 ) , participated in 4 weeks of quadriceps femoris muscle training using either portable , battery-powered home stimulators or console stimulators design ed for clinical use . Training intensities were monitored by logging the electrically elicited knee extension torque and expressing this torque as a percentage of the uninvolved quadriceps femoris muscles ' maximal voluntary contraction force . After the 4 weeks of training , isometric muscle torque was assessed and a dose-response curve was generated . The relationship between training intensity and quadriceps femoris muscle torque was assessed with Pearson Product-Moment Correlation Coefficients . RESULTS A significant , linear correlation was found between training intensity and quadriceps femoris muscle torque . Subjects training with console , clinical generators trained at higher intensities than those training with portable , battery-operated generators ; such training result ed in higher quadriceps femoris muscle torque . CONCLUSION AND DISCUSSION These results support the use of high-intensity electrical stimulation and do not support the use of low-intensity or battery-powered stimulators when the goal is recovery of quadriceps femoris muscle force production in the early phases of rehabilitation after anterior cruciate ligament surgery . [ Snyder-Mackler L , Delitto A , Stralka SW , Bailey SL . Use of electrical stimulation to enhance recovery of quadriceps femoris muscle force production in patients following anterior cruciate ligament reconstruction The purpose of this prospect i ve and r and omized study was to compare rehabilitation with early range of motion ( ROM ) training vs immobilization following anterior cruciate ligament ( ACL ) reconstruction . Fifty patients , undergoing an ACL reconstruction with a bone-patellar tendon-bone graft , were postoperatively allocated r and omly to either a plaster cast or a brace for 5 weeks . The brace group had ROM exercises from postoperative day 7 . The commencement of ROM exercises was postponed 4 weeks for the plaster group compared to the brace group , but progressed subsequently with equal speed . There was no difference between the groups in the ROM of flexion or extension 20 weeks after the ACL reconstruction and later . Twenty-four months after surgery , the muscle strength deficit in the hamstring muscles ( isokinetic measurements ; percent difference , injured vs uninjured ) was significantly larger in the brace group ( mean + /- SD : 5.9 + /- 7.8 % , P < 0.01 ) than in the plaster group ( - 0.9 + /- 11.8 % , NS ) ( brace vs plaster group , P < 0.05 ) . Furthermore , there was also a tendency in the brace group to a larger strength deficit in the quadriceps muscle ( brace : 11.1 + /- 13.2 % , P < 0.001 ; plaster : 3.8 + /- 12.9 % , NS ) ( brace vs plaster group , P= 0.07 ) . There was no difference between the groups in the total sagittal knee laxity , as measured with an arthrometer , or in the subjective knee function or activity level ( Lysholm score together with the Tegner activity level ) between the groups . It is concluded that the postoperative treatment with early range of motion training after ACL reconstruction gave as good ROM , knee stability , subjective knee function and activity level as the treatment with immobilization . It is hypothesized that the larger strength deficit observed after rehabilitation with early range of motion training is secondary to the more intensive training and physical therapist involvement that was dem and ed in order to achieve full ROM following immobilization Immediate weightbearing has been advocated after anterior cruciate ligament reconstruction and is thought to enhance the return of quadriceps muscle activity and knee extension range of motion without jeopardizing graft integrity . This study examined the effect of immediate weightbearing after anterior cruciate ligament reconstruction on the return of vastus medialis oblique electromyography activity , knee extension range of motion , knee stability , physical examination , Lysholm score , and anterior knee pain . Forty-nine patients ( 24 men and 25 women ) undergoing endoscopic central third patella tendon autograft reconstruction were r and omized prospect ively into two groups . Group 1 patients underwent immediate weightbearing as tolerated . Group 2 patients were kept nonweightbearing for 2 weeks . All measurements were taken before surgery , 2 weeks after surgery , and between 6 and 14 months ( average , 7.3 months ) followup . There was no effect of weightbearing on knee extension range of motion or vastus medialis oblique function at followup . In addition , knee stability was not compromised after surgery . Seven of 20 ( 35 % ) nonweightbearing patients and only two of 25 ( 8 % ) immediate weight-bearing patients reported anterior knee pain at followup . Overall , immediate weightbearing did not compromise knee joint stability and result ed in a better outcome with a decreased incidence of anterior knee pain Objective To examine the effective use of stairclimbing as an alternative to cycling for knee rehabilitation in an actual injured sport population . Design Repeated- measures multivariate analyses with data collected during anterior cruciate ligament ( ACL ) rehabilitation . Setting Clinical rehabilitation setting following ACL reconstruction . Participants 46 athletes with ACL reconstruction ( 32 males , 14 females ; age 25.5 ± 8.9 yrs ) were r and omly assigned to either cycle or stairclimber programs previously matched by metabolic equivalents ( METs ) and heart rate . Main Outcome Measures Isokinetic testing was performed at 4 and 12 weeks postoperatively on the uninjured knee to safely determine mean and peak concentric quadriceps , eccentric quadriceps , concentric hamstring , and eccentric hamstring peak torques . Pre/post leg girths were also measured bilaterally ( + 7.6 , + 15.2 , + 22.9 , −7.6 , −15.2 , −22.9 cm ) proximal/distal to the patella . Results Multivariate analysis of variance indicated no differences ( Wilks ' Lambda F8,37 = 1.461 ; p = 0.21 ; η2 = 0.240 ; Power = 0.556 ) in strength gains ( NM ) between cycle and stairclimbing groups , respectively , in mean concentric quadriceps ( 58.4 ± 12.0 vs. 37.1 ± 13.2 ) , peak concentric quadriceps ( 77.0 ± 14.7 vs. 36.8 ± 16.2 ) , mean eccentric quadriceps ( 57.2 ± 12.7 vs. 79.2 ± 14.0 ) , peak eccentric quadriceps ( 78.6 ± 19.3 vs. 105.5 ± 21.3 ) , mean concentric hamstring ( 14.3 ± 3.9 vs. 6.5 ± 4.3 ) , peak concentric hamstring ( 24.0 ± 6.7 vs. 22.2 ± 7.4 ) , mean eccentric hamstring ( 22.6 ± 8.6 vs. 23.8 ± 9.5 ) , or peak eccentric hamstring ( 23.5 ± 11.2 vs. 36.7 ± 12.3 ) response . A significant stairclimbing effect ( Wilks ' Lambda F6,37 = 2.95 ; p = 0.02 ; η2 = 0.324 ; Power = 0.843 ) was observed in gastrocnemius girth ( −15.2 cm ) in both injured ( 0.5 ± 0.1 cm vs. 0.3 ± 0.1 cm , p < 0.04 ) and noninjured ( 0.3 ± 0.1 cm vs. 0.0 ± 0.1 cm , p < 0.008 ) legs . Conclusions In conclusion , the results of the data suggest no deleterious effect of stairclimbing on knee isokinetic performance or limb girth measurements , and confirms the use of stairclimbing as a viable adjunct/alternative to cycle ergometry in ACL-injured athletes We evaluated the outcome of and compared two rehabilitation programs ( clinic-based versus home ) after a mid-third patellar autograft reconstruction of the anterior cruciate ligament . Thirty-seven patients ( 28 male , 9 female ; average age , 24.1 years ) completed the study . Fifteen of these patients received clinic-based rehabilitation ( three visits per week for 6 weeks prescribed ) , and 22 patients received home-based physical therapy ( number of visits determined by patient response ) . Knee ROM , Lysholm , Visual Analogy Scale , ( VAS ) pain rating , hop test , KT-1000 , and Sickness Impact Profile ( SIP ) were evaluated preoperatively and postoperatively . All patients reported good satisfaction with the function of their knee at average follow-up of 21.6 months ( range , 12 to 48 ) . Patients managed by home rehabilitation averaged 2.85 visits as compared with 14.2 for clinic-centered patient ( P < .05 ) . There were no differences in functional or subjective outcomes in the different postoperative rehabilitation regimens , with both groups reporting high satisfaction and improved quality of life . Cost savings in the home rehabilitation group were significant BACKGROUND AND PURPOSE Exercises in water have been shown to be effective for improving strength and passive range of motion ( PROM ) . Traditional rehabilitation following intra-articular anterior cruciate ligament ( ACL ) reconstruction has taken place on l and . This study was design ed to compare the effects of exercises in water on strength and girth of the thigh musculature , knee PROM , joint laxity , effusion , and functional outcome with the effects of similar exercises on l and in subjects following intra-articular reconstruction of the ACL . SUBJECTS Twenty subjects were r and omly assigned to either a group that exercised on l and or a group that exercised in water . METHODS Thigh girth , joint effusion , and knee PROM measurements were recorded at 2-week intervals for the first 8 weeks postoperatively . Isokinetic and isometric peak torque measurements for the thigh musculature , knee joint laxity assessment s , and Lysholm scores were obtained at the end of 8 weeks . RESULTS Higher outcome scores were recorded in the water group than in the l and group , as measured by Lysholm scales . No differences were noted between groups for knee PROM , thigh girth , or quadriceps femoris muscle performance . In the water group , less joint effusion was noted after the 8 weeks . In the l and group , greater peak torque for isokinetic knee flexion was recorded . CONCLUSION AND DISCUSSION Although exercise in water may not be as effective as exercise on l and for regaining maximum muscle performance , rehabilitation in water may minimize the amount of joint effusion and lead to greater self-reports of functional improvement in subjects with intra-articular ACL reconstructions Continuous passive motion ( CPM ) may have potential application as a physical modality in decreasing acute pain . The purpose of this study was to examine the effects of CPM immediately following an arthroscopically-assisted anterior cruciate ligament ( ACL ) reconstruction utilizing bone-patella-bone autograft on acute pain during the inflammatory phase of soft tissue healing . Acute pain was measured by assessing the amount of pain medication ( amount of narcotic delivered from the patient-controlled analgesia ( PCA ) pump during the first postoperative 24 hours and the total intake of oral medication during the second and third postoperative days ) , the need for pain medication ( number of times the patient pushed the PCA button during the first postoperative 24 hours ) , and perceived pain ( graphic pain scale measuring antalgic sensation ) . Thirty patients ( 15 - 45 years old ) participated in this study . The patients were prospect ively r and omized into two groups , CPM and non-CPM . Both groups followed an identical postoperative rehabilitation program except for the CPM groups using a CPM device . The design of this study included the collection of data during the inflammatory phase of soft tissue healing . The results indicated that the initiation of CPM immediately following an ACL reconstruction had a significant ( p < .05 ) effect on decreasing the amount of medication consumed by the patient and a significant ( p < .05 ) decrease in the patient 's need for medication during the inflammatory phase . There was no statistical significance in the level of perceived pain between the groups . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract . Knee extensor resistance training using open kinetic chain ( OKC ) exercise for patients recovering from anterior cruciate ligament reconstruction ( ACLR ) surgery has lost favour mainly because of research indicating that OKC exercise causes greater ACL strain than closed kinetic chain ( CKC ) exercise . In this prospect i ve , r and omized clinical trial the effects of these two regimes on knee laxity were compared in the early period after ACLR surgery . Thirty-six patients recovering from ACLR surgery ( 29 males , 7 females ; age mean=30 ) were tested at 2 and 6 weeks after ACLR with knee laxity measured using the Knee Signature System arthrometer . Between tests subjects trained using either OKC or CKC resistance of their knee and hip extensors in formal physical therapy sessions three times per week . Following adjustment for site of treatment , pretraining injured knee laxity , and untreated knee laxity at post-training , the use of OKC exercise , when compared to CKC exercise , was found to lead to a 9 % increase in looseness with a 95 % confidence interval of –8 % to + 29 % . These results indicate that the great concern about the safety of OKC knee extensor training in the early period after ACLR surgery may not be well founded Background The risk of tear of the intact anterior cruciate ligament in the contralateral knee after anterior cruciate ligament reconstruction of the opposite knee and the incidence of rupturing the anterior cruciate ligament graft during the first 2 years after surgery have not been extensively studied in a prospect i ve manner . Clinicians have hypothesized that the opposite normal knee is at equal or increased risk compared with the risk of anterior cruciate ligament graft rupture in the operated knee . Hypothesis The risk of anterior cruciate ligament graft rupture and contralateral normal knee anterior cruciate ligament rupture at 2-year follow-up is equal . Study Design Cohort study ; Level of evidence , 2 . Methods The Multicenter Orthopaedic Outcome Network ( MOON ) data base of a prospect i ve longitudinal cohort of anterior cruciate ligament reconstructions was used to determine the number of anterior cruciate ligament graft ruptures and tears of the intact anterior cruciate ligament in the contralateral knee at 2-year follow-up . Two-year follow-up consisted of a phone interview and review of operative reports . Results Two-year data were obtained for 235 of 273 patients ( 86 % ) . There were 14 ligament disruptions . Of these , 7 were tears of the intact anterior cruciate ligament in the contralateral knee ( 3.0 % ) and 7 were anterior cruciate ligament graft failures ( 3.0 % ) . Conclusion The contralateral normal knee anterior cruciate ligament is at a similar risk of anterior cruciate ligament tear ( 3.0 % ) as the anterior cruciate ligament graft after primary anterior cruciate ligament reconstruction ( 3.0 % ) This r and omized , double blind , controlled trial was design ed to determine the effectiveness of neuromuscular electrical stimulation of the knee extensor and flexor muscles in the prevention of muscular weakening after anterior cruciate ligament surgery . Neuromuscular electrical stimulation treatment was given in addition to an early exercise therapy regimen and compared with an early exercise therapy regimen alone . Forty-nine patients after anterior cruciate ligament surgery were assigned r and omly either to a neuromuscular electrical stimulation and exercise group , a transcutaneous electrical nerve stimulation as analgesic and exercise group , or an exercise alone group as control . All groups received a st and ard regimen of rehabilitation after anterior cruciate ligament surgery . The neuromuscular electrical stimulation and transcutaneous electrical nerve stimulation group additionally received electrical stimulation during the first 6 weeks after surgery . Patients were measured for isometric and isokinetic torque in the knee extensor and flexor muscles after 6 , 12 , and 52 weeks . No statistical difference among groups was observed . It is concluded that neuromuscular electrical stimulation in combination with an early exercise therapy regimen is not significantly more effective in reducing weakening than an early exercise therapy regimen alone after anterior cruciate ligament surgery Abstract Forty patients were prospect ively investigated to evaluate the effects of b and aging after reconstructive surgery of the anterior cruciate ligament ( ACL ) . For the 6 weeks of the postoperative course , the operated knee was b and aged in 20 patients ( group A ) and braced in the other 20 patients ( group B ) . The isokinetic torque for extension and flexion ( Cybex ) and the range of motion ( ROM ) were investigated after 6 , 12 , 24 and 52 weeks postoperatively . At 24 weeks and 1 year postoperatively the stability of the knee joint ( KT-1000 ) as well as the clinical outcome ( ‘ Orthopädische Arbeitsgemeinschaft Knie ’ ) were evaluated . No statistically significant differences between the two groups were found for the extension and flexion strengths . Free ROM was achieved significantly earlier in group A than in group B. No statistically significant differences regarding the stability of the operated knee joint nor the early outcome were found between the two groups . This study demonstrated that the renunciation of using a brace had no adverse effect on the early outcome with respect to stability and function . On the contrary , bracing seems not to be m and atory after ACL reconstruction when the central third of the patellar tendon is used The aim of this study was to evaluate the use of a knee brace after arthroscopic anterior cruciate ligament reconstruction using central third patellar tendon autografts . Fifty patients were r and omly allocated to two groups . The patients in Group A wore a brace for three weeks postoperatively , while the patients in Group B were rehabilitated without the use of a brace . Pre-operatively , the groups were comparable in terms of age , sex , activity level , knee laxity and muscle strength . The follow-up examination was performed by one independent observer . All the patients were followed up for a minimum of two years . At the follow-up , there were no significant differences between the study groups in terms of the Tegner activity level , Lysholm score , IKDC evaluation system , one-leg-hop quotient , KT-1000 measurements and isokinetic torque . Using the visual analogue scale , the patients in Group A evaluated their pain during the first two post-operative weeks as 1.0 ( 0 - 7 ) , compared with 2.3 ( 0 - 9 ) in Group B ( P= 0.04 ) . Furthermore , the patients in Group A had a tendency towards fewer problems with swelling , haemathrosis and wound leakage during the early post-operative period ( P=0.08 ) . We conclude that the patients who were rehabilitated with the use of a brace had less pain and a tendency towards fewer complications during the early post-operative period than the patients who were rehabilitated without the use of a brace . However , there were no differences in terms of function or knee laxity at the two-year follow-up We investigated whether preoperative perturbation training would help anterior cruciate ligament ( ACL ) deficient individuals who complain of knee instability ( " non-copers " ) regain quadriceps strength and walk normally after ACL reconstruction . Nineteen non-copers with acute ACL injury were r and omly assigned into a perturbation group ( PERT ) or a strengthening group ( STR ) . The PERT group received specialized neuromuscular training and progressive quadriceps strength training , whereas the STR group received progressive quadriceps strength training only . We compared quadriceps strength indexes and knee excursions during the mid-stance phase of gait preoperatively to data collected 6 months after ACL reconstruction . Analyses of Variance with repeated measures ( time/limb ) were conducted to compare quadriceps strength index values over time ( time x group ) and differences in knee excursions in limbs between groups over time ( limb x time x group ) . If significance was found , post hoc analyses were performed using paired and independent t-tests . Quadriceps strength indexes before intervention ( Pert : 87.2 % ; Str : 75.8 % ) improved 6 months after ACL reconstruction in both groups ( Pert : 97.1 % ; Str : 94.4 % ) . Non-copers who received perturbation training preoperatively had no differences in knee excursions between their limbs 6 months after ACL reconstruction ( p = 0.14 ) , whereas those who received just strength training continued to have smaller knee excursions during the mid-stance phase of gait ( p = 0.007 ) . Non-copers strength and knee excursions were more symmetrical 6 months postoperatively in the group that received perturbation training and progressive quadriceps strength training than the group who received strength training alone Abstract . Rehabilitation after anterior cruciate ligament ( ACL ) reconstruction has focused over the past decade on closed kinetic chain ( CKC ) exercises due to presumably less strain on the graft than with isokinetic open kinetic chain exercises ( OKC ) ; however , recent reports suggest that there are only minor differences in ACL strain values between some CKC and OKC exercises . We studied anterior knee laxity , thigh muscle torque , and return to preinjury sports level in 44 patients with unilateral ACL ; group 1 carried out quadriceps strengthening only with CKC while group 2 trained with CKC plus OKC exercises starting from week 6 after surgery . Anterior knee laxity was determined with a KT-1000 arthrometer ; isokinetic concentric and eccentric quadriceps and hamstring muscle torque were studied with a Kin-Com dynamometer before and 6 months after surgery . At an average of 31 months after surgery the patients answered a question naire regarding their current knee function and physical activity/sports to determine the extent and timing of their recovery . No significant differences in anterior knee laxity were noted between the groups 6 months postsurgery . Patients in group 2 increased their quadriceps torque significantly more than those in group 1 , but no differences were found in hamstring torque between the groups . A significantly higher number of patients in group 2 ( n=12 ) than in group 1 ( n=5 ) returned to sports at the same level as before the injury ( P<0.05 ) . Patients from group 2 who returned to sports at the same level did so 2 months earlier than those in group 1 . Thus the addition of OKC quadriceps training after ACL reconstruction results in a significantly better improvement in quadriceps torque without reducing knee joint stability at 6 months and also leads to a significantly higher number of athletes returning to their previous activity earlier and at the same level as before injury This study prospect ively r and omized 62 patients to rehabilitation programs either with or without postoperative brace for 6 weeks following bone-tendon-bone anterior cruciate ligament reconstruction . The nonbraced group had a smaller knee circumference 2 weeks after surgery . At 6-month follow-up the nonbraced group had a better Tegner score . At 2 years there was no difference between the groups . There was one partial rupture of the graft in the nonbraced group after a new trauma 1 year after surgery . There were no differences between the groups in either subjective or objective knee stability at 2 or 6 weeks or at follow-up 3 , 6 , and 24 months after surgery . This study found no benefit of using a postoperative knee brace on patients ' knee function at any stage up to 24 months after surgery . Furthermore , the braced group was not more stable than the nonbraced group , indicating that the brace does not contribute to a more stable knee during rehabilitation or 2-year follow-up Rehabilitation following anterior cruciate ligament ( ACL ) reconstruction is varied . Patients are usually prescribed an independent home exercise program , although some patients may attend physical therapy for additional supervised exercise . It is not known whether additional supervised exercise provides any further benefit . The purpose of this study was to compare efficacy for two types of rehabilitation following ACL reconstruction . A r and omized controlled trial of 31 ACL-reconstructed patients was used to test the hypothesis that a home program plus supervised rehabilitation ( Group S ) is more effective than a home program ( Group H ) alone . Function , activity level , anterior tibial translation , and muscle strength were measured preoperatively and at 3 and 6 months postoperatively . Improvement of function , activity level , muscle strength , and anterior tibial translation was evident in both groups , but no significant differences were found between groups even though the sample size was sufficient to detect small treatment effects . It was concluded that supervised exercise , in addition to a home program , has minimal extra benefit for patients who have undergone ACL reconstruction Sixty patients were prospect ively r and omized to brace and no-brace groups after bone-tendon-bone patellar tendon anterior cruciate ligament ( ACL ) reconstruction . The brace group wore a rehabilitation knee brace for 12 weeks post-operatively , while the no-brace group was mobilized immediately , and crutches were discarded 2 weeks post-operatively . The groups were comparable with respect to age , gender , time from injury to surgery and concomitant injuries . There were no differences either pre-operatively or 5 years post-operatively ( 80 % of patients review ed ) between the groups in terms of the knee score ( Lysholm ) , activity level ( Tegner ) , degree of laxity or isokinetic peak muscle torque . Thus it appears that knee braces are not needed in the post-operative rehabilitation after ACL reconstruction with the patellar tendon graft Background : There have been no long-term follow-up studies comparing a predominantly home-based rehabilitation program with a st and ard physical therapy program after anterior cruciate ligament ( ACL ) reconstruction . Demonstrating the long-term success of such a cost-effective program would be beneficial to guide future rehabilitation practice . Purpose : To determine whether there were any differences in long-term outcome between recreational athletes who performed a physical therapy-supervised rehabilitation program and those who performed a primarily home-based rehabilitation program in the first 3 months after ACL reconstruction . Study Design : R and omized clinical trial ; Level of evidence , 1 . Methods : Patients were r and omized before ACL reconstruction surgery to either the physical therapy-supervised ( 17 physical therapy sessions ) or home-based ( 4 physical therapy sessions ) program . Eighty-eight of the original 129 patients returned 2 to 4 years after surgery to assess their long-term clinical outcomes . Primary outcome was the ACL quality of life question naire ( ACL QOL ) . Secondary outcomes were bilateral difference in knee extension and flexion range of motion , sagittal plane knee laxity , relative quadriceps and hamstring strength , and objective International Knee Documentation Committee score . Unpaired t tests and a chi-square test were used for the comparisons . Results : The home-based group had a significantly higher mean ACL QOL score ( 80.0 ± 16.2 ) than the physical therapy-supervised group ( 69.9 ± 22.0 ) a mean of 38 months after surgery ( P = .02 , 95 % confidence interval [ CI ] : 1.7 , 18.4 ) . The mean change in ACL QOL score from before surgery to follow-up was not significantly different between the groups ( physical therapy = 40.0 , home = 45.8 , P = .26 , 95 % CI : −15.8 , 4.4 ) . There were no significant differences in the secondary outcome measures . Conclusion : This long-term study upholds the short-term findings of the original r and omized clinical trial by demonstrating that patients who participate in a predominantly home-based rehabilitation program in the first 3 months after ACL reconstruction have similar 2- to 4-year outcomes compared with those patients who participate in a more clinical ly supervised program Eighteen male and 20 female patients who underwent reconstruction of their anterior cruciate ligament ( ACL ) with a flap from the patellar tendon were r and omly assigned into either closed cast , isometric muscle training and electric stimulation ( ES group ) , or closed cast and isometric training alone ( control group ) . The degree of quadriceps wasting was determined from computerized tomographic scans ( CT ) before and 6 weeks after surgery . Electrical stimulation was given with a battery operated stimulator that produced a rectangular asymmetric balanced biphasic pulse shape . The pulse rate was 40 Hz and the pulse width 300 microseconds . Patients received 30 min of stimulation three times daily during 5.5 weeks . Female control patients showed a larger decrease in quadriceps area on CT than male control patients ( P less than .001 ) . No significant difference was found between male electrically stimulated patients and control patients . In female patients , there was on the contrary , a highly significant difference in favor of electrical stimulation ( P less than .001 ) When the different parts of the quadriceps were studied , a significantly lower degree of atrophy of the vastus medialis was found after electrical stimulation . Vastus lateralis did not show any difference . Measurements of CT attenuation , pre- and post-operatively , showed a decrease in attenuation of 17 % for the vastus medialis and lateralis of the operated leg after immobilization , indicating an increase in fat content . In the rectus femoris , however , there was an increase in attenuation of 14.6 % . Percutaneous muscle biopsies from the vastus lateralis obtained before , one week after , and 6 weeks after surgery revealed that the cross-sectional area of the individual muscle fibers decreased less in the electrically stimulated than in controls , but the difference was not significant . There were no differences between the two groups in the activity of an oxidative enzyme , citrate synthase , or a glycolytic enzyme , phosphofructokinase ( PFK ) . We conclude that females reacted more favorably than males to electrical stimulation of quadriceps during an immobilization period after knee surgery The effects of neuromuscular electrical stimulation on the strength of the thigh muscles and on gait were examined in ten patients after reconstruction of the anterior cruciate ligament . The patients were r and omly assigned to one of two treatment groups : neuromuscular electrical stimulation and volitional exercise , or volitional exercise alone . A four-week course of electrically elicited co-contraction of the thigh muscles result ed in significant attenuation of the characteristic loss of strength of the quadriceps as compared with volitional exercise . There was no significant difference between groups in any measure of performance of the hamstring muscles . In the group that received neuromuscular electrical stimulation , the values for cadence , walking velocity , stance time of the involved limb , and flexion-excursion of the knee during stance were significantly different from those of the volitional exercise group . Flexion-excursion of the knee during stance was directly and significantly correlated with strength of the quadriceps femoris muscle . Flexion of the knee during stance was qualitatively different in the involved extremity as compared with the uninvolved extremity in all patients . There is a rapid flexion of the knee at weight acceptance that is maintained throughout stance and probably reflects stabilization of the joint by muscular coactivation to compensate for weakness of the quadriceps . The patients who received neuromuscular electrical stimulation had stronger quadriceps muscles and more normal gait patterns than those in the volitional exercise group Patient rehabilitation following anterior cruciate ligament reconstruction is a continuing challenge for physical therapists . This study compared the effectiveness of an established protocol to a new program which included Protonics exercise . Sixty patient ( 42 males and 18 females ; mean age = 24.7 + /- 3.9 years ; age range = 19 - 30 years ) were r and omly assigned into two groups : Group 1 received the established protocol and Group 2 received a Protonics exercise regimen . Both groups were measured for the time needed for return to unrestricted activity on the basis of objective , functional , and clinical exams ; all tests were repeated at a 1-year follow-up exam . Group 2 completed treatment an average of 3.3 weeks sooner than Group 1 ( mean = 19.8 vs. 23.1 weeks ) at an average lower cost of $ 990.00 per subject . All subjects had good functional outcomes at the 1-year follow-up exam . It was concluded that the Protonics exercise program was more clinical ly and cost-effective than the other program , although both methods were successful for postsurgical anterior cruciate ligament rehabilitation The purpose of this study was to compare the clinical outcomes of rehabilitation after ACL reconstruction using a water-filled soft brace to those using a hard brace . The method used in this study was a prospect i ve r and omised clinical trial including 36 patients wearing a hard brace and 37 patients wearing a water-filled soft brace for 6 weeks after surgery . Preoperative and postoperative ( seven examinations ) clinical evaluation within a follow-up period of 1 year including effusion status , swelling and range of motion ( ROM ) , IKDC 2000 , KT1000 Arthrometer , Lysholm knee scoring scale and Tegner activity score . Mean values are presented with st and ard deviations . Data was analysed using descriptive statistics and Student 's t-test for unpaired sample s. Significantly less effusion was found in the soft brace group from 5 days ( p=0.002 ) to 12 weeks ( p<0.024 ) postoperative . Hard brace patients presented with significantly more extension deficit from 5 days ( p=0.036 ) to 12 months ( p=0.014 ) postoperative but no significant difference was detected in complete ROM , laxity or thigh atrophy at any follow-up examination . Patients treated with a soft brace had significantly higher IKDC subjective ratings at 6 weeks ( p=0.02 ) up to 12 months after operation ( p=0.002 ) and rated significantly higher in Tegner activity score ( p=0.004 ) and Lysholm knee scoring scale ( p=0.006 ) 6 and 12 months ( p<0.001 for both scores ) postoperatively . The water-filled soft brace was superior regarding effusion , swelling , extension deficit and patient-measured midterm outcome . The soft brace presents a safe , easy-to-use and effective alternative to the hard brace Background There are adverse effects associated with immobilization of the knee after anterior cruciate ligament reconstruction , yet very little is known about how much activity will promote adequate rehabilitation without permanently elongating the graft , producing graft failure , or creating damage to articular cartilage . Hypothesis Rehabilitation with either an accelerated or nonaccelerated program produces no difference in anterior-posterior knee laxity , clinical assessment , patient satisfaction , functional performance , and the synovial fluid biomarkers of articular cartilage metabolism . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Twenty-five patients who tore their anterior cruciate ligament were enrolled and underwent anterior cruciate ligament reconstruction . Patients were r and omized to accelerated rehabilitation or nonaccelerated rehabilitation . At the time of surgery and 3 , 6 , 12 , and 24 months later , measurements of anterior-posterior knee laxity , clinical assessment , patient satisfaction , functional performance , and cartilage metabolism were completed . Results At the 2-year follow-up , there was no difference in the increase of anterior knee laxity relative to the baseline values that were obtained immediately after surgery between the 2 groups ( 2.2-mm vs 1.8-mm increase relative to the normal knee ) . The groups were similar in terms of clinical assessment , patient satisfaction , activity level , function , and response of the bio-markers . After 1 year of healing , synthesis of collagen and turnover of aggrecan remained elevated in both groups . Conclusion Anterior cruciate ligament reconstruction with a bone-patellar tendon-bone graft followed by either accelerated or nonaccelerated rehabilitation produces the same increase of anterior knee laxity . Both programs had the same effect in terms of clinical assessment , patient satisfaction , functional performance , and the biomarkers of articular cartilage metabolism . There is concern that the cartilage biomarkers remained elevated for an extended period Background : Increased knee pain at the time of anterior cruciate ligament reconstruction may potentially predict more difficult rehabilitation , prolonged recovery , and /or be predictive of increased knee pain at 2 years . Hypothesis : A bone bruise and /or other preoperative factors are associated with more knee pain/symptoms at the time of index anterior cruciate ligament reconstruction , and the presence of a bone bruise would be associated with specific demographic and injury-related factors . Study Design : Cohort study ( prevalence ) ; Level of evidence , 2 . Methods : In 2007 , the Multicenter Orthopaedic Outcomes Network ( MOON ) data base began to prospect ively collect surgeon-reported magnetic resonance imaging bone bruise status . A multivariable analysis was performed to ( 1 ) determine if a bone bruise , among other preoperative factors , is associated with more knee symptoms/pain and ( 2 ) examine the association of factors related to bone bruise . To evaluate the association of a bone bruise with knee pain/symptoms , linear multiple regression models were fit using the continuous scores of the Knee injury and Osteoarthritis Outcome Score ( KOOS ) symptoms and pain subscales and the Short Form 36 ( SF-36 ) bodily pain subscale as dependent variables . To examine the association between a bone bruise and risk factors , a logistic regression model was used , in which the dependent variable was the presence or absence of a bone bruise . Results : Baseline data for 525 patients were used for analysis , and a bone bruise was present in 419 ( 80 % ) . The cohort comprises 58 % male patients , with a median age of 23 years . The median Marx activity level was 13 . Factors associated with more pain were higher body mass index ( P < .0001 ) , female sex ( P = .001 ) , lateral collateral ligament injury ( P = .012 ) , and older age ( P = .038 ) . Factors associated with more symptoms were a concomitant lateral collateral ligament injury ( P = .014 ) , higher body mass index ( P < .0001 ) , and female sex ( P < .0001 ) . Bone bruise is not associated with symptoms/pain at the time of index anterior cruciate ligament reconstruction . None of the factors included in the SF-36 bodily pain model were found to be significant . After controlling for other baseline factors , the following factors were associated with a bone bruise : younger age ( P = .034 ) and not jumping at the time of injury ( P = .006 ) . Conclusion : After anterior cruciate ligament injury , risk factors associated with a bone bruise are younger age and not jumping at the time of injury . Bone bruise is not associated with symptoms/pain at the time of index anterior cruciate ligament reconstruction Twenty patients who had undergone anterior cruciate ligament reconstructive surgery were placed r and omly and independently in an Electrical Stimulation Group ( n = 10 ) or Voluntary Exercise Group ( n = 10 ) to compare the effectiveness of these two muscle-strengthening protocol s. Patients in both groups used simultaneous contraction of quadriceps femoris and hamstring muscles during a training regimen that consisted of either voluntary exercise or electrical stimulation trials five days a week for a three-week period within the first six postoperative weeks . After patients completed the training regimen , bilateral maximal isometric measurements of gravity-corrected knee extension and flexion torque were obtained for both groups and percentages were calculated . Results showed that patients in the Electrical Stimulation Group finished the three-week training regimen with higher percentages of both extension and flexion torque when compared with patients in the Voluntary Exercise Group ( extension : t = 4.35 , p less than .05 ; flexion ; t = 6.64 , p less than .05 ) . These results indicate that patients in an electrical stimulation regimen can achieve higher individual thigh musculature strength gains than patients in a voluntary exercise regimen when simultaneous contraction of thigh muscles is prescribed during an early phase of postoperative rehabilitation Both electrical stimulation and electromyographic biofeedback have been shown to be more effective than voluntary isometric exercise alone in the recovery of quadriceps femoris muscle force following anterior cruciate ligament ( ACL ) reconstruction . In a comparison of these two modalities , 30 patients with ACL reconstruction were r and omly assigned to either a group receiving electrical stimulation in conjunction with voluntary isometric exercise or a group receiving biofeedback in conjunction with voluntary isometric exercise . Following 6 weeks of a rehabilitative exercise protocol , the quadriceps femoris muscle isometric peak torque in the operative limb was compared with that in the nonoperative limb . A t test of independent sample s indicated that the biofeedback group recovered a significantly greater percentage of their nonoperative limb 's peak torque than did the electrical stimulation group . Measurements of active knee extension were taken at weeks 1 , 2 , 4 , and 6 of the exercise program . A two-way analysis of variance ( groups x weeks ) indicated no significant difference between the rate at which each group recovered full active extension . The authors concluded that biofeedback is more effective than electrical stimulation in facilitating the recovery of peak torque and that biofeedback is comparable to electrical stimulation in the recovery of active knee extension The effect of prolonged daily electrical stimulation ( ES ) on quadriceps strength in 22 patients during the 6 weeks following anterior cruciate reconstruction was investigated . Patients were r and omly assigned to re ceive either a combination of ES and exercise or exer cise alone . Isometric quadriceps strength was meas ured at the 7th , 8th , and 9th postoperative weeks . No significant difference in strength existed between the groups as a result of ES . A significant difference in strength did exist between competitive and recreational athletes regardless of treatment . Further research is needed to determine if the addition of ES to isometric exercise during immobilization can significantly retard strength loss after anterior cruciate reconstructive sur gery Fifty-four patients who underwent arthroscopically assisted anterior cruciate ligament reconstruction with bone-patellar tendon-bone autograft or allograft were studied prospect ively to compare a postoperative home based rehabilitation program with a clinic based program . Fifty-four patients ( mean age , 30 years ) were assigned r and omly to the home based program ( 27 patients ) or the clinic based program ( 27 patients ) . The home based schedule featured six physical therapy visits during a 6-month postoperative study period , whereas the clinic based schedule specified 24 physical therapy visits during those 6 months . All patients entered in the study met strict selection criteria : age older than 15 years , no previous ligament repair or reconstruction , no complicating medical conditions , no collegiate or professional athletes , reconstruction at least 6 weeks after injury , and informed consent . At the 6-month followup , no significant statistical differences were found between the two groups in range of motion , thigh atrophy , anterior drawer compliance , hopping tests , Lysholm scores , or subjective health status scores . Thus , the authors conclude that in a selected group of patients who have undergone anterior cruciate ligament reconstruction , a home based postoperative rehabilitation program is feasible , safe , and effective BACKGROUND Aggressive early rehabilitation is recommended after reconstruction of the anterior cruciate ligament ( ACL ) using a patellar tendon-bone graft . However , rehabilitation after reconstruction of ACL using the multistr and ed hamstring is controversial . In this study , we compared the clinical results of 3-day immobilization after reconstruction of ACL using the multistr and ed hamstring , with those of 2-week immobilization prospect ively . METHODS A total of 30 consecutive patients with ruptured ACL underwent single-socket ACL reconstruction . 10 male and 5 female patients ( mean age of 29.2+/-10.0 years ) were prospect ively r and omized for a 3-day immobilization period , and 6 male and 9 female patients ( mean age of 27.3+/-10.9 years ) were r and omized for a 2-week immobilization period . We measured the anterior laxity with a KT-2000 arthrometer , joint position sense , and thigh muscle strength at 3 , 6 and 12 months after surgery . RESULTS AND CONCLUSIONS There were no statistically significant differences between the two groups . We concluded that the post-operative 3-day immobilization period is preferable to the longer 2-week period in our rehabilitation program from the viewpoint of psychological load to the patients and the duration of hospitalization after ACL reconstruction using multistr and ed hamstring tendons Eight patients undergoing reconstruction of the anterior cru ciate ligament were r and omly allocated into two groups . The control group received a st and ard plaster cast and isometric muscle training . The stimulated group received a st and ard plaster cast , isometric training , and percutaneous electrical stimulation during the recovery period . The patients were examined clinical ly and with repeated muscle biopsies before surgery , 1 week after surgery , and 5 weeks after surgery at the time of removal of the cast . The electrically stimulated group had better muscle function from a clinical point of view and their succinate dehydrogenase activities were significantly higher than those in the control group . Electrical stimulation thus could prevent the fall in oxidative enzyme activity which was noted in the control group . The results suggest that percutaneous electrical stimulation may be a way of preventing muscle atrophy after major knee ligament surgery in athletes Background Despite a lack of evidence for their effectiveness , functional knee braces are commonly prescribed to patients after anterior cruciate ligament ( ACL ) reconstruction . Purpose This trial was conducted to compare postoperative outcomes in patients using an ACL functional knee brace and patients using a neoprene knee sleeve . Hypothesis Patients using a brace will have superior outcomes than those using a sleeve . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods One hundred fifty patients were r and omized to receive a brace ( n = 76 ) or neoprene sleeve ( n = 74 ) at their 6-week postoperative visit after primary ACL reconstruction with hamstring autograft . Patients were assessed preoperatively , then 6 weeks and 6 , 12 , and 24 months postoperatively . Outcome measures included disease-specific quality of life ( Anterior Cruciate Ligament– Quality of Life [ ACL-QOL ] Question naire ) , anterior tibial translation ( KT-1000 arthrometer side-to-side difference ) , the single-limb forward hop test ( limb symmetry index ) , and Tegner Activity Scale . Outcomes at 1 and 2 years were compared after adjusting for baseline scores . Subjective ratings of how patients felt while using the brace/sleeve were also collected for descriptive purpose s using a question naire . Four a priori directional subgroup hypotheses were evaluated using tests for interactions . Results There were no significant differences between brace ( n = 62 ) and sleeve ( n = 65 ) groups for any of the outcomes at 1- and 2-year follow-ups . Adjusted mean differences at 2 years were as follows : −0.94 ( 95 % confidence interval [ CI ] , −7.52 to 5.64 ) for the ACL-QOL Question naire , −0.10 mm ( 95 % CI , −0.99 to 0.81 ) for KT-1000 arthrometer side-to-side difference , −0.87 % ( 95 % CI , −8.89 to 7.12 ) for hop limb symmetry index , and −0.05 ( 95 % CI , −0.72 to 0.62 ) for the Tegner Activity Scale . Subjective ratings of confidence in the knee provided by the brace/sleeve were higher for the brace group than the sleeve group . Subgroup findings were minimal . Adverse events were few and similar between groups . Conclusions A functional knee brace does not result in superior outcomes compared with a neoprene sleeve after ACL reconstruction . Current evidence does not support the recommendation of using an ACL functional knee brace after ACL reconstruction |
13,314 | 28,237,051 | Nonetheless , this review suggests that culturally sensitive treatments offer promise as an effective way to address substance use among racial/ethnic minority youth | This systematic review and meta- analysis synthesized findings from studies examining culturally sensitive substance use treatment for racial/ethnic minority youth . | A small r and omized trial investigated a new family-based intervention for Hispanic adolescents who met DSM-IV criteria for substance abuse disorder . The Culturally Informed and Flexible Family-Based Treatment for Adolescents ( CIFFTA ) is a tailored/adaptive intervention that includes a flexible treatment manual and multiple treatment components . The study used an " add on " design to isolate the effects on substance abuse , behavior problems , and parenting practice s attributable to the newly developed components . Twenty-eight Hispanic adolescents and their families were r and omized either to the experimental treatment or to traditional family therapy ( TFT ) and were assessed at baseline and 8-month follow-up . Despite the small sample , results revealed statistically significant time × treatment effects on both self-reported drug use ( marijuana + cocaine ) , F(1 , 22 ) = 10.59 , p < .01 , η² = .33 and adolescent reports of parenting practice s , F(1 , 22 ) = 9.01 , p < .01 , η² = .29 . Both sets of analyses favored CIFFTA participants . There was a significant time × treatment effect , F(1 , 22 ) = 6.72 , p = .02 , η² = .23 , favoring CIFFTA on parent report of parenting practice s using a composite that matched the variables used for adolescents , but only a nonsignificant trend , F(1 , 22 ) = 2.43 , p = .13 , η² = .10 , with a composite that used all parenting subscales . Parent reports of adolescent behavior problems did not show a significant time or time × treatment effect . These results show the promise of this adaptive treatment for substance abuse in Hispanic adolescents and suggest the need for a larger r and omized trial to fully investigate this treatment 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 Many family therapies for adolescent drug use include ecological interventions . The purpose of this r and omized clinical trial was to establish whether ecological interventions contribute to the impact of family therapy above and beyond the contributions of family process-only interventions . A family-based ecological approach , structural ecosystems therapy ( SET ) , was compared with family process-only condition ( FAM ) and community services control ( CS ) . One hundred ninety substance-abusing or dependent African American and Hispanic adolescents were r and omized to SET , FAM , or CS . Follow-up assessment s were conducted at 3 , 6 , 12 , and 18 months postr and omization . SET was significantly more efficacious than FAM and CS in reducing adolescent drug use . However , these improvements were limited to Hispanic adolescents . The study demonstrates the importance of investigating changes in adolescent drug use as a result of treatment condition across more than 1 racial/ethnic group OBJECTIVE The purpose of this r and omized trial was to investigate the efficacy of 2 behavioral treatments focusing on different change mechanisms in ameliorating a borderline personality disorder constellation of behaviors and substance use in adolescents referred by juvenile diversion programs . METHODS Forty adolescents 14 - 17 years of age and meeting Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ) criteria for borderline personality disorder and substance use disorders were r and omized to integrative borderline personality disorder-oriented adolescent family therapy ( I-BAFT ) or individual drug counseling . This design allowed a comparison of 2 manualized interventions , 1 family based and 1 individually oriented . Profiles of clinical change were used to detect impact and estimate treatment effect sizes . RESULTS Primary analyses showed that both interventions had a clinical ly significant impact on borderline personality disorder behaviors 12 months after baseline but with no differential treatment effects . The impact on substance use was more complex . Subgroup analyses revealed that adolescents with depression had significantly more severe profiles of borderline personality disorder and substance use . These youths were the only group to show reductions in substance use , but they only did so if they received the I-BAFT intervention . Study data also documented the high dosage of intensive residential treatment needed by this population . CONCLUSIONS AND IMPLICATION S FOR PRACTICE Results highlight the intensive treatment needs of juvenile justice-involved youths with co-occurring substance use and borderline personality disorder including depression , the hybrid outpatient and residential treatment often required by this population , and the promise of a family-oriented approach , particularly for youths with severe symptoms and co-occurring depression . ( PsycINFO Data base OBJECTIVE Although several treatments for adolescent substance abuse have been identified as promising by review ers and federal agencies , treatment effects extending beyond 12 months have not been demonstrated in r and omized clinical trials . The primary purpose of this report was to examine the 4-year outcomes of an evidence -based treatment of substance-abusing juvenile offenders . METHOD Eighty of 118 substance-abusing juvenile offenders participated in a follow-up 4 years after taking part in a r and omized clinical trial comparing multisystemic therapy ( MST ) with usual community services . A multi method ( self-report , biological , and archival measures ) assessment battery was used to measure the criminal behavior , illicit drug use , and psychiatric symptoms of the participating young adults . RESULTS Analyses demonstrated significant long-term treatment effects for aggressive criminal activity ( 0.15 versus 0.57 convictions per year ) but not for property crimes . Findings for illicit drug use were mixed , with biological measures indicating significantly higher rates of marijuana abstinence for MST participants ( 55 % versus 28 % of young adults ) . Long-term treatment effects were not observed for psychiatric symptoms . CONCLUSIONS Findings provide some support for the long-term effectiveness of an evidence d-based family-oriented treatment of substance-abusing juvenile offenders . The clinical , research , and policy implication s of these findings are noted 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 This study compared individual ( I ) to group ( G ) formats of cognitive-behavioral therapy ( CBT ) and interpersonal psychotherapy ( IPT ) for the treatment of depression in adolescents . One hundred and 12 Puerto Rican adolescents were r and omized to four conditions ( CBT-I , CBT-G , IPT-I , IPT-G ) . Participants were assessed at pretreatment and posttreatment with structured interviews to establish diagnosis and with self-report measures to assess treatment outcome . The results suggest that CBT and IPT are robust treatments in both group and individual formats . However , CBT produced significantly greater decreases in depressive symptoms and improved self-concept than IPT . The implication s of these findings are discussed AIM To examine the efficacy of two adolescent drug abuse treatments : individual cognitive behavioral therapy ( CBT ) and multidimensional family therapy ( MDFT ) . DESIGN A 2 ( treatment condition ) x 4 ( time ) repeated- measures intent-to-treat r and omized design . Data were gathered at baseline , termination , 6 and 12 months post-termination . Analyses used latent growth curve modeling . SETTING Community-based drug abuse clinic in the northeastern United States . PARTICIPANTS A total of 224 youth , primarily male ( 81 % ) , African American ( 72 % ) , from low-income single-parent homes ( 58 % ) with an average age of 15 years were recruited into the study . All youth were drug users , with 75 % meeting DSM-IV criteria for cannabis dependence and 13 % meeting criteria for abuse . MEASUREMENTS Five outcomes were measured : ( i ) substance use problem severity ; ( ii ) 30-day frequency of cannabis use ; ( iii ) 30-day frequency of alcohol use ; ( iv ) 30-day frequency of other drug use ; and ( v ) 30-day abstinence . FINDINGS Both treatments produced significant decreases in cannabis consumption and slightly significant reductions in alcohol use , but there were no treatment differences in reducing frequency of cannabis and alcohol use . Significant treatment effects were found favoring MDFT on substance use problem severity , other drug use and minimal use ( zero or one occasion of use ) of all substances , and these effects continued to 12 months following treatment termination . CONCLUSION Both interventions are promising treatments . Consistent with previous controlled trials , MDFT is distinguished by the sustainability of treatment effects This study investigated the efficacy of brief strategic family therapy ( BSFT ) with Hispanic behavior problem and drug using youth , an underrepresented population in the family therapy research literature . One hundred twenty-six Hispanic families with a behavior problem adolescent were r and omly assigned to 1 of 2 conditions : BSFT or group treatment control ( GC ) . Results showed that , compared to GC cases , BSFT cases showed significantly greater pre- to post-intervention improvement in parent reports of adolescent conduct problems and delinquency , adolescent reports of marijuana use , and observer ratings and self reports of family functioning . These results extend prior findings on the efficacy of family interventions to a difficult to treat Hispanic adolescent sample Background : Contemporary intervention models use research about the determinants of adolescent problems and their course of symptom development to design targeted interventions . Because developmental detours begin frequently during early-mid adolescence , specialized interventions that target known risk and protective factors in this period are needed . Methods : This study ( n = 83 ) examined parenting practice s as mediators of treatment effects in an early-intervention trial comparing Multidimensional Family Therapy ( MDFT ) , and a peer group intervention . Participants were clinical ly referred , low-income , predominantly ethnic minority adolescents ( average age 14 ) . Assessment s were conducted at intake , and six weeks after intake , discharge , and at 6 and 12 months following intake . Results : Previous studies demonstrated that MDFT was more effective than active treatments as well as services as usual in decreasing substance use and improving abstinence rates . The current study demonstrated that MDFT improves parental monitoring — a fundamental treatment target — to a greater extent than group therapy , and these improvements occur during the period of active intervention , satisfying state-of-the-science criteria for assessing mediation in r and omized clinical trials . Conclusions and Scientific Significance : Findings indicate that change in MDFT occurs through improvements in parenting practice s. These results set the foundation for examining family factors as mediators in other sample The effectiveness and transportability of multisystemic therapy ( MST ) were examined in a study that included 118 juvenile offenders meeting DSM-III-R criteria for substance abuse or dependence and their families . Participants were r and omly assigned to receive MST versus usual community services . Outcome measures assessed drug use , criminal activity , and days in out-of-home placement at posttreatment ( T2 ) and at a 6-month posttreatment follow-up ( T3 ) ; also treatment adherence was examined from multiple perspectives ( i.e. , caregiver , youth , and therapist ) . MST reduced alcohol , marijuana , and other drug use at T2 and total days in out-of-home placement by 50 % at T3 . Reductions in criminal activity , however , were not as large as have been obtained previously for MST . Examination of treatment adherence measures suggests that the modest results of MST were due , at least in part , to difficulty in transporting this complex treatment model from the direct control of its developers . Increased emphasis on quality assurance mechanisms to enhance treatment fidelity may help overcome barriers to transportability OBJECTIVE Previous research has found that smoking cessation messages can be design ed to appear as tailored ( placebo tailored ) and result in superior outcomes compared to st and ard messages . In the current study , we aim ed ( a ) to test the efficacy of placebo tailoring for smoking cessation and ( b ) to examine the influence of cognitive processing style . METHOD In a 2-arm r and omized controlled trial , 424 smokers ( M = 19.66 cigarettes per day ) from the community ( 57 % female , 30 % Caucasian , 40 % African American , 29 % Hispanic ; mean age = 42 years ) were r and omly assigned to receive 4 placebo-tailored booklets or 4 st and ard booklets over 3 months . Participants completed a measure of systematic versus heuristic cognitive processing style at baseline . The primary outcome was 7-day point prevalence abstinence ( ppa ) . Twenty-eight-day continuous abstinence , content evaluations , and readiness to quit were secondary outcomes . We hypothesized that placebo tailoring would be superior to st and ard material s and that the effect would be moderated by cognitive processing style ( systematic and heuristic ) . RESULTS As expected , placebo tailoring led to greater 7-day ppa at 3 months and greater 28-day continuous abstinence at 6 months . Cognitive processing style moderated the effect on 7-day ppa , such that the placebo-tailored booklets produced greater cessation among participants with heuristic information processing tendencies . CONCLUSIONS Findings support a causal role of placebo tailoring for short-term smoking cessation , particularly for individuals who process information using heuristic strategies . Implication s for tailored interventions are discussed 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 ) OBJECTIVE The aim of this study was to determine whether supplementing traditional cognitive-behavioral therapy for depression with clinical case management would reduce the rate of dropout from care and improve outcomes for ethnically diverse , impoverished medical out patients . METHODS The study was a r and omized trial that compared cognitive-behavioral group psychotherapy alone ( N=103 ) with the same therapy supplemented by clinical case management ( N=96 ) . RESULTS The patients who received supplemental case management had lower dropout rates than those who received cognitive-behavioral group therapy alone . Supplemental case management was associated with greater improvement in symptoms and functioning than cognitive-behavioral therapy alone for patients whose first language was Spanish ( N=77 ) but was less effective for those whose first language was English ( N=122 ) . CONCLUSIONS Supplemental case management improves retention in traditional mental health outpatient care and can improve outcomes for Spanish-speaking patients This article presents the results of a therapy- outcome study design ed to compare the relative effectiveness of conjoint family therapy ( CFT , therapy with the entire family present for most sessions ) and one-person family therapy ( OPFT , therapy with only one family member present for most sessions ) . The working hypothesis of the study was that it would be possible to achieve the goals of family therapy ( structural family change and symptom reduction ) by working primarily with one person . Results were presented on 37 Hispanic families r and omly assigned to one of the two treatment modalities ( i.e. , CFT or OPFT ) . Data were analyzed using a mixed- design ( repeated measures plus between-group independent variable ) analysis of variance with treatment ( OPFT vs. CFT ) as the between-group independent variable and time of assessment ( intake , termination , follow-up ) as the repeated measure . The results indicated that both conditions were highly effective in improving family functioning and that OPFT was slightly more effective in reducing identified patient symptomatology . Clinical and practical issues are discussed as well as the implication s of the findings for the current theory and practice of family therapy Abstract This r and omized clinical trial evaluated a family-based therapy ( Multidimensional Family Therapy , MDFT ; Liddle 2002a ) and a peer group therapy with 80 urban , low-income . and ethnically diverse young adolescents ( 11 to 15 years ) referred for substance abuse and behavioral problems . Both treatments were outpatient , relatively brief , manual-guided , equal in intervention dose , and delivered by community drug treatment therapists . Adolescents and their parents were assessed at intake to treatment , r and omly assigned to either MDFT or group therapy , and reassessed at six weeks after intake and at discharge . Results indicated that the family-based treatment ( MDFT . an intervention that targets teen and parent functioning within and across multiple systems on a variety of risk and protective factors ) was significantly more effective than peer group therapy in reducing risk and promoting protective processes in the individual , family , peer , and school domains . as well as in reducing substance use over the course of treatment . These results . which add to the body of previous findings about the clinical and cost effectiveness of MDFT , suppon the clinical effectiveness and dissemination potential of this family-based , multisystem and developmentally-oriented intervention AIMS This study presents preliminary analyses examining the effects of an alcohol and other drug use ( AOD ) intervention with minority juvenile offenders . Furthermore , the study investigates the impact of cultural factors on baseline AOD use among Hispanic and African American youth , as well as on treatment outcome . DESIGN , SETTING AND PARTICIPANTS Participants were 213 juvenile offenders referred for treatment ( mean age = 15.7 years ) , 97 of whom have completed treatment to date . The intervention was carried out in clinics placed within the neighborhoods in which the participants resided . Intervention Alcohol Treatment Targeting Adolescents in Need ( ATTAIN ) is a controlled clinical trial evaluating the effectiveness of a brief motivational , cognitive behavioral intervention , guided self-change ( GSC ) . Participants are assigned r and omly to the individual format of guided self-change ( I-GSC ) , the family involved format of guided self-Change ( F-GSC ) , choice of one of these two , or a waiting list control condition . Only participants involved in active intervention are included in the present report . MEASUREMENTS Data were collected via structured face-to-face interviews . Alcohol and marijuana use measures were collected using the Time-line Follow-back interview ( TLFB ) . FINDINGS There were significant reductions in alcohol and marijuana use for all ethnic groups from baseline to post-intervention . Cultural factors ( discrimination , acculturation , ethnic pride and cultural mistrust ) were associated with pre-intervention levels of alcohol and marijuana use . Among Hispanics , pre-intervention level of substance use were higher among foreign-born than US-born youth . Analyses conducted with the US-born Hispanic group showed that ethnic orientation and ethnic pride were associated positively with greater reductions in alcohol use . CONCLUSIONS The intervention provided through ATTAIN appears to be effective with a multi-ethnic population of juvenile delinquents . Cultural factors , such as ethnic orientation and ethnic mistrust , appear to constitute amenability to treatment factors , with US-born Hispanic youth lower in acculturation responding better to the intervention PROBLEM Adolescent substance abuse remains a public health problem , and more effective treatment approaches are needed . PURPOSE The study aims to determine the feasibility and preliminary effectiveness of implementing a cost-effective contingency management ( CM ) intervention in community substance abuse treatment for adolescents with marijuana use disorders . METHODS Thirty-one adolescents with primary marijuana use disorder enrolled in a community treatment were r and omized into either a prize-based CM intervention contingent when su bmi tting negative urine drug screens ( UDS ) or a noncontingent control group . FINDINGS There were no significant group differences in percent negative UDS , sustained negative UDS , or retention in treatment . CONCLUSIONS CM was difficult to integrate into community treatment programs and did not seem to be an effective adjunct to st and ard community substance abuse treatment for adolescents with marijuana use disorders . Modifying the CM procedure for adolescents , changing staff attitudes toward CM , and /or combining CM with other evidence -based psychosocial treatment may improve outcomes |
13,315 | 23,414,420 | Results indicate that organization , provider , and innovation-level constructs have the greatest number of measures available for use , whereas structural and patient-level constructs have the least .
Additionally , relatively few measures demonstrated criterion validity , or reliable association with an implementation outcome ( e.g. , fidelity ) . | Background Two of the current method ological barriers to implementation science efforts are the lack of agreement regarding constructs hypothesized to affect implementation success and identifiable measures of these constructs .
In order to address these gaps , the main goals of this paper were to identify a multi-level framework that captures the predominant factors that impact implementation outcomes , conduct a systematic review of available measures assessing constructs subsumed within these primary factors , and determine the criterion validity of these measures in the search articles . | OBJECTIVE Clinical Queries filters were developed to improve the retrieval of high- quality studies in search es on clinical matters . The study objective was to determine the yield of relevant citations and physician satisfaction while search ing for diagnostic and treatment studies using the Clinical Queries page of PubMed compared with search ing PubMed without these filters . MATERIAL S AND METHODS Forty practicing physicians , presented with st and ardized treatment and diagnosis questions and one question of their choosing , entered search terms which were processed in a r and om , blinded fashion through PubMed alone and PubMed Clinical Queries . Participants rated search retrievals for applicability to the question at h and and satisfaction . RESULTS For treatment , the primary outcome of retrieval of relevant articles was not significantly different between the groups , but a higher proportion of articles from the Clinical Queries search es met method ologic criteria ( p=0.049 ) , and more articles were published in core internal medicine journals ( p=0.056 ) . For diagnosis , the filtered results returned more relevant articles ( p=0.031 ) and fewer irrelevant articles ( overall retrieval less , p=0.023 ) ; participants needed to screen fewer articles before arriving at the first relevant citation ( p<0.05 ) . Relevance was also influenced by content terms used by participants in search ing . Participants varied greatly in their search performance . DISCUSSION Clinical Queries filtered search es returned more high- quality studies , though the retrieval of relevant articles was only statistically different between the groups for diagnosis questions . CONCLUSION Retrieving clinical ly important research studies from Medline is a challenging task for physicians . Method ological search filters can improve search retrieval Physicians often fail to provide nationally recommended preventive services for their patients . Addressing this , we have review ed selected literature on changing physician behavior using the organizational construct of the " readiness for change " transtheoretical model . This model suggests that behavior evolves through stages from precontemplation , to contemplation , to preparation , to initiation , and to maintenance of change . Traditional continuing medical education may affect knowledge and beliefs , but rarely results in behavior change . However , motivational strategies such as practice feedback reports and influential peers can foster stage change . Successful interventions aim ed at physicians preparing for change frequently use an office-system approach that targets not only physicians , but office staff and patients as well . Illustrating how the readiness to change model can guide the design and implementation of interventions , we describe strategies being used in a statewide r and omized controlled trial to improve cancer prevention counseling and early detection by primary care physicians . The multistage interventions of Partners for Prevention include support from a medical liability carrier , a motivational videotape , a task-delineated office manual , chart flowsheets , patient activation forms , practice feedback reports , a design ated prevention coordinator within each practice and regular telephone calls and office visits by project staff Background Although for more than a decade healthcare systems have attempted to provide evidence -based mental health treatments , the availability and use of psychotherapies remains low . A significant need exists to identify simple but effective implementation strategies to adopt complex practice s within complex systems of care . Emerging evidence suggests that facilitation may be an effective integrative implementation strategy for adoption of complex practice s. The current pilot examined the use of external facilitation for adoption of cognitive behavioral therapy ( CBT ) in 20 Department of Veteran Affairs ( VA ) clinics . Methods The 20 clinics were paired on facility characteristics , and 23 clinicians from these were trained in CBT . A clinic in each pair was r and omly selected to receive external facilitation . Quantitative methods were used to examine the extent of CBT implementation in 10 clinics that received external facilitation compared with 10 clinics that did not , and to better underst and the relationship between individual providers ' characteristics and attitudes and their CBT use . Costs of external facilitation were assessed by tracking the time spent by the facilitator and therapists in activities related to implementing CBT . Qualitative methods were used to explore context ual and other factors thought to influence implementation . Results Examination of change scores showed that facilitated therapists averaged an increase of 19 % [ 95 % CI : ( 2 , 36 ) ] in self-reported CBT use from baseline , while control therapists averaged a 4 % [ 95 % CI : ( -14 , 21 ) ] increase . Therapists in the facilitated condition who were not providing CBT at baseline showed the greatest increase ( 35 % ) compared to a control therapist who was not providing CBT at baseline ( 10 % ) or to therapists in either condition who were providing CBT at baseline ( average 3 % ) . Increased CBT use was unrelated to prior CBT training . Barriers to CBT implementation were therapists ' lack of control over their clinic schedule and poor communication with clinical leaders . Conclusions These findings suggest that facilitation may help clinicians make complex practice changes such as implementing an evidence -based psychotherapy . Furthermore , the substantial increase in CBT usage among the facilitation group was achieved at a modest cost Background Despite the burgeoning number of well-vali date d interventions that have been shown in r and omized trials to produce superior outcomes compared to usual services , it is estimated that only 10 % of public systems deliver evidence -based mental health services . In California , for example , more than 15,000 children are placed in group homes or residential centers with some evidence of iatrogenic effects . The present study evaluates the willingness among county leaders of child public service systems to adopt a new evidence -based model , Multidimensional Treatment Foster Care , ( MTFC ) , as a way to decrease the prevalence of out-of-home placements . Specifically , the study examines how county-level socio-demographic factors and child public service system leaders ' perceptions of their county 's organizational climate influence their decision of whether or not to consider adopting MTFC . Methods Two levels were examined in this study : Stable and historical factors from 40 California counties gathered from public records including population size , number of entries into out-of-home care , financing of mental health services , and percent minority population ; and system leaders ' perceptions of their county 's organizational climate and readiness for change measured via a web-based survey . The number of days-to-consent was the primary outcome variable defined as the duration of time between being notified of the opportunity to implement MTFC and the actual signing of a consent form indicating interest in considering implementation . Survival analysis methods were used to assess the predictors of this time-to-event measure . The present study is part of a larger r and omized trial comparing two methods of implementation where counties are r and omized to one of three time cohorts and two implementation conditions . Results The number of entries into care was the primary predictor of days-to-consent . This variable was significantly correlated to county size . System leader 's perceptions of positive climate and organizational readiness for change also contributed to but did not mediate or moderate the days-to-consent . Conclusions System leaders ' decision to consider implementing a new evidence -based model was influenced most by their objective need for the program and next by their perception of the county 's organizational climate and motivation to change . These findings highlight the importance of underst and ing the fit between the needs of the systems or agencies and the potential for addressing those needs with the proposed new program OBJECTIVE The objective of this study was to measure dietitians ' perceptions , attitudes , and knowledge of evidence -based practice ( PAK score ) , and to determine whether antecedent factors ( eg , sociodemographic characteristics , education and training , professional experiences , and employment setting ) predicted PAK score . DESIGN This cross-sectional , descriptive study used the Dietitian Research Involvement Survey following the Tailored Design Method . SUBJECTS/ SETTING This study surveyed 500 r and omly selected registered dietitians from seven dietetic practice groups of the American Dietetic Association . STATISTICAL ANALYSES PERFORMED Bivariate relationships were examined between antecedent factors and PAK score . Multiple linear regression analyses were conducted to test whether these factors predicted PAK score . RESULTS Higher PAK scores were associated with registered dietitians who completed more years of education ( r=0.28 , P<.0005 ) , had taken a research course ( r=0.28 , P<.0005 ) , frequently read research articles ( r=0.41 , P<.0005 ) , earned an advanced-level board certification ( r=0.18 , P=.004 ) , worked full-time ( r=0.26 , P<.0005 ) , or belonged to professional organizations ( r=0.18 , P=.003 ) . The strongest predictors for PAK score were " last time read research " ( beta=.33 , P<.0005 ) , work status ( beta=.20 , P<.0005 ) , level of education ( beta=.19 , P=.001 ) , and association memberships ( beta=.14 , P=.01 ) . CONCLUSIONS Results indicated that dietitians ' ability to incorporate an evidence -based approach is largely determined by their education and training , work experience , and professional association involvement . This study identified a need to integrate concepts and principles of evidence -based practice into dietetics curriculums so that practitioners are able to routinely apply research findings to clinical practice Background The Worksite Health Promotion Capacity Instrument ( WHPCI ) was developed to assess two key factors for effective worksite health promotion : collective willingness and the systematic implementation of health promotion activities in companies . This study evaluates the diagnostic qualities of the WHPCI based on its subscales Health Promotion Willingness and Health Promotion Management , which can be used to place companies into four different categories based on their level of health promotion capacity . Methods Psychometric evaluation was conducted using exploratory factor and reliability analyses with data taken from a r and om sample of managers from n = 522 German information and communication technology ( ICT ) companies . Receiver operating characteristic ( ROC ) analyses were conducted to determine further diagnostic qualities of the instrument and to establish the cut-off scores used to determine each company 's level of health promotion capacity . Results The instrument 's subscales , Health Promotion Willingness and Health Promotion Management , are based on one-dimensional constructs , each with very good reliability ( Cronbach 's alpha = 0.83/0.91 ) . ROC analyses demonstrated satisfactory diagnostic accuracy with an area under the curve ( AUC ) of 0.76 ( SE = 0.021 ; 95 % CI 0.72 - 0.80 ) for the Health Promotion Willingness scale and 0.81 ( SE = 0.021 ; 95 % CI 0.77 - 0.86 ) for the Health Promotion Management scale . A cut-off score with good sensitivity ( 71%/76 % ) and specificity ( 69%/75 % ) was determined for each scale . Both scales were found to have good predictive power and exhibited good efficiency . Conclusions Our findings indicate preliminary evidence for the validity and reliability of both subscales of the WHPCI . The goodness of each cut-off score suggests that the scales are appropriate for determining companies ' levels of health promotion capacity . Support in implementing ( systematic ) worksite health promotion can then be tailored to each company 's needs based on their current capacity level Background Psychological models are used to underst and and predict behaviour in a wide range of setting s , but have not been consistently applied to health professional behaviours , and the contribution of differing theories is not clear . This study explored the usefulness of a range of models to predict an evidence -based behaviour -- the placing of fissure sealants . Methods Measures were collected by postal question naire from a r and om sample of general dental practitioners ( GDPs ) in Scotl and . Outcomes were behavioural simulation ( scenario decision-making ) , and behavioural intention . Predictor variables were from the Theory of Planned Behaviour ( TPB ) , Social Cognitive Theory ( SCT ) , Common Sense Self-regulation Model ( CS-SRM ) , Operant Learning Theory ( OLT ) , Implementation Intention ( II ) , Stage Model , and knowledge ( a non-theoretical construct ) . Multiple regression analysis was used to examine the predictive value of each theoretical model individually . Significant constructs from all theories were then entered into a ' cross theory ' stepwise regression analysis to investigate their combined predictive value Results Behavioural simulation - theory level variance explained was : TPB 31 % ; SCT 29 % ; II 7 % ; OLT 30 % . Neither CS-SRM nor stage explained significant variance . In the cross theory analysis , habit ( OLT ) , timeline acute ( CS-SRM ) , and outcome expectancy ( SCT ) entered the equation , together explaining 38 % of the variance . Behavioural intention - theory level variance explained was : TPB 30 % ; SCT 24 % ; OLT 58 % , CS-SRM 27 % . GDPs in the action stage had significantly higher intention to place fissure sealants . In the cross theory analysis , habit ( OLT ) and attitude ( TPB ) entered the equation , together explaining 68 % of the variance in intention . Summary The study provides evidence that psychological models can be useful in underst and ing and predicting clinical behaviour . Taking a theory-based approach enables the creation of a replicable methodology for identifying factors that may predict clinical behaviour and so provide possible targets for knowledge translation interventions . Results suggest that more evidence -based behaviour may be achieved by influencing beliefs about the positive outcomes of placing fissure sealants and building a habit of placing them as part of patient management . However a number of conceptual and method ological challenges remain This paper describes findings from the Community Youth Development Study ( CYDS ) , a r and omized controlled trial of the Communities That Care ( CTC ) prevention system , on the adoption and implementation fidelity of science-based prevention programming in 24 communities . Data were collected using the Community Re source Documentation ( CRD ) , which entailed a multi-tiered sampling process and phone and web-based surveys with directors of community-based agencies and coalitions , school principals , service providers , and teachers . Four years after the initiation of the CTC prevention system , the results indicated increased use of tested , effective prevention programs in the 12 CTC intervention communities compared to the 12 control communities , and significant differences favoring the intervention communities in the numbers of children and families participating in these programs . Few significant differences were found regarding implementation quality ; respondents from both intervention and control communities reported high rates of implementation fidelity across the services provided How are characteristics of communities associated with the implementation of the principles of systems of care ( SOC ) ? This study uses multilevel modeling with a stratified r and om sample ( N = 225 ) of US counties to explore community-level predictors of the implementation factors of the System of Care Implementation Survey . A model composed of community-level social indicators fits well with 5 of 14 factors identified as relevant for effective SOCs . As hypothesized , community disadvantage was negatively and residential stability positively associated with the implementation of SOC principles . Design ation as a mental health professional shortage area was positively related to some implementation scores , as was the percentage of minority residents , while rurality was not significantly associated with any of the factors . Given the limitations of the study , the results should be interpreted with caution , but suggest that further research is merited to clarify these relationships that could inform efforts directed at promoting SOCs Background Research evidence underpins best practice , but is not always used in healthcare . The Promoting Action on Research Implementation in Health Services ( PARIHS ) framework suggests that the nature of evidence , the context in which it is used , and whether those trying to use evidence are helped ( or facilitated ) affect the use of evidence . Urinary incontinence has a major effect on quality of life of older people , has a high prevalence , and is a key priority within European health and social care policy . Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids . Objectives This study aims to advance underst and ing about the contribution facilitation can make to implementing research findings into practice via : extending current knowledge of facilitation as a process for translating research evidence into practice ; evaluating the feasibility , effectiveness , and cost-effectiveness of two different models of facilitation in promoting the uptake of research evidence on continence management ; assessing the impact of context ual factors on the processes and outcomes of implementation ; and implementing a pro-active knowledge transfer and dissemination strategy to diffuse study findings to a wide policy and practice community . Setting and sample Four European countries , each with six long-term nursing care sites ( total 24 sites ) for people aged 60 years and over with documented urinary incontinence Methods and design Pragmatic r and omised controlled trial with three arms ( st and ard dissemination and two different programmes of facilitation ) , with embedded process and economic evaluation . The primary outcome is compliance with the continence recommendations . Secondary outcomes include proportion of residents with incontinence , incidence of incontinence-related dermatitis , urinary tract infections , and quality of life . Outcomes are assessed at baseline , then at 6 , 12 , 18 , and 24 months after the start of the facilitation interventions . Detailed context ual and process data are collected throughout , using interviews with staff , residents and next of kin , observations , assessment of context using the Alberta Context Tool , and documentary evidence . A realistic evaluation framework is used to develop explanatory theory about what works for whom in what circumstances . Trial registration Current Controlled Trials IS RCT N11598502 Over the last decade evidence -based practice has become increasingly important in health care as an approach to improve patient outcomes . It is vital that dental hygienists , like other health professionals , use research findings to inform clinical practice . The objective of the present study was to investigate the extent of research utilization among dental hygienists in Sweden and to investigate the relationship between level of education and factors related to research utilization . A r and om sample of 261 dental hygienists in Sweden , 113 with 1 year and 148 with 2-year education , responded to a postal question naire covering various aspects of research utilization , i.e. their attitudes towards research , availability and support for the implementation of research findings , use of research in daily practice , their activity in seeking new research findings and their participation in a range of research -related activities . Dental hygienists with 2-year education had a more positive attitude towards research , used research to a greater extent and were more active in seeking new research findings than dental hygienists with 1-year education . Overall , relatively few dental hygienists reported that they implemented research findings in practice ; the most frequently reported activity concerned reading research articles in professional journals . The conclusions are that the length of dental hygiene education is a key factor influencing the application of research findings to practice . One-year education appears to be inadequate to achieve evidence -based practice . Moreover , not even two years of formal education guarantees necessary competence in research for evidence -based dental hygiene practice Background Team-based interventions are effective for improving safety and quality of healthcare . However , context ual factors , such as team functioning , leadership , and organizational support , can vary significantly across teams and affect the level of implementation success . Yet , the science for measuring context is immature . The goal of this study is to vali date measures from a short instrument tailored to track dynamic context and progress for a team-based quality improvement ( QI ) intervention . Methods Design : Secondary cross-sectional and longitudinal analysis of data from a clustered r and omized controlled trial ( RCT ) of a team-based quality improvement intervention to reduce central line-associated bloodstream infection ( CLABSI ) rates in intensive care units ( ICUs ) . Setting : Forty-six ICUs located within 35 faith-based , not-for-profit community hospitals across 12 states in the U.S. Population : Team members participating in an ICU-based QI intervention . Measures : The primary measure is the Team Check-up Tool ( TCT ) , an original instrument that assesses context and progress of a team-based QI intervention . The TCT is administered monthly . Validation measures include CLABSI rate , Team Functioning Survey ( TFS ) and Practice Environment Scale ( PES ) from the Nursing Work Index . Analysis : Temporal stability , responsiveness and validity of the TCT . Results We found evidence supporting the temporal stability , construct validity , and responsiveness of TCT measures of intervention activities , perceived group-level behaviors , and barriers to team progress . Conclusions The TCT demonstrates good measurement reliability , validity , and responsiveness . By having more vali date d measures on implementation context , research ers can more readily conduct rigorous studies to identify context ual variables linked to key intervention and patient outcomes and strengthen the evidence base on successful spread of efficacious team-based interventions . QI teams participating in an intervention should also find data from a vali date d tool useful for identifying opportunities to improve their own implementation AIM The purpose of this study was to test Kanter 's theory by examining relationships among structural empowerment , leader-member exchange ( LMX ) quality and nurses ' participation in personal knowledge transfer activities . BACKGROUND Despite the current emphasis on evidence -based practice in health care , research suggests that implementation of research findings in everyday clinical practice is un systematic at best with mixed outcomes . METHODS This study was a secondary analysis of data collected using a non-experimental , predictive mailed survey design . A r and om sample of 400 registered nurses who worked in urban tertiary care hospitals in Ontario yielded a final sample of 234 for a 58.5 % response rate . RESULTS Hierarchical multiple linear regression analysis revealed that the combination of LMX and structural empowerment accounted for 9.1 % of the variance in personal knowledge transfer but only total empowerment was a significant independent predictor of knowledge transfer ( β=0.291 , t=4.012 , P<0.001 ) . CONCLUSIONS Consistent with Kanter 's Theory , higher levels of empowerment and leader-member exchange quality result ed in increased participation in personal knowledge transfer in practice . IMPLICATION S FOR NURSING MANAGEMENT The results reinforce the pivotal role of nurse managers in supporting empowering work environments that are conducive to transfer of knowledge in practice to provide evidence -based care BACKGROUND The present study addresses diffusion of a psychosocial-based substance abuse prevention program , including : ( a ) teacher adoption , implementation , and maintenance ; ( b ) teacher characteristics associated with implementation ; ( c ) the relationship between integrity of program delivery and program outcomes ; and ( d ) the effectiveness of teacher training and school principal involvement in increasing implementation . METHODS Participants were teachers ( n = 60 ) , school principals ( n = 25 ) , and fifth- grade students ( n = 1147 ) from four Los Angeles area school districts . Districts were r and omly assigned to an intensive or brief teacher training condition . Schools were r and omly assigned to a principal-intervention or a no-principal-intervention condition . Assessment s included teacher and principal self-reports , classroom observations of program delivery , and evaluation of immediate program outcomes . RESULTS During the first year , 78 % of trained teachers implemented one or more program lessons . During the second year , only 25 % maintained implementation of the program . Implementors reported fewer years of teaching experience and stronger self-efficacy , enthusiasm , preparedness , teaching methods compatibility , and principal encouragement than did nonimplementors . The principal intervention increased rates of implementation , but the intensive teacher training did not . Integrity of program delivery was positively associated with immediate program outcomes . CONCLUSIONS Program implementation was highly variable , suggesting that widespread teacher use of psychosocial-based programs can not be taken for granted . Strategies for increasing implementation and maintenance need to be developed It is not uncommon for a decade to pass between the time a research problem is identified and the time that research -based solutions are translated into st and ards for care . This quasi-experimental study demonstrated the effectiveness of a collaborative research utilization model directed towards the transfer of specific research -based knowledge ( pain assessment ) into practice for the purpose of helping to solve pain management problems . At the same time , nurses who participated in the model significantly improved their competency in research utilization and their attitudes towards research when compared to a control group who did not participate in the model A new version of the Rational-Experiential Inventory ( REI ) , which measures rational and experiential thinking styles and includes subscales of self-reported ability and engagement , was examined in two studies . In Study 1 , the two main scales were independent , and they and their subscales exhibited discriminant validity and contributed to the prediction of a variety of measures beyond the contribution of the Big Five scales . A rational thinking style was most strongly and directly related to Ego Strength , Openness , Conscientiousness , and favorable basic beliefs about the self and the world , and it was most strongly inversely related to Neuroticism and Conservatism . An experiential thinking style was most strongly directly related to Extraversion , Agreeableness , Favorable Relationships Beliefs , and Emotional Expressivity , and it was most strongly inversely related to Categorical Thinking , Distrust of Others , and Intolerance . In Study 2 , a rational thinking style was inversely related and an experiential thinking style was unrelated to nonoptimal responses in a game of chance . It was concluded that the new REI is a significant improvement over the previous version and measures unique aspects of personality OBJECTIVES To assess the impact of total quality management ( TQM ) and organizational culture on a comprehensive set of endpoints of care for coronary artery bypass graft surgery ( CABG ) patients , including risk-adjusted adverse outcomes , clinical efficiency , patient satisfaction , functional health status , and cost of care . METHODS Prospect i ve cohort study of 3,045 eligible CABG patients from 16 hospitals using risk-adjusted clinical outcomes , functional health status , patient satisfaction , and cost measures . Implementation of TQM was measured by a previously vali date d instrument based on the Baldridge national quality award criteria . Organizational culture was measured by a previously vali date d 20-item instrument . Generalized estimating equations were used to control for potential selection bias , repeated measures , and intraclass correlation . RESULTS A 2- to 4-fold difference in all major clinical CABG care endpoints was observed among the 16 hospitals , but little of this variation was associated with TQM or organizational culture . Patients receiving CABG from hospitals with high TQM scores were more satisfied with their nursing care ( P = 0.005 ) but were more likely to have lengths of stay > 10 days ( P = 0.0003 ) . A supportive group culture was associated with shorter postoperative intubation times ( P = 0.01 ) but longer operating room times ( P = 0.004 ) . A supportive group culture was also associated with higher patient physical ( P = 0.005 ) and mental ( P = 0.01 ) functional health status scores 6 months after CABG . CONCLUSIONS There was little effect of TQM and organizational culture on multiple endpoints of care for CABG patients . There is a need to examine further the relationships among individual professional skills and motivations , group and microsystem team processes , specifically tailored interventions , and organization-wide culture , decision support processes , and incentives . Assessing the impact of such multifaceted approaches is an important area for further research Aim Despite increasing efforts to promote the utilisation of research in daily nursing practice it is apparent that there are a number of obstacles to address . This paper reports a study to examine the barriers to , and facilitators of , research utilisation among registered nurses in Hong Kong . Methods A survey design and a r and om sampling method was used . The final sample consisted of 1487 registered nurses working in private and public health-care sectors in Hong Kong . A bilingual version of the Research Utilisation Question naire , comprising a 31-item barriers scale , and an 8-item facilitators scale was used . The instrument was mailed to participants who were asked to return the completed question naire by mail . Results The highest ranking barriers to research utilisation reported by respondents were related mainly to organisational factors with regards to inadequate facilities , no authority to change procedures , and time constraints . Hong Kong nurses , however , did not appear to see any problem with regards to items related to characteristics of research , such as conclusions drawn from research being justified , research articles not being published fast enough , and literature reporting conflicting results . This indicates that nurses are aware of research developments in nursing and can critically analyse research reports . With regards to facilitators of research utilisation , respondents agreed that managerial and peer support are the greatest facilitators . Conclusions The results indicate that factors influencing research utilisation are multidimensional and should be taken into account by all involved in the research enterprise : research ers , practitioners , educators , managers and policy-makers . The results of this study provide directions on how to assist nurses in Hong Kong in their efforts to utilise research OBJECTIVES We examined the effects of a brief counseling intervention design ed to reduce HIV risk behaviors and sexually transmitted infections ( STIs ) among patients receiving STI services in Cape Town , South Africa . METHODS After r and omization to either a 60-minute risk reduction counseling session or a 20-minute HIV-STI educational session , patients completed computerized sexual behavior assessment s. More than 85 % of the participants were retained at the 12-month follow-up . RESULTS There were 24 % fewer incident STIs and significant reductions in unprotected vaginal and anal intercourse among participants who received risk reduction counseling relative to members of the control condition . Moderator analyses showed shorter lived outcomes for heavy alcohol drinkers than for lighter drinkers . The results were not moderated by gender . CONCLUSIONS Brief single-session HIV prevention counseling delivered to STI clinic patients has the potential to reduce HIV infections . Counseling should be enhanced for heavier drinkers , and sustained outcomes will require relapse prevention techniques . Disseminating effective , brief , and feasible behavioral interventions to those at highest risk for HIV infection should remain a public health priority Background : Physicians face challenges when search ing PubMed for research evidence , and they may miss relevant articles while retrieving too many nonrelevant articles . We investigated whether the use of search filters in PubMed improves search ing by physicians . Methods : We asked a r and om sample of Canadian nephrologists to answer unique clinical questions derived from 100 systematic review s of renal therapy . Physicians provided the search terms that they would type into PubMed to locate articles to answer these questions . We entered the physician-provided search terms into PubMed and applied two types of search filters alone or in combination : a methods -based filter design ed to identify high- quality studies about treatment ( clinical queries “ therapy ” ) and a topic-based filter design ed to identify studies with renal content . We evaluated the comprehensiveness ( proportion of relevant articles found ) and efficiency ( ratio of relevant to nonrelevant articles ) of the filtered and nonfiltered search es . Primary studies included in the systematic review s served as the reference st and ard for relevant articles . Results : The average physician-provided search terms retrieved 46 % of the relevant articles , while 6 % of the retrieved articles were nonrelevant ( the ratio of relevant to nonrelevant articles was 1:16 ) . The use of both filters together produced a marked improvement in efficiency , result ing in a ratio of relevant to nonrelevant articles of 1:5 ( 16 percentage point improvement ; 99 % confidence interval 9 % to 22 % ; p < 0.003 ) with no substantive change in comprehensiveness ( 44 % of relevant articles found ; p = 0.55 ) . Interpretation : The use of PubMed search filters improves the efficiency of physician search es . Improved search performance may enhance the transfer of research into practice and improve patient care Background There have been few studies of tailored interventions to promote colorectal cancer ( CRC ) screening . Purpose We conducted a r and omized trial of a tailored , interactive intervention to increase CRC screening . Methods Patients 50–70 years completed a baseline survey , were r and omized to one of three groups , and attended a wellness exam after being exposed to a tailored intervention about CRC screening ( tailored group ) , a public web site about CRC screening ( web site group ) , or no intervention ( survey-only group ) . The primary outcome was completion of any recommended CRC screening by 6 months . Results There was no statistically significant difference in screening by 6 months : 30 % , 31 % , and 28 % of the survey-only , web site , and tailored groups were screened . Exposure to the tailored intervention was associated with increased knowledge and CRC screening self-efficacy at 2 weeks and 6 months . Family history , prior screening , stage of change , and physician recommendation moderated the intervention effects . Conclusions A tailored intervention was not more effective at increasing screening than a public web site or only being surveyed |
13,316 | 20,546,687 | Although softeners are effective , which specific softeners are most effective remains uncertain .
Evidence on the effectiveness of methods of irrigation or mechanical removal was equivocal . | BACKGROUND Build-up of earwax is a common reason for attendance in primary care .
Current practice for earwax removal generally involves the use of a softening agent , followed by irrigation of the ear if required .
However , the safety and benefits of the different methods of removal are not known for certain .
OBJECTIVES To conduct evidence synthesis of the clinical effectiveness and cost-effectiveness of the interventions currently available for softening and /or removing earwax and any adverse events ( AEs ) associated with the interventions . | OBJECTIVES Using a microscope to achieve a view of the canal during dewaxing is the most commonly performed method of dewaxing in secondary care , but an endoscope can also be used . We set out to compare endoscopic and microscopic dewaxing . DESIGN R and omised clinical trial . SETTING Otolaryngology Outpatient Department . PARTICIPANTS One hundred participants selected sequentially from patients requiring dewaxing of their ears to allow examination of the tympanic membrane . Patients with external or middle ear pathology were excluded . METHODS Patients were r and omly assigned to have dewaxing performed using microinstruments aided by vision with a microscope or an endoscope . All participants who were entered the study completed the study . MAIN OUTCOME MEASURES Levels of pain and discomfort experienced by the participants were assessed by a visual analogue scale ( VAS ) . Difficulty of performing the dewaxing indicated by the endoscopist using a VAS . The length of time taken to perform the dewaxing was also recorded . RESULTS Endoscopic dewaxing was less uncomfortable than microscopic dewaxing for patients ( VAS median values 5 and 25 respectively ; P < 0.002 ) as well as less painful ( VAS median values 3.5 and 10 respectively ; P < 0.075 ) . Endoscopic dewaxing was easier to perform than microscopic dewaxing ( VAS median values for difficulty were 9 and 20 respectively ; P < 0.005 ) and took less time ( mean time for endoscopic dewaxing was 1.8 min versus 3.3 min for microscopic dewaxing ( P < 0.001 ) . Ninety-one per cent of ears could be dewaxed with a Jobson-Horne probe or wax hook . CONCLUSIONS The cost of an operating microscope suitable for use with dewaxing is approximately 10 times that of a suitable endoscope , dewaxing is a cheaper alternative to microscopic dewaxing that has benefits for the patient and clinician OBJECTIVE To assess the protein and simple sugar content of earwax in pursuit of better ceruminolytic agents . STUDY DESIGN Collected earwax specimens were tested in several media for dissolution before being analyzed for amino acid and carbohydrate content . PATIENTS The sample s were obtained from eight r and om patients requiring ear plug removal . RESULTS The amino acid composition differs considerably from hair and stratum corneum of glabrous skin . Sugar analysis revealed high levels of galactosamine and galactose . CONCLUSIONS This analysis of proteins and carbohydrates further characterizes earwax . Future ceruminolytic agents must dissolve lipid , keratin , and a monolayer of lipid covalently bound to the epidermal cells , which encourages cellular aggregation BACKGROUND Earwax is a common problem in general practice . The incidence of complaints owing to earwax in general practice in the Netherl and s is 39.3 per 1000 patients . AIM To determine the feasibility of a strategy using water as a quick dispersant for persistent earwax , compared with the usual strategy using oil as a dispersant for three days in a general practice setting . DESIGN OF STUDY Practice based , prospect i ve controlled intervention study . SETTING Forty-two patients ( 59 ears ) in four general practice s in the Netherl and s. METHOD Patients with persistent earwax were r and omised into an intervention group and a control group . For patients in the intervention group , water drops at body temperature were dropped into the impacted ear and the auditory meatus was blocked with a wet wad of cotton . After the patient had waited for 15 minutes in the waiting room a series of attempts at syringing was completed . Patients in the control group received the usual strategy and were instructed to soften the earwax with oil each night before sleeping and to block the auditory meatus with a wad of cotton , for three days . They were asked to come back after three days for the second attempt of syringing . For both strategies the mean number of syringing attempts ( and 95 % confidence interval ) was calculated and compared by testing the difference between the means using a t-test for independent sample s. All ears in which the wax was still persistent after another five syringing attempts were given the value of 6 in the calculations . RESULTS The mean number of syringing attempts needed per patient in the intervention group was 3.0 ( 95 % CI = 2.4 to 3.6 ) and for the control group , the mean was 2.4 ( 95 % CI = 1.7 to 3.1 ) . The difference between means ( 0.6 , 95 % CI = 0.3 to 1.5 ) was not statistically significant ( P = 0.18 ) . CONCLUSION A patient with persistent earwax can stay in the waiting room following the initial series of five attempts at syringing , with water instilled in the ear canal . After 15 minutes , the earwax is removed as easily as in the usual strategy using oil instilled for three days . The strategy using water as a dispersant for persistent earwax is quick and more convenient for the patient BACKGROUND Dispute exists over the best treatment for softening occlusive earwax . Some require the patient to go away for days before returning for syringing . Some syringe immediately with no preparation . METHODS An open , nonblinded , r and omised controlled trial was conducted in one rural general practice . Effects of instillation of water into the ear canal for 15 minutes before syringing were compared to effects of syringing immediately . RESULTS Thirty-nine ears ( of 26 patients ) were r and omised . Ear wax was removed entirely by syringing in all ears . Prior instillation of water required a mean 7.5 ( + /- 7.3 ) attempts at syringing versus a mean 25.4 ( + /- 39.4 ) attempts for ears that were syringed immediately ( p=0.043 ) . DISCUSSION Prior installation of water before syringing seems to be an effective and simple method of reducing the number of attempts required to clear the ear of occlusive wax OBJECTIVES Ongoing developments in design have improved the outlook for left-ventricular assist device ( LVAD ) implantation as a therapy in end-stage heart failure . Nevertheless , early cost-effectiveness assessment s , based on first-generation devices , have not been encouraging . Against this background , we set out ( i ) to examine the survival benefit that LVADs would need to generate before they could be deemed cost-effective ; ( ii ) to provide insight into the likelihood that this benefit will be achieved ; and ( iii ) from the perspective of a healthcare provider , to assess the value of discovering the actual size of this benefit by means of a Bayesian value of information analysis . METHODS Cost-effectiveness assessment s are made from the perspective of the healthcare provider , using current UK norms for the value of a quality -adjusted life-year ( QALY ) . The treatment model is grounded in published analyses of the R and omized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure ( REMATCH ) trial of first-generation LVADs , translated into a UK cost setting . The prospect s for patient survival with second-generation devices is assessed using Bayesian prior distributions , elicited from a group of leading clinicians in the field . RESULTS Using established thresholds , cost-effectiveness probabilities under these priors are found to be low ( approximately .2 percent ) for devices costing as much as 60,000 pounds . Sensitivity of the conclusions to both device cost and QALY valuation is examined . CONCLUSIONS In the event that the price of the device in use would reduce to 40,000 pounds , the value of the survival information can readily justify investment in further trials Thirty-six patients with symptoms of impacted ear wax were recruited to an open , r and omized , parallel group study of ' Audax ' ear drops and ' Earex ' ear drops . Patients had had their symptoms for several weeks and they were assessed on entry for the degree of impaction in each ear . After using the drops , morning and evening for 4 days , they were assessed on the fifth day for degree of impaction , ease of syringing , side-effects or discomfort , and the investigator 's and patient 's own global impression of efficacy of the ear drops . A trend was seen showing less impaction post-treatment in the ' Audax ' group than in the ' Earex ' group although the difference did not reach statistical significance . A significant difference was seen in favour of ' Audax ' for the frequency and ease of syringing ( p < 0.005 ) . No patients in the ' Audax ' group reported any side-effect or discomfort although 1 patient using ' Earex ' reported slight irritation whilst another found the smell unacceptable . The results of the investigators ' and patients ' own global impression of efficacy were significantly in favour of ' Audax ' ear drops ( p < 0.01 ) BACKGROUND Cerumen obstructing visualization of the tympanic membrane in children is a common and frustrating problem . Docusate sodium , triethanolamine polypeptide , and saline were compared to determine their effectiveness in relieving cerumen obstruction in children . METHODS A r and omized , controlled , double-blind trial was performed on pediatric patients aged 6 months through 5 years with cerumen obstruction . The enrolling physician determined whether the cerumen completely or partially obstructed visualization of the tympanic membrane . One milliliter of docusate sodium , triethanolamine polypeptide , or normal saline as control was placed into the patient 's ear canal . If the tympanic membrane was not completely visualized after 15 minutes , the ear was irrigated with 50 mL of tepid water . Irrigation was repeated a second time if needed . The main outcome was the proportion of tympanic membranes that were completely visualized after cerumeno-eblytic agents or control saline , alone or with irrigation if needed . RESULTS Of 92 patients enrolled , 34 received docusate sodium ; 30 , triethanolamine polypeptide ; and 28 , saline . Mean + /- SD patient age was 34.7 + /- 18.1 months , and 50 ( 54 % ) of the patients were girls . Groups were similar in age , race , sex , ear enrolled , wax consistency , and degree of obstruction . There was no significant difference in the proportion of tympanic membranes completely visualized after treatment with docusate ( 18/34 ; 53 % ) , triethanolamine polypeptide ( 13/30 ; 43 % ) , or saline ( 19/28 ; 68 % ) ( P = .17 ) . CONCLUSION Application of docusate sodium or triethanolamine polypeptide did not significantly improve the proportion of tympanic membranes that were completely visualized vs application of the saline control STUDY OBJECTIVE To test the hypothesis that ear irrigation with warmed normal saline solution is more comfortable and results in fewer side effects than irrigation with room temperature saline solution in normal volunteers . METHODS The study was a r and omized , single-blind , crossover trial in which each subject received 30 mL warmed normal saline solution in 1 ear and 30 mL room temperature saline solution in the opposite ear . The solutions ( warmed versus room temperature ) and the order of irrigation ( right versus left ear ) were separately r and omized . Investigators obtaining scores were blinded to solution temperature . Subjects rated the discomfort of irrigation , using separate visual analog scales , from 0 ( no pain ) to 100 mm ( worst pain ever ) . RESULTS Forty volunteers were enrolled in the study . The mean difference in visual analog scale scores favoring warmed over room temperature saline solution was 26 mm ( 95 % confidence interval [ CI ] , 19 to 33 mm ; P < .0001 ) . Twenty percent more patients reported dizziness with room temperature irrigation ( 95 % CI , 6 % to 34 % ) . There was no gender effect or order effect for the 2 solutions . CONCLUSION Warmed normal saline solution was both clinical ly and statistically more comfortable than room temperature saline solution as an ear irrigant in normal volunteers . Significantly less dizziness was reported with the warmed solution The purpose s of this study were to estimate the prevalence of impacted cerumen in a population of hospitalized elderly patients , and to evaluate the effect of cerumen removal in reversing hearing impairment . The design was a pre-test/post-test static-group comparison . Over a 1-year period , a r and om sample ( n = 226 ) was drawn every third day from daily admission lists of English-speaking patients aged 65 or older , admitted to non-intensive care units of one hospital . On either the second or third day of hospital stay , subjects were given a hearing test using an AudioScope and then their ear canals were examined for impacted cerumen . Ear canal irrigations were performed on those subjects with impacted cerumen . All subjects received a second hearing test . Results indicate that impacted cerumen is a common condition in the hospitalized elderly . Thirty-five per cent of the sample had impacted cerumen , 19.9 % bilaterally and 15.0 % unilaterally . Furthermore , removal of cerumen significantly improved hearing ability . Improved hearing scores were obtained in 75.0 % of the ears after the impacted cerumen was removed , with subjects hearing from one to three more tones per ear on the second hearing test . An analysis of variance for repeated measures on hearing was computed to test for the effect of removing cerumen from individuals who had neither , one or both ears occluded . A significant interaction ( F = 146.83 , d.f . = 2/223 , P less than 0.0001 ) between hearing tests and cerumen removal was found indicating that those with no occlusion had no change in hearing whereas both occluded groups increased with the greatest change for the bilateral group . ( ABSTRACT TRUNCATED AT 250 WORDS STUDY OBJECTIVE Assessment of the tympanic membrane is often impeded by the presence of cerumen . We compared the ceruminolytic effects of triethanolamine polypeptide and docusate sodium in patients with cerumen . METHODS We conducted a prospect i ve , r and omized , controlled , double-blind trial on a convenience sample of cooperative adult and pediatric patients presenting to a university-based emergency department who required removal of cerumen to visualize the tympanic membrane . Structured data collection was performed , and the physician determined whether visualization of the tympanic membrane was partially or totally obscured by cerumen ( interobserver agreement , rho=0.79 ) . Patients received intra-aural instillation of 1mL of either docusate sodium or triethanolamine polypeptide in a liquid form . If not completely cleared within 15 minutes , the external ear canal was irrigated with 50 or 100 mL of normal saline solution and additional attempts to visualize the tympanic membrane were made . The main outcome was the proportion of ears in which the tympanic membrane could be totally visualized after ceruminolytic instillation with or without irrigation . This study had 80 % power to detect a 40 % difference between groups in the proportion of totally visualized tympanic membranes ( chi(2 ) test , alpha=.05 ) . RESULTS Of 50 enrolled patients , 23 received triethanolamine polypeptide and 27 received docusate sodium . Mean patient age was 40 years ( range 1 to 81 years ) ; 35 % were female . Groups were similar in age , sex , and proportion of completely obscured tympanic membranes at presentation ( 78 % ) . The ability to completely visualize the tympanic membrane was significantly greater after treatment with docusate sodium versus triethanolamine polypeptide ( 81 % versus 35 % ; difference in proportions 47 % ; 95 % confidence interval [ CI ] , 22 to 71 ) particularly in children aged 5 or less ( 90 % versus 0 % ; difference in proportions 89 % ; 95 % CI 50 to 100 ) . CONCLUSION Docusate sodium solution is a more effective ceruminolytic than triethanolamine polypeptide , allowing complete or partial visualization of the tympanic membrane in most patients after a single application when followed with irrigation . Use of docusate sodium as a ceruminolytic should be encouraged , particularly in children Objectives : To evaluate the effect of topical skin treatment of the ear canal in the prevention of impacted earwax A parallel group , single-blind , r and omized study was carried out in a general practice to compare the effectiveness and tolerability of two ear drop preparations ( ' Audax ' and ' Cerumol ' ) in the softening of ear wax in 50 adult patients with impacted or hardened ear wax . Assessment s were made on entry of the amount , colour and consistency of the ear wax , symptoms , and objective hearing . Patients were then allocated at r and om to receive one or other preparation and instructed to use the drops , morning and evening , for 4 days after which they were reassessed . Details were recorded of any side-effects or discomfort caused by the study medication and both physician and patients were asked to give their overall opinion of treatment efficacy . Both treatments were shown to be effective in the softening of ear wax and were well tolerated , there being no significant difference between the two groups in these parameters . However , patients who had abnormal hearing before treatment had a significantly greater improvement in objective hearing after treatment with ' Audax ' ear drops compared to those patients treated with ' Cerumol ' ear drops . There were no between-treatment differences in either either the physician 's or patient 's overall assessment s of effectiveness OBJECTIVE To evaluate the efficacy of 2 ceruminolytic products , Cerumenex Eardrops ( Purdue Frederick Company , Norwalk , Conn ) and Murine Ear Drops ( Abbott Laboratories , Abbott Park , Ill ) , in subjects with partial or complete occlusion of the ear canal due to cerumen . DESIGN R and omized , subject- and observer-blind , placebo-controlled , clinical trial . SETTING Corporate research clinic . PARTICIPANTS From among 230 volunteers screened , 74 subjects ( age , 22 - 66 [ mean , 45 ] years ) were enrolled in the study . Participants had baseline occlusion levels of mild ( n = 10 ) , moderate ( n = 26 ) , or complete ( n = 38 ) impairment of tympanic membrane visualization . INTERVENTIONS Subjects were r and omly assigned to 1 of 3 treatments : Cerumenex ( 10 % triethanolamine polypeptide oleate-condensate ) , Murine ( 6.5 % carbamide peroxide ) , and a placebo , BSS Sterile Irrigating Solution ( Alcon Laboratories Inc , Ft Worth , Tex ) . The test medication was instilled into 1 occluded ear for up to two 15-minute applications . Following the treatment , the subject 's ear was irrigated with 50 mL of lukewarm water delivered at low pressure via a WaterPik irrigator equipped with a Grossan irrigator tip . Main Outcome Measure The degree of occlusion , measured against a previously established 4-point scale , was assessed and recorded at baseline and after each instillation and irrigation procedure . RESULTS Neither Cerumenex nor Murine was superior to saline placebo . By the end of treatment , 29.2 % , 15.4 % , and 41.7 % of subjects treated with Cerumenex , Murine , and placebo , respectively , experienced resolution of cerumen occlusion . These values were not statistically significantly different from one another . CONCLUSION The currently marketed ceruminolytic products , Cerumenex and Murine , are no more effective than a saline placebo in removing earwax OBJECTIVES An inexpensive , nontoxic ceruminolytic with reasonable efficacy that can be used by the patient or their caregivers at home could represent significant financial saving for patients and health care systems . The purpose of this study was to compare two simple ceruminolytics for in vitro efficacy . STUDY DESIGN R and omized controlled trial . METHODS Thirty-six children and 33 adults presenting to a community family practice clinic who had cerumen occluding at least one external auditory canal were r and omly assigned to compare use of 10 % aqueous sodium bicarbonate and 2.5 % aqueous acetic acid as ceruminolytics in occlusive cerumen . RESULTS We were unable to demonstrate a difference between in vivo efficacy of these two ceruminolytic solutions , but both solutions were significantly more efficacious in children than adults . CONCLUSIONS There is a role for these ceruminolytics in children with occlusive cerumen , but adults would be better treated in another way Fifteen general practitioners conducted a r and omized , double-blind comparative trial of two cerumenolytics , namely , Otocerol ® and Cerumol ® . A total of 106 patients were entered into the study ( fifty-three in each group ) . Otocerol was shown to be marginally better than Cerumol in all parameters evaluated BACKGROUND Irrigating ears to remove wax is a time-consuming procedure in UK primary care . In many other countries bulb syringes are used for self-clearance of earwax but evidence of their effectiveness is lacking . AIM To compare the effectiveness of self-treatment bulb syringes with routine care . DESIGN OF STUDY Open , r and omised , controlled trial . SETTING Seven practice s in Hampshire , UK . METHOD Participants were 237 patients attending their GP or practice nurse with symptomatic occluding earwax . A further 128 patients did not want to be part of the r and omisation but allowed their data to be analysed . Patients r and omised to intervention ( n = 118 ) were given ear drops , a bulb syringe , and instructions on its use . Patients in the control group ( n = 119 ) received ear drops , followed by ear irrigation by the GP or practice nurse . Main outcome measures were symptoms ( on a 7-point scale ) , wax clearance , need for further treatment , and the acceptability of treatment . RESULTS Comparing patients using the bulb syringe with those treated with conventional irrigation , the change in mean symptom score was -0.81 and -1.26 respectively ( difference -0.45 , 95 % confidence interval [ CI ] = -0.11 to -0.79 ) and , regarding the proportion requiring no further irrigation , 51 % and 69 % respectively . Although irrigation was preferred by more patients , most patients using the bulb syringe would use it again ( 75 % versus 100 % ) and were satisfied with treatment ( 71 % versus 99 % ) . CONCLUSIONS Advising patients with ears blocked by wax to try bulb syringing before irrigation is effective and acceptable , and could significantly reduce the use of NHS re sources |
13,317 | 27,708,846 | Our results from both the systematic review and the meta- analysis suggest that ADF is an efficacious dietary method , and may be superior to VLCD for some patients because of ease of compliance , greater fat-mass loss and relative preservation of fat-free mass . | BACKGROUND Alternate-day-fasting ( ADF ) has been proposed as an effective dieting method .
Studies have found that it also can increase life span in rodents , and reduce inflammation in humans .
The aim of this paper was to systematic ally review the efficacy of ADF compared to very-low-calorie dieting ( VLCD ) in terms of weight loss , and reduction of fat mass and fat-free mass . | OBJECTIVE This study examined whether the combination of alternate day fasting ( ADF ) plus exercise produces superior changes in body composition and plasma lipid levels when compared to each intervention alone . DESIGN AND METHODS Obese subjects ( n = 64 ) were r and omized to 1 of 4 groups for 12 weeks : 1 ) combination ( ADF plus endurance exercise ) , 2 ) ADF , 3 ) exercise , or 4 ) control . RESULTS Body weight was reduced ( P < 0.05 ) by 6 ± 4 kg , 3 ± 1 kg , and 1 ± 0 kg in the combination , ADF , and exercise groups , respectively . Fat mass and waist circumference decreased ( P < 0.001 ) , while lean mass was retained in the combination group . Low-density lipoprotein ( LDL ) cholesterol decreased ( 12 ± 5 % , P < 0.05 ) and high-density lipoprotein ( HDL ) cholesterol increased ( 18 ± 9 % , P < 0.05 ) in the combination group only . LDL particle size increased ( P < 0.001 ) by 4 ± 1 Å and 5 ± 1 Å in the combination and ADF groups , respectively . The proportion of small HDL particles decreased ( P < 0.01 ) in the combination group only . CONCLUSIONS These findings suggest that the combination produces superior changes in body weight , body composition , and lipid indicators of heart disease risk , when compared to individual treatments Obesity has been linked with low levels of ω-3 fatty acids . Generally , intervention studies have failed to establish benefits of supplementation with ω-3PUFA in reducing body weight or fat mass in humans . The aim of this study was to investigate whether supplementation with LCω-3PUFA alone , then consumed concomitantly with a very low energy diet ( VLED ) , facilitated weight loss , improvements in blood lipids and positive changes to inflammatory mediators . This was a double blind r and omised controlled trial with two parallel groups . For 4 weeks of prior supplementation , one group consumed 6 × 1 g capsules per day monounsaturated oil ( placebo ) , the other group consumed 6 × 1 g capsules per day LCω-3PUFA ( fish oil ) each comprising 70 mg EPA and 270 mg DHA , while consuming their usual diet . Each group continued with their supplements for another 4 weeks while both groups followed a VLED regimen ( n = 19 placebo , n = 20 fish oil ) . Fasting blood sample s , anthropometric measurements and 3-day food diaries were collected at baseline , at 4 weeks and at 8 weeks . At 4 weeks levels of EPA and DHA increased two-fold in the fish oil group ( P < 0.001 ) , with no significant changes to anthropometric measurements for either group . At 8 weeks a significant 3-way interaction between time , group and gender was observed for percentage reduction in weight , F(1,35 ) = 5.55 , P = 0.024 , and BMI , F(1,35 ) = 5.3 , P = 0.027 with a greater percentage decrease for females in FO compared to PB for weight ( -7.21 % vs.-5.82 % ) and BMI ( -7.43 % vs.-5.91 % ) respectively ( P < 0.05 for both ) . It would appear that supplementation with LCω-3PUFA had a time dependent effect on weight loss in females BACKGROUND : A relatively high percentage of energy intake as protein has been shown to increase satiety and decrease energy efficiency during overfeeding . AIM : To investigate whether addition of protein may improve weight maintenance by preventing or limiting weight regain after weight loss of 5–10 % in moderately obese subjects . DESIGN OF THE STUDY : In a r and omized parallel design , 148 male and female subjects ( age 44.2±10.1 y ; body mass index ( BMI ) 29.5±2.5 kg/m2 ; body fat 37.2±5.0 % ) followed a very low-energy diet ( 2.1 MJ/day ) during 4 weeks . For subsequent 3 months weight-maintenance assessment , they were stratified according to age , BMI , body weight , restrained eating , and resting energy expenditure ( REE ) , and r and omized over two groups . Both groups visited the University with the same frequency , receiving the same counseling on dem and by the dietitian . One group ( n=73 ) received 48.2 g/day additional protein to their diet . Measurements at baseline , after weight loss , and after 3 months weight maintenance were body weight , body composition , metabolic measurements , appetite profile , eating attitude , and relevant blood parameters . RESULTS : Changes in body mass , waist circumference , REE , respiratory quotient ( RQ ) , total energy expenditure ( TEE ) , dietary restraint , fasting blood-glucose , insulin , triacylglycerol , leptin , β-hydroxybutyrate , glycerol , and free fatty acids were significant during weight loss and did not differ between groups . During weight maintenance , the ‘ additional-protein group ’ showed in comparison to the nonadditional-protein group 18 vs 15 en% protein intake , a 50 % lower body weight regain only consisting of fat-free mass , a 50 % decreased energy efficiency , increased satiety while energy intake did not differ , and a lower increase in triacylglycerol and in leptin ; REE , RQ , TEE , and increases in other blood parameters measured did not differ . CONCLUSION : A 20 % higher protein intake , that is , 18 % of energy vs 15 % of energy during weight maintenance after weight loss , result ed in a 50 % lower body weight regain , only consisting of fat-free mass , and related to increased satiety and decreased energy efficiency OBJECTIVE Investigation of the effect of a green tea-caffeine mixture on weight maintenance after body weight loss in moderately obese subjects in relation to habitual caffeine intake . RESEARCH METHODS AND PROCEDURES A r and omized placebo-controlled double blind parallel trial in 76 overweight and moderately obese subjects , ( BMI , 27.5 + /- 2.7 kg/m2 ) matched for sex , age , BMI , height , body mass , and habitual caffeine intake was conducted . A very low energy diet intervention during 4 weeks was followed by 3 months of weight maintenance ( WM ) ; during the WM period , the subjects received a green tea-caffeine mixture ( 270 mg epigallocatechin gallate + 150 mg caffeine per day ) or placebo . RESULTS Subjects lost 5.9 + /-1.8 ( SD ) kg ( 7.0 + /- 2.1 % ) of body weight ( p < 0.001 ) . At baseline , satiety was positively , and in women , leptin was inversely , related to subjects ' habitual caffeine consumption ( p < 0.01 ) . High caffeine consumers reduced weight , fat mass , and waist circumference more than low caffeine consumers ; resting energy expenditure was reduced less and respiratory quotient was reduced more during weight loss ( p < 0.01 ) . In the low caffeine consumers , during WM , green tea still reduced body weight , waist , respiratory quotient and body fat , whereas resting energy expenditure was increased compared with a restoration of these variables with placebo ( p < 0.01 ) . In the high caffeine consumers , no effects of the green tea-caffeine mixture were observed during WM . DISCUSSION High caffeine intake was associated with weight loss through thermogenesis and fat oxidation and with suppressed leptin in women . In habitual low caffeine consumers , the green tea-caffeine mixture improved WM , partly through thermogenesis and fat oxidation The aim of the present study was to investigate whether capsaicin assists weight maintenance by limiting weight regain after weight loss of 5 to 10 % . In this r and omized double-blind placebo-controlled study , ninety-one moderately overweight subjects were r and omly assigned to an intensive group that underwent all the measurements , and an extensive group that underwent the same measurements except the metabolism measurements . After a 4-week very-low-energy diet ( VLED ) intervention , a 3-month weight-maintenance period followed . During weight maintenance , subjects were divided into a capsaicin ( 135 mg capsaicin/d ) and a placebo group . Body mass was measured before and after the VLED and after 1 , 2 and 3 months of weight maintenance . The mean body-mass loss during the VLED was 6.6 ( SD 2.0 ) kg ( 7.8 ( SD 1.8 ) % initial body mass ) , and was not different between the subsequent treatment and placebo group . During weight maintenance , mean % regain during treatment was not significantly different compared with placebo ( 33.3 ( SD 35.7 ) v. 19.2 ( SD 41.8 ) % , P=0.09 ) . RQ was significantly less increased during weight maintenance in the treatment group compared with placebo ( 0.04 ( SD 0.06 ) v. 0.07 ( SD 0.05 ) , P<0.05 ) , indicating a relatively more sustained fat oxidation . Fat oxidation ( g/h ) after weight maintenance was higher in the capsaicin group compared with placebo ( 4.2 ( SD 1.1 ) v. 3.5 ( SD 0.9 ) , P<0.05 ) . These results indicate that capsaicin treatment caused sustained fat oxidation during weight maintenance compared with placebo . However , capsaicin treatment has no limiting effect on 3-month weight regain after modest weight loss Since long-term weight maintenance ( WM ) is a major problem , interventions to improve WM are needed . The aim of the study was to investigate whether the addition of protein to the diet might limit weight regain after a weight loss of 5 - 10 % in overweight subjects . In a r and omised parallel study design , 113 overweight subjects ( BMI 29.3 ( SD 2.5 ) kg/m2 ) ; age 45.1 ( SD 10.4 ) years ) followed a very-low-energy diet for 4 weeks , after which there was a 6-month period of WM . During WM , subjects were r and omised into either a protein group or a control group . The protein group received 30 g/d protein in addition to their own usual diet . During the very-low-energy diet , no differences were observed between the groups . During WM , the protein group showed a higher protein intake ( 18 % v. 15 % ; P<0.05 ) , a lower weight regain ( 0.8 v. 3.0 kg ; P<0.05 ) , a decreased waist circumference ( -1.2 ( SD 0.7 ) v. 0.5 ( SD 0.5 ) cm ; P<0.05 ) and a smaller increase in respiratory quotient ( 0.03 ( SD 0.01 ) v. 0.07 0.01 ; (SD/)P < 0.05 ) compared with the control group . Weight regain in the protein group consisted of only fat-free mass , whereas the control group gained fat mass as well . Satiety in the fasted state before breakfast increased significantly more in the protein group than in the control group . After 6 months follow-up , body weight showed a significant group x time interaction . A protein intake of 18 % compared with 15 % result ed in improved WM in overweight subjects after a weight loss of 7.5 % . This improved WM implied several factors , i.e. improved body composition , fat distribution , substrate oxidation and satiety CONTEXT The scarcity of data addressing the health effects of popular diets is an important public health concern , especially since patients and physicians are interested in using popular diets as individualized eating strategies for disease prevention . OBJECTIVE To assess adherence rates and the effectiveness of 4 popular diets ( Atkins , Zone , Weight Watchers , and Ornish ) for weight loss and cardiac risk factor reduction . DESIGN , SETTING , AND PARTICIPANTS A single-center r and omized trial at an academic medical center in Boston , Mass , of overweight or obese ( body mass index : mean , 35 ; range , 27 - 42 ) adults aged 22 to 72 years with known hypertension , dyslipidemia , or fasting hyperglycemia . Participants were enrolled starting July 18 , 2000 , and r and omized to 4 popular diet groups until January 24 , 2002 . INTERVENTION A total of 160 participants were r and omly assigned to either Atkins ( carbohydrate restriction , n=40 ) , Zone ( macronutrient balance , n=40 ) , Weight Watchers ( calorie restriction , n=40 ) , or Ornish ( fat restriction , n=40 ) diet groups . After 2 months of maximum effort , participants selected their own levels of dietary adherence . MAIN OUTCOME MEASURES One-year changes in baseline weight and cardiac risk factors , and self-selected dietary adherence rates per self-report . RESULTS Assuming no change from baseline for participants who discontinued the study , mean ( SD ) weight loss at 1 year was 2.1 ( 4.8 ) kg for Atkins ( 21 [ 53 % ] of 40 participants completed , P = .009 ) , 3.2 ( 6.0 ) kg for Zone ( 26 [ 65 % ] of 40 completed , P = .002 ) , 3.0 ( 4.9 ) kg for Weight Watchers ( 26 [ 65 % ] of 40 completed , P < .001 ) , and 3.3 ( 7.3 ) kg for Ornish ( 20 [ 50 % ] of 40 completed , P = .007 ) . Greater effects were observed in study completers . Each diet significantly reduced the low-density lipoprotein/high-density lipoprotein ( HDL ) cholesterol ratio by approximately 10 % ( all P<.05 ) , with no significant effects on blood pressure or glucose at 1 year . Amount of weight loss was associated with self-reported dietary adherence level ( r = 0.60 ; P<.001 ) but not with diet type ( r = 0.07 ; P = .40 ) . For each diet , decreasing levels of total/HDL cholesterol , C-reactive protein , and insulin were significantly associated with weight loss ( mean r = 0.36 , 0.37 , and 0.39 , respectively ) with no significant difference between diets ( P = .48 , P = .57 , P = .31 , respectively ) . CONCLUSIONS Each popular diet modestly reduced body weight and several cardiac risk factors at 1 year . Overall dietary adherence rates were low , although increased adherence was associated with greater weight loss and cardiac risk factor reductions for each diet group CONTEXT Weight loss using low-calorie diets produces variable results , presumably due to a wide range of energy deficits and low-dietary adherence . OBJECTIVE Our objective was to quantify the relationship between dietary adherence , weight loss , and severity of caloric restriction . DESIGN AND SETTING Participants were r and omized to diet only , diet-endurance training , or diet-resistance training until body mass index ( BMI ) was less than 25 kg/m(2 ) . PARTICIPANTS Healthy overweight ( BMI 27 - 30 ) premenopausal women ( n = 141 ) were included in the study . INTERVENTIONS An 800-kcal/d(-1 ) diet was provided , and the exercise groups were engaged in three sessions per week . MAIN OUTCOMES Dietary adherence , calculated from total energy expenditure determined by doubly labeled water measurements and dual-energy x-ray absorptiometry body composition changes , and degree of caloric restriction were determined . RESULTS All groups had similar weight loss ( approximately 12.1 + /- 2.5 kg ) and length of time to reach target BMI ( approximately 158 + /- 70 d ) . Caloric restriction averaged 59 + /- 9 % , and adherence to diet was 73 + /- 34 % . Adherence to diet was inversely associated to days to reach target BMI ( r = -0.687 ; P < 0.01 ) and caloric restriction ( r = -0.349 ; P < 0.01 ) . Association between adherence to diet and percent weight lost as fat was positive for the diet-endurance training ( r = 0.364 ; P < 0.05 ) but negatively correlated for the diet-only group ( r = -0.387 ; P < 0.05 ) . CONCLUSIONS Dietary adherence is strongly associated with rates of weight loss and adversely affected by the severity of caloric restriction . Weight loss programs should consider moderate caloric restriction relative to estimates of energy requirements , rather than generic low-calorie diets Background Alternate day fasting ( ADF ; ad libitum “ feed day ” , alternated with 25 % energy intake “ fast day ” ) , is effective for weight loss and cardio-protection in obese individuals . Whether these effects occur in normal weight and overweight individuals remains unknown . This study examined the effect of ADF on body weight and coronary heart disease risk in non-obese subjects . Methods Thirty-two subjects ( BMI 20–29.9 kg/m2 ) were r and omized to either an ADF group or a control group for 12 weeks . Results Body weight decreased ( P < 0.001 ) by 5.2 ± 0.9 kg ( 6.5 ± 1.0 % ) in the ADF group , relative to the control group , by week 12 . Fat mass was reduced ( P < 0.001 ) by 3.6 ± 0.7 kg , and fat free mass did not change , versus controls . Triacylglycerol concentrations decreased ( 20 ± 8 % , P < 0.05 ) and LDL particle size increased ( 4 ± 1 Å , P < 0.01 ) in the ADF group relative to controls . CRP decreased ( 13 ± 17 % , P < 0.05 ) in the ADF group relative to controls at week 12 . Plasma adiponectin increased ( 6 ± 10 % , P < 0.01 ) while leptin decreased ( 40 ± 7 % , P < 0.05 ) in the ADF group versus controls by the end of the study . LDL cholesterol , HDL cholesterol , homocysteine and resistin concentrations remained unchanged after 12 weeks of treatment . Conclusion These findings suggest that ADF is effective for weight loss and cardio-protection in normal weight and overweight adults , though further research implementing larger sample sizes is required before solid conclusion can be reached The present study was conducted to investigate whether green tea may improve weight maintenance by preventing or limiting weight regain after weight loss of 5 to 10 % in overweight and moderately obese subjects . The study had a r and omised , parallel , placebo-controlled design . A total of 104 overweight and moderately obese male and female subjects ( age 18 - 60 years ; BMI 25 - 35 kg/m(2 ) ) participated . The study consisted of a very-low-energy diet intervention ( VLED ; 2.1 MJ/d ) of 4 weeks followed by a weight-maintenance period of 13 weeks in which the subjects received green tea or placebo . The green tea contained caffeine ( 104 mg/d ) and catechins ( 573 mg/d , of which 323 mg was epigallocatechin gallate ) . Subjects lost 6.4 ( sd 1.9 ) kg or 7.5 ( sd 2.2 ) % of their original body weight during the VLED ( P<0.001 ) . Body-weight regain was not significantly different between the green tea and the placebo group ( 30.5 ( sd 61.8 ) % and 19.7 ( sd 56.9 ) % , respectively ) . In the green tea treatment , habitual high caffeine consumption was associated with a higher weight regain compared with habitual low caffeine consumption ( 39 ( sd 17 ) and 16 ( sd 11 ) % , respectively ; P<0.05 ) . We conclude that weight maintenance after 7.5 % body-weight loss was not affected by green tea treatment and that habitual caffeine consumption affected weight maintenance in the green tea treatment Heterozygous p53-deficient ( p53(+/- ) ) mice , a potential model for human Li-Fraumeni Syndrome , have one functional allele of the p53 tumor suppressor gene . These mice are prone to spontaneous neoplasms , most commonly sarcoma and lymphoma ; the median time to death of p53+/- mice is 18 months . We have shown previously that juvenile-onset calorie restriction ( CR ) to 60 % of ad libitum ( AL ) intake delays tumor development in young p53-null ( -/- ) mice by a p53-independent and insulin-like growth factor 1 (IGF-1)-related mechanism . To determine whether CR is effective when started in adult p53-deficient mice , and to compare chronic CR with an intermittent fasting regimen , male p53+/- mice ( 7 - 10 months old , 31 - 32 mice/group ) were r and omly assigned to the following regimens : ( i ) AL ( AIN-76A diet ) , ( ii ) CR to 60 % of AL intake or ( iii ) 1 day/week fast . Food availability on non-fasting days was controlled to prevent compensatory over feeding . Relative to the AL group , CR significantly delayed ( P = 0.001 ) the onset of tumors in adult mice , whereas the 1 day/week fast caused a moderate delay ( P = 0.039 ) . Substantial variation in longevity and maximum body weight within treatments was not correlated with variation in growth characteristics of individual mice . In a separate group of p53+/- mice treated for 4 weeks ( n = five mice per treatment ) , plasma IGF-1 levels in CR versus AL mice were reduced by 20 % ( P < 0.01 ) and leptin levels were reduced by 71 % ( P < 0.01 ) ; fasted mice had intermediate levels of leptin and IGF-1 . Our findings that CR or a 1 day/week fast suppressed carcinogenesis-even when started late in life in mice predestined to develop tumors due to decreased p53 gene dosage-support efforts to identify suitable interventions influencing energy balance in humans as a tool for cancer prevention UNLABELLED Alternate day fasting ( ADF ) with a low-fat ( LF ) diet is effective for weight loss and cardio-protection . However , the applicability of these findings is question able as the majority of Americans consume a high-fat ( HF ) diet . OBJECTIVE The goal of this study was to determine if these beneficial changes in body weight and coronary heart disease ( CHD ) risk can be reproduced if an HF background diet is used in place of an LF diet during ADF . METHODS Thirty-two obese subjects were r and omized to an ADF-HF ( 45 % fat ) or ADF-LF diet ( 25 % fat ) , which consisted of two phases : 1 ) a 2-week baseline weight maintenance period , and 2 ) an 8-week ADF weight loss period . All food was provided during the study . RESULTS Body weight was reduced ( P<0.0001 ) by ADF-HF ( 4.8%±1.1 % ) and by ADF-LF ( 4.2%±0.8 % ) . Fat mass decreased ( P<0.0001 ) by ADF-HF ( 5.4±1.5 kg ) and ADF-LF ( 4.2±0.6 kg ) . Fat free mass remained unchanged . Waist circumference decreased ( P<0.001 ) by ADF-HF ( 7.2±1.5 cm ) and ADF-LF ( 7.3±0.9 cm ) . LDL cholesterol and triacylglycerol concentrations were reduced ( P<0.001 ) by both interventions ( ADF-HF : 18.3%±4.6 % , 13.7%±4.8 % ; and ADF-LF : 24.8%±2.6 % , 14.3%±4.4 % ) . HDL cholesterol , blood pressure , and heart rate remained unchanged . There were no between-group differences for any parameter . CONCLUSION These findings suggest that an ADF-HF diet is equally as effective as an ADF-LF diet in helping obese subjects lose weight and improve CHD risk factors OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity The ability of alternate-day fasting ( ADF ) to modulate adipocyte parameters in a way that is protective against coronary heart disease ( CHD ) has yet to be tested . Accordingly , we examined the effects of ADF on adipokine profile , body composition , and CHD risk indicators in obese adults . Sixteen obese subjects ( 12 women/4 men ) participated in a 10-week trial with three consecutive dietary intervention phases : ( i ) 2-week baseline control phase , ( ii ) 4-week ADF controlled feeding phase , and ( iii ) 4-week ADF self-selected feeding phase . After 8 weeks of treatment , body weight and waist circumference were reduced ( P < 0.05 ) by 5.7 ± 0.9 kg , and 4.0 ± 0.9 cm , respectively . Fat mass decreased ( P < 0.05 ) by 5.4 ± 0.8 kg , whereas fat-free mass did not change . Plasma adiponectin was augmented ( P < 0.05 ) by 30 % from baseline . Leptin and resistin concentrations were reduced ( P < 0.05 ) by 21 and 23 % , respectively , post treatment . Low-density lipoprotein cholesterol ( LDL-C ) and triacylglycerol concentrations were 25 % and 32 % lower ( P < 0.05 ) , respectively , after 8 weeks of ADF . High-density lipoprotein cholesterol ( HDL-C ) , C-reactive protein , and homocysteine concentrations did not change . Decreases in LDL-C were related to increased adiponectin ( r = -0.61 , P = 0.01 ) and reduced waist circumference ( r = 0.39 , P = 0.04 ) . Lower triacylglycerol concentrations were associated with augmented adiponectin ( r = -0.39 , P = 0.04 ) and reduced leptin concentrations ( r = 0.45 , P = 0.03 ) post-treatment . These findings suggest that adipose tissue parameters may play an important role in mediating the cardioprotective effects of ADF in obese humans This study compared the weight losses of 49 obese women r and omly assigned to a 52-week behavioral program combined with either moderate or severe caloric restriction . Subjects in the balanced deficit diet ( BDD ) condition were prescribed a 1,200-kcal/day diet throughout treatment , and those in the very-low-calorie diet ( VLCD ) condition were given a 420-kcal/day liquid diet for 16 weeks and a 1,200-kcal/day diet thereafter . The VLCD subjects lost significantly more weight than the BDD subjects at all periods through Week 26 , at which time mean losses were 21.45 and 11.86 kg , respectively . VLCD subjects , however , regained weight during the next 26 weeks of weekly therapy and during a 26-week weight maintenance program that provided biweekly meetings . Mean weight losses at the end of the maintenance program were 10.94 and 12.18 kg , respectively . Reports of binge eating declined in both groups , and no relationship was observed between binge eating and weight loss or attrition Inflammatory mechanisms are involved in the pathogenesis of type 2 diabetes with interleukin (IL)-6 being particularly important . While long term exercise has been shown to be associated with reduction in IL-6 serum levels in several reports , the discussion on the effect of dietary intervention on IL-6 serum levels is controversial . In the present study , we aim ed to investigate the effect of weight loss due to a very low calorie diet ( VLCD ) on insulin sensitivity and IL-6 serum levels in nondiabetic obese human individuals . 10 patients with obesity were examined during 12 weeks of a VLCD ( 800 kcal/d ) . Body composition was measured by impedance analysis . Blood sample s were taken before , during , and after the dietary intervention . Leptin , adiponectin , and IL-6 serum levels were measured by ELISA . The body weight decreased significantly from 123.9±6.2 - 103.5±5.6 kg with a significant reduction in body fat content ( 43.2±2.3 - 36.1±3.1 % ) . Leptin levels exhibited a significant decrease from 56.8±5.6 - 27.9±5.6 ng/ml while adiponectin levels increased significantly from 7.5±0.9 - 10.6±1.1 μg/ml . Thereby the leptin-to-adiponectin ratio , a novel marker for insulin sensitivity , significantly improved . Mean IL-6 serum concentrations were within the normal range ( 3.2±0.8 pg/ml ) before the study and were not significantly altered by the nutritional therapy . Despite improvement of insulin sensitivity , IL-6 serum levels did not change throughout the study period , suggesting that in nondiabetic obese human subjects IL-6 might have only a minor role in the impairment of insulin sensitivity |
13,318 | 29,737,795 | The results of this process favored L-carnitine supplementation in patients with cancer-related cachexia .
Nitrogen balance was improved either through the increase of protein synthesis or by reduction in proteolysis , inhibiting apoptosis or reversing inflammatory processes .
Although clinical studies are inconclusive , studies in animal models support L-carnitine administration to prevent oxidative stress and ameliorate mitochondrial function .
L-carnitine supplementation leads to beneficial effects on several critical mechanisms involved in pathologic skeletal muscle loss and improved fatigue-related parameters in patients with cancer . | BACKGROUND AND OBJECTIVES Cachexia is a paraneoplastic syndrome that affects the large majority of patients with end-stage cancer .
No known therapy exists to effectively overcome the severe symptoms of cachexia , which include anorexia , weight loss and fatigue .
This study considered the results of both experimental and clinical studies to evaluate the suitability of L-carnitine and its derivatives as potential therapies for cachexia in patients with cancer . | Ifosfamide and cisplatin cause urinary loss of carnitine , which is a fundamental molecule for energy production in mammalian cells . We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients . Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry . Patients were excluded if they had anaemia or other conditions thought to be causing asthenia . Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life question naire . Treatment consisted of oral levocarnitine 4 g daily , for 7 days . Fifty patients were enrolled ; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients . In the whole group , baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 ( ±6.4 ; st and ard deviation ) and the mean plasma carnitine value was 20.9 μM ( ±6.8 ; st and ard deviation ) . After 1 week , fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 ( ±5.4 ; st and ard deviation ) ( P<.001 ) . All patients achieved normal plasma carnitine levels . Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy . In selected patients , levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue . This compound deserves further investigations in a r and omised , placebo-controlled study We examined the effect of macronutrient content on glomerular filtration rate ( GFR ) , and excretion , reabsorption , and filtered load of carnitine . Ten subjects consumed five diets [ high protein ( HP ) , low protein ( LP ) , control , high fat ( HF ) , and high carbohydrate ( HC ) ] of equal energy and carnitine content for 6 d each , in a r and omized crossover manner . The rate of carnitine excretion was lower after the LP diet than after the HP diet because of lower GFR after the LP diet . The rate of carnitine reabsorption was lower after the LP diet than after the HP diet , also because of the lower GFR after the LP diet . The rate of carnitine reabsorption was not different after the HF and HC diets , nor was GFR . The filtered load of carnitine , however , was greater after the HF diet , result ing in a higher rate of carnitine excretion Cancer and its treatment can induce subjective and objective evidence of diminished functional capacity encompassing physical fatigue and cognitive impairment . Dexmethylpheni date ( D-MPH ; the D-isomer of methylpheni date ) was evaluated for treatment of chemotherapy-related fatigue and cognitive impairment . A r and omized , double-blind , placebo-controlled , parallel-group study evaluated the potential therapeutic effect and safety of D-MPH in the treatment of patients with chemotherapy-related fatigue . Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale ( FACIT-F ) total score at Week 8 was the primary outcome measure . One hundred fifty-four patients ( predominantly with breast and ovarian cancers ) were r and omized and treated . Compared with placebo , D-MPH-treated subjects demonstrated a significant improvement in fatigue symptoms at Week 8 in the FACIT-F ( P=0.02 ) and the Clinical Global Impression-Severity scores ( P=0.02 ) , without clinical ly relevant changes in hemoglobin levels . Cognitive function was not significantly improved . There was a higher rate of study drug-related adverse events ( AEs ) ( 48 of 76 [ 63 % ] vs. 22 of 78 [ 28 % ] ) and a higher discontinuation rate because of AEs ( 8 of 76 [ 11 % ] vs. 1 of 78 [ 1.3 % ] ) in D-MPH-treated subjects compared with placebo-treated subjects . The most commonly reported AEs independent of study drug relationship in D-MPH-treated subjects were headache , nausea , and dry mouth , and in placebo-treated subjects were headache , diarrhea , and insomnia . D-MPH produced significant improvement in fatigue in subjects previously treated with cytotoxic chemotherapy . Further studies with D-MPH or other agents to explore treatment response in chemotherapy-associated fatigue should be considered Summary Background . Fatigue can significantly interfere with a cancer patient ’s ability to fulfill daily responsibilities and enjoy life . It commonly co-exists with depression in patients undergoing chemotherapy , suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue . Methods . We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy r and omly assigned to receive either 20 mg of the selective serotonin re-uptake inhibitor ( SSRI ) paroxetine ( Paxil ® , SmithKline Beecham Pharmaceuticals ) or an identical-appearing placebo . Patients began their study medication seven days following their first on- study treatment and continued until seven days following their fourth on- study treatment . Seven days after each treatment , participants completed question naires measuring fatigue ( Multidimensional Assessment of Fatigue , Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist ) and depression ( Profile of Mood States-Depression subscale [ POMS-DD ] and Center for Epidemiologic Studies -Depression [ CES-D ] ) . Results . Repeated- measures ANOVAs , after controlling for baseline measures , showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D ( p=0.006 ) and the POMS-DD ( p=0.07 ) but not in reducing fatigue ( all measures , ps > 0.27 ) . Conclusions . Although depression was significantly reduced in the 44 patients receiving paroxetine compared to the 50 patients receiving placebo , indicating that a biologically active dose was used , no significant differences between groups on any of the measures of fatigued were observed . Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment BACKGROUND & AIMS A phase III , r and omized non-inferiority study was carried out to compare a two-drug combination ( including nutraceuticals , i.e. antioxidants ) with carnitine + celecoxib ± megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome ( CACS ) : the primary endpoints were increase of lean body mass ( LBM ) and improvement of total daily physical activity . Secondary endpoint was : increase of physical performance tested by grip strength and 6-min walk test . METHODS Sixty eligible patients were r and omly assigned to : arm 1 , L-carnitine 4 g/day + Celecoxib 300 mg/day or arm 2 , L-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day , all orally . All patients received as basic treatment polyphenols 300 mg/day , lipoic acid 300 mg/day , carbocysteine 2.7 g/day , Vitamin E , A , C. Treatment duration was 4 months . Planned sample size was 60 patients . RESULTS The results did not show a significant difference between tre atment arms in both primary and secondary endpoints . Analysis of changes from baseline showed that LBM ( by dual-energy X-ray absorptiometry and by L3 computed tomography ) increased significantly in both arms as well as physical performance assessed by 6MWT . Toxicity was quite negligible and comparable between arms . CONCLUSIONS The results of the present study showed a non-inferiority of arm 1 ( two-drug combination ) vs arm 2 ( two-drug combination + megestrol acetate ) . Therefore , this simple , feasible , effective , safe , low cost with favorable cost-benefit profile , two-drug approach could be suggested in the clinical practice to implement CACS treatment OBJECTIVE In April 2005 a phase III r and omized study was started to establish which was the most effective and safest treatment of cancer-related anorexia/cachexia syndrome and oxidative stress in improving identified primary endpoints : increase of lean body mass , decrease of resting energy expenditure ( REE ) , increase of total daily physical activity , decrease of interleukin-6 and tumor necrosis factor-alpha , and improvement of fatigue assessed by the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) . METHODS All patients were given as basic treatment polyphenols plus antioxidant agents alpha-lipoic acid , carbocysteine , and vitamins A , C , and E , all orally . Patients were then r and omized to one of the following five arms : 1 ) medroxyprogesterone acetate/megestrol acetate ; 2 ) pharmacologic nutritional support containing eicosapentaenoic acid ; 3 ) L-carnitine ; 4 ) thalidomide ; or 5 ) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus L-carnitine plus thalidomide . Treatment duration was 4 mo . The sample comprised 475 patients . RESULTS By January 2007 , 125 patients , well balanced for all clinical characteristics , were included . No severe side effects were observed . As for efficacy , an interim analysis on 125 patients showed an improvement of at least one primary endpoint in arms 3 , 4 , and 5 , whereas arm 2 showed a significant worsening of lean body mass , REE , and MFSI-SF . Analysis of variance comparing the change of primary endpoints between arms showed a significant improvement of REE in favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor of arms 1 , 3 , and 5 versus arm 2 . A significant inferiority of arm 2 versus arms 3 , 4 , and 5 for the primary endpoints lean body mass , REE , and MFSI-SF was observed on the basis of t test for changes . CONCLUSION The interim results obtained thus far seem to suggest that the most effective treatment for cancer-related anorexia/cachexia syndrome and oxidative stress should be a combination regimen . The study is still in progress and the final results should confirm these data Increased cytokine expression contributes to the pathogenesis of cancer anorexia – cachexia syndrome . Carnitine may reduce inflammation in chronic diseases . We tested the effects of L-propionylcarnitine ( PC group ) or saline ( C group ) on food intake ( FI ) , body composition , and inflammatory status of MCA-sarcoma-bearing rats . On tumor appearance , rats were r and omly assigned to daily i.p . injection of L-propionylcarnitine ( 250 mg/kgBW/d ; n = 8) or saline ( equal volume ; n = 8) . FI and fat-free mass wasting improved in PC rats only ( p < .01 vs. controls ) . Cytokines ’ levels decreased in PC rats vs. controls ( p < .02 ) . Results suggest that carnitine may ameliorate cancer anorexia – cachexia , via reduction of the inflammatory status Background Cachexia , a > 10 % loss of body-weight , is one factor determining the poor prognosis of pancreatic cancer . Deficiency of L-Carnitine has been proposed to cause cancer cachexia . Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospect i ve , multi-centre , placebo-controlled , r and omized and double-blinded trial to receive oral L-Carnitine ( 4 g ) or placebo for 12 weeks . At entry patients reported a mean weight loss of 12 ± 2,5 ( SEM ) kg . During treatment body-mass-index increased by 3,4 ± 1,4 % under L-Carnitine and decreased ( −1,5 ± 1,4 % ) in controls ( p < 0,05 ) . Moreover , nutritional status ( body cell mass , body fat ) and quality -of-life parameters improved under L-Carnitine . There was a trend towards an increased overall survival in the L-Carnitine group ( median 519 ± 50 d versus 399 ± 43 d , not significant ) and towards a reduced hospital-stay ( 36 ± 4d versus 41 ± 9d , n.s . ) . Conclusion While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinical ly relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine We investigated the effect of antioxidant supplementation on mitochondrial function , fat distribution , and lipid and glucose metabolism in HIV-1-infected patients with antiretroviral therapy (ART)-related lipoatrophy . 61 ART-treated HIV-1-infected patients with lipoatrophy were r and omized to receive either n-acetyl-L-carnitine ( n = 21 ) , lipoic acid + n-acetylcisteine ( LA/NAC ) ( n = 20 ) , or no supplementation ( n = 20 ) for 48 weeks . At baseline and at the end of treatment , mitochondrial function was studied by (13)C-methionine breath test and by mitochondrial (mt)-DNA quantification on circulating T-cells and subcutaneous adipose tissue . Body composition was assessed by dual-energy X-ray absorpiometry ( DEXA ) . (13)CO(2)-exhalation increased between baseline and week 48 in both supplementation arms as evidence d by a higher delta over baseline excretion at 45 min ( from mean ± SEM of 7.8 ± 1.08 to 9.9 ± 0.6 , p = 0.04 in the n-acetyl-carnitine arm , and from 7.4 ± 0.8 to 11.5 ± 1.6 , p = 0.01 in LA/NAC arm ) . Cumulative (13)CO2 excretion increased from median ( interquartile range ; IQR ) of 3.25 ( 2.55 - 4.2 ) to 4.51 ( 4.12 - 5.2 ) in the carnitine arm ; from 3.79 ( 2.67 - 4.37 ) to 4.83 ( 4.25 - 5.56 ) in the LA/NAC arm ; p = 0.004 , 0.02 , respectively . mtDNA content increased in CD4 + T-cells from patients who received n-acetyl-carnitine ( + 30 copies/cell ; p = 0.03 ) , without significant difference by the overall comparison of the study groups . Fat body mass and lipid profile did not change significantly in any of the arms . Our study showed that antioxidant supplementation may have a protective role on mitochondrial function , with limited effects on the reversal of clinical lipodystrophic abnormalities in HIV-1-infected patients Abnormally low intramuscular glutamate and glutathione ( GSH ) levels and /or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus ( SIV ) infection and may contribute to the development of cachexia . We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport . A r and omized double-blind clinical trial was design ed to study the effects of L -carnitine , i.e. an agent known to enhance mitochondrial integrity and function , on the glutamate transport and plasma glutamate level of cancer patients . The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice . In the mice , L -carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels . The carnitine-treated group in the r and omized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities . Further studies may be warranted to determine the effect of L -carnitine on the intramuscular GSH levels in cancer patients . © 2000 Cancer Research PURPOSE Fatigue and depression typically occur together in cancer patients , suggesting a common etiology , perhaps based on serotonin . This r and omized clinical trial tested whether paroxetine , a selective serotonin reuptake inhibitor antidepressant known to modulate brain serotonin , would reduce fatigue in cancer patients and whether any reduction was related to depression . PATIENTS AND METHODS Cancer patients undergoing chemotherapy for the first time were assessed for fatigue . Of 704 patients who reported fatigue at their second chemotherapy cycle , 549 patients were r and omly assigned to receive either 20 mg of oral paroxetine hydrochloride daily or placebo for 8 weeks . The assessment s of fatigue and depression were performed at cycles 3 and 4 of chemotherapy . RESULTS A total of 244 patients treated with paroxetine and 235 patients treated with placebo provided assessable data . No difference was detected in fatigue between patient groups . At the end of the study , there was a difference between groups in the mean level of depression ( Center for Epidemiologic Studies Depression scores , 12.0 v 14.8 , respectively ; P < .01 ) . CONCLUSION Paroxetine had no influence on fatigue in patients receiving chemotherapy . A possible explanation is that cancer-related fatigue does not involve a reduction in brain 5-HT levels PURPOSE L-carnitine , a popular complementary and alternative medicine product , is used by patients with cancer for the treatment of fatigue , the most commonly reported symptom in this patient population . The purpose of this study was to determine the efficacy of L-carnitine supplementation as a treatment for fatigue in patients with cancer . PATIENTS AND METHODS In this double-blind , placebo-controlled trial , patients with invasive malignancies and fatigue were r and omly assigned to either 2 g/d of L-carnitine oral supplementation or matching placebo . The primary end point was the change in average daily fatigue from baseline to week 4 using the Brief Fatigue Inventory ( BFI ) . RESULTS Three hundred seventy-six patients were r and omly assigned to treatment with L-carnitine supplementation or placebo . L-carnitine supplementation result ed in significant carnitine plasma level increase by week 4 . The primary outcome , fatigue , measured using the BFI , improved in both arms compared with baseline ( L-carnitine : -0.96 , 95 % CI , -1.32 to -0.60 ; placebo : -1.11 , 95 % CI -1.44 to -0.78 ) . There were no statistically significant differences between arms ( P = .57 ) . Secondary outcomes , including fatigue measured by the Functional Assessment of Chronic Illness Therapy-Fatigue instrument , depression , and pain , did not show significant difference between arms . A separate analysis of patients who were carnitine-deficient at baseline did not show statistically significant improvement in fatigue or other outcomes after L-carnitine supplementation . CONCLUSION Four weeks of 2 g of L-carnitine supplementation did not improve fatigue in patients with invasive malignancies and good performance status Nutritional factors are among the postulated causes of fatigue , a highly prevalent symptom in the cancer population , with serious impact on patients ' quality of life . Deficiency of the micronutrient carnitine may play a role by reducing energy production through fatty acid oxidation . We present preliminary data of an open-label , dose-finding study to determine safety and maximally tolerated dose ( MTD ) of 1 week of L-carnitine supplementation in cancer patients with fatigue and carnitine deficiency . Patients who met inclusion /exclusion criteria underwent carnitine level determination . Eighty-three percent of these patients ( 15/18 ) had carnitine deficiency . Preliminary data analysis of 13 patients showed that total carnitine increased from 30.0 + /- 6.9 to 41.0 + /- 12.1 ( mean + /- SD ) after 1 week of supplementation ( P = 0.01 ) , and free carnitine increased from 24.3 + /- 6.1 to 33.8 + /- 9.8 ( P = 0.004 ) . Outcome measures were fatigue ( BFI score ) , depression ( CES-D ) , sleep disruption ( ESS ) , and performance status ( Karnofsky ) . Median ( min , max ) BFI score at baseline was 73 ( 46 , 82 ) versus 50 ( 3 , 82 ) after 1-week supplementation ( P = 0.009 ) . CES-D score at baseline was 29 ( 16 , 42 ) and 22 ( 8 , 32 ) after 1 week ( P = 0.028 ) . ESS at baseline was 46.5 ( 0 , 69 ) and 30.4 ( 0 , 72 ) after 1 week ( P = 0.015 ) . Karnofsky score did not change significantly ( P = 0.38 ) . We are currently conducting a r and omized , double-blind , placebo-controlled study to rigorously assess the role of L-carnitine for the treatment of fatigue and depression in cancer patients PURPOSE A phase III , r and omized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass ( LBM ) , resting energy expenditure ( REE ) , and fatigue- and relevant secondary endpoints : appetite , quality of life , grip strength , Glasgow Prognostic Score ( GPS ) and proinflammatory cytokines . PATIENTS AND METHODS Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were r and omly assigned to one of five treatment arms : arm 1 , medroxyprogesterone ( 500 mg/day ) or megestrol acetate ( 320 mg/day ) ; arm 2 , oral supplementation with eicosapentaenoic acid ; arm 3 , L-carnitine ( 4 g/day ) ; arm 4 , thalidomide ( 200 mg/day ) ; and arm 5 , a combination of the above . Treatment duration was 4 months . RESULTS Analysis of variance showed a significant difference between treatment arms . A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints . An analysis of changes from baseline showed that LBM ( by dual-energy X-ray absorptiometry and by L3 computed tomography ) significantly increased in arm 5 . REE decreased significantly and fatigue improved significantly in arm 5 . Appetite increased significantly in arm 5 ; interleukin (IL)-6 decreased significantly in arm 5 and arm 4 ; GPS and Eastern Cooperative Oncology Group performance status ( ECOG PS ) score decreased significantly in arm 5 , arm 4 , and arm 3 . Toxicity was quite negligible , and was comparable between arms . CONCLUSION The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite , IL-6 , GPS , and ECOG PS score was the combination regimen that included all selected agents BACKGROUND Previously , we demonstrated that selected groups of hemodialysis patients might be more likely to have abnormalities of carnitine metabolism . The purpose of the present study was to examine the effects of carnitine therapy in these selected groups of hemodialysis patients on quality -of-life measures and erythropoietin dose . METHODS This was a double-blind , r and omized , controlled trial , in which 50 hemodialysis patients were treated with either 2 g i.v . carnitine or placebo . The treatment period was for 24 weeks . RESULTS Thirty-four patients ( 15 in the treatment group ) completed the study . The mean age was 69 + /- 15 years , 35 % were women , and 44 % had diabetes . Mean initial plasma total , free , short-chain acyl and long-chain acyl carnitine concentrations ( micromol/L ; mean + /- SEM ) were 35.9 + /- 1.8 , 18.2 + /- 1.1 , 11.6 + /- 0.6 , and 6.0 + /- 0.3 , whereas the plasma acyl-to-free-carnitine ratio was 1.02 + /- 0.05 . With respect to the Medical Outcomes Short Form-36 ( SF-36 ) , improvements from baseline were noted in the treatment group ( n = 13 ) for role-physical ( 33.9 + /- 1.9 to 43.2 + /- 3.0 , p < .05 ) and the SF-36 physical component summary score ( 36.1 + /- 2.7 to 39.7 + /- 2.3 , p = .09 ) relative to changes in the control group ( n = 14 ) . The erythropoietin dose over the 24-week period was reduced from baseline in the treatment group relative to the placebo group ( -1.62 + /- 0.91 vs 1.33 + /- 0.79 units erythropoietin/dry weight/hemoglobin concentration , respectively , p < .05 ) . CONCLUSIONS After 24 weeks of i.v . carnitine therapy , SF-36 scores were improved and erythropoietin doses were reduced in hemodialysis patients , relative to the control group Cancer‐related fatigue is a debilitating symptom affecting psychosocial functioning and quality of life in 70 % to 100 % of cancer patients during and after treatment . The authors examined the effect of 200 mg of modafinil daily on the severity of cancer‐related fatigue PURPOSE To evaluate the effectiveness of donepezil compared with placebo in cancer patients with fatigue as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue ( FACIT-F ) . PATIENTS AND METHODS Patients with fatigue score > or= 4 on a scale of 0 to 10 ( 0 = no fatigue , 10 = worst possible fatigue ) for more than 1 week were included . Patients were r and omly assigned to receive donepezil 5 mg or placebo orally every morning for 7 days . A research nurse contacted the patients by telephone daily to assess toxicity and fatigue level . All patients were offered open-label donepezil during the second week . FACIT-F and /or the Edmonton Symptom Assessment System ( ESAS ) were assessed at baseline , and days 8 , 11 , and 15 . The FACIT-F fatigue subscale score on day 8 was considered the primary end point . RESULTS Of 142 patients r and omly assigned to treatment , 47 patients in the donepezil group and 56 in the placebo group were assessable for final analysis . Fatigue intensity improved significantly on day 8 in both donepezil and placebo groups . However , there was no significant difference in fatigue improvement by FACIT-F ( P = .57 ) or ESAS ( P = .18 ) between groups . In the open-label phase , fatigue intensity continued to be low as compared with baseline . No significant toxicities were observed . CONCLUSION Donepezil was not significantly superior to placebo in the treatment of cancer-related fatigue Fatigue is very common in patients with cancer . Current guidelines suggest that psychostimulants are " reasonable to consider for severe fatigue . " This r and omized , double-blind , placebo-controlled trial investigated the hypothesis that dexamphetamine in fatigued patients with advanced cancer would produce a clinical ly significant improvement with minimal side effects . Fifty patients with advanced cancer , who were receiving palliative care , were r and omized to dexamphetamine 10 mg twice daily or placebo for eight days . Effectiveness was assessed using the Brief Fatigue Inventory and the McGill Quality -of-Life Question naire . The side effects were recorded . The results were analyzed on an intention-to-treat basis . The baseline demographics , fatigue levels , and quality -of-life scores were similar between the two arms . Patients were elderly , had impaired performance status ( Eastern Cooperative Oncology Group score=3 ) , and were taking a range of neurologically active medications . Thirty-nine patients completed the trial . There was a transient improvement in the fatigue levels on day 2 , but no significant difference in fatigue ( P=0.267 ) or quality of life ( P=0.579 ) by the end of the study . Statistical modeling did not reveal any significant predictors of response to dexamphetamine . These results suggest that dexamphetamine 20 mg daily , although well tolerated , does not significantly improve fatigue or quality of life in patients with advanced cancer , as measured by the selected instruments Abstract Background . Minimal hepatic encephalopathy ( MHE ) represents a common complication present in well-compensated cirrhotic patients that impairs patients ' daily functioning and health-related quality of life ( HRQL ) . Acetyl-l-carnitine ( ALC ) has been shown to be useful in improving blood ammonia and cognitive functions in cirrhotic patients with MHE . Objective . This study evaluated the effects of ALC treatment on HRQL and depression in patients with MHE . Study design . This was a r and omized , double-blind , placebo-controlled study . Sixty-seven patients with MHE were recruited to the study . They were r and omly assigned to two groups and received either 2 g acetyl-l-carnitine twice a day ( n = 33 ) or placebo ( n = 34 ) for 90 days . The primary efficacy measures were changes in aspartate aminotransferase , alanine aminotransferase , γ-glutamyl-transpeptidase , albumin , alkaline phosphatase , prothrombin time , and ammonia . Clinical and laboratory assessment s , psychometric tests and automated electroencephalogram ( EEG ) analysis were performed for all patients . Results . At the end of the study period , between the two groups , we observed a significant difference in physical function ( p < 0.001 ) , role physical ( p < 0.001 ) , general health ( p < 0.001 ) , social function ( p < 0.05 ) , role emotional ( p < 0.05 ) , mental health ( p < 0.05 ) , Beck Depression Inventory ( p < 0.001 ) , TMT-B s ( p < 0.001 ) , State Trait Inventory ( p < 0.001 ) , urea ( p < 0.05 ) , NH4 + ( p < 0.001 ) , and bilirubin ( p < 0.001 ) . Conclusions . This study shows that ALC treatment is associated with significant improvement in patient energy levels , general functioning and well-being . The improvement of quality of life is associated with reduction of anxiety and depression BACKGROUND Depression , anxiety , fatigue , and impaired wellbeing are common , important , and closely related in advanced cancer . We aim ed to identify the effects of an established antidepressant on these symptoms and survival in patients with advanced cancer who did not have major depression as assessed by clinicians . METHODS Between July , 2001 , and February , 2006 , 189 patients with advanced cancer were r and omly assigned sertraline 50 mg ( n=95 ) , or placebo ( n=94 ) , once per day . The primary outcome was depression as assessed by the Centre for Epidemiologic Studies Depression scale ( CES-D ) ; the main secondary outcomes were : anxiety as assessed by Hospital Anxiety and Depression Scales ( HADS-A ) ; overall quality of life and fatigue as assessed by Functional Assessment of Cancer Therapy General and Fatigue scales ( FACT-G and FACT-F , respectively ) ; and clinicians ' ratings of quality of life by use of Spizter 's Quality of Life Index ( SQLI ) . Multiple measures were used for corroboration of the most important outcomes . Primary analyses were done by intention to treat and were based on scale scores at 4 weeks and 8 weeks . The benefits of sertraline compared with placebo are expressed on a range from + 100 ( ie , maximum benefit ) to -100 ( ie , maximum harm ) ; a difference of 10 was deemed clinical ly significant . This clinical trial is registered at Current Controlled Trials website http://www.controlled-trials.com/IS RCT N72466475 . FINDINGS Sertraline had no significant effect ( scale , benefit over placebo [ 95 % CI ] ) on depression ( CES-D 0.4 [ -2.6 to 3.4 ] ) , anxiety ( HADS-A 2.0 [ -1.5 to 5.5 ] ) , fatigue ( FACT-F 0.3 [ -4.3 to 4.9 ] ) , overall quality of life ( FACT-G 1.7 [ -1.3 to 4.7 ] ) , or clinicians ' ratings ( SQLI 2.0 [ -2.5 to 6.5 ] ) , and the 95 % CI ruled out a clinical ly significant benefit for all main outcomes . Sertraline was discontinued more often and earlier than was placebo ( hazard ratio 1.46 [ 1.03 - 2.06 ] , p=0.03 ) . Recruitment was stopped after the first planned interim analysis in February 2006 ( n=150 ) showed that survival was longer in patients assigned placebo than in patients assigned sertraline ( unadjusted hazard ratio 1.60 [ 95 % CI 1.04 - 2.45 ] , log-rank p=0.04 ; adjusted hazard ratio 1.62 [ 1.06 - 2.41 ] , Cox model p=0.02 ) . However , at the final analysis in July 2006 of all patients ( n=189 ) and with longer follow-up , survival did not differ significantly between the treatment groups ( unadjusted hazard ratio 1.35 [ 0.95 - 1.91 ] , log-rank p=0.09 ; adjusted hazard ratio 1.27 [ 0.87 - 1.84 ] , Cox model p=0.20 ) . The trial was closed because it had ruled out a significant benefit of sertraline . INTERPRETATION Sertraline did not improve symptoms , wellbeing , or survival in patients with advanced cancer who do not have major depression , and should be reserved for those with a proven indication In a controlled double blind study involving 116 patients with far‐advanced gastrointestinal cancer , dexamethasone at dosages of 0.75 and 1.5 mg four times daily produced improved appetite and sense of well‐being in comparison to placebo treatment . This symptomatic palliation , however , was not accompanied by weight gain or improved performance status . Survival of the steroid treated patients was essentially identical to that of the placebo treated patients . Cancer 33:1607–1609 , 1974 |
13,319 | 24,524,926 | Smoking cessation is associated with reduced depression , anxiety , and stress and improved positive mood and quality of life compared with continuing to smoke .
The effect size seems as large for those with psychiatric disorders as those without .
The effect sizes are equal or larger than those of antidepressant treatment for mood and anxiety disorders | OBJECTIVE To investigate change in mental health after smoking cessation compared with continuing to smoke . | Summary Background Women born around 1940 in countries such as the UK and USA were the first generation in which many smoked substantial numbers of cigarettes throughout adult life . Hence , only in the 21st century can we observe directly the full effects of prolonged smoking , and of prolonged cessation , on mortality among women in the UK . Methods For this prospect i ve study , 1·3 million UK women were recruited in 1996–2001 and resurveyed postally about 3 and 8 years later . All were followed to Jan 1 , 2011 , through national mortality records ( mean 12 woman-years , SD 2 ) . Participants were asked at entry whether they were current or ex-smokers , and how many cigarettes they currently smoked . Those who were ex-smokers at both entry and the 3-year resurvey and had stopped before the age of 55 years were categorised by the age they had stopped smoking . We used Cox regression models to obtain adjusted relative risks that compared categories of smokers or ex-smokers with otherwise similar never-smokers . Findings After excluding 0·1 million women with previous disease , 1·2 million women remained , with median birth year 1943 ( IQR 1938–46 ) and age 55 years ( IQR 52–60 ) . Overall , 6 % ( 66 489/1 180 652 ) died , at mean age 65 years ( SD 6 ) . At baseline , 20 % ( 232 461 ) were current smokers , 28 % ( 328 417 ) were ex-smokers , and 52 % ( 619 774 ) were never-smokers . For 12-year mortality , those smoking at baseline had a mortality rate ratio of 2·76 ( 95 % CI 2·71–2·81 ) compared with never-smokers , even though 44 % ( 37 240/85 256 ) of the baseline smokers who responded to the 8-year resurvey had by then stopped smoking . Mortality was tripled , largely irrespective of age , in those still smoking at the 3-year resurvey ( rate ratio 2·97 , 2·88–3·07 ) . Even for women smoking fewer than ten cigarettes per day at baseline , 12-year mortality was doubled ( rate ratio 1·98 , 1·91–2·04 ) . Of the 30 most common causes of death , 23 were increased significantly in smokers ; for lung cancer , the rate ratio was 21·4 ( 19·7–23·2 ) . The excess mortality among smokers ( in comparison with never-smokers ) was mainly from diseases that , like lung cancer , can be caused by smoking . Among ex-smokers who had stopped permanently at ages 25–34 years or at ages 35–44 years , the respective relative risks were 1·05 ( 95 % CI 1·00–1·11 ) and 1·20 ( 1·14–1·26 ) for all-cause mortality and 1·84 ( 1·45–2·34 ) and 3·34 ( 2·76–4·03 ) for lung cancer mortality . Thus , although some excess mortality remains among these long-term ex-smokers , it is only 3 % and 10 % of the excess mortality among continuing smokers . If combined with 2010 UK national death rates , tripled mortality rates among smokers indicate 53 % of smokers and 22 % of never-smokers dying before age 80 years , and an 11-year lifespan difference . Interpretation Among UK women , two-thirds of all deaths of smokers in their 50s , 60s , and 70s are caused by smoking ; smokers lose at least 10 years of lifespan . Although the hazards of smoking until age 40 years and then stopping are substantial , the hazards of continuing are ten times greater . Stopping before age 40 years ( and preferably well before age 40 years ) avoids more than 90 % of the excess mortality caused by continuing smoking ; stopping before age 30 years avoids more than 97 % of it . Funding Cancer Research UK , Medical Research Council Although the relationship between nicotine and changes in heart rate and blood pressure has been demonstrated , the relationship between nicotine and subjective effects such as decreased craving , relaxation , sickness , and decreased nervousness , is less well delineated . In this study , arterial nicotine levels were drawn in 21 smokers who smoked two average nicotine ( AN ) cigarettes and one low nicotine ( LN ) cigarette . Craving for a cigarette , relaxation , sickness , and decreased nervousness were rated on a visual analog scale ( VAS ) before and after smoking each cigarette . None of these subjective measures except craving for a cigarette was changed significantly by smoking . The change in craving was significantly correlated with the area under the plasma nicotine concentration versus time curve ( r = -0.57 , p = 0.01 ) calculated from the arterial nicotine sample s drawn up to 20 min after the initiation of smoking the first AN cigarette . Although well-documented behavioral manipulations , such as smoking denicotinized cigarettes , reduce craving , increases in plasma arterial nicotine concentrations after smoking the first cigarette of the day also reduce craving . Both the psychology and pharmacology of nicotine/tobacco smoking are involved in craving reduction Among 1566 personally evaluated female twins from a population -based register , average lifetime daily cigarette consumption was strongly related to lifetime prevalence and to prospect ively assessed 1-year prevalence of major depression ( MD ) . Using the cotwin control method , we evaluated whether the association between smoking and lifetime MD was causal or noncausal . While the relative risk ( 95 % confidence interval ) for ever smoking given a lifetime history of MD was 1.48 ( 1.30 to 1.65 ) in the entire sample , it was 1.18 ( 0.88 to 1.47 ) and 0.98 ( 0.71 to 1.26 ) , respectively , in dizygotic and monozygotic twin pairs discordant for a history of MD . The relative risk for a history of MD given ever smoking was 1.60 ( 1.39 to 1.83 ) in the entire sample , while in dizygotic and monozygotic twins discordant for smoking , it was 1.29 ( 0.87 to 1.74 ) and 0.96 ( 0.59 to 1.42 ) , respectively . Controlling for personal smoking history , family history of smoking predicted risk for MD ; controlling for the personal history of MD , family history of MD predicted smoking . The best-fitting bivariate twin model suggested that the relationship between lifetime smoking and lifetime MD result ed solely from genes that predispose to both conditions . These results suggest that the association between smoking and MD in women is not a causal one but arises largely from familial factors , which are probably genetic , that predispose to both smoking and MD OBJECTIVES We evaluated the efficacy of a motivational tobacco cessation treatment combined with nicotine replacement relative to usual care initiated in inpatient psychiatry . METHODS We r and omized participants ( n = 224 ; 79 % recruitment rate ) recruited from a locked acute psychiatry unit with a 100 % smoking ban to intervention or usual care . Prior to hospitalization , participants averaged 19 ( SD = 12 ) cigarettes per day ; only 16 % intended to quit smoking in the next 30 days . Results . Verified smoking 7-day point prevalence abstinence was significantly higher for intervention than usual care at month 3 ( 13.9 % vs 3.2 % ) , 6 ( 14.4 % vs 6.5 % ) , 12 ( 19.4 % vs 10.9 % ) , and 18 ( 20.0 % vs 7.7 % ; odds ratio [ OR ] = 3.15 ; 95 % confidence interval [ CI ] = 1.22 , 8.14 ; P = .018 ; retention > 80 % ) . Psychiatric measures did not predict abstinence ; measures of motivation and tobacco dependence did . The usual care group had a significantly greater likelihood than the intervention group of psychiatric rehospitalization ( adjusted OR = 1.92 ; 95 % CI = 1.06 , 3.49 ) . CONCLUSIONS The findings support initiation of motivationally tailored tobacco cessation treatment during acute psychiatric hospitalization . Psychiatric severity did not moderate treatment efficacy , and cessation treatment appeared to decrease rehospitalization risk , perhaps by providing broader therapeutic benefit |
13,320 | 23,959,477 | The VTE risk among hematologic malignancies was higher than that among solid tumors .
The administration of ESAs was significantly associated with an increased risk of developing VTE in cancer patients receiving these drugs .
The risks of VTE may vary with various tumor types , including hematologic malignancies | Erythropoiesis-stimulating agents ( ESAs ) reduce anemia in patients with cancer and could improve their quality of life , but ESA-related safety concerns exist . | PURPOSE This open-label , r and omized phase III study was design ed to investigate the effects of erythropoietin alfa ( EPO ) in addition to adjuvant chemotherapy and pelvic radiotherapy ( CRT ) in patients with stage IB to II cervical cancer who had undergone radical hysterectomy . PATIENTS AND METHODS Two hundred fifty-seven patients were r and omly assigned to four cycles of carboplatin/ifosfamide chemotherapy followed by external-beam pelvic radiotherapy ( CRT group ) or four cycles of carboplatin/ifosfamide chemotherapy and EPO followed by pelvic radiotherapy and EPO ( CRT + EPO group ) . The primary end point was recurrence-free survival ( RFS ) . Secondary end points included overall survival ( OS ) , change in hemoglobin levels , and safety , including thromboembolic events . RESULTS The estimated 5-year RFS rates were 78 % for patients receiving CRT + EPO and 70 % for patients receiving CRT . There was no statistically significant difference in RFS , although a trend favoring patients treated with CRT + EPO was observed ( hazard ratio [ HR ] , 0.66 ; 95 % CI , 0.39 to 1.12 ; log-rank P = .06 ) . Exploratory analyses suggest a benefit with CRT + EPO for patients with stage IB to IIA disease ( HR , 0.39 ; 95 % CI , 0.18 to 0.85 ; P = .014 ) or patients with complete resection ( HR , 0.55 ; 95 % CI , 0.31 to 0.98 ; P = .039 ) . OS was similar in both groups ( HR , 0.88 ; 95 % CI , 0.51 to 1.50 ; log-rank P = .63 ) . Patients treated with EPO maintained higher hemoglobin levels throughout CRT . No significant differences in safety profiles were observed between the two groups . Incidence of thrombovascular events was low ( 2 % ) and comparable between both groups . CONCLUSION This study confirms that EPO can be added safely to CRT in patients with cervical cancer , but it failed to demonstrate a significant benefit in RFS and OS Summary Anaemia commonly occurs in cancer patients receiving chemotherapy , often necessitating blood transfusion . This multicentre study was design ed to evaluate the efficacy and safety of epoetin α in preventing the decline in haemoglobin ( Hb ) level , and to determine whether the transfusion requirement could be reduced , in patients receiving 4–6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer ( SCLC ) . A total of 130 non-anaemic SCLC patients were r and omized to receive no additional treatment ( n = 44 ) , epoetin α 150 IU kg–1 subcutaneously ( s.c . ) three times a week ( n = 42 ) or 300 IU kg–1 s.c . three times a week ( n = 44 ) . Reductions in epoetin α dosage were made during the study if Hb level increased to > 15 g dl–1 . The mean weekly dosage was 335 and 612 IU kg–1 , respectively , in the two active treatment groups . Significantly fewer ( P < 0.05 ) epoetin α-treated patients experienced anaemia ( Hb < 10 g dl–1 ) during the course of chemotherapy ( 300 IU kg–1 , 39 % ; 150 IU kg–1 , 48 % ; untreated , 66 % ) . This was reflected in the significantly lower number of treated patients transfused [ 300 IU kg–1 , 20 % ( P < 0.001 ) ; 150 IU kg–1 , 45 % ( P < 0.05 ) ; untreated , 59 % ] . Epoetin α was well-tolerated , and there was no evidence of sustained , clinical ly significant , hypertension . In summary , epoetin α is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC A multicentre study evaluated the efficacy and safety of darbepoetin alpha administered weekly ( QW ) , every 3 weeks ( Q3W ) , and every 4 weeks ( Q4W ) to anaemic patients with cancer not concurrently receiving chemotherapy or radiotherapy . The QW portion ( n=102 ) was an open-label , sequential , dose-escalation design ; cohorts received darbepoetin alpha QW by subcutaneous ( s.c . ) injection at 0.5 , 1.0 , 2.25 , or 4.5 μg kg−1 week−1 for 12 weeks . The 12-week placebo-controlled , double – blind Q3W ( 6.75 μg kg−1 ) and Q4W ( 6.75 or 10.0 μg kg−1 ) schedules ( n=86 ) , which enrolled different patients , took place after the QW schedule and were followed by a 12-week , open-label phase . Patients were evaluated for change in haemoglobin end points and red blood cell transfusions , serum darbepoetin alpha concentration , and safety . Selected domains of health-related quality of life ( HRQOL ) were measured . With QW dosing , at least 70 % of each cohort had a haemoglobin increase from baseline of ⩾2 g dl−1 or a concentration ⩾12 g dl−1 ( haematopoietic response ) . In the 4.5 μg kg−1 QW cohort , all patients achieved a haematopoietic response ( 100 % ; 95 % confidence interval (CI)=100 , 100 ) . In the Q3W and Q4W schedules , all cohorts had at least 60 % of patients who achieved a haematopoietic response . Darbepoetin alpha effectively increases haemoglobin concentration when given QW , Q3W , or Q4W . Less-frequent administration may benefit patients with chronic anaemia of cancer and their caregivers alike This multicentre , open-label , controlled clinical trial assessed the effects of epoetin alfa treatment on haematologic and quality of life ( QOL ) parameters in 182 anaemic ( Hb⩽12 g dl−1 ) ovarian cancer patients receiving platinum chemotherapy . Patients were r and omised 2 : 1 to receive epoetin alfa 10 000–20 000 IU three times weekly plus best st and ard treatment ( BST ) or BST only . Main study end points were changes from baseline in haemoglobin ( Hb ) level , transfusion requirements , and QOL . For the epoetin alfa group , mean Hb increased by 1.8 g dl−1 by weeks 4–6 and was significantly increased from baseline through study end ( P<0.001 ) . The mean change in Hb from baseline was significantly ( P<0.001 ) greater for epoetin alfa than BST patients at all postbaseline evaluations . Significantly fewer epoetin alfa than BST patients required transfusion(s ) after the first 4 weeks of treatment ( 7.9 vs 30.5 % ; P<0.001 ) . Also , significant ( P⩽0.04 ) differences favouring the epoetin alfa group over the BST group were found for all three median CLAS scores ( Energy Level , Ability to Do Daily Activities , Overall QOL ) and the median average CLAS score during chemotherapy . These findings support use of epoetin alfa to increase Hb levels , reduce transfusion use , and improve QOL in anaemic ovarian cancer patients receiving platinum chemotherapy 8527 Background : This study was design ed to assess the effect of epoetin alfa ( EPO ) on hemoglobin ( Hb ) and quality of life ( QOL ) in children with cancer receiving myelosuppressive chemotherapy ( CT ) . METHODS This was a double-blind , placebo (PBO)-controlled study of pts aged 5 - 18 y with malignant solid tumors ( ST ) , Hodgkin 's lymphoma ( HL ) , acute lymphocytic leukemia ( ALL ) , or non-Hodgkin 's lymphoma ( NHL ) and Hb < 12 g/dL. Pts were stratified by tumor type ( ST/HL or ALL/NHL ) and r and omized 1:1 to receive IV EPO 600 U/kg or PBO weekly for 16 wks . Primary end point was pt-reported Peds Quality of Life Inventory ( PedQL-I ™ ) Total Score ; secondary endpoints included parent-reported PedsQL-I and pt- and parent-reported PedsQL Cancer Module ( PedsQL-CM : Cognitive Problems , Communication , Nausea , Pain and Hurt , Physical Appearance , Procedural Anxiety , Treatment Anxiety , Worry ) , Hb , and transfusions . QOL was assessed using age-specific ( 5 - 7 y , 8 - 12 y , 13 - 18 y ) versions of each tool . RESULTS 222 pts ( 111 EPO , 111 PBO ) were included in the intent-to-treat analysis : 27 HL , 98 ST , 75 ALL , and 22 NHL . Neither the pt- nor parent-reported PedsQL-I Total Score was significantly different between groups at last value . A significant improvement was seen in the pt-reported PedsQL-I Total Score in pts 5 - 7 y ( EPO , n = 13 ; PBO , n = 32 ) receiving EPO vs PBO ( P = .043 ) . Pt- and parent-reported Cognitive Problems scores were improved in ALL/NHL pts receiving EPO vs PBO ( P=.026 and P=.014 , respectively ) , but no other PedsQL-CM domain . Mean Hb change at last value was not significantly different between groups . Repeated- measures analysis of Hb showed an improvement favoring EPO ( P = .012 ) . More pts treated with EPO vs PBO were transfusion free ( 36 % vs 23 % ; P=.038 ) . Death , serious adverse event , and discontinuation rates were similar in both groups . CONCLUSIONS IV EPO was well tolerated in pediatric cancer pts . Although few differences between QOL scores were detected , there was significant improvement in QOL in pts aged 5 - 7 y and improved Cognitive scores in ALL/NHL pts . EPO pts had greater increases in Hb and a significant reduction in transfusions vs PBO . [ Table : see text ] PURPOSE To determine whether weekly epoetin alfa could improve hemoglobin ( HgB ) levels , reduce RBC transfusions , and improve quality of life ( QOL ) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy . PATIENTS AND METHODS This double-blind , placebo-controlled study r and omly assigned patients to placebo or epoetin alfa ( Ortho Biotech , Bridgewater , NJ ) 40,000 U subcutaneous weekly for 16 weeks . QOL , HgB , and RBC transfusions were measured pretreatment and monthly . RESULTS The study accrued 344 patients ; 330 were assessable for efficacy and 305 were assessable for QOL . Placebo-treated patients had a mean increase in HgB of 0.9 g/dL ( range , -3.8 to + 5.3 ) compared with 2.8 g/dL ( range , -2.2 to + 7.5 ) for epoetin-treated patients ( P < .0001 ) . During the study , 31.7 % of placebo-treated patients achieved a > or = 2 g/dL HgB increase compared with 72.7 % of epoetin-treated patients ( P < .0001 ) . The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6 % and 25.3 % ( P = .005 ) , respectively . The placebo group received 256 units of RBCs compared with 127 units in the epoetin group ( P < .0001 ) . The incidence of toxicity in the groups was similar . Changes in the average QOL scores from baseline to the end of the study were similar in the two groups ( P = not significant ) . The HgB responders ( irrespective of treatment arm ) had a mean change in Functional Assessment of Cancer Therapy ( FACT ) fatigue score from a baseline of + 5.1 compared with -2.1 for the nonresponders ( P = .006 ) . CONCLUSION Epoetin alfa significantly improved HgB and reduced transfusions in this patient population . These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia This study evaluated the effects of epoetin alfa on patient-reported outcomes in patients with breast cancer receiving myelotoxic chemotherapy . Early intervention with epoetin alfa was well tolerated and improved anemia-related patient-reported outcomes OBJECTIVE The efficacy and safety of weekly administration of epoetin beta ( EPO ) for chemotherapy-induced anemia ( CIA ) patients was evaluated . METHODS One hundred and twenty-two patients with lung cancer or malignant lymphoma undergoing chemotherapy were r and omized to the EPO 36 000 IU group or the placebo group . Hematological response and red blood cell ( RBC ) transfusion requirement were assessed . Quality of life ( QOL ) was assessed using the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) question naire . RESULTS Mean change in hemoglobin level with EPO increased significantly over placebo ( 1.4 + /- 1.9 g/dl versus -0.8 + /- 1.5 g/dl ; P < 0.001 ) . The proportion of patients with change in hemoglobin level > or = 2.0 g/dl was higher for EPO than those for placebo ( P < 0.001 ) . After 4 weeks of administration , the proportion of RBC transfusion or hemoglobin level < 8.0 g/dl was significantly lower for EPO than those for placebo ( P = 0.046 ) . The changes in the FACT-An total Fatigue Subscale Score ( FSS ) were less deteriorated with EPO than those with placebo . Progressive disease ( PD ) did not influence the change in hemoglobin level but there was less decrease in FSS in non-PD patients . No significant differences in adverse events were observed . Thrombovascular events and pure red cell aplasia related to EPO were not observed . Retrospective analysis of survival showing the hazard ratio of EPO to placebo was 0.94 . CONCLUSION Weekly administration of EPO 36 000 IU significantly increased hemoglobin level and ameliorated the decline of QOL in CIA patients over the 8-week administration period Background : Erythropoietin-stimulating agents ( ESAs ) effectively decrease the transfusion requirements of patients with chemotherapy-induced anaemia ( CIA ) . Recent studies indicate that ESAs increase mortality and accelerate tumour progression . The studies also identify a 1.6-fold increased risk of venous thromboembolism . The ESA labelling was thus revised in Europe and the United States in 2008 . This is the first r and omised , phase III trial evaluating the efficacy and safety of epoetin-β ( EPO ) , an ESA , dosed in accordance with the revised labelling , which specifies that ESAs should be administered to CIA patients with a haemoglobin level of ⩽10 g dl–1 and that a sustained haemoglobin level of > 12 g dl–1 should be avoided . Methods : A total of 186 CIA patients ( 8.0 g dl–1⩽ haemoglobin ⩽10.0 g dl–1 ) with lung or gynaecological cancer were r and omised to receive EPO 36 000 IU or placebo weekly for 12 weeks . Results : The proportion of patients receiving transfusions or with haemoglobin < 8.0 g dl–1 between week 5 and the end of the treatment period as the primary end point was significantly lower in the EPO group ( n=89 ) than in the placebo group ( n=92 ; 10.0 % vs 56.4 % , P<0.001 ) . The proportion receiving transfusions was significantly lower in the EPO group ( 4.5 % vs 19.6 % , P=0.002 ) . Changes in quality of life were not different . No significant differences in adverse events – for example , the incidence of thromboembolic events was 1.1 % for each group – or the 1-year overall survival were observed between groups . Conclusion : Weekly EPO administered according to the revised labelling approved by the European Medicines Agency is effective and well tolerated for CIA treatment . Further investigations are needed on the effect of ESAs on mortality BACKGROUND Epoetin ( EPO ) administration reduces the need for transfusion . Identifying patients at high risk of anemia requiring red blood cell ( RBC ) transfusion is needed . This multicentric phase III trial tested epoetin alpha ( EPOalpha ) administration according to our risk model on the basis of three clinical parameters : hemoglobin ( Hb ) < 12 g/dl , lymphocytes < or=700/microl , and /or performance status ( PS ) > 1 . PATIENTS AND METHODS Patients > or=18 years with chemotherapy-treated solid or hematologic tumors were r and omized to 150 UI/kg/TIW s.c . EPOalpha ( arm 1 ) or no EPOalpha ( arm 2 ) and stratified on Hb level at day 0 , lymphocyte count , and PS . The primary end point was transfusion rate ; secondary end points included overall survival ( OS ) , safety , and quality of life . RESULTS From September 2000 to January 2005 , 218 patients ( median age 64 years , 42.7 % males ) with principally breast cancer , sarcoma , or lung carcinoma were included . In total , 93 % patients had PS > 1 and 35 % had < or=700/microl lymphocytes . Baseline Hb levels were 10.1 g/dl ( range 6.9 - 11.9 ) . Two hundred and thirteen patients were assessable for the primary end point : 36 % received RBC in arm 1 and 58 % in arm 2 ( P = 0.0012 ) . Median OS was 7.6 [ 95 % confidence interval ( CI ) : 5 - 12 ] and 6 ( 95 % CI : 5 - 8 ) months in arms 1 and 2 , respectively . Median OS was significantly worse for patients with three prognostic factors ( 3.6 months ) compared with two factors ( 8.3 months ) ( P < 0.001 ) . No difference in toxicity ( 47 % versus 41 % ) or thrombovascular events ( 4.5 % versus 3.7 % ) was observed . CONCLUSION Patients at high risk for RBC transfusion according to the ELYPSE model could be given prophylactic EPO with significantly reduced RBC transfusions and no significant impact on side-effects , progression-free survival , and OS Recent studies have suggested that epoetin treatment of anaemia may influence the survival of patients with cancer . We conducted an analysis of long‐term survival in patients with lymphoproliferative malignancies treated with epoetin‐β or placebo in a large‐scale study . This was a r and omized , double‐blind trial in which patients with transfusion‐dependent anaemia and lymphoproliferative malignancy received epoetin‐β 150 IU/kg or placebo three times weekly for 16 weeks . Long‐term survival data were analysed by st and ard Kaplan – Meier methods and differences between groups were assessed using a log‐rank test . The intention‐to‐treat population consisted of 343 patients ( epoetin‐β , n = 170 ; placebo , n = 173 ) . There were no major differences between the two treatment groups in demographic or clinical characteristics/prognostic factors . A total of 110 ( 65 % ) patients died in the epoetin‐β group ( censored , n = 60 ) and 109 ( 63 % ) died in the placebo group ( censored , n = 64 ) up to the end of long‐term follow up . Kaplan – Meier curves for survival were similar in both groups . Median survival was 17 months with epoetin‐β and 18 months with placebo . A log‐rank test indicated no significant difference in survival ( P = 0·76 ) . This long‐term follow up indicated that epoetin‐β has no significant effect on survival compared to placebo in anaemic patients with lymphoproliferative malignancies Background : Cervical cancer , in women , is the second most common cancer world wide , next to breast cancer . During the treatment of carcinoma cervix , anemia is selectively frequent and its origin is complex combining hemorrhage , iron deprivation , inflammatory reactions and infection . The objective of this study is to evaluate the role of epoetin in correction of anemia and on treatment outcomes in patients with advanced cervical cancer receiving concurrent chemoradiotherapy . Results : A total of 120 patients were enrolled in the study of which 60 patients were r and omized to receive epoetin beta in the treatment arm and 60 patients were in control arm where epoetin beta was not given . Total two and three patients absconded during treatment from treatment and control arm respectively ; therefore total evaluable patients were 115 . Mean Hb at baseline in the control arm was 10.70 + /- 0.62 g/dl and 10.45 + /- 0.43 g/dl in the treatment arm ( p = NS ) . At the end of treatment mean Hb increased by 1.55 g/dl in patients receiving epoetin beta ( p < 0.01 ) , but decreased by 1.50 g/dl in the control arm ( p < 0.01 ) . There was significant reduction in blood transfusion in patients receiving epoetin beta ( p < 0.01 ) . At the end of treatment there was also significant improvement in energy level , activity level and overall quality of life in the treatment arm ( p < 0.01 ) . There was no significant difference in overall survival ( p > 0.05 ) , or disease free survival ( p > 0.05 ) between the two study arms . Adverse events were well matched between the two study arms . No Thromboembolic events associated with epoetin beta was observed in our study . Material and methods : Total 120 , stage IIB to IIIB cervical cancer patients , aged 18 - 70 years with 9.50 - 12.50 g/dl baseline Hb value who were to receive radiotherapy together with cisplatin were r and omized to receive either epoetin beta 10,000 IU thrice weekly and oral iron starting 10 - 15 days before their 5-week course of whole pelvic irradiation and weekly cisplatin ( treatment arm ) or st and ard supportive care ( control arm ) , where epoetin beta was not given . Blood transfusion was given in patients of both the arms if hemoglobin was = 10 g/dl . Conclusions : Treatment with epoetin beta safely and effectively corrects anemia in patients with advanced cervical cancer receiving chemoradiotherapy and is not associated with adverse effects on response rate , overall survival , disease free survival and chemoradiotherapy related acute and late toxicities Anemia associated with advanced cancer is common . Contributing factors include the anemia of chronic disease , chemotherapy , radiation therapy , and bone marrow invasion with tumor . Based on the observation that endogenous erythropoietin ( EPO ) levels in anemic patients with cancer are inadequate for the degree of anemia , three r and omized double-blind , placebo-controlled trials of recombinant human erythropoietin ( rHuEPO ) treatment in anemic patients with cancer were performed in patients ( 1 ) not receiving concomitant chemotherapy ( NO CTX ) , ( 2 ) receiving myelosuppressive chemotherapy that did not include cisplatin ( CTX-NO PLAT ) , and ( 3 ) receiving myelosuppressive cisplatin-containing chemotherapy ( CTX-PLAT ) . In the NO CTX trial , patients were treated with rHuEPO 100 U/kg or placebo subcutaneously ( SQ ) three times per week for up to 8 weeks . In the CTX trials , patients were treated with rHuEPO 150 U/kg or placebo SQ three times per week for 12 weeks . Four hundred thirteen patients were enrolled ( 124 , NO CTX ; 157 , CTX-NO PLAT ; and 132 , CTX-PLAT ) . In all three trials , patients receiving rHuEPO had a significantly ( P < .004 ) greater increase in hematocrit ( HCT ) than placebo-treated patients . In the two CTX trials combined , rHuEPO-treated patients also had a significantly ( P < or = .009 ) lower transfusion requirement than placebo-treated patients after the first month of therapy . Quality of life improved significantly ( P < .05 ) in responding ( > or = 6%-point HCT increase without transfusion ) rHuEPO-treated patients compared with placebo-treated patients . Overall , no adverse events occurred more frequently in rHuEPO-treated patients compared with placebo-treated patients . Following completion of the double-blind phase , patients received rHuEPO on an open-label basis as needed for correction of anemia with the dose titrated to a maximum of 900 U/kg/wk . During total rHuEPO exposure ( either started at the beginning of double-blind therapy for patients initially r and omized to rHuEPO or at the beginning of open-label therapy for patients initially r and omized to placebo ; 363 treated/347 evaluable for efficacy ) , 40.0 % , 56.1 % , and 58.3 % of the NO-CTX , CTX-NO PLAT , and CTX-PLAT patients , respectively , responded to rHuEPO therapy with an increase of HCT > or = 6 % unrelated to transfusion . ( ABSTRACT TRUNCATED AT 400 WORDS BACKGROUND Anaemia is associated with poor cancer control , particularly in patients undergoing radiotherapy . We investigated whether anaemia correction with epoetin beta could improve outcome of curative radiotherapy among patients with head and neck cancer . METHODS We did a multicentre , double-blind , r and omised , placebo-controlled trial in 351 patients ( haemoglobin < 120 g/L in women or < 130 g/L in men ) with carcinoma of the oral cavity , oropharynx , hypopharynx , or larynx . Patients received curative radiotherapy at 60 Gy for completely ( R0 ) and histologically incomplete ( R1 ) resected disease , or 70 Gy for macroscopically incompletely resected ( R2 ) advanced disease ( T3 , T4 , or nodal involvement ) or for primary definitive treatment . All patients were assigned to subcutaneous placebo ( n=171 ) or epoetin beta 300 IU/kg ( n=180 ) three times weekly , from 10 - 14 days before and continuing throughout radiotherapy . The primary endpoint was locoregional progression-free survival . We assessed also time to locoregional progression and survival . Analysis was by intention to treat . FINDINGS 148 ( 82 % ) patients given epoetin beta achieved haemoglobin concentrations higher than 140 g/L ( women ) or 150 g/L ( men ) compared with 26 ( 15 % ) given placebo . However , locoregional progression-free survival was poorer with epoetin beta than with placebo ( adjusted relative risk 1.62 [ 95 % CI 1.22 - 2.14 ] ; p=0.0008 ) . For locoregional progression the relative risk was 1.69 ( 1.16 - 2.47 , p=0.007 ) and for survival was 1.39 ( 1.05 - 1.84 , p=0.02 ) . INTERPRETATION Epoetin beta corrects anaemia but does not improve cancer control or survival . Disease control might even be impaired . Patients receiving curative cancer treatment and given erythropoietin should be studied in carefully controlled trials PURPOSE Patients with ovarian cancer often experience dose-limiting myelotoxicity , nephrotoxicity and anemia following treatment with platinum-based chemotherapy . PATIENTS AND METHODS To investigate the ability of recombinant human erythropoietin ( epoetin alfa ) to prevent the development of anemia , 30 patients with advanced ovarian carcinoma receiving cisplatin or carboplatin were r and omly assigned to treatment with subcutaneous epoetin alfa 300 IU/kg three times a week in addition to conventional supportive treatment , or conventional supportive treatment alone , for up to six chemotherapy cycles . The dose of epoetin alfa was reduced if hemoglobin concentration exceeded 15 g/dL. RESULTS A highly significant difference in mean hemoglobin concentrations was observed between the two groups during the first cycle of chemotherapy due to a significant decrease in mean hemoglobin concentration in the control group . A maximal difference of 3.4 g/dL was achieved during cycle three . Fewer patients required blood or platelet transfusions in the epoetin alfa-treated group , although the difference was not significant compared to the control group . Epoetin alfa was well tolerated . CONCLUSION Epoetin alfa appears to be effective and well tolerated in preventing hemoglobin decline in patients undergoing aggressive cyclic platinum-based chemotherapy for advanced ovarian carcinoma BACKGROUND Patients receiving chemotherapy often develop anemia . Darbepoetin alfa ( Aranesp(TM ) ) is an erythropoiesis-stimulating glycoprotein that has been shown , in dose-finding studies , to be safe and clinical ly active when administered to patients with cancer every 1 , 2 , or 3 weeks . This phase III study compared the safety and efficacy of darbepoetin alfa with placebo in patients with lung cancer receiving chemotherapy . METHODS In this multicenter , double-blind , placebo-controlled study , 320 anemic patients ( hemoglobin < or=11.0 g/dL ) were r and omly assigned to receive darbepoetin alfa or placebo injections weekly for 12 weeks . The 297 patients who completed at least the first 28 days of study were assessed for red blood cell transfusions , the primary endpoint . Patients were also assessed for hemoglobin concentration ( i.e. , hematopoietic response ) , adverse events , antibody formation to darbepoetin alfa , hospitalizations , Functional Assessment of Cancer Therapy (FACT)-Fatigue score , and disease outcome . Efficacy endpoints were assessed using Kaplan-Meier analyses , Cox proportional hazards analyses , and chi-square tests where appropriate . All statistical tests were two-sided . RESULTS Patients receiving darbepoetin alfa required fewer transfusions ( 27 % versus 52 % ; mean difference = 25 % ; 95 % confidence interval [ CI ] = 14 % to 36 % ; P<.001 ) , required fewer units of blood ( 0.67 versus 1.92 ; mean difference = 1.25 , 95 % CI = 0.65 to 1.84 ; P<.001 ) , had more hematopoietic responses ( 66 % versus 24 % ; mean difference = 42 % ; 95 % CI = 31 % to 53 % ; P<.001 ) , and had better improvement in FACT-Fatigue scores ( 56 % versus 44 % overall improvement ; 32 % versus 19 % with > or=25 % improvement ; mean difference = 13 % ; 95 % CI = 2 % to 23 % , P = .019 ) than patients receiving placebo . Patients receiving darbepoetin alfa did not appear to have any untoward effect in disease outcome and did not develop antibodies to the drug . Adverse events were similar between the groups . CONCLUSIONS Patients with chemotherapy-associated anemia can safely and effectively be treated with weekly darbepoetin alfa therapy . Darbepoetin alfa decreased blood transfusion requirements , increased hemoglobin concentration , and decreased fatigue . Although no conclusions can be drawn about survival from this study , the potential salutary effect on disease outcome warrants further investigation in a prospect ively design ed study PURPOSE This r and omized , double-blind , placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements , hematopoietic parameters , quality of life ( QOL ) , and safety in anemic cancer patients receiving nonplatinum chemotherapy . The study also explored a possible relationship between increased hemoglobin and survival . PATIENTS AND METHODS Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels < or = 10.5 g/dL , or greater than 10.5 g/dL but < or = 12.0 g/dL after a hemoglobin decrease of > or = 1.5 g/dL per cycle since starting chemotherapy , were r and omized 2:1 to epoetin alfa 150 to 300 IU/kg ( n = 251 ) or placebo ( n = 124 ) three times per week subcutaneously for 12 to 24 weeks . The primary end point was proportion of patients transfused ; secondary end points were change in hemoglobin and QOL . The protocol was amended before unblinding to prospect ively collect and assess survival data 12 months after the last patient completed the study . RESULTS Epoetin alfa , compared with placebo , significantly decreased transfusion requirements ( P = .0057 ) and increased hemoglobin ( P < .001 ) . Improvement of all primary cancer- and anemia-specific QOL domains , including energy level , ability to do daily activities , and fatigue , was significantly ( P < .01 ) greater for epoetin alfa versus placebo patients . Although the study was not powered for survival as an end point , Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa ( P = .13 , log-rank test ) , and Cox regression analysis showed an estimated hazards ratio of 1.309 ( P = .052 ) favoring epoetin alfa . Adverse events were comparable between groups . CONCLUSION Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy . Encouraging results regarding increased survival warrant another trial design ed to confirm these findings PURPOSE To evaluate the effect of exogenous recombinant human erythropoietin ( rHuEPO ) on the increase of hemoglobin levels and on the transfusion requirements in patients with cisplatin (CDDP)-induced anemia , we performed a double-blind r and omized trial with placebo . PATIENTS AND METHODS One hundred patients with CDDP-associated anemia ( hemoglobin level < 90 g/L ) were r and omized to receive either placebo ( saline solution ) or rHuEPO ( 100 U/kg body weight subcutaneously ) three times per week . The end points of this study were the increase in hemoglobin levels to greater than 100 g/L after 3 , 6 , and 9 weeks and the effect on transfusion requirements . RESULTS Ninety-nine of 100 patients were assessable for response and toxicity . In the rHuEPO arm , mean hemoglobin levels were statistically significantly increased after the third , sixth , and ninth weeks of therapy ( 101.1 + /- 9.0 , 102.4 + /- 6.6 , and 105.1 + /- 9.4 g/L , respectively ) compared with the mean baseline value ( 86.3 + /- 6.2 g/L ) . In the placebo arm , there were no increases in mean hemoglobin levels at the third , sixth , and ninth weeks ( 81.0 + /- 5.2 , 81.3 + /- 9.2 , and 81.2 + /- 11 g/L , respectively ) compared with the mean baseline value ( 87.3 + /- 5.2 g/L ) . Furthermore only 20 % of patients required blood transfusions in the rHuEPO arm versus 56 % of patients in the placebo arm ( P = .01 ) , with a mean units of blood transfused per patient of 0.30 in the rHuEPO arm and 1.8 in the placebo arm ( P = .01 ) . Treatment was well tolerated , with no significant side effects . CONCLUSION CDDP-induced anemia is corrected by rHuEPO , which results in reduced blood transfusion requirements PURPOSE A placebo-controlled , double-blind , r and omized , phase III study was conducted in patients with extensive-stage small-cell lung cancer receiving first-line platinum-containing chemotherapy to determine if increasing or maintaining hemoglobin concentration with darbepoetin alpha could increase patient survival . PATIENTS AND METHODS Darbepoetin alpha ( 300 microg ) or placebo was administered once per week for 4 weeks then every 3 weeks for up to six cycles of chemotherapy ( carboplatin plus etoposide or cisplatin plus etoposide ) plus 3 weeks after the last dose of chemotherapy . Patients with disease progression were observed until death or until all patients completed their end-of- study visit and 496 deaths had occurred . The two co primary end points were change in hemoglobin concentration from baseline to the end of the chemotherapy period and overall survival ; statistical testing of survival was done if change in hemoglobin was significant at P < .05 . RESULTS The study enrolled 600 patients . Patients ' hemoglobin levels dropped due to the myelosuppressive chemotherapy ; however , treatment with darbepoetin alpha maintained hemoglobin levels significantly higher than placebo ( P < .001 ) . There was no statistically significant difference in overall survival between the treatment groups ( hazard ratio [ HR ] , 0.93 ; 95 % CI , 0.78 to 1.11 ; P = .431 ) . As expected , darbepoetin alpha was associated with a higher incidence of thromboembolic events ( darbepoetin alpha , 9 % ; placebo , 5 % ) . The transfusion risk was lower in the darbepoetin versus placebo group ( HR , 0.40 ; 95 % CI , 0.29 to 0.55 ) . CONCLUSION The results of this study did not demonstrate improved survival after treatment with darbepoetin alpha ; however , they reinforce the benefit of erythropoiesis-stimulating agents in reducing transfusions and their neutral impact on survival in patients with chemotherapy-induced anemia ABSTRACT Objective : Darbepoetin alfa is effective in treating chemotherapy-induced anemia ( CIA ) . Administration of subcutaneous darbepoetin alfa every 3 weeks ( Q3W ) could simplify treatment through synchronization with common Q3W chemotherapy regimens . We report results from a multicenter , r and omized , double-blind , placebo-controlled , phase 3 trial evaluating the efficacy and safety of fixed-dose Q3W darbepoetin alfa in patients with a wide variety of tumor types who experienced CIA . Research design and methods : Patients aged ≥ 18 years with anemia ( hemoglobin < 11 g/dL ) being treated for nonmyeloid malignancy were r and omized 1:1 to receive darbepoetin alfa 300 μg ( n = 193 ) or placebo ( n = 193 ) subcutaneously Q3W from weeks 1 to 13 in this 16-week study . Doses could be adjusted per prespecified rules . Main outcome measures : The primary endpoint was the proportion of patients who received ≥1 red blood cell ( RBC ) transfusion between week 5 and the end of the treatment period ( EOTP ) . The study also analyzed the proportions of patients achieving a hemoglobin concentration ≥11 g/dL and subsequently maintaining hemoglobin levels above 11 g/dL , and the change in hemoglobin concentration over time . Results : The proportion of patients requiring RBC transfusions between week 5 and EOTP was significantly lower in the darbepoetin alfa-treated group than in the placebo-treated group ( 24 vs. 41 % of patients , a 16.3 % difference , p < 0.001 ) . There were no differences between the two treatment arms in quality -of-life measures . Cardiovascular/thromboembolic adverse events were uncommon and were not associated with increases in hemoglobin levels . Study limitations suggest caution in the interpretation of these results : transfusions , the primary endpoint , were recommended but not required if hemoglobin concentrations were ≤8.0 g/dL , and protocol deviations ( primarily dosing errors ) occurred in approximately one-half of the patients in both treatment groups . Conclusions : In this study , fixed-dose Q3W darbepoetin alfa appeared to be well-tolerated and effective for the treatment of CIA . Trial registration : Clinical Trials.gov identifier : NCT00110955 PURPOSE To determine whether the addition of recombinant human erythropoietin ( Epo ) could improve the outcomes of anemic patients receiving definitive radiotherapy for squamous cell carcinoma of the head and neck ( SCCHN ) . METHODS AND MATERIAL S Eligible patients had SCCHN , with a plan for continuous-course definitive radiotherapy ( 66 - 72 Gy ) with or without chemotherapy . Patients with Stage III or IV SCCHN were required to undergo concurrent chemoradiotherapy and /or accelerated fractionation radiotherapy . Preradiotherapy hemoglobin was required to be between 9.0 g/dL and 13.5 g/dL ( 12.5 g/dL for women ) . Patients r and omized to Epo received 40,000 U once weekly , starting 7 - 10 days before start of radiotherapy . RESULTS A total of 148 patients were enrolled ; 141 were evaluable . Median pretreatment hemoglobin was 12.1 g/dL. Hemoglobin levels at 4 weeks rose by an average of 1.66 g/dL in the Epo arm , compared with an average 0.24 g/dL decrease in the control arm ( p = 0.0001 ) . Median follow-up was 2.5 years ( 3.1 years for surviving patients ) . There was no statistically significant difference in the primary endpoint of local-regional failure ( LRF ) rate between the treatment arms . The 3-year LRF rate was 36 % for control and 44 % for Epo ( p = 0.56 ) . There were also no significant differences in local-regional progression-free survival ( LRPFS ) , patterns of failure , overall survival , or toxicity . The 3-year LRPFS rate was 52 % for control and 47 % for Epo . The overall survival rate was 57 % and 56 % , respectively . CONCLUSIONS The addition of Epo to definitive radiotherapy for SCCHN did not improve outcomes . The study was not specifically design ed to detect a potential negative association between Epo and tumor progression/survival BACKGROUND The objective of this study was to compare the effect of dose-intensified neoadjuvant chemotherapy with that of st and ard epirubicin plus cyclophosphamide followed by paclitaxel in combination with or without darbepoetin on survival in primary breast cancer . PATIENTS AND METHODS A total of 733 patients received either four cycles of neoadjuvant epirubicin 90 mg/m(2 ) plus cyclophosphamide 600 mg/m(2 ) every 3 weeks followed by four cycles of paclitaxel 175 mg/m(2 ) every 3 weeks ( EC→T ) , or three cycles of epirubicin 150 mg/m(2 ) every 2 weeks followed by three cycles of paclitaxel 225 mg/m(2 ) every 2 weeks followed by three cycles of combination chemotherapy with cyclophosphamide , methotrexate , and fluorouracil ( E(dd)→T(dd)→CMF ) . The patients were r and omly assigned to receive darbepoetin or none . The primary objective was to demonstrate a superior disease-free survival ( DFS ) of E(dd)→T(dd)→CMF compared with EC→T. RESULTS Estimated 3-year DFS was 75.8 % with EC→T versus 78.8 % with E(dd)→T(dd)→CMF [ hazard ratio ( HR ) 1.14 ; P = 0.37 ] and overall survival ( OS ) 88.4 % versus 91.5 % ( HR 1.26 ; P = 0.237 ) . Three-year DFS was 74.3 % with darbepoetin versus 80.0 % without ( HR 1.31 ; P = 0.061 ) and OS 88.0 % versus 91.8 % ( HR 1.33 ; P = 0.139 ) . Patients with a pathologically documented complete response [ pathological complete response ( pCR ) ] had a significantly better DFS compared with those without achieving a pCR ( estimated 3-year DFS : 89.2 % versus 74.9 % ; HR 2.27 ; P = 0.001 ) . CONCLUSION Neoadjuvant dose-intensified chemotherapy compared with st and ard chemotherapy did not improve DFS , whereas the addition of darbepoetin might have detrimental effects on DFS This r and omised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin ( rhEPO ) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy . The patients were r and omly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously , three times a week , or open control . Patients also received up to 6 cycles of carboplatin or cisplatin , alone or in combination with other cytotoxic agents . Intention-to-treat analysis showed that 39.4 % of patients in the control group received at least one blood transfusion , compared with 9.2 % of patients treated with rhEPO . Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels < 10 g/dl ( P<0.001 and < 0.05 , respectively ) . A haemoglobin decrease < 1 g/dl during the first chemotherapy cycle , as well as a low baseline serum erythropoietin concentration , predicted a low transfusion need in rhEPO-treated patients but not in controls . During the study , 103 patients suffered at least one adverse event , but no serious , and only nine non-serious adverse events were considered possibly related to rhEPO therapy . These results indicate that treatment with rhEPO prevents anaemia , it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy , and it is well tolerated . A starting dose of 150 U/kg of rhEPO , three times a week , may be recommended PURPOSE This r and omized , double-blind , placebo-controlled trial ( N93 - 004 ) evaluated the effects of epoetin alfa on tumor response to chemotherapy and survival in patients with small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS Adult patients with hemoglobin < or = 14.5 g/dL starting chemotherapy received epoetin alfa 150 U/kg or placebo subcutaneously 3 times weekly until 3 weeks after completion of chemotherapy . Survival was assessed for 3 years . The primary end point was the proportion of patients with complete or partial response after three chemotherapy cycles . RESULTS The trial was terminated prematurely after 224 of a projected 400 patients were accrued . Baseline characteristics were similar between groups . Epoetin alfa and placebo patients ( n = 109 and n = 115 , respectively ) had mean baseline hemoglobin of 12.8 g/dL and 13.0 g/dL , respectively . Overall tumor response was similar between the epoetin alfa and placebo groups after three chemotherapy cycles ( 72 % and 67 % , respectively ; 95 % CI of difference , -6 % to 18 % ) and after completion of chemotherapy ( 60 % and 56 % , respectively ; 95 % CI of difference , -9 % to 17 % ) . Epoetin alfa and placebo groups had similar median overall survival ( 10.5 and 10.4 months , respectively ) and overall mortality ( 91.7 % and 87.8 % , respectively ; hazard ratio , 1.172 ; 95 % CI , 0.887 to 1.549 ; P = .264 ) . Hemoglobin was maintained in the prechemotherapy range in epoetin alfa patients , but decreased substantially in placebo patients . Fewer epoetin alfa patients than placebo patients required transfusion . CONCLUSION These results suggest that in newly diagnosed patients with SCLC epoetin alfa does not affect tumor response to chemotherapy or survival . However , the early trial closure makes these conclusions preliminary One hundred twenty-one anemic , transfusion-dependent patients with multiple myeloma ( MM ) or low- grade non-Hodgkin 's lymphoma ( NHL ) were r and omly allocated to receive ( a ) recombinant human erythropoietin ( rhEPO ) 10,000 U/d subcutaneously 7 days a week ( fixed dose group ) ( n = 38 ) , or ( b ) rhEPO 2,000 U/d subcutaneously for 8 weeks followed by step-wise escalation of the rhEPO dose ( titration group ) ( n = 44 ) , or ( c ) no rhEPO therapy ( control group ) ( n = 39 ) . The total treatment period was 24 weeks . There were no differences between the three groups with regard to baseline clinical , demographic , or health status measures . The cumulative response frequency , defined as elimination of the transfusion need in combination with an increase in the hemoglobin concentration by > 20 g/L , was 60 % in both rhEPO treatment groups and 24 % in the control group ( P = .01 and .02 , respectively , log rank test ) . For patients in the titration group the response rate on the first dose level ( 2,000 U/d ) was only 14 % . Cox 's univariate regression analysis revealed that an inadequately low endogenous erythropoietin concentration in relation to the degree of anemia and a baseline platelet concentration > or = 100 x 10(9)/L were significant predictors for response to rhEPO therapy ( P < .01 ) . Multivariate regression analysis showed that relative erythropoietin concentration was the most important factor and the platelet count had no additional influence on response . Treatment with rhEPO was well tolerated . We conclude that treatment with rhEPO may be indicated in anemic MM and NHL patients with a relative erythropoietin deficiency . An initial dose of 5,000 U/d subcutaneously may be recommended PURPOSE Previous trials have suggested a quality -of-life ( QOL ) improvement for anemic cancer patients treated with erythropoietin , but few used QOL as the primary outcome . We design ed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung ( NSCLC ) . PATIENTS AND METHODS A multicenter , r and omized , double-blind , placebo-controlled trial was conducted . The proposed sample size was 300 patients . Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin ( Hgb ) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo , targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks . RESULTS Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been r and omly assigned ( 33 to the active arm and 37 to the placebo arm ) . This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial ( 63 v 129 days ; hazard ratio , 1.84 ; P = .04 ) . The Steering Committee closed the trial . Patient numbers compromised the interpretation of the QOL analysis , but a positive Hgb response was noted with epoetin alfa treatment . CONCLUSION An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa . Although infrequent , other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely INTRODUCTION ADVANCED CANCER is frequently associated with significant anaemia which may be worsened by the administration of chemotherapy with myelotoxic agents such as methotrexate or nephrotoxic agents such as cisplatin . Although anaemia in cancer patients may be multifactorial in origin , it is often categorised as the anaemia of chronic disease ( ACD ) [ 1,2 ] . ACD is characterised by erythroid hypoplasia of the bone marrow , a modest decrease in red cell survival , decreased bone marrow reutilization of iron , and inappropriately low erythropoietin levels for the degree of anaemia [ 2 ] . Consistent with this A C D model , i napp rop r i a t e ly low se rum erythropoietin levels for the degree of anaemia have recently been documented in cancer patients [ 3 ] . The symptomato logy of anaemia may con t r ibu t e substantially to the overall lack of well-being that cancer patients frequently experience during their disease process . The t ransfusions often required for pal l ia t ion of these symptoms carry significant risks . There is an estimated 20 % probability of some associated adverse effect including fever , chills , rash , urticaria and exposure to hepatitis [ 4 ] . The scope of this problem is substantial when one considers that the annual transfusion estimate for this patient group in the U.S.A. alone is one million units of red blood cells/whole blood [ 5 ] . The observation that , at any given haemoglobin level , serum erythropoiet in levels tend to be lower in cancer patients than in iron deficiency patients [ 3 ] suggests that anaemia in cancer is at least partially due to a relative deficiency of e ry thropoie t in . In c o n j u n c t i o n with this observation , recent work demonstrating both the eft]caw and safety of recombinant human erythropoietin ( r-HuEPO ) in increasing haematocrit in anaemic patients with chronic renal failure [ 6,7 ] and in anaemic , zidovudine (AZT)-treated HIVinfected patients [ 8 ] offers the possibility that exogenous erythropoietin may also be an effective treatment for anaemia in cancer patients . To test this possibility , we conducted a series of double-blind , placebo-controlled trials using r-HuEPO in anaemic cancer patients in three different patient population s to examine the safety of r-HuEPO treatment , and its impact on haematocrit , t ransfusion requi rements and quality of life . The three populat ions were : pat ients receiving no chemotherapy , pa t i en t s rece iv ing cyclic n o n c i s p l a t i n c o n t a i n i n g chemothe rapy and pa t ients receiving cyclic c isp la t incontaining chemotherapy Background : Recombinant human epoetin alfa , HX575 , is the first biosimilar erythropoiesis-stimulating agent ( ESA ) with European marketing authorisation . The primary objective of this double-blind , r and omised , multicentre study was to assess the efficacy and safety of HX575 in treating chemotherapy-associated symptomatic anaemia in patients with solid tumours . Patients and Methods : The patients ( n = 114 ) were treated with HX575 or active control ( epoetin alfa ) at 150 IU/kg body weight 3 times weekly for 12 weeks , increased to 300 IU/kg body weight 3 times weekly if the haemoglobin/reticulocyte increase was insufficient after 4 or 8 weeks . Results : With HX575 , haemoglobin increased by ≥20 g/l in 62 % ( 37/60 patients ) . The confidence interval ( 48.2 % , 73.9 % ) was entirely above the pre-defined 30 % threshold . Both groups showed similar results for safety profiles and secondary efficacy parameters . Transfusion requirements were 32 % ( 19/60 ) ( HX575 ) and 38 % ( 13/34 ) ( epoetin alfa ) . Conclusions : In treating chemotherapy-associated symptomatic anaemia in patients with solid tumours , the biosimilar ESA , HX575 , is efficacious with a safety profile as expected for the therapeutic area BACKGROUND Patients with advanced cancer frequently experience clinical ly significant anemia , which is often exacerbated by myelosuppressive chemotherapy . Consistent with the anemia of chronic disease , studies have documented serum erythropoietin levels that are inappropriately low for the degree of anemia in cancer patients . Myelosuppressive chemotherapy impairs erythropoiesis , which may not fully recover between treatment cycles . Recombinant human erythropoietin ( rHuEPO ) has been used safely and effectively to treat anemia in AIDS patients receiving zidovudine ( AZT ) and in patients with chronic renal failure . PURPOSE This study was design ed to evaluate the clinical role of rHuEPO in reducing symptomatic anemia in patients with advanced cancer who were receiving myelosuppressive chemotherapy ( excluding cisplatin ) . METHODS We studied 153 anemic cancer patients receiving cyclic combination chemotherapy in a prospect i ve multicenter , double-blind , placebo-controlled trial . The patients were r and omly assigned to receive either rHuEPO ( 150 U/kg ) or placebo subcutaneously three times a week for a maximum of 12 weeks or until the hematocrit level increased to 38%-40 % . If the hematocrit reached this target level before 12 weeks , the rHuEPO dose could be reduced to maintain the hematocrit at that level for the duration of the study . Response to rHuEPO therapy was assessed by measuring changes in hematocrit level , transfusion requirements , and quality of life . Quality -of-life assessment was based on patients ' responses to question naires before and after the courses of therapy . RESULTS The increase in hematocrit in the rHuEPO-treated group compared with hematocrit in the placebo-treated group was statistically significant ( P = .0001 ) as measured by percentage point of change from baseline to final evaluation , by an increase in hematocrit level of six percentage points or more unrelated to transfusion , and by a rise in hematocrit level to 38 % or more unrelated to transfusion . There was a trend toward the reduction in mean units of blood transfused per patient during months 2 and 3 of therapy combined in rHuEPO-treated patients compared with placebo-treated patients ( 0.91 U versus 1.65 U ; P = .056 ) . In addition , rHuEPO-treated patients experienced a statistically significant improvement in energy level and ability to perform daily activities ( P < or = .05 ) . The two treatment groups showed no statistically significant differences in toxic effects except for increased incidence of diaphoresis ( P < .05 ) and diarrhea ( P = .05 ) in the rHuEPO-treated group . CONCLUSIONS We conclude that rHuEPO is safe and effective for reversing anemia related to advanced cancer or to chemotherapy for cancer The European Cancer Anaemia Survey ( ECAS ) was conducted to prospect ively evaluate the prevalence , incidence and treatment of anaemia ( haemoglobin < 12.0 g/dL ) in European cancer patients , including the relationship of mild , moderate and severe anaemia to performance status . Patients were evaluated for up to 6 months . Data ( N=15367 ) included demographics , tumour type , performance status , haemoglobin levels , cancer treatments and anaemia treatments . Prevalence of anaemia at enrollment was 39.3 % ( haemoglobin < 10.0 g/dL , 10 % ) , and 67.0 % during the survey ( haemoglobin < 10.0 g/dL , 39.3 % ) . Low haemoglobin levels correlated significantly with poor performance status . Incidence of anaemia was 53.7 % ( haemoglobin < 10.0 g/dL , 15.2 % ) . Anaemia was treated in 38.9 % of patients ( epoetin , 17.4 % ; transfusion , 14.9 % ; and iron , 6.5 % ) . Mean haemoglobin to initiate anaemia treatment was 9.7 g/dL. Anaemia prevalence and incidence in cancer patients are high . Anaemia significantly correlates with poor performance status and many anaemic patients are not treated Recombinant human erythropoietin ( r-HuEPO ) corrects cancer-related anemia and , thereby , improves quality of life . The purpose of the present study was to measure the impact of erythropoietin on hemoglobin and mood state in patients with metastatic breast cancer and mild anemia ( Hgb < 12.0 g/dL ) . Women were r and omized to receive usual care ( G1 ) or usual care plus r-HuEPO ( G2 ) . Usual care included transfusions as necessary and fatigue education . R-HuEPO was begun at 40,000U subcutaneously per week . At 4 weeks , the dose was increased to 60,000U if Hgb had not increased > or = 1.0 g/dL. The drug was discontinued at 8 weeks if hemoglobin improvement was < 1.0 g/dL. The study was terminated early ( n = 27 , G1 = 13 , G2 = 14 ) when 4/14 ( 28.5 % ) subjects in G2 developed thrombotic events ( deep vein thrombosis [ DVT ] in 1 ; DVT plus pulmonary embolism [ PE ] in 1 ; DVT plus PE 1 month after drug discontinuation in 1 ; and brachial vein thrombosis with infected Mediport in 1 ) . In all four patients , Hgb levels were normal at the time of the event . No patient in G1 developed a thrombotic event . There were no significant differences in demographic characteristics or current chemotherapy regimen in G1 vs. G2 . The decision to terminate the trial was made after considerable deliberation . The increased incidence of thrombotic events in the r-HuEPO ( G2 ) arm of this study exceeds that in prior studies in this population and prior r-HuEPO trials . This may relate to the administration of r-HuEPO in this high-risk population , but the small sample size and possible predisposing risk factors preclude definitive conclusions PURPOSE To evaluate the effect of epoetin alfa on local disease-free survival ( DFS ) , overall survival ( OS ) , and cancer treatment-related anemia and fatigue in patients with head and neck cancer receiving radical radiotherapy with curative intent . PATIENTS AND METHODS Patients ( N = 301 ) with hemoglobin ( Hb ) less than 15 g/dL were r and omly assigned in a ratio of 1:1 to receive radiotherapy plus epoetin alfa ( 10,000 U subcutaneously [ SC ] three times weekly if baseline Hb was < 12.5 g/dL ; 4,000 U SC three times weekly if baseline Hb > or = 12.5 g/dL ) or radiotherapy alone . Hb levels were monitored weekly . The primary end point was local DFS , defined as the time from r and om assignment to local disease recurrence or death . Secondary efficacy end points included OS , local tumor response , and local tumor control . Patients were followed at 1 , 4 , 8 , and 12 weeks postradiotherapy and annually for 5 years . Cancer treatment-related anemia and fatigue were evaluated with the Functional Assessment of Cancer Therapy-Anemia and Functional Assessment of Cancer Therapy-Head and Neck . Adverse events were recorded up to 12 weeks postradiotherapy . RESULTS Hb levels increased from baseline with epoetin alfa . The median duration of local DFS was not statistically different between groups ( observation , 35.42 months ; epoetin alfa , 31.47 months ; hazard ratio , 1.04 ; 95 % CI , 0.77 to 1.41 ) . Groups did not significantly differ in DFS , OS , tumor outcomes , or cancer treatment-related anemia or fatigue . No new or unexpected adverse events were observed . CONCLUSION Addition of epoetin alfa to radical radiotherapy did not affect survival , tumor outcomes , anemia , or fatigue positively or negatively in patients with head and neck cancer 8111 Background : There is good evidence that epoetin alfa ( EPO ) is effective in the treatment of moderate to severe chemotherapy-associated anemia ( CAA ) . Further research is required to clarify its role in mild CAA . METHODS This multicenter r and omized trial assessed the effect of EPO on hemoglobin level ( Hb ) , transfusion requirements and quality of life ( QOL ) in patients ( pts ) with mild CAA . Pts with Hb ≤12.1 g/dl , likely to receive 2 - 6 more cycles of platinum-based chemotherapy ( CT ) for a solid malignancy , were r and omized ( 2:1 ) to EPO ( 10,000 U t.i.w . ) or best supportive care ( BSC ) . If after 4 wks of EPO therapy , Hb < 12.1 g/dl and Hb increase < 1 g/dl , EPO dose was increased to 20,000 U t.i.w . FACT-An ( Functional Assessment of Cancer Therapy-Anemia ) and CLAS ( Cancer Linear Analogue Scale ) scores after 2 cycles of CT ( QOL-2 ) and at study completion ( 4 wks after the last cycle of CT ; QOL-end ) were compared to QOL-baseline . RESULTS A total of 315 pts ( 211 EPO vs 104 BSC ) were enrolled . There were no statistically significant differences in gender , age , and tumor type between groups . The mean study period was 97 vs 102 days . Median baseline Hb was 10.7 vs 10.8 g/dl ( EPO vs BSC ) . Hematological response was significantly higher in the EPO group . The percentage correctors ( Hb > 12.1 g/dl and not transfused in previous 28 days ) was 67 vs 30%1 ( EPO vs BSC ) , the percentage responders ( Hb increase > 2 g/dl and not transfused in previous 28 days ) 69 vs 31%1 , and the percentage hematopoietic responders ( corrector or responder ) was 76 vs 45%1 . The percentage of patients transfused during the study period was lower in the EPO group ( 37 vs 65%1 ) . QOL was comparable between groups after 2 cycles of CT ( QOL-2 ) , but both CLAS and FACT-An scores were significantly higher in the EPO group at QOL-end ( See Table ) . CONCLUSIONS EPO therapy for mild anemia results in significant increases in QOL and Hb and reduces transfusion requirements in patients receiving platinum-based CT . [ Figure : see text ] [ Table : see text ] Objectives : Platinum compounds are commonly associated with significant anemia . Erythropoietin administration has been found effective in correcting anemia in patients with solid tumors receiving chemotherapy . We conducted a r and omized , open label study to assess the efficacy of erythropoietin in preventing transfusions and significant anemia ( hemoglobin < 10 g/dl ) in patients with solid tumors receiving platinum-based chemotherapy . Methods : One hundred forty-four patients with hemoglobin < 13 g/dl were included in this study ( 72 in each arm ) . Patients in the treatment arm received 10,000 U of recombinant human erythropoietin ( rHuEPO ) thrice weekly s.c . during platinum-based chemotherapy , while patients in the control arm received no treatment . Results : All patients were evaluable for efficacy . Transfusions were reduced by the administration of rHuEPO ( 15.3 vs. 33.3 % , p = 0.019 ) , and fewer patients developed significant anemia ( 16.6 vs. 45.8 % , p < 0.0001 ) . Subgroup analysis showed that patients with observed to predicted ( O/P ) serum erythropoietin levels ≤0.9 and responders to chemotherapy benefited from erythropoietin administration in contrast to patients with O/P > 0.9 or non-responders . Conclusions : rHuEPO at a dose of 10,000 U thrice weekly prevents transfusions and development of significant anemia in patients with solid tumors receiving platinum-based chemotherapy Effects of epoetin alfa on transfusions , haemoglobin ( Hb ) and quality of life ( QOL ) were evaluated in a placebo‐controlled study of 145 patients with multiple myeloma and anaemia ( Hb < 11 g/dl ) . During the 12‐week , double‐blind phase , patients received 150 IU/kg epoetin alfa or a matching volume of placebo subcutaneously three times weekly ; the dose ( or volume ) was doubled at week 4 if Hb response was inadequate . Patients completing this phase could enter the subsequent optional 12‐week phase of open‐label epoetin alfa treatment . During double‐blind treatment , epoetin alfa significantly decreased the incidence of transfusion compared with placebo ( 28 % vs. 47 % , P = 0·017 ) , regardless of patients ' transfusion history , and increased mean Hb ( 1·8 g/dl vs. 0·0 g/dl , P < 0·001 ) . Univariate analysis showed significant ( P ≤ 0·05 ) improvement in more QOL measures with epoetin alfa than with placebo ; multivariate analysis discerned no between‐treatment differences . Significantly ( P = 0·038 ) more epoetin alfa vs. placebo patients had improved performance scores . At the end of the open‐label treatment phase , patients who had continued epoetin alfa maintained Hb status , and placebo patients who were switched to epoetin alfa had mean Hb increases of 2·4 g/dl . Adverse events were similar between treatment groups . Epoetin alfa proved effective and well tolerated for treating anaemia in patients with multiple myeloma PURPOSE Recent reports suggest that cancer control may worsen if erythropoietin is administered . We investigated whether erythropoietin receptor expression on cancer cells may correlate with this unexpected finding . PATIENTS AND METHODS Cancer tissue from patients with advanced carcinoma of the head and neck ( T3 , T4 , or nodal involvement ) and scheduled for radiotherapy was assayed retrospectively for erythropoietin receptor expression by immunohistochemistry . Patients were anemic and r and omized to receive epoetin beta ( 300 U/kg ) or placebo under double-blind conditions , given three times weekly starting 10 to 14 days before and continuing throughout radiotherapy . We administered 60 Gy following complete resection or 64 Gy subsequent to microscopically incomplete resection ; 70 Gy were given following macroscopically incomplete resection or for definitive radiotherapy alone . We determined if the effect of epoetin beta on locoregional progression-free survival was correlated with the expression of erythropoietin receptors on cancer cells using a Cox proportional hazards regression model . RESULTS We studied 154 of 157 r and omly assigned patients ; 104 sample s were positive , and 50 were negative for receptor expression . Locoregional progression-free survival was substantially poorer if epoetin beta was administered to patients positive for receptor expression compared with placebo ( adjusted relative risk , 2.07 ; 95 % CI , 1.27 to 3.36 ; P < .01 ) . In contrast , epoetin beta did not impair outcome in receptor-negative patients ( adjusted relative risk , 0.94 ; 95 % CI , 0.47 to 1.90 ; P = .86 ) . The difference in treatment associated relative risks ( 2.07 v 0.94 ) was borderline statistically significant ( P = .08 ) . CONCLUSION Erythropoietin might adversely affect prognosis of head and neck cancer patients if cancer cells express erythropoietin receptors |
13,321 | 23,291,636 | In general , the findings indicated ( a ) there were only a few cases of significant associations between craving collected as part of cue-reactivity studies and treatment outcome , ( b ) postquit craving was a stronger predictor of treatment outcome than prequit craving , and ( c ) several moderators likely influence the relationship between craving and cessation outcome .
The overall results suggest that craving is not a necessary condition of relapse .
In addition , inconsistent relationships between craving and treatment outcome call into question the value of craving as a target of treatment and underscore limitations in the prognostic utility of craving | INTRODUCTION Craving is often portrayed as a defining feature of addiction , but the role of craving in the addictive process is controversial .
Particularly contentious is the extent to which drug craving predicts subsequent relapse . | The authors present results of a r and omized clinical trial of the efficacy of extended treatment with bupropion SR in producing longer term cigarette smoking cessation . Adult smokers ( N = 362 ) received open-label treatment ( 11 weeks ) that combined relapse prevention training , bupropion SR , and nicotine patch followed by extended treatment ( 14 weeks ) with bupropion SR or matching placebo . Abstinence percentages were relatively high ( week 11 : 52 % ; week 25 : bupropion , 42 % ; placebo , 38 % ; week 52 : bupropion , 33 % ; placebo , 34 % ) , but bupropion SR did not surpass placebo . Gender and baseline craving level were identified as significant , independent moderators of treatment response . Men were more likely to abstain than women ( week 11 : 59 % vs. 43 % , p = .001 ; week 25 : 48 % vs. 31 % , p = .001 ; week 52 : 39 % vs. 27 % , p = .01 ) . Because most smokers suffer relapse with any current cessation treatment , the comparatively high abstinence percentages achieved in this trial are of interest The aims of the current study were to examine , prospect ively , ( a ) dynamic changes in affective state , self-efficacy , and urge in the hours before initial smoking and drinking lapses among individuals in concurrent alcohol and smoking treatment , and ( b ) the extent to which self-efficacy , urge to use , and /or the use of one substance predicted lapse to the other substance . Ninety-six men and women recruited for a clinical trial of concurrent alcohol and tobacco treatment were eligible for inclusion . Only data from those who experienced an initial lapse to drinking ( n=29 ) or smoking ( n=32 ) were included . Two outpatient substance abuse clinics provided concurrent alcohol and smoking treatment on a weekly basis for three months . Ecological Momentary Assessment ( EMA ) methods were employed over a 28-day monitoring period to assess antecedents to first drink , and a 14-day monitoring period was examined for initial smoking lapses . Baseline and EMA measures of positive and negative affect , alcohol/smoking urge , alcohol/smoking abstinence self-efficacy , nicotine withdrawal , and quantity/frequency of alcohol and tobacco use were examined as lapse predictors . Analyses of EMA ratings controlled for the corresponding baseline measure . Smoking lapse among individuals in concurrent alcohol and tobacco treatment was foreshadowed by higher urges to smoke , lower positive mood , and lower confidence to resist smoking . Drinking lapse was preceded by lower confidence to resist smoking , but only among individuals who reported recent smoking . Concurrent alcohol and smoking treatment should focus on the enhancement of abstinence self-efficacy , positive mood , and the curbing of urges in order to offset lapse risk Rationale Research has demonstrated that psychosocial stressors increase smoking and risk for smoking relapse . Alterations in biological systems involved in the stress response caused by chronic smoking may contribute to early relapse . Objectives We examined the extent to which pituitary – adrenocortical and cardiovascular responses to stress following the first 24 h of a quit attempt predict early relapse . Methods Seventy-two smokers interested in cessation attended a laboratory stress session 24 h after the beginning of their cessation attempt . Adrenocorticotropin ( ACTH ) , plasma and salivary cortisol concentrations , systolic and diastolic blood pressure ( BP ) , and heart rate ( HR ) responses to acute psychological stressors ( public speaking and cognitive challenges ) were used to predict relapse over a 4-week follow-up period . Results Those who relapsed within 4 weeks showed attenuated hormonal and cardiovascular responses to stress and exaggerated withdrawal symptoms . Cox proportional hazards survival analysis showed that attenuated ACTH , plasma cortisol , systolic and diastolic BP , positive affect , and exaggerated withdrawal symptoms and smoking urges during acute stress predicted early relapse . Stepwise model showed that ACTH , diastolic BP , and exaggerated withdrawal symptoms remain as significant predictors . When baseline smoking and psychological measures were included in the model , changes in ACTH , diastolic BP , and both factors of smoking urges remained significant predictors of relapse . Conclusions These results demonstrate that altered stress response predicts increased vulnerability for smoking relapse AIM The study aim ed to test simultaneously our underst and ing of the effects of bupropion sustained-release ( SR ) treatment on putative mediators and our underst and ing of determinants of post-quit abstinence , including withdrawal distress , cigarette craving , positive affect and subjective reactions to cigarettes smoked during a lapse . The specificity of bupropion SR effects was also tested in exploratory analyses . DESIGN Data from a r and omized , placebo-controlled clinical trial of bupropion SR were su bmi tted to mediation analyses . SETTING Center for Tobacco Research and Intervention , Madison , WI , USA . PARTICIPANTS A total of 403 adult , daily smokers without contraindications to bupropion SR use . INTERVENTION Participants were assigned r and omly to receive a 9-week course of bupropion SR or placebo pill and to receive eight brief individual counseling sessions or no counseling . MEASUREMENTS Ecological momentary assessment ratings of smoking behavior and putative mediators were collected pre- and post-quit . FINDINGS Results of structural equation and hierarchical linear models did not support the hypothesis that bupropion SR treatment improves short-term abstinence by reducing withdrawal distress or affecting the subjective effects of a lapse cigarette , but provided partial support for mediation by cigarette craving reduction and enhanced positive affect . Bupropion SR effects on point-prevalence abstinence at 1 month post-quit were also mediated partially by enhanced motivation to quit and self-efficacy . CONCLUSIONS Results provided some support for models of bupropion SR treatment and relapse and suggested that motivational processes may partially account for bupropion SR efficacy Little is known about the role that smoking cues play in relapse after smoking cessation . Two studies examined the psychophysiologic , behavioral and cognitive reactions of Ss who participated in a smoking cue-exposure trial ( CUET ) . Study 1 compared male relapsers , long-term quitters and nevers-mokers ( controls ) . Relapsers had significantly higher anxiety and urges to smoke than either quitters or controls . Relapsers also had greater heart-rate ( HR ) reactivity and were rated by judges as having less effective coping skills than controls . In Study 2 the CUET was tested prospect ively in a treatment outcome study for smoking cessation . Responses on the CUET at pre-treatment were related to smoking status at 6 months post-treatment . Prospect i ve quitters had significantly less HR reactivity during the CUET and reported less anxiety than the smokers . There was some lack of consistency across response modes in the results of Studies 1 and 2 . Taken together , the two studies suggest that reactivity to smoking cues may play a role in smoking relapse AIM To examine changes in nicotine withdrawal , nicotine craving , self-efficacy to quit smoking , and perceived control over withdrawal symptoms as predictors of smoking cessation following behavioral counseling and nicotine replacement therapy in a sample of smokers . DESIGN AND SETTING The data were ascertained from a r and omized effectiveness trial comparing nicotine patch to nicotine lozenge . Predictors of smoking cessation were assessed at baseline and 5 weeks post-baseline , and 24-hour point prevalence abstinence , biochemically confirmed , was assessed at the end-of-treatment ( week 15 ) and 6 months after a target quit date ( week 27 ) . PARTICIPANTS 642 treatment-seeking smokers r and omized to 12 weeks of nicotine patch or nicotine lozenge . FINDINGS Participants who showed a greater increase in self-efficacy to quit smoking ( OR=1.09 , 95 % CI : 1.02 - 1.16 , p=.01 ) and perceived control over withdrawal symptoms ( OR=1.02 , 95 % CI : 1.00 - 1.04 , p=.05 ) were significantly more likely to have quit smoking at week 15 . Participants who showed a greater increase in self-efficacy to quit smoking ( OR=1.04 , 95 % CI : 1.01 - 1.06 , p=.01 ) were significantly more likely to have quit smoking at week 27 . Changes in withdrawal symptoms and craving were not related to week 15 or week 27 abstinence rates . CONCLUSIONS The results highlight two relatively under-studied potential psychological predictors of abstinence following treatment for nicotine dependence . Behavioral counseling interventions to promote smoking cessation should help smokers develop confidence in their ability to quit smoking and increase their sense of control over withdrawal symptoms to increase their chances for cessation BACKGROUND Most ( > 50 % ) smokers who attempt to stop smoking relapse within the first year of abstinence . The effect of continued use of pharmacotherapy for smoking cessation on relapse rates is unknown . Bupropion sustained-release ( SR ) is the first non-nicotine-based therapy that is effective for achieving abstinence from smoking . OBJECTIVE This analysis explored the factors involved in relapse to smoking in patients who had successfully stopped smoking using bupropion SR . These patients were participants in a double-blind , placebo-controlled trial of bupropion SR for the prevention of relapse to smoking . METHODS Participants who had stopped smoking with 7 weeks of open-label bupropion SR were r and omly assigned to receive double-blind treatment with either bupropion SR or placebo for 45 weeks . The primary efficacy outcome of the main study was the rate of relapse to smoking . The analyses presented here examine the levels of reported cigarette craving and , in those participants who returned to smoking , the reasons associated with relapse , using patient-completed question naires . RESULTS Craving was cited most frequently as a factor contributing to relapse in those participants receiving placebo ( cited by 49.2 % of relapsers ) but significantly less frequently by participants receiving bupropion SR ( cited by 22.4 % of relapsers ) ( P < 0.05 ) . Results from patients ' diaries showed no differences between bupropion SR and placebo in terms of " craving in the past 24 hours " but significantly lower scores for " craving right now " for bupropion SR at weeks 11 and 12 ( P < 0.05 ) . Results at scheduled visits showed that " craving in the past 24 hours " was significantly less with bupropion SR compared with placebo at weeks 12 , 20 , and 48 , and " craving right now " was significantly less with bupropion SR compared with placebo at weeks 12 , 16 , 20 , 24 , 48 , and 52 ( P < 0.05 ) . CONCLUSIONS Craving continues to be a significant concern for individuals even after they have successfully stopped smoking . Bupropion SR appears to reduce reported cravings , which may contribute to the overall reduction in the rate of relapse observed with this pharmacotherapy BACKGROUND The suggested mechanism for the effects of nicotine replacement medications such as nicotine lozenges on smoking abstinence is reduction in the withdrawal symptoms of emotional distress and craving ( the subjective desire to smoke ) . OBJECTIVES This study assessed the effect of nicotine lozenges on affective withdrawal symptoms ( collectively termed emotional distress ) and craving over 6 weeks of treatment and the role of emotional distress and craving in mediating the effect of the lozenges on smoking abstinence . METHODS This was a secondary analysis of data from a r and omized , double-blind , placebo-controlled clinical trial of nicotine lozenges . High-dependence smokers ( those who smoked their first cigarette of the day within 30 minutes of waking ) were assigned to receive the 4-mg lozenge ; low-dependence smokers ( those who smoked their first cigarette of the day > 30 minutes after waking ) were assigned to receive the 2-mg lozenge . Participants were r and omized to receive active or placebo lozenges within these dose and dependence strata . Smokers were to rate their withdrawal symptoms daily during the baseline week ( while still smoking ) and for 6 weeks after starting treatment . Study analyses included the effect of the active lozenge on affective symptoms ( ie , anxiety ; anger , irritability , or frustration ; difficulty concentrating ; restlessness ; and depressed mood ) during weeks 1 through 6 in high- and low-dependence smokers ; the prospect i ve associations between these symptoms and craving and subsequent abstinence ; and the mediating influence of these symptoms on the lozenge 's effect on abstinence . The analyses included smokers who provided symptom data for the baseline period and for at least week after the initiation of treatment . RESULTS Of 1,818 smokers enrolled in the original study , this analysis included data from 1,144 . The population was predominantly white , had a mean age ranging ranging from 40.65 to 46.01 years , and included slightly more women than men . The 2-mg lozenge did not have consistently significant effects on the withdrawal symptoms of emotional distress among low-dependence smokers ; however , in high-dependence smokers , the 4-mg dose was associated with significant reductions versus placebo in overall emotional distress symptoms through week 4 ( P < 0.001-P = 0.025 ) , all individual symptoms through week 3 ( P < 0.001-P = 0.035 ) , and irritability and anxiety through week 4 ( P = 0.002-P = 0.049 ) . In the low-dependence group , the 2-mg lozenge was associated with significant reductions versus placebo in craving through week 3 ( P = 0.012-P = 0.033 ) , whereas in the high-dependence group , the 4-mg lozenge was associated with significant reductions in craving in each of the first 6 weeks ( P < 0.001-P = 0.028 ) . Among high-dependence smokers , both week-1 and week-2 emotional distress scores were associated with a return to smoking by week 6 ( P < 0.001 ) ; among low dependence smokers , the association applied only to week-2 symptoms ( P = 0.017 ) . Week-1 and week-2 craving was associated with a return to smoking at week 6 in both groups ( P < 0.001-P = 0.001 ) . Emotional distress modestly and inconsistently mediated the effects of the lozenges , accounting for 3 % to 13 % of the treatment effects , whereas craving more strongly ( though incompletely ) mediated the treatment effects , particularly among high-dependence smokers , in whom it accounted for 29 % to 39 % of the treatment effects . CONCLUSIONS In high-dependence smokers , the 4-mg nicotine lozenge significantly reduced all affective withdrawal symptoms through the first 4 weeks of treatment . Lozenge-related decreases in craving partially mediated the effect of treatment on abstinence , particularly in high-dependence smokers Previous research has shown that elevated trait-impulsivity heightens the risk for initiating tobacco use and indicates that nicotine may be disproportionately rewarding for more impulsive persons . However , the influence of impulsivity on the ability to maintain nicotine abstinence has not been studied . The present study tested the hypothesis that a higher level of trait-impulsivity would predict a more rapid relapse to smoking following 48 hr of nicotine abstinence . Participants were euthymic , regular smokers ( N=45 ) , with a history of at least one major depressive episode , who participated in a paid smoking cessation study with biological challenge ( tryptophan depletion ) . Treatment involved a 1-day skills training workshop followed by 48 hr of bioverified abstinence and weekly follow-up for 1 month . Regression analyses indicated that elevated impulsivity predicted shorter time to relapse following the workshop after controlling for treatment condition , baseline nicotine dependence , and age ( beta=-.39 , R(2 ) change=.147 , p=.011 ) . Greater impulsivity predicted more rapid relapse to smoking , which mediational analyses indicated could not be explained by positive affect , negative affect , or craving . Findings suggest a need to identify alternative mechanisms to explain impulsive smokers ' increased difficulty in maintaining abstinence and to develop targeted treatments that address the special needs of smokers high in impulsivity Rationale Tobacco withdrawal is a key factor in smoking relapse , but important questions about the withdrawal phenomenon remain . Objectives This research was intended to provide information about two core components of withdrawal ( negative affect and craving ) : ( 1 ) how various withdrawal symptom profile dimensions ( e.g. , mean level , volatility , extreme values ) differ between negative affect and craving ; and ( 2 ) how these dimensions relate to cessation outcome . Methods Adult smokers ( N = 1,504 ) in a double-blind r and omized placebo-controlled smoking cessation trial provided real-time withdrawal symptom data four times per day for 4 weeks ( 2 weeks pre-quit and 2 weeks post-quit ) via palmtop computers . Cessation outcome was biochemically confirmed 8-week point-prevalence abstinence . Results Examination of craving and negative affect dimensions following a cessation attempt revealed that craving symptoms differed from negative affect symptoms , with higher means , greater variability , and a greater incidence of extreme peaks . Regression analyses revealed that abstinence was associated with lower mean levels of both craving and negative affect and fewer incidences of extreme craving peaks . In a multivariate model , the increase in mean craving and negative affect scores each uniquely predicted relapse . Conclusions Real-time reports revealed different patterns of abstinence-related negative affect and craving and that dimensions of both predict cessation outcome , suggesting that negative affect and craving dimensions each has motivational significance . This underscores the complexity of withdrawal as a determinant of relapse and the need to measure its distinct components and dimensions Rationale Nicotine nasal spray ( NS ) is recommended as one of five first-line smoking cessation products . A clinical ly convenient tool to identify smokers most likely to benefit from NS could assist healthcare practitioners in selecting the optimal treatment for individual patients . Objectives To evaluate whether the subjective effects of an initial pre-treatment dose of NS predict 6 month abstinence rates following NS treatment for tobacco dependence . Methods One hundred and seventy-five smokers received an initial 1 mg pre-treatment dose of NS and completed a new measure of NS subjective effects ( initial spray experience , ISE ) . This measure , together with demographic and smoking history variables , was examined as a predictor of 6-month point-prevalence ( biochemically verified ) abstinence rates . Results Factor analysis revealed positive and negative effects subscales of the ISE . Smokers with higher ratings of positive effects from the pre-treatment NS dose were significantly more likely to be abstinent at 6-month follow-up . These effects were partially mediated by reduction in urge to smoke . Conclusions Pending additional validation in human laboratory and clinical studies , assessment of the acute positive subjective effects of initial NS delivery may be an efficient way to predict who will be successful with NS treatment for tobacco dependence Smokers ( N = 126 ) were r and omly assigned to 6-session smoking cessation treatments consisting of 1 of 2 counseling strategies ( skills training or support ) and 1 of 2 nicotine exposure strategies ( nicotine gum or rapid smoking ) . Counseling and nicotine strategies were completely crossed ; all four combinations result ed in equivalent 1-year abstinence rates . Skills training produced higher initial cessation and more coping responses posttreatment than did support . Rapid smoking , but not nicotine gum , produced tachycardia to the taste of cigarettes posttreatment , consistent with cigarette aversion . The treatments were differentially effective among sub population s of smokers : Subjects high in pretreatment negative affect responded best to support counseling ; those low in pretreatment negative affect responded best to skills training . Self-reports of pretreatment craving predicted response to the nicotine exposure treatments Abstract Forty-nine dependent smokers were assigned to one of three treatment conditions : rapid smoking , cue exposure or simple support . There were no differences between treatments in the proportion who stopped smoking or the average reduction in smoking at the end of treatment or at 1 yr follow-up . The overall proportion who stopped was 22 % at the end of treatment and 14 % at 1 yr follow-up . Time of the first cigarette of the day ( before tea or coffee ) and percentage reduction in consumption whilst trying to cut down unaided , predicted abstinence at 1 yr follow-up . These results do not support cl aims made for the effectiveness of rapid smoking Cue exposure paradigms have been used to examine reactivity to smoking cues . However , it is not known whether cue-provoked craving is associated with smoking cessation outcomes or whether cue reactivity can be attenuated by nicotine replacement therapy ( NRT ) in clinical sample s. Cue-provoked craving ratings and reaction time responses were measured on the 1st day of abstinence among 158 smokers who had been r and omized to high-dose nicotine ( 35 mg ) or placebo patch . The nicotine patch reduced overall levels of craving but did not attenuate cue-provoked craving increases or reaction time responses . Cue-provoked craving predicted relapse among participants on the nicotine patch but not among those on placebo . In summary , NRT users could benefit from treatment that attenuates cue-provoked craving BACKGROUND The reasons for relapse to smoking are not fully understood but several factors are of importance . Addiction to nicotine seems to play a prominent role but there are several other contributing factors . METHODS To determine predictors of outcome in smoking cessation , we performed univariate and multivariate analyses in a large smoking cessation trial comprising 289 subjects . Weight gain and withdrawal symptoms were analyzed separately as predictors . To determine self-perceived reasons for relapse we created a question naire , which was answered by 132 relapsers . RESULTS Previous attempts to quit smoking and a low saliva cotinine concentration were significantly associated with abstinence in the nicotine-treated group . A trend toward higher abstinence rates was found among males and among subjects with a low nicotine dependency score . Logistic regression analysis showed higher success rates in subjects with the largest weight gain during the first weeks of quitting in contrast to higher relapse rates in subjects who had the greatest weight gain after 3 months . A high score on withdrawal symptoms was not predictive of relapse . Subjects with " slips " had a markedly increased relapse rate . Craving for cigarettes was the most often self-reported ( 48 % ) reason for relapse . CONCLUSIONS The relation between weight gain , withdrawal scoring , and outcome seems rather complex . Craving for cigarettes was the most reported reason for relapse Results of a prospect i ve examination of factors influencing smoking relapse are reported for a sample of smokers ( N=522 ) obtained through population -based recruitment . All subjects were given a modified Fagersirom Tolerance Question naire ( modified FTQ ) , which is a 5-item self-report instrument characterizing smokers according to their degree of nicotine dependence . At 30 days postcessation . those placing in the lowest quartile of the modified FTQ at baseline had the highest survival rate ( 79 % ) and those placing in the highest quartile at baseline had the lowest survival ( non-relapse ) rate ( 43 % ) . The difference in survival among the groups was statistically significant ( p > .001 ) . At 12 months , those placing in the lowest quarrtile of baseline cigarette consumption had the highest survival rate ( 34 % ) and those placing in the highest quartile had the lowest survival rate ( 14 % ; p > .001 ) , It seems increasingly clear that level of dependence , even as indexed by comparatively crude self-report measures such as amount smoked is associated with the rate and pattern of smoking relapse Despite the efficacy of bupropion for smoking cessation , smokers exhibit variability in treatment outcome . The CYP2B6 gene has been implicated in bupropion kinetics and nicotine metabolism , and is a plausible c and i date for pharmacogenetic studies of treatment response . We investigated whether a functional genetic polymorphism in the CYP2B6 gene predicts smoking outcomes in a placebo-controlled r and omized trial . Four hundred and twenty-six smokers of European Caucasian ancestry provided blood sample s and received bupropion ( 300 mg/day for 10 weeks ) or placebo , plus counseling . Smoking status , abstinence symptoms and side-effects were recorded weekly , and smoking status was verified at the end of treatment and at 6-month follow-up . Smokers with a decreased activity variant of CYP2B6 reported greater increases in cravings for cigarettes following the target quit date and had higher relapse rates . These effects were modified by a significant gender x genotype x treatment interaction , suggesting that bupropion attenuated the effects of genotype among female smokers . We conclude that smokers with the CYP2B6 variant may be more vulnerable to abstinence symptoms and relapse . Bupropion may attenuate these effects , especially among females . Additional trials are warranted to confirm these results , as are studies to explore the neurobiological mechanisms . Such research could ultimately enable practitioners to select the optimal type and dose of medication for individual smokers Rates of smoking relapse remain high , despite the wide availability of cessation aids . Presumably factors such as craving , withdrawal symptoms , and smoking urges are key contributors to relapse , but empirical support for this presumption is not conclusive and is complicated by the high variability in symptoms across individuals and time , as well as by the lack of an absolute symptom threshold for response . Data were analyzed from 137 female smokers , aged 18 - 40 years , who completed 30 days of a protocol for a longitudinal smoking cessation trial . Subjects were assigned a quit date and followed regardless of subsequent smoking status . At baseline , subjects completed written measures of nicotine craving , withdrawal symptoms , and smoking urges . They also completed these measures daily for 30 days , beginning on their quit date , Scores were st and ardized within subjects and graphed to identify temporal symptom patterns . A total of 26 women quit smoking and 111 relapsed ( at least one cigarette puff ) . The intensity of subjects ' craving , withdrawal , and smoking urges Factors 1 and 2 peaked on the day of relapse by an average of 1.4 , 1.1 , 1.2 , and 1.1 st and ard deviations , respectively , with symptoms rising during the previous 2 - 5 days and dropping precipitously over the 2 days subsequent to relapse . Additionally , women who relapsed had higher absolute ( unst and ardized ) symptom scores on their quit day than those who were abstinent for 30 days . These findings imply that escalation of withdrawal symptoms , craving , and smoking urges during a quit attempt may contribute to smoking relapse . Frequent symptom monitoring might be clinical ly important for relapse prevention We used multimodal measurement to evaluate whether ( a ) nicotine dependence is associated with baseline and postquit negative affect and craving , ( b ) smoking relapse is associated with greater negative affect and craving than abstinence , and ( c ) craving is associated with negative affect . Treatment-seeking smokers were r and omly assigned to either a brief behaviorally based smoking-cessation treatment condition or to a delayed treatment control condition . Participants in the treatment condition attended four assessment sessions , 4 - 5 days prequit ( baseline ) , 1 - 2 days postquit , 3 - 5 days postquit , and 10 - 14 days postquit , while controls attended four sessions spaced over the same intervals . Retrospective question naires were collected at the beginning of each session , and corrugator EMG and in-session ratings were collected during viewing of affective and cigarette-related slides . The multimodal measures indicated that more dependent smokers experienced greater negative affect and craving at baseline and postquit , regardless of abstinence status . The self-report measures indicated that both relapsed and abstinent smokers reported greater negative affect and craving than control smokers . Craving was associated with negative affect across measurement modalities . These results highlight the benefits of using multimodal measures to study the impact of nicotine dependence and withdrawal on negative affect and craving OBJECTIVES Nearly all smokers who lapse experience a full-blown relapse , but the mediating mechanisms that contribute to this relationship are not well understood . A better underst and ing of these mechanisms would help to advance more effective relapse prevention treatments for smokers . The purpose of this study is to experimentally evaluate the effects of a programmed smoking lapse on smoking relapse and the effects of postlapse changes in craving on relapse . METHOD Adult smokers ( n = 63 ) who quit smoking with a brief cognitive-behavioral intervention and self-help material s were r and omly assigned to one of two experimental conditions after 48 h of abstinence : No lapse ( a no-smoking control/30-min waiting period ) or lapse ( smoking two cigarettes of their favored br and during a 30-min period ) . All participants were then followed daily for 14 days . Craving and biochemically verified self-reported abstinence were assessed on each follow-up day . Time ( days ) to relapse ( 7 consecutive days of smoking ) was the main dependent measure . RESULTS Results of Cox regression analysis revealed that participants in the lapse condition relapsed more quickly than participants in the no-lapse condition ( hazard ratio [ HR ] = 2.12 , 95 % confidence interval [ CI ] = [ 1.03 , 4.35 ] ) . These effects were attributable , in part , to episodic increases in craving among participants in the lapse condition only ( HR = 12.42 , 95 % CI = [ 2.00 , 77.1 ] ) . CONCLUSIONS Previously abstinent smokers who lapse are at risk for increased cigarette cravings and consequently , full-blown relapse . These results have implication s for both cognitive-behavioral treatments for relapse prevention and for medications design ed to help smokers manage cravings In a combined sample of more than 2600 smokers , immediate postcessation craving is shown to be prospect ively associated with smokers ' ability to maintain abstinence . Relapse is strikingly rapid among those reporting high levels of craving following cessation . More than 32 % of those with high craving scores relapsed within 1 week of cessation . In contrast , fewer than 15 % of those with low craving relapsed in the first week ( p < .001 ) . Our findings provide a warrant for an increased research effort design ed to provide a better underst and ing of the factors that control following smoking cessation and the processes by which craving influences smoking relapse AIMS To examine if menstrual phase affects relapse in women attempting to quit smoking . DESIGN An intent-to-treat r and omized smoking cessation trial where women were assigned to quit smoking in either the follicular ( F ) or luteal ( L ) menstrual phase and were followed for up to 26 weeks . They were assessed for relapse by days to relapse and relapse phase to determine if those who begin a quit attempt during the F phase were more successful than those who begin during the L phase . SETTING Tobacco Use Research Center , University of Minnesota , Minneapolis , Minnesota . PARTICIPANTS A total of 202 women . MEASUREMENTS Latency to relapse from continuous and prolonged abstinence , point prevalence , phase of relapse , first slip within the first 3 and 5 days post-quit date , subject completion rates and symptomatology ( i.e. withdrawal and craving ) . FINDINGS The mean days to relapse from continuous abstinence and relapse from prolonged abstinence for the F group were 13.9 and 20.6 days , respectively , and 21.5 and 39.2 days , respectively , for the L group . Using point prevalence analysis at 14 days , 84 % of the F group had relapsed compared with 65 % of the L group [ chi(2)=10.024 , P=0.002 ; odds ratio ( OR ) = 2.871 , 95 % confidence interval ( CI ) , 1.474 - 5.590 ] . At 30 days , 86 % of the F group relapsed , compared with 66 % of the L group ( chi(2)=11.076 , P=0.001 ; OR=3.178 , 95 % CI , 1.594 - 6.334 ) . CONCLUSION Women attempting to quit smoking in the F phase had less favorable outcomes than those attempting to quit in the L phase . This could relate to ovarian hormones , which may play a role in smoking cessation for women This article describes a multidimensional , multivariate , and multilevel approach to the assessment of nicotine withdrawal . In this prospect i ve study , 70 adult smokers assigned to an active or placebo nicotine patch condition completed multiple daily assessment s using an electronic diary . Average and individual growth curves were estimated for affective and nonaffective withdrawal symptoms . All symptoms but hunger increased significantly on the quit day and remained elevated for three weeks . Variability in symptom experiences across individuals increased from pre- to post-quit . Relations between symptom reports ( e.g. , negative affect or craving ) and episodic events ( e.g. , stressful events or seeing someone smoke ) changed from pre-quit to post-quit . Pre-quit increases in negative affect and quit-day increases in craving were inversely related to abstinence three months after the quit day , suggesting that anticipatory and immediate reactions to quitting influence success Various theories have proposed mechanisms for drug motivation and relapse . For instance , negative reinforcement theories focus on the alleviation of withdrawal . However , other theories and some data cast doubt on the importance of withdrawal as a motivator of addictive drug use . Using data from a r and omized double-blind placebo-controlled smoking cessation treatment study ( N=608 ) , this research examined the impact of withdrawal on drug motivation and the ability to maintain abstinence . Withdrawal was experimentally manipulated by r and omly assigning participants to receive active bupropion versus placebo . Mediation analyses revealed that active bupropion reduced the amount of withdrawal and craving that individuals reported in the 1st week post quit ; modest support was also found for smaller declines in positive affect . These effects , in turn , were all positively associated with posttreatment abstinence . These results implicate withdrawal as an important factor in motivating persistent tobacco use OBJECTIVES To identify distinct subgroups of treatment responders and nonresponders to aid in the development of tailored smoking-cessation interventions for long-term maintenance using signal detection analysis ( SDA ) . METHODS The secondary analyses ( n = 301 ) are based on data obtained in our r and omized clinical trial design ed to assess the efficacy of extended cognitive behavior therapy for cigarette smoking cessation . Model 1 included only pretreatment factors , demographic characteristics , and treatment assignment . Model 2 included all Model 1 variables , as well as clinical data measured during treatment . RESULTS SDA was successfully able to identify smokers with varying probabilities of maintaining abstinence from end-of-treatment to 52-week follow-up ; however , the inclusion of clinical data obtained over the course of treatment in Model 2 yielded very different partitioning parameters . CONCLUSIONS The findings from this study may enable research ers to target underlying factors that may interact to promote maintenance of long-term smoking behavior change BACKGROUND Bupropion sustained release ( bupropion SR ) has been shown to increase smoking cessation success rates in the US studies . OBJECTIVE To determine whether bupropion SR , in combination with counselling , is effective for smoking cessation in a multi-country study . METHODS This r and omized , double-blind , placebo-controlled trial enrolled 707 smokers . A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo . A total of 11 clinic visits and 10 telephone contacts were scheduled , during the course of 1 year . Seven-week and 12-month abstinence rates were the study outcomes . RESULTS Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo . The continuous abstinence rate from weeks 4 to 7 was 46 % in the bupropion SR group compared with 23 % in the placebo group [ odds ratio ( OR ) = 2.82 ; 95 % confidence interval ( CI ) 1.89 - 4.28 ; P < 0.001 ) . At month 12 , the continuous abstinence rates were 21 % for the bupropion SR group and 11 % for the placebo group ( OR = 2.19 ; 95 % CI 1.29 - 3.86 , P = 0.002 ) . For most nicotine-withdrawal symptoms small changes were measured . Adverse events were higher for the bupropion SR group compared with placebo ( insomnia 24 % vs. 15 % ; dry mouth 13 % vs. 5 % ) . CONCLUSION Bupropion SR in combination with counselling increased the abstinence rate compared with placebo , and was well tolerated Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga ( Apocynaceae family ) , a rain forest shrub that is native to western Africa . Ibogaine is used by indigenous peoples in low doses to combat fatigue , hunger and thirst , and in higher doses as a sacrament in religious rituals . Members of American and European addict self-help groups have cl aim ed that ibogaine promotes long-term drug abstinence from addictive substances , including psychostimulants and opiates . Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time . The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite . The majority of ibogaine biotransformation proceeds via CYP2D6 , including the O-demethylation of ibogaine to 12-hydroxyibogamine ( noribogaine ) . Blood concentration-time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles . Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment . We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification . Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge . Because ibogaine is cleared rapidly from the blood , the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system Smokers who recently quit ( N = 214 ) monitored smoking urges for up to 26 days after quitting . Computers administered 4 - 5 assessment s daily at r and om times ; participants rated urges on waking and when they experienced temptation episodes . Urge intensity after cessation did not generally exceed urges reported during baseline ad lib smoking . Urge intensity and temptation frequency consistently declined over the quit period . Controlling for urge intensity at baseline , all daily urge intensity measures predicted lapse the following day in proportional hazards survival analyses . Average duration of temptation episodes also predicted lapses ; frequency of temptation did not . To isolate the effect of day-to-day variations in urges , participants ' nicotine dependence and urge intensity on quit day were controlled for . Only urge intensity at waking still predicted lapse risk ; this was not because of this measured being closer in time to the day 's lapses . Among lapsers , urge intensity at waking and in temptations rose preceding a lapse Most attempts to quit smoking end in failure , with many quitters relapsing in the first few days . Responses to smoking-related cues may precipitate relapse . A modified emotional Stroop task-which measures the extent to which smoking-related words disrupt performance on a reaction time ( RT ) task-was used to index the distracting effects of smoking-related cues . Smokers ( N = 158 ) r and omized to a high-dose nicotine patch ( 35 mg ) or placebo patch completed the Stroop task on the 1st day of a quit attempt . Smokers using an active patch exhibited less attentional bias , making fewer errors on smoking-related words . Smokers who showed greater attentional bias ( slowed RT on the first block of smoking words ) were significantly more likely to lapse in the short-term , even when controlling for self-reported urges at the test session . Attentional bias measures may tap an important component of dependence BACKGROUND The nicotine patch has been widely used for smoking cessation , but not all smokers quit using the patch . Knowing which smokers are likely to succeed with the nicotine patch may improve the efficiency of nicotine patch use . OBJECTIVE To identify predictors of smoking abstinence using baseline characteristics , smoking behavior , and withdrawal symptoms . METHODS Using 2 r and omized clinical trials of pharmacologic treatment , brief counseling , and quit date formats in the outpatient research clinic setting , predictors of smoking cessation were derived in 1 sample ( n = 159 ) , then prospect ively vali date d in an independent sample ( n = 48 ) . Subjects smoked 1 pack of cigarettes per day or more and were motivated to quit smoking . Self-report of abstinence at 6 months verified by exhaled carbon monoxide of 8 ppm or less was used . RESULTS Abstinence at 6 months was 24 % in the derivation set and 25 % in the validation set . Using logistic regression , a model containing quit date abstinence ( odds ratio , 10.6 ; 95 % confidence interval [ CI ] , 2.9 - 38.7 ) and baseline nicotine dependence ( odds ratio , 0.75 ; 95 % CI , 0.6 - 1.0 per unit increase in Fagerstrom score ) provided the optimal predictive ability and was vali date d in the independent set . Quit date abstinence improved the likelihood of 6-month abstinence by 4.1 over baseline ( 95 % CI , 2.6 - 6.4 ) for low-nicotine-dependent smokers and 1.2 ( 95 % CI , 0.6 - 2.2 ) for high-nicotine-dependent smokers . Quit date smoking altered the likelihood of 6-month abstinence by 0.2 ( 95 % CI , 0.0 - 0.8 ) for low-dependent smokers and 0.1 for high-dependent smokers ( 95 % CI , 0.0 - 0.6 ) . CONCLUSIONS Abstinence on the quit date and low-nicotine dependence improve the likelihood of smoking abstinence at 6 months . Smoking on the quit date may be an indication for postponing the cessation attempt or adjusting the therapy for smoking cessation Heavy smokers ( N = 408 , smoking more than 25 cigarettes/day ) were r and omized to receive high-dose ( 25 mg ) or st and ard-dose ( 15 mg ) nicotine patch therapy delivered during the daytime only ( 16 hr ) for a period of 6 weeks . Treatment effects of each dose were similar . The percentages of participants not smoking at 2- , 6- , and 12-month follow-ups were 26 versus 20 , 14 versus 16 , and 14 versus 14 for the 15-mg and 25-mg doses , respectively . The higher dose was well tolerated , and adverse event profiles for both treatment doses were very similar . Stepwise Cox proportional hazards analyses indicated that initial postr and omization craving and baseline scores on the Center for Epidemiological Studies Depression Instrument predicted time-to-relapse during treatment ; only initial craving predicted relapse over the entire study interval ( 12 months ) . The results of this trial do not support the routine use of higher dose nicotine patch therapy in the treatment of nicotine dependence Lapses within the first 2 weeks of a smoking cessation attempt are strongly associated with a return to regular smoking ( S. L. Kenford et al. , 1994 ) . Unfortunately , little is known about how to prevent an initial lapse from progressing to a full relapse , and presently there are no vali date d lapse-responsive therapeutic interventions . The present study tested the efficacy and feasibility of rapid smoking plus counseling as a novel lapse-responsive intervention . Sixty-seven participants enrolled in a smoking treatment program involving brief counseling and a 9-week course of bupropion . Beginning on the quit day , participants ' smoking behavior was tracked daily for 14 days . Once an early smoking lapse was identified , participants were r and omly assigned to receive either 3 sessions of rapid smoking plus counseling or no intervention ( usual care ) . Consistent with previous research , participants who smoked during the first 2 weeks of the quit attempt had significantly poorer 6-month outcomes ( 3 % abstinent ) than did those who did not smoke ( 64 % abstinent ) . Compared with early abstainers , early lapsers were more nicotine dependent and reported greater cravings and lower confidence in their ability to abstain from smoking during the first 48 hours of abstinence . As expected , rapid smoking produced a variety of aversive effects , including increased nausea , dizziness , and vomiting as well as sharply decreased cravings to smoke . However , rapid smoking did not improve abstinence outcomes relative to usual care . Although rapid smoking has been shown to be an effective treatment for initial smoking cessation , in this preliminary study the authors failed to demonstrate its effectiveness as a lapse-responsive treatment This study examined the detailed time course of desire to smoke self-reports during brief periods of tobacco smoking deprivation to determine how these reports are related to amount and spacing of scheduled smoking . During four independent sessions , subjects ( n=10 ) smoked cigarettes at 30- , 60- , or 120-min intervals , or only smoked a single cigarette at the end of the 6-h session . At 15-min intervals , subjects answered four analog scale questions measuring their desire to smoke which were averaged to produce a single score . Mean desire to smoke scores were 28 , 43 , 59 and 71 in the 30- , 60- , 120- and 360-min cigarette spacing conditions , respectively , indicating an orderly relationship with amount of scheduled smoking . Patterns of change were similar across repeated observations and during several different deprivation intervals . Desire to smoke ratings , although temporarily suppressed by smoking , began rising within minutes of smoking and increased to near maximum levels ( about 80 on a 100-point scale ) after fewer than 3 h of abstinence . The observed rapid escalation in desire to smoke ratings during brief periods of abstinence is consistent with cigarette craving being reported by regular smokers who are not trying to quit . Further , if cravings can be accepted as a feature of tobacco withdrawal , the results support the view that avoidance of withdrawal is an important factor that maintains regular cigarette smoking Women are at an increased risk of relapse after a smoking cessation attempt . While the reasons for this phenomenon are not fully understood , recent research indicates that both the menstrual cycle and negative symptomatology may play a role . The goal of this study was to describe the association between withdrawal symptoms during attempted smoking cessation , and to investigate the impact of these symptoms on smoking cessation outcomes as defined by 7-day point prevalence at 14 and 30 days . Negative symptoms associated with the premenstrual period were also assessed . Participants ( n = 202 ) were 29.8 ( SD + /- 6.6 ) years old and smoked 16.6 ( SD + /- 5.6 ) cigarettes per day . They were r and omly assigned to quit smoking in the follicular ( n = 106 ) or luteal ( n = 96 ) menstrual phase . We observed several significantly more severe premenstrual and withdrawal symptoms in the luteal phase . Regardless of quit phase , most withdrawal symptoms were associated with an increased risk of relapse at 14 and 30 days post quit date . Participants attempting to quit smoking in the follicular phase who had higher levels of Anger and Craving were more likely to relapse to smoking at 14-days ( OR = 2.00 , p-value = 0.026 ; OR = 2.63 , p-value = 0.006 ; respectively ) . These data suggest that the menstrual cycle may play a role in smoking cessation outcome , as well as in the symptomatology experienced during a cessation attempt Results of a prospect i ve examination ( N = 618 ) of factors associated with smoking relapse are reported . At 1-year follow-up , a modified version of the Fagerstrom Tolerance Question naire ( Dependence Index ; DI ) and a measure of craving entered the logistic model ( odds ratio of 2.7 [ p less than .001 ] ) . At Year 2 , only the DI entered the model ( odds ratio of 2.2 [ p less than .001 ] ) . The ability of signal detection analysis ( SDA ) to produce clinical ly useful decision rules was also examined . At Year 1 , SDA produced 1 subgroup with a 25 % nonrelapse rate and another with a 9 % nonrelapse rate ( odds ratio of 3.4 [ p less than .001 ] ) . At Year 2 , SDA produced 1 subgroup with a nonrelapse rate of 19 % and another with a nonrelapse rate of 7 % ( odds ratio of 3.0 [ p less than .001 ] ) . The use of signal detection methods may help clinicians to identify those at greater or lesser risk of relapse This r and omized controlled trial tested whether extended callback counselling that proactively engaged ex-smokers with the task of embracing a smoke-free lifestyle ( four to six calls delivered 1 - 3 months after quitting , i.e. when craving levels and perceived need for help had declined ) could reduce relapse compared with a revised version of Quitline 's st and ard service ( four calls in the first month after quitting which focused primarily on the task of helping ex-smokers deal with daily cravings and now also systematic ally alerted clients to the upcoming task of adapting to life as a non-smoker ) . One thous and and four hundred and forty-four smokers or recent ex-smokers were r and omized at recruitment : 734 usual care and 710 intervention . An inclusion criterion of subsequently quitting for at least 1 week gave 346 usual care and 352 intervention participants . Seventy-four per cent of intervention participants accepted extra calls and received 4.3 on average but only 1.7 more post-quitting calls than usual care group . No significant differences were found between extended contact and usual care groups on continuous abstinence ( both 27 % at 12 months ) or any other cessation outcome . The tasks of quitting framework introduced in preparation for the trial might have contributed to service improvement in relapse prevention ( 10 % increased quit rate compared with an earlier trial ) . However , the extra sessions did not provide any benefit Nicotine replacement therapy ( NRT ) repeatedly has been shown to improve smoking treatment outcome . The major mechanism posited for this improvement in outcome is that NRT reduces nicotine craving and withdrawal . The authors tested this hypothesized mechanism of action using real-time data on craving and withdrawal , collected by ecological momentary assessment s administered on a palm-top computer . Smokers ( N = 324 ) were r and omized to receive either active high-dose ( 35 mg ) 24-hr patches or placebo . Increases in positive affect and decreases in craving , negative affect , and attention disturbance severity were related to lower risk of lapsing . Although NRT treatment did significantly decrease withdrawal and craving severity , these reductions only partially accounted for NRT 's impact on time to first lapse : The results from a mediation analysis showed that the hazard ratio for NRT , when controlling for withdrawal and craving severity , was only a third to a half lower than the uncontrolled hazard ratio for NRT alone . This suggests that other mechanisms for the effectiveness of NRT need to be examined |
13,322 | 21,415,023 | However , effects were smaller in larger and better- quality studies , suggesting publication bias .
No intervention was clearly superior , although effort-intensive interventions were less effective than simple ones .
No cost-benefit analyses established statistically significant net economic benefits . | OBJECTIVE To assess the effectiveness of interventions in community and workplace setting s to reduce sickness absence and job loss in workers with musculoskeletal disorders ( MSDs ) . | 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 Introduction It was postulated that workers , at the sub-acute stage after injury , respond differently to clinical and occupational interventions offered in a workers ’ compensation environment . Individual worker risk of disability , it was further believed , would influence the effectiveness of early intervention . The objective of the current pilot study was to evaluate return to work ( RTW ) outcomes following proactive , combined clinical , occupational and case management-based interdisciplinary early intervention , provided in a workers ’ compensation environment 4–10 weeks of onset of back pain , to workers with medium and high risk for disability . Methods The project was a controlled study comparing conventional workers ’ compensation case management with integrated , interdisciplinary and multimodal early intervention ( hereinafter referred to as “ EI ” ) . At baseline , risk status was determined by a vali date d Risk for Disability Question naire by Carragee et al. ( Spine 5(1):24–35 , 2005 ) . Seventeen workers at high risk of protracted disability and 20 workers at moderate risk of disability received conventional case management , and 17 workers assessed at high risk of protracted disability and 18 workers at moderate risk of disability received the Early Intervention . Results At 3 months post back pain onset , no statistically significant differences were identified in RTW outcomes between conventional case management and the Early Intervention . However , by 6 months post back pain onset , workers at high risk of work disability who received the Early Intervention were significantly more likely to RTW than high risk workers who received conventional case management . In contrast , moderate risk workers continued to exhibit no statistically significant differences in RTW outcomes . Conclusion Multimodal Early Intervention in the workers ’ compensation case management context is likely effective for workers with sub-acute back pain who are at high risk of occupational disability . The comprehensive Early Intervention is , however , likely redundant for workers who are not at high risk for disability and should not be applied indiscriminately . Further studies are required to determine longer-term Early Intervention outcomes , and to replicate the findings using a r and omized control design . Also , with a larger sample size , it will be possible to determine predictors of occupational outcomes & NA ; A cognitive – behavioral return‐to‐work focused program was evaluated in a r and omized controlled design , and the effects were compared between two groups of women with musculoskeletal pain . One group of patients ( n=36 ) had a history of long‐term sick leave ( > 12 months ) at the start of the program and the other ( n=36 ) had a history of short‐term sick leave ( 2–6 months ) . The outpatient treatment program , conducted by a psychologist , included 12 sessions with the primary aim to help the patients return‐to‐work . The treatment first included teaching of coping strategies such as applied relaxation , stress management , grade d activity training and pacing . Thereafter the patients were taught how to manage difficulties at their return‐to‐work and how to generalize coping strategies to different risk factors at their work places . The control condition received treatment‐as‐usual . The results showed that the cognitive – behavioral return‐to‐work program was more effective than the treatment‐as‐usual control condition in reducing the number of days on sick leave for patients on short‐term sick leave , but not for patients on long‐term sick leave . The treatment program also helped the patients on short‐term sick leave to increase their ability to control and decrease pain and to increase their general activity level compared to the control condition . These results underscore the need for an early return‐to‐work focused rehabilitation to prevent long‐term sick leave and disability Objective To evaluate the effectiveness of an integrated care programme , combining a patient directed and a workplace directed intervention , for patients with chronic low back pain . Design Population based r and omised controlled trial . Setting Primary care ( 10 physiotherapy practice s , one occupational health service , one occupational therapy practice ) and secondary care ( five hospitals ) . Participants 134 adults aged 18 - 65 sick listed for at least 12 weeks owing to low back pain . Intervention Patients were r and omly assigned to usual care ( n=68 ) or integrated care ( n=66 ) . Integrated care consisted of a workplace intervention based on participatory ergonomics , involving a supervisor , and a grade d activity programme based on cognitive behavioural principles . Main outcome measures The primary outcome was the duration of time off work ( work disability ) due to low back pain until full sustainable return to work . Secondary outcome measures were intensity of pain and functional status . Results The median duration until sustainable return to work was 88 days in the integrated care group compared with 208 days in the usual care group ( P=0.003 ) . Integrated care was effective on return to work ( hazard ratio 1.9 , 95 % confidence interval 1.2 to 2.8 , P=0.004 ) . After 12 months , patients in the integrated care group improved significantly more on functional status compared with patients in the usual care group ( P=0.01 ) . Improvement of pain between the groups did not differ significantly . Conclusion The integrated care programme substantially reduced disability due to chronic low back pain in private and working life . Trial registration Current Controlled Trials IS RCT N28478651 This study investigated the effect of a back school rehabilitation program on lost work time , lost time cost , medical cost , and number of injuries in municipal employees . Seventy back-injured workers who participated in a 6-week back school were compared on the dependent variables with 70 r and omly selected back-injured city employees who had not participated in a back school . Back school participants demonstrated a significant decrease on all dependent variables . Back school participants had significantly fewer injuries in the 6-month postintervention period . No statistically significant differences were found between groups on the time and cost variables . Actual dollars saved in lost time and medical costs between groups was of practical value to the city . Study findings offer support for the back school as a cost-effective measure Study Design . A r and omized clinical trial . Objectives . To evaluate long-term clinical and economical effects of a light mobilization program on the duration of sick leave for patients with subacute low back pain . Summary of Background Data . Twelve-month follow-up results from a previous study showed that early intervention with examination at a spine clinic , giving the patients information , reassurance , and encouragement to engage in physical activity as normal as possible had significant effect in reducing sick leave . At 12-month follow-up , 68.4 % in the intervention group were off sick leave , as compared with 56.4 % in the control group . Patients in this study were followed-up for a period of 3 years to investigate possible long-term effects . Material s and Methods . Four hundred fifty-seven patients placed on a sick list for 8 to 12 weeks for low back pain were r and omized into two groups : an intervention group ( n = 237 ) and a control group ( n = 220 ) . The intervention group was examined at a spine clinic and given information and advice to stay active . The control group was not examined at the clinic but was treated within the primary health care . Results . Over the 3 years of observation , the intervention group had significantly fewer days of sickness compensation ( average 125.7 d/person ) than the control group ( 169.6 d/person ) . This difference is mainly caused by a more rapid return to work during the first year . There was no significant difference for the second or third year . In particular , there is no increased risk for reoccurrence of illness from early return to work . At 6-month follow-up , patients in the intervention group were less likely to use bed rest and more likely to use stretching and walking to cope with their back pain compared with the control group . This effect diminished . At 12-month follow-up , the only significant difference between the groups was in the use of stretching . Economic returns of the intervention were calculated in terms of increases in the net present value of production for the society because of the reduction in number of days on sick leave . Net benefits accumulated over 3 years of treating the 237 patients in the intervention group amount to approximately $ 2,822 per person . Conclusions . For patients with subacute low back pain , a brief and simple early intervention with examination , information , reassurance , and encouragement to engage in physical activity as normal as possible had economic gains for the society . The effect occurred during the first year after intervention . There were no significant long-term effects of the intervention . The initial gain obtained during the first year does not lead to any increased costs or increased risks for reoccurrence of illness over the next 2 years Study Design . A prospect i ve cohort of approximately 1600 injured workers off work because of soft‐tissue musculoskeletal problems was followed for 1 year through a series of structured telephone interviews . Objective . To determine the effectiveness of a Workers ' Compensation Board‐sponsored early , active , exercise and education program based in the community in comparison to " usual " care . Summary of Background Data . The program established in 1990 was available in more than 100 clinics . Results from an earlier pilot study indicated lower overall cl aims costs for workers attending the program compared with non‐attenders . Methods . Subjects were recruited at the time of Workers ' Compensation Board cl aim registration . Routinely collected data and self‐reported responses to demographic , quality ‐of‐life , functional status , pain , recovery expectations , and workplace response to injury questions were used to determine selection factors for community clinic attendance . Economic and non‐economic outcomes were compared for clinic attenders and non‐attenders . Results . For the 885 male and female new back problem cases in the study , overall clinic attenders were not systematic ally different from non‐attenders at baseline . Analysis of duration of benefits showed no significant difference between attenders and non‐attenders , although health care costs for clinic attenders were significantly higher . Functional status , health‐related quality ‐of‐life , and pain measures all improved significantly throughout time for both groups , bit there were no statistically significant differences in rate of improvement . Conclusion . There was no advantage from the program compared with usual care on the outcomes measured‐a finding consistent with recent studies that examined the longer‐term effectiveness of other interventions in the first few weeks of back pain symptoms 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 Study Design . Population ‐based r and omized clinical trial . Objectives . To develop and test a model of management of subacute back pain , to prevent prolonged disability . Summary of Background Data . The present management of back pain seems inadequate , and development of innovative models has been urged . Methods . A model for the treatment of subacute work‐related back pain has been developed and evaluated in a population ‐based r and omized clinical trial . Workers ( n = 130 ) from eligible workplaces in the Sherbrooke area ( N = 31 ) , who had been absent from work for more than 4 weeks for back pain , were r and omized , based on their workplace , in one of four treatment groups : usual care , clinical intervention , occupational intervention , and full intervention ( a combination of the last two ) . The duration of absence from regular work and from any work was evaluated using survival analysis . Functional status and pain were compared at study entry and after 1 year of follow‐up . Results . The full intervention group returned to regular work 2.41 times faster than the usual care intervention group ( 95 % confidence interval 1.19‐4.89 ; P = 0.01 ) . The specific effect of the occupational intervention accounted for the most important part of this result , with a rate ratio of return to regular work of 1.91 ( 95 % confidence interval = 1.18‐3.10 ; P < 0.01 ) . Pain and disability scales demonstrated either a statistically significant reduction or a trend toward reduction in the three intervention groups , compared with the trend in the usual care intervention group . Conclusions . Close association of occupational intervention with clinical care is of primary importance in impeding progression toward chronicity of low back pain Introduction Return to work following an occupational injury is a multifactoral process although many traditional clinic-based rehabilitation programs do not appreciate the importance of workplace factors . A r and omized controlled trial was conducted to investigate the effect of workplace-based rehabilitation program on the return to work outcome of work-related rotator cuff disorder , which is based on the therapeutic use of actual work facilities and work environment . Methods A total of 103 workers were recruited and r and omly assigned into Clinic-based Work Hardening ( CWH ) or Workplace-based Work Hardening ( WWH ) groups . The CWH group were given traditional generic work hardening training while WWH group received workplace-based work hardening training with rehabilitative principles of athletic rotator cuff pathology , biomechanics and specific job activities . Results After four weeks , a higher return to work rate was obtained in WWH group compared to CWH group ( 71.4 % vs. 37 % , p < 0.01 ) . A statistically significant difference ( p < 0.05 ) was also noted in lowering of self-reported shoulder problems and functional work capabilities in the WWH group versus the CWH group . Conclusion Workplace-based rehabilitation program appeared to be more effective in facilitating the return to work process of the injured worker as assessed immediately following intervention . In particular this approached was associated with many of the psychosocial workplace factors related to separation from the work routine . The influence of peer group and /or employer could be minimized . This initial attempt with rotator cuff injuries appears promising however long-term outcome needs to be determined Low back pain patients ( n=142 ) on sick leave for at least 8 weeks were given a multi-modal cognitive behavioural treatment program ( MMCBT ) that lasted for 4 weeks . Before treatment , all patients were tested with a comprehensive test battery . The outcome at 12-month follow-up was predictable from the pretest , but only when combining medical and psychological data . Patients who returned to work ( Returners , 50 % ) in the MMCBT group were characterised by less pain , more psychological strength , were evaluated by the physiotherapist as having a good prognosis for return to work , and were less educated . Patients who did not return to work ( Non-returners ) in the MMCBT group felt tense and unfit , felt hopelessness concerning the future , were less physically active , thought their complaints would worsen if they continued working , and reported fewer difficulties driving a car . Returners to work ( 58 % ) in the r and omised control group ( n=81 ) , who received ordinary physical therapy , were characterised by high levels of energy , less subjective health complaints , less exhaustion for a condition test , and did not work in positions giving a constant load on the back . There was no significant differences between number of patients who had returned to work in the MMCBT and the control group . Non-returners in the control group lacked energy , trained less regularly , worked in occupations that gave an almost constant load on the back , and did not expect to be back to work in the course of a couple of weeks . It seems to be important to develop further diagnostic tools to identify those who might benefit from extensive or specific treatments . Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain 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 controlled trial . Objectives . To compare high- and low-intensity back schools with usual care in occupational health care . Summary of Background Data . The content and intensity of back schools vary widely and the method ologic quality of r and omized controlled trials is generally weak . Until now , no back school has proven to be superior for workers sick-listed because of subacute nonspecific low back pain . Methods . Workers ( n = 299 ) sick-listed for a period of 3 to 6 weeks because of nonspecific low back pain were recruited by the occupational physician and r and omly assigned to a high-intensity back school , a low-intensity back school , or care as usual . Outcome measures were days until return to work , total days of sick-leave , pain , functional status , kinesiophobia , and perceived recovery and were assessed at baseline and at 3 and 6 months of follow-up . Principal analyses were performed according to the intention-to-treat principle . Results . We r and omly allocated 299 workers . Workers in the low-intensity back school returned to work faster compared with usual care and the high-intensity back school , with hazard ratios of 1.4 ( P = 0.06 ) and 1.3 ( P = 0.09 ) , respectively . The comparison between high-intensity back school and usual care result ed in a hazard ratio of 1.0 ( P = 0.83 ) . The median number of sick-leave days was 68 , 75 , and 85 in the low-intensity back school , usual care , and high-intensity back school , respectively . Beneficial effects on functional status and kinesiophobia were found at 3 months in favor of the low-intensity back school . No substantial differences on pain and perceived recovery were found between groups . Conclusions . The low-intensity back school was most effective in reducing work absence , functional disability , and kinesiophobia , and more workers in this group scored a higher perceived recovery during the 6-month follow-up Background Long-term sick leave has been of concern to politicians and decision-makers in Norway for several years . In the current study we assess the efficacy of a solution-focused follow-up for sick-listed employees . Methods Employees on long-term sick leave due to psychological problems or muscle skeletal pain ( n = 703 ) were invited to participate in the project . Following self-recruitment , 103 were r and omly allocated to receive solution-focused follow-up ( n = 53 ) or " treatment as usual " ( n = 50 ) . The intervention was integrated within the regular follow up of six social security offices and organised as eight weekly solution focused work sessions . Effectiveness was measured by rate of return to work and health related quality of life ( SF-36 ) . Results Intention to treat analysis showed no significant differences between the two groups for any of the outcome measures . Secondary analysis , comparing those who attended at least 50 % of the sessions with the control group revealed a significant difference in favour of the active intervention group in the SF-36 subscale of mental health ( Effect Size 0.56 , p = 0.05 ) . When comparing the subgroup of participants with psychological problems there was a significant difference in mental health in favour of the intervention group ( Effect Size 0.71 , p = 0.041 ) . Conclusion A voluntary solution-focused intervention offered by social-security offices is no more effective than regular follow up for employees on long-term sick leave due to psychological problems or muscle skeletal pain The objective of this study is to compare the costs and benefits of a grade d activity ( GA ) intervention to usual care ( UC ) for sick-listed workers with non-specific low back pain ( LBP ) . The study is a single-blind , r and omized controlled trial with 3-year follow-up . A total of 134 ( 126 men and 8 women ) predominantly blue-collar workers , sick-listed due to LBP were recruited and r and omly assigned to either GA ( N = 67 ; mean age 39 ± 9 years ) or to UC ( N = 67 ; mean age 37 ± 8 years ) . The main outcome measures were the costs of health care utilization during the first follow-up year and the costs of productivity loss during the second and the third follow-up year . At the end of the first follow-up year an average investment for the GA intervention of € 475 per worker , only € 83 more than health care utilization costs in UC group , yielded an average savings of at least € 999 ( 95 % CI : −1,073 ; 3,115 ) due to a reduction in productivity loss . The potential cumulative savings were an average of € 1,661 ( 95 % CI : −4,154 ; 6,913 ) per worker over a 3-year follow-up period . It may be concluded that the GA intervention for non-specific LBP is a cost-beneficial return-to-work intervention 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 Context Low back pain causes frequent disability and lost productive time . Contribution This r and omized trial compared a behavioral-oriented grade d activity program with usual care in 134 Dutch airline company workers who had missed work because of persistent low back pain . Grade d activity consisted of biweekly 1-hour exercise sessions with physiotherapists who emphasized operant-conditioning principles . Over 6 months of follow-up , participants in the grade d activity program missed 58 days of work , while participants receiving usual care missed 87 days . Implication s A behavioral-oriented grade d activity program returned participants with low back pain to work more often than did usual care . The Editors Nonspecific low back pain is an uncomfortable medical condition that causes frequent disability and absence from work . Most episodes of low back pain resolve fairly quickly and cause only short periods of absence from work . However , some workers with low back pain miss work for several days to weeks and are at risk for more permanent disability ( 1 ) . To reduce the individual and socioeconomic burden related to this absenteeism , we need effective intervention strategies in occupational health care setting s that promote safe and rapid return to work . One promising and often-advocated intervention strategy for workers with prolonged nonspecific low back pain is active rehabilitation that is directed toward return to normal activity and work ( 2 ) . Examples are grade d activity interventions that include physical exercise , application of operant-conditioning behavioral principals , and promotion of improved functioning and safe return to work even if pain persists ( 3 - 6 ) . In a r and omized , controlled trial , Lindstrm and colleagues ( 3 , 4 ) found that a grade d activity intervention reduced absence from work more than did traditional care in Swedish workers employed in the automobile industry . We investigate , in a second r and omized , controlled trial , whether absence from work because of low back pain is reduced more with grade d activity intervention than with traditional care in an occupational health care setting in the Netherl and s. Methods Study Design and Sample The study was a single-blind , r and omized , controlled trial in an occupational health services center ( KLM Health , Safety and Environment ) at Schiphol Airport , Amsterdam , the Netherl and s. The center provides occupational health services for all employees of a major Dutch airline ( KLM Royal Dutch Airlines ) . The source sample ( n = 20 000 ) consisted of workers who were employed in the following organizational units of the airline : baggage and aircraft turnaround services , passenger services , engineering and maintenance , cargo , and cabin and cockpit . Workers who were listed as absent from work because of low back pain were invited for a consultation with the occupational physician . Those who were thought to be eligible for inclusion were referred to the research assistant , who judged whether they met the inclusion criteria : full or partial absence from work because of nonspecific low back pain and low back pain symptoms with a minimum duration of 4 weeks in succession . The exclusion criteria were low back pain with radiation below the knee with signs of nerve-root compression ( 7 ) ; cardiovascular contraindications for physical activity , as checked according to the Physical Activities Readiness Question naire ( 8 , 9 ) ; any conflict between worker and employer with legal involvement ; or pregnancy . Workers who met the inclusion criteria were informed of the purpose and procedures of the study and were enrolled after giving informed consent . The Medical Ethical Committee of the VU University Medical Center , Amsterdam , the Netherl and s , approved the study . Treatment Allocation The participants were assigned to grade d activity or usual care on the basis of block r and omization , after prestratification for the organizational unit in the workplace from which they were recruited ( the 5 organizational units listed earlier ) and for the severity of pain symptoms ( scored on a scale of 0 to 10 ; severity scores were < 6 or 6 points ) . This result ed in a total of 10 strata . R and omized , permuted blocks of 4 allocations were generated for each stratum through a computer-generated r and om-sequence table . Opaque , sequentially numbered , sealed envelopes were prepared for each stratum by a research er who was not involved in enrolling the participants or assigning them to their groups . The envelopes contained a sheet of paper that indicated 1 of the 2 interventions . Participants learned their group assignments after a research assistant completed the baseline measurements and delivered the sealed envelopes . Blinding The research assistants who collected the data were blinded to the treatment allocation . All participants were repeatedly asked not to reveal any information about their treatment allocation . The participants and treatment providers were not blinded to treatment allocation . Interventions In the Dutch occupational health care system , occupational physicians guide disabled workers who are absent from work through their disability period . These occupational physicians are employed by occupational health services that are paid for by the companies . The occupational physicians adhere to back pain management strategies that consist of advising workers on ergonomics , prevention , and return-to-work schedules and advising and communicating with other stakeholders ( such as health care providers and representatives of the workplace ) . Disabled workers who participated in the present study were assigned to either grade d activity or usual care within the context of the Dutch occupational health care setting . Grade d Activity The intervention group received the usual guidance from the occupational physician about work-related problems and barriers to return to work as well as the grade d activity intervention supervised by a physiotherapist . Three physiotherapists who worked in a private practice at Schiphol Airport provided the treatment according to the grade d activity protocol . Two of those physiotherapists were also trained as manual therapists , and 1 was also a human movement scientist . Before the study , the physiotherapists had been specifically trained to treat patients with low back pain according to behavioral principles . A research physiotherapist who was experienced in treating patients with chronic pain in rehabilitation centers instructed the physiotherapists in three 2-hour sessions and practice d patienttherapist interactions with them through role-play . Before the study , the physiotherapists treated several patients according to the grade d activity protocol to gain more experience . The physiotherapists made audiotapes of the intervention sessions before and during the study period . The contents of these audiotapes were assessed and discussed with the research physiotherapist in 3 additional meetings . Furthermore , the physiotherapists summarized the treatment after each session , and research ers used these summaries to review the sessions . The same physiotherapist treated participants each time , except for temporary st and -in sessions that were supervised by colleagues because of holidays or other reasons . Specific therapists were not systematic ally selected to treat specific participants ; selection was based on pragmatic reasons , such as the time available in the work schedules of the physiotherapists or the days of treatment preferred by the participants . Table 1 presents the concept and content of the grade d activity intervention . The intervention consisted of 1-hour exercise sessions that participants attended twice per week until they returned completely to regular work or until the maximum therapy duration of 3 months was reached . At the start of the intervention , the physiotherapist inquired about the participant 's medical history and completed a brief physical examination consisting of flexion , extension , and lateroflexion of the lumbar spine and a brief screening for nerve-root pain ( 10 ) . The purpose of the physical examination was to confirm the diagnosis of benign , nonspecific low back pain and to reduce participants ' fears about any presumed underlying disease . The participants were reassured that despite the annoying pain , nothing was seriously wrong with their backs . Subsequently , the physiotherapist and participant decided on a set of general exercises and individually tailored exercises . Both types of exercises had to be performed during each session . The general exercises were aerobic exercises , such as cycling or rowing , and strengthening exercises for large muscle groups , and most were carried out in a gym while using exercise equipment . The strengthening exercises were a floor abdominal sit-up exercise , a dynamic back extension exercise , a leg-press exercise , a latissimus pull-down exercise , and st and ing up from a low chair . Participants in the grade d activity group had to perform not only these general exercises but also individually tailored exercises , which imitated physical tasks at work or difficult and painful activities of daily living . For example , a participant who reported back problems while lifting and moving suitcases from a luggage wagon into an airplane might be given an exercise to practice lifting and moving a suitcase with a certain number of repetitions . During the first 3 sessions , the maximal performance ( for example , the maximum number of repetitions ) was assessed for each exercise separately , and the average score for each exercise over the 3 sessions was used as a baseline value for specifying a gradually progressive exercise scheme . Subsequently , the participant was asked to propose a date for full return to regular work , which would consequently be the end point of the physical exercise program . Before returning to full regular work , participants could return to work with modified hours and duties . Advised by the physiotherapist , the participant & NA ; An outpatient multimodal cognitive‐behavioural treatment program ( MMCBT ) for chronic spinal pain was evaluated during an 18‐month follow‐up period . The treatment included a 1‐day course for the patients ’ work supervisors . The aim of the study was to evaluate the long‐term effect of the treatment program as well as the effect of a work supervisor‐training program on the patients ’ return to work . The design was a matched cohort study with four repeated measures . Two groups of subjects suffering from non‐specific spinal pain ( treatment group n=67 , no treatment control group n=29 ) were assessed with regard to pain intensity , sick‐leave , pain coping ability and behavioural changes at work and in personal life . Recordings on supervisors attending the course and changes of supervisory behaviour were also obtained . The results show a significant between group difference in pain intensity and perceived pain coping ability at work , favouring the MMCBT group . Further , the MMCBT intervention enhances self‐reported behavioural changes in areas within the subjects ’ own control . There is not sufficient statistical support to accept the assumption of MMCBT being superior in reducing sick‐leave , either with or without the education of supervisors . Even when supervisors changed their behaviour as reported by the patient , no significant effect was found on patients ’ return to work . In conclusion , the MMCBT do not seem to be effective in reducing sick‐leave compared to no treatment , but the MMCBT program is superior in decreasing pain intensity , enhancing self‐reported behavioural changes in personal life and improving pain coping ability at work The purpose of this study was to investigate the effects of a physical training course in a group of patients ( n = 74 ) suffering from chronic tension neck . All participants in the course were employed by a bank corporation in Helsinki , Finl and . A comparable control group ( n = 77 ) consisted of office workers with tension neck from the same bank corporation who did not attend any training course . The outcome was analysed 6 months after the course . Pain and disability in the neck and shoulder region did not vary significantly between the group which participated in the training course and the control group . The experimental group had increased the amount of physical workout compared to the control group ( 83.7 % vs 69.0 % , P = 0.0448 ) . Also , regarding the frequency of relaxation and stretching exercises the two groups differed significantly : the experimental group had continued to perform exercises more often ( P = 0.0434 ) . The frequency of sick leave days did not significantly differ between the groups , but the office workers in the experimental group had more periods of extended sick leave ( > 10 days ) and the controls had more frequent short sick leaves . The experimental group did increase their physical workout significantly compared with the controls , but no differences were detected regarding pain and disability . In order to gain more benefit more attention should be paid to the educational part of the training courses in order to enhance the patients ' self-care abilities . Also , strategies to alleviate psychosocial problems and organized relaxation exercises could decrease muscle tension in the neck in office workers STUDY DESIGN A prospect i ve , r and omized , controlled trial with a stratification block design in which a Mensendieck exercise program was compared with the experience of a control group . OBJECTIVE To evaluate the effect of a Mensendieck program on the incidence of recurrent episodes of low back pain in patients with a history of the condition who currently are working . SUMMARY OF BACKGROUND DATA One episode of low back pain increases the risk of further episodes of the condition . The Mensendieck approach combines education and exercise . This approach has been used for many years in Sc and inavia and the Netherl and s. However , the effects on low back pain have not been evaluated previously in a r and omized , controlled trial . METHODS A total of 77 men and women , mean age 39.6 years ( range , 21.2 - 49.8 years ) , who had finished treatment for a low back pain episode , were stratified according to incidence of low back pain episodes and symptoms of sciatica over the preceding 3 years . The patients were assigned at r and om to either the Mensendieck program or a control group . The Mensendieck group received 20 group sessions of exercises and ergonomic education in 13 weeks . At 5- and 12-month follow-up examinations , the patients were assessed for recurrence of low back pain , days of sick leave , low back pain , and functional scores . RESULTS After 12 months , there was a significant reduction in recurrent low back pain episodes in the Mensendieck group compared with the control group ( P < 0.05 ) . There was a trend toward fewer days of sick leave because of low back pain in the Mensendieck group , but no significant differences between the groups . There was reduction in pain and improvement in function in both groups , with no significant differences between the groups . CONCLUSIONS A secondary prophylaxis Mensendieck exercise program of 20 group sessions significantly reduced the incidence of low back pain recurrences in a population with history of the condition . However , there were no differences between the groups with regard to days of sick leave , low back pain , and function This prospect i ve controlled study examined changes in fitness , health , and work ability after a work-oriented physical fitness course arranged for lumberjacks experiencing low back pain but being still at work . The 1-week courses were design ed to activate exercising during leisure time and consisted of fitness tests , various types of exercise , and lectures . Eighty-seven lumberjacks participated in the courses and 61 subjects served as controls . Question naire data obtained before and 1 year after the course were available for 78 ( 90 % ) of the course participants and 41 ( 67 % ) of the controls . In the intervention group , perceived fitness , health , and work ability improved and ergonomic strain at work decreased . Both groups reported an increased frequency of leisure-time physical activity . There were between- group differences in the development of fitness , health , distress symptoms , and subjective work ability , whereas the changes in physical activity , back and musculoskeletal symptoms , or ergonomic strain did not differ between the groups . In a 6-month follow up , muscle function improved in the intervention group , but no change was observed in aerobic capacity . There was a tendency of the number of back pain-related sickness leaves , but not of their duration , to develop more favorably in the intervention group , when data from the year before and the year after the course were compared Study Design . A subgroup of 195 patients with chronic low back pain , being part of a larger study of other musculoskeletal patients , were included in a r and omized controlled prospect i ve clinical study . Objectives . To evaluate the outcome in terms of return to work and cost-effectiveness of a light multidisciplinary treatment program with an extensive multidisciplinary program and treatment as usual initiated by their general practitioner . Summary of Background Data . Light multidisciplinary programs seem to reduce sick leave in patients with subacute low back pain . There are few , if any , previous studies of the effectiveness of light versus extensive multidisciplinary treatment on return to work in patients with chronic low back pain . Methods . Patients with chronic low back pain ( n = 195 ) , on an average sick-listed for 3 months , were included . The patients were r and omized to a light multidisciplinary treatment program , an extensive multidisciplinary program , or treatment as usual by their primary physician . Full return to work was used as outcome response , and follow-up was 26 months after the end of treatment . Cost – benefit was calculated for the treatment programs . Results . In men significantly better results for full return to work were found for the light multidisciplinary treatment compared with treatment as usual , but no differences were found between extensive multidisciplinary treatment and treatment as usual . No significant differences between any of the two multidisciplinary treatment programs and the controls were found for women . Productivity gains for the society from light multidisciplinary treatment versus “ treatment as usual ” of 57 male patients with low back pain would during the first 2 years accumulate to U.S. $ 852.000 . Conclusions . The light multidisciplinary treatment model is a cost-effective treatment for men with chronic low back pain Objective : To determine the effectiveness and cost-effectiveness of a return-to-work outpatient multidisciplinary treatment programme for sick-listed workers with non-specific upper extremity musculoskeletal complaints . Methods : A r and omized controlled trial with a 1-year follow-up was carried out . Thirty-eight subjects were allocated to multidisciplinary treatment ( intervention , n=23 ) , or to usual care provided by occupational health services ( n=15 ) . The intervention consisted of psychological and physical sessions provided by a medical specialist , a psychologist , a physiotherapist and an occupational therapist . It aims at reconditioning , “ de-medicalizing ” , unrestrained moving and return-to-work . The intervention process was evaluated on compliance to the protocol and the effectiveness of its components . The individual outcome variable was the severity of complaints . The societal outcomes included return-to-work and costs . Measurements were performed at baseline and after 2 , 6 and 12 months . Mixed model analyses were used for analysis . Results : The intervention achieves its aims : physical disabilities ( P=0.039 ) , kinesiophobia ( P<0.001 ) and physical functioning ( P=0.016 ) improved significantly as compared to usual care . In addition , the intervention was significantly more effective in reducing the severity of complaints than usual care . The intervention was equally effective compared to usual care in terms of return-to-work ( 86 % in the intervention group vs. 73 % in the usual care group ) . The extra total costs and the extra gains in terms of return-to-work were not significantly higher for the intervention as compared to usual care after 12 months . Conclusion : Multidisciplinary treatment affects individuals positively , but shows no significant difference in ( cost- ) effectiveness on the societal level as compared to usual care Objectives Given the individual and economic burden of chronic work disability in low back pain patients , there is a need for effective preventive interventions . The aim of the present study was to investigate whether problem-solving therapy had a supplemental value when added to behavioral grade d activity , regarding days of sick leave and work status . Design R and omized controlled trial . Patients and Setting Employees who were recently on sick leave as a result of nonspecific low back pain were referred to the rehabilitation center by general practitioner , occupational physician , or rehabilitation physician . Forty-five employees had been r and omly assigned to the experimental treatment condition that included behavioral grade d activity and problem-solving therapy ( GAPS ) , and 39 employees had been r and omly assigned to behavioral grade d activity and group education ( GAGE ) . Outcome Measures Days of sick leave and work status . Data were retrieved from occupational health services . Results Data analyses showed that employees in the GAPS group had significantly fewer days of sick leave in the second half-year after the intervention . Moreover , work status was more favorable for employees in this condition , in that more employees had a 100 % return-to-work and fewer patients ended up receiving disability pensions one year after the intervention . Sensitivity analyses confirmed these results . Conclusions The addition of problem-solving therapy to behavioral grade d activity had supplemental value in employees with nonspecific low back pain A r and omised controlled study with the objective to explore the effects of a group learning programme based on a phenomenological epistemology and personal construct theory . Main outcome measures were : experienced pain , pain coping strategies , absenteeism , disability pension and health care consumption . One hundred and twenty-one patients with chronic musculoskeletal pain and high absenteeism were included in this study . The intervention group ( n=77 ) consisted of nine smaller groups with 6 - 10 persons in each and were counselled by health personnel with special training . The control group consisted of 44 persons . The learning programme emphasised awareness , possible relations between bodily symptoms , emotions , mind and life situation , and change of focus from pain and disability to re sources and potentials . One year after the end of the learning programme ( T3 ) , patients in the intervention group reported significant pain reduction , increased pain-coping abilities and a higher reduction of health care consumption than the control group ( P<0.05 ) . Absenteeism was not significantly reduced compared to the control group , but there were fewer persons receiving disability pension in the intervention group at T3 ( 38 versus 59 % ) ( P<0.05 ) . This group-learning programme should be considered an important adjunct to the therapy of patients with chronic muscular pain The purpose of this study was to compare the effect of the McKenzie method of treatment with patient education in “ mini back school ” in patients with acute low-back pain . The study included 100 patients , 23 women and 77 men with the average age 34.4 ± 9.7 ( range 18 - 61 ) years . The study included only those who were employed . The patients were r and omly allocated to two groups , one group receiving treatment according to the McKenzie technique and the other group receiving education in a “ mini back school . ” Assessment s were made after 3 weeks by an independent observer and after 52 weeks they were seen by one of the authors . Patients were assessed on seven variables : return to work , sick-leave during the initial episode , sick-leave during recurrences , recurrences of pain during the year of observation , patients ' ability to self-help , pain and movement . Although the effect of attention placebo can not be ruled out , the results demonstrated that the McKenzie method of treatment for patients with acute low-back pain was superior for five out of seven variables studied . The only variables that did not show any statistically significant differences were sick-leave during recurring episodes of pain and patients ' ability to self-help This study was design ed to evaluate the effectiveness of a multidisciplinary rehabilitation programme offered to a general population with 90 days of sick-leave due to non-specific musculoskeletal pain . The results concerning return to work and re-sick-listing during a follow-up period of five years were evaluated for Swedes and immigrants separately . Compared to a control group , the rehabilitation offer result ed in improved work stability after work return among the Swedes . The immigrants , as a group , did not benefit from the programme compared to the controls in primary care & NA ; The aim of the present study was to evaluate the long‐term outcome of a behavioural medicine rehabilitation programme and the outcome of its two main components , compared to a ‘ treatment‐as‐usual ’ control group . The study employed a 4 × 5 repeated‐ measures design with four groups and five assessment periods during a 3‐year follow‐up . The group studied consisted of blue‐collar and service/care workers on sick leave , identified in a nationwide health insurance scheme in Sweden . After inclusion , the subjects were r and omised to one of the four conditions : behaviour‐oriented physiotherapy ( PT ) , cognitive behavioural therapy ( CBT ) , behavioural medicine rehabilitation consisting of PT+CBT ( BM ) and a ‘ treatment‐as‐usual ’ control group ( CG ) . Outcome variables were sick leave , early retirement and health‐related quality of life . A cost‐effectiveness analysis , comparing the programmes , was made . The results showed , consistently , the full‐time behavioural medicine programme being superior to the three other conditions . The strongest effect was found on females . Regarding sick leave , the mean difference in the per‐ protocol analysis between the BM programme and the control group was 201 days , thus reducing sick leave by about two‐thirds of a working year . Rehabilitating women has a substantial impact on costs for production losses , whereas rehabilitating men seem to be effortless with no significant effect on either health or costs . In conclusion , a full‐time behavioural medicine programme is a cost‐effective method for improving health and increasing return to work in women working in blue‐collar or service/care occupations and suffering from back/neck pain 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 Study Design . A multicenter , r and omized , single‐blinded controlled trial with 1‐year follow‐up . Objectives . To evaluate the efficiency of progressively grade d medical exercise therapy , conventional physiotherapy , and self‐exercise by walking in patients with chronic low back pain . Summary and Background Data . Varieties of medical exercise therapy and conventional physiotherapy are considered to reduce symptoms , improve function , and decrease sickness absence , but this opinion is controversial . Methods . Patients with chronic low back pain or radicular pain sick‐listed for more than 8 weeks and less than 52 weeks ( Sickness Certificate II ) were included . The treatment lasted 3 months ( 36 treatments ) . Pain intensity , functional ability , patient satisfaction , return to work , number of days on sick leave , and costs were recorded . Results . Of the 208 patients included in this study , 71 were r and omly assigned to medical exercise therapy , 67 to conventional physiotherapy , and 70 to self‐exercise . Thirty‐three ( 15.8 % ) patients dropped out during the treatment period . No difference was observed between the medical exercise therapy and conventional physiotherapy groups , but both were significantly better than self‐exercise group . Patient satisfaction was highest for medical exercise therapy . Return to work rates were equal for all 3 intervention groups at assessment 15 months after therapy was started , with 123 patients were back to work . In terms of costs for days on sick leave , the medical exercise therapy group saved 906,732 Norwegian Kroner ( NOK ) ( $ 122,531.00 ) , and the conventional physiotherapy group saved NOK 1,882,560 ( $ 254,200.00 ) , compared with the self‐exercise group . Conclusions . The efficiency of medical exercise therapy and conventional physiotherapy is shown . Leaving patients with chronic low back pain untampered poses a risk of worsening the disability , result ing in longer periods of sick leave & NA ; In general , r and omized controlled studies concerning return to work have failed to demonstrate significant treatment effects for long‐lasting musculoskeletal pain , and most treatments examined have not been economically beneficial . Individuals ( n=654 ) sick‐listed for at least 8 weeks with musculoskeletal pain , selected from the Norwegian m and atory sickness insurance system and volunteering to participate , were categorized into three groups differing in a prognosis score ( good , medium , poor ) for return to work , based on a brief , st and ardized screening of psychological and physiotherapy findings . They were then r and omly assigned to three outpatient treatments with three different levels of intensity ( ordinary treatment , light multidisciplinary , and extensive multidisciplinary treatment ) . The evaluation was based on 14 months follow‐up data on return to work collected from social security records . The patients with good prognosis for return to work do equally well with ordinary treatment as with the two more intensive treatments . The patients with medium prognosis benefit equally from the two multidisciplinary treatments . The patients with poor prognosis receiving extensive multidisciplinary treatment returned to work at a higher rate than patients with poor prognosis receiving ordinary treatment , 55 vs. 37 % ( P<0.05 ) at 14 months . Multidisciplinary treatment is effective concerning return to work , when given to patients who are most likely to benefit from that treatment . Measures of pain or quality of life are not included in this study . The cost – benefit analysis of the economic returns of the light multidisciplinary and the extensive multidisciplinary treatment programs yields a positive net present social value of the treatment . A simple , st and ardized , screening instrument including only psychological and physiotherapeutic observations may be a useful clinical tool for allocating patients with musculoskeletal pain to the right level of treatment Sickness absenteeism caused by musculoskeletal disorders ( MSDs ) is a persistent and costly occupational health challenge . In a prospect i ve controlled trial , we compared the effects on sickness absenteeism of a more proactive role for insurance case managers as well as workplace ergonomic interventions with that of traditional case management . Patients with physician-diagnosed MSDs were r and omized either to the intervention group or the reference group offered the traditional case management routines . Participants filled out a comprehensive question naire at the initiation of the study and after 6 months . In addition , administrative data were collected at 0 , 6 , and 12 months after the initiation of the project . For the entire 12-month period , the total mean number of sick days for the intervention group was 144.9 ( SEM 11.8 ) days/person as compared to 197.9 ( 14.0 ) days in the reference group ( P < 0.01 ) . Compared with the reference group , employees in the intervention group significantly more often received a complete rehabilitation investigation ( 84 % versus 27 % ) . The time for doing this was reduced by half ( 59.4 ( 5.2 ) days versus 126.8 ( 19.2 ) , P < .01 ) . The odds ratio for returning to work in the intervention group was 2.5 ( 95 % confidence interval 1.2–5.1 ) as compared with the reference group . The direct cost savings were USD 1195 per case , yielding a direct benefit-to-cost ratio of 6.8 . It is suggested that the management of MSDs should to a greater degree focus on early return to work and building on functional capacity and employee ability . Allowing the case managers a more active role as well as involving an ergonomist in workplace adaptation meetings might also be beneficial Objective : To evaluate the cost-effectiveness and cost-utility of a return to work ( RTW ) program for workers on sick-leave due to low back pain ( LBP ) , comparing a workplace intervention implemented between 2 to 8 weeks of sick-leave with usual care , and a clinical intervention after 8 weeks of sick-leave with usual care . Design : Economic evaluation alongside a r and omised controlled trial ( RCT ) . Study population : Workers sick-listed for a period of 2 to 6 weeks due to LBP . Interventions : 1 . workplace assessment , work modifications and case management ) . 2 . physiotherapy based on operant behavioural principles . 3 . usual care : provided by an occupational physician . Outcomes : The primary outcome was return to work ( RTW ) . Other outcomes were pain intensity , functional status , quality of life and general health . The economic evaluation was conducted from a societal perspective . Outcomes were assessed at baseline ( after 2–6 weeks on sick-leave ) , and 12 weeks , 26 weeks , and 52 weeks after the first day of sick-leave . Results : The workplace intervention group returned to work 30.0 days ( 95 % CI=[3.1 , 51.3 ] ) earlier on average than the usual care group at slightly higher direct costs ( ratio of 1 day : € 19 ) . Workers in the clinical intervention group that had received usual care in the first 8 weeks returned to work 21.3 days ( 95 % CI= [ −74.1 , 29.2 ] ) later on average . The group that had received the workplace intervention in the first 8 weeks and the clinical intervention after 8 weeks returned to work 50.9 days ( 95 % CI=[−89.4 , −2.7 ] ) later on average . A workplace intervention was more effective than usual care in RTW at slightly higher costs and was equally effective as usual care at equal costs on other outcomes . A clinical intervention was less effective than usual care and associated with higher costs . Conclusion : The workplace intervention results in a safe and faster RTW than usual care at reasonable costs for workers on sick-leave for two to six weeks due to LBP OBJECTIVE The objective of this study was to determine the effectiveness of a training to increase collaboration between general practitioners and occupational health physicians in the treatment of patients with low back pain ( LBP ) because more collaboration might improve a patient 's recovery and shorten sick leave . METHODS In a controlled trial , the intervention in one region was compared with usual care in a control region . Participating physicians enrolled patients with LBP on sick leave for 3 - 12 weeks . Patients filled out three question naires : at inclusion , at 3 months , and at 6 months . Information on sick leave was gathered from occupational health services . All analyses were performed on an intention-to-treat basis . RESULTS Fifty-six patients with LBP were enrolled in each region . There was little collaboration between physicians during the project . Patients in the intervention region returned to work significantly later ( P=.005 ) but were significantly more satisfied with their occupational health physician ( P=.01 ) . No differences were found between the intervention and control patients for pain , disability , quality of life , and medical consumption . CONCLUSION Our study does not show a positive effect of the training to increase collaboration between general practitioners and occupational health physicians . The training may not have improved collaboration enough to influence the prognosis of LBP Context Lumbar supports are commonly used to prevent low back pain , but evidence on their effectiveness is lacking . Contribution This trial assigned 360 home care workers with a history of low back pain to a short course on healthy work habits , with or without worker-directed use of a lumbar support . Over 12 months , participants assigned to lumbar support had a similar number of sick days but fewer days with low back pain than did those assigned to the course only . Implication Adding lumbar supports to instruction on healthy work habits may decrease low back pain recurrence , but not absenteeism , among workers with previous low back pain . The Editors Low back pain is a common problem that results in high medical expenses , work absenteeism , and disability ( 1 ) . The reported 1-year prevalence ranges from 15 % to 40 % in a general population ( 2 ) and from 44 % to 72 % among home care workers ( 3 , 4 ) . Various ergonomic aids are marketed for the prevention of low back pain . Workers frequently use lumbar supports to prevent back pain ( 5 ) , but the effectiveness of such supports remains unclear . Recent systematic review s of the sparse evidence on lumbar supports ( 6 , 7 ) concluded that no evidence exists for the effectiveness of lumbar supports in the primary prevention of low back pain in the workplace , but 2 of the 4 included r and omized , controlled trials ( 8 , 9 ) reported that lumbar supports might be effective in workers with a history of low back pain ( secondary prevention ) . However , these findings were derived from subgroup analyses , and evidence from direct research on secondary prevention was not available . In cohort studies , a history of low back pain proved to be a strong predictor for the incidence of new episodes of low back pain ( 1012 ) . Home care workers with a history of low back pain may therefore be well suited to secondary preventive measures . In a previous uncontrolled feasibility study , we found that home care workers who had frequent episodes of low back pain reported adherence rates of 61 % to 81 % with lumbar supports and a 45 % decrease in pain intensity when using lumbar supports ( 13 ) . We design ed the current trial to evaluate the effectiveness of adding worker-directed use of lumbar supports to a short course on healthy working methods to reduce low back pain and work absenteeism among home care workers with a history of low back pain . Methods Design Our r and omized , controlled trial included 2 groups . The control group received a short refresher course on healthy working methods provided by their employer at the start of their employment ( Appendix ) ; primary and secondary care for the management of low back pain was available as usual ( 14 ) . The intervention group received a lumbar support in addition to usual care . The intervention and data collection continued for 12 months after enrollment . The Medical Ethical Committee of the Erasmus University Medical Center , Rotterdam , the Netherl and s , approved the study . Participants All participants were recruited from employees of a large home care organization in Rotterdam . During staff meetings , all present team members completed a brief survey about study inclusion criteria that was distributed and collected by the team managers . We included persons who performed medical care or domestic tasks as a home care worker , were experiencing low back pain symptoms at the time of inquiry or had experienced 2 or more episodes ( on 2 consecutive days ) of low back pain symptoms in the 12 months before the inquiry , did not have specific low back pain ( for example , due to rheumatoid arthritis or vertebral fractures ) , and were not pregnant at the start of the study . Because of a possible association between lumbar supports and increased blood pressure and heart rate , we excluded workers receiving medical treatment for high blood pressure ( 15 ) . Employees who met the inclusion criteria received detailed information about the trial , and those who agreed to participate provided written consent . R and omization In the Netherl and s , home care workers provide 1 of 8 functions , each of which requires different skills and tasks . To ensure a balance in workload and working conditions between the 2 study groups , we stratified r and omization by these 8 functions . We also stratified r and omization by low back pain experience at baseline ( current pain vs. past pain ) . The r and omization process used a computer-generated r and om-number table with 16 strata ( 2 low back pain by 8 workplace functions ) , arranged in blocks of 8 within each stratum . After baseline measurements were completed , colleagues who were not otherwise involved in the study and who were blinded to participants ' baseline characteristics used the r and om-number table to allocate each participant to 1 of the study groups . Intervention All participants in the intervention group were instructed to wear the lumbar supports on working days on which they had or expected they might develop low back pain . Participants could select 1 of 4 types of lumbar supports , supplied by Bauerfeind B.V. , Haarlem , the Netherl and s. LumboTrain and LumboTrain Lady are individually adjustable , hook- and -loop fastening , fully elastic supports that are available in 5 sizes for men or women . LumboLoc and LordoLoc are more structured supports , with integrated stays in the back , that have individually adjustable hook- and -loop fastenings and are available in 6 sizes . Participants chose the lumbar support on the basis of fit and wearing comfort , and they were not given advice to direct their choice from among the 4 available supports . When measured by the research er for the lumbar support , the participants were advised to wear the support for a few days in a row , regardless of low back pain , in order to become accustomed to it . The expected duration of wearability of the lumbar supports was 1 year . The costs of the lumbar supports were 75 for LumboTrain and LumboTrain Lady , 56 for LumboLoc , and 50 for LordoLoc . Outcome Measures Our primary outcome measures were the number of days that participants reported low back pain per month and the number of calendar days of sick leave that participants took during the 12-month intervention . Secondary outcome measures were the average severity of low back pain in the previous week , rated on a scale of 0 to 10 ( 16 ) , and functional status in the previous week , measured by using a Dutch translation of the Quebec Back Pain Disability Scale ( on which 0 corresponds to no disablement and 100 corresponds to fully disabled ) ( 17 , 18 ) . Participants used a calendar to record the days per month on which they experienced low back pain . The intervention group was also asked to record on the calendar whether they had worn the lumbar support ; thus , the calendars also served as a monitor for adherence to therapy . The calendars were collected for review after 1 , 3 , 6 , 9 , and 12 months . The number of calendar days of sick leave was derived from the staff register and was provided by the home care organization at the end of the study ; this information covered 15 months , from 3 months before the start of the study until the end of the intervention . We could gather only general data on sick leave because employees are not obliged to specify their illness for the employer when they report themselves ill , and registration by a company doctor starts from 6 consecutive weeks of sick leave . We collected information on self-reported , low back painrelated sick leave ; however , this was not a predetermined outcome , and the results should be interpreted cautiously . We administered a question naire at baseline to obtain information on the secondary outcome measures and demographic characteristics ; history of low back pain ; job characteristics ( among others , the Job Content Question naire , Dutch translation [ 19 ] ) ; and other possible confounders , such as additional work ( hours per week and type ) , preference for study group assignment , confidence in pain reduction with use of the lumbar support ( scale of 0 to 10 ) , and confidence in improved functioning ( scale of 0 to 10 ) . Follow-up question naires were administered at 3 , 6 , 9 , and 12 months to measure the secondary outcomes . In the intervention group , these question naires also measured the general satisfaction with the lumbar support ( scale of 0 to 10 ) , several items on comfort of wearing ( 5-point Likert scale ) , and adherence to use of the lumbar support ( 7-point Likert scale ) . We recorded spontaneously reported side events and asked participants about side effects in the question naires . Statistical Analysis We estimated that with a power of 80 % , a significance level of 0.05 , and an SD of 20 days , we would need 140 participants in each study group to demonstrate a difference of 7 days of low back pain per year or sick leave per year between the 2 groups . To prevent inadequate power because of participant withdrawal or low adherence to therapy , we sought to enroll 400 home health care workers . We used a longitudinal marginal model with generalized estimating equation estimates to analyze the data , according to intention-to-treat principles . For the primary outcomes ( number of days of low back pain and number of days of sick leave ) , we used a negative-binomial count data model with a log-link and an exchangeable correlation structure . Covariates ( history of low back pain , body mass index , additional work , and pregnancy during follow-up ) were added to the model separately and were used in the final model if they statistically significantly contributed to the model ( P < 0.05 ) . The scale scores of the secondary outcomes were analyzed by using a normal distributed model and an exchangeable correlation structure . To investigate model misspecification and the effect of missing data , we performed sensitivity analyses in which we used various structures for the working correlation to estimate the models and used multiple imputation techniques to analyze 5 imputed data sets for missing data ( 20 ) . For all analyses , we used SAS , The aim of this paper was to study the physical performance , pain , pain behavior and disability in patients with subacute low back pain ( LBP ) . The patients were blue-collar workers and had been sick-listed for 8 weeks due to subacute low back pain . A total of 103 patients were r and omized , 51 of them to the intervention group and the other to a control group . Recordings of physical performance and complaints of LBP were done before and after treatment in the intervention group . The proportion of patients with no complaints of LBP was significantly greater in the intervention group than in the control group at the one-year follow-up . The patients who intra-individually improved their physical performance also intra-individually decreased their complaints of LBP . The intra-individual improvements were suggested to be important for the individual return to work Study Design . A prospect i ve , r and omized controlled trial . Objective . To examine long-term effects and costs of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain ( cLBP ) . Summary of Background Data . An obvious gap exists in knowledge concerning long-term efficacy and cost-effectiveness of manipulative treatment methods . Methods . Of 204 patients with cLBP whose Oswestry Disability Index ( ODI ) was at least 16 % , 102 were r and omized into a combined manipulative treatment , exercise , and physician consultation group ( i.e. , a combination group ) , and 102 to a consultation alone group . All patients were clinical ly examined , informed about their back pain , and encouraged to stay active and exercise according to specific instructions based on clinical evaluation . Treatment included 4 sessions of manual therapy and stabilizing exercises aim ed at correcting the lumbopelvic rhythm . Question naires inquired about pain ( visual analog scale [ VAS ] ) , disability ( ODI ) , health-related quality of life ( 15D Quality of Life Instrument ) , satisfaction with care , and costs . Results . Significant improvement occurred in both groups on every self-rated outcome measurement . Within 2 years , the combination group showed only a slightly more significant reduction in VAS ( P = 0.01 , analysis of variance ) but clearly higher patient satisfaction ( P = 0.001 , Pearson & khgr;2 ) as compared to the consultation group . Incremental analysis showed that for combined group compared to consultation group , a one-point change in VAS scale cost $ 512 . Conclusions . Physician consultation alone was more cost-effective for both health care use and work absenteeism , and led to equal improvement in disability and health-related quality of life . It seems obvious that encouraging information and advice are major elements for the treatment of patients with cLBP & 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 Background : The lack of efficient medical interventions for combating increasing sickness absence rates has lead to the introduction of alternative measures initiated by the Norwegian National Insurance Service or at workplaces . Aim : To determine whether minimal postal intervention had any effect on the length of sick leave . Methods : R and omised , controlled trial with a one year follow up in Northern Norway in 1997 and 1998 ; 990 consecutive newly sick-listed persons with musculoskeletal or mental disorders were studied . Within the intervention group , 495 eligible sick-listed persons received a general information letter and a question naire as their sick leave passed 14 days . Possible intervention effects were analysed by survival analysis of the probability of returning to work within one year , and logistic regressions with benefits at one year as the dependent variable . Results : The overall reduction of 8.3 ( 95 % CI −22.5 to 6.0 ) calendar days in mean length of sick leaves in the intervention group compared to controls , was not statistically significant . However , intervention significantly reduced length of sick leaves in subgroups with mental disorders , and with rheumatic disorders and arthritis , and overall for sick leaves lasting 12 weeks or more . Young people with low back pain showed an adverse effect to intervention . The overall relative risk of receiving benefits due to sickness after one year in the intervention group was 0.69 ( 95 % CI 0.51 to 0.93 ) compared to controls . Conclusion : The results should encourage employers , insurance institutions , and authorities to initiate challenges as questions on the length of sick leave and possible modified work measures , during the first few weeks of sick leave , for at least some groups of sick-listed persons Study design . Population -based r and omized controlled trial . Objective . To assess the effectiveness of workplace intervention and grade d activity , separately and combined , for multidisciplinary rehabilitation of low back pain ( LBP ) . Summary of Background Data . Effective components for multidisciplinary rehabilitation of LBP are not yet established . Methods . Participants sick-listed 2 to 6 weeks due to nonspecific LBP were r and omized to workplace intervention ( n = 96 ) or usual care ( n = 100 ) . Workplace intervention consisted of workplace assessment , work modifications , and case management involving all stakeholders . Participants still sick-listed at 8 weeks were r and omized for grade d activity ( n = 55 ) or usual care ( n = 57 ) . Grade d activity comprised biweekly 1-hour exercise sessions based on operant-conditioning principles . Outcomes were lasting return to work , pain intensity and functional status , assessed at baseline , and at 12 , 26 , and 52 weeks after the start of sick leave . Results . Time until return to work for workers with workplace intervention was 77 versus 104 days ( median ) for workers without this intervention ( P = 0.02 ) . Workplace intervention was effective on return to work ( hazard ratio = 1.7 ; 95 % CI , 1.2–2.3 ; P = 0.002 ) . Grade d activity had a negative effect on return to work ( hazard ratio = 0.4 ; 95 % CI , 0.3–0.6 ; P < 0.001 ) and functional status . Combined intervention had no effect . Conclusion . Workplace intervention is advised for multidisciplinary rehabilitation of subacute LBP . Grade d activity or combined intervention is not advised OBJECTIVE To identify subgroups of workers absent from work due to low back pain who are more or less likely to return to work earlier as a result of a grade d activity intervention , and to investigate whether this intervention is effective in reducing pain-related fears and if so , whether these reductions in pain-related fears mediate return to work . METHODS A subgroup analysis was conducted on data from a previous r and omized controlled trial of 134 Dutch airline workers , which found that a behaviorally-oriented grade d activity intervention was more effective than usual care in stimulating return to work . The subgroup analyses added interaction terms to a Cox regression model that described the relationship between treatment allocation and return to work over 12 months of followup . Furthermore , we studied the effects of grade d activity on pain-related fears and added variables indicating a reduction in pain-related fears to the model in order to investigate their influence on return to work . RESULTS Statistically significant interactions were found for disability , fear-avoidance beliefs about physical activity , and fear-avoidance beliefs about work . No indication was found that the reduction in pain-related fears in the grade d activity group mediated more favorable return-to-work results in this group . CONCLUSION Workers who perceive their disability to be moderate and workers with moderate scores for fear-avoidance beliefs return to work more rapidly as a result of the grade d activity intervention than workers with higher scores . The return to work of workers receiving the grade d activity intervention is possibly independent from the reductions in pain-related fears caused by this intervention Introduction In Denmark , the magnitude and impact of work disability on the individual worker and society has prompted the development of a new “ coordinated and tailored work rehabilitation ” ( CTWR ) approach . The aim of this study was to compare the effects of CTWR with conventional case management ( CCM ) on return-to-work of workers on sick leave due to musculoskeletal disorders ( MSDs ) . Methods The study was a r and omized controlled trial with economic evaluation undertaken with workers on sick leave for 4–12 weeks due to MSDs . CTWR consists of a work disability screening by an interdisciplinary team followed by the collaborative development of a RTW plan . The primary outcome variable was registered cumulative sickness absence hours during 12 months follow-up . Secondary outcomes were work status as well as pain intensity and functional disability , measured at baseline , 3 and 12 months follow-up . The economic evaluation ( intervention costs , productivity loss , and health care utilization costs ) was based on administrative data derived from national registries . Results For the time intervals 0–6 months , 6–12 months , and the entire follow-up period , the number of sickness absence hours was significantly lower in the CTWR group as compared to the control group . The total costs saved in CTWR participants compared to controls were estimated at US $ 1,366 per person at 6 months follow-up and US $ 10,666 per person at 12 months follow-up . Conclusions Workers on sick leave for 4–12 weeks due to MSD who underwent “ CTWR ” by an interdisciplinary team had fewer sickness absence hours than controls . The economic evaluation showed that — in terms of productivity loss — CTWR seems to be cost saving for the society Study Design . A multicenter , r and omized , controlled trial with 1-year follow-up . Objectives . To compare the effect of manual therapy to exercise therapy in sick-listed patients with chronic low back pain ( > 8 wks ) . Summary and Background Data . The effect of exercise therapy and manual therapy on chronic low back pain with respect to pain , function , and sick leave have been investigated in a number of studies . The results are , however , conflicting . Methods . Patients with chronic low back pain or radicular pain sick-listed for more than 8 weeks and less than 6 months were included . A total of 49 patients were r and omized to either manual therapy ( n = 27 ) or to exercise therapy ( n = 22 ) . Sixteen treatments were given over the course of 2 months . Pain intensity , functional disability ( Oswestry disability index ) , general health ( Dartmouth COOP function charts ) , and return to work were recorded before , immediately after , at 4 weeks , 6 months , and 12 months after the treatment period . Spinal range of motion ( Schober test ) was measured before and immediately after the treatment period only . Results . Although significant improvements were observed in both groups , the manual therapy group showed significantly larger improvements than the exercise therapy group on all outcome variables throughout the entire experimental period . Immediately after the 2-month treatment period , 67 % in the manual therapy and 27 % in the exercise therapy group had returned to work ( P < 0.01 ) , a relative difference that was maintained throughout the follow-up period . Conclusions . Improvements were found in both intervention groups , but manual therapy showed significantly greater improvement than exercise therapy in patients with chronic low back pain . The effects were reflected on all outcome measures , both on short and long-term follow-up Study Design . A r and omized controlled trial in occupational health practice was conducted . Objective . To study the efficacy of early management of workers with low back pain by occupational physicians , as compared with management by the supervisor only . Summary of Background data . Health care and university workers with back pain and on sick leave for less than 1 month were included in the study . Methods . Patients with low back pain for at least 10 days on sick leave were r and omly assigned to early management by the occupational physician ( n = 61 ) or to a reference group with management by the worker ’s supervisor during the first 3 months of sick leave ( n = 59 ) . The patients were observed for 1 year and compared in terms of time until return to work , pain intensity , functional disability , and general health perception . The occupational physicians were provided with management guidelines . Results . No significant differences were found after 3 and 12 months of follow-up evaluation in terms of time until return to work ( hazard ratio , 1.3 ; 95 % CI , 0.90–1.90 ) or in terms of other health outcomes . Recurrences , however , occurred more frequently in the intervention group , but the total duration of sick leave in 1 year did not differ between the groups . Conclusions . The findings do not show a significant positive effect of an early intervention by occupational physicians on workers with low back pain . This might reflect the early phase of disability or the low intensity of the intervention result ing from overestimation of the physicians ’ compliance with the guidelines |
13,323 | 22,372,080 | This systematic review of published literature between 1990 and 2008 on care provided by APRNs indicates patient outcomes of care provided by nurse practitioners and certified nurse midwives in collaboration with physicians are similar to and in some ways better than care provided by physicians alone for the population s and in the setting s included .
Use of clinical nurse specialists in acute care setting s can reduce length of stay and cost of care for hospitalized patients . | Advanced practice registered nurses have assumed an increasing role as providers in the health care system , particularly for underserved population s. The aim of this systematic review was to answer the following question : Compared to other providers ( physicians or teams without APRNs ) are APRN patient outcomes of care similar ? | PURPOSE the purpose of this study was to compare selected diabetes care processes and outcomes of nurse practitioners ( NPs ) and physicians ( MDs ) in the primary care of adults with type 2 diabetes . METHODS Adults with type 2 diabetes and no regular source of primary care were enrolled from the emergency room and r and omized to an NP or MD practice . Chart review s were conducted to assess processes of care ; patient interviews and hemoglobin Al C ( Al C ) testing were performed to measure patient outcomes . RESULTS NPs were more likely than MDs to document provision of general diabetes education and education about nutrition , weight , exercise , and medications . They were more likely to document patient height , urinalyses results , and Al C values . No differences were found in documenting current medications ; alcohol , illicit drug , or tobacco use ; depression ; weight and blood pressure ; foot and cardiovascular exams ; blood glucose and creatinine testing ; or referral to ophthalmologists . No differences were found in patient outcomes . CONCLUSIONS This study provides preliminary evidence of interdisciplinary differences in the processes of care employed by primary care NPs and MDs in caring for patients with type 2 diabetes . NPs documented the provision of diabetes education and selected monitoring tests more frequently than MDs ; however , these differences were not reflected in 6-month patient outcomes CONTEXT Most older adults with dementia will be cared for by primary care physicians , but the primary care practice environment presents important challenges to providing quality care . OBJECTIVE To test the effectiveness of a collaborative care model to improve the quality of care for patients with Alzheimer disease . DESIGN , SETTING , AND PATIENTS Controlled clinical trial of 153 older adults with Alzheimer disease and their caregivers who were r and omized by physician to receive collaborative care management ( n = 84 ) or augmented usual care ( n = 69 ) at primary care practice s within 2 US university-affiliated health care systems from January 2002 through August 2004 . Eligible patients ( identified via screening or medical record ) met diagnostic criteria for Alzheimer disease and had a self-identified caregiver . INTERVENTION Intervention patients received 1 year of care management by an interdisciplinary team led by an advanced practice nurse working with the patient 's family caregiver and integrated within primary care . The team used st and ard protocol s to initiate treatment and identify , monitor , and treat behavioral and psychological symptoms of dementia , stressing nonpharmacological management . MAIN OUTCOME MEASURES Neuropsychiatric Inventory ( NPI ) administered at baseline and at 6 , 12 , and 18 months . Secondary outcomes included the Cornell Scale for Depression in Dementia ( CSDD ) , cognition , activities of daily living , re source use , and caregiver 's depression severity . RESULTS Initiated by caregivers ' reports , 89 % of intervention patients triggered at least 1 protocol for behavioral and psychological symptoms of dementia with a mean of 4 per patient from a total of 8 possible protocol s. Intervention patients were more likely to receive cholinesterase inhibitors ( 79.8 % vs 55.1 % ; P = .002 ) and antidepressants ( 45.2 % vs 27.5 % ; P = .03 ) . Intervention patients had significantly fewer behavioral and psychological symptoms of dementia as measured by the total NPI score at 12 months ( mean difference , -5.6 ; P = .01 ) and at 18 months ( mean difference , -5.4 ; P = .01 ) . Intervention caregivers also reported significant improvements in distress as measured by the caregiver NPI at 12 months ; at 18 months , caregivers showed improvement in depression as measured by the Patient Health Question naire-9 . No group differences were found on the CSDD , cognition , activities of daily living , or on rates of hospitalization , nursing home placement , or death . CONCLUSIONS Collaborative care for the treatment of Alzheimer disease result ed in significant improvement in the quality of care and in behavioral and psychological symptoms of dementia among primary care patients and their caregivers . These improvements were achieved without significantly increasing the use of antipsychotics or sedative-hypnotics . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00246896 CONTEXT Low-income seniors frequently have multiple chronic medical conditions for which they often fail to receive the recommended st and ard of care . OBJECTIVES To test the effectiveness of a geriatric care management model on improving the quality of care for low-income seniors in primary care . DESIGN , SETTING , AND PATIENTS Controlled clinical trial of 951 adults 65 years or older with an annual income less than 200 % of the federal poverty level , whose primary care physicians were r and omized from January 2002 through August 2004 to participate in the intervention ( 474 patients ) or usual care ( 477 patients ) in community-based health centers . INTERVENTION Patients received 2 years of home-based care management by a nurse practitioner and social worker who collaborated with the primary care physician and a geriatrics interdisciplinary team and were guided by 12 care protocol s for common geriatric conditions . MAIN OUTCOME MEASURES The Medical Outcomes 36-Item Short-Form ( SF-36 ) scales and summary measures ; instrumental and basic activities of daily living ( ADLs ) ; and emergency department ( ED ) visits not result ing in hospitalization and hospitalizations . RESULTS Intention-to-treat analysis revealed significant improvements for intervention patients compared with usual care at 24 months in 4 of 8 SF-36 scales : general health ( 0.2 vs -2.3 , P = .045 ) , vitality ( 2.6 vs -2.6 , P < .001 ) , social functioning ( 3.0 vs -2.3 , P = .008 ) , and mental health ( 3.6 vs -0.3 , P = .001 ) ; and in the Mental Component Summary ( 2.1 vs -0.3 , P < .001 ) . No group differences were found for ADLs or death . The cumulative 2-year ED visit rate per 1000 was lower in the intervention group ( 1445 [ n = 474 ] vs 1748 [ n = 477 ] , P = .03 ) but hospital admission rates per 1000 were not significantly different between groups ( 700 [ n = 474 ] vs 740 [ n = 477 ] , P = .66 ) . In a predefined group at high risk of hospitalization ( comprising 112 intervention and 114 usual-care patients ) , ED visit and hospital admission rates were lower for intervention patients in the second year ( 848 [ n = 106 ] vs 1314 [ n = 105 ] ; P = .03 and 396 [ n = 106 ] vs 705 [ n = 105 ] ; P = .03 , respectively ) . CONCLUSIONS Integrated and home-based geriatric care management result ed in improved quality of care and reduced acute care utilization among a high-risk group . Improvements in health-related quality of life were mixed and physical function outcomes did not differ between groups . Future studies are needed to determine whether more specific targeting will improve the program 's effectiveness and whether reductions in acute care utilization will offset program costs . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00182962 Purpose : The purpose of this research was to evaluate the impact of a nurse‐directed approach to patient education , which focused on lifestyle modification , daily weight management , diet , and medication compliance to improve the quality of life ( QOL ) and functional capacity in people with heart failure . Data sources : This was a prospect i ve quasiexperimental multicenter research study of 23 patients comparing a nurse‐directed care ( NC ) group ( n= 13 ) , which received comprehensive disease management education and weekly telephone follow‐up , and the routine care ( RC ) group ( n= 10 ) that received protocol ‐driven medical management . The study length was 12 months . Conclusions : Analysis of covariance ( ANCOVA ) was used to test for e quality of variance – covariance matrices in the study population over time . ANCOVA measured baseline and two data intervals for a total of 9 months between the control and experimental ( NC and RC ) groups . There was statistically significant improvement in the NC group for the domains of total QOL : F= 3.569 , p= 0.000 ; health and function : F= 3.995 , p= 0.003 ; social and economic : F= 14.109 , p= 0.000 ; psychological and spiritual : F= 13.212 , p= 0.000 ; and family : F= 2.384 , p= 0.048 . Functional capacity was not significantly impacted by the study team interventions ( F= 0.228 , p= 0.949 ) . Implication s for practice : Results indicate that nurse‐directed patient education was effective in improving QOL . A nurse‐directed treatment strategy significantly improves patients ’ role in symptom control and disease self‐management OBJECTIVES The objective of this study was to determine if outcomes of care for nursing home residents differ between two groups of providers : nurse practitioners/physicians and physicians only . DESIGN We conducted a retrospective chart review covering the 12-month period from September 1 , 1997 , until August 31 , 1998 . SETTING We studied eight nursing homes in central Texas . PARTICIPANTS Two hundred three residents were r and omly selected who resided in one of the eight nursing homes during the specified time period . STATISTICAL ANALYSIS We used chi-squared or Fisher exact test for comparisons of percent and Student t test for comparison of means ; comparisons were made with both the FREQ procedure and the univariate procedure . RESULTS Acute visits were significantly higher for the nurse practitioner/physician team ( 3.0 + /- 2.4 ) versus the physician-only group ( 1.2 + /- 1.5 ) . The nurse practitioner/physician group treated significantly more eye , ear , nose , and throat and dermatologic diagnoses than the physician-only group . Emergency department visits , emergency department costs , hospitalizations , length of stay , hospital costs , performance of m and ated progress visits , and performance of annual history and physicals did not show significant differences between the two groups . CONCLUSION The level of care provided for patients by the two groups of providers was basically the same and of similar quality ; however , the nurse practitioner/physician group patients were seen more often . Increased visits by nurse practitioners are assumed to result in time and cost savings for physicians and improved access to care for patients This experimental pilot project examined 33 acute care patients over age 70 to determine if length of stay , cost of stay , and functional decline during hospitalization could be reduced through early assessment . A gerontological clinical nurse specialist ( GCNS ) , using three established instruments , scored all patients within 72 hours of admission to the study unit in relation to mental status , physical functioning , and ability to perform activities of daily living . The instruments included the ( a ) Mini-Mental State Exam ( MMSE ) , ( b ) PULSES Profile , and ( c ) Katz Index of Activities of Daily Living ( Katz ADL ) . The GCNS 's assessment s and recommendations for care were documented in patient charts . Subjects were r and omly assigned to experimental or control groups . Those in the experimental group received GCNS monitoring , which included daily ( except weekends ) patient visits to assess newly developed problems , response to interventions , and follow-through on previous recommendations . Other patients received only the usual care . Subjects were retested prior to discharge . The differences between change scores from admission to discharge were not statistically significant . However , the GCNS observed several positive trends in medical and nursing staff practice s in relation to increased staff awareness of geriatric care needs . Replication of this study using a larger sample of high-risk elderly patients is needed to further delineate the potential benefits of the unit-based model OBJECTIVE To compare midwifery and medical care practice s and measure optimal perinatal outcomes using a new clinimetric instrument . DESIGN Prospect i ve descriptive cohort design . SETTING A large , inner city obstetric service with medical and midwifery services . PARTICIPANTS Three hundred seventy-five of 400 consecutively enrolled patients were participated ( 25 excluded due to extreme risk status or missing data ) ; 92 % were of minority race/ethnicity and 54 % had less than a high school education . Of the 375 patients , 179 received physician care and 196 received nurse-midwife care . MAIN OUTCOME MEASURES The Optimality Index-US was measured . Health record data were extracted and scored using the Optimality Index-US to summarize the optimality of processes and outcomes of care as well as the woman 's preexisting health status . RESULTS Midwifery patients had more optimal care processes ( less use of technology and intervention ) with no difference in neonatal outcomes , even when preexisting risk was taken into account . CONCLUSION Even among moderate-risk patients , the midwifery model of care with its limited use of interventions can produce outcomes equivalent to or better than those of the biomedical model Background —Black subjects with a family history of premature coronary heart disease ( CHD ) have a marked excess risk , yet barriers prevent effective risk reduction . We tested a community-based multiple risk factor intervention ( community-based care [ CBC ] ) and compared it with “ enhanced ” primary care ( EPC ) to reduce CHD risk in high-risk black families . Methods and Results —Black 30- to 59-year-old siblings of a prob and with CHD aged < 60 years were r and omized for care of BP ≥140/90 mm Hg , LDL cholesterol ≥3.37 mmol/L , or current smoking to EPC ( n=168 ) or CBC ( n=196 ) and monitored for 1 year . EPC and CBC were design ed to eliminate barriers to care . The CBC group received care by a nurse practitioner and a community health worker in a community setting . The CBC group was 2 times more likely to achieve goal levels of LDL cholesterol and blood pressure compared with the EPC group ( 95 % CI , 1.11 to 4.20 and 1.39 to 3.88 , respectively ) with adjustment for baseline levels of age , sex , education , and baseline use of medications . The CBC group demonstrated a significant reduction in global CHD risk , whereas no reduction was seen in the EPC group ( P<0.0001 ) . Conclusions —Eliminating known barriers may not be sufficient to reduce CHD risk in primary care setting s. An alternative community care model that addresses barriers may be a more effective way to ameliorate CHD risk in high-risk black families The purpose of this study was to examine the relationships among patient length of stay , complications , and type of care manager ( clinical , nurse specialists [ CNSs ] vs. physician assistants [ PAs ] ) . A descriptive comparison of two groups was performed . Data were collected using a retrospective chart audit of 105 r and omly selected patients who had undergone elective coronary artery bypass surgery for the first time between 1991 and 1993 . Group 1 comprised patients for whom PAs and cardiac surgeons co-managed postoperative care . Group 2 comprised clients whose care was co-managed by CNSs and cardiac surgeons . Complication rates were similar between the two groups . Findings indicated that the CNS-managed group had a statistically significant shorter length of stay . Results suggested that care managed by CNSs can decrease length of stay , when compared with care managed by PAs BACKGROUND One approach to optimize clinical and economic management of congestive heart failure is the use of multidisciplinary outpatient clinics in which advanced practice nurses coordinate care . One such clinic was developed in 1995 at a southeastern university hospital to enhance management of patients with chronic congestive heart failure . OBJECTIVES To evaluate the effects of a multidisciplinary outpatient heart failure clinic on the clinical and economic management of patients with congestive heart failure . METHODS Data on hospital readmissions , emergency department visits , length of stay , charges , and reimbursement from the 6 months before 15 patients joined a heart failure clinic were compared with data from the 6 months after the patients joined the clinic . RESULTS The patients had a total of 38 hospital admissions ( 151 hospital days ) in the 6 months before joining the clinic and 19 admissions ( 72 hospital days ) in the 6 months afterward . The mean length of stay decreased from 4.3 days in the 6 months before joining to 3.8 days in the 6 months afterward , and the number of emergency department visits also decreased , although neither decrease was statistically significant . Mean inpatient hospital charges decreased from $ 10,624 per patient admission to $ 5893 . Reimbursements were $ 7751 ( 73 % collection rate ) and $ 5138 ( 87 % collection rate ) , respectively . CONCLUSIONS Patients seemed to benefit from participation in the heart failure clinic . If a healthcare provider is available to manage early signs and symptoms of worsening heart failure , hospital readmissions may be decreased and patients ' outcomes may be improved OBJECTIVES This study examined differences among obstetricians , family physicians , and certified nurse-midwives in the patterns of obstetric care provided to low-risk patients . METHODS For a r and om sample of Washington State obstetrician-gynecologists , family physicians , and certified nurse-midwives , records of a r and om sample of their low-risk patients beginning care between September 1 , 1988 , and August 31 , 1989 , were abstract ed . RESULTS Certified nurse-midwives were less likely to use continuous electronic fetal monitoring and had lower rates of labor induction or augmentation than physicians . Certified nurse-midwives also were less likely than physicians to use epidural anesthesia . The cesarean section rate for patients of certified nurse-midwives was 8.8 % vs 13.6 % for obstetricians and 15.1 % for family physicians . Certified nurse-midwives used 12.2 % fewer re sources . There was little difference between the practice patterns of obstetricians and family physicians . CONCLUSIONS The low-risk patients of certified nurse-midwives in Washington State received fewer obstetrical interventions than similar patients cared for by obstetrician-gynecologists or family physicians . These differences are associated with lower cesarean section rates and less re source use Objective Less is known about nurse practitioners ' ( NPs ' ) effectiveness in acute care than about their effectiveness in outpatient setting s. This study investigated care activities and clinical outcomes for hospitalized geriatric patients treated by NPs compared with those treated by intern and resident physicians . Data Sources A descriptive comparative research design involved r and om selection of 100 inpatient geriatric patients and a convenience sample of 17 professional providers who staffed three hospital units . A 1‐month study period produced retrospective and prospect i ve data for analysis . Self‐reports concerning 10 primary activity categories indicated that NPs spent a higher percentage of time doing progress notes and care planning than did physicians ( 28 % versus 15 % , p=.011 ) and that physicians spent more time on literature review s ( 5 % versus 1 % , p=.008 ) . When prioritizing care activities , NPs ranked advance directive discussion higher than did physicians ( 2nd versus 7th , p=.036 ) , a difference confirmed by medical record documentation . Physicians were more attentive to functional status ( 1st versus 3rd , p=.023 ) , but medical record documentation showed NPs to be more attentive to physical and occupational therapy referrals ( p=.001 ) . Analysis of 13 independent organ areas revealed that NPs cared for more musculoskeletal ( p=.036 ) and psychiatric ( p=.005 ) problems . Physicians cared for more cardiac patients ( p=.001 ) . NPs ’ patients were older ( p=.022 ) and sicker at admission ( p < . 001 ) and discharge ( p < . 001 ) . Charges per length of stay were lower ( p < . 001 ) for the physician provider group , and patients in that group had shorter stays ( p < . 001 ) . Readmission and mortality rates were similar . Implication s for Practice NPs provide effective care to hospitalized geriatric patients , particularly to those who are older and sicker Objective : The midwifery service at our hospital has been observed to have a 2 % cesarean birth rate consistently over a 10-year period . There are substantial differences in labor management style between the midwives and physicians . We sought to test the hypothesis that the low cesarean birth rate on the midwifery service was the result of patient selection bias . Methods : A r and omized blinded clinical trial was conducted in which 492 low-risk patients were assigned to either physician or midwifery management . The provider responsible for labor management was unable to determine group assignment . Patients in the midwifery group were managed by previously established protocol s , and outcome was attributed to the midwives even if the patients subsequently required transfer to physician management . Route of delivery was the primary outcome measurement . Continuous variables were analyzed using Student t test and discrete variables using x2 . Results : There were no demographic differences between the groups , and the admission pelvic examinations were the same . The patients assigned to the midwifery group had a 2.1 % cesarean birth rate , whereas those assigned to physician management had a 0.4 % rate . The higher rate of operative vaginal deliveries in the physician group was statistically significant . There were no differences in neonatal outcomes . The physician-managed group had significantly more episiotomies and third- and fourth-degree extensions . Conclusions : The 2 % cesarean birth rate observed on the midwifery service appeared to be the result of patient selection bias . A low cesarean birth rate can be achieved by either physician or midwifery management in a selected low-risk population BACKGROUND Many academic medical centers employ nurse practitioners as substitutes to provide care normally supplied by house staff . OBJECTIVE To compare outcomes in a subacute medical intensive care unit of patients managed by a team consisting of either an acute care nurse practitioner and an attending physician or an attending physician and critical care/pulmonary fellows . METHODS During a 31-month period , in 7-month blocks of time , 526 consecutive patients admitted to the unit for more than 24 hours were managed by one or the other of the teams . Patients managed by the 2 teams were compared for a variety of outcomes . RESULTS Patients managed by the 2 teams did not differ significantly for any workload , demographic , or medical condition variable . The patients also did not differ in readmission to the high acuity unit ( P = .25 ) or subacute unit ( P = .44 ) within 72 hours of discharge or in mortality with ( P = .25 ) or without ( P = .89 ) treatment limitations . Among patients who had multiple weaning trials , patients managed by the 2 teams did not differ in length of stay in the subacute unit ( P = .42 ) , duration of mechanical ventilation ( P = .18 ) , weaning status at time of discharge from the unit ( P = .80 ) , or disposition ( P = .28 ) . Acute Physiology Scores were significantly different over time ( P = .046 ) . Patients managed by the fellows had more reintubations ( P=.02 ) . CONCLUSIONS In a subacute intensive care unit , management by the 2 teams produced equivalent outcomes BACKGROUND AND METHODS The prevention of disability in elderly people poses a challenge for health care and social services . We conducted a three-year , r and omized , controlled trial of the effect of annual in-home comprehensive geriatric assessment and follow-up for people living in the community who were 75 years of age or older . The 215 people in the intervention group were seen at home by gerontologic nurse practitioners who , in collaboration with geriatricians , evaluated problems and risk factors for disability , gave specific recommendations , and provided health education . The 199 people in the control group received their regular medical care . The main outcome measures were the prevention of disability , defined as the need for assistance in performing the basic activities of daily living ( bathing , dressing , feeding , grooming , transferring from bed to chair , and moving around inside the house ) or the instrumental activities of daily living ( e.g. , cooking , h and ling finances and medication , housekeeping , and shopping ) , and the prevention of nursing home admissions . RESULTS At three years , 20 people in the intervention group ( 12 percent of 170 surviving participants ) and 32 in the control group ( 22 percent of 147 surviving participants ) required assistance in performing the basic activities of daily living ( adjusted odds ratio , 0.4 ; 95 percent confidence interval , 0.2 to 0.8 ; P = 0.02 ) . The number of persons who were dependent on assistance in performing the instrumental activities of daily living but not the basic activities did not differ significantly between the two groups . Nine people in the intervention group ( 4 percent ) and 20 in the control group ( 10 percent ) were permanently admitted to nursing homes ( P = 0.02 ) . Acute care hospital admissions and short-term nursing home admissions did not differ significantly between the two groups . In the second and third years of the study , there were significantly more visits to physicians among the participants in the intervention group than among those in the control group ( mean number of visits per month , 1.41 in year 2 and 1.27 in year 3 in the intervention group , as compared with 1.11 and 0.92 visits , respectively , in the control group ; P = 0.007 and P = 0.001 , respectively ) . The cost of the intervention for each year of disability-free life gained was about $ 46,000 . CONCLUSIONS A program of in-home comprehensive geriatric assessment s can delay the development of disability and reduce permanent nursing home stays among elderly people living at home OBJECTIVE This study compared the effects of early admission in labor and perinatal care provider on delivery method . Higher spontaneous vaginal delivery rates for certified nurse midwives as compared with physicians have been reported in observational studies and r and omized clinical trials . Certified nurse midwives , with their more expectant approach to labor management , would be expected to admit women later in labor than obstetricians . METHODS Prospect i ve cohort study of 2,196 low-risk pregnancies , with singleton , vertex infants admitted in spontaneous labor . Independent and joint effects of perinatal care provider and cervical dilation at admission on delivery method were evaluated . Confounding was addressed using restriction and multiple regression . RESULTS Fewer ( 23.4 % ) women in collaborative care were admitted in early labor ( < 4 cm cervical dilation ) than women managed by obstetricians ( 95 % CI = -27.6 to -19.2 ) . Obstetrician care had 9 % to 30 % fewer spontaneous vaginal deliveries . Women admitted early in labor also had 6 % to 34 % fewer spontaneous vaginal deliveries . Evaluation of joint effects suggested that interaction between obstetrician provider and earlier admission increased the risk of operative delivery . CONCLUSION Later admission in labor ( at 4 cm or greater cervical dilation ) and management of perinatal care by certified nurse midwives in collaboration with obstetricians increased the rate of spontaneous vaginal delivery in low-risk women This study reports results of the 2-year follow-up phase of a r and omized study comparing outcomes of patients assigned to a nurse practitioner or a physician primary care practice . In the sample of 406 adults , no differences were found between the groups in health status , disease-specific physiologic measures , satisfaction or use of specialist , emergency room or inpatient services . Physician patients averaged more primary care visits than nurse practitioner patients . The results are consistent with the 6-month findings and with a growing body of evidence that the quality of primary care delivered by nurse practitioners is equivalent to that by physicians In a r and omized , controlled trial in five regional centers with state health department clinics , 1458 women at high risk for low birth weight ( LBW ) outcome received either prenatal interventions provided by nurse-midwives and nurses under their supervision or the st and ard high-risk prenatal care provided by obstetricians . The intervention administered by the nurse-midwives included patient education to identify the signs and symptoms of preterm labor , activity counseling in response to monitoring of the cervix by frequent examinations , stress reduction by enhancing social support , nutrition counseling with emphasis on weight gain , and substance-abuse counseling . For women in the control group , care was provided by obstetricians according to local st and ards for the management of high-risk pregnancies . We hypothesized that the LBW rate among live births to women who had received care from nursemidwives would be lower than that in the control group . Although the LBW rate was lower in the intervention group than in the control group , the observed difference was not statistically significant . Race was not prespecified as a possible effect modifier , but examination of the data post hoc suggested that black women at high statistical risk of giving birth to an LBW infant may have derived benefit from the program . Although the results do not suggest any striking advantage of the nurse-midwifery intervention over st and ard obstetric care for women at high statistical risk of having an LBW infant , neither do they suggest any disadvantage . Nurse-midwives could provide care to certain population s of high-risk women and facilitate future coverage of these presently underserved population BACKGROUND This r and omized controlled trial tested the effectiveness of comprehensive , interdisciplinary postdischarge care management in improving a profile of indicators of health recovery and secondary prevention ( profile of health and prevention ) in stroke and transient ischemic attack ( TIA ) patients . METHODS Ninety-six stroke/TIA patients were r and omized to usual care or intervention at discharge from our acute stroke unit . The intervention group received an in-home biopsychosocial assessment by an advanced practice nurse at 1 month . A care plan was developed by an interdisciplinary team and implemented in collaboration with the patient 's primary care physician . The profile of health and prevention , measured at 3 months , was comprised of 5 domains : ( 1 ) Neuromotor Function , ( 2 ) Severe Complications , ( 3 ) Quality of Life , ( 4 ) Management of Risk for common poststroke complications and recurrent stroke , and ( 5 ) Stroke Knowledge . A single global hypothesis test across multiple end points was used to compare the 2 groups . RESULTS The intervention significantly improved the profile of health and prevention ( P < .0001 ) . In addition , each domain showed a positive effect of the intervention . Effect sizes ( in st and ard deviation units ) of the intervention on domains were .1 for Neuromotor Function ( 90 % confidence interval [ CI ] = -.3 to .5 ) ; .4 for Severe Complications ( 90 % CI = .1 to .8 ) ; .5 for Quality of Life ( 90 % CI = .1 to .9 ) ; .6 for Management of Risk for common poststroke complications and recurrent stroke ( 90 % CI = .3 to 1 . ) ; and 1.0 for Stroke Knowledge ( 90 % CI = .6 to 1.4 ) . CONCLUSIONS This model of care management result ed in a significantly better profile of health and prevention for stroke/TIA patients 3 months postdischarge 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 Purpose : To evaluate the cost‐effectiveness of case management by a nurse practitioner ( NP ) to lower blood lipids in patients with coronary heart disease ( CHD ) from a managed care perspective . Data sources : A total of 228 consecutive , eligible adults with hypercholesterolemia and CHD were recruited during hospitalization after coronary revascularization . Patients were r and omized to receive lipid management , including individualized lifestyle modification and pharmacologic intervention from an NP for 1 year after discharge in addition to their usual care ( NURS ) or to receive usual care ( EUC ) enhanced with feedback on lipids to their primary provider and /or cardiologist . A cost‐effectiveness ratio was calculated using incremental costs of the NURS group per unit change and percent change in low‐density lipoprotein cholesterol ( LDL‐C ) for 1 year at 2004 values . Conclusions : The annual incremental cost‐effectiveness of NP case management was $ 26.03 per mg/dL and $ 39.05 per percent reduction in LDL‐C. When costs of NURS care for the second 6 months of management were compared to the first 6 months of management , nursing salary costs were lower as patients were established on cholesterol management regimens , but the reduction in costs was offset by the increase in incremental costs of drug treatment as the NP titrated the patient to higher drug dosages that were more costly . Implication s for practice : The findings suggest that case management by an NP is a cost‐effective approach for a managed care organization to consider in improving the care of patients with cardiovascular disease PURPOSE Work hour restrictions for house staff have forced a reevaluation of the traditional roles of all health care providers . In 2001 , our level I pediatric trauma center augmented the role of our trauma pediatric nurse practitioners ( PNPs ) to include in-patient management . We hypothesized that a PNP can provide injured children a level of care commensurate with a resident ( RES ) . METHODS All children between 2 months and 17 years old admitted to the Trauma Service were considered for the study . Patients were r and omized to PNP or RES care groups . Types of injuries , injury severity score , missed injuries , readmissions , hospital length of stay ( LOS ) , and cost were recorded . Satisfaction surveys were administered to all families . RESULTS A total of 76 children were enrolled . During the study period , there were no missed injuries or readmissions . The PNP group had a significantly shorter LOS and received significantly higher satisfaction survey scores with regard to information on injuries , tests and treatment , and frequency of visits provided to the patient/family . CONCLUSIONS PNPs provide equivalent care for injured children with significantly shorter LOS and higher patient satisfaction than RESs . In-patient trauma nurse practitioners provide added value to the care of the injured child in the era of reduced RES work hours Objective : To examine the effectiveness of integrating generalist and specialist care for veterans with depression . Method : We conducted a r and omized trial of patients screening positive for depression at two Veterans Affairs Medical Center general medicine clinic firms . Control firm physicians were notified prior to the encounter when eligible patients had PRIME-MD depression diagnoses . In the intervention firm , a mental health clinical nurse specialist ( CNS ) was to : design a treatment plan ; implement that plan with the primary care physician ; and monitor patients via telephone or visits at two weeks , one month and two months . Primary outcomes ( depressive symptoms , patient satisfaction with health care ) were collected at 3 and 12 months . Results : Of 268 r and omized patients , 246 ( 92 % ) and 222 ( 83 % ) completed 3- and 12-month follow-up interviews . There were no between-group differences in depressive symptoms or satisfaction at 3 or 12 months . The intervention group had greater chart documentation of depression at baseline ( 63 % versus 33 % , p = 0.003 ) and a higher referral rate to mental health services at 3 months ( 27 % versus 9 % , p = 0.019 ) . There was no difference in the rate of new prescriptions for , or adequate dosing of , anti-depressant medications . In 40 % of patients , CNSs disagreed with the PRIME-MD depression diagnosis , and their rates of watchful waiting were correspondingly high . Conclusions : Implementing an integrated care model did not occur as intended . Experienced CNSs often did not see the need for treatment in many primary care patients identified by the PRIME-MD . Integrating integrated care models in actual practice may prove challenging Although teaching hospitals are increasingly using nurse practitioners ( NPs ) to provide inpatient care , few studies have compared care delivered by NPs and housestaff or the ability of NPs to admit and manage unselected general medical patients . In a Midwest academic teaching hospital 381 patients were r and omized to general medical wards staffed either by NPs and a medical director or medical housestaff . Data were obtained from medical records , interviews and hospital data bases . Outcomes were compared on both an intention to treat ( i.e. wards to which patients were r and omized ) and actual treatment ( i.e. wards to which patients were admitted ) basis . At admission , patients assigned r and omly to NP-based care ( n = 193 ) and housestaff care ( n= 188 ) were similar with respect to demographics , comorbidity , severity of illness and functional parameters . Outcomes at discharge and at 6 weeks after discharge were similar ( P>0.10 ) in the two groups , including : length of stay ; charges ; costs ; consultations ; complications ; transfers to intensive care ; 30-day mortality ; patient assessment s of care ; and changes in activities of daily living , SF-36 scores and symptom severity . However , after r and omization , 90 of 193 patients ( 47 % ) assigned to the NP ward were actually admitted to housestaff wards , largely because of attending physicians and NP requests . None the less , outcomes of patients admitted to NP and housestaff wards were similar ( P>0.1 ) . NP-based care can be implemented successfully in teaching hospitals and , compared to housestaff care , may be associated with similar costs and clinical and functional outcomes . However , there may be important obstacles to increasing the number of patients cared for by NPs , including physician concerns about NPs ' capabilities and NPs ' limited flexibility in managing varying numbers of patients and accepting off-hours admissions This study was design ed to determine whether differences exist between patients with total knee replacement on hospital units with or without clinical nurse specialists ( CNSs ) in terms of selected process and outcome variables . The charts of 128 r and omly chosen patients who had undergone total knee replacement were review ed . Sixty-four patients were from orthopedic units with CNSs and 64 were from orthopedic units without CNSs . This study was based on Donabedian 's framework for assessment of quality of care using structure , process , and outcome variables . Structural variables were collected on institutional and unit demographics . Data were gathered on nursing care interventions ( process variables ) using process instruments design ed by the investigator . Length of stay , total length of stay , which included rehabilitation length of stay , and complications were the outcome variables used . Patients on units with CNSs had significantly higher process scores , shorter total length of stay , and fewer complications than patients on units without CNSs . In addition , significant negative correlations were found between process instrument scores and total length of stay . Higher scores on the process instruments ( with CNS units ) were correlated with shorter total length of stay . The number of complications was also negatively correlated to the process instrument scores OBJECTIVES This study assessed the impact of a public-private certified nurse-midwife program on prenatal and delivery outcomes among medically indigent women . METHODS A population -based quasi-experimental design was used to compare 1 intervention county with 2 nonintervention counties . RESULTS The program significantly reduced the number of women who received no prenatal care and the risk of acquiring less than adequate prenatal care . Reductions in the proportion of infants born premature or with low birth-weights were of borderline significance . The use of induction and /or stimulation of labor was statistically elevated . CONCLUSIONS These results suggest that the intervention program was instrumental in reducing some , but not all , negative prenatal and delivery outcomes A two- to three-fold increase in mortality from hepatitis C is predicted in the next 10–20 years as the largest cohort of patients age . More qualified providers are needed to care for this population . The objective of this study was to assess the impact of a hepatology nurse practitioner as compared to care by a physician on the quality of life and treatment outcomes of patients with chronic hepatitis C. Seventy-five patients with chronic hepatitis C were assigned to either a nurse practitioner or physician and asked to complete a SF-36 Health Survey quarterly to measure their perceived quality of life . Two-sided t-tests comparing the quality of life scores in the physician and nurse practitioner groups at weeks 1 , 12 , and 24 were calculated using SPSS version 12.0 ( Chicago , IL ) . Although marginal differences between physicians and nurse practitioners were noted for physical function at week 1 , bodily pain at week 12 , and role physical at week 24 by the patients , no statistically significant differences were observed overall in the quality of life scores reported by the patients according to healthcare provider . The treatment outcome data for the nurse practitioner groups showed 12/25 ( 48 % ) of patients with genotype 1 achieved a sustained virologic response as did 13/22 ( 59 % ) of patients with genotype 2 or 3 . In the physician groups , 11/27 ( 41 % ) of patients with genotype 1 achieved a sustained virologic response as did 14/23 ( 61 % ) of patients with genotype 2 or 3 . These results suggest nurse practitioners can provide effective care to the chronic hepatitis C population OBJECTIVE To improve clinical and financial outcomes for neuroscience patients by using an " outcomes -managed " model of care delivery and 2 acute care nurse practitioners as outcomes managers . METHODS Baseline data from the year before implementation of the care model were compared with data from the first 6 months of implementation . A r and om list of 122 adult patients admitted to the neuroscience intensive care unit or the acute care neurosurgery unit of a university teaching hospital between January and December 1998 was generated to provide the baseline data . The prospect i ve sample included 402 patients admitted to either unit during the first 6 months of the project ( January through June 1999 ) . The acute care nurse practitioners used an evidence -based multidisciplinary plan of care to manage all patients . RESULTS No differences were found in age , sex , or ethnicity between groups . Patients managed by acute care nurse practitioners had significantly shorter overall length of stay ( P = .03 ) , shorter mean length of stay in the intensive care unit ( P < .001 ) , lower rates of urinary tract infection and skin breakdown ( P < .05 ) , and shorter time to discontinuation of the Foley catheter and mobilization ( P < .05 ) . The outcomes -managed group was hospitalized 2306 fewer days than the baseline group , at a total cost savings of $ 2,467328 . CONCLUSIONS Clinical and financial outcomes are improved significantly by identifying patients at risk , monitoring for complications , and having acute care nurse practitioners manage the patients In a r and omized clinical trial , quality of health care as reflected in patient outcomes and cost of health care was compared between two groups of high-risk childbearing women : women diagnosed with diabetes or hypertension in pregnancy . The control group ( N = 52 ) was discharged routinely from the hospital . The intervention group ( N = 44 ) was discharged early using a model of clinical nurse specialist transitional follow-up care . During pregnancy , the intervention group had significantly fewer rehospitalizations than the control group . For infants of diabetic women enrolled in the study during their pregnancy , low birth weight ( < or = 2,500 g ) was three times more prevalent in the control group ( 29 % ) than in the intervention group ( 8.3 % ) . The postpartum hospital charges for the intervention group were also significantly less than for the control group . The mean total hospital charges for the intervention group were 44 % less than for the control group . The mean cost of the clinical specialist follow-up care was 2 % of the total hospital charges for the control group . A net savings of $ 13,327 was realized for each mother-infant dyad discharged early from the hospital We tested the effectiveness of a nursing intervention model to improve health , function , and return-home outcomes in elders with hip fracture via a 2-year r and omized clinical trial . Thirty three elders ( age > 65 years ) were tracked from hospital discharge to 12 months postfracture . The treatment group had a gerontologic advanced practice nurse as postacute care coordinator for 6 months who intervened with each elder regardless of the postacute care setting , making biweekly visits and /or phone calls . The coordinator assessed health and function , and informed elders , families , long-term care staff , and physicians of the patient 's progress . The control group had care based on postacute facility protocol s. Nonnormal distribution of data led to nonparametric analysis using Freidman 's test with post hoc comparisons ( Mann — Whitney U tests , Bonferroni adjustment ) . The treatment group had better function at 12 months on several activities and instrumental activities of daily living , and no differences in health , depression , or living situation CONTEXT Studies have suggested that the quality of primary care delivered by nurse practitioners is equal to that of physicians . However , these studies did not measure nurse practitioner practice s that had the same degree of independence as the comparison physician practice s , nor did previous studies provide direct comparison of outcomes for patients with nurse practitioner or physician providers . OBJECTIVE To compare outcomes for patients r and omly assigned to nurse practitioners or physicians for primary care follow-up and ongoing care after an emergency department or urgent care visit . DESIGN R and omized trial conducted between August 1995 and October 1997 , with patient interviews at 6 months after initial appointment and health services utilization data recorded at 6 months and 1 year after initial appointment . SETTING Four community-based primary care clinics ( 17 physicians ) and 1 primary care clinic ( 7 nurse practitioners ) at an urban academic medical center . PATIENTS Of 3397 adults originally screened , 1316 patients ( mean age , 45.9 years ; 76.8 % female ; 90.3 % Hispanic ) who had no regular source of care and kept their initial primary care appointment were enrolled and r and omized with either a nurse practitioner ( n = 806 ) or physician ( n = 510 ) . MAIN OUTCOME MEASURES Patient satisfaction after initial appointment ( based on 15-item question naire ) ; health status ( Medical Outcomes Study Short-Form 36 ) , satisfaction , and physiologic test results 6 months later ; and service utilization ( obtained from computer records ) for 1 year after initial appointment , compared by type of provider . RESULTS No significant differences were found in patients ' health status ( nurse practitioners vs physicians ) at 6 months ( P = .92 ) . Physiologic test results for patients with diabetes ( P = .82 ) or asthma ( P = .77 ) were not different . For patients with hypertension , the diastolic value was statistically significantly lower for nurse practitioner patients ( 82 vs 85 mm Hg ; P = .04 ) . No significant differences were found in health services utilization after either 6 months or 1 year . There were no differences in satisfaction ratings following the initial appointment ( P = .88 for overall satisfaction ) . Satisfaction ratings at 6 months differed for 1 of 4 dimensions measured ( provider attributes ) , with physicians rated higher ( 4.2 vs 4.1 on a scale where 5 = excellent ; P = .05 ) . CONCLUSIONS In an ambulatory care situation in which patients were r and omly assigned to either nurse practitioners or physicians , and where nurse practitioners had the same authority , responsibilities , productivity and administrative requirements , and patient population as primary care physicians , patients ' outcomes were comparable Recent , large , r and omized , controlled trials of the effects of episiotomy on perineal damage have confirmed that episiotomy is associated with an increased risk of damage to the perineum . Yet episiotomy remains the most common surgical procedure women undergo . This article examines if clinician experience , rather than scientific evidence , forms the basis for continuing this practice . Perineal outcome data are analyzed for 865 low-risk women who were attended at birth by the staff nurse-midwives or faculty obstetricians at a university-based , tertiary-care hospital . Data were collected under routine , nonexperimental conditions such that the circumstances of the labor and the clinician 's preferences were allowed to determine management decisions regarding the use of episiotomy or other techniques of perineal management . Multivariate findings indicate that in the absence of episiotomy , rates of perineal integrity were highest among clinicians who usually had the lowest rate of episiotomy use . When an episiotomy was done , rates of third- and fourth-degree extensions were highest among clinicians who used episiotomy most frequently . This finding challenges the idea that clinicians who were very experienced with the use of episiotomy would avoid complications such as extensions . Future research should explore the use of nonsurgical techniques such as those employed by midwives to promote perineal integrity . Then interdisciplinary research and evidence -based education regarding these techniques can occur to improve perineal outcomes for all women This prospect i ve study examined whether the integration of acute care nurse practitioners ( ACNP ) in a “ semiclosed ” surgical intensive care unit ( SICU ) model increased compliance with clinical practice guidelines ( CPG ) . Patients were admitted to critical care services with a ( a ) “ semiclosed”/ACNP team or ( b ) “ m and atory consultation”/non-ACNP team . CPG compliance was significantly higher ( P < .05 ) on the “ semiclosed”/ACNP team for all 3 CPGs examined in the study |
13,324 | 29,067,087 | IOA got excess but not statistically significant lower visual analogue score ( VAS ) pain score during HSG or more than 30 minutes after HSG compared with the other groups .
OOA result ed in excess but not statistically significant higher VAS pain score during HSG compared with the other groups except placebo group .
CONCLUSION This new Bayesian data network meta- analysis from r and omized controlled trials demonstrated that IOA result ed in the highest probability to reduce the pain during HSG or at 30 minutes or more after HSG among the six interventions considered | OBJECTIVE We aim ed to evaluate the effectiveness of placebo , oral opioid analgesic ( OOA ) , intravenous opioid analgesic ( IOA ) , non-opioid analgesic ( NOA ) , topical anesthetic ( TA ) and locally injected anesthetic ( LIA ) for pain relief duringhysterosalpingography ( HSG ) using a Bayesian network meta- analysis of data from r and omized controlled trials . | AIM To evaluate the effectiveness of paracetamol as a prophylactic analgesic for hysterosalpingography ( HSG ) . DESIGN A prospect i ve double blind r and omized controlled trial comparing one 1 g of paracetamol ( SmithKline Beecham , Brentford , U.K. ) to placebo taken 30 min before HSG . One hundred consecutive out- patients were studied prospect ively . The analgesic effectiveness during the procedure and at 24 h and 1 week post procedure was analysed by a postal pain score question naire . Additional data on the ethnicity of the patient , sex and level of experience of the radiologist performing the hysterosalpingogram , the parity of the patient , the ease of the procedure , and whether pathology was identified were also recorded . RESULTS Eighty-eight patients ( 88 % ) replied , 39 ( 44 % ) received paracetamol and 49 placebo ( 56 % ) . During the procedure 3/39 ( 7 % ) of women in the paracetamol group were pain-free compared to 9/49 ( 18 % ) in the placebo group , which was not significant ( P = 0.11 ) . At 24 h , 15/39 ( 38 % ) of women in the paracetamol group were pain-free compared to 20/49 ( 41 % ) in the placebo group , which was not significant ( P = 0.82 ) . At 1 week , 27/39 ( 69 % ) of women in the paracetamol group were pain-free compared to 29/49 ( 59 % ) in the placebo group , which was not significant ( P = 0.33 ) . No significant difference in mean pain scores was determined during the procedure ( P = 0.91 ) , or at 24 h post procedure ( P = 0.94 ) . Similarly , no difference in mean pain scores was identified with regard to the ethnicity of the patient , the sex of the radiologist performing the procedure , the level of experience of the radiologist performing the procedure , or whether pathology was present or not . Difficult cannulations were associated with higher mean pain scores , however , there was no difference in mean pain scores between the paracetamol or placebo groups for both easy and difficult cannulations . CONCLUSION Paracetamol is not effective as a prophylactic analgesic for HSG . If a prophylactic analgesic is considered necessary for pain relief during HSG we recommend that a non-steroidal anti-inflammatory drug ( NSAID ) is used AIM To evaluate the effectiveness of a rectal nonsteroidal anti-inflammatory drug ( indomethacin ) for pain relief during a hysterosalpingography ( HSG ) . MATERIAL S AND METHODS This prospect i ve , r and omized study included 82 women divided r and omly into two groups . The study group received self-administered rectal indomethacin , while the control group received a placebo before the procedure . Degrees of pain were evaluated using the visual analog scale ( VAS ) at four different steps during the procedure and 30 min afterwards . The anxiety-depression status of the patients was evaluated using a vali date d Turkish version of the Beck anxiety-depression form before the procedure . RESULTS There were no statistically significant differences in the demographic characteristics of patients . The mean pain scores during tenaculum application ( step 2 ) , cervical traction ( step 3 ) , contrast injection ( step 4 ) and 30 min after the procedure , were significantly lower in the study than the control group ( P < 0.05 ) . Step 4 was the most painful in both groups ( VAS scores 3.2 ± 0.6 study vs. 5.3 ± 1.1 control ) . The mean pain score in step 4 for patients with abnormal HSG results was significantly higher than in patients with normal HSG results ( P < 0.05 ) . The mean anxiety and depression scores immediately before the procedure were not statistically different between the groups ( P = 0.610 and P = 0.129 , respectively ) . CONCLUSION Our study demonstrated a significant reduction in pain in patients who received a single rectal dose of indomethacin ; therefore , we recommend the use of rectal indomethacin for reducing pain during a HSG procedure Background / Aims : A hysterosalpingogram is an integral part of the evaluation of infertility , however , it is often painful . Methods : We conducted a r and omized double-blinded , placebo-controlled trial of intravenous infusion of remifentanil in women undergoing hysterosalpingography ( HSG ) . We r and omly allocated 62 patients scheduled for HSG to receive either a continuous infusion of 0.25 µg·kg–1 of remifentanil or placebo . The degree of pain was documented via 10-cm visual analog scales ( VAS ) . Patients ’ discomfort , side effects and recovery times were also recorded . Results : The VAS scores during HSG were 1.25 ± 1.31 in the remifentanil group and 4.78 ± 1.7 in the placebo group ( p < 0.001 ) . There were more patients in the remifentanil group that rated their condition as excellent ( p < 0.001 ) . The groups did not differ with regard to the incidence of side effects . The recovery times were found statistically longer in the remifentanil group ( 14 ± 5 vs. 10 ± 3 min ) . All the patients were discharged 30 min after the procedures without any side effects . Conclusion : Remifentanil infusion during HSG is superior to placebo for relief of pain with minimal opioid side effects Background : Hysterosalpingography ( HSG ) is considered as a primary test in infertility work up worldwide due to its reliability in evaluating abnormalities related to the uterus and fallopian tubes . Objectives : To assess the efficacy of applying eutectic mixture of local anesthetics ( lidocaine-prilocaine cream ) ( EMLA ) on the uterine cervix in reducing pain during HSG . Patients and Methods : Eighty patients undergoing HSG as part of infertility evaluation were r and omly allocated to groups receiving either EMLA ( N = 40 ) or placebo cream ( N = 40 ) in a double-blinded prospect i ve study . Fifteen minutes before HSG , 5 grams of 5 % cream was applied to the uterine cervix using a cervical applicator . The degree of pain experienced by the patient was evaluated during and after HSG at five predefined steps on a visual analogue scale ( VAS ) . Results : There was no significant difference in the efficacy between EMLA and placebo creams in pain perception during the entire procedure . There was no significant difference in long term pain perception half an hour after the HSG performance . Conclusions : This study does not support the use of EMLA for HSG Purpose Hysterosalpingography ( HSG ) is an important tool for evaluation of tubal factors in infertility . It does not require anesthesia but can be a painful procedure . Thus , this study was undertaken to establish the role of intracervical block as pain relief modality for HSG . Methods This prospect i ve , r and omized study included hundred women attending the Department of Obstetrics and Gynecology , at a tertiary care centre in India . They were divided r and omly through a computer generated table into two groups of 50 women each . In the study group , women received intracervical block along with premedication whereas in the control group women received premedication alone . Each patient was asked to rate her pain at six different points of time ( T1–T6 ) during HSG using Visual analogue scale ( VAS ) and Verbal descriptive score . The difference in pain scores amongst the two groups was analyzed using independent t test . Results Reduction of pain was observed from placement of tenaculum till end of procedure ( T3–T6 ) with intracervical block ( p < 0.05 ) . Pain remained at a statistically lower level during the most painful steps i.e. traction of the cervix ( VAS : 2.080.49 cm , 95 % C I 1.18–2.98 vs. 4.21.15 cm , 95 % CI 3.3–5.1 , p = 0.001 ) and with the insertion of dye ( VAS : 2.640.49 , 95 % CI 1.7–3.5 vs. 5.121.45 . 95 % CI 4.3–6.0 , p = 0.001 ) in the study group as compared to control group . Conclusion Intracervical block can be offered to all women undergoing HSG to make the procedure less painful and thus improve the compliance Summary The aim of this study was to compare the efficacy of equivalent doses of lignocaine spray vs lignocaine jelly in reducing pain during the application of a tenaculum to the cervix . A total of 58 women undergoing hysterosalpingography were prospect ively r and omised to receive either two doses of 10 % lignocaine spray or 1 ml of 2 % lignocaine jelly ( both doses equivalent to 20 mg of lignocaine base ) topically onto the cervix before tenaculum attachment . There was no difference in pain scores ( measured by visual analogue scale and 4-point verbal descriptor scale ) between lignocaine spray and lignocaine jelly during the attachment of the tenaculum to the cervix . In conclusion , there was no difference in pain during tenaculum attachment to the cervix following topical application of equivalent doses of either lignocaine jelly or spray OBJECTIVE To assess whether transcervical intrauterine topical instillation of a local anesthetic agent reduces pain at hysterosalpingography . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Department of reproductive medicine at a university teaching hospital . PATIENT(S ) One hundred ten women undergoing hysterosalpingography ( HSG ) . INTERVENTION(S ) Subjects were r and omized to receive either 2 mL of 2 % plain lignocaine or 2 mL of 0.9 % sodium chloride solution ( placebo ) topically into the uterine cavity before the HSG was performed . MAIN OUTCOME MEASURE(S ) The degree of lower abdominal pain experienced both during the injection of contrast media at HSG and 10 minutes after the procedure using a 20-cm visual analogue scale ( VAS ) and a four-point verbal descriptor scale ( VDS ) . RESULT ( S ) There was no difference in pain scores between lignocaine and placebo during the HSG . However , at 10 minutes after the HSG , subjects receiving lignocaine experienced more pain than those on placebo . CONCLUSION ( S ) Transcervical intrauterine topical instillation of 2 mL of 2 % plain lignocaine does not reduce pain during HSG and may lead to increased pain immediately after the procedure BACKGROUND The aim of our study is to evaluate the efficacy of applying lidocaine 25 mg-prilocaine-25 mg/G cream ( EMLA 5 % ) on the uterine cervix for pain relief when performing hysterosalpingography ( HSG ) . METHODS Eighty-two patients undergoing HSG as part of infertility evaluation were r and omized into groups receiving EMLA ( 42 ) or placebo cream ( 40 ) in a double-blinded prospect i ve study from which four women were later excluded . The cream was applied to the uterine cervix by means of a cervical cup 30 min before the HSG . Pain perception related to the HSG procedure was scored by visual analogue scale ( VAS ) at five predefined steps : after speculum application , after cervical instrumentation of the tenaculum and cannula , at the end of uterine filling , at completion of tubal spillage , and immediately following instrument removal . In addition , the patients were asked to retrospectively rate the pain during the entire procedure in a telephone interview the following day . RESULTS Cervical instrumentation was found to be the most painful step of HSG ( P < 0.001 ) . When comparing the VAS pain scores , cervical instrumentation in the EMLA-treated patients was associated with significantly less pain than the control group : 3.3 + /- 2.9 versus 4.9 + /- 2.7 , respectively ( P = 0.02 ) . CONCLUSIONS Topical application of EMLA 5 % cream on the uterine cervix before performing HSG significantly reduced the pain during this procedure OBJECTIVE : A hysterosalpingogram is an integral part of the evaluation of infertility but is often painful . Intrauterine anesthesia may help to alleviate the discomfort associated with this procedure . METHODS : We conducted a r and omized , double-blinded , placebo-controlled trial of intrauterine lidocaine in women undergoing hysterosalpingography ( HSG ) . All women were instructed to take a nonsteroidal analgesic before the hysterosalpingogram . Patients received 3 mL of buffered 2 % lidocaine solution or 0.9 % normal saline instilled into the uterus before HSG . The primary outcome was the degree of pain experienced documented via 10-cm visual analogue pain scales . Systematic assessment s of discomfort were also collected by the attending physician , radiology technician , and radiology physician . RESULTS : Sixty-four patients were r and omly assigned to placebo and 63 women were r and omly assigned to the lidocaine group . There were no differences in mean age , race , parity , or history of dysmenorrhea or chronic pelvic pain . There were no differences in the pain scores at baseline , during , or after the study procedure between the 2 groups . Peak pain scale scores associated with the procedure were 5.3 ± 0.4 in both the placebo and study groups . In addition , assessment s of patient discomfort revealed no significant differences between the 2 groups . CONCLUSION : We found no difference in pain between the intrauterine-lidocaine and placebo groups . Intrauterine lidocaine does not appear to be effective in decreasing pain in women undergoing HSG . LEVEL OF EVIDENCE : OBJECTIVES To compare the efficacy of oral naproxen with intrauterine instillation of 1 % lignocaine for pain relief in women undergoing hysterosalpingography ( HSG ) as an infertility investigation . METHODS One hundred women undergoing HSG were r and omly allocated into 2 groups . Group A ( n = 50 ) underwent intrauterine instillation of 5 mL of 1 % lignocaine 2 minutes prior to the procedure , while the women in group B ( n = 50 ) were instructed to self-administer a single oral dose of 375 mg of naproxen 1 hour prior to HSG . Pain scores immediately after the procedure ( 0 minutes ) and delayed pain scores ( 30 minutes ) were recorded and compared . RESULTS Women in both groups were comparable in age and parity . The mean + /- SD pain scores in group A and group B at 0 minutes and 30 minutes were not significantly different ( P = 0.12 and P = 0.07 ) . CONCLUSION Intrauterine lignocaine was no more effective than oral naproxen for pain relief during HSG There is an increasing tendency to perform minor gynecological procedure on an outpatient setting in which adequate pain management is m and atory in order to maximize the success of procedure . Topical anesthetics have been extensively studied in many minor gynecological procedures and shown to provide good pain relief especially for procedures involving the surface tissues ; however they have hardly been explored as means of reducing pain for hysterosalpingography ( HSG ) . We aim ed to investigate whether intrauterine lidocaine gel application can provide any pain relief during and after HSG . ( excerpt OBJECTIVE To compare the analgetic efficacy and side-effects of Naproxen and Tramadol following the outpatient VABRA aspiration or hysterosalpingography . SETTING Ninety-one patients from the gynaecology clinics of two university hospitals and one municipal-teaching hospital . DESIGN Multicentre double blind r and omized clinical trial . Computerised r and omisation , stratification per-centre . METHODS Semiquantitative assessment of the two drugs was performed by the patient and the gynaecologist using a 1- to 6-point scale . Pain , stress and well-being was scored by the patient using the visual analog scale ( VAS ) and the verbal description scale ( VDS ) , ranging from 0 ( good ) to 100 ( bad ) . Side-effects during the first 24 h postoperatively were recorded by the patient in a diary . RESULTS The analgetic efficacy ( pain , stress and well-being ) of Naproxen and Tramadol was identical . Subjective assessment by the patient and the doctor also revealed no differences between Naproxen and Tramadol . Side-effects of Tramadol , however , were significantly more severe than those of Naproxen and this phenomenon was responsible for a lower ability to proceed with normal activities in the Tramadol group . CONCLUSION Tramadol is a good alternative for Naproxen at outpatient VABRA or HSG procedures when Naproxen is contra-indicated AIM The aim of this study was to evaluate whether the use of lidocaine 10 % spray was effective in pain control during hysterosalpingography ( HSG ) . METHODS A total of 81 patients were r and omly assigned to three groups : Group 1 , 10 mg lidocaine hydrochloride 10 % spray ; Group 2 , 20 mg lidocaine hydrochloride 10 % spray ; and Group 3 , Placebo . We used a st and ard 10 cm Visual Analog Scale for pain scoring . The ' 0 cm ' end corresponded to ' no pain ' , and the ' 10 cm ' end represented the ' worst pain ever ' . We asked the patients to mark their pre-HSG pain expectancies initially , then to mark their pain during uterine traction after the tenaculum has been applied . Finally , they were asked to mark their pain during contrast medium injection . RESULTS In Group1 , the mean anticipated pain ( AP ) score was 64.51 + /- 12.62 , the mean pain ( MP ) score during cervical traction with uterine tenaculum was 57.48 + /- 11.32 ( P : 0.011 ) , and the MP score during contrast medium injection was 46.22 + /- 13.00 ( P : 0.005 ) . In Group 2 the mean AP score was 66.44 + /- 12.02 , the MP score during cervical traction with uterine tenaculum was 48.03 + /- 13.44 ( P : 0.001 ) , and the MP during contrast medium injection was 46.25 + /- 11.57 ( P : 0.001 ) . In Group 3 the mean AP score was 61.8 + /- 18.5 , the MP score during cervical traction with uterine tenaculum was 59.5 ( P : 0.07 ) , and the MP during contrast medium injection was 57.5 + /- 14.5 ) ( P : 0.304 ) . CONCLUSION Topical lidocaine spray is a practical and effective analgesic for decreasing pain perception scores during the HSG procedure . A 10 mg dose is comparable to a 20 mg dose in pain reduction with less chance of side effects and better cost-effectiveness Hysterosalpingography ( HSG ) is associated with pain during the four-step procedure . This prospect i ve , double-blind , r and omized , placebo-controlled study was conducted to investigate the effect of the analgesic flurbiprofen , administered prior to HSG , in 60 women . Thirty women were r and omized to receive 100 mg of flurbiprofen , orally , 1 h prior to HSG and a further 30 women were r and omized to receive placebo . Injection of contrast medium was more painful than the other steps in the HSG procedure in both groups ; however , there was no significant between-group difference in terms of pain experienced in the individual steps of HSG . Pain scores at 5 and 30 min after the procedure were compared between the two groups . There was a significant decrease in the visual analogue scale pain score in the flurbiprofen-treated group compared with the placebo-treated group at both time points . Thus , the authors recommend flurbiprofen as a prophylactic analgesic to be administered before HSG procedures The aim of this study was to assess patient tolerance of two outpatient tests . Sixty-six infertile women were prospect ively r and omized to hysterosalpingo-contrast sonography ( HyCoSy ) ( n = 34 ) or X-ray hysterosalpingography ( HSG ) ( n = 32 ) . The procedures were performed by the same operator . The uterine cavity outline and tubal patency were determined by both procedures . The mean times taken and the volume of contrast medium required for HyCoSy and HSG were similar : 12.1 + /- 5.2 and 9.5 + /- 4.8 min and 9.4 + /- 5.2 and 11.5 + /- 8.4 ml , respectively . Side-effects were assessed during the procedure , at 2 h , 24 h and 28 days . The most common side-effect was pelvic pain , in 56/66 ( 84 % ) women , occurring during the procedures ( HyCoSy 19/34 ( 56 % ) ; HSG 23/32 ( 72/% ) ) and /or in the following 24 h ( HyCoSy 14/34 ( 41 % ) ; HSG 15/32 ( 47 % ) ) . This was described as less severe or equal to their usual period pains ( HyCoSy 100 % ; HSG 85 % ) . Only 12/66 ( 18 % ) women required simple non-steroidal analgesia ( HyCoSy 8/34 ( 24 % ) ; HSG 4/32 ( 13 % ) ) . There were no significant differences between the two methods concerning the frequency or severity of pains at different stages during and after the procedure or analgesia requirements . HyCoSy and HSG are equally well tolerated outpatient procedures for assessing tubal patency and uterine abnormalities . In addition , HyCoSy avoids the risks of ovarian irradiation and allows scanning of the uterine corpus and ovaries at the same time |
13,325 | 30,430,417 | With the exception of studies on cold-stressed laying hens , the results of studies of Cr supplementation of chickens , whether broilers or laying hens , were found to be too inconsistent for any firm conclusions to be drawn other than that Cr supplementation generally leads to accumulation of Cr in tissues .
Few potential trends in terms or beneficial or deleterious effects from Cr supplementation were found regardless of strain of chicken , Cr source , Cr dose , duration of supplementation , or variable examined . | Chromium supplementation has been proposed to have beneficial effects in farm animals , particularly when under stress .
The last two decades , in particular , have seen an emphasis on examining the effects of supplemental chromium on a variety of variables in chicks and chickens .
Thus , given the recent approval of a Cr(III ) compound for use in chicken feed in the United States and the recent surge in papers on the use of Cr in chicken feed , the need for a systematic review of studies utilizing chickens is extremely urgent and timely . | This study was conducted to determine the effects of dietary supplementation with Cr nicotinate and Cr chloride and their optimum inclusion rate on performance , carcass traits , meat oxidative stability , serum metabolites , hematological parameters , and liver chromium concentration in heat-stressed broilers . A total number of 420 , 1-day-old male broiler chicks were r and omly assigned to seven treatments with four replicates of 15 chicks . The dietary treatments consisted of the basal diet supplemented with 0 ( control ) , 500 , 1,000 , and 1,500 μg/kg Cr in the form of Cr nicotinate and Cr chloride . Chicks were raised for 6 weeks in heat stress condition ( 33 ± 2 ° C ) . Supplements of organic and inorganic Cr particularly at 1,500 μg/kg incorporation increased feed consumption ( P < 0.05 ) and body mass gain of broilers ( P < 0.01 ) . Cr supplementation increased carcass yield and decreased abdominal fat ( P < 0.01 ) . Supplementation of 1,500 μg/kg Cr nicotinate ( P < 0.05 ) enhanced liver Cr concentration . Storage time increased lipid oxidation of meat ( P < 0.01 ) . Cr decreased lipid oxidation of breast and thigh muscles over 2 ( P < 0.01 ) or 6 ( P < 0.05 ) days of storage time . Birds fed 1,500 μg/kg Cr nicotinate , had lower concentration of serum glucose and triglyceride at 21 days ( P < 0.05 ) . Hematological parameters tested at 21 and 42 days , were not influenced . The results suggested that dietary Cr supplementation regardless of its source have a positive effect on productive , and carcass traits , also enhances oxidative stability of refrigerated meat in broilers reared under heat stress conditions The aim of this study was to investigate the effect of dietary supplementation of nanoparticle trivalent chromium on nutrient utilization , growth performance and serum traits of broilers . This study included two trials . In trial 1 , 32 three-week-old broilers were divided into four groups : the control , chromium chloride ( CrCl3 ) , chromium picolinate ( CrPic ) and nanoparticle chromium picolinate ( NanoCrPic ) . Chromium was added at a 1200 μg/kg level to evaluate the nutrient and chromium utilization . In trial 2 , 160 one-day-old broilers were r and omly divided into four groups as in trial 1 , with four replicates . The results of trial 1 indicated that the chromium utilization is as follows : NanoCrPic > CrPic > CrCl3 and control groups , with significant differences between groups ( p < 0.05 ) . Crude fat utilization in CrCl3 group was lower than in that the control group ( p < 0.05 ) . The results of trial 2 indicated that feed intake of 4 - 5 weeks showed better result in the CrCl3 group than that in the CrPic group ( p < 0.05 ) . The results of serum traits indicated that the LDL-cholesterol in the NanoCrPic groups was lower than that in the CrPic group ( p < 0.05 ) . The NanoCrpic and CrPic groups showed significantly increased serum chromium concentration when compared with the control and CrCl3 groups ; the triglyceride level in the CrCl3 group was lower than that in the CrPic group ( p < 0.05 ) . This study concluded that compared with CrPic , NanoCrpic supplementation could increase chromium utilization and lower the serum LDL-cholesterol of broilers The effects of 8 wk of daily chromium supplementation ( 3.3 - 3.5 mumol as chromium chloride or chromium picolinate ) or placebo ( 0.1 mumol Cr ) and weight training were examined in 36 men in a double-blind design . Strength , mesomorphy , fat-free mass , and muscle mass increased with resistance training independently of chromium supplementation ( P < 0.0001 ) . Protein , magnesium , zinc , copper , and iron intakes equalled or exceeded the recommended dietary allowance ( RDA ) or estimated safe and adequate daily dietary intake ( ESADDI ) during training and did not change significantly from pretraining intakes ( P > 0.05 ) . Chromium supplementation increased the serum chromium concentration and urinary chromium excretion without a difference as a result of the chemical form of chromium ( P < 0.05 ) . Resistance training was associated with a significant decrease ( P < 0.05 ) in serum ferritin , total-iron-binding capacity , transferrin saturation , the ratio of enzymatic to immunoreactive ceruloplasmin , and plasma copper , independently of chromium supplementation . However , transferrin saturation was decreased more with chromium picolinate supplementation ( 24 % ) than with chromium chloride or placebo ( 10 - 13 % ) . Compared with pretraining values , urinary magnesium excretion increased ( P < 0.05 ) and urinary zinc output tended to decrease during the first 4 wk of resistance training and then returned to baseline values for the final 4 wk , which suggests an adaptation in mineral excretion in response to weight training . These findings suggest that routine chromium supplementation has no beneficial effects on body- composition change or strength gain in men . Whether chromium supplementation of individuals with diminished chromium nutriture facilitates propitious changes in body structure and function remains to be determined 1 . This study investigated the effects of supplemental copper and chromium on the serum and egg traits of laying hens using 144 forty-five-week-old White Leghorn layers . The hens were r and omly assigned into 9 groups to conduct this 3 copper ( 0 , 125 and 250 mg/kg as copper sulphate ) × 3 chromium ( 0 , 800 and 1600 µg/kg as chromium picolinate ) factorial trial . 2 . Egg yolk cholesterol was significantly reduced by supplementary copper ( Cu ) and chromium ( Cr ) and there was an interaction between Cu and Cr supplementation . Egg production , egg weight , eggshell strength and eggshell thickness were not influenced by Cu or Cr supplementation . 3 . Serum cholesterol concentration was decreased by Cu supplementation and very low-density lipoprotein ( VLDL ) was reduced markedly by both Cu and Cr . On the other h and , high-density lipoprotein ( HDL ) was significantly increased by Cu and Cr . Interaction occurred between Cu and Cr in the VLDL and HDL parameters . Supplmentary Cu also reduced VLDL-cholesterol ( VLDL-C ) and enhanced HDL-cholesterol ( HDL-C ) , while supplemental Cr had a contrary effect on these two parameters . 4 . If minimum egg cholesterol content is the criterion , this study suggests that 125 mg/kg of Cu together with 800 to 1600 µg/kg of Cr provide adequate supplementary concentrations for laying hens The study investigated the effect of supplementation of chromium propionate at different dosage levels ( 100 to 3,200 µg/kg of elemental chromium in feed ) on the performance , carcass characteristics , and immune response of broiler birds . The study was conducted on male broiler chickens ( Cobb 400 ) for a period of 42 d as per the completely r and omized design . Seven hundred 1-d-old birds were r and omly segregated into 7 treatment groups , each with 10 replicates , and each replicate having 10 birds . Weight gain , feed intake , carcass characteristics , immune response , and the serum biochemical parameters of birds were studied during the supplementation period . There was no significant response to chromium supplementation on weight gain , feed intake , FCR , and lymphoid organ weights for the overall study period of 42 d. With increased chromium dosage , the breast meat yield improved linearly ( P = 0.045 ) . Antibody response to Newcastle disease vaccination improved quadratically ( P = 0.001 ) with increased dose of chromium in the diet . Improved cell-mediated immune response was indicated by the increase ( quadratic , P = 0.00 ) in lymphocyte proliferation ratio with increased dose of chromium supplementation . Heterophil : lymphocyte ratio decreased ( quadratic , P = 0.004 ) with chromium propionate dosage , suggestive of reduced stress levels . Chromium propionate supplementation also reduced serum glucose levels ( quadratic , P = 0.008 ) and improved ( quadratic , P = 0.016 ) the total protein levels In this study , the effect of the supplemental organic chromium ( Cr ) forms on the expression of ovarian orexin(hypocretin ) , glucose transporters ( GLUTs ) , heat shock proteins ( HSPs ) and nuclear factor-kappaB (NF-κB)were investigated in laying hens ( HS ) . Laying hens ( n=1800 ; 16-wk-old ; Lohmann LSL-Lite ) were allocated to 6 r and om groups according to a 2 × 3 factorial trial scheme with two different environmental temperatures [ Thermoneutral ( TN groups ; at either 22±2 ° C 24 h/d ) and heat stress ( HS groups ; at 34±2 ° C for 8 h/d , 08:00 to 17:00 h , followed by 22 ° C for 16 h for a period of 12 wks ) ] , and hens reared under both environmental conditions were fed either a basal diet or the basal diet supplemented with 1.600 mg of chromium-picolinate ( CrPic , 12.43 % Cr ) and 0.788 mg of chromium-histidinate ( CrHis , 25.22 % Cr ) per kg of diet , delivering 200 µg elemental Cr per kg diet . HS groups showed decreased levels of orexin and GLUTs(GLUT1 , GLUT4 ) , and increased NFκB , HSP60 , HSP70 and HSP90 levels compared to the TN groups in ovarian tissue of hens ( P < 0.0001 for all).However , dietary chromium supplementation ( CrPic-CrHis ) increasedorexin and GLUTs levels and significantly reduced the NF-κB and HSPs levels making them closer to those of thermoneutral group ( P < 0.0001).In conclusion , CrPic and CrHis showed supported the relief and treatment of stress complications This study was conducted to investigate the effects of chromium from chromium propionate ( CrPro ) on serum lipids , carcass traits , and breast meat quality in heat-stressed birds . A total of 210 1-day-old male broilers were r and omly allotted by initial body weight ( BW ) into 5 treatments with 7 replicates with 6 birds per replicate pen for 42 days . The treatments included a basal corn-soybean meal diet and basal diet supplemented with 0.2 , 0.4 , 0.8 , or 1.6 mg Cr/kg diet . Birds had ad libitum access to feed and distilled-deionized water at normal conditions for 1–3 weeks with little or no stress , and then birds were housed under heat stress conditions with 35 ± 2 ° C ambient temperature for 4–6 weeks . Results showed that serum triglyceride ( TG ) ( P = 0.0006 ) and low-density lipoprotein cholesterol ( LDLC ) ( P = 0.0038 ) concentrations were decreased linearly as Cr dose increased . Compared with other groups , birds receiving 0.8 or 1.6 mg Cr/kg had lower TG ( P = 0.0015 ) . Compared to control birds , birds fed diets with 0.2 , 0.4 , 0.8 , or 1.6 mg Cr/kg supplementation had lower LDLC ( P = 0.0006 ) . However , the total cholesterol ( TC ) and high density lipoprotein cholesterol ( HDLC ) concentrations in serum were not affected by treatment ( P > 0.05 ) . No difference was observed in BW , the relative weights of breast muscle , thigh muscle and abdominal fat ( P > 0.05 ) , and breast meat quality ( Ph15min , Ph24h , L * , a * , b * , cooking loss , shear force ) among the treatments ( P > 0.05 ) . Results from this study indicated that CrPro supplementation could be beneficial to serum lipids metabolism of heat-stressed broiler chickens by decreasing TG and LDLC contents , but had no impacts on meat quality and carcass traits of the heat-stressed broilers A total of 250 broilers in a completely r and omized design selected to evaluate the effect of different levels of chromium ( Cr ) supplementation on performance , carcass traits and some blood parameters of heat-stressed broiler chicks . All birds were kept under heat stress temperature ( 33 ± 3 ° C ) and divided into five treatments groups . Each treatment consisted of five pens with 10 birds in each pen . The basal diets were supplemented with 0 ppb ( control ) , 800 ppb Cr-L-Met ( T1 ) , 1,200 ppb Cr-L-Met ( T2 ) or 800 ppb CrCl3 ( T3 ) , and 1,200 ppb CrCl3 ( T4 ) . The feed intake and body mass were measured at 10 , 21 , and 42 days of age . Blood sample s were collected from two birds in each replicates to determine biological and hematological values at 28 and 42 days of age . There were no significant difference in mass gain and feed conversion of broilers that received Cr supplementations compared with controls . The serum glucose concentration decreased in broilers received organic chromium methionine supplements compared with other treatments groups . Slight but not significant increases were observed in serum high-density lipoprotein ( HDL ) concentration of treated groups than controls while the mean serum HDL concentration was significantly higher in T2 group compared with control group . Serum low-density lipoprotein level decreased in broiler received organic Cr supplements ( p < 0.05 ) The present study was conducted to investigate the effects of dietary supplementation of chromium methionine ( CrMet ) on performance , immune responses , and stress status of broiler chicks subjected to heat-stress conditions . A total of 450 day-old Ross 308 broiler chicks were r and omly distributed between 5 replicate pens ( 15 birds each ) of 6 experimental treatments according to a 2 × 3 factorial arrangement of treatments including 2 temperature conditions ( thermoneutral and heat stress ) and 3 supplemental Cr levels ( 0 , 500 , and 1,000 μg/kg as CrMet ) . For induction of heat stress , the house temperature was set at 35 ± 2 ° C from 15 to 42 d of age . Results showed that the chicks subjected to heat-stress condition had lower ( P < 0.01 ) feed intake , BW gain , and deteriorated ( P < 0.05 ) feed conversion values compared with those kept in the thermoneutral house . Dietary supplementation with CrMet increased ( P < 0.01 ) feed intake and improved ( P < 0.01 ) weight gain and feed efficiency . There were significant Cr level × temperature interactions , so that inclusion of CrMet into the diets was more effective in heat-stressed chicks . Exposure to heat stress suppressed ( P < 0.01 ) cutaneous hypersensivity response to phytohemagglutinin-P injection at 30 d of age , and dietary supplementation of 500 μg Cr/kg induced ( P < 0.05 ) this response , with the greater impacts in heat-stressed chicks , result ing in a significant ( P < 0.01 ) Cr × temperature interaction . Antibody responses against Newcastle and infectious bronchitis disease viruses were diminished ( P < 0.01 ) in heat-stressed chicks . Dietary inclusion of CrMet improved ( P < 0.05 ) antibody responses to different immunostimulants , and this effect was more pronounced in heat-stressed chicks . Exposure to heat stress caused a significant ( P < 0.05 ) decrease in the proportion of helper ( CD4 + ) T lymphocytes and increased cytotoxic ( CD8 + ) T lymphocytes , result ing in a decreased ( P < 0.01 ) CD4 + to CD8 + ratio in peripheral blood circulation . Supplementation of CrMet to heat-stressed chicks modulated ( P < 0.01 ) plasma corticosterone level . The present findings indicate that dietary CrMet supplementation could alleviate heat-stress-induced growth retardation in broiler chicks . Moreover , supplemental CrMet modulated suppressive effects of heat stress on cellular and humoral immune responses This experiment was carried out to investigate the effects of different levels of organic and inorganic chromium on the performance , immune function and some serum mineral concentrations of broilers under heat stress condition ( 23.9–37 ° C cycling ) . A total of 150 one-day-old broiler chicks according to a completely r and omized design were assigned into five treatment groups . Each treatment consisted of three replicates and each replicate contained ten chicks . Chicks were fed on corn – soybean meal basal diets with added different concentrations of chromium ( 0 , 600 and 1,200 μg kg−1 chromium chloride or 600 and 1,200 μg/kg chromium l-methionine ) from 1 to 49 days of age . Humoral immunity was assessed by intravenous injection of 7 % sheep red blood cell ( SRBC ) followed by evaluation of serum for antibody titers in primary and secondary responses . Cell-mediated immunity was assessed by the cutaneous basophil hypersensitivity ( CBH ) test to phytohemagglutinin (PHA)-P at day 32 and PHA-M at day 48 . Heterophil/lymphocyte ( H/L ) ratio was also measured as a reliable indicator of stress . The body mass , feed intake and conversion ratio were not influenced by dietary chromium ( P > 0.05 ) . Dietary supplementation of both organic and inorganic chromium significantly increased primary and secondary antibody responses ( P < 0.01 ) , and also improved H/L ratio ( P < 0.05 ) , CBH response ( P < 0.01 ) as well as relative weights of thymus ( P < 0.05 ) and spleen ( P < 0.01 ) . Both dietary organic and inorganic chromium caused an increase in serum concentrations of Cr and Zn ( P < 0.01 ) , but decreased the serum concentration of Cu ( P < 0.01 ) . These results suggest that supplemental chromium especially in organic form offers a good management practice to reduce heat stress-related depression in immunocompetence of broiler chicks An experiment was conducted to investigate the effects of dietary chromium ( Cr ) source and concentration on growth performance , carcass traits , and some serum lipid parameters of broilers under normal rearing conditions for 42 days . A total of 252 1-day-old Cobb 500 commercial female broilers were r and omly allotted by body weight ( BW ) to one of six replicate cages ( six broilers per cage ) for each of seven treatments in a completely r and omized design involved in a 2 × 3 factorial arrangement of treatments with three Cr sources ( Cr propionate ( CrPro ) , Cr picolinate ( CrPic ) , Cr chloride ( CrCl3 ) ) and two concentrations of added Cr ( 0.4 and 2.0 mg of Cr/kg ) plus a Cr-unsupplemented control diet . The results showed that dietary Cr supplementation tended to increase the breast muscle percentage compared with the Cr-unsupplemented control group ( P = 0.0784 ) , while Cr from CrPic tended to have higher breast muscle percentage compared with Cr from CrCl3 ( P = 0.0881 ) . Chromium from CrPic also tended to increase the breast intramuscular fat ( IMF ) compared with Cr from CrCl3 ( P = 0.0648 ) . In addition , supplementation of 0.4 mg/kg Cr tended to decrease low-density lipoprotein cholesterol ( LDL-C ) ( P = 0.0614 ) . Compared with the control group , broilers fed Cr-supplemented diets had higher triglyceride ( TG ) ( P = 0.0129 ) regardless of Cr source and Cr concentration . Chromium from CrPro and CrPic had lower total cholesterol ( TC ) compared with Cr from CrCl3 ( P = 0.0220 ) . These results indicate that dietary supplementation of Cr has effects on carcass characteristics and serum lipid parameters of broilers under normal rearing conditions , while supplementation of organic Cr can improve carcass characteristics and reduce the cholesterol content in serum This study evaluated the effects of supplemental dietary chromium ( Cr ) on the performance , carcass traits , and some serum parameters of broilers under a heat stress ( 23.9 to 37 ° C cycling ) condition . A total of 150 1-day-old broiler chicks ( Cobb 500 ) according to a completely r and omized design were assigned into five treatment groups . Each treatment consisted of three replicates and each replicate contained ten chicks . Treatments were supplemented with 0 ( control ) , 600 , and 1,200 μg kg−1 Cr in the form of Cr chloride ( CrCl3 ) and Cr L-methionine from 1 to 49 days of age . Blood sample s were collected from two birds in each replicate to determine serum parameters at 35 and 49 days of age . The body mass , feed intake , and conversion ratio were not influenced by dietary Cr ( P > 0.05 ) . Dietary supplementation of Cr from either CrCl3 or Cr L-methionine caused increased serum concentrations of Cr ( P < 0.05 ) , but had no effect on serum insulin and glucose concentrations at both sampling times ( P > 0.05 ) . Serum triglycerides , very low-density lipoprotein cholesterol , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol were also not significantly affected ( P > 0.05 ) by dietary treatments , whereas total cholesterol concentration decreased in chicks fed Cr L-methionine compared to the control ( P < 0.05 ) The objectives of this study were to investigate the immune responses of broiler chickens fed diets supplemented with different level of chromium methionine ( CrMet ) in heat stress ( HS ) condition . Two hundred and eighty eight male broiler chickens ( Ross 308 ) were allocated to four treatment groups ( supplementation with 0 , 200 , 400 or 800 ppb Cr in the form of CrMet ) in a completely r and omized design . The experiment was conducted at heat stressed condition and all birds were kept under temperature of 33±2 ° C . Antibody titers against Newcastle disease virus ( NDV ) and infectious bronchitis virus ( IBV ) , heterophil to lymphocyte ratios ( H/L ) , and concentration of plasma cortisol ( CPC ) were measured at 21 and 42 d. At 42 days of age two birds were chosen r and omly from each replicate , slaughtered , spleen and bursa of Fabricius were collected , weighed and expressed as a percentage of live body weight . Antibody titers against NDV and IBV at 21 and 42 days of age in broiler fed supplemental CrMet were higher than in broiler chickens fed control diet ( p<0.05 ) . CPC level in broiler chickens fed CrMet were significantly ( p<0.05 ) decreased . Increases in lymphocyte counts and consequently a decrease in heterophil to lymphocyte ratios in broiler chickens fed 800 ppb Cr were observed at 21 and 42 d. Supplementation with CrMet had no significant effect on lymphoid organs of broilers . The results suggest that dietary CrMet supplementation at a level of 800 ppb can improve some immune responses of broiler chickens under heat stress conditions The objective of this study was to investigate the effects of dietary supplemental chromium ( Cr ) on growth performance , carcass traits , and meat quality of broilers reared under heat stress . A total of 252 1-d-old Cobb 500 commercial female broilers were r and omly allotted by body weight ( BW ) to one of six replicate cages ( six broilers per cage ) for each of seven treatments in a completely r and omized design involving a 2 × 3 factorial arrangement of treatments with three Cr sources ( Cr propionate , CrPro ; Cr picolinate , CrPic ; Cr chloride , CrCl3 ) and two concentrations of added Cr ( 0.4 , or 2.0 mg of Cr/kg ) plus a Cr-unsupplemented control group . Feed and distilled-deionized water were available ad libitum for an experimental phase of 42 days . For induction of heat stress , the house temperature was set at 33 ± 2 ° C from 15 to 42 days of age . Results showed that birds supplemented with Cr , regardless of Cr source , had increased ADG ( P = 0.032 ) than controls . Birds fed 2.0 mg Cr/kg diet had greater ADG ( P = 0.005 ) than birds fed 0.4 mg Cr/kg diet . Compared to controls , birds fed with Cr had greater dressing percentage ( P = 0.021 ) . Percentage of abdominal fat decreased ( P = 0.013 ) , whereas , breast intramuscular fat ( IMF ) remained unaffected ( P = 0.147 ) in Cr supplemented vs control broilers . Broilers supplemented Cr had decreased b * values of meat color ( P = 0.042 ) in breast muscle . B*values were also lesser ( P = 0.049 ) in birds fed CrPro than birds supplemented with CrCl3 or CrPic . Regardless of Cr source , the percentage of cooking loss was decreased ( P = 0.025 ) with Cr supplementation in breast muscle when compared to controls . Results from this study indicate that Cr supplementation , independent of its source , could promote growth and improve carcass traits and meat quality of broilers under heat stress conditions . Chromium propionate seems to have greater beneficial effects on meat color in comparison with CrPic and CrCl3 This experiment was carried out to investigate the effects of different levels chromium picolinate ( CrPic ) and chromium nanoparticles ( nano-Cr ) on the performance and immune function of broilers under heat stress condition . A total of 320 Ross 308 broiler chicks ( from 21 to 42 days ) were assigned r and omly into eight treatment groups ( four replicates per treatment , and 10 chicks per replicate ) and be reared at either thermoneutral ( 21 ˚C ) or heat stress ( 36 ◦ C ) . The treatments were control ( T1 ) group without supplementation and heat stress , T2 as a heat stress group without supplementation , T3 , T4 and T5 groups which were supplemented with 500 , 1000 and 1500 ppb CrPic in diet with heat stress , respectively and T6 , T7 and T8 groups which were supplemented with 500 , 1000 and 1500 ppb nano-chromium in diet under heat stress , respectively . Supplementation of chromium and nano-chromium improved performance including weight gain and feed conversion ratio of heat-stressed chickens . Antibody titers against avian influenza ( AI ) and infectious bronchitis ( IB ) at 21 to 42 days of age in broilers fed supplemental chromium and nano-chromium were higher than broiler chickens fed control diet ( p < 0.05 ) . Nano-chromium supplementation at level of 1000 ppb and CrPic at level of 1500 ppb improved the antibody titers against AI and IB of broilers under heat stress conditions . It can be concluded from these findings that dietary supplementation of CrPic and nano-Cr can improve performance and antibody titers against AI and IB under heat stress conditions in broilers This study was conducted to investigate the effect of increasing dietary levels of inorganic chromium ( CrCl3·6H2O ) on the performance , blood chemistry , and immune response of broilers . Eighty newly hatched Ross PM3 broiler chicks were evenly distributed to five groups of 16 chicks each . Two groups ( control and only sheep red blood cell inoculated ) were fed the basal diet containing 2.2 and 4.5 mg Cr/kg and the remaining groups were fed 20 , 40 , or 80 mg/kg Cr-supplemented diets for 44 d. Chicks in all groups , except in the control , at 3 and 5 wk of age , were injected intraperitonally with sheep red blood cell for determining the primary and secondary antibody responses , respectively . When the chicks were 4 wk of age , a delayed-type hypersensitivity test was performed . White blood cells were differentiated . Blood sample s were collected for the determination of serum proteins , glucose , cholesterol , cortisol , minerals , and alkaline phosphatase activity and for antibody response . Chromium had no effect on weight gain , but 20 mg/kg supplemental Cr result ed in 18.57 % reduction in feed consumption and improved feed efficiency by 16.77 % . Chromium did not affect serum cholesterol and P levels but reduced serum glucose and increased serum protein , Cr , Ca , and Mg levels , and ALP activity . A slight reduction was observed with Cr supplementation in cortisol levels . Slight but not significant increases were observed with Cr in serum Zn and Cu . Chromium increased the ratio of bursa of Fabricius and liver to body weight . Heterophil and monocyte counts and heterophil/lymphocyte ratio were reduced and lymphocyte counts , total antibody , IgG , and IgM titers were increased by supplemental Cr . All levels of Cr increased the cell-mediated response to phytohemagglutinin . No alterations in tissues were observed by histopathological examinations A total of 240 broiler chicken of same hatch with uniform weight were used in a biological experiment with completely r and omized design to investigate the effects of incorporating organic chromium ( Cr ) in flaxseed meal based diet on the fatty acid profile , oxidative stability and functional properties of broiler chicken meat . Five diets were formulated as per the recommendations of BIS ( Nutrient requirements for poultry 13 : 9863 , Bureau of Indian St and ards , New Delhi , 1992 ) in which flaxseed meal was used to replace 10 % of soyabean in basal diet and four levels of Cr ( 0.0 , 0.5 , 1.0 and 1.5 mg/kg diet ) as Cr-picolinate were used . The results revealed that flaxseed feeding significantly increased the percentage of unsaturated fatty acids , including MUFA , PUFA , ω-3 , ω-6 fatty acids and ω-3:ω-6 and PUFA : SFA ratios , whereas , significant decline was seen in saturated fatty acids and no effect of Cr was observed on the fatty acid profile of broiler chicken . Flaxseed feeding significantly reduced the cholesterol and fat percentage of meat , whereas , significant progressive reduction was observed with increasing Cr levels . The combination of 10 % flaxseed with 1.0 mg Cr/kg diet increased the final pH of broiler meat . The addition of flaxseed significantly reduced water holding capacity , extract release volume and antioxidant potential of broiler meat , whereas , increasing Cr supplementation progressively increased them . Flaxseed feeding significantly increased the drip loss and lipid peroxidation of broiler meat , whereas , Cr supplementation decreased them . It was concluded that inclusion of 10 % flaxseed and 1.5 mg Cr/kg diet results in desirable fatty acid profile , oxidative stability and functional properties of broiler chicken meat |
13,326 | 31,113,463 | Conclusions Based on the review , autologous stem cell therapy may have a positive effect on “ no-option ” patients with PAD , but presented no significant improvement in major limb salvage . | Background Peripheral arterial disease ( PAD ) is a common cause of disability and mortality .
The reconstruction of blood circulation presents to be the key to treatment , which can be achieved by surgery and interventional therapy .
Since 40 % patients have lost the chance for the therapy , a new method is needed to reduce the amputation and mortality rate for “ no-option ” patients .
The objective of our systematic review and meta- analysis was to evaluate the efficacy and safety of autologous implantation of stem cells in patients with PAD critically , compared with active controls and placebo . | OBJECTIVES Cell therapy is a novel experimental treatment modality for patients with critical limb ischemia ( CLI ) of the lower extremities and no other established treatment options . This study was conducted to assess the safety and clinical efficacy of intramuscular injection of autologous tissue repair cells ( TRCs ) . METHODS A prospect i ve , r and omized double-blinded , placebo controlled , multicenter study ( RESTORE-CLI ) was conducted at 18 centers in the United States in patients with CLI and no option for revascularization . Enrollment of 86 patients began in April 2007 and ended in February 2010 . For the prospect ively planned interim analysis , conducted in February 2010 , 33 patients had the opportunity to complete the trial ( 12 months of follow-up ) , and 46 patients had completed at least 6 months of follow-up . The interim analysis included analysis of both patient population s. An independent physician performed the bone marrow or sham control aspiration . The aspirate was processed in a closed , automated cell manufacturing system for approximately 12 days to generate the TRC population of stem and progenitor cells . An average of 136 ± 41 × 10(6 ) total viable cells or electrolyte ( control ) solution were injected into 20 sites in the ischemic lower extremity . The primary end point was safety as evaluated by adverse events , and serious adverse events as assessed at multiple follow-up time points . Clinical efficacy end points included major amputation-free survival and time to first occurrence of treatment failure ( defined as any of the following : major amputation , death , de novo gangrene , or doubling of wound size ) , as well as major amputation rate and measures of wound healing . RESULTS There was no difference in adverse or serious adverse events between the two groups . Statistical analysis revealed a significant increase in time to treatment failure ( log-rank test , P = .0053 ) and amputation-free survival in patients receiving TRC treatment , ( log-rank test , P = .038 ) . Major amputation occurred in 19 % of TRC-treated patients compared to 43 % of controls ( P = .14 , Fisher exact test ) . There was evidence of improved wound healing in the TRC-treated patients when compared with controls at 12 months . CONCLUSIONS Intramuscular injection of autologous bone marrow-derived TRCs is safe and decreases the occurrence of clinical events associated with disease progression when compared to placebo in patients with lower extremity CLI and no revascularization options Background —Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality . There is no effective pharmacological therapy available . Injection of autologous bone marrow-derived mononuclear cells ( BM-MNC ) is a promising therapeutic option in patients with critical limb ischemia , but double-blind , r and omized trials are lacking . Methods and Results —Forty patients with critical limb ischemia were included in a multicenter , phase II , double-blind , r and omized-start trial to receive either intraarterial administration of BM-MNC or placebo followed by active treatment with BM-MNC ( open label ) after 3 months . Intraarterial administration of BM-MNC did not significantly increase ankle-brachial index and , thus , the trial missed its primary end point . However , cell therapy was associated with significantly improved ulcer healing ( ulcer area , 3.2±4.7 cm2 to 1.89±3.5 cm2 [ P=0.014 ] versus placebo , 2.92±3.5 cm2 to 2.89±4.1 cm2 [ P=0.5 ] ) and reduced rest pain ( 5.2±1.8 to 2.2±1.3 [ P=0.009 ] versus placebo , 4.5±2.4 to 3.9±2.6 [ P=0.3 ] ) within 3 months . Limb salvage and amputation-free survival rates did not differ between the groups . Repeated BM-MNC administration and higher BM-MNC numbers and functionality were the only independent predictors of improved ulcer healing . Ulcer healing induced by repeated BM-MNC administration significantly correlated with limb salvage ( r=0.8 ; P<0.001 ) . Conclusions —Intraarterial administration of BM-MNC is safe and feasible and accelerates wound healing in patients without extensive gangrene and impending amputation . These exploratory findings of this pilot trial need to be confirmed in a larger r and omized trial in patients with critical limb ischemia and stable ulcers . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00282646 Background Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia ( CLI ) . Bone marrow derived Mesenchymal Stem Cells ( BM- MSCs ) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ . The primary objective was to determine the safety of BM- MSCs in patients with CLI . Methods Prospect i ve , double blind r and omized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4 , III-5 , or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment . The primary end point was incidence of treatment – related adverse events ( AE ) . Exploratory efficacy end points were improvement in rest pain , increase in Ankle Brachial Pressure Index ( ABPI ) , ankle pressure , healing of ulcers , and amputation rates . Twenty patients ( BM-MSC : Placebo = 1:1 ) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo ( PlasmaLyte A ) at the gastrocnemius muscle of the ischemic limb . Results Improvement was observed in the rest pain scores in both the arms . Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group . Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events ( SAE ) were similar in both the arms ( 5 in BM-MSC and 4 in the placebo group ) . SAEs result ed in death , infected gangrene , amputations in these patients . It was observed that the SAEs were related to disease progression and not related to stem cells . Conclusion BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight . Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies .Trial registration NIH website ( http://www . clinical trials.gov/ct2/show/NCT00883870 BACKGROUND AIMS CD133 + cells confer angiogenic potential and may be beneficial for the treatment of critical limb ischemia ( CLI ) . However , patient selection , blinding methods and end points for clinical trials are challenging . We hypothesized that bilateral intramuscular administration of cytokine-mobilized CD133 + cells in ambulatory patients with refractory CLI would be feasible and safe . METHODS In this double-blind , r and omized sham-controlled trial , subjects received subcutaneous injections of granulocyte colony-stimulating factor ( 10 μg/kg per day ) for 5 days , followed by leukapheresis , and intramuscular administration of 50 - 400 million sorted CD133 + cells delivered into both legs . Control subjects received normal saline injections , sham leukapheresis and intramuscular injection of placebo buffered solution . Subjects were followed for 1 year . An aliquot of CD133 + cells was collected from each subject to test for genes associated with cell senescence . RESULTS Seventy subjects were screened , of whom 10 were eligible . Subject enrollment was suspended because of a high rate of mobilization failure in subjects r and omly assigned to treatment . Of 10 subjects enrolled ( 7 r and omly assigned to treatment , 3 r and omly assigned to control ) , there were no differences in serious adverse events at 12 months , and blinding was preserved . There were non-significant trends toward improved amputation-free survival , 6-minute walk distance , walking impairment question naire and quality of life in subjects r and omly assigned to treatment . Successful CD133 + mobilizers expressed fewer senescence-associated genes compared with poor mobilizers . CONCLUSIONS Bilateral administration of autologous CD133 + cells in ambulatory CLI subjects was safe , and blinding was preserved . However , poor mobilization efficiency combined with high CD133 + senescence suggests futility in this approach Case studies suggest that bone marrow-derived stem cells may improve chronic wound healing . A prospect i ve , r and omized , clinical study was conducted to compare the rate of healing chronic lower limb wounds in patients with diabetes mellitus whose wounds were treated with topically applied and locally injected bone marrow-derived cells or whole blood ( control ) . Of the 48 patients participating in the study , 25 were r and omized to study treatment and 23 to control treatment . At baseline , no significant differences were observed between the two groups for patient age ( average for treatment group was 54 years , 3 months ; range 33 to 76 years and for the control group 58 years , 7 months ; range 28 to 69 years ) , comorbidity ( 82 % in the treatment group and 78 % in the control group had diabetes mellitus ) , ulcer history ( mean duration was 14.28 months in the treatment group and 10.21 months in the control group ; SD 0.28 ) , or baseline area ( mean was 65.32 cm2 in the treatment group and 48.83 cm2 in the control group ) . After obtaining informed consent , all wounds were surgically debrided . Wounds of study participants r and omized to the treatment group were injected and oversprayed with a total of 5 cc of autologous bone marrow-derived cells . Using a similar procedure , the wounds of patients r and omized to the control group were injected with 5 cc of autologous peripheral blood . All wounds were covered with saline-moistened gauze and cotton pads . Patients were followed for a maximum of 3 months . The average decrease in wound area at 2 weeks was 17.4 % ( 39.6 - 43.4 cm2 ) in the treatment group compared to 4.84 % ( 41.6 - 42.8 cm2 ) in the control group . After 12 weeks , the average decrease in wound area was 36.4 % ( SD 0.48 ) in the treatment group compared to 27.32 % ( SD 0.32 ) in the control group . No adverse events were observed . None of the patients complained of significant pain or discomfort following the procedure , no wound infections occurred , and all patients reported resumption of normal daily activity the day after the procedure . The results of this study show that a single application of autologous bone marrow-derived cells increases the rate of healing chronic lower extremity wounds in the early weeks of treatment . Additional studies to eluci date the treatment mode of action and optimal application frequency as well as comparisons between this and other treatment modalities are warranted BACKGROUND Pre clinical studies have established that implantation of bone marrow-mononuclear cells , including endothelial progenitor cells , into ischaemic limbs increases collateral vessel formation . We investigated efficacy and safety of autologous implantation of bone marrow-mononuclear cells in patients with ischaemic limbs because of peripheral arterial disease . METHODS We first did a pilot study , in which 25 patients ( group A ) with unilateral ischaemia of the leg were injected with bone marrow-mononuclear cells into the gastrocnemius of the ischaemic limb and with saline into the less ischaemic limb . We then recruited 22 patients ( group B ) with bilateral leg ischaemia , who were r and omly injected with bone marrow-mononuclear cells in one leg and peripheral blood-mononuclear cells in the other as a control . Primary outcomes were safety and feasibility of treatment , based on ankle-brachial index ( ABI ) and rest pain , and analysis was per protocol . FINDINGS Two patients were excluded from group B after r and omisation . At 4 weeks in group B patients , ABI was significantly improved in legs injected with bone marrow-mononuclear cells compared with those injected with peripheral blood-mononuclear cells ( difference 0.09 [ 95 % CI 0.06 - 0.11 ] ; p<0.0001 ) . Similar improvements were seen for transcutaneous oxygen pressure ( 13 [ 9 - 17 ] ; p<0.0001 ) , rest pain ( -0.85 [ -1.6 to -0.12 ] ; p=0.025 ) , and pain-free walking time ( 1.2 [ 0.7 - 1.7 ] ; p=0.0001 ) . These improvements were sustained at 24 weeks . Similar improvements were seen in group A patients . Two patients in group A died after myocardial infa rct ion unrelated to treatment . INTERPRETATION Autologous implantation of bone marrow-mononuclear cells could be safe and effective for achievement of therapeutic angiogenesis , because of the natural ability of marrow cells to supply endothelial progenitor cells and to secrete various angiogenic factors or cytokines CONTEXT Few data document current cardiovascular ( CV ) event rates in stable patients with atherothrombosis in a community setting . Differential event rates for patients with documented coronary artery disease ( CAD ) , cerebrovascular disease ( CVD ) , or peripheral arterial disease ( PAD ) or those at risk of these diseases have not been previously evaluated in a single international cohort . OBJECTIVE To establish contemporary , international , 1-year CV event rates in out patients with established arterial disease or with multiple risk factors for atherothrombosis . DESIGN , SETTING , AND PARTICIPANTS The Reduction of Atherothrombosis for Continued Health ( REACH ) Registry is an international , prospect i ve cohort of 68 236 patients with either established atherosclerotic arterial disease ( CAD , PAD , CVD ; n = 55 814 ) or at least 3 risk factors for atherothrombosis ( n = 12 422 ) , who were enrolled from 5587 physician practice s in 44 countries in 2003 - 2004 . MAIN OUTCOME MEASURES Rates of CV death , myocardial infa rct ion ( MI ) , and stroke . RESULTS As of July 2006 , 1-year outcomes were available for 95.22 % ( n = 64 977 ) of participants . Cardiovascular death , MI , or stroke rates were 4.24 % overall : 4.69 % for those with established atherosclerotic arterial disease vs 2.15 % for patients with multiple risk factors only . Among patients with established disease , CV death , MI , or stroke rates were 4.52 % for patients with CAD , 6.47 % for patients with CVD , and 5.35 % for patients with PAD . The incidences of the end point of CV death , MI , or stroke or of hospitalization for atherothrombotic event(s ) were 15.20 % for CAD , 14.53 % for CVD , and 21.14 % for PAD patients with established disease . These event rates increased with the number of symptomatic arterial disease locations , ranging from 5.31 % for patients with risk factors only to 12.58 % for patients with 1 , 21.14 % for patients with 2 , and 26.27 % for patients with 3 symptomatic arterial disease locations ( P<.001 for trend ) . CONCLUSIONS In this large , contemporary , international study , out patients with established atherosclerotic arterial disease , or at risk of atherothrombosis , experienced relatively high annual CV event rates . Multiple disease locations increased the 1-year risk of CV events Critical limb ischemia ( CLI ) continues to form a substantial burden on Western health care . Despite recent advances in surgical and radiological vascular techniques , a large number of patients is not eligible for these revascularisation procedures and faces amputation as their ultimate treatment option . Growth factor therapy and stem cell therapy - both therapies focussing on augmenting postnatal neovascularisation - have raised much interest in the past decade . Based on initial pre- clinical and clinical results , both therapies appear to be promising strategies to augment neovascularisation and to reduce symptoms and possibly prevent amputation in CLI patients . However , the underlying mechanisms of postnatal neovascularisation are still incompletely understood . Both fundamental research as well as large r and omised trials are needed for further optimisation of these treatment options , and will hopefully lead to needed advances in the treatment of no-option CLI patients in the near future BACKGROUND Intermittent claudication is associated with a poor prognosis , but less is known of the risks associated with asymptomatic peripheral arterial disease . The aims of this study were to determine the incidence and natural history of claudication , and the incidence of cardiovascular events in symptomatic and asymptomatic peripheral arterial disease . METHODS In 1988 , 1592 subjects aged 55 - 74 years were selected r and omly from the age-sex register of 10 general practice s in Edinburgh , Scotl and . The presence of peripheral arterial disease was determined by the World Health Organization question naire on intermittent claudication , the ankle brachial pressure index and a reactive hyperaemia test . This cohort was followed prospect ively over 5 years for subsequent cardiovascular events and death . RESULTS One hundred and sixteen new cases of claudication were identified ( incidence density 15.5 per 1000 person-years ) . Of those with claudication at baseline , 28.8 % and still had pain after 5 years , 8.2 % underwent vascular surgery or amputation , and 1.4 % developed leg ulceration . Claudicants had a significantly increased risk of developing angina compared with normals ( RR : 2.31 , 95 % CI : 1.04 - 5.10 ) , and asymptomatic subjects had a slightly increased risk of myocardial infa rct ion and stroke . Deaths from cardiovascular disease were more likely in both claudicants ( RR : 2.67 , 95 % CI : 1.34 - 5.29 ) and subjects with major ( RR : 2.08 , 95 % CI : 1.13 - 3.83 ) or minor asymptomatic disease ( RR : 1.74 , 95 % CI : 1.09 - 2.76 ) . Subjects with major asymptomatic disease also had an increased risk of non-cardiovascular death ( RR : 2.19 , 95 % CI : 1.33 - 3.59 ) , and therefore had the highest overall risk of death ( RR : 2.44 , 95 % CI : 1.59 - 3.74 ) . CONCLUSIONS Subjects with asymptomatic peripheral arterial disease appear to have the same increased risk of cardiovascular events and death found in claudicants Background Autologous bone marrow-derived stem cells have been ascribed an important therapeutic role in No-Option Critical limb Ischemia ( NO-CLI ) . One primary endpoint for evaluating NO-CLI therapy is major amputation ( AMP ) , which is usually combined with mortality for AMP-free survival ( AFS ) . Only a trial which is double blinded can eliminate physician and patient bias as to the timing and reason for AMP . We examined factors influencing AMP in a prospect i ve double-blinded pilot RCT ( 2:1 therapy to control ) of 48 patients treated with site of service obtained bone marrow cells ( BMAC ) as well as a systematic review of the literature . Methods Cells were injected intramuscularly in the CLI limbs as either BMAC or placebo ( peripheral blood ) . Six month AMP rates were compared between the two arms . Both patient and treating team were blinded of the assignment in follow-up examinations . A search of the literature identified 9 NO-CLI trials , the control arms of which were used to determine 6 month AMP rates and the influence of tissue loss . Results Fifteen amputations occurred during the 6 month period , 86.7 % of these during the first 4 months . One amputation occurred in a Rutherford 4 patient . The difference in amputation rate between patients with rest pain ( 5.6 % ) and those with tissue loss ( 46.7 % ) , irrespective of treatment group , was significant ( p = 0.0029 ) . In patients with tissue loss , treatment with BMAC demonstrated a lower amputation rate than placebo ( 39.1 % vs. 71.4 % , p = 0.1337 ) . The Kaplan-Meier time to amputation was longer in the BMAC group than in the placebo group ( p = 0.067 ) . Projecting these results to a pivotal trial , a bootstrap simulation model showed significant difference in AFS between BMAC and placebo with a power of 95 % for a sample size of 210 patients . Meta- analysis of the literature confirmed a difference in amputation rate between patients with tissue loss and rest pain . Conclusions BMAC shows promise in improving AMP-free survival if the trends in this pilot study are vali date d in a larger pivotal trial . The difference in amp rate between Rutherford 4 & 5 patients suggests that these patients should be stratified in future RCTs Ixmyelocel-T is a patient-specific , exp and ed , multicellular therapy evaluated in patients with lower extremity critical limb ischemia ( CLI ) with no options for revascularization . This r and omized , double-blind , placebo-controlled , phase 2 trial ( RESTORE-CLI ) compared the efficacy and safety of intramuscular injections of ixmyelocel-T with placebo . Patients received one-time injections over 20 locations in a single leg and were followed for 12 months . Safety assessment s included occurrence of adverse events . Efficacy assessment s included time to first occurrence of treatment failure ( TTF ; major amputation of injected leg ; all-cause mortality ; doubling of total wound surface area from baseline ; de novo gangrene ) and amputation-free survival ( AFS ; major amputation of injected leg ; all-cause mortality ) . A total of 77 patients underwent bone marrow or sham aspiration ; 72 patients received ixmyelocel-T ( 48 patients ) or placebo ( 24 patients ) . Adverse event rates were similar . Ixmyelocel-T treatment led to a significantly prolonged TTF ( P = 0.0032 , logrank test ) . AFS had a clinical ly meaningful 32 % reduction in event rate that was not statistically significant ( P = 0.3880 , logrank test ) . Treatment effect in post hoc analyses of patients with baseline wounds was more pronounced ( TTF : P < 0.0001 , AFS : P = 0.0802 , logrank test ) . Ixmyelocel-T treatment was well tolerated and may offer a potential new treatment option OBJECTIVES We sought to investigate the effect of cardiac medication on long-term mortality in patients with peripheral arterial disease ( PAD ) . BACKGROUND Peripheral arterial disease is associated with increased cardiovascular morbidity and mortality . Treatment guidelines recommend aggressive management of risk factors and lifestyle modifications . However , the potential benefit of cardiac medication in patients with PAD remains ill defined . METHODS In this prospect i ve observational cohort study , 2,420 consecutive patients ( age , 64 + /- 11 years , 72 % men ) with PAD ( ankle-brachial index < or = 0.90 ) were screened for clinical risk factors and cardiac medication . Follow-up end point was death from any cause . Propensity scores for statins , beta-blockers , aspirin , angiotensin-converting enzyme ( ACE ) inhibitors , calcium channel blockers , diuretics , nitrates , coumarins , and digoxin were calculated . Cox regression models were used to analyze the relation between cardiac medication and long-term mortality . RESULTS Medical history included diabetes mellitus in 436 patients ( 18 % ) , hypercholesterolemia in 581 ( 24 % ) , smoking in 837 ( 35 % ) , hypertension in 1,162 ( 48 % ) , coronary artery disease in 1,065 ( 44 % ) , and a history of heart failure in 214 ( 9 % ) . Mean ankle-brachial index was 0.58 ( + /-0.18 ) . During a median follow-up of eight years , 1,067 patients ( 44 % ) died . After adjustment for risk factors and propensity scores , statins ( hazard ratio [ HR ] 0.46 , 95 % confidence interval [ CI ] 0.36 to 0.58 ) , beta-blockers ( HR 0.68 , 95 % CI 0.58 to 0.80 ) , aspirins ( HR 0.72 , 95 % CI 0.61 to 0.84 ) , and ACE inhibitors ( HR 0.80 , 95 % CI 0.69 to 0.94 ) were significantly associated with a reduced risk of long-term mortality . CONCLUSIONS On the basis of this observational longitudinal study , statins , beta-blockers , aspirins , and ACE inhibitors are associated with a reduction in long-term mortality in patients with PAD Background — Patients with severe limb ischemia may not be eligible for conventional therapeutic interventions . Pioneering clinical trials suggest that bone marrow – derived cell therapy enhances neovascularization , improves tissue perfusion , and prevents amputation . The objective of this trial was to determine whether repetitive intra-arterial infusion of bone marrow mononuclear cells ( BMMNCs ) in patients with severe , nonrevascularizable limb ischemia can prevent major amputation . Methods and Results — The Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation ( JUVENTAS ) trial is a r and omized , double-blind , placebo-controlled clinical trial in 160 patients with severe , nonrevascularizable limb ischemia . Patients were r and omly assigned to repetitive ( 3 times ; 3-week interval ) intra-arterial infusion of BMMNC or placebo . No significant differences were observed for the primary outcome , ie , major amputation at 6 months , with major amputation rates of 19 % in the BMMNC versus 13 % in the placebo group ( relative risk , 1.46 ; 95 % confidence interval , 0.62–3.42 ) . The safety outcome ( all-cause mortality , occurrence of malignancy , or hospitalization due to infection ) was not significantly different between the groups ( relative risk , 1.46 ; 95 % confidence interval , 0.63–3.38 ) , neither was all-cause mortality at 6 months with 5 % versus 6 % ( relative risk , 0.78 ; 95 % confidence interval , 0.22–2.80 ) . Secondary outcomes quality of life , rest pain , ankle-brachial index , and transcutaneous oxygen pressure improved during follow-up , but there were no significant differences between the groups . Conclusions — Repetitive intra-arterial infusion of autologous BMMNCs into the common femoral artery did not reduce major amputation rates in patients with severe , nonrevascularizable limb ischemia in comparison with placebo . The general improvement in secondary outcomes during follow-up in both the BMMNC and the placebo group , as well , underlines the essential role for placebo-controlled design of future trials . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00371371 Introduction Our study was design ed to investigate the safety and efficacy of combined autologous bone marrow mononuclear cell ( MNC ) and gene therapy in comparison to conventional drug therapy in patients with critical limb ischemia ( CLI ) . Material and methods Thirty-two patients with CLI persisting for 12–48 months ( average time 27.5 months ) were r and omized into 2 groups , each group consisting of 16 patients . In the first group , administration of autologous bone marrow MNC and vascular endothelial growth factor ( VEGF ) plasmid was performed . The patients from the second group were treated pharmacologically with pentoxifylline . Ankle-brachial index ( ABI ) was measured and angiography was performed before and finally 3 months after treatment . The pain was evaluated using the Visual Analog Scale ( VAS ) before and after 3 months . Results Ankle-brachial index improved significantly from 0.29 ±0.21 to 0.52 ±0.23 ( p < 0.001 ) in 12 patients ( 75.0 % ) 3 months after the experimental therapy in group 1 . In this group angiography showed the development of collateral vessels . Ischemic ulcers healed completely in 11 patients ( 68.75 % ) . In group 2 the ABI did not improve in any patient ; moreover the complete healing of skin ulcers was not found in any of the patients of this group . Amputation was performed in 4 ( 25.0 % ) patients in group 1 , and in 8 patients ( 50 % ) from group 2 . Conclusions These data after 3-month follow-up indicate that intramuscular injection of MNC combined with gene therapy in patients with chronic CLI is safe , and a more feasible and effective method of treatment than the conventional therapy . However , both therapies are limited by the degree of microcirculation damage AIM The aim was to evaluate the therapeutic effectiveness of granulocyte colony-stimulating factor ( G-CSF ) mobilized peripheral blood mononuclear cells ( PBMNCs ) in critical limb ischemia ( CLI ) of type 2 diabetic patients . METHOD Forty diabetic patients with CLI were enrolled and r and omized to treatment and control groups . In the treatment group , the patients received subcutaneous injections of recombinant human G-CSF ( 30 MU/day ) for 5 days to mobilize stem cells . PBMNCs were collected and transplanted by multiple intramuscular injections of 1 ml in 1 - 1.5-cm depth into ischemic limbs . RESULTS At the end of 12 weeks of follow-up , the baseline and end point results in transplant group were as follows : Fontaine score improved from 3.8±03 to 3±0.5 ( P=.0001 ) , ankle brachial pressure index increased from 0.68±0.24 to 0.87±024 ( P=.001 ) , transcutaneous oxygen increased from 33±14 mmHg to 44±10 mmHg ( P=.0001 ) , and 6-min walking distance improved from 280±82 m to 338±98 m ( P=.0001 ) . Pain score decreased from 8.2±1.3 to 5.63±1.6 ( P=.001 ) , and the number of patients with limb ulcers was reduced from 9/20 ( 45 % ) to 3/20 ( 15 % ) ( P=.031 ) . In the control group , Fontaine score , 6-min walking distance , and pain score were improved ; ankle brachial pressure index and transcutaneous oxygen pressure were not improved . The number of patients with limb ulcers did not change in the control group . There are improvement in amputation rates , collateral vessel development , and number of limb ulcers healed . CONCLUSIONS These results indicate that the autologous transplantation of G-CSF that mobilized PBMNCs in CLI diabetic patients is safe and effective in patient compliant reduction and improved perfusion OBJECTIVE To assess the application of autologous transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells ( PBMNCs ) in the treatment of critical limb ischemia ( CLI ) of diabetic patients and to evaluate the safety , efficacy , and feasibility of this novel therapeutic approach . RESEARCH DESIGN AND METHODS Twenty-eight diabetic patients with CLI were enrolled and r and omized to either the transplant group or the control group . In the transplant group , the patients received subcutaneous injections of recombinant human G-CSF ( 600 microg/day ) for 5 days to mobilize stem/progenitor cells , and their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs . All of the patients were followed up after at least 3 months . RESULTS At the end of the 3-month follow-up , the main manifestations , including lower limb pain and ulcers , were significantly improved in the patients of the transplant group . Their laser Doppler blood perfusion of lower limbs increased from 0.44 + /- 0.11 to 0.57 + /- 0.14 perfusion units ( P < 0.001 ) . Mean ankle-brachial pressure index increased from 0.50 + /- 0.21 to 0.63 + /- 0.25 ( P < 0.001 ) . A total of 14 of 18 limb ulcers ( 77.8 % ) of transplanted patients were completely healed after cell transplantation , whereas only 38.9 % of limb ulcers ( 7 of 18 ) were healed in the control patients ( P = 0.016 vs. the transplant group ) . No adverse effects specifically due to cell transplantation were observed , and no lower limb amputation occurred in the transplanted patients . In contrast , five control patients had to receive a lower limb amputation ( P = 0.007 , transplant vs. control group ) . Angiographic scores were significantly improved in the transplant group when compared with the control group ( P = 0.003 ) . CONCLUSIONS These results provide pilot evidence indicating that the autologous transplantation of G-CSF-mobilized PBMNCs represents a simple , safe , effective , and novel therapeutic approach for diabetic CLI Fifty percent of diabetics ( 7 % of general population ) suffer from peripheral arterial occlusive disease , which may lead to amputation due to critical limb ischemia ( CLI ) . The aim of our study was to prevent major limb amputation ( MLA ) in this group of patients using a local application of autologous bone marrow stem cells ( ABMSC ) concentrate . A total of 96 patients with CLI and foot ulcer ( FU ) were r and omized into groups I and II . Patients in group I ( n = 42 , 36 males , 6 females , 66.2 ± 10.6 years ) underwent local treatment with ABMSC while those in group II ( n = 54 , control , 42 males , 12 females , 64.1 ± 8.6 years ) received st and ard medical care . The frequency of major limb amputation in groups I and II was 21 % and 44 % within the 120 days of follow up , respectively ( p < 0.05 ) . Only in salvaged limbs of group I both toe pressure and toe brachial index increased ( from 22.66 ± 5.32 to 25.63 ± 4.75 mmHg and from 0.14 ± 0.03 to 0.17 ± 0.03 , respectively , mean ± SEM ) . The CD34 + cell counts in bone marrow concentrate ( BMC ) decreased ( correlation , p = 0.024 ) with age , even though there was no correlation between age and healing . An unexpected finding was made of relative , bone marrow lymphopenia in the initial bone marrow concentrates in patients who failed ABMSC therapy ( 21 % of MLA ) . This difference was statistically significant ( p < 0.040 ) . We conclude ABMSC therapy results in 79 % limb salvage in patients suffering from CLI and FU . In the remaining 21 % lymphopenia and thrombocytopenia were identified as potential causative factors , suggesting that at least a partial correction with platelet supplementation may be beneficial BACKGROUND The treatment of rest pain , ulceration , and gangrene of the leg ( severe limb ischaemia ) remains controversial . We instigated the BASIL trial to compare the outcome of bypass surgery and balloon angioplasty in such patients . METHODS We r and omly assigned 452 patients , who presented to 27 UK hospitals with severe limb ischaemia due to infra-inguinal disease , to receive a surgery-first ( n=228 ) or an angioplasty-first ( n=224 ) strategy . The primary endpoint was amputation ( of trial leg ) free survival . Analysis was by intention to treat . The BASIL trial is registered with the National Research Register ( NRR ) and as an International St and ard R and omised Controlled Trial , number IS RCT N45398889 . FINDINGS The trial ran for 5.5 years , and follow-up finished when patients reached an endpoint ( amputation of trial leg above the ankle or death ) . Seven individuals were lost to follow-up after r and omisation ( three assigned angioplasty , two surgery ) ; of these , three were lost ( one angioplasty , two surgery ) during the first year of follow-up . 195 ( 86 % ) of 228 patients assigned to bypass surgery and 216 ( 96 % ) of 224 to balloon angioplasty underwent an attempt at their allocated intervention at a median ( IQR ) of 6 ( 3 - 16 ) and 6 ( 2 - 20 ) days after r and omisation , respectively . At the end of follow-up , 248 ( 55 % ) patients were alive without amputation ( of trial leg ) , 38 ( 8 % ) alive with amputation , 36 ( 8 % ) dead after amputation , and 130 ( 29 % ) dead without amputation . After 6 months , the two strategies did not differ significantly in amputation-free survival ( 48 vs 60 patients ; unadjusted hazard ratio 1.07 , 95 % CI 0.72 - 1.6 ; adjusted hazard ratio 0.73 , 0.49 - 1.07 ) . We saw no difference in health-related quality of life between the two strategies , but for the first year the hospital costs associated with a surgery-first strategy were about one third higher than those with an angioplasty-first strategy . INTERPRETATION In patients presenting with severe limb ischaemia due to infra-inguinal disease and who are suitable for surgery and angioplasty , a bypass-surgery-first and a balloon-angioplasty-first strategy are associated with broadly similar outcomes in terms of amputation-free survival , and in the short-term , surgery is more expensive than angioplasty PURPOSE To evaluate the efficacy of autologous transplantation of granulocyte colony-stimulating factor ( G-CSF ) stimulated bone marrow mononuclear cells in the treatment of diabetic lower limb ischemic disease in a rabbit model . METHODS The diabetic model was produced by intravenous injection of 5 % alloxan into New Zeal and white rabbits . The lower limb ischemia model was created by femoral artery ligation in diabetic rabbits ( n=50 ) 14 days after alloxan injection . Animals were then r and omized into five groups ( 10 rabbits per group ) : group 1 , transplanted with G-CSF immobilized peripheral blood mononuclear cells ( PBMNC ) ; group 2 , transplanted with G-CSF stimulated bone marrow mononuclear cells ( BMMNC ) ; group 3 , animals were transplanted with non-stimulated BMMNCs ; group 4 , G-CSF group injected with G-CSF alone without transplantation ; and group 5 , PBS group treated with PBS alone . Necrosis of foot or toes and blood flow recovery in ischemic limbs was assessed . Expression of von Willebr and factor ( vWF ) and vascular endothelial cell growth factor ( VEGF ) were measured in ischemic muscles by immunohistochemistry analysis . RESULTS Blood flow in ischemic limbs was significantly improved in the G-BMMNC group ( ratio of blood flows : 0.82+/-0.06 ) in comparison with the G-PBMNC ( 0.61+/-0.09 ) and BMMNC ( 0.62+/-0.08 ) groups ( P < 0.001 ) . In the G-BMMNC group , the capillary density , a measure of vWF expression , was significantly higher than in either the G-PBMNC or BMMNC groups ( 47.9+/-2.51 vs. 36.8+/-4.16 and 39.6+/-2.72 , respectively , P < 0.05 ) . The expression of VEGF in G-BMMNC animals was significantly increased in comparison with the G-PBMNC and BMMNC groups ( 16.93+/-0.70 vs. 11.83+/-0.98 and 12.32+/-0.96 , respectively , P < 0.05 ) . CONCLUSION A combination of G-CSF stimulation and autologous transplantation of bone marrow stem cells synergistically improved neovascularization and angiogenesis in ischemic limb tissues in diabetic rabbits BACKGROUND The purpose of this study was to determine whether treatment with granulocyte colony-stimulating factor ( G-CSF ) , which mobilizes endothelial progenitor cells from bone marrow , can safely improve the clinical outcomes of patients with atherosclerotic peripheral artery disease ( PAD ) . METHODS AND RESULTS Thirty-nine patients with intractable PAD were r and omly assigned to 3 groups : a negative control group ( n=12 ) treated with conventional drug therapy ; a positive control group ( n=13 ) treated with conventional drug therapy plus bone marrow transplantation ( BMT ) ; and a G-CSF group ( n=14 ) treated with conventional therapy plus subcutaneous injection of 2 - 5 microg/kg of recombinant human G-CSF once daily for 10 days . One month after treatment , subjective symptoms improved significantly in the G-CSF and BMT groups . Ankle-brachial pressure index and transcutaneous oxygen pressure increased significantly in the BMT and G-CSF groups , but no such improvements were seen in the group receiving conventional therapy alone . CONCLUSIONS G-CSF improves the clinical signs and symptoms of patients with intractable PAD to the same degree as BMT does . This noninvasive treatment may thus represent a useful new approach to managing the disease Bone marrow (BM)-derived mesenchymal stem cells ( MSCs ) represent a promising population for supporting new concepts in cellular therapy . This study was undertaken to assess the efficacy and feasibility of autologous BM-derived MSCs in the treatment of chronic nonhealing ulcers ( diabetic foot ulcers and Buerger disease ) of the lower extremities . A total of 24 patients with nonhealing ulcers of the lower limb were enrolled and r and omized into implant and control groups . In the implant group , the patients received autologous cultured BM-derived MSCs along with st and ard wound dressing ; the control group received only the st and ard wound dressing regimen , followed up for at least a 12-week period . Wound size , pain-free walking distance , and biochemical parameters were measured before therapy and at every 2-week interval following intervention . The implant group had significant improvement in pain-free walking distance and reduction in ulcer size as compared to those in the control group . In the implant group for Buerger disease , the ulcer area decreased from 5.04 + /- 0.70 cm(2 ) to 1.48 + /- 0.56 cm(2 ) ( p < 0.001 ) , whereas the pain-free walking distance increased from 38.33 + /- 17.68 m to 284.44 + /- 212.12 m ( p < 0.001 ) . In the diabetic foot ulcer group , the ulcer size decreased from 7.26 + /- 1.41 cm(2 ) to 2 + /- 0.98 cm(2 ) ( p < 0.001 ) at 12 weeks . Mononuclear cells were cultured for a minimum of five passages and characterized by cell-surface markers showing CD90 + , CD105 + , and CD34(- ) . There was no significant alteration in the biochemical parameters observed during the follow-up period , indicating normal liver and renal function following intervention . Biopsy microsection of implanted tissues showed development of dermal cells ( mainly fibroblasts ) , including mature and immature inflammatory cells . The study indicates that autologous implantation of BM-derived MSCs in nonhealing ulcers accelerates the healing process and improves clinical parameters significantly BACKGROUND AIMS Regeneration of the occluded peripheral arteries by autologous stem cell therapy is an emerging treatment modality for no-option patients with peripheral artery disease ( PAD ) . The purpose of this study was to assess safety and efficacy of in vitro-exp and ed , peripheral blood-derived , autologous stem cells ( VesCell ) in no-option patients with PAD . METHODS A phase II , open-label , r and omized clinical study was performed on 20 patients to investigate the safety and efficacy of VesCell therapy at 1 and 3 months of follow-up . The long-term ( 2 years ) efficacy of the therapy was also evaluated . RESULTS No side effects of VesCell therapy were found . During the 3 month follow-up in the control group , one death occurred and six major amputations were performed ; in the treated group , there were no deaths or major amputations . The difference of limb loss is significant between the two groups . At 2-year follow-up in the control group , two deaths and six major amputations occurred ; in the treated group , there were three major amputations . At 3-month follow-up , the change in hemodynamic parameters showed a significant increase in the treated group over the control group ; in the treated group , further improvement was detected at 2 years . As the result of the VesCell treatment , change in pain score , wound healing and walking ability test showed an improvement compared with the control group ; at 2 years , incremental improvement was observed . CONCLUSIONS Peripheral blood-derived , in vitro-exp and ed autologous angiogenic precursor therapy appears to be a safe , promising and effective adjuvant therapy for PAD patients OBJECTIVES Stem cell transplant can induce vasculogenesis and improve the blood supply to an ischemic region , offering hope for chronic lower extremity ischemic diseases . Bone marrow mononuclear cells are one of the sources for stem cell transplants . We sought to observe the safety and efficacy of autologous bone marrow mononuclear cells transplant for treating critical limb ischemia . MATERIAL S AND METHODS Eligible patients were r and omized 1:1 to receive placebo ( 0.9 % NaCl ) or 1 × 107 piece/mL bone marrow mononuclear cell transplant . For 6 months , patients ' skin ulcers , ankle-brachial index , and rest pain were examined and recorded before and after treatment . RESULTS Six months after the bone marrow mononuclear cells transplant , clinical symptoms like rest pain and skin ulcers gradually abated ( P < .05 ) . Ankle-brachial index also increased after the transplant ( P < .01 ) . CONCLUSIONS Autologous bone marrow mononuclear cells transplant for treatment of patients with chronic limb ischemia is safe , effective , and feasible OBJECTIVES Despite advances in endovascular therapies , critical limb ischemia ( CLI ) continues to be associated with high morbidity and mortality . Patients without direct revascularization options have the worst outcomes . We sought to explore the feasibility of conducting a definitive trial of a bone marrow-derived cellular therapy for CLI in this " no option " population . METHODS A pilot , multicenter , prospect i ve , r and omized , double-blind , placebo-controlled trial for " no option " CLI patients was performed . The therapy consisted of bone marrow aspirate concentrate ( BMAC ) , prepared using a point of service centrifugation technique and injected percutaneously in 40 injections to the affected limb . Patients were r and omized to BMAC or sham injections ( dilute blood ) . We are reporting the 12-week data . RESULTS Forty-eight patients were enrolled . The mean age was 69.5 years ( range , 42 - 93 years ) . Males predominated ( 68 % ) . Diabetes was present in 50 % . Tissue loss ( Rutherford 5 ) was present in 30 patients ( 62.5 % ) , and 18 ( 37.5 % ) had rest pain without tissue loss ( Rutherford 4 ) . Patients were deemed unsuitable for conventional revascularization based on multiple prior failed revascularization efforts ( 24 [ 50 % ] ) , poor distal targets ( 43 [ 89.6 % ] ) , and medical risk ( six [ 12.5 % ] ) . Thirty-four patients were treated with BMAC and 14 with sham injections . There were no adverse events attributed to the injections . Renal function was not affected . Effective blinding was confirmed ; blinding index of 61 % to 85 % . Subjective and objective outcome measures were effectively obtained with the exception of treadmill walking times , which could only be obtained at baseline and follow-up in 15 of 48 subjects . This pilot study was not powered to demonstrate statistical significance but did demonstrate favorable trends for BMAC versus control in major amputations ( 17.6 % vs 28.6 % ) , improved pain ( 44 % vs 25 % ) , improved ankle brachial index ( ABI ; 32.4 % vs 7.1 % ) , improved Rutherford classification ( 35.3 % vs 14.3 % ) , and quality -of-life scoring better for BMAC in six of eight domains . CONCLUSIONS In this multicenter , r and omized , double-blind , placebo-controlled trial of autologous bone marrow cell therapy for CLI , the therapy was well tolerated without significant adverse events . The BMAC group demonstrated trends toward improvement in amputation , pain , quality of life , Rutherford classification , and ABI when compared with controls . This pilot allowed us to identify several areas for improvement for future trials and CLI studies . These recommendations include elimination of treadmill testing , stratification by Rutherford class , and more liberal inclusion of patients with renal insufficiency . Our strongest recommendation is that CLI studies that include Rutherford 4 patients should incorporate a composite endpoint reflecting pain and quality of life |
13,327 | 31,473,614 | Interventions demonstrating reductions of 0.6 BMI -SDS might be termed successful in reducing adiposity , a key purpose of weight management interventions . | OBJECTIVE Using meta-regression this paper sets out the minimum change in body mass index-SD score ( BMI -SDS ) required to improve adiposity as percentage body fat for children and adolescents with obesity .
RESULTS This paper explores the potential impact of BMI -SDS reduction in terms of change in percentage body fat . | Objective To determine whether modifying eating behaviour with use of a feedback device facilitates weight loss in obese adolescents . Design R and omised controlled trial with 12 month intervention . Setting Hospital based obesity clinic . Participants 106 newly referred obese young people aged 9 - 17 . Interventions A computerised device , M and ometer , providing real time feedback to participants during meals to slow down speed of eating and reduce total intake ; st and ard lifestyle modification therapy . Main outcome measures Change in body mass index ( BMI ) st and ard deviation score ( SDS ) over 12 months with assessment 18 months after the start of the intervention . Secondary outcomes were body fat SDS , metabolic status , quality of life evaluation , change in portion size , and eating speed . Results Using the last available data on all participants ( n=106 ) , those in the M and ometer group had significantly lower mean BMI SDS at 12 months compared with st and ard care ( baseline adjusted mean difference 0.24 , 95 % confidence interval 0.11 to 0.36 ) . Similar results were obtained when analyses included only the 91 who attended per protocol ( baseline adjusted mean difference 0.27 , 0.14 to 0.41 ; P<0.001 ) , with the difference maintained at 18 months ( 0.27 , 0.11 to 0.43 ; P=0.001 ) ( n=87 ) . The mean meal size in the M and ometer group fell by 45 g ( 7 to 84 g ) . Mean body fat SDS adjusted for baseline levels was significantly lower at 12 months ( 0.24 , 0.10 to 0.39 ; P=0.001 ) . Those in the M and ometer group also had greater improvement in concentration of high density lipoprotein cholesterol ( P=0.043 ) . Conclusions Retraining eating behaviour with a feedback device is a useful adjunct to st and ard lifestyle modification in treating obesity among adolescents . Trial registration Clinical Trials.gov NCT00407420 The 1990 guidelines for adult weight published by the U.S. Department of Agriculture [ 1 ] recommend higher weights than previous st and ards . In particular , the guidelines for increased weight ( about 7 kg on average ) for persons age 35 years and older , with allowance for major weight gain in midlife , have stimulated much debate [ 2 - 4 ] . The basis for these recommendations is unclear . The report by And res [ 5 ] on which the recommendations may be based is fundamentally flawed because it ignored cigarette smoking . Although no apparent biological rationale exists for suggesting that persons increase their weight as they grow older , the health consequences of weight gain during adult life have not been clearly documented . In general , a strong association between body mass index and the risk for noninsulin-dependent diabetes mellitus has been observed . However , few studies have examined the consequences of weight gain during various periods of life . From a public health perspective , weight and weight gain are more easily understood than body mass index . Also , using change in weight as a basis for recommendations is attractive because it allows for differences in frame size , which are difficult to characterize . For these reasons , we quantified the relations between change in adult weight and the risk for noninsulin-dependent diabetes mellitus among women during 14 years of follow-up . We previously reported the relation between body mass index and clinical diabetes in this cohort after 8 years of follow-up [ 6 ] . Methods Established in 1976 , the Nurses ' Health Study cohort consists of 121 700 female registered nurses aged 30 to 55 years who responded to a mail question naire about their medical history and health behaviors . Additional details have been reported elsewhere [ 7 ] . The participants for our study were the 114 824 women who did not have diagnosed diabetes mellitus , coronary heart disease , stroke , or cancer when the cohort was enrolled in 1976 . On the basis of a sub sample of participants , we estimate that 98 % of the participants are white , a percentage that reflects the ethnic background of women trained as registered nurses before 1977 [ 8 ] . Ascertainment of Risk Factors Height and weight were ascertained on the 1976 question naire . On biennial follow-up question naires , we inquired about current weight and asked for information on whether diabetes mellitus , coronary heart disease , cancer , or other major illnesses had been diagnosed during the 2 years since the previous question naire . In 1980 , we asked women to record their weight at age 18 years , and in 1982 we inquired about a history of diabetes in the participants ' mothers , fathers , brothers , or sisters . Weight reported by the participants in this study has been shown to be highly valid in two sample s of Boston-area study participants . Self-reported current weight was highly correlated with measured weight ( Spearman correlation coefficient , 0.97 ) ; the average measured weight was 1.5 kg lower [ 9 , 10 ] . In a sub study done in a cohort of nurses aged 27 to 44 years , recalled weight at age 18 years was compared with self-reported weights at ages 17 to 21 years that were recorded on nursing-school physical examination forms . The mean recalled self-reported body mass index was 21.6 kg/m2 compared with an index of 22.1 kg/m2 noted on the examination records ( mean difference in weight , 1.4 kg ) . The Pearson correlation coefficient for weight was 0.87 and was independent of current age . Participants in the Nurses ' Health Study cohort weighed , on average , 3 kg less than a national sample of women in 1976 [ 11 ] . We used body mass index ( weight in kg divided by height in m2 ) as an index of relative weight and grouped it into 10 categories using whole-number cutpoints . We divided weight change between age 18 years and 1976 into eight categories . A body mass index of 24.0 kg/m2 represents the 50th percentile for middle-aged , white U.S. women , and an index of 29.0 kg/m2 represents the 75th percentile [ 11 ] . Diagnosis of Diabetes Mellitus We mailed supplementary question naires on symptoms , diagnostic tests , and therapy for hypoglycemia to women who responded positively on any follow-up question naire to the query Have you had physician-diagnosed diabetes mellitus ? The supplementary question naires were mailed in 1984 to women who reported that diabetes had been diagnosed between 1976 and 1984 and in 1986 , 1988 , and 1990 to women who reported diabetes on the question naires in those years . We excluded women who reported that diabetes had been diagnosed before they entered the study in 1976 . An incident case of diabetes was confirmed if at least one of the following was reported on the supplementary question naire : 1 ) one or more classic symptoms ( thirst , polyuria , weight loss , hunger , pruritus ) plus a fasting plasma glucose level of at least 140 mg/dL ( 7.8 mmol/L ) or a r and om plasma glucose level of at least 200 mg/dL [ 11.1 mmol/L ] ; 2 ) two or more elevated plasma glucose values on different occasions [ fasting level 140 mg/dL or r and om level 200 mg/dL , or both , or fasting level 200 mg/dL after 2 or more hours of testing for oral glucose tolerance ] in the absence of symptoms ; or 3 ) treatment with medication for hypoglycemia ( insulin or oral hypoglycemic agent ) . All women were 30 years of age or older at diagnosis . We excluded cases ( and subsequent follow-up after diagnosis ) of incident insulin-dependent ( type 1 ) diabetes ( n = 89 ) . We also excluded women classified as having gestational diabetes only ( diabetes first diagnosed during pregnancy and that persisted no more than 1 month after the end of pregnancy , with no subsequent diagnosis of diabetes when the woman was not pregnant ) . The remaining women with confirmed diabetes ( n = 2204 ) were classified as having noninsulin-dependent diabetes mellitus ; these women form the basis for our analysis . Our criteria for diabetes classification are consistent with those proposed by the National Diabetes Data Group [ 12 ] except that we did not use any weight criteria in classifying diabetes . To document the validity of the confirmation of diabetes by the supplementary question naire , we examined medical records in a r and om sample of the participants who reported diabetes . Of 84 women who reported diabetes and were classified as having noninsulin-dependent diabetes mellitus by supplementary question naires , 71 gave permission for review of their medical records ; medical records were obtained for 62 . An endocrinologist ( JEM ) who was unaware of the information reported on the supplementary question naires review ed the available records using the National Diabetes Data Group criteria . The diagnosis of noninsulin-dependent diabetes mellitus was confirmed by medical records in 61 of the 62 women ( 98.4 % ) . Statistical Analysis We computed incidence rates of noninsulin-dependent diabetes mellitus during the 14 years of follow-up for categories of body mass index calculated at baseline in 1976 and for categories of weight change between age 18 years and 1976 . Follow-up began when the 1976 question naire was returned and ended on the date of death or diagnosis of diabetes , cardiovascular disease , or cancer , or 1 June 1990 , whichever came first . Women who reported diabetes mellitus , coronary heart disease , stroke , or cancer on the baseline or follow-up question naires were excluded from subsequent follow-up . We obtained rates by dividing the number of incident cases by the number of person-years of follow-up in each category of body mass index or weight change . We computed relative risks as the rate of noninsulin-dependent diabetes mellitus in a specific category of body mass index divided by the rate among women with a body mass index less than 22.0 kg/m2 . Because family history was recorded in 1982 , we repeated analyses from 1982 to 1990 to examine weight change within strata of family history and defined weight change in adulthood as weight in 1982 minus weight at age 18 years . We used proportional hazard models to simultaneously evaluate the association with family history , body mass index at age 18 years , and weight gain . We calculated 95 % CIs for each relative risk . Results The mean weight SD of women in this cohort at age 18 years was 126.2 19.4 pounds ( 57 8.8 kg ) . Mean weight gain between age 18 years and 1976 varied monotonically with age from 7.6 pounds ( 3.4 kg ) among women 30 years of age to 19.0 pounds ( 8.6 kg ) for women 55 years of age . Reflecting these weight changes , the mean weight for each birth cohort ( in single years ) increased from 133 pounds ( 60.3 kg ) for women 35 years of age to 144 pounds ( 65.3 kg ) for women 55 years of age . The risk for diabetes increased as attained body mass index increased over the 1976 value ( index was up date d every 2 years ) ( Table 1 ) . Even women with a body mass index of 22.0 to 22.9 kg/m2 had a significant threefold elevation in age-adjusted relative risk compared with women with an index less than 22.0 kg/m2 . Women of average weight ( body mass index , 24 to 24.9 kg/m2 ) had a relative risk of 5.0 ( 95 % CI , 3.6 to 6.6 ) compared with women with an index less than 22 kg/m2 . Women with a body mass index of 31.0 kg/m2 or more had an age-adjusted relative risk of 40.0 or greater ( Table 1 ) . This association persisted within age strata , and body mass index remained a strong risk factor , even for women as old as 69 years . After adjustment for body mass index , women aged 60 to 64 years had a relative risk of 3.4 ( CI , 2.5 to 4.6 ) compared with women aged 40 to 44 years . The relation between body mass index and diabetes mellitus was similar in white and black women . The strong association between body mass index and the risk for diabetes mellitus persisted ( that is , remained unchanged ) when we repeated analyses that were limited to symptomatic cases of noninsulin-dependent diabetes mellitus ( report of at least one symptom at diagnosis , including thirst , polyuria , weight loss , hunger , or pruritus ) . Table 1 . Attained Body Mass Index and CONTEXT There are limited and controversial data concerning the relationships between retinol-binding protein 4 ( RBP4 ) , weight status , and insulin resistance in obese humans and especially in children . OBJECTIVE Our objective was to study the longitudinal relationships among RBP4 , insulin resistance and weight status in obese children . DESIGN , SETTING , AND PATIENTS We conducted a 1-yr longitudinal follow-up study in a primary -care setting with 43 obese children ( median age 10.8 yr ) and 19 lean children of same the age and gender . INTERVENTION Our outpatient 1-yr intervention program was based on exercise , behavior , and nutrition therapy . MAIN OUTCOMES MEASURES Changes of weight status ( body mass index sd score ) , RBP4 , molar RBP4/serum retinol ( SR ) ratio , insulin resistance index homeostasis model assessment ( HOMA ) , and quantitative insulin sensitivity check index ( QUICKI ) . RESULTS Obese children had significantly ( P < 0.01 ) higher RBP4 concentrations and a higher RBP4/SR ratio compared with lean children . In multiple linear regression analyses adjusted to age , gender , and pubertal stage , RBP4 was significantly correlated to insulin and body mass index . Pubertal children demonstrated significantly decreased QUICKI and significantly increased HOMA index , insulin , and RBP4 concentrations compared with prepubertal children . Changes of RBP4 correlated significantly to changes of insulin ( r = 0.29 ) , HOMA index ( r = 0.29 ) , QUICKI ( r = 0.22 ) , and weight status ( r = 0.31 ) . Substantial weight loss in 25 children led to a significant ( P < 0.001 ) decrease of RBP4 , RBP4/SR , blood pressure , triglycerides , insulin , and HOMA index and an increase in QUICKI in contrast to the 18 children without substantial weight loss . CONCLUSION RBP4 levels were related to weight status and insulin resistance in both cross-sectional and longitudinal analyses , suggesting a relationship between RBP4 , obesity , and insulin resistance in children The evaluation of child growth trajectories and the interventions design ed to improve child health are highly dependent on the growth charts used . The U.S. CDC and the WHO , in May 2000 and April 2006 , respectively , released new growth charts to replace the 1977 NCHS reference . The WHO charts are based for the first time on a prescriptive , prospect i ve , international sample of infants selected to represent optimum growth . This article compares the WHO and CDC curves and evaluates the growth performance of healthy breast-fed infants according to both . As expected , there are important differences between the WHO and CDC charts that vary by age group , growth indicator , and specific Z-score curve . Differences are particularly important during infancy , which is likely due to differences in study design and characteristics of the sample , such as type of feeding . Overall , the CDC charts reflect a heavier , and somewhat shorter , sample than the WHO sample . This results in lower rates of undernutrition ( except during the first 6 mo of life ) and higher rates of overweight and obesity when based on the WHO st and ards . Healthy breast-fed infants track along the WHO st and ard 's weight-for-age mean Z-score while appearing to falter on the CDC chart from 2 mo onwards . Shorter measurement intervals in the WHO st and ards result in a better tool for monitoring the rapid and changing rate of growth in early infancy . Their adoption would have important implication s for the assessment of lactation performance and the adequacy of infant feeding and would bring coherence between the tools used to assess growth and U.S. national guidelines that recommend breast-feeding as the optimal source of nutrition during infancy OBJECTIVES The aim of this study was to determine the effects of physical activity on systemic blood pressure ( BP ) and early markers of atherosclerosis in pre-pubertal obese children . BACKGROUND Hypertension and endothelial dysfunction are premature complications of obesity . METHODS We performed a 3-month r and omized controlled trial with a modified crossover design : 44 pre-pubertal obese children ( age 8.9 + or - 1.5 years ) were r and omly assigned ( 1:1 ) to an exercise ( n = 22 ) or a control group ( n = 22 ) . We recruited 22 lean children ( age 8.5 + or - 1.5 years ) for baseline comparison . The exercise group trained 60 min 3 times/week during 3 months , whereas control subjects remained relatively inactive . Then , both groups trained twice/week during 3 months . We assessed changes at 3 and 6 months in office and 24-h BP , arterial intima-media thickness ( IMT ) and stiffness , endothelial function ( flow-mediated dilation ) , body mass index ( BMI ) , body fat , cardiorespiratory fitness ( maximal oxygen consumption [ VO(2)max ] ) , physical activity , and biological markers . RESULTS Obese children had higher BP , arterial stiffness , body weight , BMI , abdominal fat , insulin resistance indexes , and C-reactive protein levels , and lower flow-mediated dilation , VO(2)max , physical activity , and high-density lipoprotein cholesterol levels than lean subjects . At 3 months , we observed significant changes in 24-h systolic BP ( exercise -6.9 + or - 13.5 mm Hg vs. control 3.8 + or - 7.9 mm Hg , -0.8 + or - 1.5 st and ard deviation score [ SDS ] vs. 0.4 + or - 0.8 SDS ) , diastolic BP ( -0.5 + or - 1.0 SDS vs. 0 + or - 1.4 SDS ) , hypertension rate ( -12 % vs. -1 % ) , office BP , BMI z-score , abdominal fat , and VO(2)max . At 6 months , change differences in arterial stiffness and IMT were significant . CONCLUSIONS A regular physical activity program reduces BP , arterial stiffness , and abdominal fat ; increases cardiorespiratory fitness ; and delays arterial wall remodeling in pre-pubertal obese children . ( Effects of Aerobic Exercise Training on Arterial Function and Insulin Resistance Syndrome in Obese Children : A R and omized Controlled Trial ; NCT00801645 ) BACKGROUND AND OBJECTIVES : Endothelial dysfunction is the first , although reversible , sign of atherosclerosis and is present in obese adolescents . The primary end point of this study was to investigate the influence of a multicomponent treatment on microvascular function . Additional objectives and end points were a reduced BMI SD score , improvements in body composition , exercise capacity , and cardiovascular risk factors , an increase in endothelial progenitor cells ( EPCs ) , and a decrease in endothelial microparticles ( EMPs ) . METHODS : We used a quasi-r and omized study with 2 cohorts of obese adolescents : an intervention group ( n = 33 ; 15.4 ± 1.5 years , 24 girls and 9 boys ) treated residentially with supervised diet and exercise and a usual care group ( n = 28 ; 15.1 ± 1.2 years , 22 girls and 6 boys ) , treated ambulantly . Changes in body mass , body composition , cardiorespiratory fitness , microvascular endothelial function , and circulating EPCs and EMPs were evaluated after 5 months and at the end of the 10-month program . RESULTS : Residential intervention decreased BMI and body fat percentage , whereas it increased exercise capacity ( P < .001 after 5 and 10 months ) . Microvascular endothelial function also improved in the intervention group ( P = .04 at 10 months ; + 0.59 ± 0.20 compared with + 0.01 ± 0.12 arbitrary units ) . Furthermore , intervention produced a significant reduction in traditional cardiovascular risk factors , including high-sensitivity C-reactive protein ( P = .012 at 10 months ) . EPCs were increased after 5 months ( P = .01 ) , and EMPs decreased after 10 months ( P = .004 ) . CONCLUSIONS : A treatment regimen consisting of supervised diet and exercise training was effective in improving multiple adolescent obesity-related end points Introduction : Worldwide , overweight and obesity are known as posing serious health risks . Successful methods of prevention and therapy for overweight and obesity have remained elusive . It was the aim of the present trial to identify parameters and determinants to guarantee long-term weight reduction . Patients and methods : In total 143/159 children and adolescents ( 90 % ) with overweight and obesity completed the prospect i ve , multicenter trial ( age 13.9 ± 2.4 years , BMI 31.2 ± 5.4 kg/m2 , BMI -SDS 2.51 ± 0.57 ) . During a six-week rehabilitation patients participated in a structured treatment and teaching program ( STTP ) . Following the inpatient treatment the children and adolescents were monitored over a period of 24 months ( physical examination , measurements of BMI , BMI -SDS , body composition , carotid intima-media thickness , laboratory parameters , blood pressure , and st and ardized question naires to assess socio-demographic , socio-economic parameters , eating behavior , well-being , quality of life , intelligence , intrafamilial conflicts , self-efficacy , resilience , sense of coherence , stress-management , social support , and actual body shape ) . Results : 66 % of the children and adolescents showed non-normal laboratory parameters as well as higher blood pressure and /or an increased carotid intima-media thickness . Mean thickness of carotid intima-media was 0.53 ± 0.09 mm ( range , 0.40–0.80 ) ; 15 % of the patients showed a normal range ( < 0.45 mm ) , 40 % slightly elevated ( 0.45–0.50 mm ) and 45 % an elevated ( > 0.50 mm ) thickness . After an inpatient treatment lasting 40.4 ± 4.1 ( range , 28–49 ) days , children and adolescents reached a mean weight reduction of 5.52 ± 3.94 ( 0.4–13.3 ) kg ( p < 0.01 ) accompanied by a reduction of body fat mass . Performing multivariate analyses , the most important psychological factors associated with long-term weight reduction were identified ( R-square = 0.53 ) : Well-being ( β = −0.543 ) , resilience ( β = 0.434 ) and intrafamilial conflicts ( β = 0.315 ) . Conclusion : The different parameters ( i.e. , resilience , intrafamilial conflicts , structured daily schedule ) have demonstrated their utility and strategies should be developed allowing an adaption of these into the STTPs and the integration of intervention into the therapeutic setting Background Increasing activity levels in adolescents with obesity requires the development of exercise programs that are both attractive to adolescents and easily reproducible . The aim of this study was to develop a modular aerobic training program for adolescents with severe obesity , with a focus on variety , individual targets and acquiring physical skills . We report here the effects on aerobic fitness from a pilot study . Furthermore , we examined the feasibility of the modified shuttle test ( MST ) as an outcome parameter for aerobic fitness in adolescents with severe obesity . Methods Fifteen adolescents from an inpatient body weight management program participated in the aerobic training study ( age 14.7 ± 2.1 yrs , body mass index 37.4 ± 3.5 ) . The subjects trained three days per week for 12 weeks , with each session lasting 30–60 minutes . The modular training program consisted of indoor , outdoor and swimming activities . Feasibility of the MST was studied by assessing construct validity , test-retest reliability and sensitivity to change . Results Comparing pretraining and end of training period showed large clinical ly relevant and significant improvements for all aerobic indices : e.g. VO2 peak 17.5 % , effect size ( ES ) 2.4 ; Wmax 8 % , ES 0.8 . In addition , a significant improvement was found for the efficiency of the cardiovascular system as assessed by the oxygen pulse ( 15.8 % , ES 1.6).Construct validity , test-retest reliability and sensitivity to change of the MST were very good . MST was significantly correlated with VO2 peak ( r = 0.79 ) and Wmax ( r = 0.84 ) but not with anthropometric measures . The MST walking distance improved significantly by 32.5 % , ES 2.5 . The attendance rate at the exercise sessions was excellent . Conclusion This modular , varied aerobic training program has clinical ly relevant effects on aerobic performance in adolescents with severe obesity . The added value of our aerobic training program for body weight management programs for adolescents with severe obesity should be studied with a r and omized trial . This study further demonstrated that the MST is a reliable , sensitive and easy to administer outcome measure for aerobic fitness in adolescent body weight management trials OBJECTIVE : To determine if beneficial effects of a weight-management program could be sustained for up to 24 months in a r and omized trial in an ethnically diverse obese population . PATIENTS AND METHODS : There were 209 obese children ( BMI > 95th percentile ) , ages 8 to 16 of mixed ethnic background s r and omly assigned to the intensive lifestyle intervention or clinic control group . The control group received counseling every 6 months , and the intervention group received a family-based program , which included exercise , nutrition , and behavior modification . Lifestyle intervention sessions occurred twice weekly for the first 6 months , then twice monthly for the second 6 months ; for the last 12 months there was no active intervention . There were 174 children who completed the 12 months of the r and omized trial . Follow-up data were available for 76 of these children at 24 months . There were no statistical differences in dropout rates among ethnic groups or in any other aspects . RESULTS : Treatment effect was sustained at 24 months in the intervention versus control group for BMI z score ( −0.16 [ 95 % confidence interval : −0.23 to −0.09 ] ) , BMI ( −2.8 kg/m2 [ 95 % confidence interval : −4.0–1.6 kg/m2 ] ) , percent body fat ( −4.2 % [ 95 % confidence interval : −6.4 % to −2.0 % ] ) , total body fat mass ( −5.8 kg [ 95 % confidence interval : −9.1 kg to −2.6 kg ] ) , total cholesterol ( −13.0 mg/dL [ 95 % confidence interval : −21.7 mg/dL to −4.2 mg/dL ] ) , low-density lipoprotein cholesterol ( −10.4 mg/dL [ 95 % confidence interval : −18.3 mg/dL to −2.4 mg/dL ] ) , and homeostasis model assessment of insulin resistance ( −2.05 [ 95 % confidence interval : −2.48 to −1.75 ] ) . CONCLUSIONS : This study , unprecedented because of the high degree of obesity and ethnically diverse background s of children , reveals that benefits of an intensive lifestyle program can be sustained 12 months after completing the active intervention phase Background : Weight reduction has been accompanied with a reduction in clinic blood pressure ( BP ) in children and adolescents ; however , the effect on ambulatory BP ( ABP ) is uncertain . The objective was to investigate the impact of weight changes on ABP in obese children and adolescents . Methods : Sixty-one severely obese patients aged 10–18 years underwent lifestyle intervention at the Children 's Obesity Clinic . Patients were examined with ABP monitoring at baseline and after 1 year of treatment ( follow-up ) . To account for growth , BP and BMI were st and ardized into z scores , whereas waist circumference was indexed by height [ waist/height ratio ( WHR ) ] . Results : Patients experienced a reduction at follow-up in the degree of obesity [ & Dgr ; BMI z score : −0.21 , 95 % confidence interval ( CI ) −0.32 to −0.10 , P = 0.0003 ; and & Dgr;WHR : −0.02 , 95 % CI −0.03 to −0.004 , P = 0.009 ] . & Dgr;24-h , & Dgr;daytime and & Dgr;night-time SBP and DBP in mmHg and changes in equivalent z scores were related to & Dgr ; BMI z scores and & Dgr;WHR . These relationships were reproduced in multiple regression analyses adjusted for relevant confounders , for example , a reduction in one BMI z score corresponds to a reduction in 24-h SBP by 6.5 mmHg ( P < 0.05 ) . No relationship was found between changes in these anthropometric obesity measures and changes in clinic BP . Conclusion : Changes in obesity measures were closely related to changes in ABP , but not to changes in clinic BP , in severe obese children and adolescents after 1 year of lifestyle intervention . The findings emphasize the use of 24-h ABP measurements in children and adolescents OBJECTIVE : To compare the influence of weight-reducing diets containing different amounts of protein and CHO on body composition in obese adolescents and to examine dietary and physical activity behaviours during follow-up . METHODOLOGY : Design : Prospect i ve r and omised study comparing two weight-reducing diets with the same energy ( 1750 kcal ) and fat ( 31 % ) content , but different protein and carbohydrate contents : PROT− ( 15 % protein , 54 % CHO ) vs PROT+ ( 19 % protein , 50 % CHO ) . Patients : Massively obese 11- to 16-year-old children ( 32 boys and 89 girls ) . Setting : A 9-month treatment in a medical centre ( boarding school ) plus a 2-y follow-up in free-living patients examined at home 1 and 2 y after treatment . Measurements : Anthropometry , bioelectrical impedance , nutritional intakes and physical activity . RESULTS : Of the 121 eligible children ( 61 in PROT− and 60 in PROT+ ) , 82 % completed the trial until the end of weight loss treatment and 60 % were followed 2 y after treatment . Body mass index ( BMI ) value at inclusion was 36.3 kg/m2 or 4.3 z-scores ( 2.9–5.9 ) . BMI z-score decreased to 1.7 at the end of treatment and went back to 2.8 ( 0.8–6.1 ) 2 y after treatment . This corresponded to a weight loss of 30.3 kg and weight regain of 21.3 kg . After treatment , energy intake increased and physical activity decreased . The contribution of energy ingested at breakfast decreased while snacking increased . For all measurements , no dietary group differences existed at baseline or at any time during the intervention and follow-up . CONCLUSION : A higher protein content of the diet did not confer any benefit in the treatment of childhood obesity . Substantial weight loss was obtained with a moderately energy-restricted diet and normal fat content . After weight loss , mean weight increased in spite of moderate energy intake , together with a drift towards obesity-associated behavioural patterns . The causes of the inability to adopt normal weight subjects ’ behaviour permanently deserve to be investigated further BACKGROUND AND AIMS Lifestyle modification has been the mainstay of controlling childhood obesity and has proved to be effective in reducing cardiovascular risk factors . However , it is currently unknown whether the sub clinical atherosclerotic changes associated with nonalcoholic fatty liver disease ( NAFLD ) in such population are reversible . METHODS AND RESULTS We analyzed changes of brachial flow-mediated dilation ( FMD ) , carotid intima-media thickness ( cIMT ) , clinical , laboratory , and imaging data in 120 obese children with NAFLD , at the end of a 1-year intervention program with diet and physical exercise . The lifestyle intervention led to a significant mean decrease of body mass index ( BMI ) -st and ard deviation score ( SDS ) , waist circumference ( WC ) and fat mass , along with diastolic blood pressure , triglycerides , liver enzymes , insulin , insulin resistance ( homeostasis model assessment of insulin resistance , HOMA-IR ) , and high-sensitivity C-reactive protein . At the end of the study , FMD improved ( P < 0.0001 ) , while cIMT did not change significantly ( P = 0.20 ) . A significant decrease in hepatic fat content as measured by magnetic resonance imaging was also observed . Changes in FMD were inversely associated with changes in BMI -SDS , WC , total cholesterol , non-HDL cholesterol , liver enzymes , HOMA-IR , physical activity , and hepatic fat content . After including in the model all the significant variables as well as age , gender , pubertal status , and baseline FMD values , changes in FMD were significantly and independently associated with changes in WC and total cholesterol . CONCLUSION Also in obese children with NAFLD arterial function may be restored by improving metabolic risk factors and reducing visceral adiposity following a 1-year lifestyle intervention BACKGROUND : A low-glycemic index ( GI ) diet may be beneficial for weight management due to its effect on insulin metabolism and satiety . METHODS : Obese children aged 9–16 y were r and omly assigned either a low-GI diet or a low-fat diet ( control group ) for 6 mo . Body composition changes were measured by dual-energy X-ray absorptiometry and bioelectrical impedance analysis . Insulin sensitivity was measured by fasting plasma glucose and insulin . RESULTS : Fifty-two participants completed the study ( mean age : 12.0 ± 2.0 y , 35 boys ) ; both groups showed significantly decreased BMI z-score but similar changes in fat and fat-free mass . The low-GI group demonstrated a significant decline in fasting plasma insulin ( 22.2 ± 14.3 to 13.7 ± 10.9 mU/l ; P = 0.004 ) and homeostatic model of assessment -insulin resistance ( 4.8 ± 3.3 to 2.9 ± 2.3 ; P = 0.007 ) , whereas the control group did not . However , general linear model showed no significant difference in insulin resistance between groups after adjusting for baseline levels , suggesting that the greater reduction in insulin resistance in the low-GI group may be explained by higher baseline values . CONCLUSION : Despite subtle effects on body composition , a low-GI diet may improve insulin sensitivity in obese children with high baseline insulin . A bigger study in obese children with insulin resistance could be worthwhile to confirm our findings Obesity in adolescents is associated with metabolic risk factors for type 2 diabetes , particularly insulin resistance and excessive accumulation of intrahepatic triglyceride ( IHTG ) . The purpose of this study was to evaluate the effect of moderate weight loss on IHTG content and insulin sensitivity in obese adolescents who had normal oral glucose tolerance . Insulin sensitivity , assessed by using the hyperinsulinemic-euglycemic clamp technique in conjunction with stable isotopically labeled tracer infusion , and IHTG content , assessed by using magnetic resonance spectroscopy , were evaluated in eight obese adolescents ( BMI > or=95th percentile for age and sex ; age 15.3 + /- 0.6 years ) before and after moderate diet-induced weight loss ( 8.2 + /- 2.0 % of initial body weight ) . Weight loss caused a 61.6 + /- 8.5 % decrease in IHTG content ( P = 0.01 ) , and improved both hepatic ( 56 + /- 18 % increase in hepatic insulin sensitivity index , P = 0.01 ) and skeletal muscle ( 97 + /- 45 % increase in insulin-mediated glucose disposal , P = 0.01 ) insulin sensitivity . Moderate diet-induced weight loss decreases IHTG content and improves insulin sensitivity in the liver and skeletal muscle in obese adolescents who have normal glucose tolerance . These results support the benefits of weight loss therapy in obese adolescents who do not have evidence of obesity-related metabolic complications during a st and ard medical evaluation OBJECTIVES The present study aim ed to assess the effect of a 6-month exercise program in obese children on flow-mediated vasodilation ( FMD ) carotid intima-media thickness ( IMT ) and cardiovascular risk factors ( RF ) . BACKGROUND Childhood obesity contributes to adult obesity and subsequent cardiovascular disease . Physical inactivity is a major RF for obesity , endothelial dysfunction , and elevated carotid IMT , culminating in early atherosclerotic disease . METHODS Sixty-seven obese subjects ( age 14.7 + /- 2.2 years ) were r and omly assigned to 6 months ' exercise or non-exercise protocol . We examined the influence of exercises ( 1 h , 3 times/week ) on FMD , IMT , and cardiovascular risk profile . RESULTS Compared with lean control subjects , obese children demonstrated at baseline significantly impaired FMD ( 4.09 + /- 1.76 % vs. 10.65 + /- 1.95 % , p < 0.001 ) , increased IMT ( 0.48 + /- 0.08 mm vs. 0.37 + /- 0.05 mm , p < 0.001 ) , and a number of obesity-related cardiovascular RF . Significant improvements were observed in the exercise group for IMT ( 0.44 + /- 0.08 mm , p = 0.012 , -6.3 % ) and FMD ( 7.71 + /- 2.53 % , p < 0.001 , + 127 % ) . This improvement correlated with reduced RF , such as body mass index st and ard deviation scores , body fat mass , waist/hip ratio , ambulatory systolic blood pressure , fasting insulin , triglycerides , low-density lipoprotein/high-density lipoprotein ratio , and low-degree inflammation ( C-reactive protein , fibrinogen ) . CONCLUSIONS The present study documented increased IMT , impaired endothelial function , and various elevated cardiovascular RF in young obese subjects . Regular exercise over 6 months restores endothelial function and improves carotid IMT associated with an improved cardiovascular risk profile in obese children Background and Objective : Childhood nonalcoholic fatty liver disease ( NAFLD ) associated with insulin resistance and obesity is a growing problem and increases the risk of cirrhosis , type 2 diabetes mellitus , and cardiovascular complications . We examined the effects of a 10-week “ weight loss camp ” residency in obese children on the prevalence and degree of NAFLD and insulin sensitivity with 12-month follow-up . Methods : At the camp , 117 obese white children ( body mass index 28.0 ± 3.6 kg/m2 , age 12.1 ± 1.3 years ) exercised moderately for 1 hour/day and restricted their energy intake to induce weight loss . NAFLD was diagnosed and grade d using ultrasound and transaminasemia . Insulin sensitivity and glucose tolerance were assessed using homeostasis model assessment and oral glucose tolerance test . We performed anthropometric measurements and determined body composition using bioimpedance . Data were collected from 71 of 117 children at entry , after the 10 weeks at the camp , and 12 months after the camp ended . Results : The children showed an average weight loss of 7.1 ± 2.7 kg during the camp . At baseline , 43 % had ultrasonographic liver steatosis , 50 % elevated transaminases ( > 25 IU/L ) , and reduced insulin sensitivity . These abnormalities were mutually related and improved significantly during the camp ( P ⩽ 0.05 ) . Liver fat improvement was sustained at 12 months . At the 12-month follow-up , 17 of 71 ( 24 % ) children maintained the body weight . Conclusions : This short-term diet and exercise program induced weight loss , markedly improved all aspects of the threatening condition of NAFLD , and reduced insulin sensitivity in childhood obesity ; 24 % of the children maintained weight loss at least until the 12-month follow-up BACKGROUND Although serum TSH is often elevated in obesity and may be linked to disorders of lipid and glucose metabolism , the clinical relevance of these relationships remains unclear . SUBJECTS Subjects were obese children and adolescents ( n=206 ; mean age 14 yr ) undergoing rapid weight and fat loss in a st and ardized , multidisciplinary , 2-month , in-patient weight loss program . DESIGN This was a prospect i ve study that determined thyroid function , glucose and lipid parameters , leptin , anthropometric measures , and body composition measured by dual-energy x-ray absorption at baseline and at the end of the intervention . RESULTS At baseline , 52 % of children had TSH concentrations in the high normal range ( > 2.5 mU/liter ) , but TSH was not correlated with body weight , body mass index sd scores , lean body mass , or body fat percentage . At baseline , independent of adiposity , TSH significantly correlated with total cholesterol ( P=0.008 ) , low-density lipoprotein cholesterol ( P=0.013 ) , fasting insulin ( P=0.010 ) , homeostatic model assessment ( HOMA ) ( P=0.004 ) , and leptin ( P=0.006 ) . During the intervention , mean body fat , TSH , HOMA , and fasting insulin decreased by 21 , 11 , 53 , and 54 % , respectively . Change ( Δ ) in TSH did not correlate with Δbody weight or Δbody composition , but ΔTSH significantly correlated with , Δfasting insulin and ΔHOMA , independent of Δbody weight or Δbody composition ( P<0.05 ) . CONCLUSION TSH concentrations are elevated in obese children but are not correlated with the amount of excess body weight or fat . During weight loss , independent of changes in body weight or composition , decreases in elevated serum TSH predict decreases in fasting insulin and HOMA . These findings suggest interventions that target high TSH concentrations during weight loss in obese subjects may improve insulin sensitivity IMPORTANCE Severe childhood obesity has become a major health problem , and effective , evidence -based interventions are needed . The relative effectiveness of inpatient compared with ambulatory treatment remains unknown . OBJECTIVE To determine whether an inpatient treatment program is more effective than an ambulatory treatment program at achieving a sustained weight loss in children and adolescents with severe obesity . DESIGN , SETTING , AND PARTICIPANTS We conducted a r and omized clinical trial with a 2-year follow-up at a tertiary referral center for pediatric obesity in the Netherl and s. We recruited 90 children and adolescents aged 8 to 18 years with severe obesity ( body mass index [ BMI ] z score , ≥3.0 or > 2.3 with obesity-related health problems ) . INTERVENTIONS Patients were r and omly assigned to an inpatient ( 6 months of hospitalization on working days ) or an ambulatory ( 12 days of hospital visits at increasing intervals during a 6-month period ) treatment program . Both treatment programs involved an intensive , family-based , lifestyle intervention , including exercise , nutritional education , and behavior modification for the patients and their caregiver(s ) . MAIN OUTCOMES AND MEASURES Change in BMI z score . Secondary outcomes included fasting insulin , fasting plasma glucose , 2-hour plasma glucose , and lipid levels , insulin sensitivity , liver function test results , waist circumference , blood pressure , body composition , and aerobic fitness ( peak oxygen consumption , Vo₂ ) . Outcomes were analyzed by intention to treat . RESULTS Immediately after treatment , reductions in the BMI z score were significantly larger for the inpatient than the ambulatory groups ( mean [ SE ] difference , -0.26 [ 0.12 ; 95 % CI , -0.59 to -0.01 ] ; P = .04 ) . Change from baseline for the BMI z score in the inpatient group was -18.0 % ( P = .001 ) immediately after treatment , -8.5 % ( P = .008 ) at 18 months , and -6.3 % ( P = .38 ) at 30 months ; in the ambulatory group , changes from baseline were -10.5 % ( P = .001 ) , -6.2 % ( P = .39 ) , and -1.5 % ( P > .99 ) , respectively . The favorable outcomes of the inpatient group could not be sustained at 12 and 24 months after treatment . In addition , significant differences in favor of the inpatient group immediately after treatment were found for levels of fasting insulin ( -6.37 IU/L ; P = .02 ) , total cholesterol ( -19.51 mg/dL ; P = .01 ) , low-density lipoprotein cholesterol ( -13.48 mg/dL ; P = .03 ) , and triglycerides ( -25.39 mg/dL ; P = .01 ) , and insulin sensitivity ( -1.37 ; P = .02 ) , fat mass ( -3.31 % ; P = .03 ) , and peak Vo₂ ( 378.2 mL/min ; P = .01 ) . CONCLUSIONS AND RELEVANCE In severely obese children and adolescents , inpatient treatment was superior to ambulatory treatment immediately after treatment , but effects were not sustained at long-term follow-up . These findings stress the need to further study maintenance strategies for sustainable weight loss . TRIAL REGISTRATION trialregister.nl Identifier : NTR1172 Purpose We investigate the effects of 12-week interval training of moderate- or high-intensity exercise on blood lipids and plasma levels of adiponectin . Methods Thirty-four obese adolescent females [ age = 15.9 ± 0.3 years ; BMI and BMI -Z-score = 30.8 ± 1.6 kg/m2 and 3 ± 0.3 , respectively ] , were r and omized to high-intensity interval training ( HIIT , n = 11 ) , moderate-intensity interval training ( MIIT , n = 11 ) , or a control group ( CG , n = 12 ) . Maximal oxygen uptake ( $ $ \mathop V\limits^{. } { \text{O}}_{{2{\text{peak}}}}$$V.O2peak ) , maximal aerobic speed ( MAS ) , plasma lipids and adiponectin levels were measured in all subjects before and after training . Results Following the training program , in both training groups , body mass , BMI -Z-score , and percentage body fat ( % BF ) decreased , while $ $ \mathop V\limits^{. } { \text{O}}_{{2{\text{peak}}}}$$V.O2peak and MAS increased . Low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , and adiponectin levels were positively altered ( −12.6 and −7.4 % ; 6.3 and 8.0 % ; 35.8 and 16.2 % ; high to moderate training program , respectively ) . Waist circumference , triglyceride and total cholesterol decreased only in HIIT group ( −3.5 ; −5.3 and −7.0 % , respectively , in all P < 0.05 ) . Significant decrease in the usual index of insulin resistance ( HOMA-IR ) occurred in HIIT and MIIT groups ( −29.2 ± 5.3 and −18.4 ± 8.6 % , respectively ; P < 0.01 ) . Conclusion The results show that HIIT positively changes blood lipids and adiponectin variables in obese adolescent girls , result ing in improved insulin sensitivity , as attested by a lower HOMA-IR , and achieving better results compared to moderate-intensity exercise |
13,328 | 20,863,953 | Patients with the metabolic syndrome , but without diabetes , maintained a high cardiovascular risk .
CONCLUSIONS The metabolic syndrome is associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality .
Studies are needed to investigate whether or not the prognostic significance of the metabolic syndrome exceeds the risk associated with the sum of its individual components . | OBJECTIVES We sought to conduct a systematic review and meta- analysis of the cardiovascular risk associated with the metabolic syndrome as defined by the 2001 National Cholesterol Education Program ( NCEP ) and 2004 revised National Cholesterol Education Program ( rNCEP ) definitions .
BACKGROUND Numerous studies have investigated the cardiovascular risk associated with the NCEP and rNCEP definitions of the metabolic syndrome .
There is debate regarding the prognostic significance of the metabolic syndrome for cardiovascular outcomes . | Background —Nuclear magnetic resonance ( NMR ) offers an alternative , spectroscopic means of quantifying LDL and of measuring LDL particle size . Methods and Results —We conducted a prospect i ve nested case-control study among healthy middle-aged women to assess LDL particle size ( NMR ) and concentration ( NMR ) as risk factors for future myocardial infa rct ion , stroke , or death of coronary heart disease . Median baseline levels of LDL particle concentration ( NMR ) were higher ( 1597 vs 1404 nmol/L;P = 0.0001 ) and LDL particle size ( NMR ) was lower ( 21.5 vs 21.8 nm;P = 0.046 ) among women who subsequently had cardiovascular events ( n=130 ) than among those who did not ( n= 130 ) . Of these 2 factors , LDL particle concentration ( NMR ) was the stronger predictor ( relative risk for the highest compared with the lowest quartile=4.17 , 95 % CI 1.96–8.87 ) . This compared with a relative risk of 3.11 ( 95 % CI 1.55–6.26 ) for the ratio of total cholesterol to HDL cholesterol and a relative risk of 5.91 ( 95 % CI 2.65–13.15 ) for C-reactive protein . The areas under the receiver operating characteristic curves for LDL particle concentration ( NMR ) , total cholesterol to HDL cholesterol ratio , and C-reactive protein were 0.64 , 0.64 , and 0.66 , respectively . LDL particle concentration ( NMR ) correlated with several traditionally assessed lipid and nonlipid risk factors , and thus adjustment for these tended to attenuate the magnitude of association between LDL particle concentration ( NMR ) and risk . Conclusions —In this cohort , LDL particle concentration measured by NMR spectroscopy was a predictor of future cardiovascular risk . However , the magnitude of predictive value of LDL particle concentration ( NMR ) was not substantively different from that of the total cholesterol to HDL cholesterol ratio and was less than that of C-reactive protein BACKGROUND Recent r and omized clinical trials have suggested that estrogen plus progestin does not confer cardiac protection and may increase the risk of coronary heart disease ( CHD ) . In this report , we provide the final results with regard to estrogen plus progestin and CHD from the Women 's Health Initiative ( WHI ) . METHODS The WHI included a r and omized primary -prevention trial of estrogen plus progestin in 16,608 postmenopausal women who were 50 to 79 years of age at base line . Participants were r and omly assigned to receive conjugated equine estrogens ( 0.625 mg per day ) plus medroxyprogesterone acetate ( 2.5 mg per day ) or placebo . The primary efficacy outcome of the trial was CHD ( nonfatal myocardial infa rct ion or death due to CHD ) . RESULTS After a mean follow-up of 5.2 years ( planned duration , 8.5 years ) , the data and safety monitoring board recommended terminating the estrogen-plus-progestin trial because the overall risks exceeded the benefits . Combined hormone therapy was associated with a hazard ratio for CHD of 1.24 ( nominal 95 percent confidence interval , 1.00 to 1.54 ; 95 percent confidence interval after adjustment for sequential monitoring , 0.97 to 1.60 ) . The elevation in risk was most apparent at one year ( hazard ratio , 1.81 [ 95 percent confidence interval , 1.09 to 3.01 ] ) . Although higher base-line levels of low-density lipoprotein cholesterol were associated with an excess risk of CHD among women who received hormone therapy , higher base-line levels of C-reactive protein , other biomarkers , and other clinical characteristics did not significantly modify the treatment-related risk of CHD . CONCLUSIONS Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women , especially during the first year after the initiation of hormone use . This treatment should not be prescribed for the prevention of cardiovascular disease CONTEXT Despite decades of use and considerable research , the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain . OBJECTIVE To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled disease prevention trial ( the estrogen-alone component of the Women 's Health Initiative [ WHI ] ) conducted in 40 US clinical centers beginning in 1993 . Enrolled were 10 739 postmenopausal women , aged 50 - 79 years , with prior hysterectomy , including 23 % of minority race/ethnicity . INTERVENTION Women were r and omly assigned to receive either 0.625 mg/d of conjugated equine estrogen ( CEE ) or placebo . MAIN OUTCOME MEASURES The primary outcome was coronary heart disease ( CHD ) incidence ( nonfatal myocardial infa rct ion or CHD death ) . Invasive breast cancer incidence was the primary safety outcome . A global index of risks and benefits , including these primary outcomes plus stroke , pulmonary embolism ( PE ) , colorectal cancer , hip fracture , and deaths from other causes , was used for summarizing overall effects . RESULTS In February 2004 , after review ing data through November 30 , 2003 , the National Institutes of Health ( NIH ) decided to end the intervention phase of the trial early . Estimated hazard ratios ( HRs ) ( 95 % confidence intervals [ CIs ] ) for CEE vs placebo for the major clinical outcomes available through February 29 , 2004 ( average follow-up 6.8 years ) , were : CHD , 0.91 ( 0.75 - 1.12 ) with 376 cases ; breast cancer , 0.77 ( 0.59 - 1.01 ) with 218 cases ; stroke , 1.39 ( 1.10 - 1.77 ) with 276 cases ; PE , 1.34 ( 0.87 - 2.06 ) with 85 cases ; colorectal cancer , 1.08 ( 0.75 - 1.55 ) with 119 cases ; and hip fracture , 0.61 ( 0.41 - 0.91 ) with 102 cases . Corresponding results for composite outcomes were : total cardiovascular disease , 1.12 ( 1.01 - 1.24 ) ; total cancer , 0.93 ( 0.81 - 1.07 ) ; total fractures , 0.70 ( 0.63 - 0.79 ) ; total mortality , 1.04 ( 0.88 - 1.22 ) , and the global index , 1.01 ( 0.91 - 1.12 ) . For the outcomes significantly affected by CEE , there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years . The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years . CONCLUSIONS The use of CEE increases the risk of stroke , decreases the risk of hip fracture , and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years . A possible reduction in breast cancer risk requires further investigation . The burden of incident disease events was equivalent in the CEE and placebo groups , indicating no overall benefit . Thus , CEE should not be recommended for chronic disease prevention in postmenopausal women |
13,329 | 31,965,378 | The new findings were as follows : ( i ) dual-agent ULTs were superior to febuxostat alone , and further surveillance on the adverse effects when lesinurad is uptitrated is needed , and ( ii ) terminalia bellerica 500 mg/day , a novel xanthine oxidase inhibitor ( XOI ) made of natural fruit extracts , and topiroxostat ≥ 80 mg/day , an XOI used mostly in Japan , could be new effective options for lowering the occurrence of adherence attrition events .
Key Points • Dual-agent ULTs were superior to febuxostat alone , and further surveillance on the adverse-effects when lesinurad is uptitrated is needed . •
Terminalia bellerica 500 mg/day , a novel xanthine oxidase inhibitor ( XOI ) made of natural fruit extracts , and topiroxostat 80 mg/day , an XOI used mostly in Japan , could be new effective options for lowering the occurrence of adherence attrition events .
Key Points • Dual-agent ULTs were superior to febuxostat alone , and further surveillance on the adverse-effects when lesinurad is uptitrated is needed . •
Terminalia bellerica 500 mg/day , a novel xanthine oxidase inhibitor ( XOI ) made of natural fruit extracts , and topiroxostat 80 mg/day , an XOI used mostly in Japan , could be new effective options for lowering the occurrence of adherence attrition events | Hyperuricemia is a strong precursor of gout , which deteriorates patients ’ health and quality of life .
Sustained adherence to urate-lowering therapies ( ULTs ) is crucial for efficacy and therapeutic cost-effectiveness .
Recently , several new ULTs have been proposed .
We performed a systematic review and meta- analysis of r and omized controlled trials ( RCTs ) to reassess the efficacy and safety of the current ULTs , focusing on adherence attrition-related adverse event reporting . | WHAT IS KNOWN AND OBJECTIVE There are no clinical reports that have compared topiroxostat , a selective xanthine oxidase inhibitor , with allopurinol in serum urate-lowering efficacy . The aim of this study was to compare the efficacy and safety of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout . METHODS A phase 3 , multicentre , r and omized , double-blind , double-dummy , active-controlled , parallel-group study conducted in Japan . Patients who had inadequate serum urate levels ( a gout patient : serum urate level ≥416·4 μmol/L ; an asymptomatic hyperuricemic patient with specific complications ( urinary lithiasis , hypertension , hyperlipidemia and /or diabetes ) : serum urate level ≥475·8 μmol/L ; and an asymptomatic hyperuricemic patient with no specific complications : serum urate level ≥535·3 μmol/L ) were r and omized to topiroxostat 120 mg/day or allopurinol 200 mg/day , with an equal allocation ratio , for 16 weeks . To prevent the onset of gouty arthritis by rapid serum urate reduction , these doses were increased in a stepwise manner . The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit . RESULTS AND DISCUSSION Overall , 206 patients were r and omly assigned to topiroxostat and allopurinol . Two hundred and three patients ( allopurinol : n = 105 , topiroxostat : n = 98 ) received at least one dose of the study drug and had their serum urate level assessed at least once . The baseline characteristics were comparable between groups . The mean age of patients was 53·0 ± 11·4 years and 99 % of patients were male . The primary efficacy endpoint was -34·3 ± 11·1 % in the allopurinol group ( n = 105 ) and -36·3 ± 12·7 % in the topiroxostat group ( n = 98 ) . Non-inferiority of the serum urate-lowering efficacy of topiroxostat to allopurinol was proved by the predefined non-inferiority margin ( 95 % confidence interval , -5·3 to 1·3 % ) . The overall incidences of adverse events and adverse drug reactions were similar between both groups . WHAT IS NEW AND CONCLUSION Topiroxostat 120 mg/day provides non-inferior serum urate reduction compared with allopurinol 200 mg/day and is well tolerated in Japanese hyperuricemic patients with or without gout To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12‐month phase III trial in patients with tophaceous gout To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout ( 1 or 2 gout flares ) Objectives To assess the efficacy and tolerability of lesinurad , an oral selective uric acid reabsorption inhibitor , in combination with allopurinol versus allopurinol alone in patients with gout and an inadequate response to allopurinol . Methods Patients ( N=227 ) with an inadequate response to allopurinol , defined as serum urate ( sUA ) ≥6 mg/dL on ≥2 occasions ≥2 weeks apart despite ≥6 weeks of allopurinol , were r and omised 2:1 to 4 weeks of double-blind treatment with lesinurad ( 200 , 400 or 600 mg/day ) or matching placebo in combination with their pre study allopurinol dose ( 200–600 mg/day ) . Colchicine prophylaxis for gout flares was required . The primary end point was percent reduction from baseline sUA levels at 4 weeks . A pharmacokinetic sub study was also conducted . Safety was assessed throughout . Results Patients ( n=208 ) received ≥1 dose of blinded medication . Lesinurad 200 , 400 and 600 mg in combination with allopurinol produced significant mean percent reductions from baseline sUA of 16 % , 22 % and 30 % , respectively , versus a mean 3 % increase with placebo ( p<0.0001 , all doses vs placebo ) . Similar results were observed in patients with mild or moderate renal insufficiency ( estimated creatinine clearance 30 to < 90 mL/min ) . The incidence of ≥1 treatment-emergent adverse event was 46 % , 48 % and 54 % with lesinurad 200 , 400 and 600 mg , respectively , and 46 % with placebo ( most frequent , gout flares , arthralgia , headache and nasopharyngitis ) , with no deaths or serious adverse events . Conclusions Lesinurad achieves clinical ly relevant and statistically significant reductions in sUA in combination with allopurinol in patients who warrant additional therapy on allopurinol alone . Trial registration number NCT01001338 Background Urate-lowering therapy ( ULT ) is associated with low rates of adherence , leading to a potential risk of relapse of gouty arthritis , tophi , or urolithiasis . Our main aim was to identify the recurrence of gouty arthritis , tophi , or urolithiasis after discontinuation of ULT . Secondary aims included an assessment of ULT re introduction rates and factors associated with relapse . Methods We conducted a systematic literature review of clinical studies investigating the effect of discontinuing any ULT ( allopurinol , febuxostat , probenecid , sulfinpyrazone , benzbromarone ) in adults on long-term therapy . We search ed The Cochrane Central Register of Controlled Trials , MEDLINE , EMBASE , Science Citation Index , and Clinical Trials.gov from inception to March 2016 . Conference abstract s of the ACR/ARHP and EULAR annual conferences were h and - search ed . Study quality was assessed using the first eight items of the method ological index for non-r and omized studies ( MINORS ) tool . The review protocol is registered with PROSPERO ( CRD42016042048 ) . Results A total of 4640 articles were identified , eight of which were ultimately included . Most of these studies pre date d 2000 . MINORS scores ranged from 5 to 10 out of a possible 16 . Mean follow-up duration after discontinuation ranged from 12 to 96 months . Five studies focused on discontinuation of ULT in gouty arthritis and tophi , two in urolithiasis , and one in asymptomatic hyperuricemia . Relapse rates were high in gout ( 36—81 % ) and lower in urolithiasis ( 15 % ) . Relapses occurred 1–4.5 years after ULT discontinuation . In one study , a low serum urate level before and after ULT discontinuation was associated with lower gout recurrence . Discussion Relapse of gout is common although delayed after discontinuation of ULT . Short-term prognosis after ULT discontinuation appears favorable if the serum urate level was low before ULT discontinuation . The results of this review are limited by the paucity of existing studies and their low quality . Further comparative studies should consider larger primary care population s and discontinuation of febuxostat Objective To investigate the efficacy and safety of lesinurad , a selective uric acid reabsorption inhibitor , in a 6 month , phase 3 clinical trial and extension study . Methods Patients with gout who can not take a xanthine oxidase inhibitor ( XOI ) and have serum uric acid ( sUA ) ⩾6.5 mg/dl were r and omized to receive oral lesinurad ( 400 mg daily ) or placebo . The primary endpoint was the proportion of patients with sUA < 6.0 mg/dl at month 6 . Safety assessment s included treatment-emergent adverse events ( TEAEs ) and laboratory data . Patients who completed the study were eligible for an open-label , uncontrolled extension study of lesinurad 400 mg monotherapy . Results Patients ( n = 214 ) were primarily white males ( mean age 54.4 years ; gout duration 11.2 years ) . Significantly more patients achieved the primary endpoint with lesinurad than placebo ( 29.9 vs 1.9 % ; P < 0.0001 ) . Overall TEAE rates were higher with lesinurad ( 77.6 vs 65.4 % ) ; renal-related TEAEs ( 17.8 % ) , renal-related serious TEAEs ( 4.7 % ) and serum creatinine elevations ( 1.5 times baseline , 24.3 % ) occurred only with lesinurad . A total of 143 patients ( 65 lesinurad , 78 placebo ) enrolled in the extension study . Treatment with lesinurad 400 mg result ed in rapid and sustained sUA lowering that persisted for up to 18 months before the study was terminated prematurely . No new safety findings were observed in the extension . Conclusion In patients with gout and intolerance/contraindication to XOIs , lesinurad 400 mg monotherapy demonstrated superior sUA lowering compared with placebo , with sustained effects for up to 18 months . Due to a high incidence of serum creatinine elevations and renal-related adverse events , including serious adverse events with lesinurad 400 mg , lesinurad should not be used as monotherapy . Trial registration Clinical Trials.gov ( http://clinincaltrials.gov ) , NCT01508702 BACKGROUND Cardiovascular risk is increased in patients with gout . We compared cardiovascular outcomes associated with febuxostat , a nonpurine xanthine oxidase inhibitor , with those associated with allopurinol , a purine base analogue xanthine oxidase inhibitor , in patients with gout and cardiovascular disease . METHODS We conducted a multicenter , double‐blind , noninferiority trial involving patients with gout and cardiovascular disease ; patients were r and omly assigned to receive febuxostat or allopurinol and were stratified according to kidney function . The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point ( a composite of cardiovascular death , nonfatal myocardial infa rct ion , nonfatal stroke , or unstable angina with urgent revascularization ) . RESULTS In total , 6190 patients underwent r and omization , received febuxostat or allopurinol , and were followed for a median of 32 months ( maximum , 85 months ) . The trial regimen was discontinued in 56.6 % of patients , and 45.0 % discontinued follow‐up . In the modified intention‐to‐treat analysis , a primary end‐point event occurred in 335 patients ( 10.8 % ) in the febuxostat group and in 321 patients ( 10.4 % ) in the allopurinol group ( hazard ratio , 1.03 ; upper limit of the one‐sided 98.5 % confidence interval [ CI ] , 1.23 ; P = 0.002 for noninferiority ) . All‐cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group ( hazard ratio for death from any cause , 1.22 [ 95 % CI , 1.01 to 1.47 ] ; hazard ratio for cardiovascular death , 1.34 [ 95 % CI , 1.03 to 1.73 ] ) . The results with regard to the primary end point and all‐cause and cardiovascular mortality in the analysis of events that occurred while patients were being treated were similar to the results in the modified intention‐to‐treat analysis . CONCLUSIONS In patients with gout and major cardiovascular coexisting conditions , febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events . Allcause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol . ( Funded by Takeda Development Center Americas ; CARES Clinical Trials.gov number , NCT01101035 . AIMS Dual-urate-lowering therapy ( ULT ) with xanthine oxidase inhibitor and uricosuric medications is a treatment option for severe gout . Uricosuric agents can cause hyperuricosuria , a risk factor for nephrolithiasis and acute uric acid nephropathy . The aims of the present study were to simulate the relationship between suboptimal drug adherence and efficacy , and to quantify the risk of hyperuricosuria in gout patients receiving mono- and dual-ULTs . METHODS The impact of poor medication adherence was studied using two-compartment pharmacokinetic ( PK ) models based on published evidence , and a semi-mechanistic four-compartment pharmacodynamic ( PD ) model . The PKPD model was used to simulate mono and dual-ULT in gout patients with either under-excretion ( lowered clearance ) or overproduction of uric acid , with suboptimal adherence modelled as either a single drug holiday of increasing duration or doses taken at r and om . RESULTS Simulation results showed a surge in urinary uric acid occurring when dosing is restarted following missed doses . For under-excreters taking a 20-day drug holiday , the addition of 200 mg ( or 400 mg ) lesinurad to 80 mg febuxostat increased the percentage of patients experiencing hyperuricosuria from 0 % to 1.4 % ( or 3.1 % ) . In overproducers , restarting ULTs following drug holidays of more than 5 days leads to over 60 % of patients experiencing hyperuricosuria . CONCLUSIONS Suboptimal medication adherence may compromise the safety and efficacy of mono- and dual-ULTs , especially in patients with gout result ing from an overproduction of uric acid . Clinicians and pharmacists should consider counselling patients with respect to the risks associated with partial adherence , and offer interventions to improve adherence or tailor treatments , where appropriate Abstract Background Topiroxostat , a selective xanthine oxidase inhibitor , shows effective reduction in the serum urate level in hyperuricemic patients with or without gout . The objective of this study was to evaluate the efficacy and safety of topiroxostat in hyperuricemic stage 3 chronic kidney disease patients with or without gout . Methods The study design was a 22-week , r and omized , multicenter , double-blind study . The enrolled patients were r and omly assigned to treatment with topiroxostat 160 mg/day ( n = 62 ) or to the placebo ( n = 61 ) . The endpoints were the percent change in the serum urate level , change in the estimated glomerular filtration rate , the urinary albumin-to-creatinine ratio , the proportion of patients with serum urate levels of 356.88 μmol/L or less , blood pressure , and serum adiponectin . Results After 22 weeks , although the changes in the estimated glomerular filtration rate and blood pressure were not significant , the percent change in the serum urate level ( −45.38 vs. −0.08 % , P < 0.0001 ) and the percent change in urinary albumin-to-creatinine ratio ( −33.0 vs. −6.0 % , P = 0.0092 ) were found to have decreased in the topiroxostat as compared with the placebo . Although the incidence of ‘ alanine aminotransferase increased ’ was higher in the topiroxostat , serious adverse event rates were similar in the two groups . Conclusion Topiroxostat 160 mg effectively reduced the serum urate level in the hyperuricemic stage 3 chronic kidney disease patients with or without gout Topiroxostat , a selective xanthine oxidoreductase inhibitor , is used in Japan for the treatment of hyperuricemic patients with or without gout . In terms of the effectiveness of topiroxostat in lowering serum urate levels , the dose – response relationship has been evaluated ; however , it remains to be verified . A r and omized , multi-center , double-blinded study of topiroxostat was performed for Japanese hyperuricemic patients with or without gout . During the 16-week study , 157 Japanese hyperuricemic patients with or without gout were r and omly assigned to receive a placebo , topiroxostat at 120 or 160 mg/day , or allopurinol at 200 mg/day . The primary endpoint of this study was to determine the lowering rate of serum uric acid levels compared to those of baseline at the end of administration . A dose – response relationship ( regarding decreases in the serum urate levels ) was confirmed for the placebo and topiroxostat at 120 and at 160 mg/day . Moreover , at the end of administration , the lowering rate of serum urate levels was determined to be −44.8 % in the topiroxostat 160-mg/day group . No significant difference in the incidence of adverse events was observed among all groups , including the allopurinol group . The serum urate-lowering effect of topiroxostat was found to have a dose – response relationship in Japanese hyperuricemic patients with or without gout Background — Oxidative stress may contribute to heart failure ( HF ) progression . Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes . Methods and Results — We r and omly assigned 253 patients with symptomatic HF , left ventricular ejection fraction ⩽40 % , and serum uric acid levels ≥9.5 mg/dL to receive allopurinol ( target dose , 600 mg daily ) or placebo in a double-blind , multicenter trial . The primary composite end point at 24 weeks was based on survival , worsening HF , and patient global assessment . Secondary end points included change in quality of life , submaximal exercise capacity , and left ventricular ejection fraction . Uric acid levels were significantly reduced with allopurinol in comparison with placebo ( treatment difference , –4.2 [ –4.9 , –3.5 ] mg/dL and –3.5 [ –4.2 , –2.7 ] mg/dL at 12 and 24 weeks , respectively , both P<0.0001 ) . At 24 weeks , there was no significant difference in clinical status between the allopurinol- and placebo-treated patients ( worsened 45 % versus 46 % , unchanged 42 % versus 34 % , improved 13 % versus 19 % , respectively ; P=0.68 ) . At 12 and 24 weeks , there was no significant difference in change in Kansas City Cardiomyopathy Question naire scores or 6-minute walk distances between the 2 groups . At 24 weeks , left ventricular ejection fraction did not change in either group or between groups . Rash occurred more frequently with allopurinol ( 10 % versus 2 % , P=0.01 ) , but there was no difference in serious adverse event rates between the groups ( 20 % versus 15 % , P=0.36 ) . Conclusions — In high-risk HF patients with reduced ejection fraction and elevated uric acid levels , xanthine oxidase inhibition with allopurinol failed to improve clinical status , exercise capacity , quality of life , or left ventricular ejection fraction at 24 weeks . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00987415 Introduction The purpose of this study was to compare urate-lowering ( UL ) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate ( sUA ) ≥ 8.0 mg/dL in a six-month trial . Methods Subjects ( n = 2,269 ) were r and omized to febuxostat 40 mg or 80 mg , or allopurinol 300 mg ( 200 mg in moderate renal impairment ) . Endpoints included the proportion of all subjects with sUA < 6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA < 6.0 mg/dL. Safety assessment s included blinded adjudication of each cardiovascular ( CV ) adverse event ( AE ) and death . Results Comorbidities included : renal impairment ( 65 % ) ; obesity ( 64 % ) ; hyperlipidemia ( 42 % ) ; and hypertension ( 53 % ) . In febuxostat 40 mg , febuxostat 80 mg , and allopurinol groups , primary endpoint was achieved in 45 % , 67 % , and 42 % , respectively . Febuxostat 40 mg UL was statistically non-inferior to allopurinol , but febuxostat 80 mg was superior to both ( P < 0.001 ) . Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg ( 72 % ; P < 0.001 ) compared with febuxostat 40 mg ( 50 % ) or allopurinol ( 42 % ) , but febuxostat 40 mg showed greater efficacy than allopurinol ( P = 0.021 ) . Rates of AEs did not differ across treatment groups . Adjudicated ( APTC ) CV event rates were 0.0 % for febuxostat 40 mg and 0.4 % for both febuxostat 80 mg and allopurinol . One death occurred in each febuxostat group and three in the allopurinol group . Conclusions Urate-lowering efficacy of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol ( 300/200 mg ) , which were comparable . In subjects with mild/moderate renal impairment , both febuxostat doses were more efficacious than allopurinol and equally safe . At the doses tested , safety of febuxostat and allopurinol was comparable . Clinical Trial Registration Arhalofenate is a novel antiinflammatory uricosuric agent . The objective of this study was to evaluate its antiflare activity in patients with gout CONTEXT Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition . Pegloticase , monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase , was developed to fulfill this need . OBJECTIVE To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout . DESIGN , SETTING , AND PATIENTS Two replicate , r and omized , double-blind , placebo-controlled trials ( C0405 and C0406 ) were conducted between June 2006 and October 2007 at 56 rheumatology practice s in the United States , Canada , and Mexico in patients with severe gout , allopurinol intolerance or refractoriness , and serum uric acid concentration of 8.0 mg/dL or greater . A total of 225 patients participated : 109 in trial C0405 and 116 in trial C0406 . INTERVENTION Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion ( biweekly treatment group ) , pegloticase alternating with placebo at successive infusions ( monthly treatment group ) , or placebo ( placebo group ) . MAIN OUTCOME MEASURE Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6 . RESULTS In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group ( 47 % ; 95 % CI , 31%-62 % ) , 8 of 41 patients in the monthly group ( 20 % ; 95 % CI , 9%-35 % ) , and in 0 patients treated with placebo ( 0/20 ; 95 % CI , 0%-17 % ; P < .001 and < .04 for comparisons between biweekly and monthly groups vs placebo , respectively ) . Among patients treated with pegloticase in trial C0406 , 16 of 42 in the biweekly group ( 38 % ; 95 % CI , 24%-54 % ) and 21 of 43 in the monthly group ( 49 % ; 95 % CI , 33%-65 % ) achieved the primary end point ; no placebo-treated patients reached the primary end point ( 0/23 ; 95 % CI , 0%-15 % ; P = .001 and < .001 , respectively ) . When data in the 2 trials were pooled , the primary end point was achieved in 36 of 85 patients in the biweekly group ( 42 % ; 95 % CI , 32%-54 % ) , 29 of 84 patients in the monthly group ( 35 % ; 95 % CI , 24%-46 % ) , and 0 of 43 patients in the placebo group ( 0 % ; 95 % CI , 0%-8 % ; P < .001 for each comparison ) . Seven deaths ( 4 in patients receiving pegloticase and 3 in the placebo group ) occurred between r and omization and closure of the study data base ( February 15 , 2008 ) . CONCLUSION Among patients with chronic gout , elevated serum uric acid level , and allopurinol intolerance or refractoriness , the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months result ed in lower uric acid levels compared with placebo . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00325195 Objectives : To compare the efficacy and tolerability of allopurinol 300–600 mg/day versus benzbromarone 100–200 mg/day used to attain a target serum urate concentration ( sUr ) ⩽0.30 mmol/l ( 5 mg/dl ) . Methods : A r and omised , controlled , open-label , multicentre trial in gout patients with renal function defined as a calculated creatinine clearance ⩾50 ml/min . Patients were treated with 300 mg allopurinol or 100 mg benzbromarone once a day ( stage 1 ) . If sUr ⩽0.30 mmol/l was not attained after 2 months , the dose was doubled to allopurinol 300 mg twice a day or benzbromarone 200 mg once a day ( stage 2 ) . The primary end point was treatment success in either of the two stages , defined as clinical tolerability and attainment of biochemical target sUr . Results : Sixty-five patients were enrolled in stage 1 ; 36 received allopurinol and 29 received benzbromarone . Fifty-five patients ( 85 % ) were analysed at stage 1 : the success rates were 8/31 ( 26 % ) and 13/25 ( 52 % ) , respectively , and the difference was −0.26 ( 95 % CI from −0.486 to −0.005 ) , p = 0.049 . At stage 2 , the success rates were 21/27 ( 78 % ) and 18/23 ( 78 % ) , respectively , and the difference was −0.005 ( 95 % CI from −0.223 to 0.220 ) , p = 1.00 . Two patients stopped receiving allopurinol and three stopped receiving benzbromarone because of adverse drug reactions . Conclusions : Increasing the allopurinol dose from 300 to 600 mg/day and the benzbromarone dose from 100 to 200 mg/day according to the target sUr produced significantly higher success rates ( both 78 % successful in attaining sUr ⩽0.30 mmol/l ) . No significant differences in treatment success between benzbromarone and allopurinol were found after dose escalation . Trial registration number : IS RCT N49563848 ) To compare the efficiency and safety of febuxostat with those of allopurinol in Chinese patients with gout and hyperuricemia Background Hyperuricemia is supposed to be an independent risk factor for kidney dysfunction in diabetic patients . We attempted to examine the uric acid-lowering effect and the renoprotective effect of topiroxostat , a selective xanthine oxidoreductase inhibitor , in patients with diabetic nephropathy and hyperuricemia in this pilot study . Methods The study design was r and omized , double-blind , placebo-controlled , parallel-group study . A total of 65 patients with hyperuricemia and diabetic nephropathy with microalbuminuria were enrolled and assigned to either the topiroxostat group or the placebo group . Topiroxostat ( stepwise dosing from 40 to 160 mg/day ) or matching placebo was administered BID for 28 weeks . The primary endpoint was a change in the urinary albumin-to-creatinine ratio in the first-morning-void urine sample . Secondary endpoints were changes in the estimated glomerular filtration rate and the serum uric acid level . Results At 28 weeks , there was no significant difference in the percent change from baseline in the urinary albumin-to-creatinine ratio between the two groups ( topiroxostat : 0 vs. placebo : 17 % , p = 0.3206 ) , but the changes in the estimated glomerular filtration rate ( − 0.2 vs. − 4.0 mL/min/1.73 m2 , p = 0.0303 ) and the serum uric acid level ( − 2.94 vs. − 0.20 mg/dL , p < 0.0001 ) were significantly different between the topiroxostat and placebo groups . Gouty arthritis occurred in 1 patient in the placebo group and no patients in the topiroxostat group . Conclusion These findings support that diabetic nephropathy combined with hyperuricemia may be associated with kidney dysfunctions . Topiroxostat provides strict control of the serum uric acid level preventing decline of eGFR in these patients Lesinurad is a selective uric acid reabsorption inhibitor used for the treatment of gout in combination with a xanthine oxidase inhibitor . The Combining Lesinurad with Allopurinol St and ard of Care in Inadequate Responders ( CLEAR 1 ) study , a 12‐month , multicenter , r and omized , double‐blind , placebo‐controlled phase III trial , was conducted to investigate daily lesinurad ( 200 mg or 400 mg orally ) added to allopurinol versus placebo plus allopurinol in patients with serum urate ( UA ) levels above a target of < 6.0 mg/dl OBJECTIVE To assess the efficacy of pegloticase in achieving and maintaining plasma urate levels of < 6 mg/dl in gout patients in whom other treatments have failed , and to assess the pharmacokinetics and safety of pegloticase . METHODS Forty-one patients were r and omized to undergo 12 - 14 weeks of treatment with pegloticase at 1 of 4 dosage levels : 4 mg every 2 weeks , 8 mg every 2 weeks , 8 mg every 4 weeks , or 12 mg every 4 weeks . Plasma uricase activity , plasma urate , and antipegloticase antibodies were measured , pharmacokinetic parameters were assessed , and adverse events were recorded . RESULTS The mean plasma urate level was reduced to < or=6 mg/dl within 6 hours in all dosage groups , and this was sustained throughout the treatment period in the 8 mg and 12 mg dosage groups . The most effective dosage was 8 mg every 2 weeks . Twenty-six patients received all protocol doses . The percentage of the patients in whom the primary efficacy end point ( plasma urate < 6 mg/dl for 80 % of the study period ) was achieved ranged from 50 % to 88 % . Gout flares occurred in 88 % of the patients . The majority of adverse events ( excluding gout flare ) were unrelated to treatment and were mild or moderate in severity . Infusion-day adverse events were the most common reason for study withdrawal ( 12 of 15 withdrawals ) . There were no anaphylactic reactions . Antipegloticase antibody , present in 31 of 41 patients , was associated with reduced circulating half-life of pegloticase in some patients . CONCLUSION Pegloticase , administered in multiple doses , was effective in rapidly reducing and maintaining plasma urate levels at < or=6 mg/dl in most patients in whom conventional therapy had been unsuccessful due to lack of response , intolerability , or contraindication Objectives : This phase IIIB study compared the efficacy and safety of febuxostat and allopurinol in gout patients with or without tophi who were HLA-B*5801 negative . Method : Eligible patients were r and omized to a febuxostat group ( 80 mg QD ) or an allopurinol group ( 300 mg QD ) . Following an initial 2-week washout period , over the next 12 weeks we made five measurements of serum urate levels along with assessment s of adverse events ( AEs ) . Results : Forty-three out of 152 screened subjects ( 28.3 % ) were ineligible either because of the presence of the HLA-B*5801 allele or for various other reasons . The febuxostat group ( n = 54 ) and the allopurinol group ( n = 55 ) had no significant differences in demographic or baseline characteristics . From week 2 to week 12 , the febuxostat group had a significantly lower serum urate level than the allopurinol group ( p ≤ 0.001 for all comparisons ) and significantly more patients with serum urate levels less than 6.0 mg/dL. The serum urate levels of the febuxostat group declined by more than 40 % from week 2 to week 12 and this decrease was greater than that in the allopurinol group ( ~30 % ) . The two groups were similar in terms of AEs . Conclusions : Febuxostat was more effective than allopurinol in reducing the serum urate levels of Han Chinese patients with gout or tophaceous gout who were HLA-B*5801 negative , without causing any serious skin reactions . Febuxostat should be considered for treatment of Han Chinese patients with gout who are HLA-B*5801 negative Objectives Determine the efficacy and safety of daily lesinurad ( 200 or 400 mg orally ) added to allopurinol in patients with serum uric acid ( sUA ) above target in a 12-month , r and omised , phase III trial . Methods Patients on allopurinol ≥300 mg ( ≥200 mg in moderate renal impairment ) had sUA level of ≥6.5 mg/dL ( ≥387 µmol/L ) at screening and two or more gout flares in the prior year . Primary end point was the proportion of patients achieving sUA level of < 6.0 mg/dL ( < 357 µmol/L ) ( month 6 ) . Key secondary end points were mean gout flare rate requiring treatment ( months 7 through 12 ) and proportions of patients with complete resolution of one or more target tophi ( month 12 ) . Safety assessment s included adverse events and laboratory data . Results Patients ( n=610 ) were predominantly male , with mean ( ±SD ) age 51.2±10.90 years , gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL ( 410±71 µmol/L ) . Lesinurad at 200 and 400 mg doses , added to allopurinol , significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 ( 55.4 % , 66.5 % and 23.3 % , respectively , p<0.0001 both lesinurad+allopurinol groups ) . In key secondary end points , there were no statistically significant treatment-group differences favouring lesinurad . Lesinurad was generally well tolerated ; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy . Renal-related adverse events occurred in 5.9 % of lesinurad 200 mg+allopurinol , 15.0 % of lesinurad 400 mg+allopurinol and 4.9 % of allopurinol-alone groups , with serum creatinine elevation of ≥1.5 × baseline in 5.9 % , 15.0 % and 3.4 % , respectively . Serious treatment-emergent adverse events occurred in 4.4 % of lesinurad 200 mg+allopurinol , in 9.5 % of lesinurad 400 mg+allopurinol and in 3.9 % of allopurinol-alone groups , respectively . Conclusion Lesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy . Trial registration number NCT01493531 Objectives To evaluate the efficacy and tolerability of st and ardized aqueous extracts of Terminalia chebula and Terminalia bellerica versus febuxostat and placebo on reduction in serum uric acid levels in subjects with hyperuricemia . Material s and methods A total of 110 eligible subjects with hyperuricemia were enrolled and r and omized to either of the five treatment groups – T. chebula 500 mg twice a day ( BID ) , T. bellerica 250 mg BID , T. bellerica 500 mg BID , placebo BID , and febuxostat 40 mg once daily plus an identical placebo – for a duration of 24 weeks . Serum uric acid levels were measured at baseline and at the end of 4 , 8 , 12 , 16 , 20 , and 24 weeks . Statistical analysis was done using GraphPad Prism Software 4 . Results and interpretation All active treatment groups showed a reduction in serum uric acid levels compared to baseline and placebo . Significant reduction in mean serum uric acid levels started as early as 4 weeks following treatment , compared to baseline , with T. bellerica ( 500 and 250 mg ) , febuxostat ( P<0.001 ) , and T. chebula 500 mg ( P<0.01 ) ; an increase in serum uric acid levels was seen with placebo ( P<0.05 ) . The serum uric acid levels became steady after 16 weeks of treatment and remained the same until the end of 24 weeks . The reduction of serum uric acid levels in the T. bellerica 500 mg group was nearly twice that of the T. chebula 500 mg group as well as T. bellerica 250 mg group at all time points . T. bellerica 500 mg reduced serum uric acid levels from 8.07±0.87 to 5.78±0.25 compared to febuxostat , which reduced serum uric acid levels from 8.53±0.97 to 4.28±0.67 ( P<0.001 ) at the end of 24 weeks . The efficacy of T. bellerica appeared to be dose dependent . All the formulations were well tolerated . Conclusion T. bellerica has the potential for treating hyperuricemia as it was devoid of any serious adverse effects in the present study . Further studies are needed to confirm this potential Objective To evaluate the use of prospect i ve screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions ( SCARs ) induced by allopurinol treatment . Design National prospect i ve cohort study . Setting 15 medical centres in different regions of Taiwan , from July 2009 to August 2014 . Participants 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously . Participants were excluded if they had undergone a bone marrow transplant , were not of Han Chinese descent , and had a history of allopurinol induced hypersensitivity . DNA purified from 2910 participants ’ peripheral blood was used to assess the presence of HLA-B*58:01 . Main outcome measures Incidence of allopurinol induced SCARs with and without screening . Results Participants who tested positive for HLA-B*58:01 ( 19.6 % , n=571 ) were advised to avoid allopurinol , and were referred to an alternate drug treatment or advised to continue with their pre study treatment . Participants who tested negative ( 80.4 % , n=2339 ) were given allopurinol . Participants were interviewed once a week for two months to monitor symptoms . The historical incidence of allopurinol induced SCARs , estimated by the National Health Insurance research data base of Taiwan , was used for comparison . Mild , transient rash without blisters developed in 97 ( 3 % ) participants during follow-up . None of the participants was admitted to hospital owing to adverse drug reactions . SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01 . By contrast , seven cases of SCARs were expected , based on the estimated historical incidence of allopurinol induced SCARs nationwide ( 0.30 % per year , 95 % confidence interval 0.28 % to 0.31 % ; P=0.0026 ; two side one sample binomial test ) . Conclusions Prospect i ve screening of the HLA-B*58:01 allele , coupled with an alternative drug treatment for carriers , significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres CONTEXT In surveys based on data available prior to 2000 , clinical trials funded by for-profit organizations appeared more likely to report positive findings than those funded by not-for-profit organizations . Whether this situation has changed over the past 5 years or whether similar effects are present among jointly funded trials is unknown . OBJECTIVE To determine in contemporary r and omized cardiovascular trials the association between funding source and the likelihood of reporting positive findings . DESIGN We review ed 324 consecutive superiority trials of cardiovascular medicine published between January 1 , 2000 , and July 30 , 2005 , in JAMA , The Lancet , and the New Engl and Journal of Medicine . MAIN OUTCOME MEASURE The proportion of trials favoring newer treatments over the st and ard of care was evaluated by funding source . RESULTS Of the 324 superiority trials , 21 cited no funding source . Of the 104 trials funded solely by not-for-profit organizations , 51 ( 49 % ) reported evidence significantly favoring newer treatments over the st and ard of care , whereas 53 ( 51 % ) did not ( P = .80 ) . By contrast , 92 ( 67.2 % ) of 137 trials funded solely by for-profit organizations favored newer treatments over st and ard of care ( P<.001 ) . Among 62 jointly funded trials , 35 ( 56.5 % ) , an intermediate proportion , favored newer treatments . For 205 r and omized trials evaluating drugs , the proportions favoring newer treatments were 39.5 % , not-for-profit ; 54.4 % , jointly funded ; and 65.5 % , for-profit trials ( P for trend across groups = .002 ) . For the 39 r and omized trials evaluating cardiovascular devices , the proportions favoring newer treatments were 50.0 % , not-for-profit ; 69.2 % , jointly funded ; and 82.4 % , for-profit trials ( P for trend across groups = .07 ) . Regardless of funding source , trials using surrogate end points , such as quantitative angiography , intravascular ultrasound , plasma biomarkers , and functional measures were more likely to report positive findings ( 67 % ) than trials using clinical end points ( 54.1 % ; P = .02 ) . CONCLUSIONS Recent cardiovascular trials funded by for-profit organizations are more likely to report positive findings than trials funded by not-for-profit organizations , as are trials using surrogate rather than clinical end points . Trials jointly funded by not-for-profit and for-profit organizations appear to report positive findings at a rate approximately midway between rates observed in trials supported solely by one or the other of these entities Treatment of gout and hyperuricemia can be difficult in patients with chronic renal failure . At present , there is no study available comparing the efficacy of the most widely used agent , allopurinol , and the uricosuric benzbromarone for the control of hyperuricemia in patients with renal insufficiency . We describe an open , r and omized , actively controlled , comparative trial in patients with clearance of creatinine from 20 to 80 mL/ min/1.73 m(2 ) . Patients were r and omized to take benzbromarone ( 100 - 200 mg/day ) or allopurinol ( 100 - 300 mg/day ) . Outcome variables were the following : reduction of serum urate ( Sur ) , Sur & tl ; 6 mg/dL ( 357 micromol/L ) , reduction of gouty bouts and reduction of tophi . During 9 - 24 months of follow-up 36 patients were studied . The reduction of Sur was higher with benzbromarone , and only 1 of 17 patients taking benzbromarone did not achieve Sur < 6 mg/dL versus 7 of 19 taking allopurinol . Patients who did not reach optimal Sur levels with allopurinol were more frequently taking diuretics and showed lower fractional excretion of urate and higher initial Sur levels than patients with proper control of Sur . Seven patients with suboptimal control of serum urate were changed to benzbromarone 100 mg/day , which showed efficacy similar in those who were initially r and omized to benzbromarone . A reduction of gouty bouts and size of tophi was observed after proper control of Sur . Allopurinol is effective in controlling hyperuricemia , but patients with higher initial Sur levels or taking concomitant diuretic therapy are less prone to reach therapeutic goals .Benzbromarone is useful for the control of hyperuricemia in patients with renal insufficiency even with concomitant diuretic administration ; patients benefited include those who previously had no improvement by taking allopurinol BACKGROUND Allopurinol has been widely used for the treatment of hyperuricemia , however , it may be associated with various adverse effects . Febuxostat has been identified as a potentially safe and efficacious alternative . OBJECTIVES A multicenter study with r and omized , placebo-controlled , double-blind , parallel , intergroup comparison was carried out to evaluate the dose-response relationship , efficacy , and safety of febuxostat in 202 patients with hyperuricemia ( including patients with gout ) in Japan . METHODS The subjects were treated with febuxostat at fixed maintenance doses ( 20 - 80 mg/d ) or a placebo for 16 weeks . The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 16 weeks of treatment were evaluated . RESULTS The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less at 16 weeks was 87.8 % in the 80-mg/d dose group , 83.3 % in the 60-mg/d group , 82.9 % in the 40-mg/d group , 46.5 % in the 20-mg/d group , and 2.6 % in the placebo group ( P < 0.001 , Mantel-Haenszel test ) . A statistically significant dose-response relationship was found . The percent change in serum uric acid levels after 16 weeks of treatment differed significantly between each febuxostat dose group and the placebo group and increased in a dose-dependent manner above 40 mg/d . No deaths , events posing a clinical problem , or serious adverse reactions attributable to febuxostat were noted . Similar results were obtained regardless of gout history . CONCLUSIONS Febuxostat can safely reduce serum uric acid levels to 6.0 mg/dL or less in 80 % or more of patients with hyperuricemia ( including gout ) at doses of 40 mg/d or higher BACKGROUND Febuxostat has been reported to have a stronger effect on hyperuricemia than allopurinol . METHODS AND RESULTS Cardiac surgery patients with hyperuricemia ( n=141 ) were r and omized to a febuxostat group or an allopurinol group . The study was single-blind , so the treatment was not known by the investigators . The primary endpoint was serum uric acid ( UA ) level . Secondary endpoints included serum creatinine , urinary albumin , cystatin-C , oxidized low-density lipoprotein ( LDL ) , eicosapentaenoic acid/arachidonic acid ratio , total cholesterol , triglycerides , LDL , high-density lipoprotein , high-sensitivity C-reactive protein , blood pressure , heart rate , pulse wave velocity ( PWV ) , ejection fraction , left ventricular mass index ( LVMI ) , and adverse reactions . UA level was significantly lower in the febuxostat group than the allopurinol group from 1 month of treatment onward . Serum creatinine , urinary albumin , cystatin-C and oxidized LDL were also significantly lower in the febuxostat group . There were no significant changes in systolic blood pressure , PWV , and LVMI in the allopurinol group , but these parameters all had a significant decrease in the febuxostat group . CONCLUSIONS Febuxostat was effective for high-risk cardiac surgery patients with hyperuricemia because it reduced UA more markedly than allopurinol . Febuxostat also had a renoprotective effect , inhibited oxidative stress , showed anti-atherogenic activity , reduced blood pressure , and decreased PWV and LVMI WHAT IS KNOWN AND OBJECTIVE In Japan , although topiroxostat , a selective xanthine oxidoreductase inhibitor , has been used for the treatment of patients with hyperuricemia including gout , no published r and omized controlled studies evaluating the dose-dependent relationship with respect to the serum urate-lowering efficacy have been reported . The aim of this study was to evaluate the dose-dependent relationship with serum urate-lowering efficacy and safety of topiroxostat in Japanese hyperuricemic patients including gout . METHODS We conducted an exploratory , phase 2a , multicentre , r and omized , double-blind , 8-week , placebo-controlled study in Japanese hyperuricemic patients with or without gout . The study arms were placebo and topiroxostat 40 , 60 , 80 or 120 mg/day . The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit . RESULTS AND DISCUSSION One hundred and eighty-seven eligible patients were r and omized and 186 received at least one dose of the study drug . The study results demonstrated a dose-dependent serum urate reduction effect ranging from 40 to 120 mg/day ( P < 0·001 , Jonckheere-Terpstra test ) . The mean per cent change in serum urate level from baseline at the final visit was -30·8 % in the 120-mg group and 1·6 % with placebo , with a between-group difference of -32·4 % ( [ 95 % confidence interval , -38·9 % to -25·9 % ] ; P < 0·001 ) . Incidences of overall adverse events ( AEs ) in the topiroxostat groups were comparable to those in the placebo group ; however , the incidence of AEs in the 120-mg group was statistically lower than that in the placebo group . The incidences of gouty arthritis were not statistically but numerically higher in the topiroxostat 80- and 120-mg groups . WHAT IS NEW AND CONCLUSIONS A dose-dependent serum urate-lowering efficacy of topiroxostat was observed in Japanese hyperuricemic male patients with or without gout . Further clinical studies aim ed at evaluating the long-term safety and clinical efficacy are warranted OBJECTIVE Gout affects approximately 1 - 2 % of the American population . Current options for treating hyperuricemia in chronic gout are limited . The purpose of this study was to assess the safety and efficacy of febuxostat , a nonpurine selective inhibitor of xanthine oxidase , in establishing normal serum urate ( sUA ) concentrations in gout patients with hyperuricemia ( > or=8.0 mg/dl ) . METHODS We conducted a phase II , r and omized , double-blind , placebo-controlled trial in 153 patients ( ages 23 - 80 years ) . Subjects received febuxostat ( 40 mg , 80 mg , 120 mg ) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after r and omization . The primary end point was the proportion of subjects with sUA levels < 6.0 mg/dl on day 28 . RESULTS Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level < 6.0 mg/dl at each visit ( P < 0.001 for each comparison ) . The targeted sUA level was attained on day 28 in 0 % of those taking placebo and in 56 % of those taking 40 mg , 76 % taking 80 mg , and 94 % taking 120 mg of febuxostat . The mean sUA reduction from baseline to day 28 was 2 % in the placebo group and 37 % in the 40-mg , 44 % in the 80-mg , and 59 % in the 120-mg febuxostat groups . Gout flares occurred with similar frequency in the placebo ( 37 % ) and 40-mg febuxostat ( 35 % ) groups and with increased frequency in the higher dosage febuxostat groups ( 43 % taking 80 mg ; 55 % taking 120 mg ) . During colchicine prophylaxis , gout flares occurred less frequently ( 8 - 13 % ) . Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups . CONCLUSION Treatment with febuxostat result ed in a significant reduction of sUA levels at all dosages . Febuxostat therapy was safe and well tolerated BACKGROUND AND OBJECTIVES Higher urinary uric acid excretion is a suspected risk factor for calcium oxalate stone formation . Febuxostat , a xanthine oxidoreductase inhibitor , is effective in lowering serum urate concentration and urinary uric acid excretion in healthy volunteers and people with gout . This work studied whether febuxostat , compared with allopurinol and placebo , would reduce 24-hour urinary uric acid excretion and prevent stone growth or new stone formation . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In this 6-month , double-blind , multicenter , r and omized controlled trial , hyperuricosuric participants with a recent history of calcium stones and one or more radio-opaque calcium stone ≥ 3 mm ( as seen by multidetector computed tomography ) received daily febuxostat at 80 mg , allopurinol at 300 mg , or placebo . The primary end point was percent change from baseline to month 6 in 24-hour urinary uric acid . Secondary end points included percent change from baseline to month 6 in size of index stone and change from baseline in the mean number of stones and 24-hour creatinine clearance . RESULTS Of 99 enrolled participants , 86 participants completed the study . Febuxostat led to significantly greater reduction in 24-hour urinary uric acid ( -58.6 % ) than either allopurinol ( -36.4 % ; P=0.003 ) or placebo ( -12.7 % ; P<0.001 ) . Percent change from baseline in the size of the largest calcium stone was not different with febuxostat compared with allopurinol or placebo . There was no change in stone size , stone number , or renal function . No new safety concerns were noted for either drug . CONCLUSIONS Febuxostat ( 80 mg ) lowered 24-hour urinary uric acid significantly more than allopurinol ( 300 mg ) in stone formers with higher urinary uric acid excretion after 6 months of treatment . There was no change in stone size or number over the 6-month period Background Febuxostat immediate release ( IR ) , a xanthine oxidase inhibitor , is indicated for the management of hyperuricemia in patients with gout by lowering urate levels . An extended release ( XR ) formulation of febuxostat was developed to provide equal or superior efficacy on urate lowering compared with the IR formulation and potentially lower the risk of treatment-initiated gout flares due to an altered pattern of drug exposure . The present study evaluated the efficacy and safety of febuxostat XR and IR formulations in patients with gout and moderate renal impairment ( estimated glomerular filtrate rate ≥ 30 and < 60 ml/min ) . Methods This was an exploratory , 3-month , phase II , multicenter , placebo-controlled , double-blind proof-of-concept study . Patients ( n = 189 ) were r and omized 1:1:1:1:1 to receive placebo or febuxostat IR 40 mg , XR 40 mg , IR 80 mg , or XR 80 mg once daily . Endpoints included : proportion of patients with serum uric acid ( sUA ) < 5.0 mg/dl at month 3 ( primary endpoint ) , proportion of patients with sUA < 6.0 mg/dl at month 3 , and proportion of patients with ≥ 1 gout flare requiring treatment over 3 months . Results At month 3 , all febuxostat treatment groups were associated with greater proportions of patients achieving sUA < 5.0 mg/dl ( p < 0.05 vs placebo ) . A greater proportion of patients receiving XR 40 mg achieved sUA < 5.0 mg/dl versus those receiving IR 40 mg ( p = 0.034 ) ; proportions were similar in the IR 80 mg and XR 80 mg groups . Higher proportions of febuxostat-treated patients achieved sUA < 6.0 mg/dl at month 3 ( p < 0.05 vs placebo ) and experienced ≥ 1 gout flare ( significant for all comparisons , except XR 40 mg ) . Incidences of treatment-related adverse events were low across all treatment groups ; the majority were mild or moderate with no apparent trends correlating with IR or XR doses . The most common treatment-emergent adverse event was hypertension . One death ( unrelated to the study drug ) was reported . Conclusions These exploratory data demonstrate that febuxostat ( XR and IR ) formulations were effective and well tolerated in patients with gout and moderate renal impairment . Trial registration Clinical Trials.gov , NCT02128490 Registered on 29 April 2014 OBJECTIVE To compare the urate-lowering efficacy and safety of febuxostat , allopurinol , and placebo in a large group of subjects with hyperuricemia and gout , including persons with impaired renal function . METHODS Subjects ( n = 1,072 ) with hyperuricemia ( serum urate level > or = 8.0 mg/dl ) and gout with normal or impaired ( serum creatinine level > 1.5 to < or = 2.0 mg/dl ) renal function were r and omized to receive once-daily febuxostat ( 80 mg , 120 mg , or 240 mg ) , allopurinol ( 300 or 100 mg , based on renal function ) , or placebo for 28 weeks . RESULTS Significantly ( P < or = 0.05 ) higher percentages of subjects treated with febuxostat 80 mg ( 48 % ) , 120 mg ( 65 % ) , and 240 mg ( 69 % ) attained the primary end point of last 3 monthly serum urate levels < 6.0 mg/dl compared with allopurinol ( 22 % ) and placebo ( 0 % ) . A significantly ( P < 0.05 ) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg ( 4 [ 44 % ] of 9 ) , 120 mg ( 5 [ 45 % ] of 11 ) , and 240 mg ( 3 [ 60 % ] of 5 ) achieved the primary end point compared with those treated with 100 mg of allopurinol ( 0 [ 0 % ] of 10 ) . Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups , although diarrhea and dizziness were more frequent in the febuxostat 240 mg group . The primary reasons for withdrawal were similar across groups except for gout flares , which were more frequent with febuxostat than with allopurinol . CONCLUSION At all doses studied , febuxostat more effectively lowered and maintained serum urate levels < 6.0 mg/dl than did allopurinol ( 300 or 100 mg ) or placebo in subjects with hyperuricemia and gout , including those with mild to moderately impaired renal function RATIONALE & OBJECTIVE Epidemiologic and clinical studies have suggested that urate-lowering therapy may slow the progression of chronic kidney disease ( CKD ) . However , definitive evidence is lacking . STUDY DESIGN R and omized , double-blind , placebo-controlled trial . SETTING & PARTICIPANTS 467 patients with stage 3 CKD and asymptomatic hyperuricemia at 55 medical institutions in Japan . INTERVENTION Participants were r and omly assigned in a 1:1 ratio to receive febuxostat or placebo for 108 weeks . OUTCOMES The primary end point was the slope ( in mL/min/1.73m2 per year ) of estimated glomerular filtration rate ( eGFR ) . Secondary end points included changes in eGFRs and serum uric acid levels at 24 , 48 , 72 , and 108 weeks of follow-up and the event of doubling of serum creatinine level or initiation of dialysis therapy . RESULTS Of 443 patients who were r and omly assigned , 219 and 222 assigned to febuxostat and placebo , respectively , were included in the analysis . There was no significant difference in mean eGFR slope between the febuxostat ( 0.23±5.26mL/min/1.73m2 per year ) and placebo ( -0.47±4.48mL/min/1.73m2 per year ) groups ( difference , 0.70 ; 95 % CI , -0.21 to 1.62 ; P=0.1 ) . Subgroup analysis demonstrated a significant benefit from febuxostat in patients without proteinuria ( P=0.005 ) and for whom serum creatinine concentration was lower than the median ( P=0.009 ) . The incidence of gouty arthritis was significantly lower ( P=0.007 ) in the febuxostat group ( 0.91 % ) than in the placebo group ( 5.86 % ) . Adverse events specific to febuxostat were not observed . LIMITATIONS GFR was estimated rather than measured , and patients with stages 4 and 5 CKD were excluded . CONCLUSIONS Compared to placebo , febuxostat did not mitigate the decline in kidney function among patients with stage 3 CKD and asymptomatic hyperuricemia . FUNDING Funded by Teijin Pharma Limited . TRIAL REGISTRATION Registered at the UMIN ( University Hospital Medical Information Network ) Clinical Trials Registry with study number UMIN000008343 PURPOSE The purpose of this study was to test a pharmacist-led intervention to improve gout treatment adherence and outcomes . METHODS We conducted a site-r and omized trial ( n=1463 patients ) comparing a 1-year , pharmacist-led intervention to usual care in patients with gout initiating allopurinol . The intervention was delivered primarily through automated telephone technology . Co- primary outcomes were the proportion of patients adherent ( proportion of days covered ≥0.8 ) and achieving a serum urate < 6.0 mg/dl at 1 year . Outcomes were reassessed at year 2 . RESULTS Patients who underwent intervention were more likely than patients of usual care to be adherent ( 50 % vs 37 % ; odds ratio [ OR ] 1.68 ; 95 % confidence interval [ CI ] 1.30 , 2.17 ) and reach serum urate goal ( 30 % vs 15 % ; OR 2.37 ; 95 % CI 1.83 , 3.05 ) . In the second year ( 1 year after the intervention ended ) , differences were attenuated , remaining significant for urate goal but not for adherence . The intervention was associated with a 6%-16 % lower gout flare rate during year 2 , but the differences did not reach statistical significance . CONCLUSIONS A pharmacist-led intervention incorporating automated telephone technology improved adherence and serum urate goal in patients with gout initiating allopurinol . Although this light-touch , low-tech intervention was efficacious , additional efforts are needed to enhance patient engagement in gout management and ultimately to improve outcomes BACKGROUND Allopurinol has been widely used for the treatment of hyperuricemia , however , it may be associated with various adverse effects . Febuxostat has been identified as a potentially safe and efficacious alternative . OBJECTIVES Febuxostat was administered to patients with hyperuricemia including gout in Japan to compare its efficacy and safety with those of allopurinol . METHODS The starting dose of febuxostat and allopurinol was 10 and 100 mg/d , respectively , and was increased to the fixed maintenance dose of 40 or 60 mg/d for febuxostat and 300 mg/d for allopurinol for 16 weeks . RESULTS : The percent change in the serum uric acid level at 16 weeks compared with the baseline serum uric acid level was -42.96 % ± 13.33 % and -52.47 % ± 9.79 % for the febuxostat 40- and 60-mg/d groups , respectively , and -36.55 % ± 18.59 % for the allopurinol group , indicating that the hypouricemic effects of febuxostat increased in a dose-dependent manner and equaled to or surpassed those of allopurinol ( P = 0.0239 , 2- sample t test ) . The percentage of patients with serum uric acid levels of 6.0 mg/dL or less at 16 weeks was 88.9 % and 100 % for the febuxostat 40- and 60-mg/d groups , respectively , and 68.8 % for the allopurinol group , showing higher achievements for the febuxostat groups compared with the allopurinol group . All adverse drug reactions were mild to moderate in severity , and there were no severe symptoms or reactions leading to drug discontinuation . CONCLUSIONS These results suggest that febuxostat is safe at doses of 40 and 60 mg/d and has equal or greater efficacy than 300 mg/d allopurinol |
13,330 | 28,427,509 | All three drugs significantly improved overall response and progression-free survival ; however , only bortezomib showed significantly greater overall survival compared with the control arm ( induction therapy , continuous therapy , or at any phase of treatment ) .
The main concerns on adverse events were thrombosis/embolism events , peripheral neuropathy , and second primary malignancies . | This overview summarizes evidence for the efficacy and safety of bortezomib , thalidomide , and lenalidomide in patients with multiple myeloma . | BACKGROUND AND OBJECTIVE To conduct a pilot study to compare the frequency of errors that accompany single vs. double data extraction , compare the estimate of treatment effect derived from these methods , and compare the time requirements for these methods . METHODS Review ers were r and omized to the role of data extractor or data verifier , and were blind to the study hypothesis . The frequency of errors associated with each method of data extraction was compared using the McNemar test . The data set for each method was used to calculate an efficacy estimate by each method , using st and ard meta-analytic techniques . The time requirement for each method was compared using a paired t-test . RESULTS Single data extraction result ed in more errors than double data extraction ( relative difference : 21.7 % , P = .019 ) . There was no substantial difference between methods in effect estimates for most outcomes . The average time spent for single data extraction was less than the average time for double data extraction ( relative difference : 36.1 % , P = .003 ) . CONCLUSION In the case that single data extraction is used in systematic review s , review ers and readers need to be mindful of the possibility for more errors and the potential impact these errors may have on effect estimates We investigated the impact of subcutaneous versus intravenous bortezomib in the MM5 trial of the German-Speaking Myeloma Multicenter Group which compared bortezomib , doxorubicin , and dexamethasone with bortezomib , cyclophosphamide , and dexamethasone induction therapy in newly diagnosed multiple myeloma . Based on data from relapsed myeloma , the route of administration for bortezomib was changed from intravenous to subcutaneous after 314 of 604 patients had been enrolled . We analyzed 598 patients who received at least one dose of trial medication . Adverse events were reported more frequently in patients treated with intravenous bortezomib ( intravenous=65 % ; subcutaneous=56 % , P=0.02 ) . Rates of grade 2 or more peripheral neuropathy were higher in patients treated with intravenous bortezomib during the third cycle ( intravenous=8 % ; subcutaneous=2 % , P=0.001 ) . Overall response rates were similar in patients treated intravenously or subcutaneously . The presence of International Staging System stage III disease , renal impairment or adverse cytogenetic abnormalities did not have a negative impact on overall response rates in either group . To our knowledge this is the largest study to present data comparing subcutaneous with intravenous bortezomib in newly diagnosed myeloma . We show better tolerance and similar overall response rates for subcutaneous compared to intravenous bortezomib . The clinical trial is registered at eudract.ema.europa.eu as n. 2010 - 019173 - 16 At the end of a long week in the office , you sink back into your chair , reflecting on some of the more memorable patients you cared for and counseled . Through gentle history taking , you discovered that urinary incontinence is the underlying cause of an elderly patient 's increasing social isolation . During a careful physical examination , you detected bruising on the torso of a woman with chronic headaches and began to explore the longst and ing abusive relationship between the woman and her alcoholic partner . You discontinued procainamide therapy in a 72-year-old man who had asymptomatic premature ventricular contractions after myocardial infa rct ion . To prevent bleeding from esophageal varices , you started -blocker therapy in a woman with long-st and ing cryptogenic cirrhosis and portal hypertension . In couples ' therapy , discussing the future quality of life of a middle-aged gay man with human immunodeficiency virus infection , you journeyed through emotionally intense dialogue about advance directives . You presented the risk factors for major and minor bleeding to a 39-year-old woman who was considering warfarin therapy because of recently diagnosed atrial fibrillation and valvular heart disease . You listened to , made diagnoses for , treated , advised , and comforted many patients . Yet there were some hiccoughs in your practice along the way . You stumbled while debating the pros and cons of breast cancer screening with a healthy 48-year-old woman who has been staying current with information on the Internet . You question ed the merits of a personalized walking program suggested to you by a motivated 66-year-old man with severe claudication . Explaining that you wanted to review the best current evidence on these issues , you resolved to address your uncertainties before these patients made their next office visits , in a week 's time . Sighing deeply , you acknowledge that you have little time to read . You subscribe to three journals , which you browse months after they arrive-either when your journal stack becomes precariously high or when your guilt is sufficiently motivational . You sometimes find the conclusions of individual articles conflicting or confusing . You know that some of the decisions and suggestions you made this week , specifically your decisions about stopping procainamide therapy and starting -blocker therapy and your advice about bleeding risks from anticoagulant therapy , were based on the best current research evidence [ 1 - 3 ] . On the other h and , your patients ' inquiries about breast cancer screening and exercise treatment for claudication highlight your need for a concise , current , rigorous synthesis of the best available evidence on each of these topics : in brief , a systematic review [ 4 , 5 ] . Incorporating Research Evidence into Clinical Decision Making The foregoing scenario is familiar to practitioners . In a typical week , we encounter patients with diverse problems ; exercise numerous clinical , interpersonal , and technical skills ; and make many decisions . The factors that affect these decisions and their outcomes are complex . For instance , each patient has unique sociodemographic characteristics , cultural circumstances , and personal preferences . Each physician has unique knowledge , experiences , and values . Moreover , practitioners and their patients make decisions within the context of a rapidly changing health care system that influences the availability , accessibility , and cost of diagnostic tests and therapies [ 6 ] . Timely , useful evidence from the biomedical literature should be an integral component of clinical decision making . If one treatment has been shown to be better than another , we need to know , so that we can recommend the treatment to the appropriate patients . The worldwide effort to develop new tests and treatments , and to determine their usefulness , has never been stronger , and our patients and their families expect us to be fonts of the knowledge that results from this effort [ 7 ] . Unfortunately , it is easy for current best research evidence to pass us by [ 8 ] . We may lack the time , motivation , and basic skills needed to find , critically appraise , and synthesize information , all of which we must do if we are to integrate the results of original studies into our practice . Fortunately , several potent methods are emerging that can greatly enhance our ability to interpret and apply research evidence ; foremost among them is the systematic review . This article begins a series in Annals that will examine systematic review s in detail and explore their many applications . Systematic review s represent the best chance that most practitioners will have to underst and and accurately apply the key signals arising from the robust and increasingly productive search for solutions to medical problems . A properly conducted systematic review faithfully summarizes the evidence from all relevant studies on the topic of interest , and it does so concisely and transparently . What Is a Systematic Review ? Systematic review s are scientific investigations in themselves , with pre-planned methods and an assembly of original studies as their subjects . They synthesize the results of multiple primary investigations by using strategies that limit bias and r and om error [ 9 , 10 ] . These strategies include a comprehensive search of all potentially relevant articles and the use of explicit , reproducible criteria in the selection of articles for review . Primary research design s and study characteristics are appraised , data are synthesized , and results are interpreted . When the results of primary studies are summarized but not statistically combined , the review may be called a qualitative systematic review . A quantitative systematic review , or meta- analysis , is a systematic review that uses statistical methods to combine the results of two or more studies . The term overview is sometimes used to denote a systematic review , whether quantitative or qualitative . Summaries of research that lack explicit descriptions of systematic methods are often called narrative review s. Review articles are one type of integrative publication ; practice guidelines , economic evaluations , and clinical decision analyses are others . These other types of integrative articles often incorporate the results of systematic review s. For example , practice guidelines are systematic ally developed statements intended to assist practitioners and patients with decisions about appropriate health care for specific clinical circumstances [ 11 ] . Evidence -based practice guidelines are based on systematic review s of the literature , appropriately adapted to local circumstances and values . Economic evaluations compare both the costs and the consequences of different courses of action ; the knowledge of consequences that are considered in these evaluations is often generated by systematic review s of primary studies . Decision analyses quantify both the likelihood and the valuation of the expected outcomes associated with competing alternatives . Differences between Systematic and Narrative Review s All review s , narrative and systematic alike , are retrospective , observational research studies and are therefore subject to systematic and r and om error . Accordingly , the quality of a review - and thus its worth-depends on the extent to which scientific review methods have been used to minimize error and bias . This is the key feature that distinguishes traditional narrative review s from systematic review s ( Table 1 ) . If a review is prepared according to the steps outlined in the right column of Table 1 , it is more likely to be systematic and to provide unbiased conclusions . If review methods approximate those found in the middle column of Table 1 , the article is more likely to be a narrative review , and the conclusions are less likely to be based on an unbiased summary of all relevant evidence . Table 1 . Differences between Narrative Review s and Systematic Review s Systematic review s are generated to answer specific , often narrow , clinical questions in depth . These questions can be formulated explicitly according to four variables : a specific population and setting ( such as elderly out patients ) , the condition of interest ( for example , hypertension ) , an exposure to a test or treatment ( such as pharmacologic management ) , and one or more specific outcomes ( such as cardiovascular and cerebrovascular events and mortality ) [ 12 ] . Thus , an example of a well-formulated , clinical ly relevant question is , Does pharmacologic treatment of hypertension in the elderly prevent strokes and myocardial infa rct ions or delay death ? If the question that is driving the review is not clear from the title , abstract , or introduction , or if no methods section is included , the paper is more likely to be a narrative review than a systematic review [ 13 ] . Most narrative review articles deal with a broad range of issues related to a given topic rather than addressing a particular issue in depth [ 9 ] . For example , a narrative review on diabetes ( such as that which might be found in a textbook chapter ) might include sections on the physiology and pathophysiology of carbohydrate , lipid , and protein metabolism ; the epidemiology of and prognosis associated with diabetes ; diagnostic and screening approaches ; and preventive , therapeutic , rehabilitative , and palliative interventions . Thus , narrative review s may be most useful for obtaining a broad perspective on a topic ; they are less often useful in furnishing quantitative answers to specific clinical questions . Narrative review s are appropriate for describing the history or development of a problem and its management . Narrative review s may better describe cutting-edge developments if research is scant or preliminary or if studies are very limited by flawed design or execution [ 13 ] . They may be particularly useful for discussing data in light of underlying theory and context . Narrative review s can draw analogies and can conceptually integrate two independent fields of research , such as BACKGROUND This open-label , r and omized , phase 3 study compared melphalan at a dose of 200 mg per square meter of body-surface area plus autologous stem-cell transplantation with melphalan-prednisone-lenalidomide ( MPR ) and compared lenalidomide maintenance therapy with no maintenance therapy in patients with newly diagnosed multiple myeloma . METHODS We r and omly assigned 273 patients 65 years of age or younger to high-dose melphalan plus stem-cell transplantation or MPR consolidation therapy after induction , and 251 patients to lenalidomide maintenance therapy or no maintenance therapy . The primary end point was progression-free survival . RESULTS The median follow-up period was 51.2 months . Both progression-free and overall survival were significantly longer with high-dose melphalan plus stem-cell transplantation than with MPR ( median progression-free survival , 43.0 months vs. 22.4 months ; hazard ratio for progression or death , 0.44 ; 95 % confidence interval [ CI ] , 0.32 to 0.61 ; P<0.001 ; and 4-year overall survival , 81.6 % vs. 65.3 % ; hazard ratio for death , 0.55 ; 95 % CI , 0.32 to 0.93 ; P=0.02 ) . Median progression-free survival was significantly longer with lenalidomide maintenance than with no maintenance ( 41.9 months vs. 21.6 months ; hazard ratio for progression or death , 0.47 ; 95 % CI , 0.33 to 0.65 ; P<0.001 ) , but 3-year overall survival was not significantly prolonged ( 88.0 % vs. 79.2 % ; hazard ratio for death , 0.64 ; 95 % CI , 0.36 to 1.15 ; P=0.14 ) . Grade 3 or 4 neutropenia was significantly more frequent with high-dose melphalan than with MPR ( 94.3 % vs. 51.5 % ) , as were gastrointestinal adverse events ( 18.4 % vs. 0 % ) and infections ( 16.3 % vs. 0.8 % ) ; neutropenia and dermatologic toxic effects were more frequent with lenalidomide maintenance than with no maintenance ( 23.3 % vs. 0 % and 4.3 % vs. 0 % , respectively ) . CONCLUSIONS Consolidation therapy with high-dose melphalan plus stem-cell transplantation , as compared with MPR , significantly prolonged progression-free and overall survival among patients with multiple myeloma who were 65 years of age or younger . Lenalidomide maintenance , as compared with no maintenance , significantly prolonged progression-free survival . ( Funded by Celgene ; Clinical Trials.gov number , NCT00551928 . ) PURPOSE We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma ( MM ) . PATIENTS AND METHODS In all , 827 eligible patients with newly diagnosed symptomatic MM were r and omly assigned to receive induction therapy with vincristine , doxorubicin , and dexamethasone ( VAD ) or bortezomib , doxorubicin , and dexamethasone ( PAD ) followed by high-dose melphalan and autologous stem-cell transplantation . Maintenance consisted of thalidomide 50 mg ( VAD ) once per day or bortezomib 1.3 mg/m(2 ) ( PAD ) once every 2 weeks for 2 years . The primary analysis was progression-free survival ( PFS ) adjusted for International Staging System ( ISS ) stage . RESULTS Complete response ( CR ) , including near CR , was superior after PAD induction ( 15 % v 31 % ; P < .001 ) and bortezomib maintenance ( 34 % v 49 % ; P < .001 ) . After a median follow-up of 41 months , PFS was superior in the PAD arm ( median of 28 months v 35 months ; hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.62 to 0.90 ; P = .002 ) . In multivariate analysis , overall survival ( OS ) was better in the PAD arm ( HR , 0.77 ; 95 % CI , 0.60 to 1.00 ; P = .049 ) . In high-risk patients presenting with increased creatinine more than 2 mg/dL , bortezomib significantly improved PFS from a median of 13 months to 30 months ( HR , 0.45 ; 95 % CI , 0.26 to 0.78 ; P = .004 ) and OS from a median of 21 months to 54 months ( HR , 0.33 ; 95 % CI , 0.16 to 0.65 ; P < .001 ) . A benefit was also observed in patients with deletion 17p13 ( median PFS , 12 v 22 months ; HR , 0.47 ; 95 % CI , 0.26 to 0.86 ; P = .01 ; median OS , 24 months v not reached at 54 months ; HR , 0.36 ; 95 % CI , 0.18 to 0.74 ; P = .003 ) . CONCLUSION Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS |
13,331 | 28,152,545 | Conclusions : Blood-based miRNAs distinguish patients with CRC from healthy controls with high sensitivity and specificity comparable to other common and invasive currently used screening methods for CRC . | Background : Colorectal cancer ( CRC ) is common and associated with significant mortality .
Current screening methods for CRC lack patient compliance .
microRNAs ( miRNAs ) , identified in body fluids , are negative regulators of gene expression and are dysregulated in many cancers , including CRC .
This paper summarises studies identifying blood-based miRNAs dysregulated in CRC compared with healthy controls in an attempt to evaluate their use as a screening tool for the diagnosis of CRC . | Context Several immunochemical fecal occult blood tests ( FOBTs ) that use different antibodies against human blood components are available . Contribution This study compared characteristics of 6 qualitative immunochemical FOBTs and 1 guaiac-based FOBT to identify adenomas among adults who attended screening colonoscopy . The FOBTs had widely varying performance characteristics . Sensitivity and specificity for detecting advanced adenomas ranged from 25 % to 72 % and 70 % to 97 % , respectively , for the immunochemical tests and were 9 % and 96 % , respectively , for the guaiac test . Caution One-day stool sample s were used , and stool was frozen before testing . Implication Qualitative immunochemical FOBTs have varying performance characteristics for detecting precancerous colorectal lesions . The Editors Colorectal cancer ( CRC ) is the third most common cancer in the world ( 1 ) , with about 1 million new cases and more than 500000 deaths per year . Because most cases of CRC are sporadic and develop from removable precancerous lesions ( adenomas ) and curable early- stage cancer ( 2 ) , screening for CRC has high potential for reducing morbidity and mortality . R and omized , controlled trials have demonstrated reduced mortality with guaiac-based fecal occult blood testing ( FOBT ) followed by colonoscopy or sigmoidoscopy if the FOBT result is positive ( 3 ) . However , guaiac-based FOBT , which detects the pseudoperoxidase activity of heme or hemoglobin , has important limitations . It is not specific for human hemoglobin , and false-positive and false-negative results can result from certain compounds or medications in foods ( for example , red meat or vitamin C ) ( 4 ) that should be avoided during the days before testing . Another important limitation is the low diagnostic performance for precursors to CRC . An advantage of guaiac-based FOBT is the simple analysis , which can easily be done at the physician 's office , even though reliable interpretation of test results requires training ( 5 , 6 ) . Immunochemical FOBTs that use specific antibodies against human blood components overcome the problem of diet or medication restriction . Unlike quantitative immunochemical FOBTs , qualitative immunochemical FOBTs that mostly use immunochromatographic technology also allow simple , office-based analysis . However , there are differences among qualitative immunochemical FOBTs . For example , the antibodies used and the different detection limits may influence the diagnostic performance , especially with respect to detection of precursor lesions . We aim ed to determine and compare performance characteristics of different qualitative immunochemical FOBTs for the detection of colorectal adenomas in a large sample of women and men undergoing screening colonoscopy . Methods Study Design and Sample The analyses were part of the BliTz study ( Begleitende Evaluierung innovativer Testverfahren zur Darmkrebsfrherkennung ) , an ongoing screening study conducted in cooperation with 20 gastroenterology practice s in southwestern Germany since January 2006 that aims to comparatively evaluate new tests for early detection of CRC . The study includes participants undergoing screening colonoscopya procedure that the German health care system has offered since October 2002 to average-risk persons 55 years or older . In Germany , preliminary consultation for any type of cancer screening is mostly done by general practitioners . For screening colonoscopy , patients are referred to the gastroenterologist only when the decision to have colonoscopy is made . All participants had a preliminary consultation with a gastroenterologist to receive detailed information and advice about screening colonoscopy . They were informed about and invited to participate in the study at that time . After we received written informed consent , we asked patients scheduled for screening colonoscopy to provide a stool sample before bowel preparation . Physicians who did colonoscopy and histologic examination were blinded to FOBT results . After colonoscopy , we collected reports on colonoscopic and histologic findings and extracted information in a st and ardized manner while blinded to the results of stool testing . We did not query patients about adverse events of testing ( such as psychological distress ) . The ethics committee of the University of Heidelberg , Heidelberg , Germany , approved the study . We included patients who provided stool sample s for qualitative immunochemical FOBTs until 13 December 2007 . The Figure shows the numbers of all potentially eligible patients . Figure . Study flow diagram . FOBadv = FOB advanced ( ulti med , Ahrensburg , Germany ) ; FOBplus = Bionexia FOBplus ( DIMA , Gttingen , Germany ) ; Hb/Hp C = Bionexia Hb/Hp Complex ( DIMA ) ; HO = HemOccult ( Beckman Coulter , Krefeld , Germany ) ; immoCare = immoCARE-C ( CAREdiagnostica , Voerde , Germany ) ; PreventID CC = PreventID CC ( Preventis , Bensheim , Germany ) ; QuickVue = QuickVue iFOB ( Quidel , San Diego , California ) . * The exclusion of 44 patients overall was due to missing or noninterpretable test cards . Of 1785 patients undergoing screening colonoscopy who agreed to participate , 111 were excluded because of visible rectal bleeding or preceding positive FOBT result . We excluded 13 patients because of inflammatory bowel disease . These patients usually receive close colonoscopic surveillance and would not be regarded as the target population for primary FOBT screening . We excluded 117 patients because they had undergone colonoscopy in the past 5 years and thus would not be eligible for primary FOBT screening ( if the previous colonoscopy result was positive , they are recommended for colonoscopic surveillance ; if the result was negative , they are at very low risk for colorectal neoplasia ) . We further excluded participants whose stool sample s were collected after colonoscopy only ( and thus violated the study protocol [ n= 65 ] ) , those with inadequate bowel preparation before colonoscopy ( n= 79 ) , and those with incomplete colonoscopy ( that is , the cecum was not reached , [ n= 22 ] ) . We excluded patients who received a histologically confirmed diagnosis of CRC ( this subgroup comprised only 11 participants by the end of 2007 and would not allow meaningfully precise performance estimates for this end point ) . Sensitivity with respect to CRC will be analyzed separately after continued recruitment of a much larger number of screening participants . We excluded 10 participants with nondefined polyps ( no histologic reports were available ) because we could not definitively determine the presence or absence of advanced adenomas in this group . Finally , we excluded participants with pseudopolyps ( n= 38 ) because these patients probably have had ulcerative colitis or undocumented inflammatory bowel disease . Stool Sample Collection Participants undergoing screening colonoscopy typically present at the gastroenterology practice for preliminary consultation about 1 week before colonoscopy . At that time , eligible patients received a study package that contained 1 test card for guaiac-based FOBT ( HemOccult , Beckman Coulter , Krefeld , Germany ) , a small container ( 60 mL ) for stool collection , a collection tissue for avoiding contact of the stool with toilet water , and detailed instructions for stool collection . Stool sample s were collected at home with no specific recommendations for diet or medicine restrictions . Patients received detailed instructions for sampling : Collect 1 bowel movement by using the collection tissue ; apply stool with a spatula ( provided in the study package ) on 2 windows of 1 HemOccult test card and store the test card at room temperature ; and fill at least half of the small container with stool by using plastic spoons ( provided in the study package ) , and store a plastic bag with the container in the freezer or , if not possible , in the refrigerator . Although the amount of stool provided varied widely , sufficient stool was available to adequately perform the different tests in all cases . On the day of colonoscopy , patients provided the HemOccult test card and the stool-filled container at the gastroenterology practice . The latter was stored at 20C , then shipped on dry ice to a central laboratory and stored at 20C until analysis . We documented the date s of stool sampling , arrival at the central laboratory , and performance of the immunochemical FOBTs . Laboratory Analyses Physician assistants who were blinded to the results of immunochemical testing analyzed HemOccult test cards at the gastroenterology practice on receipt according to the manufacturer 's instructions . They did analyses of HemOccult without rehydration , and test results were classified as positive , negative , or not interpretable ( for example , owing to incorrect sampling ) . We thawed the stool-filled containers at a median interval of 4 days on arrival at the central laboratory to do qualitative immunochemical FOBTs . Overall , we did 5 tests to determine fecal hemoglobin levels ( Bionexia FOBplus , DIMA , Gttingen , Germany ; PreventID CC , Preventis , Bensheim , Germany ; immoCARE-C , CAREdiagnostica , Voerde , Germany ; FOB advanced , ulti med , Ahrensburg , Germany ; and QuickVue iFOB , Quidel , San Diego , California ) and 1 test to determine both fecal hemoglobin and hemoglobinhaptoglobin levels ( Bionexia Hb/Hp Complex , DIMA ) . All tests are based on immunochromatographic technology . The lower detection limits indicated by the manufacturers were 10 ng/mL ( PreventID CC ) , 25 ng/mL ( Bionexia Hb/Hp Complex ) , 40 ng/mL ( Bionexia FOBplus and FOB advanced ) , and 50 ng/mL ( immoCARE-C and QuickVue iFOB ) . We did all analyses according to the manufacturers ' instructions and under st and ardized conditions . One trained investigator who was blinded to colonoscopy and HemOccult results classified all test results as positive or negative . Although classification was sometimes difficult for borderline results , we did not use an additional category for such results because the distinction between these and positive or negative results would be similarly difficult and Introduction The Bowel Cancer Screening Programme in Engl and began operating in 2006 with the aim of full roll out across Engl and by December 2009 . Subjects aged 60–69 are being invited to complete three guaiac faecal occult blood tests ( 6 windows ) every 2 years . The programme aims to reduce mortality from colorectal cancer by 16 % in those invited for screening . Methods All subjects eligible for screening in the National Health Service in Engl and are included on one data base , which is populated from National Health Service registration data covering about 98 % of the population of Engl and . This analysis is only of subjects invited to participate in the first ( prevalent ) round of screening . Results By October 2008 almost 2.1 million had been invited to participate , with tests being returned by 49.6 % of men and 54.4 % of women invited . Uptake ranged between 55–60 % across the four provincial hubs which administer the programme but was lower in the London hub ( 40 % ) . Of the 1.08 million returning tests 2.5 % of men and 1.5 % of women had an abnormal test . 17 518 ( 10 608 M , 6910 F ) underwent investigation , with 98 % having a colonoscopy as their first investigation . Cancer ( n=1772 ) and higher risk adenomas ( n=6543 ) were found in 11.6 % and 43 % of men and 7.8 % and 29 % of women investigated , respectively . 71 % of cancers were ‘ early ’ ( 10 % polyp cancer , 32 % Dukes A , 30 % Dukes B ) and 77 % were left-sided ( 29 % rectal , 45 % sigmoid ) with only 14 % being right-sided compared with expected figures of 67 % and 24 % for left and right side from UK cancer registration . Conclusion In this first round of screening in Engl and uptake and fecal occult blood test positivity was in line with that from the pilot and the original European trials . Although there was the expected improvement in cancer stage at diagnosis , the proportion with left-sided cancers was higher than expected BACKGROUND An accurate , noninvasive test could improve the effectiveness of colorectal-cancer screening . METHODS We compared a noninvasive , multitarget stool DNA test with a fecal immunochemical test ( FIT ) in persons at average risk for colorectal cancer . The DNA test includes quantitative molecular assays for KRAS mutations , aberrant NDRG4 and BMP3 methylation , and β-actin , plus a hemoglobin immunoassay . Results were generated with the use of a logistic-regression algorithm , with values of 183 or more considered to be positive . FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive . Tests were processed independently of colonoscopic findings . RESULTS Of the 9989 participants who could be evaluated , 65 ( 0.7 % ) had colorectal cancer and 757 ( 7.6 % ) had advanced precancerous lesions ( advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension ) on colonoscopy . The sensitivity for detecting colorectal cancer was 92.3 % with DNA testing and 73.8 % with FIT ( P=0.002 ) . The sensitivity for detecting advanced precancerous lesions was 42.4 % with DNA testing and 23.8 % with FIT ( P<0.001 ) . The rate of detection of polyps with high- grade dysplasia was 69.2 % with DNA testing and 46.2 % with FIT ( P=0.004 ) ; the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4 % and 5.1 % , respectively ( P<0.001 ) . Specificities with DNA testing and FIT were 86.6 % and 94.9 % , respectively , among participants with nonadvanced or negative findings ( P<0.001 ) and 89.8 % and 96.4 % , respectively , among those with negative results on colonoscopy ( P<0.001 ) . The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy , 166 with DNA testing , and 208 with FIT . CONCLUSIONS In asymptomatic persons at average risk for colorectal cancer , multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results . ( Funded by Exact Sciences ; Clinical Trials.gov number , NCT01397747 . ) Much clinical and epidemiologic evidence suggests that a timely colonoscopy and removal of colonic polyps may reduce the risk for cancer in the colon and rectum [ 1 - 5 ] . Nevertheless , it has remained unproved that endoscopic procedures other than rigid proctosigmoidoscopy can truly protect against the development of cancer . Besides financial constraints , the lack of unequivocal evidence in favor of endoscopy is the most important reason why colorectal endoscopy with flexible instruments has not been used more widely for the prevention of cancer . Colonoscopy is associated with an overall complication rate of 1 % to 2 % , a perforation rate of 0.1 % , and a death rate of 0.05 % [ 6 ] . Therefore , before a large segment of the population is subjected to endoscopic procedures on a regular basis , it is important to show that these procedures actually do reduce the risk for cancer in the large intestine . We hypothesized that colonoscopy , flexible sigmoidoscopy , and polypectomy protect against the future development of colorectal cancer . We tested this hypothesis among U.S. military veterans , using a casecontrol study design . The study compared the frequency with which flexible endoscopies were done during the period preceding the first diagnosis of cancer among patients with colorectal cancer and among controls without cancer . Methods Data Source The Patient Treatment File consists of many individual data files . The data files are managed by the Department of Veterans Affairs ' Central Automation Center in Austin , Texas . The main files contain records of all inpatient treatments from all Veterans Affairs hospitals throughout the United States . Files are available for each fiscal year since 1970 . Although the contents of the files and their structure have changed over the past two decades , information on essential demographic and health characteristics are available in similar form from all main files . Since 1984 , other files have been added to cover treatment outside Veterans Affairs facilities and in nursing homes . Each patient record contains one primary and up to nine secondary discharge diagnoses . From 1970 to 1980 , the diagnoses were coded according to the 8th revision of the Clinical Modification of the International Classification of Diseases ( ICD-8-CM ) ; since 1981 , the 9th revision of the ICD has been used [ 7 ] . Individual patients can be identified by their social security numbers . Diagnostic procedures and surgical procedures were initially included in the main files . Separate surgical and medical procedure files were initiated in 1984 and 1988 , respectively . Procedures are also coded according to ICD-9-CM , the coding scheme that makes it possible to record in both the medical and surgical procedure files up to five procedures per day of hospitalization . Since 1990 , outpatient procedures have been included in the Patient Treatment File . All outpatient procedures are listed by codes taken from the Current Procedural Terminology ( CPT-code ) [ 8 ] . Identification of Case- Patients and Controls Information on all veterans who were discharged with a diagnosis of colon cancer ( ICD codes 153.0 to 153.9 , except 153.5 ) or rectal cancer ( ICD codes 154.0 to 154.1 ) between 1988 and 1993 was extracted from the Patient Treatment File . Their social security numbers were then used to search all of their previous discharge records since 1970 , and patients with a diagnosis of colon or rectal cancer before 1988 were excluded from the case population . The remaining patients were assumed to represent incident cases with a first diagnosis of colorectal cancer between 1988 and 1993 . Patients who had had a previous diagnosis of Crohn disease ( ICD code 555 ) , ulcerative colitis ( ICD code 556 ) , or familial polyposis ( ICD code 759.6 ) between 1970 and 1993 were also excluded from the case population . Ulcerative colitis and Crohn disease are both associated with an increased risk for colon cancer [ 9 , 10 ] . Patients with inflammatory bowel disease have frequent endoscopies to assess colonic involvement , diagnose complications , and screen for dysplasia . Procedures in these patient population s are determined by considerations other than those in the general population . For each case-patient , one control was selected from among the patients who were discharged during the same fiscal year that the case-patient was first diagnosed with colorectal cancer . Each control was matched to his or her case-patient based on age , sex , and race . Controls who had had any previous discharge diagnosis of colorectal cancer between 1970 and 1993 were excluded from the complete annual files of 1988 through 1993 . Similarly , controls who had had any previous diagnosis of Crohn disease , ulcerative colitis , or familial polyposis were excluded . After the exclusions , the remaining patient records of each year from 1988 to 1993 were r and omized . For each case-patient , the r and omized annual file was scanned sequentially until a control of the same age , race , and sex as the case-patient was identified . Ten-year age categories were used for matchingfor example , less than 25 years , 25 to 34 years , 35 to 44 years , and so on . Extraction of Procedures and Previous Diagnoses Detailed procedural codes based on the ICD-9-CM have been available in the Patient Treatment File since 1981 . Therefore , for case- patients and controls recruited during the last 6 years , we were able to search the procedure files dating from 7 to 13 years before recruitment for a history of previous procedures of the large intestine . The procedure files from 1981 until the date on which cancer was first diagnosed ( or corresponding time of hospitalization in controls ) were search ed for all of the procedural codes shown in Table 1 . The procedure that was used to establish the first diagnosis of cancer was not considered in the analysis . Table 1 . Definition of 9th Revision of the Clinical Modification of the International Classification of Diseases and Current Procedural Terminology Codes In a second search , we followed case- patients and controls backward through the annual files ( all main files since 1970 ) to assess the overall duration of health coverage by the Veterans Affairs system and to determine the number of all hospital discharges before the first diagnosis of colorectal cancer . These two variables were created to adjust for the extent of medical care that an individual veteran received through the Veterans Affairs system . In a third search , we followed case- patients and controls backward through the annual Patient Treatment Files of the 5 years preceding the first diagnosis of colorectal cancer to record all previous discharge diagnoses . Indicator variables were created for the following primary or secondary discharge diagnoses : colorectal polyps ( ICD codes 211.3 , 211.4 , and 569.0 ) , carcinoma in situ ( codes 230.3 and 230.4 ) , any form of anemia ( codes 280 to 285 ) , hemorrhoids and any form of gastrointestinal hemorrhage ( codes 455 , 569.3 , 578.1 , and 578.9 ) , signs and symptoms that suggested intestinal obstruction ( codes 560.0 , 560.3 , 560.9 , 564.0 , and 569.2 ) , diverticulosis and diverticulitis of the colon ( codes 562.10 to 562.13 ) , various types of nonspecific gastrointestinal complaints ( codes 558.9 , 569.4 , 569.8 , 569.9 , 789.0 , and 789.9 ) , abnormal weight loss ( code 783.2 ) , and abdominal or pelvic swelling or mass ( code 789.3 ) . These diagnoses may often be associated with a diagnosis of colorectal cancer , or they may precede its definitive diagnosis ; it is highly unlikely that cancer would be misdiagnosed , for example , as hemorrhoids or bleeding peptic ulcer , for more than 5 years . Arthritis and related disorders ( codes 714 to 716 and 720 to 721 ) were common conditions in the Patient Treatment File that were likely to be treated with nonsteroidal anti-inflammatory drugs . Such drugs have been shown to reduce the risk for death from colorectal cancer [ 11 , 12 ] . Currently , no separate ICD code identifies patients with hereditary nonpolyposis colon cancer ( the Lynch syndrome ) . Statistical Analysis Except for the duration of coverage by the Veterans Affairs system and the number of hospital discharges , all variables were coded as dichotomous variables : Code 1 was used to indicate the attribute of interest , and code 0 was used to indicate its absence . The development of colon or rectal cancer served as the outcome variable . Any type of flexible endoscopy done before the first diagnosis of colorectal cancer served as the main predictor variable . Different types of discharge diagnoses that preceded the diagnosis of colorectal cancer ( for example , polyps or anemia ) represented the other predictor variables . The duration of coverage ( in years ) by the Veterans Affairs system and the number of hospital discharges were transformed into categorical predictor variables according to their quartile ranges . For each pair of predictor variables , the Kendall correlation coefficient or the Spearman correlation coefficient was calculated . The proportional hazards regression procedure of the Statistical Analysis System was used for all types of univariate and multivariate conditional logistic regression analyses [ 13 ] . We did univariate conditional logistic regression analyses in which we considered each predictor variable separately . We also did multivariate conditional logistic regression analyses in which we considered all predictor variables simultaneously [ 14 ] . Besides main-effect models , the possibility of interaction terms among the variables were assessed . We did separate analyses to identify the efficacy of specific procedures . During their follow-up in the Veterans Affairs system , many of the case- patients and controls had the same procedure more than once and different colorectal procedures in varying temporal sequences . Also , the different codes of the ICD-9-CM do not represent completely distinct procedures , whereas some identical procedures , such as colonoscopy or flexible sigmoidoscopy , may be assigned multiple procedural In patients with colorectal cancer , circulating micro RNA-21 ( miR-21 ) is overexpressed and may act as a potential diagnostic and prognostic biomarker . In the present study , serum miR-21 level was determined in patients with colorectal cancer and control subjects in an attempt to explore its potential clinical diagnostic and prognostic value . Serum levels of miR–21 were measured in 40 patients with colorectal adenocarcinoma and 40 control subjects using a quantitative reverse-transcriptase polymerase chain reaction ( qRT-PCR ) assay . Serum miR-21 levels were compared in the colorectal cancer patients and control subjects . Furthermore , the association between serum miR-21 level and the clinical stages of tumors was also examined in the patients . Serum miR-21 level was significantly elevated in colorectal adenocarcinoma patients relative to control subjects ( P = 0.0001 ) , and it was revealed as a potential diagnostic biomarker for differentiating the patients from control subjects . Increased levels of serum miR-21 were associated with clinical stages of tumors in the patients ( P = 0.01 ) . These results indicated that serum miR-21 levels could serve as a reliable diagnostic and prognostic biomarker for colorectal adenocarcinoma We carried out this study to present proof-of-principal application , showing that by using a global microarray expression analysis , followed by quantitative stem-loop reverse transcriptase in conjunction with TaqMan ® polymerase chain reaction ( PCR ) analysis of micro(mi)RNA genes , on limited number of plasma and tissue sample s obtained from 20 individuals ( five healthy , five TNM stage 0 - 1 colon cancer , five stage 2 and five stage 3 ) , we were able to quantitatively monitor miRNA changes at the various TNM stages of colon cancer progression , particularly at the early , pre-malignant adenoma stage ( e.g. polyps ≥ 1 cm with high grade dysplasia ) . The expression of some of the tested miRNAs showed less variability in tissue than in plasma . Nevertheless , our limited preliminary data on the plasma by itself show that plasma is well-suited for screening , and that the quantitative changes in the expression of a few cell-free circulatory mature miRNA molecules in plasma , that are associated with colon cancer progression , would provide for more sensitive and specific markers than those tests currently available on the market . In addition , analysis of miRNA molecules offers a quantitative and cost-effective non-invasive diagnostic approach for screening , than currently employed methods in a prevalent cancer that can be cured if it is detected at the early TNM stages , and that becomes deadly if not diagnosed before metastasis . Thus , a larger prospect i ve and properly r and omized clinical study using plasma derived from many control individuals and at various stages of colon cancer ( TNM stages 0-IV ) from patients , in order to corroborate the initial results , is now urgently needed in order to allow for a statistically valid analysis , st and ardizing test conditions which will provide a means for determining the true sensitivity and specificity of a miRNA-screening approach . This approach , when combined with bioinformatics analysis to correlate miRNA seed data with mRNA target data , would allow for a mechanistic underst and ing of how miRNAs regulate mRNA gene expression , and would offer a better comprehensive diagnostic screening test for early-detection of colon cancer non-invasively |
13,332 | 28,151,791 | Study findings demonstrated educational interventions can improve support for FPDR , as well as intent to offer it as an option . | Background : Family presence during resuscitation ( FPDR ) remains controversial among nurses .
Individual studies have shown educational interventions can improve support for FPDR ; however , a systematic review of the literature has not been performed to appraise and synthesize the evidence .
Objectives : The aim of this systematic review was to appraise and synthesize studies conducted to test the effect of education on nurses ’ and providers ’ support for FPDR . | Purpose To evaluate the psychological consequences among family members given the option to be present during the CPR of a relative , compared with those not routinely offered the option . Methods Prospect i ve , cluster-r and omized , controlled trial involving 15 prehospital emergency medical services units in France , comparing systematic offer for a relative to witness CPR with the traditional practice among 570 family members . Main outcome measure was 1-year assessment included proportion suffering post-traumatic stress disorder ( PTSD ) , anxiety and depression symptoms , and /or complicated grief . Results Among the 570 family members [ intention to treat ( ITT ) population ] , 408 ( 72 % ) were evaluated at 1 year . In the ITT population ( N = 570 ) , family members had PTSD-related symptoms significantly more frequently in the control group than in the intervention group [ adjusted odds ratio , 1.8 ; 95 % confidence interval ( CI ) 1.1–3.0 ; P = 0.02 ] as did family members to whom physicians did not propose witnessing CPR [ adjusted odds ratio , 1.7 ; 95 % CI 1.1–2.6 ; P = 0.02 ] . In the observed cases population ( N = 408 ) , the proportion of family members experiencing a major depressive episode was significantly higher in the control group ( 31 vs. 23 % ; P = 0.02 ) and among family members to whom physicians did not propose the opportunity to witness CPR ( 31 vs. 24 % ; P = 0.03 ) . The presence of complicated grief was significantly greater in the control group ( 36 vs. 21 % ; P = 0.005 ) and among family members to whom physicians did not propose the opportunity to witness resuscitation ( 37 vs. 23 % ; P = 0.003 ) . Conclusions At 1 year after the event , psychological benefits persist for those family members offered the possibility to witness the CPR of a relative in cardiac arrest BACKGROUND Family presence during resuscitation ( FPDR ) is supported by patients and their family members . Nurses , however , including critical care nurses who frequently implement resuscitative care , have mixed views . OBJECTIVES To determine the impact of online learning on critical care nurses ' perception of and self-confidence with FPDR . METHODS A 2-group , r and om assignment , pretest and posttest quasi-experimental study was conducted with critical care nurses recruited nationally . An online learning module on FPDR was developed and administered to the intervention group . Perceptions and self-confidence for FPDR were measured by using the Family Presence Risk- Benefit Scale ( FPR-BS ) and the Family Presence Self-confidence Scale ( FPS-CS ) . Two-factor , mixed-model factorial analysis of variance was used to compare mean scores . RESULTS A total of 74 critical care nurses participated in the study . Mean FPR-BS and FPS-CS scores were significantly greater in the intervention group than in the control group . For the intervention group , mean scores on the FPR-BS increased from 3.63 to 4.07 ( P < .001 ) and on the FPS-CS increased from 4.24 to 4.57 ( P < .001 ) , signifying improved perception and self-confidence . Scores did not change significantly in the control group : mean FPR-BS score increased from 3.82 to 3.88 ( P = .23 ) and the mean FPS-CS score of 4.40 did not change ( P > .99 ) . CONCLUSIONS Online learning is a feasible and effective method for educating large numbers of critical care nurses about FPDR . Online learning can improve perceptions and self-confidence related to FPDR , which may promote more widespread adoption of FPDR into practice BACKGROUND Increasingly , patients ' families are remaining with them during cardiopulmonary resuscitation and invasive procedures , but this practice remains controversial and little is known about the practice s of critical care and emergency nurses related to family presence . OBJECTIVE To identify the policies , preferences , and practice s of critical care and emergency nurses for having patients ' families present during resuscitation and invasive procedures . METHODS A 30-item survey was mailed to a r and om sample of 1500 members of the American Association of Critical-Care Nurses and 1500 members of the Emergency Nurses Association . RESULTS Among the 984 respondents , 5 % worked on units with written policies allowing family presence during both resuscitation and invasive procedures and 45 % and 51 % , respectively , worked on units that allowed it without written policies during resuscitation or during invasive procedures . Some respondents preferred written policies allowing family presence ( 37 % for resuscitation , 35 % for invasive procedures ) , whereas others preferred unwritten policies allowing it ( 39 % for resuscitation , 41 % for invasive procedures ) , Many respondents had taken family members to the bedside ( 36 % for resuscitation , 44 % for invasive procedure ) or would do so in the future ( 21 % for resuscitation , 18 % for invasive procedures ) , and family members often asked to be present ( 31 % for resuscitation , 61 % for invasive procedures ) . CONCLUSIONS Nearly all respondents have no written policies for family presence yet most have done ( or would do ) it , prefer it be allowed , and are confronted with requests from family members to be present . Written policies or guidelines for family presence during resuscitation and invasive procedures are recommended BACKGROUND The effect of family presence during cardiopulmonary resuscitation ( CPR ) on the family members themselves and the medical team remains controversial . METHODS We enrolled 570 relatives of patients who were in cardiac arrest and were given CPR by 15 prehospital emergency medical service units . The units were r and omly assigned either to systematic ally offer the family member the opportunity to observe CPR ( intervention group ) or to follow st and ard practice regarding family presence ( control group ) . The primary end point was the proportion of relatives with post-traumatic stress disorder (PTSD)-related symptoms on day 90 . Secondary end points included the presence of anxiety and depression symptoms and the effect of family presence on medical efforts at resuscitation , the well-being of the health care team , and the occurrence of medicolegal cl aims . RESULTS In the intervention group , 211 of 266 relatives ( 79 % ) witnessed CPR , as compared with 131 of 304 relatives ( 43 % ) in the control group . In the intention-to-treat analysis , the frequency of PTSD-related symptoms was significantly higher in the control group than in the intervention group ( adjusted odds ratio , 1.7 ; 95 % confidence interval [ CI ] , 1.2 to 2.5 ; P=0.004 ) and among family members who did not witness CPR than among those who did ( adjusted odds ratio , 1.6 ; 95 % CI , 1.1 to 2.5 ; P=0.02 ) . Relatives who did not witness CPR had symptoms of anxiety and depression more frequently than those who did witness CPR . Family-witnessed CPR did not affect resuscitation characteristics , patient survival , or the level of emotional stress in the medical team and did not result in medicolegal cl aims . CONCLUSIONS Family presence during CPR was associated with positive results on psychological variables and did not interfere with medical efforts , increase stress in the health care team , or result in medicolegal conflicts . ( Funded by Programme Hospitalier de Recherche Clinique 2008 of the French Ministry of Health ; Clinical Trials.gov number , NCT01009606 . ) OBJECTIVE . When a child presents to a trauma center with a serious injury , family members are often excluded from the initial trauma team evaluation . The objective of this study was to evaluate the outcomes of a structured program of family presence during pediatric trauma team activations by measuring ( 1 ) the need for termination of family presence , ( 2 ) times to completion of key parts of the trauma evaluation , and ( 3 ) the opinions of staff surveyed immediately after conclusion of family presence . METHODS . This was a cross-sectional study that combined prospect ively obtained data and surveys from trauma team evaluations in which family presence occurred , with retrospective chart review of all trauma activations during an 18-month study period . The study was conducted at a level 1 pediatric trauma center with a preestablished family presence program that assigns a staff member to screen family members for family presence , provide support , and record events . Times to completion of key components of the trauma evaluation were calculated and compared for cases with and without family presence . Cross-sectional surveys were performed immediately after each trauma team evaluation . RESULTS . A total of 197 family members participated in family presence . There were no cases of interference with medical care by family members . Seven family members were asked to leave the trauma area by staff after initiation of family presence for various reasons . Times to completion of key components of the trauma evaluation did not differ significantly between enrolled patients with family presence and those without family presence . Surveys were completed for 136 cases , and the majority of providers reported that family presence either had no effect on or improved medical decision-making ( 97 % ) , institution of patient care ( 94 % ) , communication among providers ( 92 % ) , and communication with family members ( 98 % ) . CONCLUSIONS . This prospect i ve study suggests that there is an overall low prevalence of negative outcomes associated with family presence during pediatric trauma team evaluation after implementation of a structured family presence program . Excluding family members as a routine because of provider concerns about negative impact on clinical care does not seem to be indicated |
13,333 | 24,580,409 | Overall , the results of comparisons between monotherapy and combined therapy in individual trials were differentiated , and some combinations were not more effective than monotherapy ( bortezomib plub bevacizumab vs. bortezomib and thalidomide plus INFα vs. thalidomide ) which emphasizes the role of individualized therapy in relapsed/refractory MM especially in the elderly or patients with significant comorbidities .
Conclusions The results of this meta- analysis showed that combined therapy is superior to monotherapy only in some end points and it is less tolerated in patients with relapsed/refractory MM .
Thus , the overall superiority of complex therapy to monotherapy depends on the combination of the targeted agents | Abstract Objectives The aim of this systematic review was to evaluate the efficacy and safety of targeted agents used as monotherapy or combined therapy in patients with relapsed/refractory multiple myeloma ( MM ) . | This subgroup analysis of the phase III APEX ( Assessment of Proteasome Inhibition for Extending Remissions ) trial examined whether prior exposure to specific therapies affected the relative efficacy of bortezomib versus dexamethasone in relapsed/refractory myeloma . Time to progression and overall survival were superior with bortezomib in all subgroups , with no evidence of interaction between any prior therapies and assignment to study therapy . Patients with prior thalidomide exposure had worse outcomes overall , but neither prior thalidomide nor prior autologous stem cell transplantation affected the relative efficacy of bortezomib versus dexamethasone . These results confirm the superiority of bortezomib over dexamethasone , regardless of prior exposure to specific therapies ( clinical trials.gov : NCT00048230 ) Recently , cereblon ( CRBN ) expression was found to be essential for the activity of thalidomide and lenalidomide . In the present study , we investigated whether the clinical efficacy of thalidomide in multiple myeloma is associated with CRBN expression in myeloma cells . Patients with newly diagnosed multiple myeloma were included in the HOVON-65/GMMG-HD4 trial , in which postintensification treatment in 1 arm consisted of daily thalidomide ( 50 mg ) for 2 years . Gene-expression profiling , determined at the start of the trial , was available for 96 patients who started thalidomide maintenance . In this patient set , increase of CRBN gene expression was significantly associated with longerprogression-free survival ( P = .005 ) . In contrast , no association between CRBN expression and survival was observed in the arm with bortezomib maintenance . We conclude that CRBN expression may be associated with the clinical efficacy of thalidomide . This trial has been registered at the Nederl and s Trial Register ( www.trialregister.nl ) as NTR213 ; at the European Union Drug Regulating Authorities Clinical Trials ( EudraCT ) as 2004 - 000944 - 26 ; and at the International St and ard R and omized Controlled Trial Number ( IS RCT N ) as 64455289 Immunoglobulin production by myeloma plasma cells depends on the unfolded protein response for protein production and folding . Recent studies have highlighted the importance of IRE1alpha and X box binding protein 1 ( XBP1 ) , key members of this pathway , in normal B-plasma cell development . We have determined the gene expression levels of IRE1alpha , XBP1 , XBP1UNSPLICED ( XBP1u ) , and XBP1SPLICED ( XBP1s ) in a series of patients with myeloma and correlated findings with clinical outcome . We show that IRE1alpha and XBP1 are highly expressed and that patients with low XBP1s/u ratios have a significantly better overall survival . XBP1s is an independent prognostic marker and can be used with beta2 microglobulin and t(4;14 ) to identify a group of patients with a poor outcome . Furthermore , we show the beneficial therapeutic effects of thalidomide in patients with low XBP1s/u ratios . This study highlights the importance of XBP1 in myeloma and its significance as an independent prognostic marker and as a predictor of thalidomide response OBJECTIVE To study the clinical course of patients with multiple myeloma ( MM ) that relapses after initial therapy . PATIENTS AND METHODS Patients with MM , seen at the Mayo Clinic in Rochester , Minn , between January 1 , 1985 , and December 31 , 1998 , were identified from a prospect ively maintained data base . Our study population consisted of 578 patients with newly diagnosed MM who were followed up and monitored throughout their clinical course at our institution . RESULTS The median age of the 578 patients with MM was 65 years ( range , 26 - 92 years ) ; 228 patients ( 39 % ) were women . The median follow-up of 71 surviving patients was 55 months ( range , 0 - 202 months ) . The overall survival ( OS ) for the 578 patients at 1 , 2 , and 5 years was 72 % , 55 % , and 22 % , respectively ; the median OS from initial therapy was 28.4 months . The median OS of 355 patients who experienced relapse after initial treatment was 17.1 months from initiation of the second therapy , and 84 % died within 5 years . The duration of response decreased consistently with each successive regimen . Patients with a high plasma cell labeling index ( > or = 1.0 % ) , low platelet count ( < 150 x 10(9)/L ) , high creatinine level ( > or = 2.0 mg/dL ) , and low albumin level ( < 3.0 g/dL ) had a poorer prognosis . CONCLUSIONS Our study revealed decreasing response duration with increasing number of salvage regimens , probably reflecting acquired drug resistance and an increasing proliferative rate of the myeloma cells . Patients who experienced relapse after initial treatment and received salvage therapy had a median survival of nearly 1.5 years . This must be remembered when making treatment decisions for these patients and must be factored in when assessing the efficacy of new therapies The potential synergistic anti-myeloma effect for thalidomide combining with interferon alpha was not yet clear clinical ly . From March 2001 to January 2004 , a total of 28 heavily pretreated multiple myleoma ( MM ) patients were enrolled in this open-labeled , r and omized Phase II study . Patients with refractory MM were r and omized to receive either thalidomide alone ( 200 mg/day up to the maximum dose 800 mg/day , arm B ) or the combination of thalidomide and interferon alpha ( 3 MIU/m2 subcutaneous injection 3 times weekly , arm A ) . The objective of this study was to compare the safety and efficacy of thalidomide alone to combined regimen . The patients ' characteristics were similar between the 2 arms . However , the average treatment duration was significantly longer in the arm B than the arm A ( 236 days versus 101 days , p = 0.029 ) . Serum levels of paraprotein decline ≥ 25 percent were obtained in 6 of 12 patients ( 50.0 percent ) treated with arm B and 3 of the 16 patients ( 18.8 percent ) treated with arm A. The estimated time to event was 7.9 months ( 95 percent confidence interval [ 95%CI ] , 0.5–15.4 ) for arm B and 1.5 months ( 95%CI , 0.0–3.4 ) for arm A ( log-rank test , p = 0.0193 ) . The major adverse events in both arms consisted of neutropenia , anemia , thrombocytopenia , constipation , somnolence , and skin rash . Our study showed that thalidomide alone was effective and tolerated in patients with relapsed or refractory MM . The thalidomide combined with interferon alpha result ed in a lower frequency of paraprotein response , shorter treatment- duration and 25 percent of patients ' refusing rate . It may be concluded that the combined regimen is not well tolerated in our patients and needed to be further evaluated in the future PURPOSE This phase III international study compared the efficacy and safety of a combination of pegylated liposomal doxorubicin ( PLD ) plus bortezomib with bortezomib monotherapy in patients with relapsed or refractory multiple myeloma . PATIENTS AND METHODS Six hundred forty-six patients were r and omly assigned to receive either intravenous bortezomib 1.3 mg/m(2 ) on days 1 , 4 , 8 , and 11 of an every 21-days cycle , or the same bortezomib regimen with PLD 30 mg/m(2 ) on day 4 . RESULTS Median time to progression was increased from 6.5 months for bortezomib to 9.3 months with the PLD + bortezomib combination ( P = .000004 ; hazard ratio , 1.82 [ monotherapy v combination therapy ] ; 95 % CI , 1.41 to 2.35 ) . The 15-month survival rate for PLD + bortezomib was 76 % compared with 65 % for bortezomib alone ( P = .03 ) . The complete plus partial response rate was 41 % for bortezomib and 44 % for PLD + bortezomib , a difference that was not statistically significant . Median duration of response was increased from 7.0 to 10.2 months ( P = .0008 ) with PLD + bortezomib . Grade 3/4 adverse events were more frequent in the combination group ( 80 % v 64 % ) , with safety profiles consistent with the known toxicities of the two agents . An increased incidence in the combination group was seen of grade 3/4 neutropenia , thrombocytopenia , asthenia , fatigue , diarrhea , and h and -foot syndrome . CONCLUSION PLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed or refractory multiple myeloma . The combination therapy is associated with a higher incidence of grade 3/4 myelosuppression , constitutional symptoms , and GI and dermatologic toxicities |
13,334 | 29,035,966 | The qualitative findings showed social acceptability of rifampicin .
Conclusions Chemoprophylaxis with one dose of rifampicin is found to be effective in preventing contacts of leprosy patients from contracting the disease .
Also , there is indication that this strategy is socially accepted | Background Individuals in contact with patients who have leprosy have an increased risk of disease exposure , which reinforces the need for chemoprophylactic measures , such as the use of rifampicin .
Objectives The objective of the review was to synthesize the best available evidence regarding the effectiveness of rifampicin chemoprophylaxis for contacts with patients with leprosy , and to synthesize the best available evidence on the experience and acceptability of rifampicin chemoprophylaxis as reported by the contacts and health professionals involved in the treatment of leprosy or Hansen 's disease . | Background Despite almost 30 years of effective chemotherapy with MDT , the global new case detection rate of leprosy has remained quite constant over the past years . New tools and method ologies are necessary to interrupt the transmission of M. leprae . Single-dose rifampicin ( SDR ) has been shown to prevent 57 % of incident cases of leprosy in the first two years , when given to contacts of newly diagnosed cases . Immunization of contacts with BCG has been less well documented , but appears to have a preventive effect lasting up to 9 years . However , one major disadvantage is the occurrence of excess cases within the first year after immunization . The objective of this study is to examine the effect of chemoprophylaxis with SDR and immunoprophylaxis with BCG on the clinical outcome as well as on host immune responses and gene expression profiles in contacts of newly diagnosed leprosy patients . We hypothesize that the effects of both interventions may be complementary , causing the combined preventive outcome to be significant and long-lasting . Methods / design Through a cluster r and omized controlled trial we compare immunization with BCG alone with BCG plus SDR in contacts of new leprosy cases . Contact groups of around 15 persons will be established for each of the 1300 leprosy patients included in the trial , result ing in approximately 20,000 contacts in total . BCG will be administered to the intervention group followed by SDR , 2 months later . The control group will receive BCG only . In total 10,000 contacts will be included in both intervention arms over a 2-year period . Follow-up will take place one year as well as two years after intake . The primary outcome is the occurrence of clinical leprosy within two years . Simultaneously with vaccination and SDR , blood sample s for in vitro analyses will be obtained from 300 contacts participating in the trial to determine the effect of these chemo- and immunoprophylactic interventions on immune and genetic host parameters . Discussion Combined chemoprophylaxis and immunoprophylaxis is potentially a very powerful and innovative tool aim ed at contacts of leprosy patients that could reduce the transmission of M. leprae markedly . The trial intends to substantiate this potential preventive effect . Evaluation of immune and genetic biomarker profiles will allow identification of pathogenic versus ( BCG-induced ) protective host biomarkers and could lead to effective prophylactic interventions for leprosy using optimized tools for identification of individuals who are most at risk of developing disease . Trial registration Netherl and s Trial Register : Background With 249,007 new leprosy patients detected globally in 2008 , it remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae . We assessed the economic benefits of single dose rifampicin ( SDR ) for contacts as chemoprophylactic intervention in the control of leprosy . Methods We conducted a single centre , double blind , cluster r and omised , placebo controlled trial in northwest Bangladesh between 2002 and 2007 , including 21,711 close contacts of 1,037 patients with newly diagnosed leprosy . We gave a single dose of rifampicin or placebo to close contacts , with follow-up for four years . The main outcome measure was the development of clinical leprosy . We assessed the cost effectiveness by calculating the incremental cost effectiveness ratio ( ICER ) between the st and ard multidrug therapy ( MDT ) program with the additional chemoprophylaxis intervention versus the st and ard MDT program only . The ICER was expressed in US dollars per prevented leprosy case . Findings Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy . In total , $ 6,009 incremental cost was invested and 38 incremental leprosy cases were prevented , result ing in an ICER of $ 158 per one additional prevented leprosy case . It was the most cost-effective in neighbours of neighbours and social contacts ( ICER $ 214 ) , slightly less cost-effective in next door neighbours ( ICER $ 497 ) and least cost-effective among household contacts ( ICER $ 856 ) . Conclusion Chemoprophylaxis with single dose rifampicin given to contacts of newly diagnosed leprosy patients is a cost-effective intervention strategy . Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world Chemoprophylaxis was carried out on high risk group of extended contacts of new leprosy cases in Nyaungdon Township , Ayeyarwaddy Division , Myanmar and serological response was followed up for two years . In September 2003 , blood sample s were collected from 829 contacts after getting informed consent and sera were tested for immunoglobulin M antibodies using NTP-BSA ELISA test . These 300 seropositives were r and omized to treated and non-treated groups . In each group 102 each were enrolled in adults and 48 each in children . A single dose of ROM ( rifampicin , ofloxacin and minocycline ) and RMP ( rifampicin ) by body weight was administered to treated group of above 15 years and those below 15 years respectively . The vitamins were administered to non-treated group . The blood sample s of all contacts were collected again in September 2004 and September 2005 and ELISA was carried out on paired sample s on one plate . The mean optical density ( OD ) titers before vs after chemoprophylaxis were 0.24 vs 0.10 and 0.20 vs 0.09 in treated and non-treated group respectively in adults and 0.25 vs 0.11 and 0.22 vs 0.11 respectively in children after one year . These were 0.24 vs 0.17 and 0.20 vs 0.19 respectively in adults and 0.25 vs 0.19 and 0.22 vs 0.20 respectively in children after two years . The difference of mean antibody titers before and after chemoprophylaxis in treated group was significantly reduced compared to non-treated group in adults but was not significant in children . The findings show that there is a significant role of chemoprophylaxis on serological response in the form of decreasing antibody titer among the adult group of extended contacts ABSTRACT A total of 100 untreated new leprosy patients were recruited prospect ively and examined for the presence of phenolic glycolipid I ( PGL-I ) antigen in their serum specimens by dot enzyme-linked immunosorbent assay ( ELISA ) using rabbit anti-PGL-I antiserum . The presence of circulating PGL-I antigen was closely related to the bacterial indices ( BI ) of the patients . The PGL-I antigen was detectable in 27 ( 93.1 % ) of 29 patients with a BI of 4.0 or above and in 15 ( 68.2 % ) of 22 patients with a BI of 3.0 to 3.9 . However , none of the 37 patients with a BI of less than 1.9 had detectable PGL-I antigen by the methods used in this study . The level of PGL-I in serum declined rapidly by about 90 % 1 month after the start of multidrug therapy . This study showed clearly that anti-PGL-I IgM antibodies and circulating PGL-I antigen levels reflect the bacterial loads in untreated leprosy patients . The serological parameters based on the PGL-I antigen may therefore be useful in the assessment of leprosy patients at the time of diagnosis and possibly in monitoring patients following chemotherapy BACKGROUND : After the introduction of the multidrug therapy , there was a decline in the coefficients of prevalence and detection of new cases of leprosy . However , the records of drug resistance and relapses are threatening factors in leprosy control . Hence , new alternative schemes and monitoring of adverse effects to avoid treatment ab and onment are important considerations . OBJECTIVE : Describe the side effects of a multidrug regimen containing minocycline , ofloxacin , and clofazimine in multibacillary leprosy patients . METHODS : We conducted a prospect i ve , descriptive , and observational study with multibacillary patients , including cases of intolerance to st and ard MDT and relapses . The study was carried out at Fundação Alfredo da Matta ( Alfredo da Matta Foundation ) , in Manaus , Amazonas , from April 2010 to January 2012 . The patients received alternative therapy , which consisted of daily self-administered doses of 100 mg of minocycline , 400 mg of ofloxacin , and 50 mg of clofazimine and a supervised monthly dose of 300 mg of clofazimine for six months , followed by eighteen months of daily doses of ofloxacin 400 mg , clofazimine 50 mg , and a supervised monthly dose of clofazimine 300 mg . Results : Twenty-one cases were included . Mild and transitory side effects occurred in 33.3 % of patients . Of the total episodes , 45.9 % were attributed to ofloxacin and they included abdominal pain , nausea , vomiting , headache , and insomnia ; 21.6 % were due to clofazimine , with 100 % of patients presenting skin pigmentation . The mean time for the development of adverse effects after beginning the therapy was 15.2 days . CONCLUSION : All patients tolerated the drugs well , and compliance was satisfactory , with no serious events . Unlike other st and ard MDT studies had shown , no treatment was stopped due to side effects . Nevertheless , patient follow-up and studies with bigger sample s are necessary to guarantee the efficacy and safety of the alternative regimen as a second-line scheme in multi-drug therapy OBJECTIVES The COLEP trial in Bangladesh showed a 57 % reduction in leprosy incidence among contacts of newly diagnosed patients in the first 2 years after chemoprophylaxis with single dose rifampicin ( SDR ) . We assessed the impact of this intervention after 6 years and identified characteristics of the leprosy index patients predicting the effectiveness of this intervention . DESIGN The cohort of 1037 patients and their 28 092 contacts that participated in the r and omised placebo controlled field trial with single dose rifampicin was followed for 6 years . The leprosy status of contacts was established at 2 , 4 and 6 years after the intervention . We assessed the association between characteristics of the index leprosy patients and the development of clinical leprosy among their contacts using logistic regression . RESULTS The protective effect of SDR was seen only in the first 2 years , with no additional effect after 4 and 6 years . However , the total impact of the intervention was still statistically significant ( P = 0.025 ) after 6 years and no excess cases were observed in the SDR arm at a later stage . The intervention prevented leprosy in contacts that actually received SDR , but did not offer protection to members of the same contact group who did not take chemoprophylaxis . The intervention was most effective in contact groups of female index patients , an enhanced effect was also observed in contact groups of patients belonging to a cluster of two or more leprosy patients at intake as well . CONCLUSION These easy to recognise patient characteristics indicate a possible enhanced risk of transmission of Mycobacterium leprae to contacts in the vicinity of patients and are useful for deciding about preventive measures , such as early detection or chemoprophylaxis Review question / objective What is the effectiveness of rifampicin chemoprophylaxis in preventing leprosy in contacts of patients with leprosy ? What are the experiences and acceptability with the use of rifampin chemoprophylaxis in the prevention of disease from contacts with patients who have leprosy , in patients with leprosy following treatment and in family and health care professionals ? Background Leprosy is globally acknowledged as a millenary and stigmatizing disease and a condition with attributed consequences such as physical deformities and disabilities . From a multi‐causal perspective , there is evidence that leprosy occurs more often in men than in women , is distributed across all age groups and occurs mainly among people living in unfavorable socioeconomic circumstances , who are also the most affected by public segregation policies . 1–4 In 2013 , a total of 215,656 new cases of leprosy were detected worldwide . Regions with the highest number of cases are Southeast Asia ( 72.1 % ) the Americas ( 15.3 % ) . Whereas the countries with the highest prevalence were India ( 58.8 % ) and Brazil ( 14.4 % ) . 5 Hansen 's bacillus ( Mycobacterium leprae ) is considered a microorganism of high infectivity and low pathogenicity and virulence . It is transmitted via nasal oropharyngeal secretions and breaks in the skin of infected patients . Therefore , the main form of transmissibility is inter‐human and the greatest risk of contagion is cohabitation with these patients .1–3 It is estimated that most individuals have a natural resistance to Mycobacterium leprae ( M. leprae ) and that some are prone to developing a severe form of the disease , the multibacillary forms . Studies on exogenous reinfection and endogenous reactivation in chronic diseases , such as tuberculosis and leprosy , show that susceptible individuals become infected by the bacillus through contact with multibacillary patients .1–3,6,7 The surveillance of leprosy contacts is a priority action for control of the disease . Children are exposed to the highest risk of becoming infected by being in contact with a family member or anyone close to them who has the disease . Having a current case of leprosy in the family is associated with a 2.9 times greater risk of a healthy family member becoming infected , and that risk increases when the family has a history of the disease.3,6–9 Bakker et al.7 reported that household contacts of multibacillary patients presented a four times greater risk of becoming infected with the disease compared to non‐contacts . For Ximenes et al.,10 the condition of being a contact of individuals with leprosy represented twice the risk of retreatment due to recurrence in relation to the control group . Therefore , alternative or complementary strategies , such as chemoprophylaxis , must be sought as a form of prevention of the disease . Chemoprophylaxis is defined as the administration of drugs capable of preventing an infection or keeping infected individuals from falling ill . In leprosy , the preventive strategy consists of employing medications to prevent the infection by M. leprae in people with a higher risk of exposure to the disease , i.e. those in contact with the patient . Therefore , chemoprophylaxis plays an important role in the protection of individuals vulnerable to the disease . However , studies regarding its effective utilization are inconclusive.11–15 The first investigations of the utilization of prophylaxis in leprosy contacts in the 1960s and 1970s included dapsone and acedapsone and later in the 1980s and 1990s rifampicin . However , interest in this type of research decreased after 1982 when the World Health Organization ( WHO ) introduced multidrugtherapy ( MDT ) for the treatment of leprosy.16–19 Multidrugtherapy is a combination of three drugs , dapsone , rifampicin and clofazimine , to prevent the selection of resistant strains . As of 1997 , the WHO adopted the alternative rifampicin , ofloxacin and minocycline ( ROM ) regimen , recommended for paucibacillary cases with a single lesion without the involvement of nerve stems.19,20 Adoption of these measures was expected to result in a reduction in the incidence of leprosy as a public health problem ; however , the observed result was not significant in terms of reducing the incidence of newly detected cases . Furthermore , considering the evidence of resistance to monotherapy with dapsone , there was a rise in interest in intervention studies , particularly using rifampicin in household and community contacts.1,2,5,11,12 However , some studies have indicated little or no protection against the disease through the use of rifampicin . While Moet et al.14 and Feenstra et al.21 observed protection of two years in household contacts with a single dose of rifampicin , Bakker et al.13 showed no difference between the experimental group and the control group with two doses of rifampicin , 600 mg for adults and 300 mg for children . Another study of people at high risk of contracting the disease that used a single dose of ROM and rifampicin showed that there was a reduction of type immunoglobulin M antibodies among adults in both interventions .22 Meta‐analyis of dapsone , acepdapsone and rifampicin compared with placebo showed that chemoprophlasys is an effective measure to prevent leprosy . 12 Currently , strategies using a combination of the Bacillus Calmette‐Guérin ( BCG ) and chemoprophylaxis with rifampicin in leprosy contacts appear to be complementary measures for protection against the disease . This strategy showed a protective effect of 80%.23 Studies of acceptability and experience of chemoprophylaxis to control leprosy with individuals and health professionals are scarce . In a qualitative study , Feenstra et al.24 concluded that chemoprophylaxis for household contacts of leprosy patients is an effective and socially acceptable addition to the current leprosy control program . A preliminary search of the Joanna Briggs Data base of Systematic Review s and Implementation Reports , the Cochrane Library , CINAHL , PubMed and PROSPERO has revealed that there are no systematic review s ( either published or underway ) on this topic . In this context , it is un question ably useful to integrate the scientific evidence from studies that evaluated the effectiveness of the rifampicin chemoprophylaxis in leprosy contacts , the experiences and acceptability of contacts of leprosy patients , patients with leprosy following treatment and family and health care professionals about this strategy for the prevention of the disease . This knowledge can support the measures adopted to reduce endemicity , which strengthens the quality of the care delivered to the population most vulnerable to becoming ill . Operational definitions : Leprosy patients : individuals who present one or more of the following cardinal signs and who require multidrugtherapy : lesion(s ) and /or skin areas with altered sensitivity ; affected peripheral nerve(s ) , with or without thickening , associated with sensitive and /or motor and /or autonomic changes ; and a positive skin smear bacilloscopy . Cases are classified as paucibacillary or multibacillary based on the number of lesions and /or bacilloscopy when available ; cases are considered paucibacillary when patients present five or fewer skin lesions and /or negative bacilloscopy , corresponding to the undetermined and tuberculoid clinical forms ; multibacillary cases are when patients present more than five skin lesions and positive bacilloscopy , corresponding to the dimorphous and Virchow 's forms of the disease.1–4,25 Leprosy case : term used in epidemiology to identify individuals with leprosy for purpose s of monitoring the health conditions of a population .2,26 Chemoprophylaxis : the administration of drugs capable of preventing the infection or keeping infected individuals from falling ill.11,12 Contacts : those who cohabit or have cohabited with leprosy patients .12,14,21 Index case : the first case of the disease among several similar cases that are epidemiologically related with the secondary case ( index case contacts).21 Recurrence : the reappearance of signs and symptoms of the disease after recuperation from a first occurrence of the disease , usually within five years.6,10,27 Treatment ab and onment : interrupting treatment for over twelve months.6,10 Therapeutic regimen established for confirmed leprosy cases : for paucibacillary ( PB ) cases , six monthly supervised doses of rifampicin ( RFM ) 450‐600 mg , and daily self‐administered doses of dapsone ( DDS ) 50‐100 mg , for up to nine months ; for multibacillary ( MB ) cases , twelve supervised monthly doses of rifampicin ( RFM ) 450‐600 mg and clofazimine ( CFZ ) 100‐300 mg , associated to daily self‐administered doses of dapsone ( DDS ) 50‐100 mg and CFZ 50 mg , for up to 18 months . An alternative treatment for MB is 24 doses within 36 months.1,2,19 Rifampicin chemoprophylaxis regimens : single‐dose rifampicin of 25 mg/kg or monthly dose for six months ; double‐dose rifampicin or combined regimens of ROM ‐ rifampicin ( 600 mg ) , ofloxacin ( 400 mg ) and minocycline ( 100 mg ) , according to body weight.13–15,21 Efficacy/effectiveness : proof ( or not ) of successful intervention . Efficacy is the result of an intervention performed under ideal , well‐controlled conditions , such as in r and omized clinical trials . Effectiveness refers to the result of an intervention applied under usual medical practice conditions.28 Operational classification : paucibacillary and multibacillary.1,2 , 25 Comorbidities : morbidities possibly associated with leprosy , such as tuberculosis , diabetes , HIV/AIDS , and others.1,2 BCG vaccination scar : result ing from the intradermal injection of Bacillus Calmette‐Guérin ( BCG ) vaccine on the deltoid , used to prevent tuberculosis and leprosy.23,29 Adverse events : negative effects result ing from the actions of drugs.1,2 Incidence rate : measures the frequency or likelihood of new cases of diseases occurring in a population .30 Estimated effect of an intervention : shows the theoretical distribution of possible effects BCG vaccination and rifampicin chemoprophylaxis are both strategies for leprosy prevention . While the combined effect is unknown , the combination may give the desired push to halt leprosy transmission . Secondary analysis was done on results from a single centre , double blind , cluster r and omized , and placebo-controlled trial . Individually , BCG ( given at infancy ) and rifampicin showed to protect against leprosy ( 57 % [ 95 % CI : 24 - 75 % ] and 58 % [ 95 % CI : 30 - 74 % ] , respectively ) . The combined strategies showed a protective effect of 80 % ( 95 % CI : 50 - 92 % ) . This is the first time that the additive effect of BCG and rifampicin are shown ; the combined strategies can possibly lower leprosy incidence BACKGROUND Close contacts of patients with leprosy have a higher risk of developing leprosy . Several risk factors have been identified , including genetic relationship and physical distance . Their independent contributions to the risk of developing leprosy , however , have never been sufficiently quantified . METHODS Logistic-regression analysis was performed on intake data from a prospect i ve cohort study of 1037 patients newly diagnosed as having leprosy and their 21,870 contacts . RESULTS Higher age showed an increased risk , with a bimodal distribution . Contacts of patients with paucibacillary ( PB ) leprosy with 2 - 5 lesions ( PB2 - 5 ) and those with multibacillary ( MB ) leprosy had a higher risk than did contacts of patients with single-lesion PB leprosy . The core household group had a higher risk than other contacts living under the same roof and next-door neighbors , who again had a higher risk than neighbors of neighbors . A close genetic relationship indicated an increased risk when blood-related children , parents , and siblings were pooled together . CONCLUSIONS Age of the contact , the disease classification of the index patient , and physical and genetic distance were independently associated with the risk of a contact acquiring leprosy . Contact surveys in leprosy should be not only focused on household contacts but also extended to neighbors and consanguineous relatives , especially when the patient has PB2 - 5 or MB leprosy |
13,335 | 11,405,964 | Discomfort during vaginal examination and other adverse effects ( bleeding , irregular contractions ) were more frequently reported by women allocated to sweeping .
REVIEW ER 'S CONCLUSIONS Routine use of sweeping of membranes from 38 weeks of pregnancy onwards does not seem to produce clinical ly important benefits . | BACKGROUND This is one of a series of review s of methods of cervical ripening and labour induction using st and ardised methodology .
Sweeping of the membranes , also commonly named stripping of the membranes , is a relatively simple technique usually performed without admission to hospital .
During vaginal examination , the clinician 's finger is introduced into the cervical os .
Then , the inferior pole of the membranes is detached from the lower uterine segment by a circular movement of the examining finger .
This intervention has the potential to initiate labour by increasing local production of prostagl and ins and , thus , reduce pregnancy duration or pre-empt formal induction of labour with either oxytocin , prostagl and ins or amniotomy .
OBJECTIVES To determine the effects of membrane sweeping for third trimester induction of labour . | OBJECTIVE To compare intracervical prostagl and in E2 gel and membrane sweeping for cervical ripening . STUDY DESIGN Fifty patients were r and omized to either intracervical prostagl and in E2 or membrane sweeping . A Bishop score was assigned by a blinded examiner prior to and 24 hours following the procedure . RESULTS The Bishop scores assigned 24 hours after prostagl and in instillation and membrane sweeping were not significantly different ( 3.4 , SE 0.42 , vs. 3.3 , SE 0.37 , respectively ; P > .05 ) . The proportions of women entering active labor or delivering within 24 hours were similar in the prostagl and in and membrane groups ( 21 % and 19 % , respectively ; P > .05 ) . CONCLUSION When both intracervical prostagl and in insertion and membrane sweeping are feasible , their salutary effects are comparable Objective To determine whether cervical membrane sweeping ( stripping ) during induction of labor is beneficial . Methods We compared outcomes of labor after induction in pregnant women at term in a r and omized trial . Women were assigned to having their membranes swept or not during induction . Outcome measures included duration of labor , maximum dose of oxytocin used , induction-labor interval , and mode of delivery . Results We recruited 130 nulliparas ( 64 sweep , 66 non-sweep ) and 118 multiparas ( 60 sweep , 58 nonsweep ) . Among nulliparas who received intravaginal prostagl and in ( PG ) E2 and oxytocin , those who had simultaneous sweeping had significantly shorter mean ( ± st and ard error of mean ) induction-labor interval ( 13.6 ± 1.4 versus 17.3 ± 1.2 hours , P = .048 ) , lower mean maximum dose of oxytocin ( 6.8 ± 0.8 versus 10.35 ± 1.1 mU/minute , P = .01 ) , and increased normal delivery rates ( vaginal delivery 83.3 % versus 58.2 % , P = .01 ) . Sweeping also had a favorable effect on nulliparas who received oxytocin alone ( mean induction-labor interval 5.8 ± 3.1 versus 11.2 ± 3.6 hours , P = .04 ; mean maximum dose 8.8 ± 1.3 versus 16.3 ± 1.9 mU/min , P = .01 ) . Those differences were limited to women with unfavorable cervices . There were no differences in any outcome measures in multiparous women . Conclusion Sweeping of the membranes during induction of labor had a beneficial effect on labor and delivery , which appeared to be limited to nulliparas with unfavorable cervices who needed cervical priming with PGE2 OBJECTIVES To assess the efficacy of stripping of membranes in initiation of labor and to study its effect on maternal and perinatal morbidity . METHOD One-hundred primigravidae with certain gestational date s were r and omized at 38 weeks gestation to either receive stripping of membranes or only gentle cervical examination . Cervical swabs were taken before pelvic examination at 38 weeks and again at the onset of labor . Placental membranes were sent for bacteriological study after delivery in all patients . RESULTS The mean gestational age , parity and Bishop score were similar in both groups at recruitment . Gestational age at delivery was lower in the study group ( 38.70 + /- 0.63 ) compared to the control group . Seventy-two percent of the study group and 8 % of the control group had spontaneous onset of labor within 7 days of examination . Labor was induced in one patient ( 2 % ) of the study group and 16 patients ( 32 % ) of the control group . No statistically significant difference was noted in incidence of premature rupture of membranes ( PROM ) , mode of delivery , intrapartum events and perinatal outcome . No increase in neonatal morbidity was seen in association with this procedure . No patient in the study group had clinical evidence of chorioamnionitis . There was no statistically significant difference in the microbiological flora of both groups . CONCLUSION Stripping of the fetal membranes is a safe and efficacious procedure for induction of labor . It decreases the incidence of induction of labor with no increase in incidence of maternal and neonatal morbidity Objecfive To determine the proper management of pregnancy in uncomplicated cases going beyond 42 weeks Objective To assess the efficacy of sweeping of membranes beyond 40 weeks of gestation in reducing the incidence of induction of labour , when induction was planned at 42 weeks OBJECTIVE To determine whether routine antepartum stretching of the cervix and stripping of the membranes at term would shorten the length of pregnancies , and whether this correlated with cervical status and fetal and maternal parameters . DESIGN A prospect i ve , r and omised , controlled study of 293 term gravidas , free of medical complications , divided into two groups : stretching/stripping , and non-stretching/stripping . Digital separation of the fetal membranes from the lower uterine segment , and cervical stretching , were performed during routine vaginal examination of the first group . In the second group , only routine vaginal examination was performed . RESULTS Of 293 patients , 152 underwent a trial of stretching and stripping ; 141 served as a control group . The mean interval ( hours to delivery after the procedure ) was 136 h ( S.D. 10 ) , compared to 161 h ( S.D. 11 ) in the control group ( P = 0.095 ; not significant ) , but with only a trend towards the shorter interval in the first group . When patients were matched according to weeks of gestation and fetal and maternal parameters , only those at 41 weeks ' gestation or more had a significant reduction in the interval from the procedure to delivery ( mean 91 h ( S.D. 8) compared to mean 125 h ( S.D. 10 ) in the control group ; P < 0.007 ) . This observation was independent of cervical status and other maternal or fetal parameters . CONCLUSIONS Only patients > or = 41 weeks ' gestation benefitted from stretching of the cervix and stripping of the fetal membranes . The effect was not dependent on the cervical status or other maternal and fetal parameters Concentrations of 13,14-dihydro-15-keto-PGF2 alpha ( PGFM ) were measured in plasma of six carefully selected primigravid women with an unripe cervix at term before and at various intervals after extra-amniotic insertion of a Foley catheter with or without methylhydroxyethylcellulose ( Tylose ) gel . The procedure caused an acute elevation of PGFM levels within 5 min ( P less than 0.025 ) , which was maintained for at least 6 hours in the absence of uterine activation at 179 + /- 32 % of the initial values ( P less than 0.01 ) . Extra-amniotic administration of Tylose gel caused an increase in PGFM levels which was both higher and more prolonged ( greater than 12 hours ) than insertion of a Foley catheter alone . The observations indicate that cervical ripening without concomitant uterine activation is associated with an increase in PGFM levels . They also demonstrate that prolonged activation of ( intra ) uterine prostagl and in synthesis may occur several hours before the onset of labor-like uterine activity . A chance finding further suggests that spontaneous rupture of the membranes too may be preceeded by an increase in ( intra ) uterine prostagl and in synthesis . In their totality these observations lend strong support to the proposition that an increase in ( intra ) uterine prostagl and in production is a prerequisite to rather than a consequence of the initiation of labor OBJECTIVE Our purpose was to determine whether the risk for postdatism can be reduced by serial membrane sweeping in women with an unfavorable cervix at 39 weeks ' gestation and a negative fetal fibronectin test result . STUDY DESIGN Women with uncomplicated pregnancies , who were c and i date s for a vaginal delivery with an unfavorable cervix at 39 weeks ' gestation and a negative fetal fibronectin test result were asked to participate in this investigation . Patients were chosen at r and om and assigned to a group for membrane sweeping every 3 days or to a control group who received gentle examinations every 3 days . RESULTS Sixty-five women were selected at r and om for serial membrane sweeping ( n = 33 ) or for the control group ( n = 32 ) . Although gestational age and Bishop score at study entry were similar , the gestational age on admission for delivery was earlier in the membrane sweeping group ( 39.9 + /- 0.3 ) versus the control group ( 41.5 + /- 0.6 , P < .0001 ) . The Bishop score on admission to labor and delivery was greater ( 8.8 + /- 2.1 ) in the membrane sweeping group than in the control group ( 6.2 + /- 2.7 , P < .0001 ) . The number of women admitted for labor inductions at 42 weeks ' gestation was 18 of 32 ( 56 % ) in the control group versus none ( 0 of 24 ) in the membrane-sweeping group ( P < .0001 ) . CONCLUSIONS Women with an unfavorable cervix at 39 weeks ' gestation and a negative fetal fibronectin test result are at risk for not being delivered by 41 completed weeks and thus may require post date s induction or antenatal testing . Serial membrane sweeping significantly reduces the risk of postdatism and induction of labor The aim of this study was to evaluate whether sweeping of the membranes at term could shorten the length of pregnancy and reduce the incidence of postterm pregnancies . We r and omly selected 104 nulliparas with uncomplicated pregnancy and gestational age between 281 and 287 days . Our patients were divided into three groups . Group A consisted of 34 women who were subjected to sweeping of the membranes . Uterine stimulation with oxytocin was applied in 35 women ( group B ) , and 35 women ( group C ) were used as a control group . We had no significant reduction of the time interval from sweeping of the membranes until delivery ( 1.9 ± 1.2 days ) , compared to that of group B ( 2.1 ± 0.8 days ) as well as that of the control group ( 2.5 ± 0.9 days ) . The incidence of spontaneous labor in patients after sweeping of the membranes was greater ( 67.6 % ) when compared with oxytocin-stimulated patients and the control group ( p < 0.05 ) . Furthermore , a better Bishop score was noted in patients of group A. No statistically significant difference was noted in the mode of delivery between the groups , but sweeping of the membranes significantly decreased the incidence of postterm pregnancies ( p < 0.05 ) . We concluded that sweeping of the membranes is an effective method for initiating labor in women with a gestational age between 40 and 41 weeks , thus reducing the need for induction OBJECTIVE Our purpose was to determine the optimal management of pregnancies beyond 41 weeks ' gestation with a cervix unfavorable for induction . STUDY DESIGN All uncomplicated pregnancies that reached 41 weeks ' gestation with a Bishop score of < or = 4 were r and omly assigned to one of three groups : ( 1 ) daily cervical examinations , ( 2 ) daily membrane stripping , or ( 3 ) daily placement of prostagl and in gel until 42 weeks . RESULTS In 105 pregnancies the Bishop score on admission to labor and delivery was significantly greater in the groups receiving prostagl and in or stripping of the membranes versus the control group , whereas the converse was time of gestational age at delivery ( p = 0.0001 ) . Fewer patients required induction in the two treatment groups ( 20 % , 17 % ) versus the control ( 69 % ) patients ( p < 0.0001 ) . CONCLUSIONS Daily membrane stripping or daily placement of prostagl and in gel is successful in reducing the number of inductions at 42 weeks for postdatism Objective To determine whether sweeping the membranes in pregnancies of longer than 40 weeks gestation results in an accelerated onset of labour and a reduction in the incidence of induction of labour OBJECTIVE Our purpose was to determine what factors occurring after digital separation of the chorionic membranes from the lower uterine segment ( membrane stripping ) are involved in observed clinical changes compared with patients not so treated . STUDY DESIGN Thirty patients were r and omly divided among a study population and two control groups to assess uterine contractions and microbiologic , histologic , and biochemical markers associated with parturitional events over a 7-hour time frame . RESULTS Clinical ly , an increased frequency of uterine contractile activity was observed among patients in the membrane-stripped group ( p < 0.03 ) . There was a significant increase in plasma 13,14-dihydro-15-keto-prostagl and in F2 alpha ( p < 0.001 ) and endocervical phospholipase A2 activity ( p < 0.04 ) among those who underwent membrane stripping . Blood leukocyte counts , sedimentation rates , prostagl and in E2 metabolite concentrations , and fibronectin levels revealed no significant change during the 7-hour study session . CONCLUSION Membrane stripping was associated with increases in phospholipase A2 activity and prostagl and in F2 alpha concentrations , indicating a possible correlation with initiation of the cascade of parturitional events OBJECTIVE : To determine the best method of cervical ripening to prevent post date inductions in women with an unfavorable cervix at 41 weeks ’ gestation . STUDY DESIGN : Women presenting at 41 weeks ’ gestation with a Bishop score of ≤4 received daily dinoprostone ( Cervidil ) vaginal inserts ( group I ) or daily membrane sweeping ( group II ) . RESULTS : One-hundred and eighty-two women were prospect ively r and omized with 91 women in each arm . The women in group II , membrane sweeping , had Bishop scores significantly greater on admission for delivery ( p < 0.001 ) , had less time elapsed from admission to delivery ( p = 0.018 ) , and had fewer labor inductions at 42 weeks ( p = 0.04 ) than the women in group I , the dinoprostone group . In addition , a greater number of women in group II were admitted in spontaneous labor ( p = 0.006 ) than in group I. Total antenatal costs for the membrane sweeping group was $ 15,120 versus $ 59,540 for the dinoprostone group . CONCLUSION : Daily membrane sweeping was more effective than dinoprostone administration with fewer post date inductions at one-fourth the cost Objective 1 . To evaluate the effectiveness of sweeping of the membranes to reduce the need for a formal induction of labour ; 2 . to evaluate the side effects of this intervention This study was carried out to evaluate the efficacy and safety of membrane stripping at term in reducing the incidence of post-term ( 41 weeks or greater ) pregnancies . One hundred and thirty-seven pregnant women at 38 weeks gestation were r and omised to receive either membrane stripping ( 69 ) or gentle cervical examination ( 68 ) . Women who received stripping had earlier delivery ( 4·8 vs. 12·1 days ; P < 0·001 ) and less incidence of delivery at 41 weeks or greater ( 3 % vs. 16 % ; P = 0·009 ) . No statistically significant difference was noted in incidence of premature rupture of membranes , clinical evidence of chorioamnionitis , intrapartum characteristics and perinatal outcome . We conclude that membrane stripping is a safe method to reduce the incidence of post-term pregnancy The purpose of the study was to determine the safety and efficacy of outpatient intravaginal prostagl and in E2 ( PGE2 ) and membrane stripping in promoting labor in the uncomplicated post date pregnancy . In a double-blind placebo-controlled study , 150 enrollees were r and omized to one of four treatment groups ; group I , no membrane stripping and placebo gel ; group II , no membrane stripping and PGE2 gel ; group III , membrane stripping and placebo gel ; and group IV , membrane stripping and PGE2 gel . The treatments were administered at 287 days ( 41 weeks ) and 294 days ( 42 weeks ) of gestation , then every 3 - 4 days until 307 days ( 43 completed weeks ) of gestation . The patients in group IV had the shortest interval to delivery with a median of 1 day , P = .001 , and the fewest antenatal surveillance visits with only 21 % requiring more than one visit , P = .02 . Group I patients in comparison , had a 7-day median to delivery , and 61 % required more than one visit . The time spent in labor and delivery and the need for oxytocin augmentation was not significantly reduced in groups II , III , and IV . No adverse side effects to either mother or neonate could be directly attributed to this outpatient treatment combination . We conclude that intravaginal PGE2 gel combined with membrane stripping reduces postterm pregnancies and antenatal visits in our patients OBJECTIVE This study was undertaken to estimate the risk of fetal and maternal complications associated with postterm delivery in Denmark . STUDY DESIGN A cross-sectional study that used records from the Danish Medical Birth Registry from 1978 to 1993 was performed . All women with registered prolonged pregnancy ( n = 78022 ) and a 5 % r and om sample of all women who gave birth ( n = 47021 ) were linked to the Danish National Discharge Register . We established a postterm group of 77956 singleton deliveries and a term group of 34140 singleton spontaneous deliveries . Logistic regression models were used to analyze data . RESULTS The risk of perinatal and obstetric complications was high in postterm delivery compared with term delivery ( adjusted odds ratios between 1.2 and 3.1 ) . The risk of perinatal death was 1.33 ( 1.05 - 1.68 ) . CONCLUSION Postterm delivery was associated with significantly increased risks of perinatal and maternal complications in Denmark in the period from 1978 to 1993 Membrane stripping has been used clinical ly for many years but has not been well studied . An investigation was undertaken to determine whether weekly membrane stripping beginning at 38 weeks could safely reduce post-term pregnancies . One hundred eighty patients with firm gestational date s were r and omized to either a treatment or control group . Control subjects received a gentle cervicovaginal examination each week to assess Bishop scores , whereas the treatment group also underwent weekly stripping of membranes . Women who received treatment had earlier delivery ( mean ± SEM 8.60 ± 0.74 versus 15.14 ± 0.83 days ; P<.0001 ) and fewer post-term deliveries than those in the control group ( three versus 14 ; P<.004 ) . The reduction of post-term pregnancies was most notable in nulliparous women with unfavorable Bishop scores . Complications were similar in both groups . Membrane stripping was safe and was associated with earlier delivery and a decreased incidence of post-term gestation Objective To determine the effectiveness of membrane stripping at term to promote the onset of labor . Methods One hundred twenty gravidas at 38 weeks ' gestation , who were attending an antenatal clinic and planned to deliver at Maharaj Nakorn Chiang Mai University Hospital in northern Thail and , were assigned r and omly to one of two groups . One group had weekly pelvic examinations only , and the other also had membrane stripping beginning at 38 week 's gestation and continuing until the onset of labor or until 42 completed weeks ' gestation . Outcome measures included the proportion of patients who delivered within 7 days after the first examination , Bishop scores among those who did not deliver , days from the first examination to delivery , incidence of postterm pregnancy , and maternal and fetal complications . Results Twenty-five of 61 patients ( 41 % ) assigned to membrane stripping delivered within 1 week , compared with 12 of 59 controls ( 20.3 % ) , a statistically significant difference ( P = .014 ) . There was also a statistically significant difference ( P = .013 , Mann-Whitney U test ) in the Bishop scores among those who did not deliver within 1 week ( 4 ± 2.5 versus 2.6 ± 1.7 in the study and control groups , respectively ) . A significant difference was also observed with respect to the mean number of days to delivery ( 8.8 ± 6.7 versus 13.6 ± 7.5 , respectively ; P < .001 ) . The incidence of postterm pregnancy was one of 61 ( 1.6 % ) and three of 59 ( 5.1 % ) in the stripping and control groups , respectively . No significant differences were observed in maternal and fetal complications . Conclusion Membrane stripping is safe and effective in promoting the onset of labor at term Objective To determine whether sweeping or stripping membranes at 38–40 weeks ' gestation leads to spontaneous labor within 7 days . Methods One hundred fifty antenatal low-risk patients at 38–40 weeks ' gestation were assigned r and omly to sweeping or control ( ie , Bishop score only ) groups and stratified based on the ability to pass a finger through the internal os . The primary outcome was the rate of spontaneous labor within 7 days . Major secondary outcomes included the spontaneous labor rate before 41 weeks and the overall spontaneous labor rate . Other outcomes included maternal and neonatal morbidity . The sample size was calculated based on doubling of the spontaneous labor rate within 7 days from 28 % to 56 % ( α = 0.05 , β = 0.10 ) . Results The subjects were demographically similar between the groups . There were no differences between the groups in the primary outcome of spontaneous labor within 7 days ( 33 % sweeping , 38 % control ; P = .39 ) or in the secondary outcomes of spontaneous labor before 41 weeks ( P = .66 ) or the overall spontaneous labor rate ( P = .09 ) . The Bishop score predicted spontaneous labor within 7 days ( P = .003 ) , and gestational age at enrollment predicted spontaneous labor before 41 weeks ( P = .008 ) and the overall spontaneous labor rate ( P = .008 ) , using logistic regression to control for potential confounders . Conclusions Sweeping membranes once at 38–40 weeks ' gestation does not significantly increase the proportion of women who begin spontaneous labor within 7 days Objective To determine whether weekly sweeping of the membranes from 39 weeks of gestation results in a reduction in the number of women reaching 41 completed weeks and subsequently in a reduction of the number of women who will need induction of labour Objective To evaluate weekly stripping of membranes at term to determine its safety and effectiveness in reducing the incidence of prolonged and postterm pregnancies . Methods One hundred forty-two pregnant women with certain gestational date s were r and omly selected to receive , starting at 38 weeks , either weekly stripping of membranes ( 73 patients ) or weekly gentle cervical examinations ( 69 patients ) . Results Women who received stripping had earlier delivery ( 8.2 versus 12.2 days ; P < .005 ) and less incidence of delivery at 41 weeks or greater ( three versus 13 patients ; P < .01 ) . The reduction remained consistent for favorable and unfavorable Bishop scores , and for nulliparas and multiparas . Only three subjects in the study delivered at 42 weeks or greater . No woman reported rupture of membranes after stripping . Conclusion Stripping of membranes is a safe method to reduce the incidence of prolonged pregnancies and the length of term gestations . Larger trials on population s with a higher incidence of postterm pregnancies are needed to evaluate its efficacy in reducing the incidence of postterm pregnancies |
13,336 | 23,379,540 | FES harboured more plaque at their implants than PES .
Modified bleeding index scores were significantly higher in FES , but no differences in bleeding on probing , implant loss and probing pocket depth were observed between FES and PES .
CONCLUSION FES and PES show comparable implant survival rates .
However , no conclusion can be drawn regarding differences in prevalence of peri-implant mucositis and peri-implantitis between FES and PES | AIM The aim of this study was to compare peri-implant conditions between fully edentulous ( FES ) and partially edentulous subjects ( PES ) . | OBJECTIVES The aim of the present split-mouth study is to assess the peri-implant conditions around early-loaded s and blasted and acid-etched ( SLA ) implants , 5 years after abutment connection and to compare , in the same patients , the results obtained with a st and ard protocol using identical implants with a TPS surface . MATERIAL AND METHODS Surgical procedure was performed by the same operator and was identical at test ( SLA ) and control ( TPS ) sites , in 32 healthy patients . Abutment connection was carried out at 35 N cm 6 weeks postsurgery for test sites and 12 weeks for the controls . Patients were seen regularly , for control and professional cleaning . At 60 months , clinical measures and radiographic bone changes were recorded by the same operator , blind to the type of surface of the implant , on 27 patients , as five patients were lost to follow-up . RESULTS A total number of 106 implants were examined . No implant was lost . No significant differences were found with respect to the presence of plaque [ modified plaque index ( mPI ) 0.27+/-0.56 vs. 0.32+/-0.54 ] , bleeding on probing ( 29 % vs. 32 % ) , mean pocket depth ( 3.2+/-1 vs. 3.2+/-1 mm ) or mean marginal bone loss ( 0.32+/-1.04 vs. 0.44+/-1.12 mm ) between test and control . Four implants that presented ' spinning ' at the time of abutment connection presented no significant differences from the rest of the test sites . CONCLUSION The results of this prospect i ve study confirm that SLA implants , under defined conditions , are suitable for early loading at 6 weeks in both the m and ible and the maxilla . Limited implant spinning , occasionally found at abutment connection , produces no detrimental effect on the clinical outcome when properly h and led This paper describes the 5-year results of a comparative study between Astra Tech and Brånemark system implants . The aim was to compare the systems primarily with regard to bone level changes , and also with regard to other variables of interest . Sixty-six patients with edentulous jaws were included in the study . R and omisation schedules were used to allocate the patients to the two implant systems . 184 Astra Tech implants with a titanium-blasted surface and 187 Brånemark implants with a turned surface were used . The implants were inserted with a two-stage technique and the insertion followed the routines for the respective implant system . All patients were provided with full-arch fixed bridges . All patients were followed up with clinical and radiographic examinations from fixture insertion to the 5-year follow-up . The total mean bone level change in the upper jaw between fixture insertion and the 5-year examination was -1.74+/-0.45 mm at the Astra implants and -1.98+/-0.21 at the Brånemark implants . The corresponding values for the lower jaw were -1.06+/-0.19 for Astra and -1.38+/-0.17 for Brånemark . The major postoperative changes of the marginal bone level took place between fixture insertion and baseline . During this period , there was also a different pattern of bone remodelling between the implant systems . Between baseline ( prosthesis connection ) and the 5-year examination , the marginal bone level changes were small , with no difference between the implant systems . The implant stability was examined with the supraconstructions removed . At the 5-year examination , the survival rate for Astra Tech implants was 98.4 % and for the Brånemark implants it was 94.6 % . The difference was not statistically significant The aim of this study was to determine the influence of age on peri-implant tissues in patients treated with implant-supported overdentures in the m and ible . A prospect i ve study was carried out with 2 groups of healthy edentulous patients . The mean age of the younger group ( n = 32 ) was 46 years ( range 35 to 50 years ) ; the mean age of the older group ( n = 26 ) was 68 years ( range 60 to 80 years ) . Two dental implants were placed in the interforaminal region of the m and ible , and after a 3-month healing period , overdentures were fabricated . Clinical and radiographic parameters were evaluated immediately after completion of the prosthetic treatment , after 1 year , and after 3 years . The evaluated clinical parameters were implant loss , Plaque Index , Gingival Index , Bleeding Index , and probing depth . Radiographic evaluation was performed using a st and ardized long-cone technique with a direction device . Statistical analysis was carried out with SPSS software . One implant in the older group was lost during the healing period . After 3 years , the mean scores for Plaque Index , Gingival Index , and Bleeding Index were between 0 and 1 for both groups ( out of possible scores of 0 to 3 ) , and the mean probing depth was 3 mm in both groups . The mean bone loss after 3 years was 1.2 mm in the younger group and 0.8 mm in the older group , but this difference was not significant . It was concluded from this study population that the clinical performance of implant-supported overdentures in the m and ible is equally successful in younger and older patients This report is an up date on a group of 46 clinical trial patients who each received 3 free-st and ing Endopore dental implants placed using a 2-stage surgical approach in the anterior m and ible . After an initial healing interval of 10 weeks , the implants were used in each case to retain an over-denture , and at the time of the report , all patients had passed 5 years of continuous function . The 5-year cumulative " survival " rate based on a life table analysis was 93.4 % and this remained unchanged after 6 years . The 5-year " success rate " was 83.3 % when assessed qualitatively with the published criteria of others using a four-field table analysis categorizing every implant in the study as one of " Grade 1 Success " , " survival " , " unaccounted for " or " failure " . Modified periodontal parameters verified continued peri-implant soft tissue health . No implant still in function had more than 1.8 mm cumulative bone loss during the first 5 years of function . These results provide clear evidence that Endopore implants despite their short lengths function at least as well as other dental implant design s used in much longer lengths PURPOSE This r and omized controlled clinical trial aim ed to evaluate the efficacy of splinted implants versus unsplinted implants in overdenture therapy over a 10-year period . MATERIAL S AND METHODS The study sample comprised 36 completely edentulous patients , 17 men and 19 women ( mean age 63.7 years ) . In each patient , 2 implants ( Brånemark System , Nobel Biocare , Göteborg , Sweden ) were placed in the interforaminal area . Three to 5 months after placement , they were connected to st and ard abutments . The patients were then rehabilitated with ball-retained overdentures , magnet-retained overdentures , or bar-retained overdentures ( the control group ) . Patients were followed for 4 , 12 , 60 , and 120 months post-abutment connection . Group means as well as linear regression models were fitted with attachment type and time as classification variables and corrected for simultaneous testing ( Tukey ) . RESULTS After 10 years , 9 patients had died and 1 was severely ill . Over 10 years , no implants failed . Mean Plaque Index , Bleeding Index , change in attachment level , Periotest values , and marginal bone level at the end of the follow-up period were not significantly different among the groups . DISCUSSION The annual marginal bone loss , excluding the first months of remodeling , was comparable with that found around healthy natural teeth . CONCLUSION The fact that no implants failed and that overall marginal bone loss after the first year of bone remodeling was limited suggested that implants in a 2-implant m and ibular overdenture concept have an excellent prognosis in this patient population , irrespective of the attachment system used Osseointegrated implants as anchors for various prosthetic reconstructions have become a predictable treatment alternative . It was expected that implants required submucosal placement during the healing period for successful tissue integration . However , it has been demonstrated that healing and long-term health of implants could be achieved with equal predictability in a 1-stage , non-submerged approach . This prospect i ve 5-year study not only calculates implant success by life table analysis , but also evaluates the correlation between observed bone level changes with clinical parameters as measured by suppuration , plaque indices , bleeding indices , probing depth , attachment level and mobility . A total of 112 ITI dental implants were inserted in different areas of the jaws . Clinical and radiographic parameters were evaluated annually for 5 years , whereas a portion of the study group for which 6-year evaluations were available were included in the life-table analysis . The overall success rate after 5 years in service was 99.1 % , while after 6 years it was reduced to 95.5 % due to the fracture of 3 implants in 1 patient . The mean crestal bone loss experienced during the first year was 0.6 mm followed by an annual yearly loss of approximately 0.05 mm . No significant differences could be found between the amount of bone loss measured at each of the yearly follow-up visits . This suggests that statistically the followed implants did not show any radiographically measurable bone loss following the initial period of bone loss associated with implant placement and osseointegration . Low levels of correlation between the individual and cumulative clinical parameters with radiographically measured bone loss suggests that these parameters are of limited clinical value in assessing and predicting future peri-implant bone loss The aim of this prospect i ve r and omized controlled clinical trial was to evaluate and compare clinical aspects and satisfaction during the first year following treatment and consecutively the change in treatment during the next 4 years of follow-up . Patients were allocated to one of the following treatment modalities : an implant-retained overdenture ( IRO-group , 2 endosseous implants , n = 61 ) or a complete denture ( CD-group , n = 60 ) . One year after placement of the denture , unsatisfied patients of the CD-group got the opportunity for a retreatment including an implant-retained overdenture . In the IRO-group 4 implants were lost during the first year and again 4 implants were lost during the next 4 years ( survival rate : 93 % ) . All patients could be re-operated successfully . In the CD-group 14 patients ( 23 % ) chose an implant-retained overdenture after 1 year . Patients of the IRO-group were significantly more satisfied than patients of the CD-group after 1 year ( satisfaction score 8.3 versus 6.6 , scale 1 - 10 ) and after 5 years ( 7.4 versus 6.4 ) . From this study it can be concluded that endosseous implants have a high survival rate after 5-years ' follow-up . Satisfaction score of the IRO-group is diminishing in time , probably because patients get used to an improved situation . After 5 years , the mean satisfaction score of the CD-group ( including patients who got implants ) was still lower than of the IRO-group , in spite of the opportunity to a retreatment and have implant-retained overdentures OBJECTIVE The purpose of this prospect i ve study was to evaluate one-stage dental implants clinical ly and radiographically after 10 years in function . MATERIAL AND METHODS Twenty-five patients with a total of 68 implants [ 46 hollow screws ( HS ) and 22 hollow cylinders ( HC ) ] who previously participated in 5-year prospect i ve clinical study returned for a 10-year follow-up . For each patient , informed consent was obtained , medical and dental history was review ed and soft and hard tissue conditions were evaluated using the modified plaque index , modified sulcus bleeding index , probing depth , suppuration , attachment level , distance from the implant crown margin to the coronal border of the peri-implant mucosa keratinized mucosa and periapical radiographs to calculate crestal bone-level changes . RESULTS As expected , the mean crestal bone-level changes were the greatest in the first year following restoration placement , while only minimal changes were noticed in the subsequent years . HC implants showed a statistically significant higher mean crestal bone loss when compared with HS implants at year 10 . Gender was also statistically significantly related to the mean crestal bone loss at years 1 , 3 , 5 and 10 , with male subjects exhibiting more bone loss than female subjects . However , age and peri-implant soft tissue parameters showed low levels of correlation with the mean crestal bone-level changes , and proved to be weak predictors for the mean crestal bone loss at years 5 and 10 . CONCLUSIONS This study confirms that the mean crestal bone loss rates of the HS and HC implants are well within the clinical ly acceptable parameters . In addition , some of the clinical parameters could be used to assess and predict future crestal bone loss BACKGROUND Dental implants with moderately rough surfaces are commonly used in the treatment of edentulous patients . However , long-term data on survival rates and marginal bone conditions are lacking . PURPOSE This prospect i ve study evaluated the cumulative survival rate of the TiOblast implant ( Astra Tech AB , Mölndal , Sweden ) after 10 years of prosthetic loading . MATERIAL S AND METHODS A total of 199 TiOblast implants were placed in 36 consecutive edentulous patients ( 23 males and 13 females ) . All patients were treated at one clinic and by the same team . The patients were edentulous in either the maxilla ( n = 16 ) or the m and ible ( n = 20 ) . The average age of the patients at the start of the trial was 64 years ( range , 59 - 82 years ) . Of the 199 implants inserted 108 were in the m and ible and 91 were in the maxilla . Clinical evaluations were undertaken after completion of the prosthetic superstructure ( baseline ) and after 6 months , 1 year , 3 years , 5 years , 7 years , and 10 years . Mean marginal bone level was evaluated for the first 100 placed implants for up to 7 years . RESULTS Six implants failed during the study ( 3 in the m and ible and 3 in the maxilla ) . All failures occurred within the first year , giving a cumulative survival rate of 96.9 % ( 96.6 % in the maxilla and 97.2 % in the m and ible ) after 10 years of follow-up . The survival rate for the superstructures was 100 % . The mean marginal bone level in the measured sample was 0.2 mm ( st and ard deviation [ SD ] , 0.31 ) below the reference point at baseline , 0.28 mm ( SD , 0.20 ) and 1.27 mm ( SD , 1.15 ) below the same point 7 years later ( mean , 0.15 mm per year ) . CONCLUSION This study showed that titanium dioxide-blasted implants offer predictable long-term results as supports for fixed prostheses in both the maxilla and m and ible PURPOSE The present study evaluated implant and peri-implant outcomes as well as prosthodontic maintenance efforts for implant/bar-supported m and ibular prostheses with different prosthesis anchorage systems . MATERIAL S AND METHODS Seventy-six patients who received two or four interforaminal implants were assigned to one of three different bar design s and subsequently to different prosthesis supporting systems . Forty-nine patients received implants and a mucosa-supported implant-retained overdenture ( OD ) with an ovoid bar ( two implants ; design 1 ) or multiple ovoid bars ( four implants ; design 2 ) . Twenty-seven patients received four implants and a rigid implant-supported prosthesis ( ISP ) with a milled bar ( design 3 ) . Implant survival , peri-implant parameters ( marginal bone resorption , pocket depth , and plaque , bleeding , gingival , and calculus indices ) , and postinsertion prosthodontic maintenance were followed over a 5-year period and compared among the different retention modalities . At the most recent follow-up examination , subjective patient satisfaction was additionally evaluated using a simplified scoring system ( ranging from 1 = not satisfactory to 5 = excellent ) . RESULTS Implant survival rates ( 100 % ) and all peri-implant parameters evaluated showed no differences among the three design s used for implant prosthesis anchorage . Prosthodontic maintenance did not differ between the different ODs ( OD design 1 : average of 1.04 maintenance visits/year/patient ; OD design 2 : 1.2 maintenance visits/year/patient ) , but it was significantly lower for the dentures that were rigidly stabilized with milled bars ( ISP : 0.37 maintenance visits/year/patient ) . A high subjective satisfaction rate ( range : 4.5 to 5.0 ) was registered at the final examination , without any differences among the design s used . CONCLUSIONS Rigid anchorage with milled bars on four-implant prostheses combined with a metal-reinforced framework showed a lower extent of prosthodontic maintenance issues than round bars on two- or four-implant overdentures with resilient denture stabilization . Nevertheless , implants and peri-implant structures were not negatively affected by either resilient or rigid anchorage mechanisms BACKGROUND AND PURPOSE Because of poor retention of complete removable dentures for edentulous patients , implant-supported m and ibular overdentures have lately become a popular alternative for them . The aims of this prospect i ve study were to evaluate treatment outcomes of m and ibular overdentures supported by two unsplinted early-loaded implants and compare these results with those for delayed-loaded implants . MATERIAL S AND METHODS A total of 26 edentulous patients were treated with two unsplinted implants supporting a m and ibular overdenture . All implants were placed in the canine regions of each m and ible according to the one-stage surgical protocol . There were two groups : test group , in which the overdenture was connected 1 week after surgery , and control group , in which the overdenture was connected 3 months after surgery . St and ardized clinical and radiographic parameters were recorded at surgery , and after 3 , 6 , 12 , and 18 months , and 2 , 3 , 4 , and 5 years . RESULTS No implants were lost , and 0.93 + /- 0.3 mm marginal bone resorption was noted for all implants after 5 years . Clinical implant stability measurements , clinical peri-implant parameters , and marginal bone resorptions showed no statistically significant differences between the two groups over 5 years . CONCLUSION The results of this prospect i ve clinical study suggest that there is no significant difference in the clinical and radiographic state of patients treated with implant supported m and ibular overdentures loaded either 1 week or 3 months after surgery AIM To determine the incidence of peri-implantitis in individuals with mucositis in a 5-year follow-up study . MATERIAL AND METHODS A sample of 212 partially edentulous individuals , rehabilitated with dental implants , underwent periodontal and peri-implant clinical examinations in 2005 ( baseline ) . Five years later , 80 individuals who had been diagnosed with mucositis in the baseline examination were re-examined . These individuals were divided into two groups : one group with preventive maintenance during the study period ( GTP ; n = 39 ) , and another group without preventive maintenance ( GNTP ; n = 41 ) . The following parameters were clinical ly evaluated : plaque index , bleeding on periodontal and peri-implant probing , periodontal and peri-implant probing depth , suppuration and peri-implant bone loss . The influence of biological and behavioural risk variables associated with the occurrence of peri-implantitis was analysed using univariate and multivariate logistic regression analyses . RESULTS The incidence of peri-implantitis in the global sample was 31.2 % ( GNTP = 43.9 % and GTP = 18.0 % ) . CONCLUSION The absence of preventive maintenance in individuals with pre-existing peri-implant mucositis was associated with a high incidence of peri-implantitis . Clinical parameters , such as bleeding on peri-implant probing , periodontal probing depth and the presence of periodontitis were associated with a higher risk of developing peri-implantitis AIM To evaluate the success and maintenance requirements of cylindrical , hydroxyapatite coated implants used as single-tooth implants . DESIGN A five-year prospect i ve trial . METHOD Twenty patients , attending the Department of Prosthetic Dentistry at GKT Dental Institute , London , were provided with 23 Calcitek , Integral Omniloc single tooth implants . Annual review s were undertaken for five years . Assessment criteria included implant survival ; abutment or crown looseness ; radiographic evidence of bone loss ; evidence of plaque and inflammation of the mucosal cuff ; the patient 's perception of the restoration . RESULTS All implants integrated . Two subjects , with three crowns , dropped out giving a known cumulative survival rate of 87 % . Twelve implants exhibited no measurable bone loss and six demonstrated funnel formation up to 2 mm in depth which , at five years , appeared to be stable ; three implants exhibited continuing bone loss and their inclusion as failures gives a known success rate of 74 % . The abutments came loose on four occasions ; the crowns decemented on 12 occasions ; two crowns were repaired and one remade . The appearance was judged to be good or very good . CONCLUSION The prospect i ve study indicated that hydroxyapatite coated implants can be successful as single tooth implants , over a five-year period One hundred seven Brånemark implants were placed in 92 patients participating in an international multicenter trial on single-implant restorations at seven centers . The patients were followed for 5 years in a prospect i ve study focusing on implant success and crown function . Plaque and gingival indexes , as well as probing depths , were recorded around teeth and implants . The marginal bone level at implants was determined from intraoral radiographs . Only three implants ( 2.8 % ) had been lost at the final annual checkup . During the follow-up period , a total of 17 patients dropped out or were excluded because of nonconformity with the protocol . Based on the remaining patients , a total of 86 implants were clinical ly and radiographically evaluated at the 5-year follow-up period , result ing in a cumulative success rate of 96.6 % ( 71 implants ) in the maxillae and 100 % ( 15 implants ) in the m and ibles . Plaque and gingival indexes showed a similar pattern of good health around both natural teeth and titanium abutments . The marginal bone loss during the 5-year period did not exceed 1 mm as a mean for all implants analyzed . The most frequent complication recorded during the follow-up was loosening of the abutment fixation screw . The outcome of this study indicated that safe and highly predictable results can be obtained for 5 years when Brånemark implants are used to support single-tooth restorations In this multicenter prospect i ve study , the results achieved with the use of Brånemark implants for single tooth replacement were evaluated . The overall cumulative success rate was 95.9 % for implants and 91.1 % for crowns . Two of the 99 implants placed had to be removed before the prosthodontic stage of treatment ; thus , 97 were restored with CeraOne crowns . Seventy-seven implants were evaluated radiographically at the 1-year follow-up , 57 at 3 years , and 47 at 5 years . Mean marginal bone resorption was well within the limits set by Albrektsson et al in 1986 . The status of the soft tissue around crowns and adjacent teeth remained stable over the evaluation period . The gold abutment screw in the CeraOne system seems to have eliminated the problem of loosening abutment screws in single tooth replacements . The results suggest that the Brånemark system can be safely used for tissue-integrated replacement of single teeth BACKGROUND The question of the importance of keratinized mucosa around dental implants for the prevention of peri-implant disease could not be answered in the relevant literature so far . OBJECTIVE To investigate the influence of peri-implant keratinized mucosa on long-term peri-implant soft-tissue health and stability over a period of 5 years . MATERIAL AND METHODS A total of 386 m and ibular dental implants were placed in 73 completely edentulous patients , and subsequently restored with fixed full-arch prostheses . At prosthesis delivery ( baseline ) and after 3 , 6 , 12 , 18 , 24 , 36 , 48 and 60 months , modified plaque index ( mPlI ) , modified sulcus bleeding index ( mBI ) , distance between implant shoulder and mucosal margin ( DIM ) and width of peri-implant keratinized mucosa ( KM ) were recorded . Statistical analysis included multivariate logistic regression , multivariate ordinal logistic regression , generalized estimating equations and Bonferroni 's correction . RESULTS Fifty-eight patients with 307 implants completed the 5-year study . Statistically significantly higher plaque accumulation on lingual sites ( mean mPlI 0.67 , SD 0.85 ) , bleeding tendencies on lingual sites ( mean mBI 0.22 , SD 0.53 ) and larger soft-tissue recession on buccal sites ( mean DIM -0.69 mm , SD 1.11 mm ) were found when the width of KM was < 2 mm , compared to sites with > or=2 mm of KM ( mean mPlI 0.40 , SD 0.68 , P=0.001 ; mean mBI 0.13 , SD 0.41 , P<0.01 ; mean DIM -0.08 mm , SD 0.86 mm , P<0.001 ) . The width of keratinized mucosa had no effect on bleeding tendency or plaque accumulation on buccal sites ( P>0.05 ) . CONCLUSION In patients exercising good oral hygiene and receiving regular implant maintenance therapy , implants with a reduced width of < 2 mm of peri-implant keratinized mucosa were more prone to lingual plaque accumulation and bleeding as well as buccal soft-tissue recession over a period of 5 years OBJECTIVE The aim of this 5-year prospect i ve comparative study was to evaluate treatment outcome ( survival rate , condition of hard and soft peri-implant tissues , patient satisfaction , prosthetic and surgical aftercare ) of m and ibular overdentures supported by two or four implants . MATERIAL AND METHODS Sixty edentulous patients with a m and ibular height between 12 and 18 mm participated . Thirty patients were treated with an overdenture supported by two IMZ implants ( group A ) and 30 patients were treated with an overdenture supported by four IMZ implants ( group B ) . St and ardised clinical and radiographic parameters were evaluated 6 weeks after completion of the prosthetic treatment and after 1 , 2 , 3 , 4 and 5 years of functional loading . Prosthetic and surgical aftercare was scored during the evaluation period . RESULTS One implant was lost ( group A ) during the healing period . There were no significant differences with regard to any of the studied clinical or radiographic parameters of the peri-implant tissues between the groups . None of the patients reported sensory disturbances in the lip or chin region . No differences in satisfaction were observed between the groups . With regard to aftercare , there was a tendency of a greater need of prosthetic interventions in group A , while correction of soft-tissue problems was restricted to patients of group B. CONCLUSION There is no difference in clinical and radiographical state of patients treated with an overdenture on two or four implants during a 5-year evaluation period . Patients of both groups were as satisfied with their overdentures PURPOSE The aim of this prospect i ve cohort study was to determine the 5-year implant survival and success rates associated with early loading ( 6 weeks after nonsubmerged placement ) of s and blasted and acid-etched ( SLA ) Straumann implants in the edentulous m and ible . A secondary objective was to determine the peri-implant tissue response and measure alterations in peri-implant crestal bone levels . MATERIAL S AND METHODS SLA implants were placed and primarily loaded 6 weeks later with 35 Ncm during abutment placement . The peri-implant bone and mucosal conditions of the participants were monitored radiographically and clinical ly over a 5-year period . RESULTS Fourteen patients received 60 implants . Thirteen patients and 54 implants were examined at the 5-year appointment . Two of 60 implants failed during the healing period , and four implants were lost during follow-up and considered as dropouts . The remaining implants showed favorable clinical and radiographic findings and were considered successfully integrated at the 5-year examination . The mean loss of crestal bone height after 5 years was 0.77 mm ( SEM 0.09 ) . This result ed in a 5-year cumulative success rate of 96.7 % . CONCLUSION In this prospect i ve study , the early loading of Straumann implants with the SLA surface in the edentulous m and ible after a healing time of 6 weeks provided successful osseointegration with high predictability . Successful integration was maintained for 5 years PURPOSE For dental implants to be successful , osseointegration must occur , but it is unknown how much time must pass for osseointegration to be established . Pre clinical studies suggested that titanium implants with a s and blasted and acid-etched ( SLA ) surface were more osteoconductive and allowed more rapid osseointegration than machined or turned implant surfaces . The hypothesis of this study was that implants with an SLA surface could be loaded in half the conventional healing time of machined-surface implants and that , after loading , the implants would be successful for 5 years . MATERIAL S AND METHODS A prospect i ve multicenter clinical study was conducted with 439 implants placed in native bone in 135 edentulous and partially edentulous patients . Abutments were attached to the implant with 35 Ncm of torque without countertorque after 6 weeks in type I to III bone and after 12 weeks in type IV bone . The patients were carefully evaluated for 5 years . RESULTS Most implants were placed in nonsmoking , nondiabetic patients with a mean age of 55 years ( range , 21 to 82 years ) . Eighty percent of the implants were 10 or 12 mm long , 96 % had a diameter of 4.1 mm , and 78 % were placed in type II or III bone . Patients maintained good oral hygiene and were satisfied with the restorations . Four implants failed , and one implant was deemed unsuccessful between surgery and the 1-year postloading visit . No implants failed or were unsuccessful in subsequent years . The cumulative survival and success rates for 385 implants in 120 patients after 5 years were 99.1 % and 98.8 % , respectively . CONCLUSION Implants with an SLA surface can be restored in 6 weeks for type I to III bone and 12 weeks for type IV bone . Furthermore , they can be maintained after loading for 5 years with very high success and survival rates PURPOSE The aim of this 5-year prospect i ve study was to compare the results of single-tooth implant treatments planned and performed at four general practitioners ' offices with the results from a specialist clinic . MATERIAL S AND METHODS The group comprised 38 patients . Nineteen patients , with 19 implants/crowns , were planned and treated by four general practitioners , and the outcome was compared to a matched group of patients from a specialist clinic . RESULTS Three patients did not complete the study . None of the implants failed ; one crown failed . This was a very positive result , as the single failure , a crown at the specialist clinic , was caused by an extraordinary trauma and was not related to a common cause such as bite forces or fatigue . No significant differences were observed between the groups when the radiographic findings were compared . Some minor differences , for bleeding and the position of the mucosal level around implants and adjacent teeth , were observed between the two groups . CONCLUSION The small discrepancies that were observed between treatment performed by the four general practitioners at their own offices and treatment performed at the specialist clinic were not regarded to be of any clinical importance . This indicates that complete single-tooth implant treatment may be performed for many patients by general practitioners who have received adequate training , allowing the possibility of referring complicated treatments to specialists and other treatments to general practitioners PURPOSE The use of implants for prosthetic rehabilitation of partially edentulous patients is increasing . However , the possibilities of placing implants in the posterior part of the m and ible are often limited . The purpose of this longitudinal study with 10 years of follow-up was to evaluate the use of short implants supporting fixed partial dentures ( FPD ) in the posterior part of the m and ible , and to compare implant supported FPDs to tooth-implant supported FPDs . MATERIAL S AND METHODS The patient material comprised 23 patients with residual m and ibular anterior teeth , and each patient received FPDs unilaterally . On one side the FPD was supported by two implants , and on the other side by one implant and one tooth , thus permitting intraindividual comparison . The distribution of the two types of FPDs in each jaw was r and omized . Implant success rates , marginal bone changes , and mechanical complications were studied . RESULTS The tooth-implant connection did not demonstrate any negative influences on the overall success rates for the 10-year period , nor were the shorter implants found to be less favorable . CONCLUSION It is suggested that a prosthetic construction supported by both a tooth and an implant may be recommended as a predictable and reliable treatment alternative in the posterior m and ible OBJECTIVES To evaluate clinical ly and radiographically immediate implants 5 years after insertion and to compare them with delayed-placed implants in the same subjects . MATERIAL AND METHODS Twenty-two consecutive patients that needed at least two implants for replacing hopeless teeth , one immediately upon extraction and the other in a delayed fashion ( at least 4 months post- extraction ) were selected in this prospect i ve cohort study . Post- extraction immediate implants ( II ) and delayed implants ( DI ) groups were defined . One and 5 years after implant loading , clinical and radiographical outcome variables were recorded and analysed both at site and at implant level . Intra-group and inter-group comparisons were performed . RESULTS The intergroup comparison did not show significant differences for plaque index , bleeding on probing and suppuration . These parameters worsen in both groups along the study . This trend was stronger for the plaque index in the group II , which increased from 15.6 % at 1 year to 25.9 % at 5 years ( P < 0.04 ) . One year after loading , the sites with probing depth ≥5 mm were higher for the group II compared to DI ( 2.5 % vs. 0 % ; P = 0.049 ) . At the end of the study , no significant statistical differences were found . Radiographically , bone crestal changes did not yield significant differences . During the follow-up period , 25 % of the implants ( 26.4 % in group II and 23.5 % in DI ) showed biological complications : mucositis ( 20 % ) and /or periimplantitis ( 5.8 % ) . No differences between groups were found . CONCLUSIONS Within the same patients , the implants placed with the immediate protocol demonstrated a higher tendency to crestal bone loss and to peri-implantitis , although these differences were not statistically significant OBJECTIVES To assess prospect ively over 10 years the incidences of technical and /or biological complications and failures occurring in a cohort of consecutive partially edentulous patients with fixed reconstructions on implants of the ITI Dental Implant System . METHODS Eighty-nine patients were available , 34 ( 38.2 % ) were male , 55 ( 61.8 % ) were female . At the 10-year examination ( range 8 - 12 years ) , they were 58.9 years old ( range 28 - 88 years ) . RESULTS Single crowns ( SC ) : 48 patients had been restored with 69 SC on 69 implants . Five of the implants with the crowns were lost because of biological failures . Two crowns ( 2.9 % ) were remade because of technical failures . Total failure amounted to seven ( 10 % ) . Implant borne fixed partial dentures ( I-I FPD ) : In 29 patients who had been restored with 33 implant borne suprastructures , the total number of failed I-I FPD was 2 ( 6.1 % ) . Tooth-implant borne fixed partial dentures ( I-T FPD ) : In 21 patients , 22 mixed tooth-implant borne reconstructions were constructed . The number of failed FPD reached 7 ( 31.8 % ) . Statistically significantly fewer biological failures occurred with I-I FPD compared with the I-T FPDs ( ANOVA , Bonferroni , P=0.022 ) . The I-T FPDs experienced statistically significantly more frequent technical failures compared with the other two groups of suprastructures ( P=0.003 , 0.031 ) . Consequences of complications : The occurrence of loss of retention as a complication increased the odds ratio ( OR ) to 17.6 ( P<0.001 ) to end up in a technical failure . Similarly , the event of a porcelain fracture increased the OR for the suprastructure to be a failure at 10 years to 11.0 ( P < or = 0.004 ) . Treatment of periimplantitis increased the OR to 5.44 ( P < or = 0.011 ) to result in a biological failure compared with implants in which this type of treatment was not applied . CONCLUSION The three groups of suprastructures demonstrated marked differences in their patterns of failures and complications . Complications increased the risk for failure . Support by CRF , University of Berne , Switzerl and PURPOSE The purpose of the current prospect i ve multicenter study was to evaluate the 5-year implant success and peri-implant conditions of smooth-surface Brånemark System implants when using a novel technique including a 1-stage surgical procedure with early loading in edentulous m and ibles . MATERIAL S AND METHODS The study protocol included 1-stage surgery as well as placement of the definitive prosthesis within 6 weeks after implant insertion ( ie , early loading ) . Clinical evaluation , as well as evaluation of function and esthetics , was performed at each follow-up visit . Radiographs were obtained at connection of the prostheses and at the 1 , 3- , and 5-year check-ups . RESULTS A total of 40 patients with a mean age of 56 years ( range , 30 to 70 ) were included in the study . In all , 170 implants were placed in between the mental foramina , of which 120 implants in 30 patients were associated with overdenture treatment and 50 implants in 10 patients with fixed complete dentures . Twelve implants failed in 6 patients . The cumulative implant survival rate was 92.9 % after both 1 and 5 years of follow-up . Another 3 implants were recorded as mobile but still in function when individually checked at the 5-year visit , which result ed in a cumulative success rate of 91.0 % . Mean bone remodeling over the study period was less than 0.1 mm/y after the first year of loading , result ing in a mean marginal bone level of 0.66 mm ( SD 0.73 , n = 138 ) apical to the implant collar reference point after 5 years . CONCLUSIONS One-stage , early loaded smooth-surface Brånemark System implants functioned well for the majority of patients with edentulous m and ibles . Stable peri-implant conditions were observed . Bone remodeling result ed in a mean bone level above the first implant thread after 5 years . The somewhat lower success rate of 91.0 % compared to a 2-stage procedure may be related to generous inclusion criteria and to a learning curve involving a novel treatment procedure The clinical results of 85 Screw Vent implants are described with respect to 7-year success , including radiographically detectable bone loss , survival and prosthetic quality . The 1-year results of the same material have been reported previously ( De Bruyn et al. 1992 ) . Implants were considered as successful when they were meeting with the success criteria proposed by the European Academy for Periodontology . From the 85 implants originally installed , 16 failed during the 7-year interval ( 18.8 % ) , 6 were unaccounted for ( 7 % ) , 21 ( 24.7 % ) did not meet the success criteria yet survived and 42 implants ( 49.4 % ) were successful . The success rate was 65.2 % for the m and ibular and 43.5 % for the maxillary implants . Implant failures were irrespective of implant length , smoking habits , prosthetic quality or oral hygiene level . From 24 patients with a corresponding number of 60 implants , radiographs were available for bone loss analysis . The mean bone loss after 7 years was 2.92 mm ( range -0.5 to 6.3 ) 18 out of 60 examined implants ( 30 % ) showed unacceptable radiological bone loss beyond the critical value of 2.7 mm . Implant material analysis and histomorphometric analysis of a retrieved implant are discussed . In the present clinical study , the Screw Vent implant system does not meet the success criteria proposed by the European Academy for Periodontology . The ongoing bone loss increases the risk for future implant failures and peri-implant disease A total of 114 ITI solid-screw implants was consecutively placed in 55 partially edentulous patients and restored with 68 fixed prostheses . The patients were followed for at least 5 years in a prospect i ve study that focused on implant success and longitudinal reactions of the peri-implant hard and soft tissues . During the study period , 5 implants failed and 15 implants were lost to follow-up , result ing in a cumulative survival rate of 95.3 % after 5 years of loading . The success analysis included additional strictly defined events ( " first occurrence of marginal bone loss > or = 4 mm , " " first occurrence of pocket depth > or = 4 mm , " and " first occurrence of crevicular fluid volume > or = 2.5 mm " ) and result ed in a cumulative 5-year success rate of 89.0 % . Median loss of marginal bone , as observed on radiographs , was 0.7 mm between implant placement and prosthetic treatment and 0.5 mm between prosthesis placement and the 5-year evaluation . Compared to the previous year 's value , the annual increase in marginal bone loss did not reach a level of statistical significance between 1 and 5 years of function , so that a steady state prevailed . The incidence of lingual-palatal surfaces affected with remarkable plaque deposits increased from 13 % after prosthesis placement to 23 % after 5 years . Sulcus Bleeding index , probing depth , attachment level , and crevicular fluid volume were used to describe the health of the peri-implant soft tissues . The research parameters remained almost unchanged and indicated a soft tissue response within physiologic levels . Most mechanical complications were experienced during the first year of loading and were related to loosening of occlusal screws , which occurred in 8 ( 12 % ) of 68 restorations The long-term success of endosseous implants is related to healthy peri-implant tissues . Attached keratinized mucosa does not seem important for the prevention of soft tissue complications . Prevention of muscle attachment near the implants , however , seems more decisive for maintaining a favourable peri-implant environment . We treated 150 patients from 1990 - 91 with two Intramobil Zylinder implants and modified vestibuloplasty , 65 of whom were r and omly selected for evaluation at 1 year ; 48 of the 65 were also seen at 5 years . The vestibuloplasty was done by the technique of Pichler and Trauner , to prevent muscle pull and to create a thin layer of mucosa around the implants , and endosseous osseointegrated implants were inserted . The results show an adequately depended vestibulum with no muscle pull around the implants and significantly lower pocket depth after 5 years of follow-up compared with similar studies INTRODUCTION Many studies have dealt with the clinical outcome of oral implants , yet none applied a r and omized split-mouth design for a long-term follow-up of similar implant systems . AIM To evaluate two oral implant systems with different surface characteristics in a r and omized split-mouth design and to radiologically analyse peri-implant bone level and density over an up to 16-year period . MATERIAL S AND METHODS The study comprised clinical and radiographic records of 18 partially edentulous patients treated with both implant types r and omly placed in either left or right jaw sides . Outcome was evaluated over time . RESULTS Clinical and radiographic parameters showed no significant differences over time for both systems . Ten years after implant placement , a significantly increasing peri-implant bone density was noted , while Periotest values were found to be significantly decreasing . Fifteen years after implant loading , mean bone loss was 0.02 mm ( range -1.15 to 1.51 ; SD 0.45 ) for Astra Tech ® implants ( n=24 ) and 0.31 mm ( range -0.98 to 2.31 ; SD 0.69 ) for Brånemark ® implants ( n=23 ) . CONCLUSIONS The study failed to demonstrate significant differences in the outcome of the peri-implant bone for two implant systems with different surface characteristics . The marginal bone level around oral implants changed < 0.5 mm after 15 years of loading The purpose of the present clinical study was to evaluate the 5-year results of the first 12 implants inserted at the University of Berne in regenerated bone following successful ridge augmentation with the membrane technique . The patients were recalled and examined with clinical and radiographic parameters routinely utilized in prospect i ve studies with st and ard implants in non-regenerated bone . Based on clinical and radiographic findings , all 12 implants were considered successfully integrated according to strict criteria of success . The detailed analysis of clinical parameters revealed no differences to results of prospect i ve studies on st and ard implants in non-regenerated bone . All implants demonstrated ankylotic stability which was confirmed by a mean Periotest value of -2.08 . The radiographic analysis showed stable bone crest levels with a mean bone loss between the 1- and 5-year examination of 0.30 mm . However , 2 implants exhibited a bone loss of more than 1 mm between the 1- and 5-year examination . Therefore , the prognosis of these 2 implants seems question able at the present time . It can be concluded that bone regenerated with the membrane technique reacts to implant placement like non-regenerated bone , since all 12 implants achieved successful tissue integration with functional ankylosis . Furthermore , this bone is also load-bearing , since all 12 implants maintained osseointegration over a 5-year period PURPOSE This prospect i ve investigation studied the clinical and radiographic performance of m and ibular fixed prostheses supported by osseointegrated implants over more than 20 years . MATERIAL S AND METHODS A total of 273 st and ard Brånemark implants ( 10 mm long ) were placed in 47 patients between 1978 and 1982 . Clinical and radiographic data collected at several examinations over the 20-year observation period have been reported previously . This study presents the outcome of the latest follow-up after 20 to 23 years . RESULTS Thirty patients ( 64 % ; 75 % of those still alive ) attended the 20-year follow-up examination . Three implants were lost during the entire observation period , and the 20-year implant cumulative survival rate was 98.9 % . All patients had continuous prosthesis function , but two had their m and ibular prostheses remade during the 20 years . No implants or prostheses were lost or fractured during the last 5 years , and only a few prosthodontic complications were noted . The mean bone level was 1.6 mm ( SD 0.90 ) below the reference point after 20 years , and mean bone loss was 0.2 mm ( SD 0.22 ) between the 15- and 20-year follow-ups . Thirty-seven implants ( 24 % ) showed more than two exposed threads at the 15-year follow-up examination , but only four implants ( 3 % ) presented pain and /or bone loss exceeding one thread ( 0.6 mm ) during the last 5 years . CONCLUSION The successful treatment result after 15 years continued up to more than 20 years in function . During the last 5 years , a majority of the implants with several exposed implant threads could be maintained without any complications , and the frequency of implants showing signs of ongoing peri-implantitis was less than 3 % BACKGROUND The aim of this prospect i ve study is to evaluate the three-dimensional marginal bone level around implants 5 to 15 years after loading in partially edentulous patients treated for generalized chronic periodontitis ( GCP ) and generalized aggressive periodontitis ( GAgP ) . METHODS Seventeen patients with GCP and 17 patients with GAgP were treated with a total of 119 implants . Patients were examined clinical ly on a 3-month recall schedule after insertion of the superstructure , and radiographs were taken at fixed intervals . At the end of the observation period , cone-beam computed tomography was used for the analysis of the circumferential three-dimensional bone level ( mesial , distal , buccal , and lingual/palatal ) and determination of keratinized mucosa thickness ( KMT ) . RESULTS In both groups , a significant bone loss at implants was observed buccally ( GAgP group : 4.49 ± 2.93 mm ; GCP group : 3.57 ± 2.94 mm ) with significantly more average bone loss in patients with GAgP ( 3.00 ± 1.67 mm ) compared to in patients with GCP ( 2.45 ± 1.08 mm ) . The lowest values for KMT in both groups were found in the anterior m and ible ( GAgP group : 0.99 ± 1.13 mm ; GCP group : 0.82 ± 0.91 mm ) . There were significant correlations between clinical parameters and bone loss in m and ibles of patients with GAgP. CONCLUSIONS The lowest value for KMT in both groups was found in the m and ible . Bone loss was observed buccally and was more pronounced in patients with GAgP , with a significant correlation with keratinized mucosa and increased inflammation PURPOSE The aim of this prospect i ve r and omized clinical trial was to evaluate 10 years of treatment of patients receiving a m and ibular implant-retained overdenture ( IRO ) or a conventional complete denture ( CD ) . MATERIAL S AND METHODS One hundred twenty-one edentulous patients were treated with an IRO ( 2 endosseous implants , n = 61 ) or a conventional CD ( n = 60 ) . Clinical aspects and patient satisfaction were evaluated . One year after placement of the denture , unsatisfied patients of the CD group were given the opportunity to receive implants . RESULTS In the IRO group , 4 implants were lost during the first year and 4 implants were lost during the next 4 years . Between 5 and 10 years , no implants were lost ( survival rate : 93 % ) . In the CD group , 24 patients ( 40 % ) chose an IRO between 1 and 10 years . DISCUSSION Patients in the IRO group were significantly more satisfied than patients in the CD group after 1 year ( satisfaction score 8.3 versus 6.6 on a scale of 1 to 10 ) , after 5 years ( 7.4 versus 6.4 ) , and after 10 years ( 7.7 versus 6.8 ) . CONCLUSION The mean satisfaction score of the CD group ( including patients who later received implants ) was still lower than that of the IRO group , in spite of the opportunity for retreatment with IROs . Endosseous implants had a high survival rate after 10 years of follow-up The aim of this prospect i ve r and omized controlled clinical trial was to evaluate the clinical outcomes and prosthetic aftercare of edentulous patients with a m and ibular overdenture retained by two IMZ implants or two Brånemark implants during a 10-year period . Patients were allocated to the IMZ group ( n=29 ) or the Brånemark group ( n=32 ) by a computerized balancing method . In the IMZ group , four implants were lost during the 10-year follow-up ( survival rate : 93 % ) . In the Brånemark group , nine implants were lost ( survival rate : 86 % ) . All patients were re-operated successfully . Multiple prosthetic revisions were necessary in both groups ; especially the precision attachment system in the overdenture ( 23 % of the total number of revisions ) and the denture base and teeth ( 26 % of the total number of revisions ) were subject to frequent fracture . From this study , it can be concluded that both the IMZ implant and the Brånemark implant systems supporting an overdenture are functioning well after 10 years of follow-up . There are no indications of a worsening of clinical or radiographical state after 10 years AIM The aim of this 10-year study ( observation time 8 - 12 years , mean : 10 years ) was to compare the survival rates , success rates and incidences of biological complications using three different implant design s of the ITI Dental Implant System . MATERIAL AND METHODS In 89 dental patients treated comprehensively , a total of 112 hollow screw ( HS ) , 49 hollow cylinder ( HC ) and 18 angulated hollow cylinder ( AHC ) implants were installed depending on the available bone volume and according to prosthetic needs . One and 10 years after surgical placement , clinical and radiographic parameters were assessed . The incidences of peri-implantitis according to various thresholds were registered over 10 years of maintenance . RESULTS Success criteria at 10 years were set at : pocket probing depth ( PPD ) < or = 5 mm , bleeding on probing (BoP)- , bone loss < 0.2 mm annually . The survival rate for HS was 95.4 % , for HC 85.7 % and for AHC 91.7 % . Ninety percent of all the HS , 71 % of the HC and 88 % of the AHC did not present with an incidence of peri-implantitis over the 10 years , HC having significantly higher incidence of peri-implantitis than HS ( P < 0.004 ) . With the success criteria set above , a success rate for HS of 74 % , for HC of 63 % and for AHC of 61 % was identified at 10 years . However , including a definition of PPD < or = 6 mm , BoP - and bone loss < 0.2 mm annually for success , the rates for HS were 78 % , for HC 65 % and for AHC 67 % , respectively . Basing success criteria purely on clinical parameters ( without radiographic analysis ) , such as : PPD < or = 5 mm and BoP- , the success rates increased to 90 % , 76 % and 89 % , respectively . With PPD < or = 6 mm and BoP - as success criteria chosen , the respective rates were 94 % , 82 % and 94 % for HS , HC and AHC implants , respectively . CONCLUSIONS A significantly higher survival rate as well as a significantly lower incidence of peri-implantitis was identified for hollow screw design ITI Dental Implants after 10 years of service when compared to hollow cylinder design ITI Dental Implants ( 95.4 % vs. 85.7 % ; 10 % vs. 29 % ) . Depending on the setting of the threshold criteria for success , success rates are highly variable and hence , reporting of success rates with elaboration on the criteria set appears crucial for comparison of different studies BACKGROUND Implant-supported single-tooth replacements are an increasingly used method to replace teeth , especially in young patients . Therefore , long-term validation of different treatment modalities with different implant systems is of great importance . PURPOSE The aim of the present study was to make a biologic , technical , and aesthetic evaluation of single-tooth replacement supported by the Astra Tech implant ( Astra Tech AB , Mölndal , Sweden ) during a 5-year period . MATERIAL S AND METHODS Twenty patients were divided into two consecutively treated groups . In group A the implants were placed " early " in the extraction sockets , and st and ard single-tooth abutments were used . In group B the implants were placed " delayed , " and preparable abutments were used . Clinical examinations including registration of plaque , bleeding , crown lengths , soft tissue marginal level , papilla height , complications , and radiography were performed yearly . At the 3-year control examination the patient and a dentist evaluated aesthetic appearance with a visual analog scale . RESULTS An implant survival rate of 100 % and a crown survival rate of 95 % over a period of 5 years were found . The mean loss of marginal bone adjacent to implants and neighboring teeth was less than 0.5 mm during the 5-year period , and there was no significant difference after crown placement between the treatment modality for group A and that for B. There were fewer clinical complications and repairs in group B than in group A. Soft tissue dimensions were more natural around implant crowns in group B as compared to group A , but this was not reflected in the patients ' satisfaction with aesthetic appearance . On the other h and the dentist judged the restorations in group B higher concerning aesthetics than in group A. CONCLUSION Implant-supported single-tooth replacement with the Astra Tech system is a reliable treatment result ing in a good 5-year prognosis and only few complications This prospect i ve clinical study evaluated the 5-year survival and success rates of 66 titanium implants placed in bone that had been previously augmented with autografts and nonresorbable barrier membranes . During the observation period , three patients with five implants dropped out of the study . None of the remaining 61 implants were lost during the follow-up period ( implant survival rate of 100 % ) . One implant exhibited a periimplant infection , whereas 60 implants were considered clinical ly successful at the 5-year examination , result ing in a 5-year success rate of 98.3 % . It can be concluded that the clinical results of implants in regenerated bone are comparable to those of implants in nonregenerated bone OBJECTIVES The aim of this prospect i ve comparative study was to evaluate the survival rate , condition of peri-implant tissues , patient satisfaction and surgical and prosthetic aftercare of the IMZ-implant system ( two-stage cylinder type ) , the Brånemark-implant system ( two-stage screw type ) and the ITI-implant system ( one-stage screw type ) supporting a m and ibular overdenture during a 10-year follow-up period . MATERIAL S AND METHODS Three groups of 30 edentulous patients were treated with two endosseous implants in the interforaminal region of the m and ible . Clinical and radiographic parameters were evaluated immediately after completion of the prosthetic treatment and after 1 , 5 and 10 years of functional loading . Prosthetic and surgical aftercare was scored during the evaluation period , as well as patient satisfaction . RESULTS The 10-year survival rate was 93 % for the IMZ group , 98 % for the Brånemark group and 100 % for the ITI group ( IMZ < ITI , p<0.05 ) . Mean marginal bone loss was limited over a period of 10 years . No differences in satisfaction and aftercare were observed between the groups . CONCLUSION It is concluded that two implants placed in the interforaminal region , connected with a bar , supply a proper base for the support of a m and ibular overdenture in the edentulous patient . After10 years , no relevant changes had developed between the three implant systems OBJECTIVES The aim of this prospect i ve study was to evaluate the 5-year performance and success rate of titanium screw-type implants with the titanium plasma spray ( TPS ) or the s and -blasted , large grit , acid-etched ( SLA ) surface inserted in a two-stage sinus floor elevation ( SFE ) procedure in the posterior maxilla . MATERIAL AND METHODS A total of 59 delayed SFEs were performed in 56 patients between January 1997 and December 2001 , using a composite graft with autogenous bone chips combined with deproteinized bovine bone mineral ( DBBM ) or synthetic porous beta-tricalcium phosphate ( beta-TCP ) . After a healing period averaging 7.75 months , 111 dental implants were inserted . After an additional 8 - 14-week healing period , all implants were functionally loaded with cemented crowns or fixed partial dentures . The patients were recalled at 12 and 60 months for clinical and radiographic examination . RESULTS One patient developed an acute infection in the right maxillary sinus after SFE and did not undergo implant therapy . Two of the 111 inserted implants had to be removed because of a developing atypical facial pain , and 11 implants were lost to follow-up and were considered drop-outs . The remaining 98 implants showed favorable clinical and radiographic findings at the 5-year examination . The peri-implant soft tissues were stable over time ; the mean probing depths and mean attachment levels did not change during the follow-up period . The measurement of the bone crest levels ( DIB values ) indicated stability as well . Based on strict success criteria , all 98 implants were considered successfully integrated , result ing in a 5-year success rate of 98 % ( for TPS implants 89 % , for SLA implants 100 % ) . CONCLUSION This prospect i ve study assessing the performance of dental implants inserted after SFE demonstrated that titanium implants can achieve and maintain successful tissue integration with high predictability for at least 5 years of follow-up in carefully selected patients BACKGROUND The aim of this prospect i ve 10-year study of partially edentulous subjects treated for generalized aggressive periodontitis and periodontally healthy subjects was a clinical , microbiologic , and radiographic comparison of teeth and implants and assessment of the implants ' success rate . METHODS Five subjects treated for generalized aggressive periodontitis ( GAgP ) and five periodontally healthy subjects who were orally rehabilitated with osseointegrated implants participated in the study . First , they were examined 2 to 4 weeks before extraction of the non-retainable teeth ( baseline ) and 3 weeks after insertion of the final abutments . All further examinations were performed during a 3-month recall schedule over a 10-year period . At every session , clinical parameters were recorded , and the composition of the subgingival microflora was determined . Radiographs were taken at baseline after insertion of the superstructure and 1 , 3 , 5 , 8 , and 10 years later . RESULTS Throughout the follow-up period , the peri-implant gingival index of GAgP subjects was significantly higher than in periodontally healthy subjects . There was no difference in plaque index between teeth and implants or between the two groups . The peri-implant probing depths were comparable in the two groups and remained < or = 4 mm throughout the follow-up . The probing depth was significantly higher around the teeth of the GAgP subjects compared to periodontally healthy subjects . Implants of GAgP subjects showed a significantly higher attachment loss ( Ø 2.4 mm ) . The attachment level at teeth and implants of the periodontally healthy subjects and at teeth of the GAgP subjects was almost unchanged . Microbiologically , GAgP subjects had fewer cocci and more motile rods and filaments at teeth and implants than periodontally healthy subjects . GAgP subjects showed significantly more peri-implant bone loss in the first year ( Ø 2.07 mm ) and in the subsequent 9 years ( total 1.3 mm ) . Bone loss at teeth also was significantly higher at baseline ( Ø 26.39 % ) and in the following years ( total 9.3 % ) . Implant survival rates were 100 % in periodontally healthy subjects versus 83.33 % in GAgP subjects . CONCLUSIONS This 10-year study showed that partially edentulous subjects treated for GAgP can be rehabilitated successfully with osseointegrated implants . However , the bone and attachment loss at the implants were higher than in periodontally healthy subjects PURPOSE In this prospect i ve multicenter clinical study , 1,179 3i st and ard threaded and self-tapping implants were followed for up to 6 years and monitored according to established success criteria . MATERIAL S AND METHODS A total of 493 patients ( 240 men and 253 women ) with a mean age of 45.1 years at implant surgery were enrolled at 6 research centers after being screened for exclusion criteria . Implants were placed according to a 2-stage surgical protocol with a minimum of 4 months of submerged healing in the m and ible and 6 months in the maxilla . Restorations included 633 prostheses , the majority of which were fixed partial dentures in the posterior m and ible or maxilla or single-tooth replacements in the anterior maxilla . RESULTS One hundred four implants ( 8.8 % ) did not meet success criteria and were design ated as failures , and 222 implants ( 18.8 % ) were lost to follow-up . The cumulative success rate according to life table methods was 91.1 % at 6 years . DISCUSSION Sixty percent of the failed implants were short ( < or = 10 mm long ) , and their cumulative success rate as a group at 6 years was 89.0 % , compared to 93.1 % for longer implants ( P < .05 ) . Thirty-three percent of all failures were implants placed in the posterior maxilla , for a 5-year cumulative success rate of 87.4 % . CONCLUSION It appears that limited bone dimensions and poor- quality bone have an impact on the performance of these machined-surface implants BACKGROUND Implant-supported restorations are a commonly used treatment modality . However , insufficient data are available that compare treatment outcomes of implant restorations using different protocol s. Similarly , data comparing the treatment outcomes of different implant design s are limited . METHODS This retrospective , non-r and omized study evaluates 241 single implants in 241 patients ( 127 males and 114 females ; mean age : 49.3 years ; range : 45 to 75 years ) . Tapered-type ( TAP ; n = 118 ) and cylindric screw-type ( CYL ; n = 123 ) implants were used . Implants were grouped into the treatment categories of immediate placement , delayed placement , immediate non-occlusal loading , and delayed loading . Clinical parameters , including clinical attachment level ( CAL ) , plaque index ( PI ) , and bleeding on probing ( BOP ) , were recorded at examinations at baseline ( BSL ) and 1 ( E1 ) , 3 ( E3 ) , and 5 years ( E5 ) after loading with the final restoration . RESULTS Eleven implants were lost ( five CYL and six TAP ) . CAL and PI outcomes were similar for both implant types . No significant influence of implant position was found . A CAL loss of 1.5 mm was observed during the first 3 years . The type of implant and timing of placement showed no significant influence on the survival rate , whereas the failure rate was lower for immediate non-occlusal loaded implants . CONCLUSION The type of implant , position , and timing of placement and loading did not influence the survival rate of this treatment method BACKGROUND The dual acid-etched ( DAE ) implant was commercially introduced in 1996 with a hybrid design incorporating a machined surface in the coronal region from approximately the third thread to the seating surface . This design was intended to reduce the risks of peri-implantitis and other related soft tissue complications that were reported for implants with surface roughness in the coronal region . The objective of this prospect i ve , r and omized-controlled clinical trial was to determine the incidence of peri-implantitis for a fully etched implant with the DAE surface extending to the implant platform . METHODS Patients had implant sites r and omly assigned to receive one hybrid control implant and at least one fully etched test implant in support of a short-span fixed restoration to ensure that variables ( e.g. , demographics , jaw locations , and bone density ) were consistent between groups . Prostheses were inserted 2 months after implant placement with follow-up evaluations scheduled annually for 5 years to assess mucosal health based on bleeding on probing , suppuration , and probing depths . Evaluations also included radiographic and mobility assessment s. RESULTS One hundred twelve patients who were enrolled at seven centers received 139 control and 165 test implants ( total : 304 implants ) . With > 5 years of postloading evaluations , there was one declaration of peri-implantitis associated with a control implant that was successfully treated later . Clinical probing and radiographic assessment s did not reveal differences between groups in mucosal health outcomes or other signs of peri-implantitis . CONCLUSION Five-year results of this r and omized-controlled study showed no increased risk of peri-implantitis for fully etched implants compared to hybrid- design ed implants PURPOSE The aim of the present study was to evaluate the periimplant conditions and the maintenance requirements for implant-supported overdentures in the m and ible retained with ball or bar attachments during a 5-year period . MATERIAL S AND METHODS Twenty-six completely edentulous patients had two Astra Tech dental implants placed in the anterior part of the m and ible . The denture attachment system for the patients was chosen r and omly by drawing lots . Eleven patients drew the bar attachment system and fifteen patients drew the ball attachment system . Plaque Index , Gingival Index , and probing pocket depth were assessed around each implant . Periotest values were recorded , and periodically identical intraoral radiographs were obtained with a specially design ed film-holding device . RESULTS No implants were lost from baseline to the 5-year registration . The periimplant conditions were very healthy after 5 years . No significant differences of the periimplant variables were recorded between the bar and the ball groups . During the first year of function , significantly more complications/repairs were registered in the bar group than in the ball group . In the following years , no significant differences were registered . The mean frequency of complications/repairs per patient per year was 1.0 in the bar group and 0.6 in the ball group during the 5-year observation period . CONCLUSION Two implants with ball or bar attachment supported an overdenture in the m and ible for 5 years with a 100 % survival rate . No differences in marginal bone loss or health of the periimplant mucosa were observed between bar and ball attachment , but the frequency of technical complications/repairs per patient was higher around bar than ball attachments BACKGROUND As a complement to the earlier reported 3-year results from a prospect i ve multicenter study of immediate and delayed placement of implants into fresh extraction sockets , the 5-year results are reported . PURPOSE The purpose of this 5-year report was to evaluate the immediate and long-term success of implants placed into fresh extraction sockets , with respect to implant size and type , bone quality and quantity , implant position , initial socket depth , and reason for tooth extraction . MATERIAL S AND METHODS This paper presents the 5-year results of the original 12 centers that participated with 143 consecutively included patients . A total of 264 implants were placed either immediately after tooth extraction or after a short soft-tissue healing time ( 3 - 5 weeks ) . The patients were divided into five subgroups , depending on the type of insertion method used . RESULTS The outcome demonstrated that the cumulative implant survival rate after 5 years of loading has not changed and remains 92.4 % in the maxilla and 94.7 % in the m and ible . No difference in failure rates can be seen between the groups when relating the failures to insertion method . CONCLUSION This prospect i ve study demonstrated that placing Brånemark implants into fresh extraction sites can be successful over a period of 5 years of loading . One of the outcomes of the study shows that there is a clinical correlation between implant failure and periodontitis as a reason for tooth extraction , even if it is difficult to give it a casual association . It can be hypothesized that periodontitis affected tissues might have a negative local influence because of the presence of infrabony defects that could possibly increase the gap between bone and implant or jeopardize achievement of primary stability OBJECTIVES The purpose of this study was to evaluate the survival rate , success rate and primary complications associated with m and ibular fixed implant-supported rehabilitations with distal cantilevers over 5 years of function . MATERIAL AND METHODS In this prospect i ve multi-center trial , 45 fully edentulous patients were treated with implant-supported m and ibular hybrid prostheses with distal extension cantilevers . Data were collected at numerous time points , including but not limited to : implant placement , abutment placement , final prosthesis delivery , 3 months and 5 years post-loading . Biological , implant and prosthetic parameters defining survival and success were evaluated for each implant including : sulcus bleeding ndex ( SBI ) at four sites per implant , width of facial and lingual keratinized gingiva ( mm ) , peri-implant mucosal level ( mid-facial from the top of the implant collar , measured in mm ) , modified plaque index ( MPI ) at four sites per implant , mobility and peri-implant radiolucency . Survival was defined as implants or prostheses that did not need to be replaced . Success rate was defined as meeting well-established criteria that were chosen to indicate healthy peri-implant mucosa osseointegration , prostheses success and complications . RESULTS A total of 237 implants in 45 completely edentulous patients were included in the study . In each patient , four to six implants were placed to support hybrid prostheses with distal cantilevers . Cantilevers ranged in length from 6 to 21 mm , with an average length of 15.6 mm . The ages of the patients ranged from 34 to 78 with a mean age of 59.5 years . The survival rate of implants was 100 % ( 237/237 ) and for prostheses 95.5 % ( 43/45 ) . The overall treatment success rate was calculated as 86.7 % ( 39/45 ) . Of the six patients that have not met the criteria for success , two patients required replacement of the entire prosthesis and four patients presented > four complications events . CONCLUSION Fixed implant-supported rehabilitation with distal cantilever result ed in a reliable treatment modality over the 5-year observation period . Although biological parameters of MPI , SBI , keratinized tissue and peri-implant mucosal levels showed statistically significant differences over time , the mean values for each patient remained within the normal limits of oral health . Complications were categorized as biological or technical . The majority of complications were technical complications ( 54/79 ) and of these most involved fracture of the acrylic teeth and base ( 20/54 ) . While the survival rate was 100 % for implants and 95.5 % for prostheses , the application of strict criteria for treatment success result ed in an overall treatment success rate of 86.7 % OBJECTIVES The aims of this study were to ( 1 ) compare prospect ively the clinical and radiographic changes in periodontal and peri-implant conditions , ( 2 ) investigate the association of changes in periodontal parameters and peri-implant conditions over a mean observation period of 10 years ( 8 - 12 years ) after implant installation , and ( 3 ) evaluate patient risk factors known to aggravate the periodontal conditions for their potential influence on the peri-implant tissue status . MATERIAL S AND METHODS Eighty-nine partially edentulous patients with a mean age of 58.9 years ( 28 - 88 years ) were examined at 1 and 10 years after implant placement . The patients contributed with 179 implants that were placed after comprehensive periodontal treatment and restored with crowns or fixed partial dentures . One hundred and seventy-nine matching control teeth were chosen as controls . Also , the remaining teeth ( n=1770 ) in the dentitions were evaluated . Data on smoking habits and general health aspects were collected at 1 and 10 years as well . RESULTS At 10 years , statistically significant differences existed between implants and matching control teeth with regard to most of the clinical and radiographic parameters ( P<0.01 ) with the exception of plaque index ( PII ) and recession . Multiple regression analyses were performed to associate combinations of periodontal diagnostic parameters to the peri-implant conditions : probing attachment level ( PAL ) at implants at 10 years was associated with implant location , full-mouth probing pocket depth ( PPD ) and full-mouth PAL ( P=0.0001 , r2=0.36 ) . PPD at implants at 10 years correlated to implant location , full-mouth PPD and full-mouth PAL ( P<0.001 , r2=0.47 ) . Marginal bone level at implants at 10 years was significantly associated to smoking , general health condition , implant location , full-mouth PAL and change over time in full-mouth PPD ( P<0.001 , r2=0.39 ) . CONCLUSIONS These results present evidence for the association between periodontal and peri-implant conditions and the changes in these tissues over 10 years in partially edentulous patients BACKGROUND Documentation of early loading of m and ibular overdentures supported by different implant systems is scarce . PURPOSE This study aim ed to compare the biologic and prosthetic outcome of m and ibular overdentures supported by unsplinted early-loaded one- and two-stage oral implants after 5 years of function . MATERIAL S AND METHODS Twenty-eight consecutive patients were screened following an inclusion and exclusion criteria , and r and omly allocated to treatment groups . Ball-retained m and ibular overdentures were fabricated on two unsplinted Straumann ( Institut Straumann AG , Basel , Switzerl and ) and Brånemark ( Nobel Biocare AB , Göteborg , Sweden ) dental implants and subjected to an early-loading protocol . During the 5-year period , prosthetic complications were recorded . At 5-years of function , plaque , peri-implant inflammation , bleeding , and calculus index scores were recorded , and st and ard periapical radiographs were obtained from each implant for measurement of marginal bone loss . RESULTS All implants survived during the observation period . The peri-implant inflammation , bleeding , and calculus index scores around Straumann and Brånemark implants were similar ( p > .05 ) . The marginal bone loss around Brånemark implants ( 1.21 + /- 0.1 ) was higher than Straumann implants ( 0.73 + /- 0.06 ) at 5 years of function ( p = .002 ) . Kaplan-Meier tests revealed that 1- and 5-year survival of overdentures on Straumann and Brånemark implants were similar ( p = .85 ) . Wear of the ball abutment in the Brånemark group was higher than in the Straumann group ( p < .05 ) . Complications regarding the retainer and the need for occlusal adjustments were higher in the Straumann group ( p < .05 ) . Chi-square test revealed that the frequency of retightening of the retainer was higher in the Straumann group than in the Brånemark group ( p < .05 ) . CONCLUSIONS M and ibular overdentures supported by unsplinted early-loaded Straumann and Brånemark implants lead to similar peri-implant soft tissue and prosthetic outcomes , although higher marginal bone loss could be observed around Brånemark implants after 5 years PURPOSE The goal of this multicenter prospect i ve clinical trial was to compare clinical outcome and post-treatment care and patient satisfaction with different implant systems used for m and ibular overdenture treatment during a 6-year follow-up period . PATIENTS AND METHODS A total of 87 edentulous patients with a severely resorbed m and ible ( bone height , 8 to 15 mm ) received treatment involving either 2 Intra Mobiele Zylinder implants ( IMZ group , n = 41 ) ( Friedrichsfeld AG , Mannheim , Germany ) , 2 Brånemark implants ( Brå group , n = 17 ) ( Nobel Biocare AB , Gothenburg , Sweden ) or a Transm and ibular Implant ( TMI ; Krijnen Medical , Beesd , The Netherl and s ) ( TMI group , n = 29 ) . The evaluation involved clinical parameters , radiographs , surgical and prosthetic post-treatment care , clinical implant performance ( CIP scale ) , and patient satisfaction . RESULTS After 6 years , there was a significant difference in the mean plaque index : the mean plaque index of the TMI group was significantly higher than that of the IMZ and Brå groups . Other clinical parameters showed no significant differences . The implant survival rate of 97.5 % was noted in the IMZ group , 97.1 % in the Brå group , and 72.0 % in the TMI group . The CIP scale were significantly worse for the TMI group . CONCLUSION It was concluded that the IMZ and the Brånemark implant systems have a better survival rate and clinical implant performance than the TMI system . Based on these data , these systems should be the choice for the edentulous m and ible with a height between 8 and 15 mm The aim of this study was to longitudinally follow up osseointegrated titanium implants in partially dentate patients by clinical , radiographic and microbiological parameters in order to evaluate possible changes in the peri-implant health over time . Fifteen individuals treated with titanium implants , ad modum Brånemark , and followed for ten years were included in the study . Before implant placement ten years previously , the individuals had been treated for advanced periodontal disease and thereafter been included in a maintenance care program . The survival rate of the implants after ten years was 94.7 % . The bone loss was 1.7 mm when using the abutment-fixture junction as a reference point . Of the individuals , 50 % were positive for plaque at the implants . Bleeding on sulcus probing was present at 61 % of the implant surfaces . Ten years previously , the individuals had been carriers of putative periodontal pathogens , such as Porphyromonas gingivalis , Prevotella intermedia , Actinobacillus actinomycetemcomitans , Capnocytophaga spp . and Campylobacter rectus , and were also carriers of these species at the current examination . The results of the present study suggest that the presence of these putative periodontal pathogens at implants may not be associated with an impaired implant treatment . These species are most likely part of the normal resident microbiota of most individuals and may therefore be found at r and om at both stable and progressing peri-implant sites OBJECTIVES The aim of this prospect i ve comparative study was to evaluate the survival rate and the condition of the peri-implant tissues of the IMZ implant system ( two-stage cylindertype ) , the Brånemark implant system ( two-stage screwtype ) and the ITI implant system ( one-stage screwtype ) supporting a m and ibular overdenture during a 5-year follow-up period . MATERIAL AND METHODS Three groups of 30 edentulous patients were treated with two endosseous implants in the interforaminal region of the m and ible . Clinical and radiographic parameters were evaluated immediately after completion of the prosthetic treatment and after 1 , 2 , 3 , 4 and 5 years of functional loading . RESULTS The five-year survival rate is 98.3 % for the IMZ group , 98.3 % for the Brå group and 100 % for the ITI group . Mean scores on indices for plaque , calculus , gingiva and bleeding were very low at all evaluation periods . Mean marginal bone loss over a period of 5 years , was 1.4 mm for the IMZ group , 0.7 mm for the Brå group and 0.9 mm for the ITI group . CONCLUSION It is concluded that two implants placed in the interforaminal region , connected with a bar , supply a proper base for the support of a m and ibular overdenture in the edentulous patient . After 5 years no clinical ly relevant and statistically significant radiographic changes had developed between the three implant systems BACKGROUND Comparatively few studies are available reporting at least 5 years of follow-up data of implant-supported single-tooth replacements . OBJECTIVE To evaluate prospect ively the 5-year outcome of implant-supported single-tooth prosthetic restorations . MATERIAL AND METHODS Forty subjects ( mean age 41 years ) , 23 males and 17 females , who required single-tooth prosthetic replacement for a missing tooth were recruited . A total of 45 self-tapping implants ( Astra Tech ST-implants)--40 in the maxilla and five in the m and ible -- were installed in a two-stage procedure . Abutment connection was performed 3 - 6 months after implant installation . Clinical and radiographic examinations were performed at the completion of the prosthetic treatment and once a year during a 5-year follow-up period . The analysis of peri-implant bone level alteration was performed on subject and implant levels and by the use of analysis of variance and binary logistic regression . RESULTS Three patients were lost during the 5 years of follow-up . One implant was lost after 2.5 years in function and another four implants could not be accounted for at the 5-year follow-up examination . The overall failure rate at 5 years was 2.6 % ( subject level ) and 2.3 % ( implant level ) . The mean loss of marginal bone at the implants during the first year in function was 0.06 mm ( SD 0.67 ) on the subject level and 0.02 mm ( 0.65 ) on the implant level . During the subsequent 4 years the annual change in peri-implant bone level amounted to -0.02 mm ( 0.22 ) on both subject and implant levels . Thus , the mean total bone level change over the 5-year interval was -0.14 mm ( 1.04 ) on subject level and -0.11 mm ( 1.00 ) on the implant level of analysis ( p>0.05 ) . The frequency of implants with a 5-year bone loss of > or = 1 mm was 13 % . Approximately 50 % of the implants demonstrated no bone loss . CONCLUSION The present clinical trial on single-tooth replacements with the Astra Tech implant system demonstrated that the bone loss during the first year of function as well as annually thereafter was small PURPOSE To compare the subgingival microbiota around two differently design ed implant systems that were in function for more than 12 years in a r and omised split-mouth study design , and to compare the outcome with natural dentition . MATERIAL S AND METHODS A total of 18 partially edentulous patients received at least two TiOblast ™ ( Astra Tech ) and two Brånemark ( Nobel Biocare ) implants following a split-mouth design . At the last follow-up visit , periodontal parameters ( probing depth , bleeding on probing and plaque ) were recorded and intraoral radiographs were taken to calculate bone loss . Subgingival plaque sample s were collected for culture , qPCR and checkerboard DNA-DNA hybridisation analysis . These data were related to implant design and bone loss . This study setup allowed a comparison of 34 Astra Tech ( Impl A ) with 32 Brånemark ( Impl B ) implants . RESULTS During the 12-year follow up , five patients dropped out . One Brånemark implant was lost before abutment connection in a dropout patient . Mean bone loss between loading and year 12 was 0.7 mm ( range : -0.8 - 5.8 ) ( Impl A ) , and 0.4 mm ( range : -1.1 - 4.1 ) ( Impl B ) . No significant microbiological differences ( qualitative and quantitative ) could be observed between both implant types . Compared to teeth , subgingival plaque sample s from implants did not reach the concentration of pathogens , even after 12 years of function . CONCLUSIONS These data show that both implant systems ( with differences in macro- design and surface characteristics ) , in patients with good oral hygiene and a stable periodontal condition , can maintain a successful treatment outcome without significant subgingival microbiological differences after 12 years of loading . The presence of periodontopathogens did not necessarily result in bone loss Thirty-six completely edentulous patients were enrolled for a 5-year prospect i ve study testing the treatment outcome between splinted and unsplinted implants retaining a m and ibular hinging overdenture . The patients were r and omized into 3 groups of equal size depending on the attachment system used such as : magnets , ball attachments or bars ( reference group ) . Only 1 implant out of the 72 had failed at the abutment stage . Not a single implant failed during the 5-year loading period . The accumulation of plaque was significantly higher for the Magnet than for the Ball group . Bleeding on probing , as well as marginal bone level , attachment level and Periotest values did not statistically differ among the groups , neither at year 1 nor at year 5 . However , the Periotest values were significantly lower at year 5 compared to year 1 for all groups , which indicates a higher rigidity at the bone-implant interface . No correlation was found between bleeding on probing and marginal bone loss . We conclude that the connection state of 2 implants retaining a hinging overdenture did not influence the peri-implant outcome BACKGROUND The aim of this study was to evaluate the feasibility of using a two-piece implant system in a non-submerged procedure and to study the impact of the microgap between the implant and abutment . METHODS Sixty edentulous patients ( Cawood Class V-VI ) participated in this study . After r and omization , 20 patients received two two-piece implants placed in a non-submerged procedure , 20 patients received two two-piece implants placed in the traditional submerged procedure , and 20 patients were treated with two one-piece dental implants placed in the traditional non-submerged procedure . The implants were placed in the m and ible for overdenture treatment . A st and ardized clinical evaluation was performed and radiographs were taken immediately after denture insertion and yearly up to 5 years . Peri-implant sample s were collected 12 , 36 , and 60 months after loading with sterile paper points and analyzed for the presence of putative periodontal pathogens using culture techniques . RESULTS One two-piece implant of the non-submerged group and one two-piece implant of the submerged group were lost after 6 and 12 months , respectively . After 5 years of functioning , no significant clinical , radiological , or microbiological differences were found between the three groups . No association was found between the level of the microgap and the amount of bone loss . CONCLUSIONS The results of this study indicate that dental implants design ed for a submerged implantation procedure can also be used in a non-submerged procedure and may be as predictable as when used in a submerged procedure or as one-piece implants . The microgap at the crestal level in two-piece implants does not appear to have an adverse effect on the amount of peri-implant bone loss PURPOSE The aim of this prospect i ve study was to present the results after 5 years of loading of 65 CeraOne ( Nobel Biocare ) crowns . MATERIAL S AND METHODS Sixty-two implants in the maxilla and 3 implants in the m and ible were placed in 57 patients . Sixty-two all-ceramic and three metal-ceramic crowns were cemented . The group comprised the first patients treated with the CeraOne prosthodontic concept . RESULTS Eight patients did not complete the study . Only one implant failed , giving a cumulative success rate for implants of 98.5 % . The failed implant was replaced : a crown was cemented and then followed for 5 years without any complications . Four crowns were recorded as failures , giving a cumulative success rate for crowns of 93.7 % . It should be observed that this result was very positive , as all crown failures were related to extraordinary causes and not one was a result of common bite forces or fatigue . The initial bone loss was in accordance with other studies on Brånemark implants , and a stable situation was recorded after 2 years for the supporting bone around implants and adjacent teeth when the conical implants were excluded . Soft tissues around implants and adjacent teeth appeared healthy , and the cementation and the placement of the abutment shoulder in the peri-implant sulcus did not cause any recession of the peri-implant mucosa . CONCLUSION CeraOne experienced virtually no complications and proved to be a highly predictable and safe prosthodontic concept . CeraOne also eliminated problems with abutment screw loosening and created a platform for good esthetic results and satisfied patients |
13,337 | 16,437,478 | Ibuprofen reduces urine output .
Prophylactic use of ibuprofen reduces the incidence of PDA , the need for rescue treatment with cyclo-oxygenase inhibitors and surgical closure .
Prophylactic treatment therefore exposes a large proportion of infants unnecessarily to a drug that has important side effects ( mainly involving the kidneys ) without conferring any important short term benefits . | BACKGROUND A patent ductus arteriosus ( PDA ) often complicates the clinical course of preterm infants and increases the risk of intraventricular hemorrhage ( IVH ) , necrotizing enterocolitis ( NEC ) , chronic lung disease ( CLD ) and death .
The st and ard treatment to close a PDA is indomethacin .
Its use is associated with renal , gastrointestinal and cerebral side-effects .
Ibuprofen has been shown to be effective in closing a PDA without reducing blood flow velocity to the brain , gut or kidneys .
OBJECTIVES To determine the effectiveness and safety of prophylactic ibuprofen compared to placebo/no intervention or other cyclo-oxygenase inhibitor drugs ( indomethacin , mefenamic acid , etc ) in the prevention of PDA in preterm infants . | A prospect i ve r and omized controlled trial was performed to compare the effects of ibuprofen with indomethacin on cerebral hemodynamics measured using near infrared spectroscopy in preterm infants during treatment for patent ductus arteriosus . Infants were r and omly assigned to three intravenous doses of either indomethacin ( 0.20–0.25 mg/kg , 12 hourly ) or ibuprofen ( 5–10 mg/kg , 24 hourly ) and also received a dose of saline . The primary end points of the study were the effects of the first dose on cerebral blood flow ( CBF ) and cerebral blood volume . Fifteen infants received indomethacin and 18 received ibuprofen . The group mean ( SD ) values for CBF ( mL·100 g−1·min−1 ) before and after the first dose of indomethacin were 13.6 ( 4.1 ) and 8.3 ( 3.1 ) , respectively , the change being significant ( p < 0.001 ) . In contrast , no significant changes in CBF were observed with the first dose of ibuprofen , the respective before and after values being 13.3 ( 3.2 ) and 14.9 ( 4.7 ) mL·100 g−1·min−1 . The median ( interquartile range ) value for change in cerebral blood volume ( mL/100 g ) after the first dose in the indomethacin group was −0.4 ( −0.3 to −0.6 ) and in the ibuprofen group was 0.0 ( 0.1 to −0.1 ) , the difference between the two groups being significant ( p < 0.001 ) . Cerebral oxygen delivery changed significantly after the first dose in the indomethacin group but not in the ibuprofen group . Significant reductions in CBF , cerebral blood volume , and cerebral oxygen delivery also occurred after the 24-h dose of indomethacin , but there were no significant changes after the 48-h dose of saline in the indomethacin group or after the 24- and 48-h doses of ibuprofen . The patent ductus arteriosus closure rates after indomethacin and ibuprofen were 93 and 78 % , respectively . We conclude that ibuprofen , unlike indomethacin , has no adverse effects on cerebral hemodynamics and appears to mediate patent ductus arteriosus closure The effect of repeated doses of indomethacin on mean peak velocity ( MPV ) and time-averaged mean velocity in the middle cerebral artery was assessed in 10 ventilated neonates with a patent ductus arteriosus using colour/duplex Doppler technique prior to , and 10 , 30 , and 120 min after the first and the third dose . Velocities were significantly reduced up to 120 min after the first dose . The third dose result ed in a significant reduction in MPV at 10 and 30 min following treatment . This reduction was half of that observed after the first dose . Systemic blood pressure ( BP ) and heart rate did not change significantly after each separate dose . However , by the third dose , mean and diastolic BP were significantly increased from pretreatment levels . The attenuated response of cerebral blood flow ( CBF ) velocities to the third dose of indomethacin compared with the first dose is probably related to altered haemodynamics . Indomethacin should be used cautiously in infants with other conditions which are known to decrease CBF such as hypotension , hypocarbia and polycythaemia OBJECTIVE To determine whether a course of low-dose indomethacin therapy , when initiated within 24 hours of birth , would decrease ductal shunting in premature infants who received prophylactic surfactant in the delivery room . DESIGN Ninety infants , with birth weights of 600 to 1250 gm , were entered into a prospect i ve , r and omized , controlled trial to receive either indomethacin , 0.1 mg/kg per dose , or placebo less than 24 hours and again every 24 hours for six doses . Echocardiography was performed on day 1 before treatment and on day 7 , 24 hours after treatment . A hemodynamically significant patent ductus arteriosus ( PDA ) was confirmed with an out-of- study echocardiogram , and the nonresponders were treated with st and ard indomethacin or ligation . RESULTS Forty-three infants received indomethacin ( birth weight , 915 + /- 209 gm ; gestational age , 26.4 + /- 1.6 weeks ; 25 boys ) , and 47 received placebo ( birth weight , 879 + /- 202 gm ; gestational age , 26.4 + /- 1.8 weeks ; 22 boys ) ( P = not significant ) . Of 90 infants , 77 ( 86 % ) had a PDA by echocardiogram on the first day of life before study treatment ; 84 % of these PDAs were moderate or large in size in the indomethacin-treated group compared with 93 % in the placebo group . Nine of forty indomethacin-treated infants ( 21 % ) were study -dose nonresponders compared with 22 ( 47 % ) of 47 placebo-treated infants ( p < 0.018 ) . There were no significant differences between both groups in any of the long-term outcome variables , including intraventricular hemorrhage , duration of oxygen therapy , endotracheal intubation , duration of stay in neonatal intensive care unit , time to regain birth weight or reach full caloric intake , incidence of bronchopulmonary dysplasia , and survival . No significant differences were noted in the incidence of oliguria , elevated plasma creatinine concentration , thrombocytopenia , pulmonary hemorrhage , or necrotizing enterocolitis . CONCLUSION The prophylactic use of low doses of indomethacin , when initiated in the first 24 hours of life in low birth weight infants who receive prophylactic surfactant in the delivery room , decreases the incidence of left-to-right shunting at the level of the ductus arteriosus OBJECTIVE The authors evaluated the risk of necrotizing enterocolitis ( NEC ) in very low birth weight infants receiving indomethacin ( INDO ) to close patent ductus arteriosus ( PDA ) . BACKGROUND DATA Controversy exists regarding the best method of managing very low birth weight infants with PDA and whether to employ medical management using INDO or surgical ligation of the ductus . METHODS Two hundred fifty-two premature infants with symptomatic PDA were given intravenously INDO 0.2 mg/kg every 12 hours x 3 in an attempt to close the ductus . Patients were evaluated for sex , birth weight , gestational age , ductus closure , occurrence of NEC , bowel perforation , and mortality . RESULTS There were 135 boys and 117 girls . The PDA closed or became asymptomatic in 224 cases ( 89 % ) , whereas 28 ( 11 % ) required surgical ligation . Ninety infants ( 35 % ) developed evidence of NEC after INDO therapy . Fifty-six were managed medically ; surgical intervention was required in 34 of 90 cases ( 37.8 % ) or 13 % of the entire PDA/INDO study group . Bowel perforation was noted in 27 cases ( 30 % ) . Factors associated with the onset of NEC included gestational age < 28 weeks , birth weight < 1 kg , and prolonged ventilator support . The overall mortality rate was 25.5 % , but was higher in infants with NEC versus those without . The highest mortality was noted in perforated NEC cases . The PDA/INDO patients were compared with a control group of 764 infants with similar sex distribution , birth weights , and gestational ages without PDA who did not receive INDO . Necrotizing enterocolitis occurred in 105 of 764 control patients ( 13.7 % ) , including 13 ( 12.3 % ) with perforation . The overall mortality rate of controls was 25 % , which was similar to the overall 25.5 % mortality rate in the PDA/INDO study group . CONCLUSION These data indicate that there is increased risk of NEC and bowel perforation in premature infants with PDA receiving INDO . Mortality was higher in the PDA/INDO group with NEC than those PDA/INDO infants without NEC In the course of a double-blind trial of intravenous indomethacin therapy in premature infants with patent ductus arteriosus , renal function and urinary kallikrein were studied in 21 infants following one dose of either saline placebo or indomethacin . Ten infants were assigned to the control group and 11 were in the indomethacin group . Significantly lower urine output , fraction excretion of sodium , fraction excretion of chloride , and urinary kallikrein were noted by 45 % , 59 % , 63 % , and 51 % , respectively , in the indomethacin group as compared to the control group . There was a concomitant decrease in serum sodium concentration ( P less than .05 ) at 24 hours following indomethacin therapy . No significant difference in glomerular filtration rate was seen between the control group and the indomethacin-treated infants Near infrared spectroscopy was used to investigate the effects of intravenously administered indomethacin ( 0.1 - 0.2 mg/kg ) on cerebral haemodynamics and oxygen delivery in 13 very preterm infants treated for patent ductus arteriosus . 7 infants received indomethacin by rapid injection ( 30 s ) and 6 by slow infusion ( 20 - 30 min ) . In all the infants cerebral blood flow , oxygen delivery , blood volume , and the reactivity of blood volume to changes in arterial carbon dioxide tension fell sharply after indomethacin . There were no differences in the effects of rapid and slow infusion . These falls in cerebral oxygen delivery and the disruption of cerebrovascular control might compromise cellular oxygen availability , particularly in regions of the brain where the arterial supply is precarious . Care should be taken to ensure that oxygen delivery is optimum before the administration of indomethacin to preterm infants OBJECTIVE To evaluate the effect of intravenous ibuprofen and indomethacin for treatment of patent ductus arteriosus ( PDA ) on mesenteric and renal blood flow velocity in preterm infants . STUDY DESIGN Seventeen mechanically ventilated preterm infants ( <33 weeks ' gestation ) with PDA received either 0.2 mg/kg indomethacin ( n = 8) or 10 mg/kg ibuprofen ( n = 9 ) , infused over 15 minutes . Mesenteric and renal blood flow velocity were measured by using Doppler ultrasonography . RESULTS Indomethacin caused a significant reduction in mesenteric and renal blood flow velocity 30 minutes after drug administration ; mesenteric and renal blood flow velocity did not return to the pretreatment values by 120 minutes . Ibuprofen did not alter blood flow 30 minutes after treatment , and blood flow increased 120 minutes after treatment . Mesenteric and renal blood flow velocity changes were significantly different between the 2 treatment groups . CONCLUSIONS Compared with indomethacin , ibuprofen did not significantly reduce mesenteric and renal blood flow velocity |
13,338 | 22,983,474 | Also , the public display of the distribution of responses either reaffirms their underst and ing or can be used to help gauge the learner ’s own responses against the group norm .
However , a recent r and omized , controlled study in the continuingmedical education ( CME ) setting failed to show improved knowledge-gain from ARS versus the traditional didactic lecture environment ( 9 ) . | Electronic-response systems ( ERS ) or audience-response systems ( ARS ) can be powerful instructional tools .
Since the earliest adoption of ARS in the mid-1960s , the technology has changed significantly , especially in recent years , with advances in wireless communications .
Over the years , ARS has become more sophisticated , more userfriendly , and cheaper .
Typical ARS technology now allows instructors to present questions to the audience , and individual audience members respond with a keypad ; responses are then automatically tabulated and displayed in a variety of graphic formats on-screen for feedback to the group .
The tool is similar to that of the TV show “ Who Wants to Be a Millionaire ? ”
where every member of the audience transmits his or her response , and the distribution of responses is displayed on-screen .
According to a recent study , the diffusion of this instructional technology is so widespread now that almost all universities in the United States and over 3,000 schools at the primary and secondary levels are currently using ARS ( 1 ) .
To increase learner-engagement , medical education and health-profession education , in general , including many continuing medical education programs are increasingly turning to ARS as a tool to promote learner participation and create an interactive learning environment ( 2 , 3 ) .
ARS cl aims to promote student participation and engagement through elicitation of content-underst and ing and creating a safer , anonymous environment for learners to participate freely without fear of embarrassment or being singled out .
The purpose of this review is to provide a theoretical framework for underst and ing the context for the intended and unintended consequences of using ARS .
This thematic review presents the findings from the literature in the context of existing learning theories and assessment models to help build upon the previous literature review s. Although use of ARS has grown rapidly over the last decade , reports on efficacy of the technology have mostly focused on perceived benefits to learners , with the exception of a small number of studies on knowledge-retention , which showed inconsistent results ( 6 ) .
Recent studies from both health-profession education and higher-education setting s have reported significant improvement in learning and knowledge-retention ( 7 , 8) .
Despite widespread adoption in certain fields ( 5 , 10 ) , there is limited systematic review of the impact of ARS on instruction and learning outcomes . | Background Electronic Voting Systems have been used for education in a variety of disciplines . Outcomes from these studies have been mixed . Because results from these studies have been mixed , we examined whether an EVS system could enhance a lecture 's effect on educational outcomes . Methods A cohort of 127 Year 5 medical students at the University of Adelaide was stratified by gender , residency status and academic record then r and omised into 2 groups of 64 and 63 students . Each group received consecutive 40-minute lectures on two clinical topics . One group received the EVS for both topics . The other group received traditional teaching only . Evaluation was undertaken with two , 15- question multiple-choice question naires ( MCQ ) assessing knowledge and problem solving and undertaken as a written paper immediately before and after the lectures and repeated online 8–12 weeks later . St and ardised institutional student question naires were completed for each lecture and independent observers assessed student behaviour during the lectures . Lecturer 's opinions were assessed by a question naire developed for this study . Results Two-thirds of students r and omised to EVS and 59 % of students r and omised to traditional lectures attended . One-half of the students in the EVS group and 41 % in the traditional group completed all question naires . There was no difference in MCQ scores between EVS and traditional lectures ( p = 0.785 ) . The cervical cancer lectures showed higher student ranking in favour of EVS in all parameters . The breast cancer lectures showed higher ranking in favour of traditional lectures in 5 of 7 parameters ( p < 0.001 ) . The observed higher-order lecturer-students interactions were increased in the EVS lecture for one lecturer and reduced for the other . Both lecturers felt that the EVS lectures were difficult to prepare , that they were able to keep to time in the traditional lectures , that the educational value of both lecture styles was similar , and that they were neutral-to-slightly favourably disposed to continue with the EVS technology . The 2 lecturers disagreed regarding the ease of preparation of the traditional lecture , their ability to keep to time in the EVS lecture , and personal satisfaction with the EVS lecture . The lecturers felt that EVS encouraged student participation and helped identify where students were having difficulty . Conclusion In this setting , EVS technology used in large group lectures did not offer significant advantages over the more traditional lecture format Background Electronic voting systems have been used in various educational setting s with little measurement of the educational impact on students . The goal of this study was to measure the effects of the inclusion of an electronic voting system within a small group tutorial . Method A prospect i ve r and omised controlled trial was run at the Royal Adelaide Hospital , a teaching hospital in Adelaide , Australia . 102 students in their first clinical year of medical school participated in the study where an electronic voting system was introduced as a teaching aid into a st and ard tutorial . Long-term retention of knowledge and underst and ing of the topics discussed in the tutorials was measured and student response to the introduction of the electronic voting system was assessed . Results Students using the electronic voting system had improved long-term retention of underst and ing of material taught in the tutorial . Students had a positive response to the use of this teaching aid . Conclusion Electronic voting systems can provide a stimulating learning environment for students and in a small group tutorial may improve educational outcomes Background : Teaching methods that provide an opportunity for individual engagement and focussed feedback are required to create an active learning environment for case-based teaching in large groups . Aims : A prospect i ve observational controlled study was conducted to evaluate whether the use of an audience response system ( ARS ) would promote an active learning environment during case-based discussion s in large groups , have an impact on student motivation and improve long-term retention . Methods : Group A ( N = 83 ) participated in large group case discussion s where student participation was voluntary , while for group B ( N = 86 ) an ARS was used . Data collection methods included student and teacher surveys , student focus group interviews , independent observations and 1-year post-course testing . Results : Results indicated that the use of an ARS provided an active learning environment during case-based discussion s in large groups by favouring engagement , observation and critical reflection and by increasing student and teacher motivation . Although final exam results were significantly improved in group B , long-term retention was not significantly different between groups . Conclusions : It was concluded that ARS use significantly improved the learning experience associated with case-based discussion s in a large group of undergraduate students Introduction : Continuing medical education ( CME ) for physicians and other health personnel is becoming increasingly important in light of recertification requirements . Interactive learning is more effective and may be useful in a continuing education setting . This study examines the use of an audience response system ( ARS ) as an interactive learning tool for health care providers . Method : We conducted a national r and omized controlled trial to evaluate the utility of an ARS to enhance attention and learning . Speakers at 42 clinical round table ( CRT ) programs in five regions across the United States were r and omized to “ use ” or “ no use ” of an ARS during their lectures . We surveyed participants to collect data regarding presentation and speaker quality , impressions of the ARS , and knowledge of the material presented . We collected information from speakers regarding ease of use and overall opinions of the ARS . Results : A total of 283 surveys were completed ( 164 from participants using the ARS and 119 from participants not using the ARS ) . ARS participants rated the quality of the presentation , the quality of the speaker , and their level of attention more highly than non‐ARS participants ( p < .05 ) . Knowledge scores ( of material presented ) were not significantly different between the two groups . Both participants and speakers felt that the ARS was easy to use and preferred to use the system in future CRTs . Discussion : Participants in CRTs with the ARS rated presentation and speaker quality more favorably than those participants in CRTs without the tool . Participant knowledge scores , however , were not significantly different . ARSs may provide easy‐to‐use tools to enhance attention and enthusiasm in CME learners BACKGROUND AND OBJECTIVES The use of an electronic audience response system ( ARS ) that promotes active participation during lectures has been shown to improve retention rates of factual information in nonmedical setting s. This study ( 1 ) tested the hypothesis that the use of an ARS during didactic lectures can improve learning outcomes by family medicine residents and ( 2 ) identified factors influencing ARS-assisted learning outcomes in family medicine residents . METHODS We conducted a prospect i ve controlled crossover study of 24 family medicine residents , comparing quiz scores after didactic lectures delivered either as ordinary didactic lectures that contained no interactive component , lectures with an interactive component ( asking questions to participants ) , or lectures with ARS . RESULTS Post-lecture quiz scores ( maximum score 7 ) were 4.25 + /- 0.28 ( 61 % correct ) with non-interactive lectures , 6.50 + /- 0.13 ( n=22 , 93 % correct ) following interactive lectures without ARS , and 6.70 + /- 0.13 ( n=23 , 96 % correct ) following ARS lectures . The difference in scores following ARS or interactive lectures versus non-interactive lectures was significant ( P < .001 ) . Mean quiz scores declined over 1 month in all three of the lecture groups but remained highest in the ARS group . Neither lecture factors ( monthly sequence number ) nor resident factors ( crossover group , postgraduate training year , In-Training Examination score , or post-call status ) contributed to these differences , although postcall residents performed worse in all lecture groups . CONCLUSIONS Both audience interaction and ARS equipment were associated with improved learning outcomes following lectures to family medicine residents OBJECTIVE In an era of increasing clinical volume and longer workdays , the time devoted to education may be diminished in many medical centers . The goal of our study was to develop techniques for optimizing educational time . SUBJECTS AND METHODS Radiology residents in our program were r and omized into two groups stratified by level of training . The control group received a st and ard didactic midday lecture , and the experimental group received the identical lecture material with an audience response system integrated into the lecture delivery . RESULTS The group who used the interactive audience response software had significantly higher learning ( p = 0.02 ) and long-term retention ( p = 0.001 ) scores on postlecture quizzes administered to both groups of residents on the day of the lecture and 3 months later . CONCLUSION Use of appropriate interactive teaching techniques facilitates residents ' learning and retention of material . In our study , long-term retention was especially improved with use of an interactive lecture style Student performance was compared on written and psychomotor skill tests of freshman dental students receiving conventional lectures versus the same lectures containing interactive components using TurningPoint , a wireless audience response system ( ARS ) . The research design was a controlled crossover study with seventy-seven freshman dental students conducted in a pre clinical operative dentistry course . Two r and omized groups alternated the two study lectures , one with ARS and the other without ARS . Student knowledge retention was measured through written examination using immediate posttest , as well as questions on the unit and final examinations . Psychomotor skill tests were given on both lecture topics . Statistically significant differences indicating superiority of ARS were identified for performance on the immediate posttest and psychomotor skill test only for the lecture " Principles of Dental Bonding . " The other examinations/skill testing showed no significant difference . These results indicate that ARS is a promising teaching tool for dental education OBJECTIVE The purpose of the study was to compare delivery methods of lecture material regarding contraceptive options by either traditional or interactive lecture style with the use of an audience response system with obstetrics and gynecology residents . STUDY DESIGN A prospect i ve , r and omized controlled trial that included 17 obstetrics and gynecology residents was conducted . Group differences and comparison of pre/posttest scores to evaluate efficacy of lecture styles were performed with the Student t test . Each participant completed an evaluation to assess usefulness of the audience response system . RESULTS Residents who received audience response system interactive lectures showed a 21 % improvement between pretest and posttest scores ; residents who received the st and ard lecture demonstrated a 2 % improvement ( P = .018 ) . The evaluation survey showed that 82 % of residents thought that the audience response system was a helpful learning aid . CONCLUSION The results of this r and omized controlled trial demonstrate the effectiveness of audience response system for knowledge retention , which suggests that it may be an efficient teaching tool for residency education |
13,339 | 30,756,163 | Conclusions Our study is the first meta- analysis comparing anastomoses in LDG and introduces novel criteria for consideration when selecting reconstructions in LDG . | Background In this modern era , laparoscopic distal gastrectomy ( LDG ) has largely replaced open distal gastrectomy for the treatment of gastric cancer ; however , a quantitative review of reconstruction methods applied exclusively using LDG has not yet been published .
Thereafter , we compared three reconstruction methods ( Billroth I , Billroth II , and Roux-en Y ) using the data derived solely from LDG patients . | AIM To identify which technique is better for avoiding biliary reflux and gastritis between uncut Roux-en-Y and Billroth II reconstruction . METHODS A total of 158 patients who underwent laparoscopy-assisted distal gastrectomy for gastric cancer at the First Hospital of Jilin University ( Changchun , China ) between February 2015 and February 2016 were r and omized into two groups : uncut Roux-en-Y ( group U ) and Billroth II group ( group B ) . Postoperative complications and relevant clinical data were compared between the two groups . RESULTS According to the r and omization table , each group included 79 patients . There was no significant difference in postoperative complications between groups U and B ( 7.6 % vs 10.1 % , P = 0.576 ) . During the postoperative period , group U stomach pH values were lower than 7 and group B pH values were higher than 7 . After 1 year of follow-up , group B presented a higher incidence of biliary reflux and alkaline gastritis . However , histopathology did not show a significant difference in gastritis diagnosis ( P = 0.278 ) , and the amount of residual food and gain of weight between the groups were also not significantly different . At 3 mo there was no evidence of partial recanalization of uncut staple line , but at 1 year the incidence was 13 % . CONCLUSION Compared with Billroth II reconstruction , uncut Roux-en-Y reconstruction is secure and feasible , and can effectively reduce the incidence of alkaline reflux , residual gastritis , and heartburn . Despite the incidence of recanalization , uncut Roux-en-Y should be widely applied To determine the clinical efficacy of Roux-en-Y reconstruction ( RY ) after distal gastrectomy , we compared postoperative outcomes of patients who underwent RY or conventional Billroth I reconstruction ( B-I ) . A total of 50 patients were prospect ively r and omized to either B-I or RY reconstruction , and complications , postoperative course , and nutritional status were compared . Bile reflux and inflammation in the remnant stomach and lower esophagus were evaluated by postoperative follow-up endoscopy at 6 months . Operative time and blood loss as well as postoperative nutrition did not show significant differences between the two groups . As anticipated , 5 of 24 patients with RY reconstruction developed gastrojejunal stasis in the early postoperative period , which led to a longer postoperative hospital stay as compared with the B-I group ( mean ± S.D ; B-I ; 19.0 ± 6.2 , RY ; 31.8 ± 21.7 days ) ( P < 0.05 ) . Endoscopic examination revealed that the frequency of bile reflux ( P < 0.01 ) and degree of inflammation in the remnant stomach ( P < 0.05 ) were less in the RY group than in the B-I group . However , inflammatory findings in the lower esophagus were observed in 7 ( 27 % ) of B-I , and 8 ( 35 % ) of the RY group , suggesting that late phase esophagitis was not improved in the RY group . Roux-en-Y reconstruction was effective in preventing duodenogastric reflux and result ing gastritis , but it did not prevent esophagitis . Because RY reconstruction induces the frequent complication of Roux-en-Y stasis , causing longer postoperative hospital stay , this method has limited advantages over B-I anastomosis after distal gastrectomy Purpose The Roux en Y method has rarely been performed due to longer operation time and high risk of complication , despite several merits including prevention of bile reflux . We conducted a retrospective review of the result of Roux en Y reconstruction using two circular staplers after subtotal gastrectomy . Material s and Methods From December 2008 to May 2009 , a total of 26 patients underwent Roux en Y reconstruction using two circular staplers after subtotal gastrectomy , and seventy-two patients underwent Billroth-I reconstruction . Roux en Y anastomosis was performed using two circular staplers without h and sewing anastomosis . We compared clinicopathologic features and surgical outcomes between the two groups . All patients underwent gastrofiberscopy between six and twelve months after surgery to compare the bile reflux . Results No significant differences in clinicopathologic findings were observed between the two groups , except for the rate of minimal invasive surgery ( P=0.004 ) and cancer stage ( P=0.002 ) . No differences in the rate of morbidity ( P=0.353 ) and admission duration ( P=0.391 ) were observed between the two groups . Gastrofiberscopic findings showed a significant reduction of bile reflux in the remnant stomach in the Roux en Y group ( P=0.019 ) . Conclusions When compared with Billroth-I reconstruction , Roux en Y reconstruction using the double stapler technique was found to reduce bile reflux in the remnant stomach without increasing postoperative morbidity . Based on these results , we planned to begin a r and omized controlled clinical trial for comparison of Roux en Y reconstruction using this method with Billroth-I anastomosis Background We performed this prospect i ve r and omized study to evaluate what is the best reconstruction method after distal gastrectomy for gastric cancer . Methods One hundred fifty-nine patients who underwent laparoscopy-assisted or open gastrectomy for gastric cancer were analyzed from March 2006 to August 2007 . Billroth I ( B-I ) anastomosis , Billroth II ( B-II ) with Braun anastomosis , and Roux-en-Y ( R-Y ) anastomosis were applied r and omly . Additionally , the patients were divided into two groups based on treatment type : laparoscopic and open operation . Endoscopy and hepatobiliary scans were performed to investigate gastric stasis and enterogastric reflux . The Gastrointestinal Quality of Life Index ( GIQLI ) was used to evaluate postoperative quality of life , and the hematologic test was used to assess nutritional aspect . Results Endoscopy revealed that reflux after the R-Y anastomosis procedure was significantly less frequent than after the other anastomosis types at 12 months . Comparison of the GIQLI and the nutritional parameters between the reconstruction types revealed that there were no differences , but a significantly higher GIQLI score was observed in the laparoscopic group immediately following the procedure ( P = 0.042 ) . Conclusions R-Y anastomosis is superior to B-I and B-II with Braun anastomosis in terms of frequency of bile reflux , despite the fact that there is no difference in the postoperative quality -of-life index and nutritional status between reconstructive procedures . The laparoscopic approach is the better option than open surgery in terms of QOL in the immediate postoperative period Background Laparoscopic gastrectomy has recently been gaining popularity as a treatment for cancer ; however , little is known about the benefits of intracorporeal ( IC ) gastrointestinal anastomosis with pure laparoscopic distal gastrectomy ( LDG ) compared with extracorporeal ( EC ) anastomosis with laparoscopy-assisted distal gastrectomy ( LADG ) . Methods Between June 2000 and December 2011 , we assessed 449 consecutive patients with early-stage gastric cancer who underwent LDG . The patients were classified into three groups according to the method of reconstruction LADG followed by EC h and -sewn anastomosis ( LADG + EC ) ( n = 73 ) , using any of three anastomosis methods ( Billroth-I ( B-I ) , Billroth-II ( B-II ) or Roux-en-Y ( R-Y ) ; LDG followed by IC B-I anastomosis ( LDG + B-I ) ( n = 248 ) ; or LDG followed by IC R-Y anastomosis ( LDG + R-Y ) ( n = 128 ) ) . The analyzed parameters included patient and tumor characteristics , operation details , and post-operative outcomes . Results The tumor location was significantly more proximal in the LDG + R-Y group than in the LDG + B-I group ( P < 0.01 ) . Mean operation time , intra-operative blood loss , and the length of post-operative hospital stay were all shortest in the LDG + B-I group ( P < 0.05 ) . Regarding post-operative morbidities , anastomosis-related complications occurred significantly less frequently in with the LDG + B-I group than in the LADG + EC group ( P < 0.01 ) , whereas there were no differences in the other parameters of patients ’ characteristics . Conclusions Intracorporeal mechanical anastomosis by either the B-I or R-Y method following LDG has several advantages over at the LADG + EC , including small wound size , reduced invasiveness , and safe anastomosis . Although additional r and omized control studies are warranted to confirm these findings , we consider that pure LDG is a useful technique for patients with early gastric cancer Purpose Intracorporeal anastomosis during laparoscopic gastrectomy is becoming increasingly prevalent . However , selection of the anastomosis method after laparoscopic distal gastrectomy is equivocal because of a lack of technical feasibility and safety . We compared intracorporeal gastroduodenostomy with gastrojejunostomy using linear staplers to evaluate the technical feasibility and safety of intracorporeal anastomoses as well as its ' minimally invasiveness . Material s and Methods Retrospective analyses of a prospect ively collected data base for gastric cancer revealed 47 gastric cancer patients who underwent laparoscopic distal gastrectomy with either intracorporeal gastroduodenostomy or gastrojejunostomy from March 2011 to June 2011 . Perioperative outcomes such as operation time , postoperative complication , and hospital stay were compared according to the type of anastomosis . Postoperative inflammatory response was also compared between the two groups using white blood cell count and high sensitivity C-reactive protein . Results Among the 47 patients , 26 patients received gastroduodenostomy , whereas 21 patients received gastrojejunostomy without open conversion or additional mini-laparotomy incision . There was no difference in mean operation time , blood loss , and length of postoperative hospital stays . There was no statistically significant difference in postoperative complication or mortality between two groups . However , significantly more staplers were used for gastroduodenostomy than for gastrojejunostomy ( n=6 ) than for gastroduodenostomy and ( n=5 ) . Conclusions Intracorporeal anastomosis during laparoscopic gastrectomy using linear stapler , either gastroduodenostomy or gastrojejunostomy , shows comparable and acceptable early postoperative outcomes and are safe and feasible . Therefore , surgeons may choose either anastomosis method as long as oncological safety is guaranteed OBJECTIVE Intracorporeal reconstruction of the digestive tract is technically challenging . The V-Loc 180 wound closure device ( Covidien ) is a self-anchoring unidirectional barbed suture that obviates the need for knot tying . The aim of this prospect i ve cohort study was to investigate the use of the novel suture in gastrointestinal enterotomy closure . METHODS The subjects comprised patients with malignant disease who were scheduled to undergo laparoscopic gastrectomy with curative intent . The barbed suture was used to close the entry hole for the linear stapler during intracorporeal reconstruction following laparoscopic gastric resection . The primary endpoint was the proportion of patients who developed anastomotic leakage at the site where the barbed suture was applied . RESULTS Between July 2012 and March 2015 , 242 patients were enrolled . Of 362 anastomoses , the enterotomy hole at 256 sites was closed using the barbed suture . These 256 sites consisted of 95 gastroduodenostomies , 25 gastrogastrostomies , 13 gastrojejunostomies , 90 jejunojejunostomies , 17 esophagojejunostomies and 16 primary closures of the stomach following local gastric resection . There were no anastomosis-related complications , conversion to usual sutures , mechanical closure of the entry hole and reoperation due to adhesive obstructions or mortality over a median follow-up period of 17.8 months . CONCLUSIONS The use of the unidirectional barbed absorbable suture for gastrointestinal closure is safe and effective in laparoscopic gastrectomy The purpose of this study is to compare the effect of diabetes control induced by Roux-en-Y gastrojejunostomy(RY ) vs Billroth-I reconstruction(BI ) after distal gastrectomy in patients with early gastric cancer(EGC ) and type 2 diabetes(T2DM ) . Forty EGC patients with T2DM , aged 20–80 years , who were expected to undergo curative distal gastrectomy were r and omized 1:1 to RY(n = 20 ) or BI(n = 20 ) . Diabetes medication status , biochemical and hormonal data including blood glucose , HbA1c , insulin , C-peptide , HOMA-IR , ghrelin , leptin , GLP-1 , PYY , and GIP were evaluated for 12 months after surgery . Although pre- and postoperative 12-month fasting and postpr and ial glucose levels did not show a significant difference , HbA1c , C-peptide , and HOMA-IR levels were significantly improved at 12 months after surgery in both BI and RY groups . Sixty percent of RY patients and 20 % of BI patients decreased their medication satisfying FBS<126 mg/dL and HbA1c<6.5 % and 5 % of BI patients stopped their medication satisfying the criteria of FBS<126 mg/dL and HbA1c<6.0 % . The improvement patterns were more sustainable with less fluctuation in RY than in BI . On hormonal analysis , ghrelin and leptin levels were decreased and PYY and GIP levels were increased at 12 months after surgery in both groups without significant difference according to the reconstruction type and diabetic improvement status except ghrelin . In gastric cancer surgery , RY reconstruction showed better and more durable diabetes control compared to BI during the first year after surgery . Gastric cancer surgery led to decreased ghrelin and leptin and increased PYY and GIP , which might have a role in improving insulin resistance and glucose homeostasis BACKGROUND Controversy persists regarding digestive reconnection following subtotal gastrectomy for carcinoma . A r and omized prospect i ve trial comparing Billroth I and Billroth II procedures for mortality , digestive comfort , survival , and patterns of recurrence was conducted . STUDY DESIGN Thirty patients underwent Billroth I and 32 patients underwent Billroth II procedures . Stages I , II , III , and IV of the tumor-node-metastasis ( TNM ) staging system accounted for 27 , 16 , 47 , and 10 percent of tumors , respectively . Billroth I and II groups were well-matched for clinicopathologic variables . RESULTS Duration of surgery , volume of blood transfused , and abdominal drainage were similar in the two groups . The duration and volume of gastric drainage were greater in patients following Billroth I procedures . Four fistulas were noted in the Billroth I group and one fistula developed in a patient following Billroth II gastrectomy . Billroth I gastrectomy and low preoperative serum albumin were independent risk factors for fistula development . Fistula development accounted for an increase in the duration of hospital stay following Billroth I procedures . Hospital mortality was similar in the two groups . Five-year actuarial survival rate was 42 and 40 percent for patients undergoing Billroth I and Billroth II procedures , respectively . Long-term survival was similar for patients having each procedure , and this was verified for all TNM stages . There were seven recurrences at the hepatic pedicle in the Billroth I group and one recurrence of this type in the Billroth II group , requiring four re interventions . CONCLUSIONS Digestive comfort and long-term survival are similar after Billroth I and Billroth II gastrectomy for carcinoma . Billroth I gastrectomy is associated with an increased risk of fistula development and of recurrence of carcinoma at the hepatic pedicle BACKGROUND / AIMS Gastroduodenostomy ( Billroth I ) or gastrojejunostomy ( Billroth II ) after distal gastrectomy is associated with duodenogastric reflux and remnant gastritis . This study sought to determine which reconstructive procedure is least likely to cause remnant gastritis and to determine the correlation between duodenogastric reflux and remnant gastritis . METHODOLOGY Sixty patients who underwent curative distal gastrectomy for gastric cancer were classified into three groups by reconstructive procedure : group A , Roux-Y ( n=18 ) ; group B , Billroth I ( n=25 ) ; group C , Billroth II ( n=17 ) . Intragastric bile reflux was monitored using the Bilitec 2000 14 days after surgery , and endoscopy was performed and a patient question naire was completed 12 weeks after surgery . RESULTS Bile reflux occurred in 23.9 % , 40.4 % , and 73.4 % of the time ( p<0.001 ) , and remnant gastritis developed in 33 % , 76 % , and 100 % of patients ( p<0.001 ) , in groups A , B , and C , respectively . Helicobacter pylori infection did not correlate with remnant gastritis ( p=0.57 ) . Symptoms following Roux-Y reconstruction were comparable to those following Billroth I and II reconstructions . CONCLUSIONS Roux-Y reconstruction following distal gastrectomy is superior to Billroth I and II reconstruction in preventing remnant gastritis because it reduces duodenogastric reflux Purpose This study aims to compare the effectiveness of Billroth-II with Braun and Roux-en-Y reconstruction after laparoscopic distal gastrectomy . Methods From April 2010 to August 2012 , 66 patients underwent laparoscopic distal gastrectomy ( Billroth-II with Braun reconstruction , 26 ; Roux-en-Y , 40 ) . The patients ’ data were collected prospect ively and review ed retrospectively . Results The mean operation and reconstruction times were statistically shorter for Billroth-II with Braun reconstruction than Roux-en-Y ( 198.1 ± 33.0 vs. 242.3 ± 58.1 min , p = 0.001 ) . One case of postoperative stricture was observed in each group . One case each of intra-abdominal abscess and delayed gastric emptying occurred in the Billroth-II with Braun group . At 1 year postoperatively , gastric residue and reflux esophagitis were not significantly different between the groups . Gastritis and bile reflux were more frequently observed in the Billroth-II with Braun group ( p = 0.004 and p < 0.001 , respectively ) . At 2 years postoperatively , gastric residue was not significantly different , but gastritis , bile reflux , and esophagitis were more frequent in the Billroth-II with Braun group ( p = 0.029 , p < 0.001 , and p = 0.036 , respectively ) . Conclusion The postoperative effectiveness of Roux-en-Y reconstruction may be superior to Billroth-II with Braun reconstruction after laparoscopic distal gastrectomy |
13,340 | 30,827,823 | Benefits from resistant starch , resistant dextrin , and oligofructose-enriched inulin were most frequent .
Based on these results , there is fair evidence that prebiotics and substances with prebiotic properties may improve metabolic and inflammatory biomarkers related to T2DM in women aged 18 years at least .
Interventions with resistant starch , resistant dextrin , and oligofructose-enriched inulin exhibited the strongest evidence for improvements due to the quantity of publications and quality grade s. Other prebiotics and substances with prebiotic properties show promise but the number of studies is few . | BACKGROUND Intestinal bacteria composition and prebiotics may play a role in the management of type 2 diabetes mellitus ( T2DM ) .
OBJECTIVE The objective of this systematic review was to evaluate the effect of prebiotics and substances with prebiotic properties on the metabolic and inflammatory biomarkers of individuals with T2DM compared with placebo . | PURPOSE This trial was conducted to evaluate the effects of oligofructose-enriched inulin on some of cardiovascular disease risk factors in women with type 2 diabetes . METHODS 52 females ( 25 < BMI < 35 kg/m2 ) with type 2 diabetes were r and omly assigned to two groups . Participants received 10g/d oligofructose-enriched inulin ( n=27 ) or 10g/d placebo ( n=25 ) for 8 weeks . Fasting blood sample s were taken to measure metabolic profiles , malondialdehyd and antioxidant enzymes at baseline and after the 8 weeks intervention . Paired , unpaired sample t-test and analysis of covariance were used to comparison of quantitative variables . RESULTS After 8 weeks , in the oligofructose-enriched inulin group there was a significant increase in total antioxidant capacity ( 0.2 mmol/l , 20.0 % ) and a significant decrease in fasting plasma glucose ( 19.2 mg/dL , 9.4 % ) HbA1c ( 0.5 % , 8.4 % ) , total cholesterol ( TC ) ( 28.0 mg/dL , 14.1 % ) , low-density lipoprotein cholesterol ( LDL-c ) ( 22.0 mg/dL , 21.7 % ) , TC/HDL-c ratio ( 0.73 , 20.7 % ) , LDL-c/HDL-c ratio ( 0.55 , 27.5 % ) and malondialdehyd ( 1.7 nmol/ml , 39.7 % ) compared to the placebo group . Changes in concentrations of triglycerides , high-density lipoprotein cholesterol ( HDLc ) , superoxide dismutase , catalase and glutathione peroxidase were not significant in oligofructose-enriched inulin group compared to the placebo group . CONCLUSION Oligofructose-enriched inulin may improve glycemic indices , lipid profile , antioxidant status and malondialdehyd in women with type 2 diabetes Abstract To evaluate the effects of the new resistant starch ( RS ) formula , PPB-R-203 , on glucose homeostasis in healthy subjects and subjects with type 2 diabetes . A cohort consisting of 40 healthy participants received test and control diets and was checked for up to 3 hours post-meal . A r and omized , 2-regimen , cross-over , comparative study was conducted in 44 subjects with type 2 diabetes and glycemic control was assessed with a continuous glucose monitoring system . In healthy participants , serum glucose values and incremental areas under the glucose curves ( AUC ) were significantly lower in the PPB-R-203 than the control group ( P < 0.05 ) . In patients with type 2 diabetes , mean blood glucose concentrations for subjects on the control regimen were higher than those for subjects on the PPB-R-203-based regimen ( 7.9 ± 1.7 , 95 % confidence interval [ CI ] 7.4–8.4 vs 7.4 ± 1.6 , 95 % CI 6.9–7.9 mmol/L , respectively ; P = 0.023 ) . AUCs for total blood glucose and hyperglycemia ( glucose > 10 mmol/L ) were also reduced for subjects on the PPB-R-203-based regimen as compared with those on control regimen ( total blood glucose : 16.2 ± 4.0 , 95 % CI 14.9–17.4 vs 18.7 ± 4.0 , 95 % CI 17.6–20.1 , P < 0.001 ; hyperglycemia : 4.9 ± 5.7 , 95 % CI 3.1–6.6 vs 6.3 ± 6.4 , 95 % CI 4.3–8.3 mmol/L × day , P = 0.021 ) . However , AUC measurements for hypoglycemia ( glucose < 3.9 mmol/l ) were not statistically significant . A PPB-R-203-based diet reduced postpr and ial hyperglycemia in patients with type 2 diabetes without increasing the risk of hypoglycemia or glucose excursion Resistant starch ( RS ) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome , but its effects on human type 2 diabetes ( T2DM ) are unknown . This study aim ed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postpr and ial metabolites and body fat in T2DM . Seventeen individuals with well-controlled T2DM ( HbA1c 46.6±2 mmol/mol ) consumed , in a r and om order , either 40 g of type 2 RS ( HAM-RS2 ) or a placebo , daily for 12 weeks with a 12-week washout period in between . At the end of each intervention period , participants attended for three metabolic investigations : a two-step euglycemic – hyperinsulinemic clamp combined with an infusion of [ 6,6 - 2H2 ] glucose , a meal tolerance test ( MTT ) with arterio-venous sampling across the forearm , and whole-body imaging . HAM-RS2 result ed in significantly lower postpr and ial glucose concentrations ( P=0.045 ) and a trend for greater glucose uptake across the forearm muscle ( P=0.077 ) ; however , there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity , or on HbA1c . Fasting non-esterified fatty acid ( NEFA ) concentrations were significantly lower ( P=0.004 ) and NEFA suppression was greater during the clamp with HAM-RS2 ( P=0.001 ) . Fasting triglyceride ( TG ) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 ( P=0.039 and P=0.027 respectively ) . Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption ( P=0.049 ) , postpr and ial GLP1 excursions during the MTT were significantly greater ( P=0.009 ) . HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM , but demonstrated beneficial effects on meal h and ling , possibly due to higher postpr and ial GLP1 BACKGROUND Fructooligosaccharides have been cl aim ed to lower fasting glycemia and serum total cholesterol concentrations , possibly via effects of short-chain fatty acids produced during fermentation . OBJECTIVE We studied the effects of fructooligosaccharides on blood glucose , serum lipids , and serum acetate in 20 patients with type 2 diabetes . DESIGN In a r and omized , single-blind , crossover design , patients consumed either glucose as a placebo ( 4 g/d ) or fructooligosaccharides ( 15 g/d ) for 20 d each . Average daily intakes of energy , macronutrients , and dietary fiber were similar with both treatments . RESULTS Compliance , expressed as the proportion of supplements not returned , was near 100 % during both treatments . Fructooligosaccharides did not significantly affect fasting concentrations ( mmol/L ) of serum total cholesterol ( 95 % CI : -0.07 , 0.48 ) , HDL cholesterol ( -0.04 , 0.04 ) , LDL cholesterol ( -0.06 , 0.34 ) , serum triacylglycerols ( -0.21 , 0.44 ) , serum free fatty acids ( -0.08 , 0.04 ) , serum acetate ( -0.01 , 0.01 ) , or blood glucose ( -0.37 , 0.40 ) . CONCLUSIONS We conclude that 20 d of dietary supplementation with fructooligosaccharides had no major effect on blood glucose , serum lipids , or serum acetate in patients with type 2 diabetes . This lack of effect was not due to changes in dietary intake , insufficient statistical power , or noncompliance of the patients Short-chain fructooligosaccharides ( FOS ) are prebiotics , which escape digestion in the small intestine and are fermented by the colonic microflora into short-chain fatty acids . Recently , we found that the daily consumption of 20 g FOS decreased basal hepatic glucose production in healthy subjects without any effect on insulin-stimulated glucose metabolism . In this study , we evaluated the effects of the chronic ingestion of FOS on plasma lipid and glucose concentrations , hepatic glucose production and insulin resistance in type 2 diabetics . Type 2 diabetic volunteers ( n = 10 ; 6 men , 4 women ) received either 20 g/d FOS or sucrose for 4 wk in a double-blind crossover design . FOS did not modify fasting plasma glucose and insulin concentrations or basal hepatic glucose production . The plasma glucose response to a fixed exogenous insulin bolus did not differ at the end of the two periods . Erythrocyte insulin binding also did not differ . Serum triacylglycerol , total and HDL cholesterol , free fatty acid , apolipoproteins A1 and B and lipoprotein ( a ) concentrations were not modified by the chronic ingestion of FOS . We conclude that 4 wk of 20 g/d of FOS had no effect on glucose and lipid metabolism in type 2 diabetics Improvement of insulin resistance and inflammation is a basic strategy in the management of type 2 diabetes . There is limited evidence that prebiotics improve insulin resistance and inflammation . However , the ameliorating effect of resistant dextrin , as a prebiotic , on insulin resistance and inflammation in patients with type 2 diabetes has not been investigated so far . Therefore , the present study aim ed to examine the effects of resistant dextrin on insulin resistance and inflammation in type 2 diabetic patients . In a r and omised controlled clinical trial , fifty-five women with type 2 diabetes were assigned to two groups : the intervention group ( n 30 ) and the control group ( n 25 ) . The intervention group received a daily supplement of 10 g resistant dextrin and the control group received a similar amount of maltodextrin as placebo for 8 weeks . Fasting plasma glucose ( FPG ) , HbA1c , insulin , high-sensitivity C-reactive protein ( hs-CRP ) , IL-6 , TNF-α , malondialdehyde ( MDA ) and serum endotoxin concentrations were measured before and after the intervention . Data were analysed using SPSS ( version 13 ) . Paired and unpaired t tests and ANCOVA were used to compare quantitative variables after the intervention . Patients supplemented with resistant dextrin exhibited a significant decrease in fasting insulin ( 20.1 pmol/l , 22.8 % ) , homeostasis model assessment of insulin resistance ( 1.3 , 24.9 % ) , quantitative insulin sensitivity check index ( 0.2 , 7.2 % ) , IL-6 ( 1.4 pg/ml , 28.4 % ) , TNF-α ( 5.4 pg/ml , 18.8 % ) , MDA ( 1.2 nmol/ml , 25.6 % ) and endotoxin ( 6.2 endotoxin units/ml , 17.8 % ) concentrations than those supplemented with maltodextrin ( P < 0.05 ) . Decreases in FPG ( 0.05 mmol/l , 0.6 % ) , HbA1c ( 0.5 % , 9.6 % ) and hs-CRP ( 2.7 ng/ml , 35.1 % ) concentrations in the resistant dextrin group were not significant when compared with the maltodextrin group . In conclusion , resistant dextrin supplementation can modulate inflammation and improve insulin resistance in women with type 2 diabetes AIM Previous studies have shown that the water-soluble dietary fibre betaglucan , a natural component of oats , reduces cholesterol and postpr and ial hyperglycaemia . The aim of the present study was to investigate the effect of betaglucan-enriched bread consumption on the lipid profile and glucose homoeostasis of patients with type 2 diabetes ( T2D ) . METHODS We conducted a r and omized , double-blind study in which 46 patients with T2D and LDL-C greater than 3.37 mmol/l ( 130 mg/dl ) were r and omized to incorporate into their diet , for 3 weeks , either bread enriched with betaglucan ( providing 3g/day of betaglucan ) or white bread without betaglucan . RESULTS The consumption of bread containing betaglucan led to significant reductions ( vs the control group ) in LDL-C of 0.66 mmol/l ( 15.79 % ) versus 0.11 mmol/l ( 2.71 % ) ( P=0.009 ) , in total cholesterol of 0.80 mmol/l ( 12.80 % ) versus 0.12 mmol/l ( 1.88 % ) ( P=0.006 ) , in Fasting plasma insulin ( FPI ) of 3.23 microU/ml versus an increase of 3.77 microU/ml ( P=0.03 ) and in Homa-IR ( Homoeostasis model assessment -insulin resistance ) by 2.08 versus an increase of 1.33 ( P=0.04 ) . CONCLUSIONS Betaglucan enriched bread may contribute to the improvement of the lipid profile and insulin resistance in patients with T2D BACKGROUND S AND AIMS Type 2 diabetic mellitus ( T2DM ) as one of the main causes of morbidity and mortality is associated with immune system disturbances and metabolic abnormalities . In the current study we aim ed to evaluate the effects of enriched chicory inulin supplementation on liver enzymes , serum calcium and phosphorous concentrations and hematological parameters in patients with T2DM . METHODS Forty-six diabetic females patients were r and omly allocated into intervention ( n=27 ) and control ( n=22 ) groups . Subjects in the intervention group received a daily dose of 10 g of chicory and subjects in control group received a placebo for two months . Anthropometric variables , glucose homeostasis , hematological parameters and metabolic indices including serum alanine aminotransfersae ( ALT ) , aspartate aminotransferase ( AST ) , alkaline phosphatase ( ALP ) , calcium and phosphorous as well as creatinine concentrations , glomerular filtration rate ( GFR ) and blood pressure were assessed at the beginning and end of the trial . RESULTS Significant reductions in fasting serum glucose ( FSG ) , Hb A1C , AST and ALP concentrations were observed in chicory-treated group . Systolic and diastolic blood pressures were also reduced in chicory-treated group . Serum calcium significantly increased after chicory supplementation but no change in placebo treated group has been occurred ( P=0.014 ) . Supplementation with enriched chicory for two months significantly reduced hematocrit and mean corpuscular volume ( MCV ) values ( P<0.05 ) . Changes in serum insulin , creatinine and GFR were not significant . CONCLUSION The present study showed beneficial effects of oligofructose-enriched chicory on the improvement of the glucose and calcium homeostasis , liver function tests , blood pressure and reduction in hematologic risk factors of diabetes in female patients with T2DM . Further studies in both genders are needed to generalize these findings to total population The purpose of this study was to evaluate the effect of xylooligosaccharide ( XOS ) on the blood sugar , lipids and oxidative status in type 2 diabetes mellitus ( DM ) . A total of 26 outpatient subjects of Taichung Veterans General Hospital , Taiwan , with HbA1c levels between 7.0 and 10.0 % and triglyceride < 400 mg/dL were enrolled in the present study . Subjects were supplemented with 4 g/d XOS ( n=12 ) or a placebo ( n=14 ) for 8 wk in a r and omized double-blind clinical design . The results showed that the anthropometric values and nutrient intakes did not change during the experimental period . XOS supplementation not only reduced the glucose , HbA1c and fructosamine concentrations , but also decreased the levels of total cholesterol , low density lipoprotein ( LDL ) cholesterol , oxidized low density lipoprotein ( ox-LDL ) and apolipoprotein B. The activity of catalase of the erythrocyte sample decreased in the XOS group , but not the activities of superoxide dismutase and glutathione peroxidase . In conclusion , the dietary supplementation with XOS for 8 wk was effective in improving the blood sugar and lipids in type 2 diabetes , indicating that XOS-containing diets might be beneficial to DM subjects Background The purpose of this study was to evaluate the effects of high performance inulin supplementation on blood glycemic control and antioxidant status in women with type 2 diabetes . Methods In a r and omized , triple-blind controlled trial , 49 females ( fiber intake < 30 g/day , 25<body mass index < 35 kg/m2 ) with type 2 diabetes were recruited from the Iran Diabetes Society and from endocrinology and metabolism clinics associated with the Tabriz University of Medical Science . The participants were divided into one of two groups in which the participants either received 10 g/day of inulin ( intervention , n=24 ) or maltodextrin ( control , n=25 ) for 2 months . Fasting blood sample s were obtained and both glycemic control and antioxidant status were determined at baseline and at the end of the study . Results At the end of the study period , there were significant decreases in fasting plasma glucose ( 8.47 % ) , glycosylated hemoglobin ( 10.43 % ) , and malondialdehyde ( 37.21 % ) levels and significant increases in total antioxidant capacity ( 18.82 % ) and superoxide dismutase activity ( 4.36 % ) in the inulin group when compared to the maltodextrin group ( P<0.05 ) . Changes in fasting insulin , homeostasis model assessment of insulin resistance , and catalase activity were not significant in the inulin group when compared with the maltodextrin group . Glutathione peroxidase activity remained unchanged in both groups . Conclusion Inulin supplementation may improve some glycemic and antioxidant indices and decrease malondialdehyde levels in women with type 2 diabetes . Further investigations are needed in order to confirm the positive effects that inulin may have on the glycemic and antioxidant indices of patients with type 2 diabetes Type 2 diabetes is associated with a higher cardiovascular risk and there has been a growing interest in using dietary intervention to improve lipid profile and glucose control . The present work aims at analysing the effects of the enrichment of a normal diet with beta-glucan ( 3.5 g/d ) in free-living type 2 diabetic subjects for 2 months , using a palatable soup . This trial was a parallel , placebo-controlled , double-blinded r and omised study performed in fifty-three type 2 diabetic subjects . During a 3-week run-in period , subjects daily consumed a ready meal control soup ( without beta-glucan ) . For the following 8 weeks , subjects were r and omly assigned to consume daily either a control soup or a beta-glucan soup . Changes in lipid profile ( total cholesterol ( TC ) , HDL- and LDL-cholesterol ( HDLc and LDLc ) , apo B and TAG ) and in glucose control ( HbA1c and fasting glucose ) were measured . There was no significant alteration in lipid profile in the two groups ( TC , HDLc , LDLc and apo B ) . TAG decreased significantly in the beta-glucan group compared with the control group ( - 0.12 ( SD 0.38 ) v. 0.12 ( SD 0.44 ) mmol/l , P = 0.03 ) . HbA1c and fasting glucose were not reduced in any group . A single daily ingestion of 3.5 g beta-glucan , as required by official dietary recommendations , for 8 weeks did not change the lipid profile and HbA1c in type 2 diabetic subjects . To improve the metabolic profile of type 2 diabetic subjects in the long term , the quantity , the food vectors and the tolerability of beta-glucan products may be re-evaluated Aims : This trial aims to determine the effects of resistant starch ( RS ) subtype 2 ( RS2 ) on glycemic status , metabolic endotoxemia and markers of oxidative stress . Methods : A r and omized , controlled , parallel-group clinical trial group of 56 females with type 2 diabetes mellitus ( T2DM ) was divided to 2 groups . The intervention group ( n = 28 ) and control group ( n = 28 ) received 10 g/day RS2 or placebo for 8 weeks , respectively . Fasting blood sample s were taken to determine glycemic status , endotoxin , high sensitivity C-reactive protein ( hs-CRP ) , malondialdehyde ( MDA ) , total antioxidant capacity ( TAC ) , antioxidant enzymes concentrations as well as uric acid at baseline and after the intervention . Results : After 8 weeks , RS2 caused a significant decrease in the levels of MDA ( -34.10 % ) , glycosylated hemoglobin ( -9.40 % ) , insulin ( -29.36 % ) , homeostasis model of insulin resistance ( -32.85 % ) and endotoxin ( -25.00 % ) , a significant increase in TAC ( 18.10 % ) and glutathione peroxidase ( 11.60 % ) as compared with control . No significant changes were observed in fasting plasma glucose , quantitative insulin sensitivity check index , hs-CRP , superoxide dismutase , catalase and uric acid in the RS2 group as compared with the control group . Conclusion : Supplementation with RS2 may be improved glycemic status , endotoxemia and markers of oxidative stress in patients with T2DM Ageing is associated with changes in physiology and morphology ; nutritional strategies to decrease morbidity and to prolong life are of high interest . The aim of the study was to investigate the effects of lifelong supplementation with an oligofructose-enriched inulin on morphological and biological markers and lifespan in male and female rats . Male and female rats , age 3 months , were r and omised into two groups to receive either a diet with 10 % of an oligofructose-enriched inulin ( Synergy 1 ) or a st and ard diet ( control ) for 27 months . The rats were weighed every 2 weeks and their food intake was evaluated on four successive days every 4 - 6 weeks . Sample s were taken at 12 , 18 and 24 months of age . During the whole intervention period , male rats receiving Synergy 1 ( SYN1-M ) displayed lower body weight , cholesterol and plasma triacylglycerolaemia compared with the controls ( Cont-M ) . The survival rate at 24 months of age of SYN1-M rats was 35.3 % greater than that of Cont-M rats . In female rats , the Synergy 1 supplementation ( SYN1-F ) group also reduced body weight , cholesterol and triacylglycerolaemia levels , but results were less consistent over the experiment . The survival rate at 24 months of age in SYN1-F rats was 33.3 % greater compared with that of the control ( Cont-F ) group . To conclude , lifelong intervention with Synergy 1 improved biological markers during ageing and survival rate ( lifespan ) of rats Resistant starch ( RS ) consumption can modulate postpr and ial metabolic responses , but its effects on carbohydrate ( CHO ) h and ling in type 2 diabetics ( T2D ) are unclear . It was hypothesized that a bagel high in RS would improve glucose and insulin homeostasis following the 1st meal , regardless of the amount of available CHO , and that in association with incretins , the effects would carry over to a 2nd meal . Using a r and omized crossover design , 12 T2D ingested four different bagel treatments ( their 1st meal ) determined by available CHO and the weight or amount of bagel consumed : treatment A , without RS ( 50 g of available CHO ) ; treatment B , with RS ( same total CHO as in A ) ; treatment C , with RS ( same available CHO as in A ) ; and treatment D , with the same RS as in B and available CHO as in A and C. A st and ard 2nd meal was ingested 3 h later . Following the first meal , B elicited a lower glucose incremental area under the curve ( iAUC ) than C ( P < 0.05 ) , D ( P < 0.05 ) , and A ( trend ; P = 0.07 ) , lower insulin iAUC than A ( P < 0.05 ) and C ( P < 0.05 ) , and lower glucose-dependent insulinotropic polypeptide ( GIP ) iAUC than A ( P < 0.05 ) . There was a positive correlation ( P < 0.05 ) between GIP and insulin iAUCs after the 2nd meal , and C had a 3 times greater slope than the other treatments ( r = 0.91 , P < 0.001 ) , yet lacked a significant concomitant improvement in glucose disposal . These results show that for the 1st meal , RS was effective when it replaced a portion of the available CHO , while ingesting more RS influenced the GIP-insulin axis following the 2nd meal Studies on humans with diabetes mellitus showed that the crosstalk between the intestinal microbiota and the host has a key role in controlling the disease . The aim of this study was to evaluate the effects of sodium butyrate and high performance inulin supplementation simultaneously or singly on glycemic status , lipid profile , and glucagon-like peptide 1 level in adults with type 2 diabetes mellitus . Sixty patients were recruited for the study . The participants were r and omly allocated , using r and omized block procedure , to one of the four treatment groups ( A , B , C , or D ) . Group A received sodium butyrate capsules , group B received inulin supplement powder , group C was exposed to the concomitant use of inulin and sodium butyrate , and group D consumed placebo for 45 consecutive days . Markers of glycemia , lipid profile , and glucagon-like peptide 1 were measured pre- and post-intervention . Dietary supplementation in groups A , B , and C significantly reduced diastolic blood pressure in comparison with the placebo group ( p<0.05 ) . Also , intra-group statistical analysis showed that only treatment with sodium butyrate + inulin ( group C ) significantly reduced fasting blood sugar ( p=0.049 ) and waist to hip ratio ( p=0.020 ) . Waist circumference in groups B and C reduced significantly after the intervention ( p=0.007 and p=0.011 ; respectively ) . The post hoc Tukey tests showed significant increase in glucagon-like peptide 1 concentration in groups A and C in comparison with group D ( p<0.05 ) . The results suggest that inulin supplementation may be useful to diabetic patients and these effects could be increased with butyrate supplement BACKGROUND Type 2 diabetes mellitus , as a noncommunicable disease , is the main public health challenge in the 21st century . The prevalence of diabetes mellitus adjusted for the world population in Iran was 8 % until the year 2010.Lipid levels are considered as important parameters to be evaluated , as high serum lipid levels are often reported as a complication in patients with diabetes mellitus . It is cl aim ed that functional foods may improve complications of diabetes mellitus , so this study was design ed to evaluate the effects of high performance inulin on glycemic status and lipid profile of women with type 2 diabetes . METHODS The study was a r and omized controlled clinical trial . Forty-nine type 2 diabetic females ( fiber intake < 30g/d , 25 < BMI < 35 kg/m2 ) were divided into two groups . Patients in the intervention group ( n=24 ) received 10g/d inulin and patients in the control group ( n=25 ) received 10g/d maltodextrin for 8 weeks . Glycemic status and lipid profile indices were measured pre and post intervention . Data were analyzed using SPSS software ( verision11.5 ) . Paired , unpaired t-test and ANCOVA were used to compare quantitative variables . RESULTS Supplementation with inulin caused a significant reduction in FBS ( 8.50 % ) , HbA1c ( 10.40 % ) , total cholesterol ( 12.90 % ) , triglyceride ( 23.60 % ) , LDL-c ( 35.30 % ) , LDL-c/HDL-c ratio ( 16.25 % ) and TC/HDL-c ratio ( 25.20 % ) and increased HDL-c ( 19.90 % ) . The changes for the control group parameters were not significant at the end of study . CONCLUSION Inulin may help to control diabetes and its complications via improving glycemic and lipid parameters Aberrant microbiota composition and function have been linked to several pathologies , including type 2 diabetes . In animal models , prebiotics induce favourable changes in the intestinal microbiota , intestinal permeability ( IP ) and endotoxaemia , which are linked to concurrent improvement in glucose tolerance . This is the first study to investigate the link between IP , glucose tolerance and intestinal bacteria in human type 2 diabetes . In all , twenty-nine men with well-controlled type 2 diabetes were r and omised to a prebiotic ( galacto-oligosaccharide mixture ) or placebo ( maltodextrin ) supplement ( 5·5 g/d for 12 weeks ) . Intestinal microbial community structure , IP , endotoxaemia , inflammatory markers and glucose tolerance were assessed at baseline and post intervention . IP was estimated by the urinary recovery of oral 51Cr-EDTA and glucose tolerance by insulin-modified intravenous glucose tolerance test . Intestinal microbial community analysis was performed by high-throughput next-generation sequencing of 16S rRNA amplicons and quantitative PCR . Prebiotic fibre supplementation had no significant effects on clinical outcomes or bacterial abundances compared with placebo ; however , changes in the bacterial family Veillonellaceae correlated inversely with changes in glucose response and IL-6 levels ( r -0·90 , P=0·042 for both ) following prebiotic intake . The absence of significant changes to the microbial community structure at a prebiotic dosage/length of supplementation shown to be effective in healthy individuals is an important finding . We propose that concurrent metformin treatment and the high heterogeneity of human type 2 diabetes may have played a significant role . The current study does not provide evidence for the role of prebiotics in the treatment of type 2 diabetes A r and omized crossover study of 5-g guar minitablets against placebo , given three times per day with main meals for 8 wk , was done in 29 non-insulin-dependent diabetes mellitus ( NIDDM ) patients who had near-normal fasting plasma glucose concentrations on treatment with diet alone , additional sulfonylurea , or ultralente insulin . Guar did not reduce the excessive postpr and ial glycemic excursion , glycosylated hemoglobin values , basal plasma glucose concentrations , basal or incremental plasma C-peptide values , or body weight . There were few side effects with either guar or placebo therapy . Mean low-density lipoprotein cholesterol levels were significantly reduced ( P < .001 ) by guar administration ( 116 ± 23 vs. 104 ± 19 mg/dl ) . Guar additives did not improve the excessive postpr and ial glycemia found in NIDDM patients in whom near-normal fasting plasma glucose levels had been obtained Objectives : The present study was design ed to evaluate effects of konjac glucomannan ( KGM ) supplement ( 3.6 g/day ) for 28 days on blood lipid and glucose levels in hyperlipidemic type 2 diabetic patients and the possible mechanism for the reductions in blood lipid levels . Methods : Twenty-two diabetic subjects ( age 64.2 + 8.4 years , BMI 25.5 + 3.2 kg/m2 ) with elevated blood cholesterol levels ( fasting glucose between 6.7–14.4 mmol/L ) , but currently not taking lipid-lowering medication , were recruited to participate in a two 28-day period , r and omized , double-blind , crossover clinical trial . Fasting blood sample s drawn on the initial and final days of each period were determined for plasma lipids and glucose levels . Feces collected at the end of each experimental period were analyzed for neutral sterol and bile acid contents . Results : Compared with placebo , KGM effectively reduced plasma cholesterol ( 11.1 % , p = 0.0001 , adjusted α = 0.006 ) , LDL-cholesterol ( 20.7 % , p = 0.0004 , adjusted α = 0.006 ) , total/HDL cholesterol ratio ( 15.6 % , p = 0.0005 , adjusted α = 0.007 ) , ApoB ( 12.9 % , p = 0.0001 , adjusted α = 0.006 ) and fasting glucose ( 23.2 % , p = 0.002 , adjusted α = 0.008 ) . Plasma triglyceride , HDL-cholesterol , LDL/HDL cholesterol , postpr and ial glucose and body weight were not significant after adjustment by the Bonferroni-Hochberg procedure . Fecal neutral sterol and bile acid concentrations were increased by 18.0 % ( p = 0.004 ) and 75.4 % ( p < 0.001 ) , respectively , with KGM supplement . Conclusions : The KGM supplement improved blood lipid levels by enhancing fecal excretion of neutral sterol and bile acid and alleviated the elevated glucose levels in diabetic subjects . KGM could be an adjunct for the treatment of hyperlipidemic diabetic subjects OBJECTIVE The aim of the present study was to determine effects of Resistant Starch ( RS2 ) on metabolic parameters and inflammation in women with type 2 diabetes ( T2DM ) . METHODS In this r and omized controlled clinical trial , 60 females with T2DM were divided into intervention ( n = 28 ) and placebo groups ( n = 32 ) . They received 10 g/d RS2 or placebo for 8 weeks , respectively . Fasting blood sugar ( FBS ) , glycated hemoglobin ( HbA1c ) , lipid profile , high-sensitive C-reactive protein ( hs-CRP ) , interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha ( TNF-α ) were measured at baseline and at the end of the trial . Paired t test , unpaired t-test and ANCOVA were used to compare the quantitative variables . The data were analyzed using SPSS software version 13.0 . RESULTS RS2 decreased HbA1c ( -0.3 % , -3.6 % ) , TNF-α ( -3.4 pg/mL , -18.9 % ) , triglyceride ( -33.4 mg/dL , -15.4 % ) , and it increased HDL-c ( + 9.4 mg/dL , + 24.6 % ) significantly compared with the placebo group ( p < 0.05 ) . Changes in FBS , total cholesterol , low-density lipoprotein , hs-CRP and IL-6 were not significant in the RS2 group compared with the control group . RS2 can improve glycemic status , inflammatory markers and lipid profile in women with T2DM . CONCLUSIONS Although findings of the present study indicated positive effects of RS2 on inflammation and metabolic parameters , more studies are needed to confirm efficacy of RS2 as an adjunct therapy in diabetes BACKGROUND S AND AIMS Type 2 diabetic mellitus ( T2DM ) asone of the main causes of morbidity and mortality is associated with immune system disturbances and metabolic abnormalities . In the current study we aim ed to evaluate the effects of oligofructose-enriched inulin on T-cell subsets and their related cytokines , anthropometric and metabolic parameters in patients with T2DM . METHODS Forty-six diabetic females patients were r and omly allocated into intervention ( n=27 ) and control ( n=22 ) groups . Subjects in the intervention group received a daily dose of 10 g of oligofructose-enriched inulin and subjects in control group received a placebo for two months . Anthropometric variables , metabolic parameters including fasting serum glucose ( FSG ) , hemoglobin A1c ( HbA1c ) , lipid profile and blood pressure were measured at the beginning and after two months . Immune markers also included serum interleukin (IL)-4 , IL-12 and interferon (IFN)-γ concentrations were assessed and CD3(+ ) , CD4(+ ) , CD8(+ ) and CD11b(+)T-cell counts were determined by flow cytometry at baseline and end of the trial . RESULTS After two months intervention , significant improvements in anthropometric variables , blood pressure and serum lipids occurred in prebiotic-treated group ( P<0.001 ) . Serum IL-4 , IL-12 and IFN-γ concentrationsalso significantly decreased in intervention group ( P<0.001 ) . No significant changes in CD3(+ ) , CD4(+ ) , CD8(+ ) and CD11b(+ ) T-cell counts were observed in treatment groups after intervention . CONCLUSION The present study showed several beneficial effects of oligofructose-enriched inulin on the improvement of the glycemic status , lipid profile , and immune markers in patients with T2DM . Further studies are needed to confirming our findings and to better clarify the underlying mechanisms |
13,341 | 26,184,395 | The meta-analyses of three studies for ticlopidine ( an anti-platelet treatment ) , which all used the same dose of treatment but with a short follow-up of only one month , suggest ticlopidine may have a beneficial effect as an adjuvant treatment to increase the patency of AV fistulae and grafts in the short term .
There was insufficient evidence to determine if there was a difference in graft patency between placebo and other treatments such as aspirin , fish oil , clopidogrel , PRT-201 , dipyridamole , dipyridamole plus aspirin , warfarin , and sulphinpyrazone . | BACKGROUND End-stage renal disease ( ESRD ) patients often require either the formation of an arteriovenous ( AV ) fistula or an AV interposition prosthetic shunt for haemodialysis .
These access sites should ideally have a long life and a low rate of complications ( for example thrombosis , infection , stenosis , aneurysm formation and distal limb ischaemia ) .
Although some of the complications may be unavoidable , any adjuvant technique or medical treatment aim ed at decreasing complications would be welcome .
This is the second up date of the review first published in 2004 .
OBJECTIVES To assess the effects of adjuvant drug treatment in ESRD patients on haemodialysis via autologous AV fistulae or prosthetic interposition AV shunts . | Development of dialysis therapy over the last decade caused considerable increase in the number of patients receiving haemodialyses as kidney substitution therapy . However , a wider use result ed in greater number of A-V fistula complications . Uraemia patients were reported to develop plasmatic and platelet haemostasis disorders which provoke dialysis fistula thrombosis . The aim of the paper was to answer how Ticlopidine affected decrease in the number of late thrombosis complications in freshly created A-V fistula . The study included 60 patients , 30 of whom were given Ticlopidine ( 125 mg twice every 24h ) . The other 30 patients constituted the control group and did not received the drug . The follow-up lasted 27 months . It was concluded that preventive administration of Ticlopidine significantly reduces the extent of late thrombosis complications Background The Dialysis Access Consortium ( DAC ) was developed to investigate interventions to improve hemodialysis vascular access outcomes . The autogenous arteriovenous fistula created by direct connection of native artery to vein is the recommended vascular access for hemodialysis . However , it fails frequently due to clotting after surgery . Purpose The DAC Early AV Fistula Thrombosis Trial tests the hypothesis that clopidogrel can prevent early fistula failure and increase the number of fistulas that ultimately become usable for hemodialysis access . This is one of two initial and concurrent trials being performed by the DAC . The companion trial investigates pharmacologic approaches to prevent venous stenosis leading to AV graft failure . Methods This is a multicenter , r and omized , double-blind , placebo-controlled trial that will enroll 1284 patients over four years . Patients undergoing creation of a new native arteriovenous ( AV ) fistula are r and omized to treatment with clopidogrel or placebo for six weeks following fistula creation surgery . The primary outcome is fistula patency at six weeks . The major secondary outcome is fistula suitability for dialysis . Results This paper examines key aspects of this study that have broad relevance to trial design including : 1 ) the selection of an intermediate event as the primary outcome , 2 ) timing of the intervention to balance efficacy and safety concerns , 3 ) ethical considerations arising from required modifications of concomitant drug therapy , and 4 ) choosing an efficacy or effectiveness evaluation of the intervention . Conclusions This is the first , large , multicenter trial evaluating a pharmacologic approach to prevent early AV fistula failure and promote more usable fistulas for hemodialysis . The method ologic challenges identified and addressed during the development of this trial should help to inform the design of future vascular access trials , and are relevant to clinical trials addressing a wide range of questions Previous studies demonstrated a high incidence of local thrombosis in patients in whom external arteriovenous shunts were used for vascular access . This procedure provides , therefore , a useful model for the evaluation of potential antithrombotic agents . The effect of the hemorheologically and hemostasiologically active drug Pentoxifylline on the incidence of thrombosis of arteriovenous shunts ( Ramires shunt ) was investigated in a long-term , double-blind , placebo-controlled study in 51 patients on chronic hemodialysis . The two treatment groups were comparable in age , sex , concomitant medication , and dialysis program ( three times per week for four hours ) . Drugs known to affect platelet function or coagulation were excluded , with the exception of heparin , during the dialysis procedure . All shunts were placed in the forearm and inserted into the distal part of the radial artery and basilic antebrachial vein . Simultaneously , for medical reasons , in all patients an arteriovenous fistula was performed ( proximal part of radial artery and cephalic antebrachial vein ) . Shunt thrombosis was assumed when the flow in the shunt discontinued under visual and auscultatory control . Thrombi were documented by physical removal from the arterial part of the shunt by use of gentle suction or by complete shunt thrombosis ( both arterial and venous part of the shunt ) . Thereafter , the patients ' trial period terminated . The total number of thrombi during the observation period was 44 in the pentoxifylline group ( 26 patients ) , compared with 82 in the placebo group ( 25 patients ) . The mean number of thrombi per patient was 1.69±1.29 in the pentoxifylline group , significantly lower than that in the placebo group ( 3.28±1.99 / p < 0.05 ) . Further , the periods until the occurrence of first thrombosis ( in the arterial part of the shunt ) and complete shunt thrombosis were assessed per patient in days : in the pentoxifylline group the first shunt thrombosis occurred after 34.8±6.7 days ( x±s.e . ) and with placebo after 16.7±4.4 days ( p < 0.05 ) . The complete thrombosis was recorded in the pentoxifylline group after 46.8±6.5 days and with placebo after 24.6±5.8 days ( p < 0.05 ) . These findings indicate that pentoxifylline medication markedly reduced the incidence of thrombosis of arteriovenous shunt and distinctly extended the shunt survival period , suggesting an effective antithrombotic property of the drug The effect of sulfinpyrazone on the incidence of thrombosis of arterio-venous shunts was investigated in a double-blind crossover study in 45 patients on chronic hemodialysis over a period of 12 months . The incidence of thrombosis was reduced from 0.64 thrombi per patient month when on placebo to 0.21 thrombi per patient month when on sulfinpryazone ( P < 0.001 ) . The therapeutic effect was more striking in men than in women and became evident within a week of starting the drug . The side effects were minimal , requiring withdrawal from the study of only one patient . This crossover study strengthens the findings in the previous report that sulfinpyrazone is of value in the prevention of thrombosis Since platelet cyclo-oxygenase is much more sensitive to inactivation by aspirin than is the enzyme in the arterial wall and low doses of aspirin may prevent thrombosis by blocking thromboxane synthesis , we conducted a r and omized , double-blind trial of aspirin ( 160 mg per day ) vs. placebo in 44 patients on chronic hemodialysis . The study was continued until there were 24 patients with thrombi and both groups had been under observation for a mean of nearly five months . Thrombi occurred in 18 of 25 ( 72 per cent ) of patients given placebo and 16 of 19 ( 32 per cent ) of those given aspirin ( P less than 0.01 ) . The incidence of thrombosis was reduced from 0.46 thrombi per patient month in the placebo group to 0.16 thrombi per patient month in the aspirin group ( p less than 0.005 ) . A dose of 160 mg of aspirin per day is an effective , nontoxic antithrombotic regimen in patients on hemodialysis Since fish oil has been reported to reduce platelet aggregability , to reduce blood viscosity by increasing red blood cell deformability and to lower blood pressure , we studied the effect of dietary supplementation with fish oil on the occurrence of adverse effects in patients receiving recombinant human erythropoietin ( rHuEPO ) . In a prospect i ve , r and omized , double blind cross-over design we studied the effect of daily ingestion of 3 g fish oil versus 3 g corn oil ( placebo ) for 5 months , with a wash-out period of 3 months in between . Thirty-two dialysis patients newly treated with rHuEPO participated . rHuEP0 was given using a low and slow dose regimen ( 25 U/kg twice weekly s.c . ) . Target Hct was 35 % . Blood pressure , red blood cell deformability , plasma viscosity , fatty acid composition of plasma phospholipids , and fibrinogen levels were measured at 0 , 5 , 8 and 13 months . In both groups a stable target Hct ( 35 % ) was reached within 3 months . Blood pressure was not significantly different between the groups at any time point . In 4 patients ( 2 on fish oil and 2 on placebo ) antihypertensives had to be increased to regulate blood pressure adequately , whereas shunt occlusion occurred in one patient on placebo . Despite a significant increase in the omega-3 fatty acid content of plasma phospholipids during ingestion of fish oil , no significant changes in red blood cell deformability were observed . Since hypertension and shunt occlusion occurred at rates comparable to those reported in the literature , long-term ingestion of fish oil does not appear to mitigate the side effects of low and slow dose rHuEPO When constructing arteriovenous fistulas for haemodialysis in chronic renal failure patients , one of the main problems is still their clotting tendency . Ticlopidine is an effective inhibitor of platelet aggregation . In this r and omized double-blind study placebo or ticlopidine 250 mg twice daily was given to chronic uremic patients up to 4 weeks after construction of an arteriovenous fistula . 42 patients were recruited and 36 completed the trial . The fistula clotted in 8 patients on placebo and in 2 patients on ticlopidine . The difference is significant . This effect was achieved without an increased frequency of side effects compared with placebo . It is concluded that ticlopidine has a function as a thromboprophylactic drug in chronic uremic patients Background : The most common complication of hemodialysis ( HD ) access graft is thrombosis . Clopidogrel , an inhibitor of platelet aggregation , was assessed to prevent this serious complication . Methods : A prospect i ve study in which 24 patients on chronic HD whose vascular accesses were grafts were divided into two groups : group A ( n = 12 , 50 % ) consisted of patients who did not receive antithrombotic therapy after graft creation , and group B ( n = 12 , 50 % ) received clopidogrel 75 mg/day from 2 days after surgery onwards . Both groups were not different according to age , gender , cause of renal failure , hematocrit levels , platelet counts and Kt/V. All patients ’ thrombotic episodes were followed up from the day of graft surgery until thrombosis was diagnosed . Finally , the patient survival difference between both groups was determined . Results : Eleven thrombotic episodes were diagnosed in group A while one event was reported in group B ( p < 0.001 ) . Graft access days of patency were significantly longer in group B compared to group A ( 380.8 ± 170 vs. 90.1 ± 57.2 , p < 0.001 ) . Time that elapsed from dialysis initiation to graft creation was not different ( group A 18 ± 12 days , group B 20 ± 10 days ) . Days on HD were different between both groups ( group A 208.9 ± 97.2 vs. group B 583.2 ± 287.0 , p < 0.001 ) and all patients from group A ( n = 12 , 100 % ) and 2 patients from group B ( 16.7 % ) died ( p = 0.001 ) . Major bleeding events were not reported . Conclusions : Clopidogrel significantly decreased thrombotic graft episodes . Patients on clopidogrel had a prolonged vascular access patency , longer time on HD and better survival Vascular access malfunction , usually presenting with an inadequate access flow ( Qa ) , is the leading cause of morbidity and hospitalization in hemodialysis ( HD ) patients . Many methods of thermal therapy have been tried for improving Qa but with limited effects . This r and omized trial was design ed to evaluate the effect of far-infrared ( FIR ) therapy on access flow and patency of the native arteriovenous fistula ( AVF ) . A total of 145 HD patients were enrolled with 73 in the control group and 72 in the FIR group . A WS TY101 FIR emitter was used for 40 min , and hemodynamic parameters were measured by the Transonic HD(02 ) monitor during HD . The Qa(1)/Qa(2 ) and Qa(3)/Qa(4 ) were defined as the Qa measured at the beginning/at 40 min later in the HD session before the initiation and at the end of the study , respectively . The incremental change of Qa in the single HD session with FIR therapy was significantly higher than that without FIR therapy ( 13.2 + /- 114.7 versus -33.4 + /- 132.3 ml/min ; P = 0.021 ) . In comparison with control subjects , patients who received FIR therapy for 1 yr had ( 1 ) a lower incidence ( 12.5 versus 30.1 % ; P < 0.01 ) and relative incidence ( one episode per 67.7 versus one episode per 26.7 patient-months ; P = 0.03 ) of AVF malfunction ; ( 2 ) higher values of the following parameters , including Delta(Qa(4 ) - Qa(3 ) ) ( 36.2 + /- 82.4 versus -12.7 + /- 153.6 ml/min ; P = 0.027 ) , Delta(Qa(3 ) - Qa(1 ) ) ( 36.3 + /- 166.2 versus -51.7 + /- 283.1 ml/min ; P = 0.035 ) , Delta(Qa(4 ) - Qa(2 ) ) ( 99.2 + /- 144.4 versus -47.5 + /- 244.5 ml/min ; P < 0.001 ) , and Delta(Qa(4 ) - Qa(2 ) ) - Delta(Qa(3 ) - Qa(1 ) ) ( 62.9 + /- 111.6 versus 4.1 + /- 184.5 ml/min ; P = 0.032 ) ; and ( 3 ) a better unassisted patency of AVF ( 85.9 versus 67.6 % ; P < 0.01 ) . In conclusion , FIR therapy , a noninvasive and convenient therapeutic modality , can improve Qa and survival of the AVF in HD patients through both its thermal and its nonthermal effects The optimal vascular access for chronic maintenance hemodialysis is the arteriovenous fistula ( AVF ) . Several studies suggest a role for antiplatelet agents in the prevention of primary AVF failure . A double-blind , r and omized trial was conducted to assess the efficacy and safety of clopidogrel in hemodialysis patients . Ninety three patients were r and omized to receive 75 mg/daily of clopidogrel or placebo . The treatment was initiated 7–10 days prior to scheduled access surgery and continued up to six weeks postoperatively , and then patients were monitored for six months . The primary outcome was AVF failure eight weeks after fistula creation . With a permuted block r and omization schedule , 46 patients received clopidogrel and 47 patients received control placebo . The primary AVF failures at two months were 21.6 % in placebo group and 5.2 % in clopidogrel group ( P = 0.03 ) . The hazard ratio for the incidence of primary AVF failure was 0.72 ( CI 95 % , 0.41–1.01 ) . Analysis of covariables indicated that this effect occurred principally as a result of clopidogrel administration . First hemodialysis from newly created AVF in clopidogrel group was significantly more successful than placebo group ( P = 0.008 ) . No life-threatening adverse event or severe bleeding was recorded in both groups . Clopidogrel seems to be effective and safe for prevention of primary AVF failure in hemodialysis patients Background Haemodialysis ( HD ) is critically dependent on the availability of adequate access to the systemic circulation , ideally via a native arteriovenous fistula ( AVF ) . The Primary failure rate of an AVF ranges between 20–54 % , due to thrombosis or failure of maturation . There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s ) for the prevention of AVF thrombosis . We present the study protocol for a r and omised , double-blind , placebo-controlled , clinical trial examining whether the use of the anti-platelet agents , aspirin and omega-3 fatty acids , either alone or in combination , will effectively reduce the risk of early thrombosis in de novo AVF . Methods / Design The study population is adult patients with stage IV or V chronic kidney disease ( CKD ) currently on HD or where HD is planned to start within 6 months in whom a planned upper or lower arm AVF is to be the primary HD access . Using a factorial- design trial , patients will be r and omised to aspirin or matching placebo , and also to omega-3 fatty acids or matching placebo , result ing in four treatment groups ( aspirin placebo/omega-3 fatty acid placebo , aspirin/omega-3 fatty acid placebo , aspirin placebo/omega-3 fatty acid , aspirin/omega-3 fatty acid ) . R and omisation will be achieved using a dynamic balancing method over the two stratification factors of study site and upper versus lower arm AVF . The medication will be commenced pre-operatively and continued for 3 months post surgery . The primary outcome is patency of the AVF at three months after r and omisation . Secondary outcome measures will include functional patency at six and twelve months , primary patency time , secondary ( assisted ) patency time , and adverse events , particularly bleeding . Discussion This multicentre Australian and New Zeal and study has been design ed to determine whether the outcome of surgery to create de novo AVF can be improved by the use of aspirin and /or omega-3 fatty acids . Recently a placebo-controlled trial has shown that clopidogrel is effective in safely preventing primary AVF thrombosis , but ineffective at increasing functional patency . Our study presents significant differences in the anti-platelet agents used , the study design , and surgical and patient demographics that should contribute further evidence regarding the efficacy of anti-platelet agents . Trial Registration Australia & New Zeal and Clinical Trials Register ( ACTRN12607000569404 ) Extended-release dipyridamole plus low-dose aspirin ( ERDP/ASA ) prolongs primary unassisted graft patency of newly created hemodialysis arteriovenous grafts , but the individual contributions of each component are unknown . Here , we analyzed whether use of aspirin at baseline associated with primary unassisted graft patency among participants in a r and omized trial that compared ERDP/ASA and placebo in newly created grafts . We used Cox proportional hazards regression , adjusting for prespecified baseline comorbidities and covariates . Of all participants , 43 % reported use of aspirin at baseline ; of these , 82 % remained on non study aspirin ( i.e. , excluding ERDP/ASA ) at 1 year . After 1 year of follow-up , the incidence of primary unassisted patency among participants using aspirin at baseline was 30 % ( 95 % CI : 24 to 35 % ) and among those not using aspirin was 23 % ( 95 % CI : 18 to 27 % ) . Use of aspirin at baseline associated with a dose-dependent prolongation of primary unassisted graft patency that approached statistical significance ( adjusted HR , 0.83 ; 95 % CI : 0.68 to 1.01 ; P=0.06 ) . Use of aspirin at baseline did not associate with prolongation of cumulative graft patency or participant survival . In conclusion , use of aspirin associates with a trend toward longer primary unassisted patency of newly placed hemodialysis grafts similar to that observed for ERDP/ASA Purpose To explore the safety and efficacy of PRT-201 applied to the outflow vein of a newly created arteriovenous graft ( AVG ) . Methods R and omized , double-blind , placebo-controlled , single-dose escalation study of PRT-201 ( 0.01 to 9 mg ) applied to the graft-vein anastomosis and adjacent outflow vein immediately after AVG placement . The primary outcome measure was safety . The efficacy measures were intraoperative increases in outflow vein diameter and blood flow rate , primary unassisted patency , and secondary patency by dose groups ( placebo , low , medium , high and All PRT-201 ) . Results A total of 89 patients were treated ( 28 placebo and 61 PRT-201 ) . There were no significant differences in the proportion of placebo and PRT-201 patients reporting adverse events . Intraoperative outflow vein diameter increased 5 % ( p=0.14 ) in the placebo group compared with 13 % ( p=0.01 ) , 15 % ( p=0.07 ) and 12 % ( p<0.001 ) , in the low , medium and high groups , respectively . The comparison between the high and placebo groups was marginally statistically significant ( p=0.06 ) . The intraoperative blood flow did not change in the placebo group , and increased in the low , medium and high groups by 19 % ( p=0.34 ) , 36 % ( p=0.09 ) and 46 % ( p=0.02 ) , respectively . The low group had the longest primary unassisted and secondary patency and the fewest procedures to restore or maintain patency ; however , the differences between groups were not statistically significant . Conclusions PRT-201 was well tolerated and increased AVG intraoperative outflow vein diameter and blood flow . Low dose tended to increase secondary patency and decrease the rate of procedures to restore or maintain patency . Larger studies with these doses will be necessary to confirm these results No st and ard presently exists for the use of systemic heparin during angioaccess surgery to decrease the incidence of postoperative thrombotic complications . Our objective was to study the effects of intraoperatively administered heparin on 30-day patency and postoperative bleeding complications in patients undergoing autogenous arteriovenous ( AV ) fistula surgery . A prospect i ve , double-blinded , r and omized controlled study was performed on 48 patients undergoing AV fistula creation from April 2007 through November 2009 . Of the 48 patients , 22 were r and omized to the control group and received no heparin . Twenty-six were r and omized to receive heparin ( 75 units/kg intravenously ) before clamping of the artery . There was no significant difference in 30-day patency between the heparin and control groups ( 92 % vs 86 % , P = 0.65 ) , respectively . Three patients ( 12 % ) developed hematomas in the heparin group compared with one ( 5 % ) in the control group ; however the difference was not statistically significant ( P = 0.61 ) . The results suggest that intraoperative administration of heparin has no statistically significant effect on 30-day patency rates or postoperative bleeding complications . Larger trials with longer term follow-up and assessment of maturation rates are needed to determine the effect of intraoperative anticoagulation on these outcomes of arteriovenous fistula surgery Although arterialovenous fistulae ( AVF ) is considered to be vital for chronic kidney disease ( CKD ) patients , but they may cause complications and problems . For instance they may fail soon after their creation . The most important cause of failure in these cases is intrafistula thrombus formation . Whereas anti-platelet drugs are not routinely used after fistulae creation , we conducted this study to determine the effect of these drugs ( aspirin and dipyridamol ) on the patency of AVFs . From Sep 2003 to Aug 2007 , all CKD patients who needed AVF for hemodilysis were included in our study . After fistulae creation , they were r and omly divided in 3 groups . The first group was received aspirin and the second one with dipyridamol and the third one was the control group that received placebo . Each group consisted of 130 patients . Exclusion criteria were bleeding tendency , active peptic ulcer disease , pregnancy , lactation , use of anticoagulant and or non steroidal anti-inflammatory drugs , hepatic insufficiency and history of significant side effects from aspirin or dipyridamol . The patency of AVF in the control , aspirin and dipyridamol groups were obtained 69.2 % , 70.8 % and 75.4 % respectively . Although the patency in the aspirin and the dipyridamol group were 1.6 % and 6.2 % more than the control group , but there was no statistically significant difference between them and placebo ( The p-value was 0.892 for the aspirin group and 0.332 for the dipyridamol group ) . Our study showed that neither the aspirin nor the dipyridamol can be effective on the patency of AVF after 72 h even within six months period Background Arteriovenous grafts ( AVG ) are the predominant form of permanent vascular access used among hemodialysis ( HD ) patients in North America but suffer from high intervention and complication rates associated with vascular stenosis . The fish oil inhibition of stenosis in hemodialysis grafts ( FISH ) study evaluates the efficacy of fish oil in improving HD graft patency . Methods This study is a multi-center , r and omized , double blind placebo-controlled clinical trial of 232 chronic HD patients who require a new graft access . Participants are r and omized to fish oil versus placebo post-operatively . The primary endpoint is the proportion of AVG with loss of native patency within 12 months of creation . Secondary endpoints are aim ed to determine the effect of fish oil on factors that may promote stenosis and thrombosis . Cumulative patency rates , survival analysis , and analysis of inflammatory markers and adverse events will provide a better underst and ing of the potential effect of fish oil on a patient 's vascular access and cardiovascular system . The FISH study is registered at current controlled trials ( www.controlled-trials.com ) IS RCT N : 15838383 . Results Details of the study protocol are described including mechanisms of reducing bias through r and omization and double blinding , sample size determination , evaluation of patient adherence , access monitoring , and the safety of using fish oil . The main challenges of design ing and implementing this study , including using a natural supplement as an intervention in modern medical practice and recruitment of graft recipients in the ` fistula first ' environment are discussed . Conclusion This is the first large , multicenter , r and omized controlled trial of a natural supplement in preventing HD graft stenosis and thrombosis . Clinical Trials 2007 ; 4 : 357—367 . Thrombosis of hemodialysis vascular access grafts represents a major medical and economic burden . Experimental and clinical models suggest a role for antiplatelet agents in the prevention of thrombosis . The study was design ed to determine the efficacy of the combination of aspirin and clopidogrel in the prevention of graft thrombosis . The study was a r and omized , double-blind trial conducted at 30 hemodialysis units at Veterans Affairs medical centers . Participants undergoing hemodialysis with a polytetrafluoroethylene graft in the arm were r and omized to receive either double placebos or aspirin ( 325 mg ) and clopidogrel ( 75 mg ) daily . Participants were to be monitored while receiving study medications for a minimum of 2 yr . The study was stopped after r and omization of 200 participants , as recommended by the Data Safety and Monitoring Board because of a significantly increased risk of bleeding among the participants receiving aspirin and clopidogrel therapy . The cumulative incidence of bleeding events was significantly greater for those participants , compared with participants receiving placebos [ hazard ratio , 1.98 ; 95 % confidence interval ( CI ) , 1.19 to 3.28 ; P = 0.007 ] . Twenty-three participants in the placebo group and 44 participants in the active treatment group experienced a bleeding event ( P = 0.006 ) . There was no significant benefit of active treatment in the prevention of thrombosis ( hazard ratio , 0.81 ; 95 % CI , 0.47 to 1.40 ; P = 0.45 ) , although there was a trend toward a benefit among participants who had not experienced previous graft thrombosis ( hazard ratio , 0.52 ; 95 % CI , 0.22 to 1.26 ; P = 0.14 ) . In the hemodialysis population , therapy with aspirin and clopidogrel was associated with a significantly increased risk of bleeding and probably would not result in a reduced frequency of graft thrombosis The greatest threat of arteriovenous fistula ( AVF ) is early thrombosis . There remains limited evidence for the use of agents for the prevention of AVF thrombosis . A total of 180 patients with stage 4 or 5 chronic kidney disease were enrolled in the present study . They were expected to have hemodialysis ( HD ) within the next six months and a planned lower arm AVF is expected to be the primary HD access . They were r and omly divided into a control group with 60 patients , a heparin ( H ) treatment group with 60 patients and a heparin/anisodamine (H/A)-treatment group with 60 patients . The H/A-treatment group was given 50 IU/kg of heparin and 10 mg of anisodamine for seven days after the AVF was generated . The H-treatment group was given 50 IU/kg of heparin for seven days whereas the control group was given no treatment . The diameter and blood flow rate of the AVF were evaluated by color Doppler ultrasound at the fourth week after the operation . Patency rates of AVF were 96.7 % in the H/A-treatment group , 86.7 % in the H-treatment group ( P < 0.05 ) and 83.3 % in the control group ( P < 0.05 ) . The present research indicates that combined application of heparin and anisodamine can effectively relieve the vessel spasm that often occurs after establishment of an AVF and reduce the risk of early thrombosis . However , further evidence is required to vali date the maintenance of long-term patency of AVF The role of per-operative systemic heparin to improve primary patency rate of vascular access surgery is controversial . The aim of this study was to assess the risk and benefit of systemic heparin during creation of vascular access for hemodialysis in patients with chronic renal failure . Patients undergoing creation of side to end radio-cephalic arteriovenous fistula over distal forearm for hemodialysis were prospect ively r and omized into two groups . First group received 5000 IU of intravenous heparin during surgery whereas second group did not receive any anticoagulation . Post-operative complications and outcome of surgery were compared between the two groups . Among 50 patients , 25 received heparin and 25 did not . Although there was no significant difference in operative times between these two groups ( p = 0.24 ) , early post-operative bleeding complication was more common in patients receiving heparin ( p < 0.01 ) . The primary 6-week patency was 96.0 % for patients receiving heparin and 92.0 % for those not ( p = 0.46 ) . Thus per-operative systemic anticoagulation during vascular access surgery is associated with increased incidence of bleeding complication and offers no benefit in terms of primary The objective of this study was to determine the probabilities of specific morbid events or death among patients with end-stage renal disease ( ESRD ) treated by hemodialysis . A prospect i ve cohort study was performed between March 1988 and September 1989 in 18 hemodialysis centers in 13 Canadian cities , representing about one third of the hemodialysis population in Canada . The inception cohort consisted of 496 patients entering hemodialysis who had survived 1 month . The few new hemodialysis patients who received erythropoietin ( EPO ) in the last 3 months of the study were excluded . Survival curves were compared using the Cox proportional hazards regression model . Older age and history of cardiovascular disease were independently associated with a greater probability of death . Age and history of cardiovascular disease were also associated with a greater probability of nonfatal circulatory events ( myocardial infa rct ion , angina requiring hospitalization , or stroke ) , while a serum albumin level less than or equal to 30 g/L ( 3.0 g dL ) was associated with an increased probability of pulmonary edema . The probability of surviving 12 months without receiving a blood transfusion was 47.2 % for males and 27.5 % for females . The incidence of non-A , non-B hepatitis , as estimated by unexplained elevations in serum aspartate aminotransferase ( AST ) values , was not different between patients receiving and not receiving blood transfusions . The probability of hospitalization for any cause was greater for patients with grafts for vascular access than for those with fistulae , for those with a history of cardiovascular disease , for those with a serum albumin level less than or equal to 30 g/L , and for those with renal disease due to diabetes or vascular disease . Hospitalization due to circulatory disease was more likely among those with a history of cardiovascular disease and among those with a lower serum albumin level . Hospitalization for infectious disease was more likely among those with a lower serum albumin level and less likely among those with a fistula for vascular access . Among all patients receiving hemodialysis treatment for more than 6 months , there were 14.8 hospital days per year . ( ABSTRACT TRUNCATED AT 400 WORDS CONTEXT Synthetic arteriovenous grafts , an important option for hemodialysis vascular access , are prone to recurrent stenosis and thrombosis . Supplementation with fish oils has theoretical appeal for preventing these outcomes . OBJECTIVE To determine the effect of fish oil on synthetic hemodialysis graft patency and cardiovascular events . DESIGN , SETTING , AND PARTICIPANTS The Fish Oil Inhibition of Stenosis in Hemodialysis Grafts ( FISH ) study , a r and omized , double-blind , controlled clinical trial conducted at 15 North American dialysis centers from November 2003 through December 2010 and enrolling 201 adults with stage 5 chronic kidney disease ( 50 % women , 63 % white , 53 % with diabetes ) , with follow-up for 12 months after graft creation . INTERVENTIONS Participants were r and omly allocated to receive fish oil capsules ( four 1-g capsules/d ) or matching placebo on day 7 after graft creation . MAIN OUTCOME MEASURE Proportion of participants experiencing graft thrombosis or radiological or surgical intervention during 12 months ' follow-up . RESULTS The risk of the primary outcome did not differ between fish oil and placebo recipients ( 48/99 [ 48 % ] vs 60/97 [ 62 % ] , respectively ; relative risk , 0.78 [ 95 % CI , 0.60 to 1.03 ; P = .06 ] ) . However , the rate of graft failure was lower in the fish oil group ( 3.43 vs 5.95 per 1000 access-days ; incidence rate ratio [ IRR ] , 0.58 [ 95 % CI , 0.44 to 0.75 ; P < .001 ] ) . In the fish oil group , there were half as many thromboses ( 1.71 vs 3.41 per 1000 access-days ; IRR , 0.50 [ 95 % CI , 0.35 to 0.72 ; P < .001 ] ) ; fewer corrective interventions ( 2.89 vs 4.92 per 1000 access-days ; IRR , 0.59 [ 95 % CI , 0.44 to 0.78 ; P < .001 ] ) ; improved cardiovascular event-free survival ( hazard ratio , 0.43 [ 95 % CI , 0.19 to 0.96 ; P = .04 ] ) ; and lower mean systolic blood pressure ( -3.61 vs 4.49 mm Hg ; difference , -8.10 [ 95 % CI , -15.4 to -0.85 ] ; P = .01 ) . CONCLUSIONS Among patients with new hemodialysis grafts , daily fish oil ingestion did not decrease the proportion of grafts with loss of native patency within 12 months . Although fish oil improved some relevant secondary outcomes such as graft patency , rates of thrombosis , and interventions , other potential benefits on cardiovascular events require confirmation in future studies . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N15838383 Purpose While vitamin D is critical for optimal skeletal health , it also appears to play a significant role in vascular homeostasis . This pilot study compared arteriovenous ( AV ) access outcomes following cholecalciferol supplementation compared to placebo in end-stage renal disease patients preparing to undergo AV access creation . Methods A total of 52 adult hemodialysis patients preparing for arteriovenous fistula ( AVF ) creation were r and omized to receive perioperative high-dose cholecalciferol versus placebo in this double-blind , r and omized , placebo-controlled pilot study . The primary outcome was mean response to high-dose oral cholecalciferol versus placebo , and secondary outcome AV access maturation at 6 months . Logistic regression was used to assess the association between AV access maturation and baseline , posttreatment and overall change in vitamin D concentration . Results A total of 45 % of cholecalciferol-treated and 54 % of placebo-treated patients were successfully using their AVF or arteriovenous graft ( AVG ) at 6 months ( p=0.8 ) . Baseline serum concentrations of 25(OH)D and 1,25(OH)2D did not differ between those who experienced AVF or AVG maturation and those who did not ( p=0.22 and 0.59 , respectively ) . Similarly , there was no relationship between AVF or AVG maturation and posttreatment serum 25(OH)D and 1,25(OH)2D concentration ( p=0.24 and 0.51 , respectively ) . Conclusions Perioperative high-dose vitamin D3 therapy does correct 25(OH)D level but does not appear to have an association with AV access maturation rates . Future research may include extended preoperative vitamin D3 therapy in a larger population or in certain sub population s at high risk for AVF failure BACKGROUND Vascular access failure is a major cause of morbidity and hospitalization in hemodialysis population s worldwide . Erythropoietin ( EPO ) potentially can contribute to vascular access stenosis and occlusion by promoting intimal hyperplasia and thrombosis . Intravenous administration of EPO results in a severe , but transient , increase in drug concentration within the vascular access , whereas subcutaneous administration leads to a mild , but sustained , increase in the systemic circulation . The effect of route of administration of EPO on vascular access outcomes is uncertain . STUDY DESIGN R and omized controlled trial . SETTING & PARTICIPANTS 78 Korean hemodialysis patients were r and omly assigned to receive either intravenous ( n = 40 ) or subcutaneous ( n = 38 ) EPO . INTERVENTIONS EPO was administered during dialysis , and the dose was titrated to maintain hemoglobin levels between 9 to 12 g/dL. All patients received EPO 2 or 3 times/wk . Study duration was 4 to 77 months . OUTCOMES & MEASUREMENTS The primary end point was time to vascular access failure . Analysis was performed using Cox regression analysis . RESULTS The incidence of access failure was 4.7%/patient-year in the intravenous-therapy group and 12.0%/patient-year in the subcutaneous-therapy group , with an unadjusted hazard ratio of 3.24 ( 95 % confidence interval , 1.31 to 8.00 ; P = 0.01 ) . After adjustment for dialysis access type , vascular access age , previous intervention , serum phosphorus level , and diabetes mellitus , subcutaneous EPO administration was independently associated with increased vascular access failure ( hazard ratio , 3.56 ; 95 % confidence interval , 1.20 to 10.58 ; P = 0.02 ) . There were no significant differences in either hemoglobin concentration or EPO dosage between the 2 groups during the study period . LIMITATIONS Relatively small sample size and lack of complete symmetry between the 2 groups with respect to some baseline characteristics . CONCLUSIONS This study suggests that the risk of vascular access failure may be greater with subcutaneous compared with intravenous administration of EPO in hemodialysis patients Purpose To explore the safety and efficacy of PRT-201 . Methods R and omized , double-blind , placebo-controlled , single-dose escalation study of PRT-201 ( 0.0033 to 9 mg ) applied after arteriovenous fistula ( AVF ) creation . Participants were followed for one year . The primary outcome measure was safety . Efficacy measures were the proportion with intra-operative increases in AVF outflow vein diameter or blood flow ≥25 % ( primary ) , changes in outflow vein diameter and blood flow , AVF maturation and lumen stenosis by ultrasound criteria and AVF patency . Results The adverse events in the PRT-201 group ( n=45 ) were similar to those in the placebo group ( n=21 ) . There were no differences in the proportion with ≥25 % increase in vein diameter or blood flow , successful maturation or lumen stenosis . There was no statistically significant difference in primary patency between the dose groups ( placebo n=21 , Low Dose n=16 , Medium Dose n=17 and High Dose n=12 ) . In a subgroup analysis that excluded three participants with early surgical failures , the hazard ratio ( HR ) for primary patency loss of Low Dose compared with placebo was 0.38 ( 95 % CI 0.10 - 1.41 , P=0.15 ) . In a Cox model , Low Dose ( HR 0.27 , 95 % CI 0.04 - 0.79 , P=0.09 ) , white race ( HR 0.17 , 95 % CI 0.03 - 0.79 , P=0.02 ) , and age < 65 years ( HR 0.25 , CI 0.05 - 1.15 , P=0.08 ) were associated ( P<0.10 ) with a decreased risk of primary patency loss . Conclusions PRT-201 was not different from placebo for safety or efficacy measures . There was a suggestion for improved AVF primary patency with Low Dose PRT-201 that is now being studied in a larger clinical trial BACKGROUND High on-treatment platelet reactivity ( HTPR ) is frequent in patients on hemodialysis ( HD ) receiving clopidrogel . OBJECTIVES The primary aim of this study was to determine the antiplatelet effects of prasugrel vs. high-dose clopidogrel in patients on HD with HTPR . PATIENTS / METHODS We performed a prospect i ve , single-center , single-blind , investigator-initiated , r and omized , crossover study to compare platelet inhibition by prasugrel 10 mg day(-1 ) with that by high-dose 150 mg day(-1 ) clopidogrel in 21 patients on chronic HD with HTPR . Platelet function was assessed with the VerifyNow assay , and genotyping was performed for CYP2C19 * 2 carriage . RESULTS The primary endpoint of platelet reactivity ( PR , measured in P2Y12 reaction units [ PRU ] ) was lower in patients receiving prasugrel ( least squares [ LS ] estimate 156.6 , 95 % confidence interval [ CI ] 132.2 - 181.1 ) than in those receiving high-dose clopidogrel ( LS 279.9 , 95 % CI 255.4 - 304.3 ) , P < 0.001 ) . The LS mean differences between the two treatments were - 113.4 PRU ( 95 % CI - 152.9 to - 73.8 , P < 0.001 ) and - 163.8 PRU ( 95 % CI - 218.1 to - 109.2 , P < 0.001 ) in non-carriers and carriers of at least one CYP2C19 * 2 allele , respectively . HTPR rates were lower for prasugrel than clopidogrel , in all patients ( 19 % vs. 85.7 % , P < 0.001 ) and in non-carriers ( 25.7 % vs. 80 % , P = 0.003 ) . All carriers continued to show HTPR while receiving high-dose clopidogrel , but none showed it while receiving prasugrel . CONCLUSIONS In HD patients exhibiting HTPR following st and ard clopidogrel treatment , prasugrel 10 mg day(-1 ) is significantly more efficient than doubling the clopidogrel dosage in achieving adequate platelet inhibition . Neither effect seems to be influenced by carriage of the loss-of-function CYP2C19 * 2 allele Summary In a prospect i ve double blind study prophylactic administration of Acetylsalicylic acid ( ASA ) in low doses decreased significantly the rate of fistula clotting in the immediately p.o . period in uremic patients . The risk of fistula clotting was related to poor arterial blood flow , female sex and number of unsuccessful previous fistula operations . The incidence of side effects ( g.i . and non g.i . bleeding ) was acceptable with low doses of ASA and prophylactic administration of antacids . ZusammenfassungIn einer prospektiven Doppelblindstudie wurde der Einfluß von Acetylsalicylsäure auf die Häufigkeit von Cimino-Fistelthrombosen in der ersten p.o . Phase untersucht . Durch prophylaktische Gabe von Acetylsalicylsäure ließ sich der thrombotische Fistelverschluß auf 4 % senken ( Placebogruppe : 23 % ) . Ein erhöhtes Thromboserisiko best and bei schlechtem arteriellen Blutfluß , weiblichem Geschlecht und vorausgegangenen erfolglosen Fisteloperationen . Die Nebenwirkungen von Acetylsalicylsäure waren vertretbar , sofern Aspirin in niedriger Dosierung und in Verbindung mit Antacida verabreicht wurde Two hundred and fifty-eight patients with uremia who were offered surgery for placement of an arteriovenous fistula for hemodialysis were recruited in nine regional dialysis centers . The patients were r and omized to receive the platelet aggregation inhibitory compound ticlopidine , 250 mg b.d . , or matching placebo . Study medication was targeted at 7 , minimum 3 , days before scheduled surgery and continued for 28 days after surgery . The overall rate of occlusion was 41/260 evaluable operations ( 16 % ) , 25/131 ( 19 % ) in the placebo group and 16/129 ( 12 % ) in the ticlopidine group . The risk of early occlusion was a non-significant 35 % lower in the ticlopidine group . Limited risk factor analysis did not clearly identify any subgroup other than females at greater risk of early thrombosis nor any subgroup deriving particular benefit from ticlopidine treatment Treatment of the anaemia of renal disease with recombinant human erythropoietin results in an improvement of haemostasis and an increased risk of thrombovascular accidents . In this prospect i ve , placebo-controlled , double-blind , and cross-over study , the effects of low-dose acetylsalicylic acid ( 30 mg daily ) on thrombotic and bleeding events during the initial period of treatment with erythropoietin in anaemic haemodialysis patients without previous thrombovascular accidents or known increased risk for thrombosis were investigated . During correction of the haematocrit and the first 3 months thereafter , group A ( n = 68 ) received placebo and group B ( n = 69 ) 30 mg acetylsalicylic acid daily . Cross-over took place after the 3rd month of a stable haematocrit . The study ended 3 months later . Target haematocrit ( 30 - 35 % ) was reached in 12.4 + /- 8 weeks ( M + /- SD ) . In group A the bleeding time was 382 + /- 285 s , decreasing to 282 + /- 208 before cross-over ( P < 0.01 ) , and increasing to 395 + /- 271 ( P < 0.05 ) thereafter . In group B the bleeding time was 390 + /- 381 s , 406 + /- 267 ( NS ) , and 285 + /- 238 ( P < 0.05 ) respectively . Twenty-two thrombovascular accidents were seen ( 16 % , 13 during acetylsalicylic acid and 9 during placebo , NS ) , including 17 fistula thromboses . The incidence of bleeding events was not significantly different between regimens . In conclusion , erythropoietin treatment result ed in a reduction of the bleeding time . When 30 mg acetylsalicylic acid was taken during the treatment , the bleeding time did not decrease . ( ABSTRACT TRUNCATED AT 250 WORDS Hemodialysis ( HD ) vascular access thrombosis remains a major cause of morbidity , accounting for 17.4 % of all HD patient hospital admissions in 1986 . We initiated this prospect i ve , r and omized , double-blind , placebo-controlled , parallel group study to examine if dipyridamole and /or aspirin decreased the rate of thrombosis of exp and ed polytetrafluoroethylene ( ePTFE ) grafts in HD patients . Two patient groups were studied : Type I -- with a new ePTFE graft ; and Type II -- with thrombectomy and /or revision of a previously placed ePTFE graft . One hundred and seven patients were followed for 18 months or until the first thrombotic episode . Actuarial analysis of Type I patients showed cumulative thrombosis rates ( mean + /- SEM ) of 21 + /- 9 % on dipyridamole alone , compared with 25 + /- 11 % on dipyridamole and aspirin combination , 42 + /- 13 % on placebo , and 80 + /- 12 % on aspirin alone . The relative risk of thrombosis with dipyridamole was 0.35 ( P = 0.02 ) and that for aspirin was 1.99 ( P = 0.18 ) . In Type II patients , the rate of thrombosis was high in all study drug and placebo groups ( overall 78 % thrombosis ) and actuarial analysis was not carried out because of the small number of patients enrolled . We conclude that dipyridamole is beneficial in patients with new ePTFE grafts and that aspirin does not improve the risk of thrombosis in ePTFE grafts . Neither dipyridamole nor aspirin has any beneficial effect in patients with prior thrombosis of ePTFE grafts The benefit of intravenous heparin as an anticoagulant to avoid thrombotic complications during angioaccess surgery for hemodialysis is unknown . We prospect ively r and omized 115 consecutive patients referred to our institution for permanent hemodialysis access to receive systemic anticoagulation or no anticoagulation during angioaccess surgery . Patient demographics , comorbid conditions , procedure time , complications , and patency were recorded in accordance with st and ards recommended by the Society for Vascular Surgery . Of the 115 patients r and omized , 58 received no anticoagulation and 57 received systemic anticoagulation with intravenous heparin . Arteriovenous fistulas were created in 84 patients and 31 arteriovenous grafts were inserted . Operative times were longer for grafts compared to fistulas , but there were no significant differences in operative times between patients receiving anticoagulation and those not ( p = 0.31 ) . Perioperative bleeding complications were more common in patients receiving heparin ( p = 0.008 ) . The primary 30-day patency was 84 % for patients receiving heparin and 86 % for those not ( p = 0.79 ) . The 3-month functional patency was 68 % for both groups ( p = 0.99 ) . Age , gender , operative time , and incidence of bleeding complications had no impact on patency . In our experience , systemic anticoagulation for angioaccess surgery is associated with an increased incidence of bleeding complications and offers no advantage in terms of early patency Hemodialysis access complications remain a major cause of morbidity for patients with end-stage renal disease who are undergoing chronic hemodialysis . Vascular access complications occur in approximately 40 % of patients with polytetrafluorethylene ( PTFE ) grafts within the first 6 months , primarily due to stenosis and thrombosis . Thrombosis at the site of vascular access increases the risk of infection and the need for hospitalization , and may lead to loss of potential new sites for vascular access . To a large extent , the failure of hemodialysis access is due to the rapid development of an intimal hyperplastic lesion in the region of anastomosis between the PTFE graft and the vein . The hospital costs related to hemodialysis access procedures are estimated to be around $ 1.3 billion per year and the total cost of hemodialysis complications to the US healthcare system is thought to be in excess of $ 2 billion per year . Ark Therapeutics Ltd. are developing a vascular endothelial growth factor D ( VEGF-D ) gene in an adenoviral vector which is delivered locally to the adventitial surface of a graft-vein anastomosis by means of a collagen collar device . The proposed indication for this product ( Trinam ) is the prevention of intimal hyperplasia at the graft-vein anastomosis site in patients who require vascular access to facilitate hemodialysis for end-stage renal disease . The rationale for Trinam to prevent intimal hyperplasia at the graft-vein anastomosis follows the discovery that VEGF has a ' vasculoprotective ' action , result ing in inhibition of smooth muscle cell migration and proliferation . The fundamental mechanism for this vasculoprotective effect of VEGF , as distinct from its more widely appreciated ' angiogenic ' role , is that VEGF acts on surface receptors on endothelial cells result ing in increased production of nitric oxide and prostacyclin . These entities diffuse into the media of the blood vessel wall and counter the tendency for intimal hyperplasia to develop . In an in vivo rabbit model of intimal thickening in carotid arteries , adventitial delivery of VEGF using a silastic collar as a gene delivery reservoir prevented smooth muscle cell proliferation without evidence of new blood vessel formation , indicating that the mechanism by which VEGF inhibited intimal hyperplasia did not involve angiogenesis . The objective of the proposed study is to assess the efficacy and safety of local delivery of Trinam when applied to the graft-vein anastomosis site in patients with end-stage renal disease who require vascular access for hemodialysis . At the time of surgical placement of a PTFE arm graft , patients will be r and omized to either a single administration of Trinam or to ' no treatment ' ( i.e. , control group ) . It is hypothesised that Trinam administration will result in less stenosis at the graft-vein anastomosis site ( as measured by fistulography ) compared with controls and therefore will reduce the need for interventions in dialysis patients . Approximately 210 patients will be enrolled from 10 - 15 centers and patients will be evaluated for efficacy and safety over 6 months . The total dose of Trinam will be 1 x 10(11 ) viral particles ( replication-deficient adenoviral vector ) . This dose of Trinam was not associated with any significant toxicology findings in a pre clinical study of pigs in which a PTFE loop-graft was anastomosed from the carotid artery to the internal jugular vein to mimic hemodialysis vascular access surgery CONTEXT The arteriovenous fistula is the preferred type of vascular access for hemodialysis because of lower thrombosis and infection rates and lower health care expenditures compared with synthetic grafts or central venous catheters . Early failure of fistulas due to thrombosis or inadequate maturation is a barrier to increasing the prevalence of fistulas among patients treated with hemodialysis . Small , inconclusive trials have suggested that antiplatelet agents may reduce thrombosis of new fistulas . OBJECTIVE To determine whether clopidogrel reduces early failure of hemodialysis fistulas . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial conducted at 9 US centers composed of academic and community nephrology practice s in 2003 - 2007 . Eight hundred seventy-seven participants with end-stage renal disease or advanced chronic kidney disease were followed up until 150 to 180 days after fistula creation or 30 days after initiation of dialysis , whichever occurred later . INTERVENTION Participants were r and omly assigned to receive clopidogrel ( 300-mg loading dose followed by daily dose of 75 mg ; n = 441 ) or placebo ( n = 436 ) for 6 weeks starting within 1 day after fistula creation . MAIN OUTCOME MEASURES The primary outcome was fistula thrombosis , determined by physical examination at 6 weeks . The secondary outcome was failure of the fistula to become suitable for dialysis . Suitability was defined as use of the fistula at a dialysis machine blood pump rate of 300 mL/min or more during 8 of 12 dialysis sessions . RESULTS Enrollment was stopped after 877 participants were r and omized based on a stopping rule for intervention efficacy . Fistula thrombosis occurred in 53 ( 12.2 % ) participants assigned to clopidogrel compared with 84 ( 19.5 % ) participants assigned to placebo ( relative risk , 0.63 ; 95 % confidence interval , 0.46 - 0.97 ; P = .018 ) . Failure to attain suitability for dialysis did not differ between the clopidogrel and placebo groups ( 61.8 % vs 59.5 % , respectively ; relative risk , 1.05 ; 95 % confidence interval , 0.94 - 1.17 ; P = .40 ) . CONCLUSION Clopidogrel reduces the frequency of early thrombosis of new arteriovenous fistulas but does not increase the proportion of fistulas that become suitable for dialysis . Trial Registration clinical trials.gov Identifier : NCT00067119 Polytetrafluoroethylene ( PTFE ) dialysis grafts in patients with end-stage renal disease ( ESRD ) are prone to thrombotic failure . The objective of this multicenter , r and omized , double-blind , placebo-controlled clinical trial was to determine if warfarin reduces the risk of failure of PTFE dialysis grafts . Patients with ESRD and newly placed PTFE grafts were studied at community and academic dialysis centers in Southwestern Ontario . Patients were allocated to receive warfarin or matching placebo , with the warfarin administered to achieve a target INR of 1.4 to 1.9 . Time to graft failure was the main outcome measure . A total of 107 patients ( 56 allocated to warfarin ) were r and omized . The time-to-event analysis revealed no significant difference in the likelihood of graft survival between the two groups ( odds ratio , 1.76 in favor of placebo ; 95 % confidence interval , 0.72 to 4.34 ) . Six major bleeds occurred in five patients allocated to warfarin compared with none in the patients who received placebo ( P = 0.03 ) . In conclusion , low-dose warfarin was associated with an excess of clinical ly important major bleeding in patients with ESRD enrolled in this study . Furthermore , low-intensity , monitored-dose warfarin does not appear to prolong PTFE graft survival Background Surgically created arteriovenous ( AV ) grafts are the most common type of hemodialysis vascular access in the United States , but fail frequently due to the development of venous stenosis . The Dialysis Access Consortium ( DAC ) Aggrenox Prevention of Access Stenosis Trial tests the hypothesis that Aggrenox ( containing dipyridamole and aspirin ) can prevent stenosis and prolong survival of arteriovenous grafts . Methods This is a multicenter , r and omized , double-blind , placebo-controlled trial that will enroll 1056 subjects over four years with one-half year follow-up . Subjects undergoing placement of a new AV graft for hemodialysis are r and omized to treatment with Aggrenox or placebo immediately following access surgery . The primary outcome is primary unassisted patency defined as the time from access placement until thrombosis or an access procedure carried out to maintain or restore patency . The major secondary outcome is cumulative access patency . Monthly access flow monitoring is incorporated in the study design to enhance detection of a hemodynamically significant access stenosis before it leads to thrombosis . Results This paper describes the key issues in trial design , broadly including : 1 ) ethical issues surrounding the study of a clinical procedure that , although common , is no longer the clinical intervention of choice ; 2 ) acceptable risk ( bleeding ) from the primary intervention ; 3 ) inclusion of subjects already receiving a portion of the study intervention ; 4 ) inclusion of subjects with incident rather than prevalent qualifying clinical conditions ; 5 ) timing of the study intervention to balance safety and efficacy concerns ; and 6 ) the selection of primary and secondary study endpoints . Conclusions This is the first , large , multicenter trial evaluating a pharmacologic approach to prevent AV graft stenosis and failure , an important and costly problem in this patient population . Numerous design issues were addressed in implementing the trial and these will form a roadmap for future trials in this area The antiplatelet drug ticlopidine was assessed as an agent for improving the patency of Brescia-Cimino arteriovenous fistulas as access for hemodialysis . In a double-blind r and omized study over 1 month , two of six fistulas in the ticlopidine group and five of nine in the placebo group failed . A further one placebo and two ticlopidine patients still had functioning fistulas at the time of withdrawal for technical reasons from the trial . Ticlopidine appears , therefore , to enhance the efficacy of Brescia-Cimino fistulas , at least in the short term BACKGROUND Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis . Procedural interventions may restore patency but are costly . Although there is no proven pharmacologic therapy , dipyridamole may be promising because of its known vascular antiproliferative activity . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of extended-release dipyridamole , at a dose of 200 mg , and aspirin , at a dose of 25 mg , given twice daily after the placement of a new arteriovenous graft until the primary outcome , loss of primary unassisted patency ( i.e. , patency without thrombosis or requirement for intervention ) , was reached . Secondary outcomes were cumulative graft failure and death . Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates . RESULTS At 13 centers in the United States , 649 patients were r and omly assigned to receive dipyridamole plus aspirin ( 321 patients ) or placebo ( 328 patients ) over a period of 4.5 years , with 6 additional months of follow-up . The incidence of primary unassisted patency at 1 year was 23 % ( 95 % confidence interval [ CI ] , 18 to 28 ) in the placebo group and 28 % ( 95 % CI , 23 to 34 ) in the dipyridamole-aspirin group , an absolute difference of 5 percentage points . Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency ( hazard ratio , 0.82 ; 95 % CI , 0.68 to 0.98 ; P=0.03 ) and inhibited stenosis . The incidences of cumulative graft failure , death , the composite of graft failure or death , and serious adverse events ( including bleeding ) did not differ significantly between study groups . CONCLUSIONS Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts . ( Clinical Trials.gov number , NCT00067119 . The aim of our prospect i ve study was to find out if the expansion of blood volume can improve early arteriovenous fistula ( AVF ) function after construction in patients with marginal vessel quality . Before AVF construction , the arteries of the upper arm were examined by duplex sonography . Patients with critical values of internal artery diameter ( IDA ) < 1.6 mm , resistance index ( RI ) at reactive hyperemia ( RH ) > 0.7 and feeding artery blood flow ( ABF ) < 24 mL/min were divided into two groups by r and om sampling . One group received plasma exp and er ( hydroxyethyl starch ) during surgery and the other did not . During the surgical procedures to construct 43 AVFs in 37 patients with critical artery quality , the patients received a mean volume of 720 mL ( range 320 - 1000 mL ) of plasma exp and er . The primary patency rate in this group was 86 % ( 37/43 ) . In the other group of 37 patients with critical artery quality , 42 AVFs were constructed and no plasma exp and er was given during surgery . The primary patency rate was 26.2 % ( 11/42 , P > 0.001 ) . The two-year survival of the AVF in the group given plasma exp and er was 66.3 % , and in the other group it was 13.3 % . In our study , the infusion of plasma exp and er in patients with critical artery quality increased the primary patency rate after AVF construction . Based on the morphological and functional characteristics of arteries determined by pre-operative duplex sonography , the need for blood volume expansion could be predicted BACKGROUND Malfunction of the arteriovenous fistula ( AVF ) is an important cause of morbidity and hospitalization in hemodialysis ( HD ) patients . The aim of this study is to evaluate the effect of far infrared therapy on the maturation and patency of newly created AVFs in patients with chronic kidney disease stage 4 or 5 . STUDY DESIGN R and omized controlled study . SETTING & PARTICIPANTS Patients with estimated glomerular filtration rate of 5 - 20 mL/min/1.73 m² . INTERVENTION 40 minutes of far infrared therapy 3 times weekly for a year . OUTCOMES The primary outcome is the rate of AVF malfunction within 12 months , with malfunction defined as either : ( 1 ) thrombosis without thrill for AVFs not undergoing HD or ( 2 ) receiving any type of interventional procedure due to a lower Kt/V ( < 1.2 ) for patients undergoing HD . Secondary outcomes include : ( 1 ) cumulative primary unassisted AVF patency , defined as time from creation of the AVF to the first episode of AVF malfunction ; ( 2 ) physiologic maturation of the AVF by the definition of AVF access blood flow ( Qa ) ≥500 mL/min and AVF diameter ≥4 mm at 3 months ; and ( 3 ) clinical maturation of the AVF suitable for HD at 1 year . MEASUREMENTS AVF Qa was measured by Doppler ultrasonography at 2 days and 1 , 2 , 3 , and 12 months . RESULTS We enrolled 122 patients who were r and omly allocated to the intervention ( n = 60 ) and control ( n = 62 ) groups . In comparison to controls , patients in the intervention group had higher Qa values at 1 , 2 , 3 , and 12 months ; a higher rate of physiologic maturation ( 90 % vs 76 % ; P = 0.04 ) at 3 months ; and a lower rate of AVF malfunction ( 12 % vs 29 % ; P = 0.02 ) but higher rates of AVF cumulative unassisted patency ( 87 % vs 70 % ; P = 0.01 ) and clinical maturation ( 82 % vs 60 % ; P = 0.008 ) within 12 months . LIMITATIONS This is a single-center nonblinded study . CONCLUSIONS Far infrared therapy improves the access flow , maturation , and patency of newly created AVFs in patients with chronic kidney disease stages 4 and 5 OBJECTIVE This study explored the safety and efficacy of recombinant type I pancreatic elastase ( PRT-201 ) topically applied once to the external surface of an arteriovenous fistula . METHODS This was a r and omized , double-blind , placebo-controlled trial . Adults with kidney disease undergoing creation of a radiocephalic fistula ( RCF ) or brachiocephalic fistula were r and omized to treatment with placebo ( n = 51 ) , PRT-201 at 10 μg ( n = 51 ) , or PRT-201 at 30 μg ( n = 49 ) . The primary efficacy measure was unassisted primary patency ( PP ) over 1 year . Secondary efficacy measures were secondary patency ( SP ) , unassisted maturation by ultrasound interrogation , use for hemodialysis , and hemodynamically significant lumen stenosis . RESULTS Median PP was 224 days for placebo and > 365 days for the PRT-201 groups . At 1 year , 45 % , 54 % , and 53 % of placebo , 10-μg , and 30-μg patients retained PP . The risk of PP loss was nonsignificantly reduced for 10 μg ( hazard ratio [ HR ] , 0.69 ; P = .19 ) and 30 μg ( HR , 0.67 ; P = .17 ) vs placebo . In the subset ( 44 % of patients ) with a RCF , the median PP was 125 days for placebo and > 365 days for the PRT-201 groups . At 1 year , 31 % , 50 % , and 63 % of placebo , 10-μg , and 30-μg RCFs retained PP . The risk of RCF PP loss was nonsignificantly reduced by 10 μg ( HR , 0.59 ; P = .18 ) and significantly reduced by 30 μg ( HR , 0.37 ; P = .02 ) vs placebo . At 1 year , 77 % , 81 % , and 83 % of placebo , 10-μg , and 30-μg patients retained SP . The risk of SP loss was nonsignificantly reduced for 10 μg ( HR , 0.79 ; P = .61 ) and 30 μg ( HR , 0.76 ; P = .55 ) vs placebo . In the subset with RCFs , 65 % , 82 % , and 90 % of placebo , 10-μg , and 30-μg patients retained SP at 1 year . The risk of RCF SP loss was nonsignificantly reduced for 10 μg ( HR , 0.45 ; P = .19 ) and 30 μg ( HR , 0.27 ; P = .08 ) vs placebo . At month 3 , 67 % , 87 % ( P = .03 ) , and 92 % ( P < .01 ) of the placebo , 10-μg , and 30-μg group fistulas had unassisted maturation by ultrasound interrogation . At month 3 in the subset with an RCF , 47 % , 74 % ( P = .17 ) , and 93 % ( P < .01 ) of placebo , 10-μg , and 30-μg group fistulas had unassisted maturation by ultrasound interrogation . Adverse event reports were not meaningfully different between groups . CONCLUSIONS PRT-201 appeared safe . The primary efficacy end point was not met . However , both PRT-201 doses were associated with improved unassisted maturation . The 30-μg dose was associated with increased PP in the subset with RCF |
13,342 | 24,719,027 | Serious adverse events were not reported consistently ; rashes were associated with carbamazepine .
Carbamazepine is probably effective in some people with chronic neuropathic pain , but with caveats . | BACKGROUND This is an up date of a Cochrane review entitled ' Carbamazepine for acute and chronic pain in adults ' published in Issue 1 , 2011 .
Some antiepileptic medicines have a place in the treatment of neuropathic pain ( pain due to nerve damage ) .
This up date d review considers the treatment of chronic neuropathic pain and fibromyalgia only , and adds no new studies .
The up date uses higher st and ards of evidence than the earlier review , which results in the exclusion of five studies that were previously included .
OBJECTIVES To assess the analgesic efficacy of carbamazepine in the treatment of chronic neuropathic pain and fibromyalgia , and to evaluate adverse events reported in the studies . | The effect of Tegretol has been investigated in 71 patients with facial pain , using a single blind technique . Tegretol was found to have an immediate good effect in 83 per cent of patients with typical trigeminal neuralgia , in 87 per cent of those with atypical neuralgia , and in 53 per cent of those with non‐neuralgiform facial pain . Pain disappeared within the first 24 hours of treatment in 69 per cent and within the following 24 hours in a further 24 per cent . The 54 patients with a good immediate effect of Tegretol continued to take the drug after discharge , and 69 per cent of these were free of pain for over two years . Complications made withdrawal of treatment necessary in 5 per cent of the patients . One patient developed cardiac pain , three rash , three headache , nausea and vomiting , and two dizziness . Tegretol acts by reducing the bulbar and spinal polysynaptic reflexes . It has a central action , in particular on the reticulo‐thalamic system . Our present knowledge of the mode of action of Tegretol supports the hypothesis that trigeminal neuralgia is due to pathological multineuronal reflexes in the trigeminal system on the level spinal trigeminal nuclei‐thalamus Objective The aim of this study was to evaluate whether early treatment with carbamazepine decreases the incidence of neuropathic pain ( NP ) or its intensity in patients with spinal cord injury . Design This study was a r and omized , double-blind , placebo-controlled clinical trial at a third-level university hospital involving patients older than 18 yrs with a diagnosis of spinal cord injury sustained within 2 wks before enrollment and without evidence of NP . The patients received either carbamazepine up to 600 mg/day or placebo for 1 mo . Pain intensity was measured with a 10-cm visual analog scale and the SF-36 bodily pain subscale ; quality -of-life , with the Short Form 36 ( SF-36 ) Scale ; and depression , with the Zung Self-Rating Depression Scale . Measurements were carried out at the start of the r and omized trial and at the 1- , 3- , and 6-month follow-up assessment s. Results Twenty-one of 46 patients developed NP . At the 1- , 3- , and 6-month follow-up assessment s , NP was present in 4 , 11 , and 10 patients of the carbamazepine group and in 8 , 9 , and 8 patients of the placebo group , respectively . At 1 mo , two patients in the carbamazepine group vs. eight patients in the placebo group reported moderate/intense pain ( visual analog scale , ≥4.0 ; P = 0.024 ) . At the 3- and 6-month follow-up appointments , moderate/intense pain was reported by eight vs. six ( P = 0.498 ) and six vs. eight patients ( P = 0.298 ) , carbamazepine and placebo group , respectively . There was no difference in the depression ratings or in any of the SF-36 scales . Conclusions Early intervention with carbamazepine decreased NP incidence at the 1-month but not at the 3- and 6-month follow-ups in the group of patients with acquired spinal cord injury 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 Carbazepine , Tegretol ( 5-carbamyl-dibenz (b , f)azepin ) , originally known as G.32883 and introduced in 1959 as an anticonvulsant , was first shown to have some effect in relieving the pain oftrigeminal neuralgia by Blom ( 1962 , 1963 ) . Since then Spillane ( 1963 , 1964 ) , McArdle ( 1963 ) , and Taylor ( 1963 ) have confirmed that this drug has a specific effect in relieving the pain of trigeminal neuralgia in some 60 to 80 % of patients . This paper describes a controlled trial of carbazepine carried out simultaneously at The National Hospital , Queen Square , London , Cardiff Royal Infirmary , and Guy 's Hospital , London TIC DOULOUREUX is an often incapacitating affliction for which no completely satisfactory medical treatment has been available . While early observations that diphenylhydantoin has beneficial effects have been generally confirmed , 1 - 4 results with this drug are variable . Low doses are often ineffective , while the high dosages sometimes required for symptom control are poorly tolerated . Recently , Blom 5,6 and others 7 - 13 have reported that the paroxysmal pain of trigeminal neuralgia is promptly and consistently suppressed by the administration of carbamazepine ( Tegretol ) , an iminostilbene derivative with anticonvulsant activity . Chemically , the compound is 5 carbamyl-5H-dibenz ( b , f ) -azepine , and , as indicated by the structural formula ( Fig 1 ) , it is related to the antidepressant imipramine , but not to the hydantoins . While results with carbamazepine in typical tic douloureux are reported to be highly promising , the benefits observed in postherpetic and atypical facial neuralgias have been minimal . No controlled clinical trials with carbamazepine have been reported BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences & NA ; The current analysis compares changes in pain with changes in function and health status in individuals with painful diabetic peripheral neuropathy ( DPN ) . The post hoc analysis is based on a 12 week , multinational , placebo‐controlled trial of pregabalin in which 401 patients were r and omized to treatment . Study measures included the Brief Pain Inventory short‐form ( BPI‐sf ) , EQ‐5D and other patient‐reported outcomes . Cutpoints were derived on the BPI‐sf 0–10 average pain numeric rating scale [ NRS ] to classify pain grade s of “ mild ” ( 1–3 ) , moderate ( 4–6 ) and severe ( 7–10 ) , adjusting for geographical regions where data were collected . Two different metrics were used to classify the importance of change in pain severity from baseline to 12 weeks : changes in pain severity grade s ( defined by cutpoint categories ) and percent reduction in the NRS ( categories ranging from 0–9 % to ≥50 % ) . An improvement in one pain grade or a ≥30 % reduction in the NRS served as determinants of a clinical ly important difference . Patients with a one‐ grade reduction in pain severity , either from “ severe‐to‐moderate ” or “ moderate‐to‐mild , ” had a 3‐point improvement the BPI‐sf Pain Interference Index ( PII ; a composite measure of function ) ; a reduction from “ severe‐to‐mild ” pain corresponded to a 6‐point improvement in the PII . Similarly , a reduction in the NRS of ≥30 % and ≥50 % corresponded to a 3‐point and a 5‐point improvement in the PII , respectively . Changes in pain were also associated with changes in health status . Results suggest that patients whose pain is not reduced to a mild level of severity can still experience clinical ly important changes in function and health status Background : Anticonvulsants are regarded as useful for the treatment of neuropathic pain . In this study , we evaluated the efficacy and occurrence of side effects of lamotrigine ( LTG ) in comparison with carbamazepine ( CBZ ) , in trigeminal neuralgia ( TN ) patients . Methods : The study was an interventional and crossover comparison . Twenty‐one patients with TN were administered with LTG in comparison to CBZ . The clinical trials comprised two phases of 40 days each , with an intervening three‐day washout period . The final titration in dose for LTG was 400 mg and 1,200 mg for CBZ . Efficacy of the medications involved was determined by visual analog scale ( VAS ) and verbal rating scale ( VRS ) . Side effects were recorded through marking of the profiles of side effects encountered on administration of LTG and CBZ , together with baseline haematological , hepatic and renal investigations . Results : Both on VAS and VRS assessment s , in terms of proportion of patients , CBZ benefitted 90.5 % ( 19/21 ) of the patients with pain relief ( p < 0.05 ) , in contrast to 62 % ( 13/21 ) from LTG . On VAS assessment , of the 13 patients who gained pain relief from LTG and 19 from CBZ , 77 % ( 10/13 ) obtained a “ complete ” degree of pain relief from LTG , as compared with 21 % ( 4/19 ) from CBZ . On VRS assessment , with LTG , 84 % ( 11/13 ) of the patients accomplished “ much better ” degree of pain relief , as compared with 26 % ( 5/19 ) with CBZ . On LTG , 67 % ( 14/21 ) of patients endured general pharmacological side effects , as compared with 57 % ( 12/21 ) of patients on CBZ ( p > 0.05 ) . Meanwhile , LTG inflicted 14 % ( 3/21 ) of the patients with haematological , hepatic and renal derangements , as compared with 48 % ( 10/21 ) on CBZ . Conclusion : LTG is generally an effective and safe treatment for management of TN , compared to CBZ We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11 Summary A double blind crossover study with placebo and carbamazepine was done in 30 diabetic patients who presented diverse clinical types of peripheral diabetic neuropathy . The active drug offered symptomatic relief of all sensory manifestations in 28 cases . No effort was made to assess the action of carbamazepine upon motor or visceral manifestations of neuropathy . There were two complete failures . Untoward effects were frequent but usually mild and transient ; two patients presented a rash that required discontinuation of the drug . RésuméUne étude de cross over double aveugle avec placebo et carbamazépine a été effectuée chez 30 patients diabétiques présentant divers types cliniques de neuropathie diabétique périphérique . La drogue active apportait un soulagement symptomatique de toutes les manifestations sensorielles dans 28 cas . Aucun effort n'a été fait pour évaluer l'action de la carbamazépine sur les manifestations motrices ou viscérales de la neuropathie . Il y eut deux échecs complets . Les effets secondaires étaient fréquents , mais en général légers et temporaires . Deux patients présentèrent une éruption qui nécessita l'arrêt du traitement . ZusammenfassungAn 30 Diabetikern , die unterschiedliche Formen einer peripheren diabetischen Neuropathie aufwiesen , wurde eine Doppel-Blind-Austausch-Untersuchung mit Carbamazepin und einem Plazebo-Präparat durchgeführt . Bei 28 der Patienten führt die aktive Droge zu einer symptomatischen Besserung sämtlicher Symptome von Seiten des sensiblen Nevensystems . Die Wirkung von Carbamazepin auf die motorischen und visceralen Erscheinungsformen der Neuropathie wurde nicht geprüft . Es traten zwei komplette Therapie-Versager auf . Nebenwirkungen waren häufig festzustellen ; sie waren jedoch gewöhnlich leicht und klangen schnell ab . Bei zwei Patienten zwang das Auftreten eines Exanthems zum Absetzen des Präparates UNLABELLED Progress in the underst and ing of chronic pain with neuropathic features has been hindered by a lack of epidemiologic research in the general population . The Leeds Assessment of Neuropathic Symptoms and Signs score ( S-LANSS ) was recently vali date d for use in postal surveys , making the identification of pain of predominantly neuropathic origin possible . Six family practice s in 3 UK cities ( Aberdeen , Leeds , and London ) generated a total r and om sample of 6,000 adults . The mailed question naire included demographic items , chronic pain identification , and intensity questions , the S-LANSS , the Level of Expressed Needs question naire , and the Neuropathic Pain Scale . With a corrected response rate of 52 % , the prevalence of any chronic pain was 48 % and the prevalence of pain of predominantly neuropathic origin was 8 % . Respondents with this chronic neuropathic pain were significantly more likely to be female , slightly older , no longer married , living in council rented accommodation , unable to work , have no educational qualifications , and be smokers than all other respondents . Multiple logistic regression modeling found that pain of predominantly neuropathic origin was independently associated with older age , gender , employment ( being unable to work ) , and lower educational attainment . Respondents with this pain type also reported significantly greater pain intensity , higher scores on the NPS , higher levels of expressed need , and longer duration of pain . This is the first estimate of the prevalence and distribution of pain of predominantly neuropathic origin in the general population , using a previously vali date d and reliable data collection instrument . PERSPECTIVE Chronic pain with neuropathic features appears to be more common in the general population than previously suggested . This type of pain is more severe than other chronic pain but distributed similarly throughout sociodemographic groups & NA ; Chronic pain is associated with a range of other problems , including disturbed sleep , depression , anxiety , fatigue , reduced quality of life , and an inability to work or socialise . We investigated whether good symptom control of pain ( using definitions of moderate and substantial benefit ) is associated with improvement in other symptoms . Individual patient data from four r and omised trials in fibromyalgia ( 2575 patients ) lasting 8–14 weeks were used to calculate percentage pain reduction for each completing patient ( 1858 ) , divided into one of five groups according to pain reduction , irrespective of treatment : substantial benefit – ≥50 % pain reduction ; moderate – 30 % to < 50 % ; minimal – 15 % to < 30 % ; marginal – 0 % to < 15 % ; worse – < 0 % ( increased pain intensity ) . We then calculated change from baseline to end of trial for measures of fatigue , function , sleep , depression , anxiety , ability to work , general health status , and quality ‐adjusted life year ( QALY ) gain over a 12‐month period . Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures , with values by trial end at or approaching normative values . Substantial pain intensity reduction result ed in 0.11 QALYs gained , and moderate pain intensity reduction in 0.07 QALYs gained over a 12‐month period . Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief . Pain intensity reduction is a simple and effective predictor of which patients should continue treatment , and which should discontinue and try an alternative therapy Abstract Objective : To determine whether inappropriate subgroup analysis together with chance could change the conclusion of a systematic review of several r and omised trials of an ineffective treatment . Design : 44 r and omised controlled trials of DICE therapy for stroke were performed ( simulated by rolling different coloured dice ; two trials per investigator ) . Each roll of the dice yielded the outcome ( death or survival ) for that “ patient . ” Publication bias was also simulated . The results were combined in a systematic review . Setting : Edinburgh . Main outcome measure — Mortality . Results : The “ hypothesis generating ” trial suggested that DICE therapy provided complete protection against death from acute stroke . However , analysis of all the trials suggested a reduction of only 11 % ( SD 11 ) in the odds of death . A predefined subgroup analysis by colour of dice suggested that red dice therapy increased the odds by 9 % ( 22 ) . If the analysis excluded red dice trials and those of poor method ological quality the odds decreased by 22 % ( 13 , 2P=0.09 ) . Analysis of “ published ” trials showed a decrease of 23 % ( 13 , 2P=0.07 ) while analysis of only those in which the trialist had become familiar with the intervention showed a decrease of 39 % ( 17 , 2P=0.02 ) . Conclusion : The early benefits of DICE therapy were not confirmed by subsequent trials . A plausible ( but inappropriate ) subset analysis of the effects of treatment led to the qualitatively different conclusion that DICE therapy reduced mortality , whereas in truth it was ineffective . Chance influences the outcome of clinical trials and systematic review s of trials much more than many investigators realise , and its effects may lead to incorrect conclusions about the benefits of treatment OBJECTIVE The purpose of this study was to evaluate the effect of carbamazepine on chronic pain in patients with major depression . DESIGN Off-on-off-on carbamazepine treatment design . SETTING Department of Anesthesiology , Hirosaki University Hospital , Japan . PATIENTS Fifteen patients with a diagnosis of major depression and chronic pain . INTERVENTION Depressed patients maintained on antidepressants that had failed to help depression or pain were initially placed on 450 mg carbamazepine at 150 mg three times per day . Carbamazepine was then increased until the patients experienced satisfactory relief of pain . This dose was then maintained for 3 weeks . Afterward , the medication was stopped , and a lactose placebo was administered orally three times per day for 3 weeks . Thereafter , carbamazepine was given for 3 additional weeks at the dose that previously produced satisfactory pain relief . OUTCOME MEASURE Pain scores were assessed four times during the course of the study : before and after the first and the second treatments with carbamazepine , using a visual analog scale in which 0 represents no pain and 10 unbearable pain . The Hamilton Depression scale was used to judge improvement in the symptoms of depression . RESULTS Carbamazepine produced a statistically significant reduction in the pain scores , from 8.2 + /- 2.3 to 4.0 + /- 1.1 after the first treatment . The pain score significantly increased to 8.0 + /- 1.0 after stopping carbamazepine , but it decreased significantly to 4.1 + /- 1.8 after the second treatment . The Hamilton scores significantly decreased from 27.4 + /- 7.2 to 20.2 + /- 6.1 after the carbamazepine treatment . CONCLUSIONS These results may indicate that carbamazepine has both an antidepressive and an analgesic action in depressed patients . Thus , carbamazepine may offer an acceptable therapeutic option in depressed patients with chronic pain that is unresponsive to antidepressants . Alternatively , these results may indicate that carbamazepine appears to help depression in this group of pain patients because of its analgesic effect ( i.e. , helps depression as a result of helping pain or vice versa ) Forty otherwise healthy patients over 50 years of age with early , severe painful herpes zoster were r and omly allocated to two groups for treatment . Twenty patients received prednisolone 40 mg daily with gradual reduction over a period of 4 weeks , whilst the other twenty patients received carbamazepine 100 mg four times daily . Thirteen of the twenty patients ( 65 % ) in the carbamazepine treated group developed post‐herpetic neuralgia lasting up to 2 years , whilst only three of the twenty prednisolone treated patients ( 15 % ) had post‐herpetic neuralgia lasting up to 6 months only . Thus the incidence and duration of post‐herpetic neuralgia were considerably reduced in the prednisolone treated group . In neither group did disseminated zoster or other complications occur & NA ; A double‐blind , 3‐phase , cross‐over , placebo‐controlled trial of the pain‐relieving effect of amitriptyline and carbamazepine was carried out in 15 patients with central post‐stroke pain ( CPSP ) but without signs of depression . Treatment was given , in r and omized order , for periods of 4 weeks , separated by 1 week wash‐out . The final doses were 75 and 800 mg/day , respectively , for amitriptyline and carbamazepine . The treatment effects were assessed by daily ratings of pain intensity on a 10‐step verbal scale and at the end of each treatment period by a global rating of the analgesic effect on a 5‐step verbal scale . For the assessment of depression the Comprehensive Psychopathological Rating Scale ( CPRS ) was used . Amitriptyline produced a statistically significant reduction of pain when compared to placebo . According to the global rating , 10 of the 15 patients were responders to this drug . The effect could already be noticed during the second treatment week and it appeared to be correlated to the plasma concentration , since the median total ami‐ and nortriptyline concentrations were 497 and 247 nmol/1 , respectively , for responders and non‐responders . The early onset , together with the fact that the patients were not depressed , nor did they obtain reduced scores on ratings of depressive symptoms and signs , provides strong support for the conclusion that the pain relief was not caused by an antidepressive effect . Five of the 14 patients treated with carbamazepine reported some pain relief , but the effect did not reach statistical significance when compared to placebo . No correlation was found between effect and plasma concentration . In general , the patients tolerated the planned final dose of amitriptyline well . No final dose reduction was necessary . Carbamazepine caused more side effects and the final dose had to be reduced in 4 patients . However , only 1 patient had to be taken off medication , on day 25 , due to drug interaction We compared the efficacy and tolerance of the combination of nortriptyline-fluphenazine ( NF ) vs. carbamazepine ( CMZ ) in the symptomatic therapy of patients with severe , distal , symmetrical , predominantly sensitive diabetic polyneuropathy ( DPN ) . We followed a double blind , crossover , r and omized and double placebo design . Sixteen patients with severe DPN participated in the study . Patients received either NF ( 1 tablet three times a day ( tid ) ) , for 2 weeks and 2 tablets tid for the next 2 weeks or CMZ 1/2 tablet tid for 2 weeks and 1 tablet tid for the next 2 weeks . After this , patients received placebos of both drugs ( wash-out period ) , until symptoms returned to baseline levels ( 100 % ) , then they were crossed over to receive the other comparing drug schedule . A visual analogue scale was used to evaluate the percent changes in pain and paresthesia . HbA1 , fasting serum glucose , and safety tests were performed at 2- and 4-week intervals , respectively . Both therapies produced significant improvement of both pain and paresthesia . No statistically significant differences were observed between both therapies for either pain or paresthesia . No significant biochemical changes were observed with any of the two therapies . Side effects were mild and more frequent in the NF period . In this study no superiority of either drug schedule was demonstrated ; therefore , the decision to use any of them should be made according to the associated pathology and potential side effects of each drug Forty-three patients with peripheral neuropathic pain , exclusively pain reduced by spinal cord stimulation ( SCS ) , were switched into a painful state after SCS inactivation . This mode was used to assess the pain-relieving effect of carbamazepine ( CMZ ) and opioids in a double-blinded , placebo-controlled trial . In Phase 1 , the patients were r and omly allocated to receive either CMZ ( 600 mg/d ) or placebo during an SCS-free period of 8 days . In Phase 2 , after a CMZ elimination interval of 7 days , 38 patients received either sustained-release morphine ( 90 mg/d ) or placebo for 8 days . In cases of intolerable pain , the patients were authorized to reactivate their SCS . The pain intensity was rated on a numeric analog scale . In 38 patients who completed Phase 1 , significant delay in pain increase was observed in the CMZ group as compared with placebo ( P = 0.038 ) . In Phase 2 , the trend observed with morphine was insignificant ( P = 0.41 ) . Two CMZ patients and one morphine patient showed complete pain relief and preferred to continue the medication . Thirty-five patients returned to SCS . We conclude that CMZ is effective in peripheral neuropathic pain . Morphine obviously requires larger individually titrated dosages than those used in this study for results to be adequately interpreted . Implication s This study included patients with neuropathic pain suppressed by spinal cord stimulation ( SCS ) . After deactivation of SCS , different drug effects were evaluated . In contrast to morphine , carbamazepine showed significant pain relief compared with placebo CARBAMAZEPINE ( Tegretol ) has been used for more than eight years in other countries for the treatment of epilepsy and , more recently , trigeminal neuralgia . The earliest reports on its effect in trigeminal neuralgia were by Blom 1,2 in Sweden , Bonduelle et al 3 in France , and Spillane 4 and Taylor 5 in Engl and . Since then , there have been a number of additional papers . 6 - 9 The authors are in agreement on the effectiveness of this drug in trigeminal neuralgia , but the type and number of side effects have been quite variable . There have been occasional reports of serious hematopoietic effects , 10,11 but no repeated blood studies over long periods have been reported . The present study was undertaken to evaluate the side effects and also the application of this drug in some of the other neuralgias such as postherpetic , tabetic , and atypical facial neuralgia . A double-blind technique was necessary . Carbamazepine is In a double-blind study the efficacy and tolerability of tizanidine was compared with those of carbamazepine in the management of trigeminal neuralgia . Six patients were allocated to treatment with tizanidine and six to carbamazepine . After individual titration the maximum daily doses were 18 mg and 900 mg , respectively . Among the efficacy factors used , the visual analog scale ( VAS ) and the overall efficacy as assessed by patients and investigator turned out to be the most appropriate . The results indicate that tizanidine was well tolerated , but the effects , if any , were inferior to those of carbamazepine ABSTRACT Facial pain has a considerable impact on quality of life . Accurate incidence estimates in the general population are scant . The aim was therefore to estimate the incidence rate ( IR ) of trigeminal neuralgia ( TGN ) , postherpetic neuralgia ( PHN ) , cluster headache ( CH ) , occipital neuralgia ( ON ) , local neuralgia ( LoN ) , atypical facial pain ( AFP ) , glossopharyngeal neuralgia ( GPN ) and paroxysmal hemicrania ( PH ) in the Netherl and s. In the population ‐based Integrated Primary Care Information ( IPCI ) medical record data base potential facial pain cases were identified from codes and narratives . Two medical doctors review ed medical records , question naires from general practitioners and specialist letters using criteria of the International Association for the Study of Pain . A pain specialist arbitrated if necessary and a r and om sample of all cases was evaluated by a neurologist . The date of onset was defined as date of first specific symptoms . The IR was calculated per 100,000 PY . Three hundred and sixty‐two incident cases were ascertained . The overall IR [ 95 % confidence interval ] was 38.7 [ 34.9–42.9 ] . It was more common among women compared to men . Trigeminal neuralgia and cluster headache were the most common forms among the studied diseases . Paroxysmal hemicrania and glossopharyngeal neuralgia were among the rarer syndromes . The IR increased with age for all diseases except CH and ON , peaking in the 4th and 7th decade , respectively . Postherpetic neuralgia , CH and LoN were more common in men than women . From this we can conclude that facial pain is relatively rare , although more common than estimated previously based on hospital data & NA ; Tocainide is a derivative of lidocaine with anti‐arrhythmic action and , unlike lidocaine , can be used for oral treatment . Tocainide was alternatively with carbamazepine given to 12 patients with trigeminal neuralgia in a double‐blind cross‐over study for 2 weeks . The analgesic effect was estimated each day by the patients using a 0–10‐point scale summarizing the frequency and severity of the attacks . The similarity in analgesic effect of the two drugs was striking . A possible analgesic mechanism could be that tocainide blocks the sodium channels in the hyperexcitable nerve membranes in the pain‐producing foci in trigeminal neuralgia |
13,343 | 27,693,521 | In a systematic review and meta‐ analysis , we found case‐control but not cohort studies to associate consumption of red and processed meat with risk of pancreatic cancer .
However , in cohort studies , consumption of red and processed meat appeared to increase risk of pancreatic cancer in men but not in women | BACKGROUND & AIMS The relationship between consumption of red and processed meat and pancreatic cancer risk is inconclusive .
We conducted a systematic review and meta‐ analysis to analyze this relationship . | Pancreatic cancer is the fourth most common cause of cancer death worldwide with large geographical variation , which implies the contribution of diet and lifestyle in its etiology . We examined the association of meat and fish consumption with risk of pancreatic cancer in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . A total of 477,202 EPIC participants from 10 European countries recruited between 1992 and 2000 were included in our analysis . Until 2008 , 865 nonendocrine pancreatic cancer cases have been observed . Calibrated relative risks ( RRs ) and 95 % confidence intervals ( CIs ) were computed using multivariable-adjusted Cox hazard regression models . The consumption of red meat ( RR per 50 g increase per day = 1.03 , 95 % CI = 0.93 - 1.14 ) and processed meat ( RR per 50 g increase per day = 0.93 , 95 % CI = 0.71 - 1.23 ) were not associated with an increased pancreatic cancer risk . Poultry consumption tended to be associated with an increased pancreatic cancer risk ( RR per 50 g increase per day = 1.72 , 95 % CI = 1.04 - 2.84 ) ; however , there was no association with fish consumption ( RR per 50 g increase per day = 1.22 , 95 % CI = 0.92 - 1.62 ) . Our results do not support the conclusion of the World Cancer Research Fund that red or processed meat consumption may possibly increase the risk of pancreatic cancer . The positive association of poultry consumption with pancreatic cancer might be a chance finding as it contradicts most previous findings There have been few prospect i ve studies relating diet to pancreatic cancer , with most having fewer than 100 cases and only one examining dietary nutrients . The authors prospect ively examined dietary factors hypothesized to be associated with exocrine pancreatic cancer in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study cohort in Finl and . Of the 27,111 male smokers aged 50 - 69 years with complete dietary information , as ascertained from a self-administered dietary history question naire given at baseline ( 1985 - 1988 ) , 163 developed pancreatic cancer from 1985 through November 1997 . Cox proportional hazards models were used to estimate smoking- and age-adjusted hazard ratios and 95 % confidence intervals . Energy-adjusted butter consumption and saturated fat intake were positively associated with pancreatic cancer ( highest quintile vs. lowest : hazard ratio ( HR ) = 1.40 , 95 % confidence interval ( CI ) : 0.87 , 2.25 ( p trend = 0.04 ) , and HR = 1.60 , 95 % CI : 0.96 , 2.64 ( p trend = 0.02 ) , respectively ) . Energy intake and energy-adjusted carbohydrate intake were inversely associated with the disease ( highest quintile vs. lowest : HR = 0.62 , 95 % CI : 0.36 , 1.07 ( p trend = 0.05 ) , and HR = 0.62 , 95 % CI : 0.37 , 1.03 ( p trend = 0.02 ) , respectively ) . These results support the hypothesis that a high intake of saturated fat may increase the risk of pancreatic cancer in smokers , while greater intakes of energy and carbohydrate may reduce the risk Objectives Pancreatic adenocarcinoma has one of the worst survival rates of all the cancers . Established risk factors for this malignancy are smoking , body mass index ( BMI ) and family history of pancreatic cancer . Findings are inconsistent regarding pancreatitis , diabetes , allergies , intake of fruit , vegetables , red meat , alcohol , caffeine , vitamin C , calcium , and folate supplements . Possible pancreatic cancer risk factors were evaluated within the population -based Ontario Pancreas Cancer Study . Methods Pathologically confirmed pancreatic cancer cases ( n = 422 ) were identified from the Ontario Cancer Registry between 2003 and 2007 . Controls ( n = 312 ) were recruited through r and om digit dialing . Data were collected using self-administered question naires . Multivariate logistic regression was used to obtain odds ratios . Results Smoking , BMI , family history of pancreatic cancer , and caffeine were significantly associated with increased pancreatic cancer risk , while fruit intake and allergies significantly decreased risk . No other significant associations were observed in the multivariate model . Effect modification by smoking status was suggested for caffeine , family history of pancreatic cancer , BMI , and fruit . Conclusions This study further clarifies the association between several lifestyle , dietary and medical history factors , and pancreatic cancer risk , many of which are potentially modifiable . Possible effect modification by smoking status should be further explored in future etiologic studies BACKGROUND Advanced glycation end products ( AGEs ) are a heterogeneous group of compounds present in uncooked foods as well as in foods cooked at high temperatures . AGEs have been associated with insulin resistance , oxidative stress , and chronic inflammation in patients with diabetes . Dietary AGEs are an important contributor to the AGE pool in the body . N(ϵ)-(carboxymethyl)lysine ( CML ) AGE is one of the major biologically and chemically well-characterized AGE markers . The consumption of red meat , which is CML-AGE rich , has been positively associated with pancreatic cancer in men . OBJECTIVES With the use of a published food CML-AGE data base , we estimated the consumption of CML AGE in the prospect i ve NIH-AARP Diet and Health Study and evaluated the association between CML-AGE consumption and pancreatic cancer and the mediating effect of CML AGE on the association between red meat consumption and pancreatic cancer . DESIGN Multivariate Cox proportional hazard regression models were used to estimate HRs and 95 % CIs for pancreatic cancer . RESULTS During an average of 10.5 y of follow-up , we identified 2193 pancreatic cancer cases ( 1407 men and 786 women ) from 528,251 subjects . With the comparison of subjects in the fifth and the first quintiles of CML-AGE consumption , we observed increased pancreatic cancer risk in men ( HR : 1.43 ; 95 % CI : 1.06 , 1.93 , P-trend = 0.003 ) but not women ( HR : 1.14 ; 95 % CI : 0.76 , 1.72 , P-trend = 0.42 ) . Men in the highest quintile of red meat consumption had higher risk of pancreatic cancer ( HR : 1.35 ; 95 % CI : 1.07 , 1.70 ) , which attenuated after adjustment for CML-AGE consumption ( HR : 1.20 ; 95 % CI : 0.95 , 1.53 ) . CONCLUSION Dietary CML-AGE consumption was associated with modestly increased risk of pancreatic cancer in men and may partially explain the positive association between red meat and pancreatic cancer IMPORTANCE Red meat consumption has been consistently associated with an increased risk of type 2 diabetes mellitus ( T2DM ) . However , whether changes in red meat intake are related to subsequent T2DM risk remains unknown . OBJECTIVE To evaluate the association between changes in red meat consumption during a 4-year period and subsequent 4-year risk of T2DM in US adults . DESIGN AND SETTING Three prospect i ve cohort studies in US men and women . PARTICIPANTS We followed up 26,357 men in the Health Professionals Follow-up Study ( 1986 - 2006 ) , 48,709 women in the Nurses ' Health Study ( 1986 - 2006 ) , and 74,077 women in the Nurses ' Health Study II ( 1991 - 2007 ) . Diet was assessed by vali date d food frequency question naires and up date d every 4 years . Time-dependent Cox proportional hazards regression models were used to calculate hazard ratios with adjustment for age , family history , race , marital status , initial red meat consumption , smoking status , and initial and changes in other lifestyle factors ( physical activity , alcohol intake , total energy intake , and diet quality ) . Results across cohorts were pooled by an inverse variance-weighted , fixed-effect meta- analysis . MAIN OUTCOMES AND MEASURES Incident T2DM cases vali date d by supplementary question naires . RESULTS During 1,965,824 person-years of follow-up , we documented 7540 incident T2DM cases . In the multivariate-adjusted models , increasing red meat intake during a 4-year interval was associated with an elevated risk of T2DM during the subsequent 4 years in each cohort ( all P < .001 for trend ) . Compared with the reference group of no change in red meat intake , increasing red meat intake of more than 0.50 servings per day was associated with a 48 % ( pooled hazard ratio , 1.48 ; 95 % CI , 1.37 - 1.59 ) elevated risk in the subsequent 4-year period , and the association was modestly attenuated after further adjustment for initial body mass index and concurrent weight gain ( 1.30 ; 95 % CI , 1.21 - 1.41 ) . Reducing red meat consumption by more than 0.50 servings per day from baseline to the first 4 years of follow-up was associated with a 14 % ( pooled hazard ratio , 0.86 ; 95 % CI , 0.80 - 0.93 ) lower risk during the subsequent entire follow-up through 2006 or 2007 . CONCLUSIONS AND RELEVANCE Increasing red meat consumption over time is associated with an elevated subsequent risk of T2DM , and the association is partly mediated by body weight . Our results add further evidence that limiting red meat consumption over time confers benefits for T2DM prevention Meat contains numerous carcinogens , such as heterocyclic amines , polycyclic aromatic hydrocarbons , and N‐nitroso compounds , which can be derived either from natural food or during the process of food preparation . These carcinogens may increase pancreatic cancer risk . Furthermore , studies in animals showed that polyunsaturated fatty acids , especially linoleic acid , increase pancreatic cancer risk . We examined prospect ively the relation between pancreatic cancer risk and intake of fresh meat , processed meat , fish , eggs , total fat , and different types of fat . The Netherl and s Cohort Study consisted of 120,852 men and women who completed a baseline question naire in 1986 . After 13.3 years of follow‐up , 350 pancreatic cancer cases ( 66 % microscopically confirmed ) were available for analysis . A vali date d 150‐item food‐frequency question naire was used to calculate intake of fresh meat , processed meat , fish , eggs , fat and different types of fat . No association was found when examining the association between intake of fresh meat , other types of meat , fish , eggs , dietary intake of total fat and different types of fat and risk of pancreatic cancer . It is important for future studies to investigate the relation between different meat‐cooking methods and pancreatic cancer . © 2009 High meat consumption has been associated with increased risk of pancreatic cancer in several , although not all , case-control studies . However , prospect i ve data on this relationship are sparse , and the results have been inconsistent . We prospect ively evaluated meat , fish , poultry , and egg consumption in relation to pancreatic cancer incidence in a population -based cohort of 61,433 Swedish women . Diet was assessed with a food-frequency question naire at baseline ( 1987 - 1990 ) and again in 1997 . Pancreatic cancers were ascertained through linkage to the Swedish Cancer Register . Cox proportional hazards models were used to estimate multivariate hazard ratios with 95 % confidence intervals ( CI ) . During the 941,218 person-years of follow-up , from 1987 through 2004 , 172 incident cases of pancreatic cancer were diagnosed . Long-term red meat consumption ( using data from both dietary question naires ) was positively associated with risk of pancreatic cancer ( p-trend = 0.01 ) , whereas long-term poultry consumption was inversely ( p-trend = 0.04 ) associated with risk . The multivariate hazard ratios for the highest versus the lowest category of consumption were 1.73 ( 95 % CI = 0.99 - 2.98 ) for red meat and 0.44 ( 95 % CI = 0.20 - 0.97 ) for poultry . There were no significant associations with processed meat , fish or egg consumption . Findings from this prospect i ve study suggest that substituting poultry for red meat might reduce the risk of pancreatic cancer BACKGROUND Epidemiological studies report positive associations between high-temperature cooked meat intake and pancreatic cancer . We assessed associations between dietary intake of heterocyclic amines ( HCAs ) and benzo(a)pyrene (BaP)-mutagens formed in meat cooked at high temperatures- and incident exocrine pancreatic cancer in a prospect i ve cohort . METHODS The 62 581 subjects r and omized to screening in the Prostate , Lung , Colorectal , and Ovarian Screening Trial ( PLCO ) who completed an initial dietary survey that assessed meat intake , cooking methods , and doneness preferences defined the cohort . Subjects were surveyed annually for incident cancers through 2007 . A National Cancer Institute research data base ( CHARRED ) was used to estimate HCA and BaP intake and a Mutagenic Activity Index ( MAI ) from survey data . Proportional hazard ratios ( HRs ) for risk of pancreatic cancer were estimated from multi-variate Cox regression models by quintile of intake , with the lowest quintile as the referent . RESULTS During follow-up ( median : 10 yr ) , 248 cases of exocrine pancreatic cancer were confirmed . Preferences for well and very well done meat were generally associated with increased risks . Significant elevations in pancreatic cancer risk were found in upper quintiles of MAI , and individual mutagens 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline ( DiMeIQx ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline ( MeIQx ) . Compared to the lowest quintile of MAI , the third and fifth quintiles brought HRs of 1.86 ( 1.22 , 2.85 ) and 1.87 ( 1.16 , 3.02 ) , respectively . These three exposures exhibited significant ( P-trend : 0.01 - 0.03 ) positive trends in risk as their levels increased CONCLUSION Consuming well-done meat cooked at high temperatures , which contains high mutagen levels , appears to confer increased risk of pancreatic cancer INTRODUCTION Current evidence is inconsistent about the association between dietary protein intake and risk of pancreatic cancer ( PC ) . The aim of this study was to evaluate the association between total intake of major dietary protein sources and risk of PC in a large prospect i ve study in Golestan Cohort Study ( GCS ) . METHODS We examined the association of total intake of major dietary protein sources with risk of PC in the 50,045 participants ( 20,855 men and 28,255 women ) of the GCS in northeastern Iran . Participants were aged 40 and older at baseline and actively followed from 2004 to the present time . Dietary data were collected using a vali date d semi-quantitative food-frequency question naire that was administered at baseline . Cox proportional hazards models were used to estimate Multivariable hazard ratios with 95 % confidence intervals ( CI ) . RESULTS During 383,630 person-years of follow-up , 54 cases of pancreatic cancer were ascertained . There was only a statistically significant inverse association between risk of PC for the second versus lowest tertile of plant based protein intake in the first and multivariable models ( HR = .27 , 95 % CI = .12-.64 , HR = .28 , 95 % CI = .12 -.65 respectively ) ; however , this association was not significant anymore when comparing the highest tertile with the lowest one , in the first and multivariable models ( HR = .49 , 95 % CI = .19 - 1.24 , HR = .52 , 95 % CI = .20 - 1.34 respectively ) . CONCLUSION In this large prospect i ve cohort , we did not observe any clear and consistent evidence for an association between main dietary Case-control studies suggest that meat and cholesterol intakes may be related to elevated risks of pancreatic cancer . Few prospect i ve studies have examined associations between diet and pancreatic cancer , although in one recent study saturated fat consumption was related to higher risk . In a cohort of US women , the authors confirmed 178 pancreatic cancer cases over 18 years of follow-up . A mailed 61-item food frequency question naire was self-administered at baseline , and health and lifestyle variables were up date d biennially . Analyses were performed using Cox proportional hazards models to adjust for potential confounders . Intakes of total fat , different types of fats , and cholesterol were not associated with pancreatic cancer risk . Similarly , total meat , red meat , and dairy products were not related to risk . Individual food items contributing to intakes of total meat and dairy products , as well as fish and eggs , did not reveal any specific association . Updating dietary exposures by using question naires from 1980 , 1984 , 1986 , and 1990 produced similar findings . The authors ' data do not support previous findings that meat or saturated fat intakes are related to pancreatic cancer risk . Future prospect i ve studies should examine the influence of cooking practice s as well as other dietary habits on the risk of pancreatic cancer Meat intake , particularly red meat , has been positively associated with pancreatic cancer in some epidemiologic studies . Detailed meat-cooking methods and related mutagens formed in meat cooked at high temperatures have not been evaluated prospect ively as risk factors for this malignancy . We investigated the association between meat , meat-cooking methods , meat-mutagen intake , and exocrine pancreatic cancer in the NIH-American Association of Retired Persons ( NIH-AARP ) Diet and Health Study cohort of 537,302 individuals , aged 50 to 71 years , with complete baseline dietary data ( 1995 - 1996 ) ascertained from a food frequency question naire . A meat-cooking module was completed by 332,913 individuals 6 months after baseline . During 5 years of follow-up , 836 incident pancreatic cancer cases ( 555 men , 281 women ) were identified . Four hundred and fifty-nine cases had complete meat module data . We used Cox proportional hazard models to calculate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) . Total , red , and high-temperature cooked meat intake was positively associated with pancreatic cancer among men ( fifth versus first quintile : HR , 1.41 , 95 % CI , 1.08 - 1.83 , P trend = 0.001 ; HR , 1.42 , 95 % CI , 1.05 - 1.91 , P trend = 0.01 ; and HR , 1.52 , 95 % CI , 1.12 - 2.06 , P trend = 0.005 , respectively ) , but not women . Men showed significant 50 % increased risks for the highest tertile of grilled/barbecued and broiled meat and significant doubling of risk for the highest quintile of overall meat-mutagenic activity ( P trends < 0.01 ) . The fifth quintile of the heterocyclic amine , 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline intake showed a significant 29 % ( P trend = 0.006 ) increased risk in men and women combined . These findings support the hypothesis that meat intake , particularly meat cooked at high temperatures and associated mutagens , may play a role in pancreatic cancer development . ( Cancer Epidemiol Biomarkers Prev 2007;16(12):2664–75 Abstract Aims /hypothesisEpidemiological studies have found that a diet high in fibre and coffee , but low in red meat , reduces the risk for type 2 diabetes . We tested the hypothesis that these nutritional modifications differentially improve whole-body insulin sensitivity ( primary outcome ) and secretion . Methods Inclusion criteria were : age 18–69 years , BMI ≥30 kg/m2 , type 2 diabetes treated with diet , metformin or acarbose and known disease duration of ≤5 years . Exclusion criteria were : HbA1c > 75 mmol/mol ( 9.0 % ) , type 1 or secondary diabetes types and acute or chronic diseases including cancer . Patients taking any medication affecting the immune system or insulin sensitivity , other than metformin , were also excluded . Of 59 patients ( r and omised using r and omisation blocks [ four or six patients ] with consecutive numbers ) , 37 ( 54 % female ) obese type 2 diabetic patients completed this controlled parallel-group 8-week low-energy dietary intervention . The participants consumed either a diet high in cereal fibre ( whole grain wheat/rye : 30–50 g/day ) and coffee ( ≥5 cups/day ) , and free of red meat ( L-RISK , n = 17 ) or a diet low in fibre ( ≤10 g/day ) , coffee-free and high in red meat ( ≥150 g/day ) diet ( H-RISK , n = 20 ) . Insulin sensitivity and secretion were assessed by hyperinsulinaemic – euglycaemic clamp and intravenous glucose tolerance tests with isotope dilution . Whole-body and organ fat contents were measured by magnetic resonance imaging and spectroscopy . Results Whole-body insulin sensitivity increased in both groups ( mean [ 95 % CI ] ) ( H-RISK vs L-RISK : 0.8 [ 0.2 , 1.4 ] vs 1.0 [ 0.4 , 1.7 ] mg kg−1 min−1 , p = 0.59 ) , while body weight decreased ( −4.8 % [ −6.1 % , −3.5 % ] vs −4.6 % [ −6.0 % , −3.3 % ] , respectively ) . Hepatic insulin sensitivity remained unchanged , whereas hepatocellular lipid content fell in both groups ( −7.0 % [ −9.6 % , −4.5 % ] vs −6.7 % [ −9.5 % , −3.9 % ] ) . Subcutaneous fat mass ( −1,553 [ −2,767 , −340 ] cm3 vs −751 [ −2,047 ; 546 ] cm3 , respectively ) visceral fat mass ( −206 [ −783 , 371 ] cm3 vs −241 [ −856 , 373 ] cm3 , respectively ) and muscle fat content ( −0.09 % [ −0.16 % , −0.02 % ] vs −0.02 % [ −0.10 % , 0.05 % ] , respectively ) decreased similarly . Insulin secretion remained unchanged , while the proinflammatory marker IL-18 decreased only after the L-RISK diet . Conclusions /interpretationNo evidence of a difference between both low-energy diets was identified . Thus , energy restriction per se seems to be key for improving insulin action in phases of active weight loss in obese type 2 diabetic patients , with a potential improvement of sub clinical inflammation with the L-RISK diet . Trial Registration : Clinical trials.gov NCT01409330 Funding : This study was supported by the Ministry of Science and Research of the State of North Rhine-Westphalia ( MIWF NRW ) , the German Federal Ministry of Health ( BMG ) , the Federal Ministry for Research ( BMBF ) to the Center for Diabetes Research ( DZD e . V. ) and the Helmholtz Alliance Imaging and Curing Environmental Metabolic Diseases ( ICEMED ) Abstract Objectives : Cigarette smoking is considered an important risk factor for pancreatic cancer , but other purported risk factors are less well established . To learn more about the epidemiology of this important cause of mortality we examined associations with a variety of possible risk factors for death from pancreatic cancer in a large , prospect i ve study of United States adults . Methods : We used proportional hazards models to obtain adjusted estimates of relative risks ( hazards ratios ) . During 14 years of follow-up , 3751 persons died of pancreatic cancer in a cohort of 483,109 men and 619,199 women who had no reported history of cancer at enrollment in 1982 . Results : Cigarette smoking at baseline was associated with fatal pancreatic cancer among men ( multivariate relative risk [ RR ] = 2.1 , 95 % confidence interval [ CI ] 1.9–2.4 ) and among women ( RR = 2.0 , 95 % CI 1.8–2.3 ) . A trend in risk was observed with increasing number of cigarettes smoked per day among current smokers at baseline . With several variables included in separate models for men and women , we found additional factors to be predictive of pancreatic cancer mortality , including family history of pancreatic cancer , black race , diabetes , and increased body mass index . History of gallstones was predictive of pancreatic cancer among men . An inverse association with vegetable consumption was observed among men , that was not statistically significant . Conclusion : Our findings confirm that cigarette smoking is an important predictor of pancreatic cancer mortality , and identify several other factors that may contribute to increased risk BACKGROUND Meat intake has been associated with risk of exocrine pancreatic cancer , but previous findings have been inconsistent . This association has been attributed to both the fat and cholesterol content of meats and to food preparation methods . We analyzed data from the prospect i ve Multiethnic Cohort Study to investigate associations between intake of meat , other animal products , fat , and cholesterol and pancreatic cancer risk . METHODS During 7 years of follow-up , 482 incident pancreatic cancers occurred in 190,545 cohort members . Dietary intake was assessed using a quantitative food frequency question naire . Associations for foods and nutrients relative to total energy intake were determined by Cox proportional hazards models stratified by gender and time on study and adjusted for age , smoking status , history of diabetes mellitus and familial pancreatic cancer , ethnicity , and energy intake . Statistical tests were two-sided . RESULTS The strongest association was with processed meat ; those in the fifth quintile of daily intake ( g/1000 kcal ) had a 68 % increased risk compared with those in the lowest quintile ( relative risk = 1.68 , 95 % confidence interval = 1.35 to 2.07 ; Ptrend < .01 ) . The age-adjusted yearly incidence rates per 100,000 persons for the respective quintiles were 41.3 and 20.2 . Intakes of pork and of total red meat were both associated with 50 % increases in risk , comparing the highest with the lowest quintiles ( both Ptrend < .01 ) . There were no associations of pancreatic cancer risk with intake of poultry , fish , dairy products , eggs , total fat , saturated fat , or cholesterol . Intake of total and saturated fat from meat was associated with statistically significant increases in pancreatic cancer risk but that from dairy products was not . CONCLUSION Red and processed meat intakes were associated with an increased risk of pancreatic cancer . Fat and saturated fat are not likely to contribute to the underlying carcinogenic mechanism because the findings for fat from meat and dairy products differed . Carcinogenic substances related to meat preparation methods might be responsible for the positive association Introduction : Identifying modifiable risk factors for pancreatic cancer is important because of its poor prognosis . Previous findings on diet are inconsistent . Methods : Associations between intake of nutrients , food groups , dietary patterns , and pancreatic cancer risk were examined among 34,642 postmenopausal women in the Iowa Women 's Health Study ( IWHS ) . Results : No significant associations were observed between intake of nutrients and food groups or dietary patterns and pancreatic cancer . Conclusion : Our findings do not support the hypothesis that fruits , vegetables , and red meat are associated with risk of pancreatic cancer . Impact : Dietary intake , assessed in multiple aspects in a large prospect i ve cohort study , was not associated with pancreatic cancer . Cancer Epidemiol Biomarkers Prev ; 20(4 ) ; 711–4 . © 2011 AACR BACKGROUND Pancreatic cancer is the sixth leading cause of cancer death with an increasing trend in China . Dietary intake is believed to play an important role in pancreatic cancer carcinogenesis . The aim of this paper was to evaluate associations between some dietary factors and risk of pancreatic cancer in a multi-centre case-control study conducted in China . MATERIAL S AND METHODS Cases ( n=323 ) were ascertained from four provincial cancer hospitals . Controls ( n=323 ) were r and omly selected from the family members of patients without pancreatic cancer in the same hospitals , 1:1 matched to cases by gender , age and study center . Data were collected with a question naire by personal interview . Odds ratios ( OR ) and 95 % confidence intervals ( 95%CI ) were estimated using conditional logistic regression . RESULTS Tea intake ( OR = 0.49 ; 95%CI : 0.30 - 0.80 ) was associated with a half reduction in risk of pancreatic cancer . Reduced vegetable consumption ( P trend : 0.04 ) was significant related to pancreatic cancer . Although no significant association was found for meat and fruit , ORs were all above or below the reference group . A protective effect was found for fruit ( OR=1.73 for consumption of 1 - 2 times/week vs more than 3 times/week ; 95%CI : 1.05 - 2.86 ) . A high intake of meat was associated to a higher risk of pancreatic cancer ( OR=0.59 for consumption of 1 - 2 times /week vs. more than 3 times /week ; 95%CI : 0.35 - 0.97 ) . CONCLUSIONS The present study supports fruit consumption to reduce pancreatic cancer risk and indicates that high consumption of meat is related to an elevated risk . Direct inverse relations with tea and vegetable intake were also confirmed |
13,344 | 28,991,903 | Considering the positive effect of EMF on medication adherence , EMF might be a promising intervention to enhance medication adherence .
However , the effect of EMF on clinical outcomes was inconclusive . | OBJECTIVE This study aims to assess the efficacy of Electronic Monitoring Feedback ( EMF ) as an intervention to improve medication adherence ( i.e. dose- or full adherence ) and clinical outcomes in adult patients . | This study examined the role of a Medication Event Monitoring System ( MEMS ) to assess pill-taking behavior and enhance compliance within a r and omized trial of bupropion-SR for smoking cessation . Female participants ( N = 97 ) received MEMS bottles containing bupropion-SR 150 mg or placebo , to be taken twice daily . A r and omly selected “ feedback ” group of participants was told about the recording device in the bottle cap and received weekly graphic feedback showing their pill-taking behavior with specific instructions for improving compliance . A “ no-feedback ” group was not informed about the MEMS bottles , and did not receive further instruction or feedback beyond the st and ard dosing instructions . Compliance outcomes were the total doses taken and number of doses taken within the prescribed time interval . Results indicated significantly higher compliance over time for the feedback group . Participation in the feedback group predicted higher compliance beyond demographic , smoking , and health belief variables , suggesting significant benefit in providing brief feedback and instruction throughout the medication regimen Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items BACKGROUND Well- design ed r and omized controlled trials ( RCTs ) testing efficacy of post-transplant medication adherence enhancing interventions and clinical outcomes are scarce . METHODS This r and omized controlled trial enrolled adult heart , liver , and lung transplant recipients who were > 1 year post-transplant and on tacrolimus twice daily ( convenience sample ) ( visit 1 ) . After a 3-month run-in period , patients were r and omly assigned 1:1 to intervention group ( IG ) or control group ( CG ) ( visit 2 ) , followed by a 6-month intervention ( visits 2 - 4 ) and a 6-month adherence follow-up period ( visit 5 ) . All patients used electronic monitoring for 15 months for adherence measurement , generating a daily binary adherence score per patient . Post-intervention 5-year clinical event-free survival ( mortality or retransplantation ) was evaluated . The IG received staged multicomponent tailored behavioral interventions ( visits 2 - 4 ) building on social cognitive theory and trans-theoretical model ( e.g. , electronic monitoring feedback , motivational interviewing ) . The CG received usual care and attended visits 1 - 5 only . Intention-to-treat analysis used generalized estimating equation modeling and Kaplan-Meier survival analysis . RESULTS Of 247 patients , 205 were r and omly assigned ( 103 IG , 102 CG ) . At baseline , average daily proportions of patients with correct dosing ( 82.6 % IG , 78.4 % CG ) and timing adherence ( 75.8 % IG , 72.2 % CG ) were comparable . The IG had a 16 % higher dosing adherence post-intervention ( 95.1 % IG , 79.1 % CG ; p < 0.001 ) , result ing in odds of adherence being 5 times higher in the IG than in the CG ( odds ratio 5.17 , 95 % confidence interval 2.86 - 9.38 ) . This effect was sustained at end of follow-up ( similar results for timing adherence ) . In the IG , 5-year clinical event-free survival was 82.5 % vs 72.5 % in the CG ( p = 0.18 ) . CONCLUSION Our intervention was efficacious in improving adherence and sustainable . Further research should investigate clinical impact , cost-effectiveness , and scalability In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Background / Aims . One of the causes of uncontrolled secondary hyperparathyroidism ( sHPT ) is patient 's poor drug adherence . We evaluated the clinical benefits of an integrated care approach on the control of sHPT by cinacalcet . Methods . Prospect i ve , r and omized , controlled , multicenter , open-label study . Fifty hemodialysis patients on a stable dose of cinacalcet were r and omized to an integrated care approach ( IC ) or usual care approach ( UC ) . In the IC group , cinacalcet adherence was monitored using an electronic system . Results were discussed with the patients in motivational interviews , and drug prescription adapted accordingly . In the UC group , drug adherence was monitored , but results were not available . Results . At six months , 84 % of patients in the IC group achieved recommended iPTH targets versus 55 % in the UC group ( P = 0.04 ) . The mean cinacalcet taking adherence improved by 10.8 % in the IC group and declined by 5.3 % in the UC group ( P = 0.02 ) . Concomitantly , the mean dose of cinacalcet was reduced by 7.2 mg/day in the IC group and increased by 6.4 mg/day in the UC group ( P = 0.03 ) . Conclusions . The use of a drug adherence monitoring program in the management of sHPT in hemodialysis patients receiving cinacalcet improves drug adherence and iPTH control and allows a reduction in the dose of cinacalcet BACKGROUND Poor long-term adherence is an important cause of uncontrolled hypertension . We examined whether monitoring drug adherence with an electronic system improves long-term blood pressure ( BP ) control in hypertensive patients followed by general practitioners ( GPs ) . METHODS A pragmatic cluster r and omised controlled study was conducted over one year in community pharmacists/GPs ' networks r and omly assigned either to usual care ( UC ) where drugs were dispensed as usual , or to intervention ( INT ) group where drug adherence could be monitored with an electronic system ( Medication Event Monitoring System ) . No therapy change was allowed during the first 2 months in both groups . Thereafter , GPs could modify therapy and use electronic monitors freely in the INT group . The primary outcome was a target office BP<140/90 mmHg . RESULTS Sixty-eight treated uncontrolled hypertensive patients ( UC : 34 ; INT : 34 ) were enrolled . Over the 12-month period , the likelihood of reaching the target BP was higher in the INT group compared to the UC group ( p<0.05 ) . At 4 months , 38 % in the INT group reached the target BP vs. 12 % in the UC group ( p<0.05 ) , and 21 % vs. 9 % at 12 months ( p : ns ) . Multivariate analyses , taking account of baseline characteristics , therapy modification during follow-up , and clustering effects by network , indicate that being allocated to the INT group was associated with a greater odds of reaching the target BP at 4 months ( p<0.01 ) and at 12 months ( p=0.051 ) . CONCLUSION GPs monitoring drug adherence in collaboration with pharmacists achieved a better BP control in hypertensive patients , although the impact of monitoring decreased with time Effective antiretroviral therapy ( ART ) requires excellent adherence . Little is known about how to improve ART adherence in many HIV/AIDS-affected countries , including China . We therefore assessed an adherence intervention among HIV-positive patients in southwestern China . Eighty subjects were enrolled and monitored for 6 months . Sixty-eight remaining subjects were r and omized to intervention/control arms . In months 7–12 , intervention subjects were counseled using EDM feedback ; controls continued with st and ard of care . Among r and omized subjects , mean adherence and CD4 count were 86.8 vs. 83.8 % and 297 vs. 357 cells/μl in intervention vs. control subjects , respectively . At month 12 , among 64 subjects who completed the trial , mean adherence had risen significantly among intervention subjects to 96.5 % but remained unchanged in controls . Mean CD4 count rose by 90 cells/μl and declined by 9 cells/μl among intervention and control subjects , respectively . EDM feedback as a counseling tool appears promising for management of HIV and other chronic diseases In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted This study was conducted to replicate and extend initial positive findings on the usefulness of a Medication Event Monitoring System ( MEMS ) to assess pill-taking behavior and enhance compliance with bupropion for smoking cessation . Participants ( N=55 ) received MEMS bottles containing bupropion-SR ( 150 mg ) to be taken twice daily for 7 weeks . For participants r and omly assigned to the Enhanced Therapy group ( n=27 ) , weekly individual smoking cessation therapy sessions included an additional 10 min of MEMS feedback and compliance enhancement counseling using CBT techniques . The Usual Care group ( n=28 ) received weekly individual smoking cessation sessions only . Compliance outcomes included total doses taken and number of doses taken within the prescribed time interval . Results indicated significantly higher compliance over time for the Enhanced Therapy group . Smoking abstinence rates did not differ between the two groups , although results from the pooled sample analysis showed a significant association between level of medication compliance and abstinence status at treatment weeks 3 and 6 . Incorporating MEMS-based compliance interventions into smoking pharmacotherapy trials is recommended BACKGROUND Medication nonadherence contributes to hospitalization and mortality , yet there have been few interventions tested that improve adherence and reduce hospitalization and mortality in heart failure ( HF ) . Our objective was to determine whether an education intervention improved medication adherence and cardiac event-free survival . METHODS AND RESULTS A r and omized controlled trial was conducted on 82 HF patients . The intervention was based on the theory of planned behavior ( TPB ) and included feedback of medication-taking behavior using the Medication Event Monitoring System ( MEMS ) . Patients were assigned to one of three groups : 1 ) theory-based education plus MEMS feedback ; 2 ) theory-based education only ; or 3 ) usual care ( control ) . Cardiac events were collected for 9 months . Patients in both intervention groups were more adherent over follow-up compared with the control group . In Cox regression , patients in either intervention group had a longer event-free survival compared with those in the control group before and after controlling age , marital status , financial status , ejection fraction , New York Heart Association functional class , angiotensin-converting enzyme inhibitor use , and presence or absence of a significant other during the intervention ( P < .05 ) . CONCLUSIONS Use of an intervention based on the TPB improves medication adherence and outcomes in patients with HF and therefore offers promise as a clinical ly applicable intervention to help patients with HF to adhere to their prescribed regimen STUDY OBJECTIVES To evaluate whether direct feedback discussion on inhaled steroid use might influence subsequent adherence with this therapy . DESIGN AND SETTING A 10-week , single-blind , r and omized trial in asthma patients . Inclusion criteria included forced expiratory volume in 1 second < 80 % , one or more markers for low socioeconomic status , and the use of inhaled steroids . Inhaled steroid and beta-agonist use were electronically monitored . All patients received st and ard asthma care . The treatment group received direct clinician-to-patient feedback discussion on their inhaled steroid and beta-agonist use on all subsequent visits , whereas this information was withheld during the study period in the control group . MEASURES 1 ) Mean weekly inhaled steroid adherence [ ( number of actuations/prescribed number of actuations ) x 100 ] ; 2 ) number of days with overuse of inhaled steroids ; 3 ) 24-hour and nighttime albuterol use ; 4 ) included forced expiratory volume in 1 second ; and 5 ) Asthma Quality of Life Question naire total score . RESULTS Ten treatment and nine control patients completed the study . Mean weekly inhaled steroid adherence over the first week was not significantly different in the treatment and control groups : 61 + /- 9 % versus 51 + /- 5 % , respectively . However , by the second week , adherence increased to 81 + /- 7 % in the treatment group , whereas it decreased to 47 + /- 7 % in the control group ( P = 0.003 ) . Adherence remained above 70 % in the treatment group for the entire trial , but continued to decrease in the control group . Overuse of inhaled steroids was low in both groups . There were no group differences in any of the asthma outcomes . CONCLUSIONS Direct clinician-to-patient feedback discussion on inhaled steroid use using electronic printouts did improve adherence in the short-term in asthma patients at high-risk for poor adherence 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 6-month r and omized controlled trial evaluated the impact on quality of life ( QOL ) of a medication reminder device for patients with HIV . Patients were eligible if they had taken three or fewer highly active antiretroviral therapy ( HAART ) regimens or were treatment naïve . The intervention group received the Disease Management Assistance System ( DMAS ) , a prompting device that verbally reminds patients at medication times and electronically records doses , and a monthly 30 minute adherence educational session . Controls received education only . QOL was measured at baseline and 6 months using the Centers for Epidemiologic Studies Depression Scale ( CES-D ) , Instrumental Activities of Daily Living ( IADLs ) , and the Medical Outcomes Study HIV Health Survey ( MOS-HIV ) . At baseline , 62 patients completed surveys ( 31 control , 31 DMAS ) ; at month 6 , 48 patients completed surveys ( 23 control , 25 DMAS ) . At month 6 , controls had improved QOL scores for CES-D , IADLs , physical health , general health , pain , QOL , and role functioning , while participants in the DMAS arm had some deterioration in QOL scores . These differences persisted after controlling for demographics , baseline CD4 , and adherence . DMAS was associated with improved adherence but decreased QOL Abstract : Background : Although non‐adherence to an immunosuppressive regimen ( NAH ) is a major risk factor for poor outcome after renal transplantation ( RTx ) , very few studies have examined non‐adherence intervention in this context . This pilot r and omized controlled trial ( RCT ) tested the efficacy of an educational – behavioural intervention to increase adherence in non‐adherent RTx patients . We also assessed how NAH evolves over time OBJECTIVE To investigated the effectiveness of an adherence intervention ( AIMS ) design ed to fit HIV-clinics ' routine care procedures . DESIGN Through block r and omization , patients were allocated to the intervention or control group . The study included 2 months baseline measurement , 3 months intervention , and 4 months follow-up . HIV-nurses delivered a minimal intervention ( " adherence sustaining " ) to patients scoring > 95 % adherence at baseline , and an intensive intervention ( " adherence improving " ) to patients with < 95 % adherence . Control participants received high- quality usual care . MAIN OUTCOME MEASURES Electronically monitored adherence and viral load . RESULTS 133 patients were included ( 67 control , 66 intervention ) , 60 % had < 95 % adherence at baseline , and 87 % ( 116/133 ) completed the trial . Intent-to-treat analyses showed that adherence improved significantly in the complete intervention sample . Subgroup analyses showed that this effect was caused by participants scoring < 95 % at baseline ( mean difference = 15.20 % ; p < .001 ) . These effects remained stable during follow-up . The number of patients with an undetectable viral load increased in the intervention group compared to the control group ( OR = 2.96 , p < .05 ) . Treatments effects on viral load were mediated by the improvements in adherence . CONCLUSIONS The AIMS -intervention was effective and can be integrated in routine clinical care for HIV-infected patients . Future research should study its (cost)effectiveness among more heterogeneous sample s and in setting s with variable levels of st and ard care BACKGROUND Improving inhaled corticosteroid ( ICS ) adherence should improve asthma outcomes . OBJECTIVE In a r and omized controlled trial we tested whether an individualized problem-solving ( PS ) intervention improves ICS adherence and asthma outcomes . METHODS Adults with moderate or severe asthma from clinics serving urban neighborhoods were r and omized to PS ( ie , defining specific barriers to adherence , proposing/weighing solutions , trying the best , assessing , and revising ) or st and ard asthma education ( AE ) for 3 months and then observed for 3 months . Adherence was monitored electronically . Outcomes included the following : asthma control , FEV(1 ) , asthma-related quality of life , emergency department ( ED ) visits , and hospitalizations . In an intention-to-treat- analysis longitudinal models using r and om effects and regression were used . RESULTS Three hundred thirty-three adults were r and omized : 49 ± 14 years of age , 72 % female , 68 % African American , 7 % Latino , mean FEV(1 ) of 66 % ± 19 % , and 103 ( 31 % ) with hospitalizations and 172 ( 52 % ) with ED visits for asthma in the prior year . There was no difference between groups in overall change in any outcome ( P > .20 ) . Mean adherence ( 61 % ± 27 % ) decreased significantly ( P = .0004 ) over time by 14 % and 10 % in the AE and PS groups , respectively . Asthma control improved overall by 15 % ( P = .002 ) . In both groups FEV(1 ) and quality of life improved by 6 % ( P = .01 ) and 18 % ( P < .0001 ) , respectively . However , the improvement in FEV(1 ) only occurred during monitoring but not subsequently after r and omization . Rates of ED visits and hospitalizations did not significantly decrease over the study period . CONCLUSION PS was not better than AE in improving adherence or asthma outcomes . However , monitoring ICS use with provision of medications and attention , which was imposed on both groups , was associated with improvement in FEV(1 ) and asthma control |
13,345 | 25,290,098 | RESULTS Method ological studies illustrated appropriate use of FE analysis for simulation of foot mechanics , incorporating nonlinear tissue mechanics , contact and rigid body movements .
FE studies of pathomechanics have provided estimates of internal soft tissue stresses , and suggest that such stresses may often be considerably larger than those measured at the plantar surface and are proportionally greater in the diabetic foot compared to controls .
FE analysis allowed evaluation of insole performance and development of new insole design s , footwear and corrective surgery to effectively provide intervention strategies .
The technique also presents the opportunity to simulate the effect of changes associated with the diabetic foot on non-mechanical factors such as blood supply to local tissues . | BACKGROUND Over the past two decades finite element ( FE ) analysis has become a popular tool for research ers seeking to simulate the biomechanics of the healthy and diabetic foot .
The primary aims of these simulations have been to improve our underst and ing of the foot 's complicated mechanical loading in health and disease and to inform interventions design ed to prevent plantar ulceration , a major complication of diabetes .
This article provides a systematic review and summary of the findings from FE analysis -based computational simulations of the diabetic foot . | Aims /hypothesisThe aim of the present study was to investigate re source utilisation and associated costs in patients with diabetic foot ulcers and to analyse differences in re source utilisation between individuals with or without peripheral arterial disease ( PAD ) and /or infection . Methods Data on re source utilisation were collected prospect ively in a European multicentre study . Data on 1,088 patients were available for the analysis of re source use , and data on 821 patients were included in the costing analysis . Costs were calculated for each patient by multiplying the country-specific direct and indirect unit costs by the number of re sources used from inclusion into the study up to a defined endpoint . Country-specific costs were converted into purchasing power st and ards . Results Re source use and costs varied between outcome groups and between disease severity groups . The highest costs per patient were for hospitalisation , antibiotics , amputations and other surgery . All types of re source utilisation and costs increased with the severity of disease . The total cost per patient was more than four times higher for patients with infection and PAD at inclusion than for patients in the least severe group , who had neither . Conclusions /interpretationImportant differences in re source use and costs were found between different patient groups . The costs are highest for individuals with both peripheral arterial disease and infection , and these are mainly related to substantial costs for hospitalisation . In view of the magnitude of the costs associated with in-hospital stay , reducing the number and duration of hospital admissions seems an attractive option to decrease costs in diabetic foot disease A numerical-experimental approach has been developed to characterize heel-pad deformation at the material level . Left and right heels of 20 diabetic subjects and 20 nondiabetic subjects matched for age , gender and body mass index were indented using force-controlled ultrasound . Initial tissue thickness and deformation were measured using M-mode ultrasound ; indentation forces were recorded simultaneously . An inverse finite-element analysis of the indentation protocol using axisymmetric models adjusted to reflect individual heel thickness was used to extract nonlinear material properties describing the hyperelastic behavior of each heel . Student 's t-tests revealed that heel pads of diabetic subjects were not significantly different in initial thickness nor were they stiffer than those from nondiabetic subjects . Another heel-pad model with anatomically realistic surface representations of the calcaneus and soft tissue was developed to estimate peak pressure prediction errors when average rather than individualized material properties were used . Root-mean-square errors of up to 7 % were calculated , indicating the importance of subject-specific modeling of the nonlinear elastic behavior of the heel pad . Indentation systems combined with the presented numerical approach can provide this information for further analysis of patient-specific foot pathologies and therapeutic footwear design 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 A major goal of therapeutic footwear in patients with pain or those at risk for skin injury is to relieve focal loading under prominent metatarsal heads . One frequent approach is to place plugs of compliant material into the midsole of the shoe . This study investigated 36 plug design s , a combination of three material s , six geometries , and two placements using a two-dimensional ( 2D ) finite element model . Realistic loading conditions were obtained from plantar pressures ( PP ) recorded during walking in five subjects who wore control midsoles manufactured using Microcell Puff . Measured peak pressures underneath the second metatarsal head were similar to the results of the control model . PP obtained from simulations with the plugs built into a firm midsole were compared to the simulation results of the control midsole . Large plugs ( e.g. 40 mm width ) , made out of Microcell Puff Lite or Plastazote Medium , placed at peak pressure sites , result ed in highest reductions in peak pressures ( 18 - 28 % ) . Smaller plugs benefited from tapering when placed at high pressure areas . Case studies were completed on a healthy male subject and a diabetic female patient to address the efficacy of a plug design favored by our simulations ( pressure based placement , 40 x 20 mm , Plastazote Medium ) . Successful reductions of second metatarsal head pressures were observed with a mediolateral load redistribution that was not represented by our model . 2D computer simulations allowed systematic investigation of plug properties without the need for high volume experimentation on human subjects and established basic guidelines for plug selection . In particular , plugs that are placed based on plantar pressure measurements were proven to be more effective when compared to those positioned according to the projection of the bony l and mark on the foot-shoe plantar contact area |
13,346 | 29,468,065 | A small number of consistent findings emerged in individuals in the acute phase of illness with BN or BED including : volume reduction and increases across a range of areas ; hypoactivity in the frontostriatal circuits ; and aberrant responses in the insula , amygdala , middle frontal gyrus and occipital cortex to a range of different stimuli or tasks ; a link between illness severity in BN and neural changes ; diminished attentional capacity and early learning ; and in SPECT studies , increased rCBF in relation to disorder-related stimuli .
One clear finding is that illness severity , exclusively defined as the frequency of binge eating or bulimic episodes , is related to greater neural changes . | Objective In recent decades there has been growing interest in the use of neuroimaging techniques to explore the structural and functional brain changes that take place in those with eating disorders .
However , to date , the majority of research has focused on patients with anorexia nervosa .
This systematic review addresses a gap in the literature by providing an examination of the published literature on the neurobiology of individuals who binge eat ; specifically , individuals with bulimia nervosa ( BN ) and binge eating disorder ( BED ) . | BACKGROUND Abnormalities in perception and evaluation of body shape are a hallmark of eating disorders . METHODS Brain responses to line drawings of underweight , normal weight , and overweight female bodies were measured with functional magnetic resonance imaging in 9 women with bulimia nervosa , 13 with anorexia nervosa , and 18 healthy women . Participants rated the stimuli for fear and disgust . RESULTS In the three groups , the lateral fusiform gyrus , inferior parietal cortex , and lateral prefrontal cortex were activated in response to body shapes compared with the control condition ( drawings of houses ) . The responses in the lateral fusiform gyrus and in the parietal cortex were less strong in patients with eating disorders compared with healthy control subjects . Patients with eating disorders rated the body shapes in all weight categories as more aversive than did healthy women . In the group with eating disorders , the aversion ratings correlated positively with activity in the right medial apical prefrontal cortex . CONCLUSIONS Processing of female body shapes engages a distributed neural network , parts of which are underactive in women with eating disorders . The considerable variability in subjective emotional reaction to body shapes in patients with eating disorders is associated with differential activity in the prefrontal cortex OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity We used single photon emission computed tomography ( SPECT ) with Tc-99m-HMPAO to examine the characteristics of regional cerebral blood flow ( rCBF ) in five patients with bulimia nervosa ( BN ) , eight patients with anorexia nervosa ( AN ) , and in nine healthy controls . The SPECT examinations were performed before and after food intake stimulus , and the values of the corrected ratio ( R ) for rCBF in 10 cerebral cortical regions before ( Rbefore ) and after eating ( Rafter ) were calculated . The asymmetry indices ( AI ) of the R values for the left and right side of each cortical region and the percent change from Rbefore to Rafter ( % change ) were computed . In comparison with the other two groups , BN patients showed significantly higher Rbefore values in the bilateral inferior frontal and left temporal regions . The AN patients showed significantly lower Rbefore values in the left parietal region than the control group . There were no significant differences in Rafter values among the three groups . The % change values in the AN group showed the greatest increase in 9 out of the 10 regions . In contrast to the positive values obtained from the 10 regions observed in the AN group , 5 out of the 10 regions in the BN group showed negative values . Among the three groups , significant differences in % change were observed on both sides of the inferior frontal , temporal , parietal , and occipital regions . These findings indicate that differences in cerebral function of BN and AN patients can be characterized through SPECT imaging OBJECTIVE To assess the functioning of mesolimbic and fronto-striatal areas involved in reward-based spatial learning in teenaged girls with bulimia nervosa ( BN ) that might be involved in the development and maintenance of maladaptive behaviors characteristic of the disorder . METHOD We compared functional magnetic resonance imaging blood oxygen level-dependent response in 27 adolescent girls with BN to that of 27 healthy , age-matched control participants during a reward-based learning task that required learning to use extra-maze cues to navigate a virtual 8-arm radial maze to find hidden rewards . We compared groups in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudo-r and omly to experimentally prevent learning . RESULTS Both groups learned to navigate the maze to find hidden rewards , but group differences in brain activity associated with maze navigation and reward processing were detected in the fronto-striatal regions and right anterior hippocampus . Unlike healthy adolescents , those with BN did not engage the right inferior frontal gyrus during maze navigation , activated the right anterior hippocampus during the receipt of unexpected rewards ( control condition ) , and deactivated the left superior frontal gyrus and right anterior hippocampus during expected reward receipt ( learning condition ) . These patterns of hippocampal activation in the control condition were significantly associated with the frequency of binge-eating episodes . CONCLUSION Adolescents with BN displayed abnormal functioning of the anterior hippocampus and fronto-striatal regions during reward-based spatial learning . These findings suggest that an imbalance in control and reward circuits may arise early in the course of BN . Clinical trial registration information-An fMRI Study of Self-Regulation in Adolescents With Bulimia Nervosa ; https:// clinical trials.gov/ ; NCT00345943 The present study is a r and omized controlled trial that aims to evaluate the efficacy of Neurofeedback compared to st and ard pharmacological intervention in the treatment of attention deficit/hyperactivity disorder ( ADHD ) . The final sample consisted of 23 children with ADHD ( 11 boys and 12 girls , 7 - 14 years old ) . Participants carried out 40 theta/beta training sessions or received methylpheni date . Behavioral rating scales were completed by fathers , mothers , and teachers at pre- , post-treatment , two- , and six-month naturalistic follow-up . In both groups , similar significant reductions were reported in ADHD functional impairment by parents ; and in primary ADHD symptoms by parents and teachers . However , significant academic performance improvements were only detected in the Neurofeedback group . Our findings provide new evidence for the efficacy of Neurofeedback , and contribute to enlarge the range of non-pharmacological ADHD intervention choices . To our knowledge , this is the first r and omized controlled trial with a six-month follow-up that compares Neurofeedback and stimulant medication in ADHD BACKGROUND Craving or the " urge to consume " is a characteristic of bulimic eating disorders and addictions . Dysfunction of the dorsolateral prefrontal cortex ( DLPFC ) is associated with craving . We investigated whether stimulation of the DLPFC reduces food craving in people with a bulimic-type eating disorder . METHODS Thirty-eight people with bulimic-type eating disorders were r and omly allocated to receive one session of real or sham high-frequency repetitive transcranial magnetic stimulation ( rTMS ) to the left DLPFC in a double-blind procedure . Outcome measures included self-reported food craving immediately after the stimulation session and frequency of bingeing over a 24-hour follow-up period . RESULTS Compared with sham control , real rTMS was associated with decreased self-reported urge to eat and fewer binge-eating episodes over the 24 hours following stimulation . CONCLUSIONS High-frequency rTMS of the left DLPFC lowers cue-induced food cravings in people with a bulimic eating disorder and may reduce binge eating . These results provide a rationale for exploring rTMS as a treatment for bulimic eating disorders |
13,347 | 28,378,919 | Our study indicated that DPP-4 inhibitors show greater efficacy in Japanese patients than in non-Japanese patients , which may be an important consideration in the global development strategy of new diabetic medications | A systematic review of the differences in the efficacy of dipeptidyl peptidase-4 ( DPP-4 ) inhibitors between Japanese and non-Japanese subjects was conducted . | The stimulation of insulin vs. inhibition of glucagon secretion in relation to the antidiabetic action of glucagon-like peptide-1 ( GLP-1 ) is not established . Here , the influence of a 4-wk increase in circulating GLP-1 by inhibition of dipeptidyl peptidase-4 ( DPP-4 ) on 24-h glucose and insulin and glucagon responses to breakfast was studied in subjects with dietary controlled diabetes [ age : 65 + /- 8 yr ( SD ) , body mass index : 27.3 + /- 3.3 kg/m(2 ) , fasting plasma glucose : 9.0 + /- 1.3 mmol/liter ] . Compared with placebo ( n = 19 ) , a specific DPP-4 inhibitor [ ( 1-[[(3-hydroxy-1-adamantyl ) amino ] acetyl]-2-cyano-(S)-pyrrolidine ) ( LAF237 ) ; 100 mg daily , n = 18 ] reduced fasting glucose by 0.70 mmol/liter ( P = 0.037 ) , 4-h pr and ial glucose excursion by 1.45 mmol/liter ( P < 0.001 ) , and mean 24-h glucose by 0.93 mmol/liter ( P < 0.001 ) . Baseline and postpr and ial active GLP-1 were increased by LAF237 . The glucagon response to breakfast was reduced by LAF237 ( glucagon levels at 60 min were 88 + /- 8 pg/ml before treatment vs. 77 + /- 5 pg/ml after ; P = 0.001 ) . In contrast , the overall insulin levels were not altered . The 4-wk reduction in glucagon correlated with the reduction in 2-h glucose ( r = 0.61 ; P = 0.008 ) . No such association was observed for insulin . Thus , improved metabolic control by DPP-4 inhibition in type 2 diabetes is seen in association with reduced glucagon levels and , despite the lower glycemia , unaltered insulin levels Introduction Saxagliptin , sitagliptin , and vildagliptin are dipeptidyl peptidase-4 ( DPP-4 ) inhibitors widely approved for use in patients with type 2 diabetes . Using a crossover design , the present study compared trough levels of DPP-4 inhibition provided by these agents in a single cohort of patients with type 2 diabetes . Methods This was a r and omized , placebo-controlled , open-label , five-period crossover study . Eligible patients were 18–65 years of age , either treatment-naïve or off prior antihyperglycemic agent therapy for at least 6 or 12 weeks ( depending on the prior therapy ) , and had glycated hemoglobin ( HbA1C ) ≥6.5 % and ≤10.0 % . In separate study periods , patients received 5 mg saxagliptin q.d . ( saxa-5 ) , 100 mg sitagliptin q.d . ( sita-100 ) , 50 mg vildagliptin q.d . ( vilda-50-q.d . ) , 50 mg vildagliptin b.i.d . ( vilda-50-b.i.d . ) , or placebo for 5 days . The primary endpoint was trough % DPP-4 inhibition , derived by comparing DPP-4 activity 24 h after the Day-5 morning dose with predose activity in the same period and analyzed using a linear mixed-effects model with fixed-effects terms for treatment and period . Results Mean ( range ) baseline HbA1C was 7.4 % ( 6.4–9.0 % ; N = 22 ) . Least-squares ( LS ) mean trough % DPP-4 inhibition was 73.5 % , 91.7 % , 28.9 % , 90.6 % , and 3.5 % after saxa-5 , sita-100 , vilda-50-q.d . , vilda-50-b.i.d . , and placebo , respectively . In patients treated with sita-100 , the LS-mean difference in trough % DPP-4 inhibition was 18.2 % greater than with saxa-5 ( p < 0.001 ) , 62.9 % greater than with vilda-50-q.d . ( p < 0.001 ) , 1.1 % greater than with vilda-50-b.i.d . ( p = 0.128 ) , and 87.8 % greater than with placebo ( p < 0.001 ) . Mean % DPP-4 inhibition was nearly maximal at 12 h postdose regardless of active treatment . Thus , these between-group comparisons at trough primarily reflected differences in duration of action . Adverse events reported during the study were transient and mild or moderate in intensity . Conclusion Once daily treatment with sitagliptin provided trough DPP-4 inhibition significantly greater than saxagliptin or vildagliptin administered once daily , and similar to that provided by vildagliptin administered twice daily Aim : To investigate the safety , tolerability , pharmacokinetics and pharmacodynamics of linagliptin in patients with type 2 diabetes mellitus ( T2DM ) |
13,348 | 22,581,194 | Conclusions Measurement of functional performance more than 2 years after ACL reconstruction consists of concentric or isometric strength , the single-leg hop for distance or a combination .
The Limb Symmetry Index is used as the main outcome parameter to compare the involved leg with the uninvolved . | Purpose The purpose of this systematic review was to identify the measurements that are used in clinical practice to assess the quantity and quality of functional performance in men and women more than 2 years after ACL reconstruction with bone patellar-tendon bone ( BPTB ) or semitendinosus/gracilis ( STG ) graft . | Background and Purpose Although various hop tests have been proposed as performance-based outcome measures following anterior cruciate ligament ( ACL ) reconstruction , limited reports of their measurement properties exist . The purpose of this study was to investigate the reliability and longitudinal validity of data obtained from hop tests during rehabilitation after ACL reconstruction . Subjects Forty-two patients , 15 to 45 years of age , who had undergone ACL reconstruction participated in the study . Methods and Measures The study design was prospect i ve and observational with repeated measures . The subjects performed a series of 4 hop tests on 3 separate occasions within the 16th week following surgery and on a fourth occasion 6 weeks later . The tests were a single hop for distance , a 6-m timed hop , a triple hop for distance , and crossover hops for distance . Performance on the ACL-reconstructed limb was expressed as a percentage of the performance on the nonoperative limb , termed the “ limb symmetry index . ” Subjects also completed the Lower Extremity Functional Scale and a global rating of change question naire . Results Intraclass correlation coefficients for limb symmetry index values ranged from .82 to .93 . St and ard errors of measurement were 3.04 % to 5.59 % . Minimal detectable changes , at the 90 % confidence level , were 7.05 % to 12.96 % . Changes in hop test scores on the operative limb were statistically greater than changes on the nonoperative limb . Pearson correlations ( r ) between change in hop performances and self-reported measures ranged from .26 to .58 . Discussion and Conclusion The results show that the described series of hop tests provide a reliable and valid performance-based outcome measure for patients undergoing rehabilitation following ACL reconstruction . These findings support the use and facilitate the interpretation of hop tests for research and clinical practice A more sports-specific and detailed strength assessment has been advocated for patients after anterior cruciate ligament ( ACL ) injury and reconstruction . The purpose of this study was to develop a test battery of lower extremity strength tests with high ability to discriminate between leg power development on the injured and uninjured sides in patients after ACL injury and in patients who have undergone ACL reconstruction . Twenty-three patients were tested 6 months after ACL injury and 44 patients were tested 6 months after ACL reconstruction . Twenty-four of the 44 patients were operated on using a hamstrings graft and 20 patients were operated on using a patellar tendon graft . All the patients performed a test battery of three strength tests for each leg in a r and omised order . The three strength tests were chosen to reflect quadriceps and hamstring muscular power in a knee-extension and a knee-flexion test ( open kinetic chain ) and lower-extremity muscular power in a leg-press test ( closed kinetic chain ) . There was a higher sensitivity for the test battery to discriminate abnormal leg power compared with any of the three strength tests individually . Nine out of ten patients after ACL reconstruction and six out of ten of the patients after ACL injury exhibited abnormal leg power symmetry using the test battery . Thus , this test battery had high ability in terms of discriminating between the leg power performance on the injured and uninjured side , both in patients with an ACL injury and in patients who have undergone ACL reconstruction . It is concluded that a test battery consisting of a knee-extension , knee-flexion and leg-press muscle power test had high ability to determine deficits in leg power 6 months after ACL injury and reconstruction . Only a minority of the patients had restored leg muscle power . The clinical relevance is that the test battery may contribute to the decision-making process when deciding whether and when patients can safely return to strenuous physical activities after an ACL injury or reconstruction Background : R and omized controlled trials after anterior cruciate ligament reconstructions with long-term follow-up including assessment of health-related quality of life are rare . Purpose : To compare clinical outcome and health-related quality of life 8 years after anterior cruciate ligament reconstruction using 2 types of graft . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Long-term follow-up of 164 patients with anterior cruciate ligament injury r and omized to arthroscopic reconstruction with a quadrupled semitendinosus graft or a bone – patellar tendon – bone graft was undertaken . After a mean 8 years , 153 patients were available for follow-up , including instrumented laxity , 1-legged hop test , a knee-walking test , and assessment with International Knee Documentation Committee , Lysholm , Tegner , and patellofemoral pain score . Health-related quality of life was assessed with Knee Osteoarthritis Outcome Score and Short Form–36 . Results : Patients in both graft groups retained the same stability , knee function , and health-related quality of life . The patellofemoral pain score was similar for both groups ; the bone – patellar tendon – bone group had more donor site morbidity from kneeling and knee walking . In the bone – patellar tendon – bone group , 19 patients had no kneeling problems , 23 slight problems , 31 moderate problems , and 5 unable to kneel . Corresponding figures for the semitendinosus group were 25 , 32 , 16 , and 2 ( P < .001 ) . Patients with early reconstructions ( < 5 months ) had a lower risk for meniscal injuries ( 37 % ) than did later reconstructed ( 62 % , P = .008 ) . Health-related quality of life regarding physical functioning in Short Form–36 was better for the early-reconstructed patients than for the later reconstructed ( 92 vs 85 ; P = .014 ) . Patients without medial meniscal surgery had higher Knee Osteoarthritis Outcome Scores for all subscales than did patients with medial meniscal surgery , with most significant difference for sport and recreation ( 63 vs 75 , P = .008 ) . Conclusion : In the long term , the semitendinosus graft provided similar stability , knee function , and health-related quality of life but with less kneeling morbidity than did the bone – patellar tendon – bone graft The purpose of this study was to evaluate prospect ively the results of anterior cruciate ligament ( ACL ) reconstruction with doubled hamstring tendon graft in a selected group of 18 rugby players . The graft was fixed with a transcondylar screw ( Transfix ) on the femur , and with an absorbable interference screw and a metallic staple on the tibia . All the patients followed the same rehabilitation program . Return to sports activities was allowed after 6 months . Follow-up was 2 years in all cases . The athletic level of the patients was rated according to the Tegner scoring system . Clinical results were evaluated using the International Knee Documentation Committee ( IKDC ) scoring system . Furthermore , an instrumented evaluation of the anterior laxity with a KT–1000 arthrometer , and an isokinetic evaluation were performed 6 and 24 months after surgery . The Tegner mean score at follow-up ( 8.2 ) was similar to that prior to injury ( 8.3 ) . IKDC overall results were normal in ten cases ( 55.6 % ) , nearly normal in six cases ( 33.3 % ) , and abnormal in two cases ( 11.1 % ) . Side-to-side difference of anterior laxity measured with KT–1000 at 6 and 24 months did not show an impairment of knee stability with time . Isokinetic evaluation showed a significant improvement on peak torque both in extension and flexion on comparison between 6- and 24-month measurements . The results reported in this study showed that the use of doubled hamstring tendon graft for ACL reconstruction in athletes that were at risk for high-energy traumas to the knees , such as rugby players , gave normal or nearly normal results in about 90 % of the cases . Recovery of muscle strength was almost complete 2 years after surgery , and there was no impairment of knee stability with time PURPOSE The aim of this study was to determine the rates of contralateral anterior cruciate ligament ( ACL ) rupture and of ACL graft rupture after ACL reconstruction using either patellar tendon or hamstring tendon autograft , and to identify any patient characteristics that may increase this risk . TYPE OF STUDY Case series . METHODS Over a 2-year period , 760 endoscopic ACL reconstructions were performed in 743 patients . Bone-patellar tendon-bone autograft was used in 316 patients and 4-str and hamstring tendon in 427 patients . Those patients with a previous contralateral ACL rupture or those who underwent a simultaneous bilateral ACL reconstruction were excluded , leaving 675 knees ( 675 patients ) for review . Persons not involved in the index operation or the care of the patient conducted follow-up assessment by telephone interview conducted 5 years after surgery . Patients were question ed about the incidence of ACL graft rupture , contralateral ACL rupture , symptoms of instability or significant injury , family history of ACL injury , and activity level according to the International Knee Documentation Committee scale . From our prospect i ve data base we obtained further information on graft source , meniscal or articular surface injury , and gender . Binary logistic regression was used to measure the relative association between the measured variables and the risk of graft rupture and contralateral ACL rupture . RESULTS Five years after primary ACL reconstruction , 612 of the 675 patients ( 90.7 % ) were assessed . ACL graft rupture occurred in 39 patients ( 6 % ) and contralateral ACL rupture occurred in 35 patients ( 6 % ) . Three patients suffered both a graft rupture and a contralateral ACL injury . The odds of ACL graft rupture were increased 3-fold by a contact mechanism of initial injury . Return to level 1 or 2 sports increased the risk of contralateral ACL injury by a factor of 10 . The risk of sustaining an ACL graft rupture was greatest in the first 12 months after reconstruction . No other studied variable increased the risk of repeat ACL injury . CONCLUSIONS After reconstruction , repeat ACL injury occurred in 12 % of patients over 5 years . Twelve months after reconstruction , the ACL graft is at no greater risk than the contralateral ACL , suggesting that adequate graft and muscular function for most activities is achieved by this time . Risk factors for repeat ACL injury identified included a return to competitive side-stepping , pivoting , or jumping sports , and the contact mechanism of the index injury . Female patients were at no greater risk of repeat ACL injury than male patients and graft choice did not affect the rate of repeat ACL injury . LEVEL OF EVIDENCE Level IV , case series In a two-centre study , 164 patients with unilateral instability of the anterior cruciate ligament were prospect ively r and omised to arthroscopic reconstruction with either a patellar tendon graft using interference screw fixation or a quadruple semitendinosus graft using an endobutton fixation technique . The same postoperative rehabilitation protocol was used for all patients and follow-up at a median of 31 months ( 24 to 59 ) was carried out by independent observers . Four patients ( 2 % ) were lost to follow-up . No significant differences were found between the groups regarding the Stryker laxity test , one-leg hop test , Tegner activity level , Lysholm score , patellofemoral pain score , International Knee Documentation Committee ( IKDC ) score or visual analogue scale , reflecting patient satisfaction and knee function . Slightly decreased extension , compared with the non-operated side , was found in the patellar tendon group ( p < 0.05 ) . Patients with associated meniscal injuries had lower IKDC , visual analogue ( p < 0.01 ) and Lysholm scores ( p < 0.05 ) than those without such injuries . Patients in whom reconstruction had been carried out less than five months after the injury had better final IKDC scores than the more chronic cases ( p < 0.05 ) . We conclude that patellar tendon and quadruple semitendinous tendon grafts have similar outcomes in the medium term . Associated meniscal pathology significantly affects the final outcome and early reconstruction seems to be beneficial STUDY DESIGN Nonexperimental method ological study . OBJECTIVES To determine the interrater and intrarater reliability and validity of using observational risk-screening guidelines to evaluate dynamic knee valgus . BACKGROUND A deficiency in the neuromuscular control of the hip has been identified as a key risk factor for noncontact anterior cruciate ligament ( ACL ) injury in postpubescent females . This deficiency can manifest itself as a valgus knee alignment during tasks involving hip and knee flexion . There are currently no scientifically tested methods to screen for dynamic knee valgus in the clinic or on the field . METHODS Three physiotherapists used observational risk-screening guidelines to rate 40 adolescent female soccer players according to their risk of ACL injury . The rating was based on the amount of dynamic knee valgus observed on a drop-jump l and ing . Ratings were evaluated for intrarater and interrater agreement using kappa coefficients . Sensitivity and specificity of ratings were evaluated by comparing observational ratings , with measurements obtained using 3-dimensional ( 3-D ) motion analysis . RESULTS Kappa coefficients for intrarater and interrater agreement ranged from 0.75 to 0.85 , indicating that ratings were reasonably consistent over time and between physiotherapists . Sensitivity values were inadequate , ranging from 67 % to 87 % . This indicated that raters failed to detect up to a third of " truly high-risk " individuals . Specificity values ranged from 60 % to 72 % , which was considered adequate for the purpose s of the screening . CONCLUSION Observational risk screening is a practical and cost-effective method of screening for ACL injury risk . Rater agreement and specificity were acceptable for this method , but sensitivity was not . To detect a greater proportion of individuals at risk of ACL injury , coaches and clinicians should ensure that they include additional tests for other high-risk characteristics in their screening protocol To prospect ively evaluate the effect of neuromuscular training on the incidence of knee injury in female athletes , we monitored two groups of female athletes , one trained before sports participation and the other not trained , and a group of untrained male athletes throughout the high school soccer , volleyball , and basketball seasons . Weekly reports included the number of practice and competition exposures and mechanism of injury . There were 14 serious knee injuries in the 1263 athletes tracked through the study . Ten of 463 untrained female athletes sustained serious knee injuries ( 8 noncontact ) , 2 of 366 trained female athletes sustained serious knee injuries ( 0 noncontact ) , and 2 of 434 male athletes sustained serious knee injuries ( 1 noncontact ) . The knee injury incidence per 1000 athlete-exposures was 0.43 in untrained female athletes , 0.12 in trained female athletes , and 0.09 in male athletes ( P 0.02 , chi-square analysis ) . Untrained female athletes had a 3.6 times higher incidence of knee injury than trained female athletes ( P 0.05 ) and 4.8 times higher than male athletes ( P 0.03 ) . The incidence of knee injury in trained female athletes was not significantly different from that in untrained male athletes ( P 0.86 ) . The difference in the incidence of noncontact injuries between the female groups was also significant ( P 0.01 ) . This prospect i ve study demonstrated a decreased incidence of knee injury in female athletes after a specific plyometric training program Background : Few authors have investigated the effectiveness of preventive intervention in European team h and ball . Purpose : The aim of the present study was to evaluate the effects of a prevention program on the incidence of injuries in female European team h and ball players . Study design : Prospect i ve controlled study . Methods : Ten female h and ball teams ( 134 players ) took part in the prevention program ( 1 . Information about injury mechanism , 2 . Balance-board exercises , 3 . Jump training ) while 10 other teams ( 142 players ) were instructed to train as usual . Over one season all injuries were documented weekly . Results : Ankle sprain was the most frequent diagnosis in both groups with 11 ankle sprains in the control group and 7 ankle sprains in the intervention group ( Odds ratio : 0.55 , 95 % confidence interval : 0.22–1.43 ) . The knee was the second frequent injury site . In the control group 5 of all knee injuries were anterior cruciate ligament ( ACL ) ruptures ( incidence : 0.21 per 1000 h ) in comparison with one in the intervention group ( incidence : 0.04 per 1000 h ) . Odds ratio was 0.17 with 95 % confidence interval of 0.02–1.5 . Conclusions : This study confirms that proprioceptive and neuromuscular training is appropriate for the prevention of knee and ankle injuries among female European team h and ball players The aim of the study was to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third , bone-patellar tendon-bone ( BPTB Group ) ( n = 45 ) and four-str and semitendinosus/gracilis ( ST/G Group ) ( n = 78 ) autografts in male patients . The type of study is non-r and omised , prospect i ve consecutive series . A consecutive series of 126 male patients , all with unilateral ACL ruptures , was included in the study . In both groups , interference screw fixation of the graft was used at both ends and 123/126 ( 97 % ) of the patients returned for the follow-up examination after a period of 25 ( 23–33 ) months . The pre-operative assessment s in both groups were similar in terms of the Tegner activity level , the Lysholm knee scoring scale , KT-1000 measurements , one-leg-hop test and knee-walking test . A significant reduction in knee laxity as measured with the KT-1000 arthrometer , compared with the pre-operative assessment s , was found in both groups ( P < 0.001 ) . No significant differences in the post-operative knee-laxity measurements were found between the groups . Both groups had a significantly improved functional outcome at follow-up in terms of the Lysholm knee scoring scale , Tegner activity level and one-leg-hop test . The BPTB Group had a significantly higher Tegner activity level at follow-up , compared with the ST/G Group ( P = 0.02 ) . Moreover , the patients in the BPTB Group were significantly more likely to have a Tegner activity level of 6 or above ( P = 0.03 ) . Otherwise , no significant differences were found between the two study groups at the 2-year follow-up . Two years after an ACL reconstruction , the two groups displayed no significant differences in terms of functional outcome and knee laxity . However , more patients in the BPTB Group returned to a higher Tegner activity level than that in the ST/G Group Purpose . To compare the results of anterior cruciate ligament ( ACL ) reconstructions using either a patella-tendon autograft or a semitendinosus-tendon autograft . Methods . Based on surgeon experience and preference , 68 patients underwent ACL reconstruction using either a quadruple-str and semitendinosus autograft ( n=34 ) or a central one-third bone-patella tendon-bone autograft ( n=34 ) . Each patient was assessed preoperatively and postoperatively at 3 , 6 , and 24 months using the International Knee Documentation Committee ( IKDC ) knee score , Biodex muscle strength and endurance testing , and the KT1000 instrumented arthrometer test of knee laxity to anterior translation . All assessment s at the 2-year follow-up were performed by the same physician and physiotherapist . Results . While ACL reconstruction improved knee stability and IKDC knee scores significantly , there was no statistically significant difference between semitendinosus- and patella-tendon autograft reconstructions in terms of long-term knee score or laxity to anterior translation . Semitendinosus graft reconstruction was associated with less donor-site morbidity and hamstring weakness . Meniscectomy was associated with poorer long-term knee scores . Conclusion . ACL reconstruction is associated with a significantly better IKDC knee score and laxity measurement at 2-year follow-up . However , we were unable to demonstrate a significantly better long-term outcome in knee score or laxity to anterior translation with either a patella-tendon autograft or a semitendinosus-tendon autograft Abstract This study included 527 patients ( 178 female and 349 male ) with unilateral anterior cruciate ligament ( ACL ) rupture who underwent arthroscopic ACL reconstruction using bone-patellar tendon-bone autograft and interference screw fixation . The follow-up examination was performed by independent observers at a median of 38 ( 21–68 ) months after the index operation . At the follow-up , the Lysholm score was 86 ( 14–100 ) points , the Lysholm instability subscore was 22 ( 0–25 ) points and the Lysholm pain subscore was 19 ( 0–25 ) points . The Tegner activity level was 6 ( 1–10 ) . The one-leg-hop test was 91 (0–167)% of the non-injured knee . The difference in the anterior side-to-side laxity as measured with the KT-1000 arthrometer at 89 Newton ( N ) was 1.5 ( –5–13 ) mm and the total KT-1000 side-to-side difference at 89 N was 2 ( –7–11 ) mm . Using the International Knee Documentation Committee ( IKDC ) evaluation system , 177 ( 33.6 % ) patients were classified as normal ( group A ) , 211 ( 40 % ) as nearly normal ( group B ) , 109 ( 20.7 % ) as abnormal ( group C ) and 30 ( 5.7 % ) as severely abnormal ( group D ) . The highest correlation coefficients were recorded between the IKDC evaluation system and the Lysholm score ( ρ = 0.66 ) , the patients ’ subjective evaluation ( ρ = 0.53 ) , the Tegner activity level ( ρ = 0.34 ) , all the laxity tests ( ρ≥ 0.34 ) and the one-leg-hop test ( ρ = 0.28 ) . The resumption of sporting activities and work as evaluated by the Tegner activity level correlated with the patients ’ subjective evaluation ( ρ = 0.34 ) but did not correlate with the laxity tests , i.e. , the manual Lachman test ( ρ = –0.06 ) and the total and anterior KT-1000 tests ( ρ = –0.06 ) . Furthermore , none of the laxity tests correlated with the functional tests or the patients ’ subjective evaluation . We conclude that the IKDC evaluation system is a reliable and useful tool for evaluating the post-operative outcome after an ACL reconstruction The aim of the study is to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third , bone-patellar tendon-bone ( BTB group ) ( n=28 ) and four-str and semitendinosus/gracilis ( ST/G group ) ( n=31 ) autografts in female patients . The type of study was non-r and omised prospect i ve consecutive series . A consecutive series of 61 female patients , all with unilateral ACL ruptures , was included in the study . In both groups , interference screw fixation of the graft was used at both ends , and 59/61 ( 97 % ) of the patients returned for the follow-up examination after a period of 26 ( 23–31 ) months . The pre-operative assessment s in both groups were similar in terms of the Lysholm score , KT−1000 measurements , one-leg-hop test , and knee-walking test . At the 2-year follow-up , the knee-walking test was significantly worse in the BTB group than in the ST/G group ( P=0.003 ) . Furthermore , the knee-walking test was significantly worse at follow-up than pre-operatively in the BTB group ( P<0.005 ) . The corresponding finding was not made in the ST/G group . A reduction in knee laxity compared with the pre-operative assessment s was found in both groups . No significant difference in the post-operative knee laxity measurement was found between the groups . A significant increase in activity level and subjective scores was found in both groups compared with pre-operative values , without any significant differences between the groups . Two years after ACL reconstruction , the groups displayed no significant differences in terms of functional outcome and knee laxity . However , the use of ST/G autografts rendered significantly less discomfort during the knee-walking test than the use of BTB autografts The purpose of this investigation was to determine the interrater reliability of peak torque and total work values obtained with isokinetic measures of knee flexion and extension . Eight male and eight female students were evaluated on four occasions by four different examiners ( range of isokinetic test experience : 0 to 10 yrs ) using a st and ardized isokinetic measurement protocol . Subjects were r and omly assigned to participate in a test sequence determined by a 4 x 4 balanced Latin square . Peak torque and total work values at 60 degrees /sec and 180 degrees /sec were obtained for the concentric measures of knee extension and flexion . The measures of peak torque and total work were corrected for the effects of gravity . Intraclass correlation coefficients and st and ard error of measurement estimates were used to estimate the interrater reliability for each test condition ( test speed x muscle group ) . Intraclass correlation coefficient values ranged from .90 to .96 for peak torque and .90 to .95 for total work . St and ard error of measurement estimates ranged from 8.9 to 13.3 Nm for peak torque and 11.3 to 16.8 Nm for total work . The results of this investigation demonstrate that reliable measures of isokinetic muscle performance of knee extension and flexion may be obtained by four clinicians with varied experience when following a st and ardized measurement protocol BACKGROUND The aim of the study was to compare the results after arthroscopic anterior cruciate ligament ( ACL ) reconstruction using central -third bone-patellar tendon-bone ( BTB ) autografts and triple/quadruple semitendinosus ( ST ) autografts . HYPOTHESIS In the long-term , ACL reconstruction using BTB autografts will render more donor-site problems than ST autografts . STUDY DESIGN R and omized controlled trial ; Level of evidence , 1 . METHODS A r and omized series of 71 patients ( 22 women and 49 men ) with a unilateral ACL rupture who underwent reconstructive surgery were included in the study . The BTB graft was used in 34 patients ( BTB group ) and the ST-tendon graft was used in 37 patients ( ST group ) . The patients were examined a median of 86 months ( range , 68 to 114 months ) after the reconstruction . RESULTS Sixty-eight of 71 patients ( 96 % ) were examined at follow-up . The clinical assessment s at follow-up revealed no significant differences between the BTB group and the ST group in terms of the Lysholm score , Tegner activity level , International Knee Documentation Committee evaluation system , 1-legged hop test , KT-1000 arthrometer laxity measurements , manual Lachman test , and range of motion . A significant improvement was seen in both groups compared with the preoperative values in terms of most clinical assessment s. Donor-site morbidity in the form of knee-walking ability , kneeling ability , and area of disturbed anterior knee sensitivity revealed no significant differences between the groups . CONCLUSION Seven years after ACL reconstruction , the subjective and objective outcomes were similar after using the central -third BTB autograft and triple/quadruple ST autograft . Furthermore , no difference in terms of donor-site morbidity was found between the 2 groups Abstract . Bone – patellar tendon autograft is probably the most widely used graft for ACL reconstruction . Several methods for graft fixation have been described . To avoid intra-articular hardware we adopt biological fixation with a femoral conical press-fit fixation . A prospect i ve study was performed on 40 consecutive active athletes who underwent ACL reconstruction with this technique by the same surgeon between November 1994 and September 1995 ( mean follow-up 46 months , range 36–62 ) . Results were evaluated by an independent examiner using radiography , computed tomography , subjective and objective evaluation , and isokinetic and functional strength tests . Assessment using the IKDC knee scoring revealed 85 % of the patients with a normal or nearly normal knee joint ; Tegner 's score was 7.5 preoperatively and 6.0 postoperatively , with 60 % of the athletes returning to the preinjury sport and level . No patients had instability , with 90 % having less than 3 mm side-to-side difference on computerized analysis . The isokinetic test showed mild quadriceps deficit at 3 and 6 months , with no deficit at final follow-up ; four patients complained of anterior knee pain and had a positive kneeling test . We found no graft dislocation . All cases showed radiological evidence of graft integration at 3 months time . Long-term results support this technique as × a simple , cost-effective , and reliable alternative for patellar tendon fixation in ACL reconstruction Hamstring muscles play a major role in knee-joint stabilization after anterior cruciate ligament ( ACL ) injury . Weakness of the knee extensors after ACL reconstruction with patellar tendon ( PT ) graft , and in the knee flexors after reconstruction with hamstring tendons ( HT ) graft has been observed up to 2 years post surgery , but not later . In these studies , isokinetic muscle torque was used . However , muscle power has been suggested to be a more sensitive and sport-specific measures of strength . The aim was to study quadriceps and hamstring muscle power in patients with ACL injury treated with surgical reconstruction with PT or HT grafts at a mean of 3 years after surgery . Twenty subjects with PT and 16 subjects with HT grafts ( mean age at follow up 30 years , range 20–39 , 25 % women ) , who were all included in a prospect i ve study and followed the same goal -based rehabilitation protocol for at least 4 months , were assessed with reliable , valid , and responsive tests of quadriceps and hamstring muscle power at 3 years ( SD 0.9 , range 2–5 ) after surgery . The mean difference between legs ( injured minus uninjured ) , the hamstring to quadriceps ( H : Q , hamstring divided by quadriceps ) ratio , and the limb symmetry index ( LSI , injured leg divided by uninjured and multiplied by 100 ) value , were used for comparisons between the groups ( analysis of variance ) . The mean difference between the injured and uninjured legs was greater in the HT than in the PT group for knee flexion power ( –21.3 vs. 7.7 W , p = 0.001 ) . Patients with HT graft had lower H : Q ratio in the injured leg than the patients with PT graft ( 0.63 vs. 0.77 , p = 0.012 ) . They also had lower LSI for knee flexion power than those in the PT group ( 88 vs. 106 % , p < 0.001 ) . No differences were found between the groups for knee extension power . The lower hamstring muscle power , and the lower hamstring to quadriceps ratio in the HT graft group than in the PT graft group 3 years ( range 2–5 ) after ACL reconstruction , reflect imbalance of knee muscles after reconstruction with HT graft that may have a negative effect on dynamic knee-joint stabilization BACKGROUND The purpose of this study was to determine whether current post-operative rehabilitation protocol s return the strength of the contralateral uninjured limb knee flexors and extensors after an anterior cruciate ligament ( ACL ) reconstruction to those of an uninjured control group . METHODS Subjects with a hamstring tendon ACL reconstruction ( n=12 ) were compared to an active control group ( n=30 ) . Comprehensive bilateral knee flexor and extensor isovelocity strength testing was performed ( five speeds , 5 - 95 degrees , concentric and eccentric contractions ) . FINDINGS After hamstring tendon ACL reconstruction and rehabilitation , bilateral strength normalization ( within 10 % of the contralateral limb ) is achieved by the knee extensors but not the knee flexors . When compared to the uninjured control group , large and statistically significant strength deficits were demonstrated in the knee extensors and knee flexors of both the anterior cruciate ligament reconstructed ( extensors 24.8 % ; flexors 26.8 % ) and the contralateral uninjured ( extensors 21 % ; flexors 13.5 % ) limbs . INTERPRETATION These findings suggest that improvement can be made in knee flexor rehabilitation after ACL reconstruction and limit the validity of the use of a contralateral leg as a rehabilitation endpoint or as a control in the ACL reconstructed population Background There are still controversies about graft selection for primary anterior cruciate ligament reconstruction . Prospect i ve r and omized long-term studies are needed to determine the differences between the material s. Hypothesis Five years after anterior cruciate ligament reconstruction , there is a difference between hamstring and patellar tendon grafts in development of degenerative knee joint disease . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods From June 1999 to March 2000 , 64 patients were included in this prospect i ve study . A single surgeon performed primary arthroscopically assisted anterior cruciate ligament reconstruction in an alternating sequence . In 32 patients , anterior cruciate ligament reconstruction was performed with hamstring tendon autograft , whereas in the other 32 patients , anterior cruciate ligament reconstruction was performed with patellar tendon autograft . Results At the 5-year follow-up , no statistically significant differences were seen with respect to the Lysholm score , clinical and KT-2000 arthrometer laxity testing , anterior knee pain , single-legged hop test , or International Knee Documentation Committee classification results ; 23 patients ( 82 % ) in the hamstring tendon group and 23 patients ( 88 % ) in the patellar tendon group returned to their preinjury activity levels . Graft rupture occurred in 2 patients from the hamstring tendon group ( 7 % ) and in 2 patients from the patellar tendon group ( 8 % ) . Grade B abnormal radiographic findings were seen in 50 % ( 13/26 ) of patients in the patellar tendon group and in 17 % ( 5/28 ) of patients in the hamstring tendon group ( P = . 012 ) . Conclusion Both hamstring and patellar tendon grafts provided good subjective outcomes and objective stability at 5 years . No significant differences in the rate of graft failure were identified . Patients with patellar tendon grafts had a greater prevalence of osteoarthritis at 5 years after surgery Background : The purpose of this investigation was to evaluate replacement of a torn anterior cruciate ligament with either a bone-patellar tendon-bone autograft or a two-str and semitendinosus-gracilis autograft to compare the results of clinical testing , patient satisfaction , activity level , functional status , and muscle strength . Methods : Fifty-six patients with a torn anterior cruciate ligament were enrolled in a prospect i ve , r and omized , controlled study . Twenty-eight underwent reconstruction with a bone-patellar tendon-bone autograft , and twenty-eight were treated with a two-str and semitendinosus-gracilis autograft . Patients were followed for an average of thirty-nine months ( range , thirty-six to fifty-seven months ) . At the time of final follow-up , twenty-two patients in each group were evaluated in terms of clinical test findings , patient satisfaction , activity level , functional status , and isokinetic muscle strength . Results : The objective outcome of replacement of the torn anterior cruciate ligament with a bone-patellar tendon-bone graft was superior to that obtained with a two-str and semitendinosus-gracilis graft . At the three-year follow-up interval , the patients in whom a hamstring graft had been used had an average of 4.4 mm of increased anterior knee laxity compared with the laxity of the contralateral , normal knee , whereas the patients in whom a bone-patellar tendon-bone graft had been used had an average of 1.1 mm of increased knee laxity . Fourteen percent ( three ) of the twenty-two patients with a hamstring graft had a mild pivot shift , and 27 % ( six ) had a moderate pivot shift . Only 14 % ( three ) of the twenty-two patients with a bone-patellar tendon-bone graft had a mild pivot shift , and none had a moderate pivot shift . At the same follow-up interval , the patients in whom a hamstring graft had been used had significantly lower peak knee-flexion strength than those who had a bone-patellar tendon-bone graft ( p = 0.039 ) . In contrast , the two treatments produced similar outcomes in terms of patient satisfaction , activity level , and knee function ( ability to perform a one-legged hop , bear weight , squat , climb stairs , run in place , and duckwalk ) . Conclusions : After three years of follow-up , the objective results of anterior cruciate ligament replacement with a bone-patellar tendon-bone autograft were superior to those of replacement with a two-str and semitendinosus-gracilis graft with regard to knee laxity , pivot-shift grade , and strength of the knee flexor muscles . However , the two groups had comparable results in terms of patient satisfaction , activity level , and knee function Background Debate exists regarding the optimal graft for anterior cruciate ligament reconstruction . Few studies have compared the differences in outcome after reconstruction using similar fixation methods . Hypothesis Similar outcomes will be seen after anterior cruciate ligament reconstruction with bone-patellar tendon-bone or quadruple-str and semitendinosus/gracilis tendons fixed with bioabsorbable interference screws . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Ninety-nine patients were prospect ively r and omized to bone-patellar tendon-bone ( 46 patients ) or quadruple-str and semitendinosus/gracilis ( 53 patients ) reconstruction groups . The bone-patellar tendon-bone group had slightly lower preinjury Tegner scores ( 6.7 vs 7.1 , P = .03 ) ; otherwise , the groups were similar . All surgeries were performed by a single surgeon using an endoscopic technique with bioabsorbable interference screw fixation . Patients were evaluated at 3 , 6 , 12 , and 24 months . Results Forty-six bone-patellar tendon-bone and 50 quadruple-str and semitendinosus/gracilis patients were available at 24 months ( 97 % ) . No differences in International Knee Documentation Committee grade , Lysholm score , Tegner activity level , range of motion , single-legged hop test , KT-1000 arthrometer manual maximum difference , Short Form-36 , or patient knee rating were found . The bone-patellar tendon-bone group had better flexion strength in the operated leg than in the nonoperated leg ( 102 % vs 90 % , P = .0001 ) , fewer patients complaining of difficulty jumping ( 3 % vs 17 % , P = .03 ) , and a greater number of patients returning to preinjury Tegner level ( 51 % vs 26 % , P = .01 ) . The quadruple-str and semitendinosus/gracilis group had better extension strength in the operated leg than in the nonoperated leg ( 92 % vs 85 % , P = .04 ) , fewer patients with sensory deficits ( 14 % vs 83 % , P = .0001 ) , and fewer patients with difficulty kneeling ( 6 % vs 20 % , P = .04 ) . Both groups showed significant improvement in KT-1000 arthrometer manual maximum difference , Lysholm score , Tegner activity level , International Knee Documentation Committee grade , and patient knee rating score . Conclusions Good outcomes were seen in both the bone-patellar tendon-bone and quadruple-str and semitendinosus/gracilis groups . Subtle differences were noted between the groups , which may help guide optimal graft choice Background Among female athletes it has not been established whether a neuromuscular and proprioceptive sports-specific training program will consistently reduce the incidence of anterior cruciate ligament injuries . Purpose To determine whether a neuromuscular and proprioceptive performance program was effective in decreasing the incidence of anterior cruciate ligament injury within a select population of competitive female youth soccer players . Study Design Cohort study ; Level of evidence , 2 . Methods In 2000 , 1041 female subjects from 52 teams received a sports-specific training intervention in a prospect i ve non-r and omized trial . The control group consisted of the remaining 1905 female soccer players from 95 teams participating in the same league who were age and skill matched . In the 2001 season , 844 female athletes from 45 teams were enrolled in the study , with 1913 female athletes ( from 112 teams ) serving as the age- and skill-matched controls . All subjects were female soccer players between the ages of 14 and 18 and participated in either their traditional warm-up or a sports-specific training intervention before athletic activity over a 2-year period . The intervention consisted of education , stretching , strengthening , plyometrics , and sports-specific agility drills design ed to replace the traditional warm-up . Results During the 2000 season , there was an 88 % decrease in anterior cruciate ligament injury in the enrolled subjects compared to the control group . In year 2 , during the 2001 season , there was a 74 % reduction in anterior cruciate ligament tears in the intervention group compared to the age- and skill-matched controls . Conclusion Using a neuromuscular training program may have a direct benefit in decreasing the number of anterior cruciate ligament injuries in female soccer players Background Athletes who return to sport participation after anterior cruciate ligament reconstruction ( ACLR ) have a higher risk of a second anterior cruciate ligament injury ( either reinjury or contralateral injury ) compared with non — anterior cruciate ligament— injured athletes . Hypotheses Prospect i ve measures of neuromuscular control and postural stability after ACLR will predict relative increased risk for a second anterior cruciate ligament injury . Study Design Cohort study ( prognosis ) ; Level of evidence , 2 . Methods Fifty-six athletes underwent a prospect i ve biomechanical screening after ACLR using 3-dimensional motion analysis during a drop vertical jump maneuver and postural stability assessment before return to pivoting and cutting sports . After the initial test session , each subject was followed for 12 months for occurrence of a second anterior cruciate ligament injury . Lower extremity joint kinematics , kinetics , and postural stability were assessed and analyzed . Analysis of variance and logistic regression were used to identify predictors of a second anterior cruciate ligament injury . Results Thirteen athletes suffered a subsequent second anterior cruciate ligament injury . Transverse plane hip kinetics and frontal plane knee kinematics during l and ing , sagittal plane knee moments at l and ing , and deficits in postural stability predicted a second injury in this population ( C statistic = 0.94 ) with excellent sensitivity ( 0.92 ) and specificity ( 0.88 ) . Specific predictive parameters included an increase in total frontal plane ( valgus ) movement , greater asymmetry in internal knee extensor moment at initial contact , and a deficit in single-leg postural stability of the involved limb , as measured by the Biodex stability system . Hip rotation moment independently predicted second anterior cruciate ligament injury ( C = 0.81 ) with high sensitivity ( 0.77 ) and specificity ( 0.81 ) . Conclusion Altered neuromuscular control of the hip and knee during a dynamic l and ing task and postural stability deficits after ACLR are predictors of a second anterior cruciate ligament injury after an athlete is released to return to sport Background Controversy remains over the most appropriate graft for anterior cruciate ligament reconstruction . Hypothesis There is no significant difference in outcomes after 4-str and hamstring and patellar tendon autograft anterior cruciate ligament reconstructions using similar fixation techniques . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Between August 2000 and May 2003 , 64 Keller Army Hospital patients with complete anterior cruciate ligament tears were r and omized to hamstring ( n = 32 ) or patellar tendon ( n = 32 ) autograft anterior cruciate ligament reconstruction . Operative graft fixation and rehabilitative techniques were the same for both groups . Follow-up assessment s included the Single Assessment Numeric Evaluation score , Lysholm score , International Knee Documentation Committee score , and Knee Injury and Osteoarthritis Outcome Score . Postoperative radiographs were analyzed for tunnel location and orientation . Results Eleven women and 53 men were r and omized . Eighty-three percent of the patients ( 53 of 64 ) had follow-up of greater than 2 years , or to the point of graft rupture or removal ( average follow-up , 36 months ) . Four hamstring grafts ( 12.5 % ) and three patellar tendon grafts ( 9.4 % ) ( P = .71 ) ruptured . One deep infection in a hamstring graft patient necessitated graft removal . Forty-five of the 56 patients with intact grafts had greater than 2-year follow-up . Patients with patellar tendon grafts had greater Tegner activity scores ( P = .04 ) . Single Assessment Numeric Evaluation scores were 88.5 ( 95 % confidence interval : 83.1 , 93.8 ) and 90.1 ( 95 % confidence interval : 85.2 , 96.1 ) for the hamstring and patellar tendon groups , respectively ( P = .53 ) . Lysholm scores were 90.3 ( 95 % confidence interval : 84.4 , 96.1 ) and 90.4 ( 95 % confidence interval : 84.5 , 96.3 ) for the hamstring and patellar tendon groups , respectively ( P = .97 ) . There were no significant differences in knee laxity , kneeling pain , isokinetic peak torque , International Knee Documentation Committee score , or Knee Injury and Osteoarthritis Outcome Scores . Postoperative graft rupture correlated with more horizontal tibial tunnel orientation . Conclusion Hamstring and patellar tendon autografts provide similar objective , subjective , and functional outcomes when assessed at least 2 years after anterior cruciate ligament reconstruction |
13,349 | 19,091,823 | Probiotics appear to be efficacious in IBS , but the magnitude of benefit and the most effective species and strain are uncertain | INTRODUCTION Probiotics may benefit irritable bowel syndrome ( IBS ) symptoms , but r and omised controlled trials ( RCTs ) have been conflicting ; therefore a systematic review was conducted . | AIM To evaluate the effects of a combination probiotic on symptoms and colonic transit in patients with irritable bowel syndrome ( IBS ) and significant bloating . METHODS Forty-eight patients with Rome II IBS were r and omized in a parallel group , double-blind design to placebo or VSL # 3 twice daily ( 31 patients received 4 weeks and 17 patients 8 weeks of treatment ) . Pre- and post-treatment colonic transit measurements were performed using scintigraphy with (111)In charcoal . Symptoms were summarized as an average daily score for the entire period of treatment and separately for the first 4 weeks of treatment . Weekly satisfactory relief of abdominal bloating was assessed . RESULTS Treatment with VSL # 3 was associated with reduced flatulence over the entire treatment period ( placebo 39.5 + /- 2.6 vs VSL # 3 29.7 + /- 2.6 , P = 0.011 ) ; similarly , during the first 4 weeks of treatment , flatulence scores were reduced ( placebo 40.1 + /- 2.5 vs VSL # 3 30.8 + /- 2.5 , P = 0.014 ) . Proportions of responders for satisfactory relief of bloating , stool-related symptoms , abdominal pain and bloating scores were not different . Colonic transit was retarded with VSL # 3 relative to placebo ( colon geometric center 2.27 + /- 0.20 vs 2.83 + /- 0.19 , P = 0.05 respectively ) . CONCLUSION VSL # 3 reduces flatulence scores and retards colonic transit without altering bowel function in patients with IBS and bloating BACKGROUND : Probiotic bacteria exhibit a variety of properties , including immunomodulatory activity , which are unique to a particular strain . Thus , not all species will necessarily have the same therapeutic potential in a particular condition . We have preliminary evidence that Bifidobacterium infantis 35624 may have utility in irritable bowel syndrome ( IBS ) . OBJECTIVES : This study was design ed to confirm the efficacy of the probiotic bacteria B. infantis 35624 in a large-scale , multicenter , clinical trial of women with IBS . A second objective of the study was to determine the optimal dosage of probiotic for administration in an encapsulated formulation . METHODS : After a 2-wk baseline , 362 primary care IBS patients , with any bowel habit subtype , were r and omized to either placebo or freeze-dried , encapsulated B. infantis at a dose of 1 × 106 , 1 × 108 , or 1 × 1010 , cfu/mL for 4 wk . IBS symptoms were monitored daily and scored on to a 6-point Likert scale with the primary outcome variable being abdominal pain or discomfort . A composite symptom score , the subject 's global assessment of IBS symptom relief , and measures of quality of life ( using the IBS-QOL instrument ) were also recorded . RESULTS : B. infantis 35624 at a dose of 1 × 108 cfu was significantly superior to placebo and all other bifidobacterium doses for the primary efficacy variable of abdominal pain as well as the composite score and scores for bloating , bowel dysfunction , incomplete evacuation , straining , and the passage of gas at the end of the 4-wk study . The improvement in global symptom assessment exceeded placebo by more than 20 % ( p < 0.02 ) . Two other doses of probiotic ( 1 × 106 and 1 × 1010 ) were not significantly different from placebo ; of these , the 1 × 1010 dose was associated with significant formulation problems . No significant adverse events were recorded . CONCLUSIONS : B. infantis 35624 is a probiotic that specifically relieves many of the symptoms of IBS . At a dosage level of 1 × 108 cfu , it can be delivered by a capsule making it stable , convenient to administer , and amenable to widespread use . The lack of benefits observed with the other dosage levels of the probiotic highlight the need for clinical data in the final dosage form and dose of probiotic before these products should be used in practice OBJECTIVE Experimental and clinical studies have shown that a novel symbiotic ( known as SCM-III ) exerts a beneficial effect on gut translocation and local and systemic inflammatory and microbial metabolic parameters . The present investigation was a preliminary trial on the effectiveness of SCM-III for irritable bowel syndrome ( IBS ) . METHODS Sixty-eight consecutive adult patients with IBS who were free from lactose malabsorption , abdominal surgery , overt psychiatric disorders and ongoing psychotropic drug therapy or ethanol abuse were studied prospect ively and divided into 2 groups that were comparable for age , gender , body size , education and pattern of presenting symptoms . The 2 groups were blindly given for 12 weeks either SCM-III 10 mL t.i.d or the same dosage of heat-inactivated symbiotic . RESULTS Treatment with SCM-III was ' effective ' or ' very effective ' in more than 80 % of the patients ( P < 0.01 vs baseline values and control ) . Less than 5 % reported ' not effective ' as the final evaluation compared with over 40 % of patients in the control group . After 6 weeks of treatment , a significant improvement of pain and bloating was reported in the treatment group compared with control and baseline values . There was also a benefit for bowel habits , mostly for patients with constipation or alternating bowel habits . No overt clinical or biochemical adverse side-effects were recorded . CONCLUSION Compared with baseline values and the control group , SCM-III result ed in a significant increase in lactobacilla , eubacteria and bifidobacteria , which suggests that some selected IBS patients could benefit substantially from symbiotics , but the treatment may need to be given on a cyclic schedule because of the temporary modification of the fecal flora BACKGROUND / AIMS Irritable bowel syndrome ( IBS ) is a functional gastrointestinal ( GI ) tract disorder that has heterogeneous clinical presentations such as abdominal pain , diarrhea , constipation , and abdominal distension . It is known that several mechanisms are involved in the pathogenesis of IBS . Probiotics may target one or more pathophysiologic pathways in IBS and may improve the symptoms of IBS . However , the results of studies about probiotics on IBS are controversial . Therefore , the aim of this study was to evaluate the effect of probiotics on GI symptoms and intestinal gas volume changes in patients with IBS . METHODS Forty patients were r and omly allocated to be treated with Medilac DS ( Bacillus subtilis , Streptococcus faecium ) ( n=20 ) or placebo ( n=20 ) in a double-blind , prospect i ve manner . The change in intestinal gas volume and symptom scores after 4-week treatment were evaluated for the efficacy . RESULTS There was no significant difference in bloating , frequency of gas expulsion , frequency of defecation , and hardness of stool before and after the treatment . However , the severity of abdominal pain and the frequency of abdominal pain decreased significantly in Medilac DS group ( 2.4+/-1.3 cm/day -- > 1.6+/-1.6 cm/day , 1.7+/-1.3/day -- > 1.0+/-1.0/day ) ( p=0.044 , p=0.038 ) , but not in placebo group ( 2.1+/-2.0 cm/day -- > 1.8+/-2.1 cm/day , 1.3+/-1.2/day -- > 1.4+/-1.9/day ) . In both groups , intestinal gas volume at baseline , after 2-week treatment , and after 4-week treatment did not show significant change . Medilac DS was well tolerated without adverse events . CONCLUSIONS Medilac DS is a safe and useful probiotic agent for the treatment of abdominal pain in patients with IBS Probiotic bacteria exhibit a variety of properties , which are unique to a particular strain . Lactobacillus acidophilus-SDC 2012 , 2013 are new strains isolated from Korean infants ’ feces . The potential utility of Lactobacillus acidophilus-SDC 2012 , 2013 in irritable bowel syndrome ( IBS ) was studied . Forty IBS patients were r and omized into a placebo ( n = 20 ) and probiotics group ( n = 20 ) . Four weeks of treatment with L. acidophilus-SDC 2012 , 2013 was associated with a reduced score for abdominal pain or discomfort compared to the baseline ( P = 0.011 ) . The percent reduction in abdominal pain or discomfort exceeded the placebo scores by more than 20 % ( 23.8 and 0.2 % for probiotics and placebo , respectively , P = 0.003 ) . There was a significant difference in the proportion of responders between the probiotics and placebo groups ( P = 0.011 ) . There was no drop out or adverse events for either group during the study period . Lactobacillus acidophilus-SDC 2012 , 2013 appeared to have a beneficial effect in patients with IBS . Further studies are warranted Aim : To investigate the effects of a probiotic formulation , VSL#3 , on gastrointestinal transit and symptoms of patients with Rome II irritable bowel syndrome with predominant diarrhoea OBJECTIVES The purpose of this study was to evaluate the effects of a probiotic combination on symptoms in patients with irritable bowel syndrome ( IBS ) . METHODS We investigated the efficiency of a probiotic dietary supplement , containing four strains of lactic acid bacteria , on symptoms of IBS . One hundred and sixteen patients with IBS fulfilling the Rome II criteria were r and omized in a parallel group , double-blind study to receive a placebo or a probiotic combination ( 1 x 10(10 ) cfu once daily ) for four weeks . The symptoms that were monitored weekly included discomfort , abdominal pain , and stool frequency and quality . Quality of life was assessed before and at the end of the treatment using the SF36 and FDD- quality -of-life question naires . RESULTS One hundred subjects completed the study ( 48 probiotic combination , 52 placebo ) . The probiotic combination was not superior to the placebo in relieving symptoms of IBS ( 42.6 versus 42.3 % improvement ) . However , the decrease of abdominal pain between the first and the fourth week of treatment was significantly higher in probiotic treated patients ( -41.9 versus -24.2 % , P=0.048 ) . Interesting findings from the IBS sub-groups were also observed such as a lower pain score at end point in patients with alternating bowel habits ( P=0.023 ) and an increase of stool frequency in the constipated sub-group from the first week of probiotic treatment ( P=0.043 ) . CONCLUSIONS The probiotic combination was not significantly superior to the placebo in relieving symptoms of IBS . Despite the apparent high placebo response , interesting findings from IBS sub-groups were observed in the field of abdominal pain and stool frequency OBJECTIVE : The influence of the gastrointestinal ( GI ) microflora in patients with irritable bowel syndrome ( IBS ) has not been clearly eluci date d. This study was undertaken to see if patients with IBS have an imbalance in their normal colonic flora , as some bacterial taxa are more prone to gas production than others . We also wanted to study whether the flora could be altered by exogenous supplementation . In a previous study we have characterized the mucosa-associated lactobacilli in healthy individuals and found some strains with good colonizing ability . Upon colonization , they seemed to reduce gas formation . METHODS : The study comprised 60 patients with IBS and a normal colonoscopy or barium enema . Patients fulfilling the Rome criteria , without a history of malabsorption , and with normal blood tests underwent a sigmoidoscopy with biopsy . They were r and omized into two groups , one receiving 400 ml per day of a rose-hip drink containing 5 × 107 cfu/ml of Lactobacillus plantarum ( DSM 9843 ) and 0.009 g/ml oat flour , and the other group receiving a plain rose-hip drink , comparable in color , texture , and taste . The administration lasted for 4 wk . The patients recorded their own GI function , starting 2 wk before the study and continuing throughout the study period . Twelve months after the end of the study all patients were asked to complete the same question naire regarding their symptomatology as at the start of the study . RESULTS : All patients tolerated the products well . The patients receiving Lb . plantarum had these bacteria on rectal biopsies . There were no major changes of Enterobacteriaceae in either group , before or after the study , but the Enterococci increased in the placebo group and remained unchanged in the test group . Flatulence was rapidly and significantly reduced in the test group compared with the placebo group ( number of days with abundant gas production , test group 6.5 before , 3.1 after vs 7.4 before and 5.6 after for the placebo group ) . Abdominal pain was reduced in both groups . At the 12-month follow-up , patients in the test group maintained a better overall GI function than control patients . There was no difference between the groups regarding bloating . Fifty-nine percent of the test group patients had a continuous intake of fermented products , whereas the corresponding figure for the control patients was 73 % . CONCLUSIONS : The results of the study indicate that the administration of Lb . plantarum with known probiotic properties decreased pain and flatulence in patients with IBS . The fiber content of the test solution was minimal and it is unlikely that the fiber content could have had any effect . This type of probiotic therapy warrants further studies in IBS patients A comparison of Paraghurt tablets ( freeze-dried culture of Streptococcus faecium ) and placebo was carried out in patients with irritable bowel syndrome in a double-blind trial in Danish general practice s. Fifty-four patients ( 42 females and 12 males ) with an average duration of the disease of seven years were treated for four weeks . The clinical symptoms were registered prior to the treatment and after two and four weeks . The clinical effect was assessed according to changes in number of abdominal symptoms , the patients ' registration s on rating scales , and the physicians ' overall estimations . According to all three parameters a markedly better effect of Paraghurt was seen . Thus , after four weeks 81 % of the Paraghurt- and 41 % of the placebo-treated patients had improved according to the physicians ' overall assessment ( p = 0.002 ) . The result of the trial suggests that Paraghurt is a valuable alternative in the treatment of irritable bowel syndrome BACKGROUND & AIMS The aim of this study was to compare the response of symptoms and cytokine ratios in irritable bowel syndrome ( IBS ) with ingestion of probiotic preparations containing a lactobacillus or bifidobacterium strain . METHODS Seventy-seven subjects with IBS were r and omized to receive either Lactobacillus salivarius UCC4331 or Bifidobacterium infantis 35624 , each in a dose of 1 x 10 10 live bacterial cells in a malted milk drink , or the malted milk drink alone as placebo for 8 weeks . The cardinal symptoms of IBS were recorded on a daily basis and assessed each week . Quality of life assessment , stool microbiologic studies , and blood sampling for estimation of peripheral blood mononuclear cell release of the cytokines interleukin (IL)-10 and IL-12 were performed at the beginning and at the end of the treatment phase . RESULTS For all symptoms , with the exception of bowel movement frequency and consistency , those r and omized to B infantis 35624 experienced a greater reduction in symptom scores ; composite and individual scores for abdominal pain/discomfort , bloating/distention , and bowel movement difficulty were significantly lower than for placebo for those r and omized to B infantis 35624 for most weeks of the treatment phase . At baseline , patients with IBS demonstrated an abnormal IL-10/IL-12 ratio , indicative of a proinflammatory , Th-1 state . This ratio was normalized by B infantis 35624 feeding alone . CONCLUSIONS B infantis 35624 alleviates symptoms in IBS ; this symptomatic response was associated with normalization of the ratio of an anti-inflammatory to a proinflammatory cytokine , suggesting an immune-modulating role for this organism , in this disorder Background : Irritable bowel syndrome is a gastrointestinal disorder of unknown aetiology . The effect of probiotics in this syndrome remains unclear The efficacy of Lactobacillus GG yoghurt in preventing erythromycin associated diarrhoea was studied . Sixteen healthy volunteers were given erythromycin acistrate 400 mg t.i.d for a week . The volunteers were r and omly assigned into two groups taking twice daily 125 ml of either Lactobacillus GG fermented yoghurt or pasteurized regular yoghurt as placebo during the drug treatment . Subjects receiving Lactobacillus GG yoghurt with erythromycin had less diarrhoea than those taking pasteurized yoghurt . Other side effects of erythromycin , such as abdominal distress , stomach pain and flatulence , were less common in the GG yoghurt group than in the placebo yoghurt group . The subjects receiving Lactobacillus GG yoghurt were colonized with these bacteria even during erythromycin treatment as measured by faecal counts of total Lactobacillus GG . No Lactobacillus GG was found in the faecal sample s of volunteers in the group taking pasteurized yoghurt BACKGROUND It was suggested that the intestinal microflora may play a role in the pathogenesis of irritable bowel syndrome ( IBS ) . Probiotics may ease symptoms in IBS patients by changing gut microflora , reducing mucosal inflammation and exerting antibacterial effects . AIM To assess the short- and long-term effects of Lactobacillus reuteri administration on clinical symptoms of IBS . METHODS This is a double blind , placebo-controlled 6-month trial . Subjects consumed 1x10(8)cfu/tablet twice a day . The clinical severity of the IBS symptoms was evaluated by the Francis Severity score and the IBS quality -of-life score at study entry and then monthly . RESULTS In total , 54 subjects were r and omized for treatment and 39 concluded the study . Both groups ( treatment and placebo ) improved significantly in all the studied parameters with no significant differences between groups . Two parameters , constipation and passing gases , were marginally different between the main groups ( P=0.0714 and 0.0971 , respectively ) . CONCLUSIONS IBS symptoms did not improve with probiotic treatment with L. reuteri . A strong placebo effect and a lack of uniformity of the IBS population may have hindered a clearer demonstration of the effect Background Irritable bowel syndrome ( IBS ) is a widespread functional disorder of the digestive tract . Its aetiology is unknown and therapeutic options are limited . Recent reports suggest that probiotics may have a role in regulating the motility of the digestive tract . Aim To assess the efficacy of Lactobacillus plantarum 299V ( LP299V ) in patients with IBS . Patients and methods Forty patients were r and omized to receive either LP299V in liquid suspension ( 20 patients ) or placebo ( 20 patients ) over a period of 4 weeks . Clinical examination was performed at baseline and at the end of the study . Additionally , patients assessed their symptoms by applying a scoring system . Results All patients treated with LP299V reported resolution of their abdominal pain as compared to 11 patients from a placebo group ( P = 0.0012 ) . There was also a trend towards normalization of stools frequency in constipated patients in six out of 10 patients treated with LP299V compared with two out of 11 treated with placebo ( P = 0.17 ) . With regards to all IBS symptoms an improvement was noted in 95 % of patients in the LP299V group vs 15 % of patients in the placebo group ( P < 0.0001 ) . Conclusions LP299V seems to have a beneficial effect in patients with IBS . Further studies on larger cohorts of patients and with longer duration of therapy are required in order to establish the place of L. plantarum in the treatment of IBS OBJECTIVE To explore the best program for treatment of irritable bowel syndrome ( IBS ) of constipation type . METHODS Ninety-five cases of IBS were r and omly divided into 3 groups . Group A ( n = 30 ) were treated by acupuncture combined with microorganism pharmaceutical preparations , group B ( n = 35 ) by oral administration of medicine for loosening the bowel to relieve constipation plus microorganism pharmaceutical preparations , and group C ( n = 30 ) by simple acupuncture . RESULTS The total effective rates were 90.0 % , 77.2 % and 66.7 % , in the group A , B and C , respectively , with a very significant differences as the group A compared with those in the groups B , C ( P < 0.01 ) , and with no significant difference as the group B compared with that of the group C ( P > 0 . 05 ) . The intestinal available bacteria , bilidobacteria and lactobacillus , increased and enteric bacilli decreased in varying degrees in the 3 groups . CONCLUSION Acupuncture combined with microorganism pharmaceutical preparations has a better therapeutic effect on irritable bowel syndrome of constipation type |
13,350 | 15,684,173 | There was no dose-response relationship between homocysteine concentration and severity of preeclampsia .
: Homocysteine concentrations are slightly increased in normotensive pregnancies that later develop preeclampsia and are considerably increased once preeclampsia is established . | OBJECTIVE : We conducted a systematic review to examine the hypothesized mechanism through which homocysteine could lead to preeclampsia . | Recent meta-analyses have created uncertainties regarding the appropriate clinical role of colloid resuscitation fluids in critically ill patients and prompted changes in fluid management practice . Such changes may not be justified in view of method ological limitations inherent in the meta-analyses . Further research is nevertheless needed to resolve the questions raised concerning the relationship between choice of resuscitation fluid and patient outcome . Animal studies can play an important part by reliably indicating whether particular fluids are likely to prove effective and safe in clinical trials . It is important to avoid costly large-scale clinical trials that fail to demonstrate the clinical utility of the tested therapy , as re sources expended in failed trials raise overall development costs and thereby restrict the range of therapies meeting criteria of commercial feasibility . Promising therapies may thus not be pursued , even though an urgent clinical need may exist . An alternative pathway of pre clinical research may be of value in avoiding some of the major clinical trial failures of recent years , particularly in the area of sepsis . This alternative pathway commences with the formulation of hypotheses by therapeutics developers . Independent pre clinical investigators are challenged , by means of a competitive request for proposals , to test the hypotheses in rigorous r and omized studies employing clinical ly relevant animal models . Promising proposals would then be selected for further development with the aid of peer review . The results of the r and omized animal studies , along with other pre clinical data , could also be evaluated using accepted principles of ' critical appraisal ' commonly applied to clinical trial results . This critical appraisal might , where appropriate , include meta- analysis of animal study findings . This alternative pre clinical pathway to new product evaluation should be completed before the commencement of large-scale clinical trials OBJECTIVE The purpose of this study was to determine whether second-trimester plasma homocysteine levels are elevated among women whose pregnancies are subsequently complicated by pregnancy-induced hypertension , preeclampsia , or intrauterine growth restriction . STUDY DESIGN Women with normal but relatively low plasma zinc levels were r and omly assigned to receive zinc supplementation or placebo from 19 weeks ' gestation until delivery . Plasma homocysteine concentration and plasma and erythrocyte folate levels were determined for all available stored sample s ( zinc group , 231/294 ; placebo group , 206/286 ) at 26 and 37 weeks ' gestation . Among all women with available sample s , pregnancy-induced hypertension ( n = 12 ) or preeclampsia ( n = 4 ) developed in 16 women , and 22 pregnancies were complicated by intrauterine growth restriction . RESULTS Mean homocysteine levels in women with pregnancy-induced hypertension and preeclampsia were similar to those of control subjects at 26 weeks ' gestation but were significantly higher at 37 weeks ' gestation . Homocysteine levels were similar between women with pregnancies complicated by intrauterine growth restriction and control subjects at both time points . CONCLUSION Second-trimester plasma homocysteine concentrations do not predict the subsequent development of pregnancy-induced hypertension , preeclampsia , and intrauterine growth restriction OBJECTIVE Our purpose was to assess the incidence of hyperhomocysteinemia in patients with a history of preeclampsia or fetal growth restriction , to evaluate the effects of vitamin supplementation on the methionine loading test , and to study the course of subsequent pregnancies in women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction . STUDY DESIGN A total of 207 consecutive patients with a history of preeclampsia or fetal growth restriction was tested for hyperhomocysteinemia . Thirty-seven were found to be positive and were treated with folic acid and vitamin B6 , and 27 had a second methionine loading test after vitamin supplementation . Fourteen patients became pregnant again while receiving vitamins and aspirin . RESULTS All patients who underwent a methionine loading test after vitamin supplementation had a completely normalized methionine loading test . Of the 14 pregnancies in women receiving vitamins and aspirin , 7 were complicated by preeclampsia . Birth weights were 2867 + /- 648 g compared with 1088 + /- 570 g in the previous pregnancies . CONCLUSIONS Vitamin B6 and folic acid correct the methionine loading test in patients with hyperhomocysteinemia . Perinatal outcome in patients with a history of preeclampsia or fetal growth restriction and hyperhomocysteinemia appears to be favorable We hypothesized that physiological increments in plasma homocysteine after low-dose oral methionine or dietary animal protein induce vascular endothelial dysfunction and that there is a grade d , inverse relationship between homocysteine concentration and endothelial function . We studied 18 healthy volunteers aged 18 to 59 years . Brachial artery flow-mediated and glyceryltrinitrate-induced dilatation were measured after 1 ) oral L-methionine ( 10 , 25 , and 100 mg/kg ) , 2 ) dietary animal protein ( lean chicken 551+/-30 g , comprising 3.2+/-0.2 g methionine ) , and 3 ) methionine-free amino acid mix ( 100 mg/kg ) . Methionine ( 10 , 25 , and 100 mg/kg ) induced a dose-related increase in homocysteine ( 9.4+/-1.3 to 12.2+/-2.1 , 17 . 6+/-2.6 , and 26.1+/-4.2 micromol/L , respectively ; P<0.001 ) and a reduction in flow-mediated dilatation ( 4.1+/-0.8 to 2.1+/-0.8 , 0 . 3+/-0.8 , and -0.7+/-0.8 % , respectively ; P<0.001 ) at 4 hours . Compared with usual meal , animal protein increased plasma homocysteine ( 9.6+/-0.8 to 11.2+/-0.9 micromol/L , P=0.005 ) and reduced flow-mediated dilatation ( 4.5+/-0.7 % to 0.9+/-0.6 % , P=0.003 ) . Methionine-free amino acid mix did not induce any changes . Glyceryltrinitrate-induced dilatation was unchanged throughout . In this study , small physiological increments in plasma homocysteine after low-dose methionine and dietary animal protein induced vascular endothelial dysfunction . We propose that protein intake-induced increments in plasma homocysteine may have deleterious effects on vascular function and contribute to the development and progression of atherosclerosis Objective : Elevated plasma homocyst(e)ine is a risk factor for endothelial dysfunction and vascular disease . In late gestation , levels of homocyst(e)ine are higher in preeclamptics , as compared with normotensive pregnant women . Our objective was to determine whether homocyst(e)ine elevations precede the development of preeclampsia . Study Design : We used a prospect i ve nested case-control study design to compare second trimester maternal serum homocyst(e)ine concentrations in 52 patients who developed preeclampsia ( pregnancy-induced hypertension with proteinuria ) compared with 56 women who remained normotensive throughout pregnancy . Study subjects were selected from a base population of 3,042 women who provided blood sample s at an average gestational age of 16 weeks and later delivered at our center . Serum homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection . Results : Approximately 29 % of preeclamptics , as compared to 13 % of controls had homocyst(e)ine levels ≥5.5 μmol/l ( upper decile of distribution of control values ) . Adjusted for maternal age , parity , and body mass-index , a second trimester elevation of homocyst(e)ine was associated with a 3.2-fold increased risk of preeclampsia ( adjusted OR = 3.2 ; 95 % CI 1.1–9.2 ; p = 0.030 ) . There was evidence of a interaction between maternal adiposity ( as indicated by her prepregnancy body mass index ) and parity with second trimester elevations in serum homocyst(e)ine . Nulliparous women with elevated homocyst(e)ine levels experienced a 9.7-fold increased risk of preeclampsia as compared with multiparous women without homocyst(e)ine elevations ( 95 % CI 2.1–14.1 ; p = 0.003 ) . Women with a higher prepregnancy body mass index ( ≥21.4 kg/m2 , or upper 50th percentile ) and who also had elevated homocyst(e)ine levels , as compared with leaner women without homocyst(e)ine elevations were 6.9 times more likely to later develop preeclampsia ( 95 % CI 1.4–32.1 ; p = 0.016 ) . Conclusion : Our findings are consistent with other indications of vascular endothelial dysfunction predating clinical preeclampsia . Studies design ed to examine the effect of dietary and /or pharmacological mediators of homocyst(e)ine metabolism in preeclampsia are warranted UNLABELLED Preeclampsia and eclampsia are the primary causes of maternal mortality . In the state of Nuevo León , from 1990 to 1998 , these conditions represented 44.1 % of maternal deaths . The presence of thrombogenic substances ( homocysteine , C protein , and anticardiolipin antibodies ) in the mother 's blood has been related to this problem . The C677 T polymorphism of the enzyme methylene tetrahydrofolate reductase ( MTHFR ) favors the increase of homocysteine levels , while folic acid ( FA ) supplementation decreases its levels . OBJECTIVE To establish the role of FA in the physiopathology of preeclampsia in our environment . KIND OF STUDY : Longitudinal , prospect i ve and comparative . MATERIAL AND METHODS CASES Women with severe preeclampsia and /or eclampsia ( n-13 ) . CONTROLS Women in the third trimester of a normal pregnancy ( n + 15 ) . 20 mL Blood sample s were taken during the first 24 hours of puerperium , and their AF , homocysteine and MTHFR polymorphism were measured . The t Student test and the Exact Fisher test were used to compare between both groups . RESULTS The values obtained for homocysteine were ( x + SD ) : CASES 9.85 micromoles/L + 2.88 , and controls : 7.61 micromoles/L + 1.32 ( p < 0.04 ) . The frequency ( % ) of the genetic polymorphism for MTHFR was : positive homozygotes ( T/T ) : 38.46 vs. 20 , heterozygotes ( C/T ) : 38.46 vs. 26.6 , negative homozygotes ( C/C ) : 23 vs 53 , for cases and controls , respectively . CONCLUSIONS According to our study , the frequency of the homozygote state ( T/T ) of MTHFR and increased blood levels of homocysteine is greater in women suffering from preeclampsia OBJECTIVE The purpose of this study was to evaluate prospect ively midtrimester homocysteine concentration levels for the prediction of superimposed preeclampsia in women with chronic hypertension . STUDY DESIGN Between March 1 , 2000 , and February 1 , 2002 , pregnancies that were complicated by chronic hypertension that required medication had homocysteine , vitamin B(12 ) , and folate concentrations measured between 16 and 20 weeks of gestation . All women received folate supplementation . An upper limit threshold for increased homocysteine was defined as the mean value plus 2 SDs . RESULTS Fifty-seven women were enrolled . Mean homocysteine concentration levels were 5.1+/-1.7 micromo/L for the 16 women who had preeclampsia compared with 4.7+/-1.3 micromo/L for the 41 women without preeclampsia ( P=.56 ) . Two of 16 women with preeclampsia ( 13 % ) had concentration levels that exceeded the 95th percentile ( 6.9 micromo/L ) compared with 2 of 41 women ( 5 % ) without preeclampsia ( P=.31 ) . The sensitivity and specificity were 13 % ( 95 % CI , 1.6 - 38.3 ) and 95.1 % ( 95 % CI , 83.5 - 99.4 ) , respectively . CONCLUSION Second-trimester homocysteine concentration levels were not helpful in the prediction of preeclampsia in chronically hypertensive women It is well established that folic acid supplementation in early pregnancy significantly reduces the incidence of neural tube defects ( NTDs ) [ 1 ] . Consistent with national guidelines [ 2 ] , it is current practice in the UK to advise pregnant women to take folic acid supplementation until 12 weeks gestation . A recent report , however , suggests that supplementation with folic acid throughout pregnancy may effect a reduction in adverse pregnancy outcomes [ 3 ] , although this is not yet confirmed . If folic acid supplementation throughout pregnancy led to a reduction in such outcomes , it would be a safe , simple , and inexpensive therapeutic intervention Increased blood homocysteine is a potentially modifiable risk factor for cardiovascular disease . In a recent meta analysis of individual participant data from prospect i ve epidemiologic studies , a 25 % lower homocysteine concentration was associated with an 11 % lower risk for ischemic heart disease and a 19 % lower risk for stroke ( 1 ) . Blood homocysteine is easily lowered by folic acid supplementation , and several large-scale r and omized trials are currently underway to assess the effects of homocysteine-lowering vitamin supplements on the risk of vascular disease . If such trials demonstrate benefit , there will be increasing interest in homocysteine determinations to assess vascular disease risk . In addition , further large-scale epidemiologic studies may be required to investigate the association between homocysteine and cardiovascular disease in a wider range of population s. These would be facilitated by simple and cost-effective methods for blood collection and analysis . One of the chief constraints in homocysteine measurements is the continuing production and release of homocysteine by red blood cells after venipuncture , which causes an artificial increase in plasma concentration of ∼10 % per hour (2)(3 ) . It has been recommended , therefore , that blood sample s for homocysteine measurements be drawn into tubes containing EDTA , chilled , or placed on ice immediately after collection and that the plasma be separated from the red cells within 1 h. Such procedures can be difficult to implement in large-scale epidemiologic studies or other situations in which sample s have to be collected remotely ( e.g. , in multiple clinics or in people ’s homes ) and transported to a central laboratory . Use of NaF or acidic citrate has been advocated for stabilization of homocysteine in whole blood at ambient temperature |
13,351 | 23,824,722 | Establishing field st and ards in the study of SSB intake and health outcomes would facilitate interpretation across research studies and thereby increase the utility of systematic review s/meta-analyses and ultimately the efficiency of research efforts . | BACKGROUND Evidence maps are a new method that systematic ally characterize the range of research activity in broad topic areas and are used to guide research priority setting , systematic review s , and meta-analyses .
OBJECTIVE We exp and ed evidence mapping methods by demonstrating their usefulness as a tool for organizing epidemiologic research on sugar-sweetened beverage ( SSB ) intake and health outcomes : obesity , type 2 diabetes , metabolic syndrome , and coronary heart disease/stroke . | OBJECTIVE : To examine demographic , behavioral and dietary correlates of frequency of fast food restaurant use in a community-based sample of 891 adult women . DESIGN : A survey was administered at baseline and 3 y later as part of a r and omized , prospect i ve intervention trial on weight gain prevention . SUBJECTS : Women ( n=891 ) aged 20–45 y who enrolled in the Pound of Prevention study . MEASUREMENTS : Frequency of fast food restaurant use , dietary intake , demographic and behavioral measures were self-reported . Dietary intake was measured using the 60-item Block Food Frequency Question naire . Body weight and height were directly measured . RESULTS : Twenty-one percent of the sample reported eating ≥3 fast food meals per week . Frequency of fast food restaurant use was associated with higher total energy intake , higher percentage fat energy , more frequent consumption of hamburgers , French fries and soft drinks , and less frequent consumption of fiber and fruit . Frequency of fast food restaurant use was higher among younger women , those with lower income , non-White ethnicity , greater body weight , lower dietary restraint , fewer low-fat eating behaviors , and greater television viewing . Over 3 y , increases in frequency of fast food restaurant use were associated with increases in body weight , total energy intake , percentage fat intake , intake of hamburgers , French fries and soft drinks , and with decreases in physical activity , dietary restraint and low-fat eating behaviors . Intake of several other foods , including fruits and vegetables , did not differ by frequency of fast food restaurant use . CONCLUSION : Frequency of fast food restaurant use is associated with higher energy and fat intake and greater body weight , and could be an important risk factor for excess weight gain in the population The long-term physiological effects of refined carbohydrates on appetite and mood remain unclear . Reported effects when subjects are not blind may be due to expectations and have rarely been studied for more than 24 h. The present study compared the effects of supplementary soft drinks added to the diet over 4 weeks on dietary intake , mood and BMI in normal-weight women ( n 133 ) . Subjects were categorised as ' watchers ' or ' non-watchers ' of what they ate then received sucrose or artificially sweetened drinks ( 4 x 250 ml per d ) . Expectancies were varied by labelling drinks ' sugar ' or ' diet ' in a counter-balanced design . Sucrose supplements provided 1800 kJ per d and sweetener supplements provided 67 kJ per d. Food intake was measured with a 7 d diary and mood with ten single Likert scales . By 4 weeks , sucrose supplements significantly reduced total carbohydrate intake ( F(1,129 ) = 53.81 ; P<0.001 ) , fat ( F(2,250 ) = 33.33 ; P<0.001 ) and protein intake ( F(2,250 ) = 28.04 ; P<0 - 001 ) compared with sweetener supplements . Mean daily energy intake increased by just under 1000 kJ compared with baseline ( t ( 67 df ) = 3.82 ; P < 0.001 ) and was associated with a non-significant trend for those receiving sucrose to gain weight . There were no effects on appetite or mood . Neither dietary restraint status as measured by the Dutch Eating Behaviour Question naire nor the expectancy procedure had effects . Expectancies influenced mood only during baseline week . It is concluded that sucrose satiates , rather than stimulates , appetite or negative mood in normal-weight subjects BACKGROUND The consumption of beverages that contain sugar is associated with overweight , possibly because liquid sugars do not lead to a sense of satiety , so the consumption of other foods is not reduced . However , data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain . METHODS We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age . Participants were r and omly assigned to receive 250 ml ( 8 oz ) per day of a sugar-free , artificially sweetened beverage ( sugar-free group ) or a similar sugar-containing beverage that provided 104 kcal ( sugar group ) . Beverages were distributed through schools . At 18 months , 26 % of the children had stopped consuming the beverages ; the data from children who did not complete the study were imputed . RESULTS The z score for the body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group ; the 95 % confidence interval ( CI ) of the difference was -0.21 to -0.05 . Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group ( 95 % CI for the difference , -1.54 to -0.48 ) . The skinfold-thickness measurements , waist-to-height ratio , and fat mass also increased significantly less in the sugar-free group . Adverse events were minor . When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study , the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group ( P=0.06 ) . CONCLUSIONS Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children . ( Funded by the Netherl and s Organization for Health Research and Development and others ; DRINK Clinical Trials.gov number , NCT00893529 . ) BACKGROUND Increased intake of sugar-sweetened beverages and fruit juice has been associated with overweight in children . OBJECTIVE This study prospect ively assessed beverage consumption patterns and their relationship with weight status in a cohort of children born at different risk for obesity . METHODS AND PROCEDURES Participants were children born at low risk ( n = 27 ) or high risk ( n = 22 ) for obesity based on maternal prepregnancy BMI ( kg/m(2 ) ) . Daily beverage consumption was generated from 3-day food records from children aged 3 - 6 years and coded into seven beverage categories ( milk , fruit juice , fruit drinks , caloric and non-caloric soda , soft drinks including and excluding fruit juice ) . Child anthropometric measures were assessed yearly . RESULTS High-risk children consumed a greater percentage of daily calories from beverages at age 3 , more fruit juice at ages 3 and 4 , more soft drinks ( including fruit juice ) at ages 3 - 5 , and more soda at age 6 compared to low-risk children . Longitudinal analyses showed that a greater 3-year increase in soda intake was associated with an increased change in waist circumference , whereas a greater increase in milk intake was associated with a reduced change in waist circumference . There was no significant association between change in intake from any of the beverage categories and change in BMI z-score across analyses . DISCUSSION Children 's familial predisposition to obesity may differentially affect their beverage consumption patterns . Future research should examine the extent to which dietary factors may play a role in pediatric body fat deposition over time Background — Sugar-sweetened beverage consumption is associated with weight gain and risk of type 2 diabetes mellitus . Few studies have tested for a relationship with coronary heart disease ( CHD ) or intermediate biomarkers . The role of artificially sweetened beverages is also unclear . Methods and Results — We performed an analysis of the Health Professionals Follow-Up Study , a prospect i ve cohort study including 42 883 men . Associations of cumulatively averaged sugar-sweetened ( eg , sodas ) and artificially sweetened ( eg , diet sodas ) beverage intake with incident fatal and nonfatal CHD ( myocardial infa rct ion ) were examined with proportional hazard models . There were 3683 CHD cases over 22 years of follow-up . Participants in the top quartile of sugar-sweetened beverage intake had a 20 % higher relative risk of CHD than those in the bottom quartile ( relative risk=1.20 ; 95 % confidence interval , 1.09–1.33 ; P for trend < 0.01 ) after adjustment for age , smoking , physical activity , alcohol , multivitamins , family history , diet quality , energy intake , body mass index , pre-enrollment weight change , and dieting . Artificially sweetened beverage consumption was not significantly associated with CHD ( multivariate relative risk=1.02 ; 95 % confidence interval , 0.93–1.12 ; P for trend=0.28 ) . Adjustment for self-reported high cholesterol , high triglycerides , high blood pressure , and diagnosed type 2 diabetes mellitus slightly attenuated these associations . Intake of sugar-sweetened but not artificially sweetened beverages was significantly associated with increased plasma triglycerides , C-reactive protein , interleukin-6 , and tumor necrosis factor receptors 1 and 2 and decreased high-density lipoprotein , lipoprotein(a ) , and leptin ( P<0.02 ) . Conclusions — Consumption of sugar-sweetened beverages was associated with increased risk of CHD and some adverse changes in lipids , inflammatory factors , and leptin . Artificially sweetened beverage intake was not associated with CHD risk or biomarkers BACKGROUND During the nutrition transition in Chile , dietary changes were marked by increased consumption of high-energy , nutrient-poor products , including sugar-sweetened beverages ( SSBs ) . Obesity is now the primary nutritional problem in posttransitional Chile . OBJECTIVE We conducted a r and omized controlled trial to examine the effects on body composition of delivering milk beverages to the homes of overweight and obese children to displace SSBs . DESIGN We r and omly assigned 98 children aged 8 - 10 y who regularly consumed SSBs to intervention and control groups . During a 16-wk intervention , children were instructed to drink 3 servings/d ( approximately 200 g per serving ) of the milk delivered to their homes and to not consume SSBs . Body composition was measured by dual-energy X-ray absorptiometry . Data were analyzed by multiple regression analysis according to the intention-to-treat principle . RESULTS For the intervention group , milk consumption increased by a mean ( + /- SEM ) of 452.5 + /- 37.7 g/d ( P < 0.0001 ) , and consumption of SSBs decreased by -711.0 + /- 33.7 g/d ( P < 0.0001 ) . For the control group , milk consumption did not change , and consumption of SSBs increased by 71.9 + /- 33.6 g/d ( P = 0.04 ) . Changes in percentage body fat , the primary endpoint , did not differ between groups . Nevertheless , the mean ( + /- SE ) accretion of lean body mass was greater ( P = 0.04 ) in the intervention ( 0.92 + /- 0.10 kg ) than in the control ( 0.62 + /- 0.11 kg ) group . The increase in height was also greater ( P = 0.01 ) in the intervention group ( 2.50 + /- 0.21 cm ) than in the control group ( 1.77 + /- 0.20 cm ) for boys but not for girls . CONCLUSION Replacing habitual consumption of SSBs with milk may have beneficial effects on lean body mass and growth in children , despite no changes in percentage body fat . This trial was registered at clinical trials.gov as NCT00149695 This study examined the effect of food group intake on subsequent 2-y weight change . Food-frequency question naire-based food intake data of 17,369 nonsmoking subjects of the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort were examined in their relation to a subsequent weight change . Dietary data , collected from 1994 to 1998 , were grouped into 24 food groups . Weight change per year follow-up was the outcome of interest ; large weight gain was defined as > or = 2 kg ; small weight gain as > or = 1 kg to < 2 kg ; large weight loss as < or = -2 kg ; small weight loss as < or = -1 kg to > -2 kg and weight maintenance as + /- 1 kg . For each food group , a separate polytomous logistic regression model with stable weight as the reference group was constructed , controlling for age , body mass index , previous weight change , and behavioral and lifestyle factors . Odds ratios ( OR ) and 95 % confidence intervals ( CI ) estimated the increase in risk associated with each 100 g/d increment in food group intake . In women , consumption of high energy , high fat food groups significantly predicted large weight gain , e.g. , fats ( OR = 1.75 ; 95 % CI , 1.01 - 3.06 ) , sauces ( OR = 2.12 ; 95 % CI , 1.17 - 3.82 ) and meat ( OR = 1.36 ; 95 % CI , 1.04 - 1.79 ) , and the consumption of cereals predicted large weight loss ( OR = 1.43 ; 95 % CI , 1.09 - 1.88 ) . In men , intake of high energy , high sugar foods , i.e. , sweets , was significantly predictive of large weight gain ( OR = 1.48 ; 95 % CI , 1.03 - 2.13 ) . Our data show that a diet rich in high fat and high energy foods predicts short-term weight gain even if controlled for many potential confounding factors To examine whether artificial sweeteners aid in the control of long-term food intake and body weight , we gave free-living , normal-weight subjects 1150 g soda sweetened with aspartame ( APM ) or high-fructose corn syrup ( HFCS ) per day . Relative to when no soda was given , drinking APM-sweetened soda for 3 wk significantly reduced calorie intake of both females ( n = 9 ) and males ( n = 21 ) and decreased the body weight of males but not of females . However , drinking HFCS-sweetened soda for 3 wk significantly increased the calorie intake and body weight of both sexes . Ingesting either type of soda reduced intake of sugar from the diet without affecting intake of other nutrients . Drinking large volumes of APM-sweetened soda , in contrast to drinking HFCS-sweetened soda , reduces sugar intake and thus may facilitate the control of calorie intake and body weight BACKGROUND High consumption of sugar-sweetened drinks has been associated with weight gain and obesity in the United States . This trend may also be affecting population s with different eating patterns who increasingly are adopting typical US dietary patterns . OBJECTIVE We assessed whether the consumption of sweetened drinks and other food items increased the likelihood of weight gain in a Mediterranean population . DESIGN This was a prospect i ve cohort analysis of 7194 men and women with a mean age of 41 y who were followed-up for a median of 28.5 mo with mailed question naires . Dietary exposure was assessed with a previously vali date d semiquantitative food-frequency question naire . RESULTS During follow-up , we observed that 49.5 % of the participants increased their weight ( x weight gain : 0.64 kg ; 95 % CI : 0.55 , 0.73 kg ) . In the participants who had gained > or =3 kg in the 5 y before baseline , the adjusted odds ratio of subsequent weight gain for the fifth quintile compared with the first quintile of sugar-sweetened soft drink consumption was 1.6 ( 95 % CI : 1.2 , 2.1 ; P for trend = 0.02 ) . This association was absent in the participants who had not gained weight in the 5-y period before baseline . The consumption of hamburgers , pizza , and sausages ( as a proxy for fast-food consumption ) was also independently associated with weight gain ( adjusted odds ratio for the fifth compared with the first quintile = 1.2 ; 95 % CI : 1.0 , 1.4 ; P for trend = 0.05 ) . We also found a significant , but weaker , association between weight gain and both red meat and sweetened fruit juice consumption . CONCLUSION In a Mediterranean cohort , particularly in the participants who had already gained weight , an increased consumption of sugar-sweetened soft drinks and of hamburgers , pizza , and sausages was associated with a higher risk of additional subsequent weight gain BACKGROUND Previous studies have linked full-calorie sugar-sweetened beverages ( SSBs ) with greater weight gain and an increased risk of type 2 diabetes . OBJECTIVE We prospect ively examined the association between consumption of SSBs and the risk of coronary heart disease ( CHD ) in women . DESIGN Women ( n = 88,520 ) from the Nurses ' Health Study aged 34 - 59 y , without previously diagnosed coronary heart disease ( CHD ) , stroke , or diabetes in 1980 , were followed from 1980 to 2004 . Consumption of SSBs was derived from 7 repeated food-frequency question naires administered between 1980 and 2002 . Relative risks ( RRs ) for CHD were calculated by using Cox proportional hazards models and adjusted for known cardiovascular disease risk factors . RESULTS During 24 y of follow-up , we ascertained 3105 incident cases of CHD ( nonfatal myocardial infa rct ion and fatal CHD ) . After st and ard and dietary risk factors were adjusted for , the RRs ( and 95 % CIs ) of CHD according to categories of cumulative average of SSB consumption ( < 1/mo , 1 - 4/mo , 2 - 6/wk , 1/d , and > or = 2 servings/d ) were 1.0 , 0.96 ( 0.87 , 1.06 ) , 1.04 ( 0.95 , 1.14 ) , 1.23 ( 1.06 , 1.43 ) , and 1.35 ( 1.07 , 1.69 ) ( P for trend < 0.001 ) . Additional adjustment for body mass index , energy intake , and incident diabetes attenuated the associations , but they remained significant . Artificially sweetened beverages were not associated with CHD . CONCLUSION Regular consumption of SSBs is associated with a higher risk of CHD in women , even after other unhealthful lifestyle or dietary factors are accounted for BACKGROUND Consumption of liquid calories from beverages has increased in parallel with the obesity epidemic in the US population , but their causal relation remains unclear . OBJECTIVE The objective of this study was to examine how changes in beverage consumption affect weight change among adults . DESIGN This was a prospect i ve study of 810 adults participating in the PREMIER trial , an 18-mo r and omized , controlled , behavioral intervention trial . Measurements ( weight , height , and 24-h dietary recall ) were made at baseline , 6 mo , and 18 mo . RESULTS Baseline mean intake of liquid calories was 356 kcal/d ( 19 % of total energy intake ) . After potential confounders and intervention assignment were controlled for , a reduction in liquid calorie intake of 100 kcal/d was associated with a weight loss of 0.25 kg ( 95 % CI : 0.11 , 0.39 ; P < 0.001 ) at 6 mo and of 0.24 kg ( 95 % CI : 0.06 , 0.41 ; P = 0.008 ) at 18 mo . A reduction in liquid calorie intake had a stronger effect than did a reduction in solid calorie intake on weight loss . Of the individual beverages , only intake of sugar-sweetened beverages ( SSBs ) was significantly associated with weight change . A reduction in SSB intake of 1 serving/d was associated with a weight loss of 0.49 kg ( 95 % CI : 0.11 , 0.82 ; P = 0.006 ) at 6 mo and of 0.65 kg ( 95 % CI : 0.22 , 1.09 ; P = 0.003 ) at 18 mo . CONCLUSIONS These data support recommendations to limit liquid calorie intake among adults and to reduce SSB consumption as a means to accomplish weight loss or avoid excess weight gain . This trial was registered at clinical trials.gov as NCT00000616 BACKGROUND Type 2 diabetes mellitus is an increasingly serious health problem among African American women . Consumption of sugar-sweetened drinks was associated with an increased risk of diabetes in 2 studies but not in a third ; however , to our knowledge , no data are available on African Americans regarding this issue . Our objective was to examine the association between consumption of sugar-sweetened beverages , weight gain , and incidence of type 2 diabetes mellitus in African American women . METHODS A prospect i ve follow-up study of 59,000 African American women has been in progress since 1995 . Participants reported on food and beverage consumption in 1995 and 2001 . Biennial follow-up question naires ascertained new diagnoses of type 2 diabetes . The present analyses included 43,960 women who gave complete dietary and weight information and were free from diabetes at baseline . We identified 2713 incident cases of type 2 diabetes mellitus during 338,884 person-years of follow-up . The main outcome measure was the incidence of type 2 diabetes mellitus . RESULTS The incidence of type 2 diabetes mellitus was higher with higher intake of both sugar-sweetened soft drinks and fruit drinks . After adjustment for confounding variables including other dietary factors , the incidence rate ratio for 2 or more soft drinks per day was 1.24 ( 95 % confidence interval , 1.06 - 1.45 ) . For fruit drinks , the comparable incidence rate ratio was 1.31 ( 95 % confidence interval , 1.13 - 1.52 ) . The association of diabetes with soft drink consumption was almost entirely mediated by body mass index , whereas the association with fruit drink consumption was independent of body mass index . CONCLUSIONS Regular consumption of sugar-sweetened soft drinks and fruit drinks is associated with an increased risk of type 2 diabetes mellitus in African American women . While there has been increasing public awareness of the adverse health effects of soft drinks , little attention has been given to fruit drinks , which are often marketed as a healthier alternative to soft drinks BACKGROUND St and ard behavioral obesity treatment produces poor long-term results . Focusing on healthy eating behaviors rather than energy intake may be an alternative strategy . In addition , important behaviors might differ for short- vs long-term weight control . OBJECTIVE Our aim was to describe and compare associations between changes in eating behaviors and weight after 6 and 48 months . DESIGN We performed secondary analysis of data collected during a r and omized weight-loss intervention trial with 48-month follow-up . PARTICIPANTS We studied 481 overweight and obese postmenopausal women enrolled in the Women on the Move through Activity and Nutrition ( WOMAN ) Study . MAIN OUTCOME MEASURES We measured changes in weight from baseline to 6 and 48 months . STATISTICAL ANALYSES PERFORMED Linear regression models were used to examine the associations between 6- and 48-month changes in eating habits assessed by the Conner Diet Habit Survey and changes in weight . Analyses were conducted in the combined study population and stratified by r and omization group . RESULTS At 6 months in the combined population , weight loss was independently associated with decreased desserts ( P<0.001 ) , restaurant eating ( P=0.042 ) , sugar-sweetened beverages ( P=0.009 ) , and fried foods ( P<0.001 ) , and increased fish consumption ( P=0.003 ) . Results were similar in intervention participants ; only reduced desserts and fried foods associated with weight loss in controls . At 48 months in the combined population , weight loss was again associated with decreased desserts ( P=0.003 ) and sugar-sweetened beverages ( P=0.011 ) , but also decreased meats/cheeses ( P=0.024 ) and increased fruits/vegetables ( P<0.001 ) . Decreased meats/cheeses predicted weight loss in intervention participants ; desserts , sugar-sweetened beverages , and fruits/vegetables were independently associated in controls . CONCLUSIONS Changes in eating behaviors were associated with weight change , although important behaviors differed for short- and long-term weight change and by r and omization group . Future studies should determine whether interventions targeting these behaviors could improve long-term obesity treatment outcomes BACKGROUND The consumption of sucrose-sweetened soft drinks ( SSSDs ) has been associated with obesity , the metabolic syndrome , and cardiovascular disorders in observational and short-term intervention studies . Too few long-term intervention studies in humans have examined the effects of soft drinks . OBJECTIVE We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition ( in liver and muscle tissue ) . DESIGN Overweight subjects ( n = 47 ) were r and omly assigned to 4 different test drinks ( 1 L/d for 6 mo ) : SSSD ( regular cola ) , isocaloric semiskim milk , aspartame-sweetened diet cola , and water . The amount of intrahepatic fat and intramyocellular fat was measured with (1)H-magnetic resonance spectroscopy . Other endpoints were fat mass , fat distribution ( dual-energy X-ray absorptiometry and magnetic resonance imaging ) , and metabolic risk factors . RESULTS The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat ( 132 - 143 % , sex-adjusted mean ; P < 0.01 ) , skeletal muscle fat ( 117 - 221 % ; P < 0.05 ) , visceral fat ( 24 - 31 % ; P < 0.05 ) , blood triglycerides ( 32 % ; P < 0.01 ) , and total cholesterol ( 11 % ; P < 0.01 ) . Total fat mass was not significantly different between the 4 beverage groups . Milk and diet cola reduced systolic blood pressure by 10 - 15 % compared with regular cola ( P < 0.05 ) . Otherwise , diet cola had effects similar to those of water . CONCLUSION Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk , diet cola , and water . Thus , daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases . This trial is registered at clinical trials.gov as NCT00777647 Soft drinks and other sweetened beverages may contribute to risk of type 2 diabetes and obesity . However , research has not addressed higher risk and Asian population s. The authors examined the association between soft drinks and juice and the risk of type 2 diabetes among Chinese Singaporeans enrolled in a prospect i ve cohort study of 43,580 participants aged 45 - 74 years and free of diabetes and other chronic diseases at baseline . The incidence of physician-diagnosed type 2 diabetes was assessed by interview and vali date d ; 2,273 participants developed diabetes during follow-up . After adjustment for potential lifestyle and dietary confounders , participants consuming > or = 2 soft drinks per week had a relative risk of type 2 diabetes of 1.42 ( 95 % confidence interval ( CI ) : 1.25 , 1.62 ) compared with those who rarely consumed soft drinks . Similarly , consumption of > or = 2 juice beverages per week was associated with an increased risk ( relative risk ( RR ) = 1.29 , 95 % CI : 1.05 , 1.58 ) . The association was modified by 5-year weight gain for > or = 2 soft drinks per week among those who gained > or =3 kg ( RR = 1.70 , 95 % CI : 1.34 , 2.16 ) compared with those who gained less weight ( RR = 1.20 , 95 % CI : 1.03 , 1.41 ) . Relatively frequent intake of soft drinks and juice is associated with an increased risk for development of type 2 diabetes in Chinese men and women SamenvattingObesitas bij kinderen heeft epidemische vormen aangenomen.2 De belangrijkste oorzaken voor excessieve gewichtstoename bij kinderen zijn genetisch , endocrien bepaald en kan ontstaan onafhankelijk van and ere ziekten.3 Nu is veronderstelling dat de consumptie van zoete koolzuurhoudende dranken bijdraagt aan overgewicht bij kinderen . Uit onderzoek is gebleken dat kinderen die regelmatig koolzuurhoudende zoete frisdrank drinken gemiddeld 10 procent hogere energie-inname hebben vergeleken met kinderen die deze frisdrank niet consumeren.4 In Engel and drinkt meer dan 70 procent van de adolescenten frequent koolzuurhoudende frisdrank Background Dietary factors such as low energy density and low glycemic index were associated with a lower gain in abdominal adiposity . A better underst and ing of which food groups/items contribute to these associations is necessary . Objective To ascertain the association of food groups/items consumption on prospect i ve annual changes in “ waist circumference for a given BMI ” ( WC BMI ) , a proxy for abdominal adiposity . Design We analyzed data from 48,631 men and women from 5 countries participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years . WC BMI was defined as the residuals of waist circumference regressed on BMI , and annual change in WC BMI ( ΔWC BMI , cm/y ) was defined as the difference between residuals at follow-up and baseline , divided by follow-up time . The association between food groups/items and ΔWC BMI was modelled using centre-specific adjusted linear regression , and r and om-effects meta-analyses to obtain pooled estimates . Results Higher fruit and dairy products consumption was associated with a lower gain in WC BMI whereas the consumption of white bread , processed meat , margarine , and soft drinks was positively associated with ΔWC BMI . When these six food groups/items were analyzed in combination using a summary score , those in the highest quartile of the score – indicating a more favourable dietary pattern –showed a ΔWC BMI of −0.11 ( 95 % CI −0.09 to −0.14 ) cm/y compared to those in the lowest quartile . Conclusion A dietary pattern high in fruit and dairy and low in white bread , processed meat , margarine , and soft drinks may help to prevent abdominal fat accumulation Previous studies have yielded inconsistent results when documenting the association between key dietary factors and adolescent weight change over time . The purpose of this study was to examine the extent to which changes in adolescent sugar-sweetened beverage ( SSB ) , diet soda , breakfast , and fast-food consumption were associated with changes in BMI and percent body fat ( PBF ) . This study analyzed data from a sample of 693 Minnesota adolescents followed over 2 years . R and om coefficient models were used to examine the relationship between dietary intake and BMI and PBF and to separate cross-sectional and longitudinal associations . Adjusting for total physical activity , total energy intake , puberty , race , socioeconomic status , and age , cross-sectional findings indicated that for both males and females , breakfast consumption was significantly and inversely associated with BMI and PBF , and diet soda intake was significantly and positively associated with BMI and PBF among females . In longitudinal analyses , however , there were fewer significant associations . Among males there was evidence of a significant longitudinal association between SSB consumption and PBF ; after adjustment for energy intake , an increase of one serving of SSB per day was associated with an increase of 0.7 units of PBF among males . This study adds to previous research through its method ological strengths , including adjustment for physical activity and energy intake assessed using state-of-the-art methods ( i.e. , accelerometers and 24-h dietary recalls ) , as well as its evaluation of both BMI and PBF . Additional research is needed to better underst and the complex constellation of factors that contribute to adolescent weight gain over time OBJECTIVE To study changes in lifestyle in relation to changes in body weight and waist circumference associated with occupational retirement in men . DESIGN A prospect i ve cohort study with 5 years of follow-up . At baseline and at follow-up , question naires were completed and body weight and waist circumference were measured . SETTING The Doetinchem Cohort Study , consisting of inhabitants of Doetinchem , a town in a rural area of The Netherl and s. SUBJECTS In total 288 healthy men aged 50 - 65 years at baseline , who either remained employed or retired over follow-up . RESULTS The effect of retirement on changes in weight and waist circumference was dependent on type of former occupation . Increase in body weight and waist circumference was higher among men who retired from active jobs ( 0.42 kg year(-1 ) and 0.77 cm year(-1 ) , respectively ) than among men who retired from sedentary jobs ( 0.08 kg year(-1 ) and 0.23 cm year(-1 ) , respectively ) . Weight gain and increase in waist circumference were associated with a decrease in fruit consumption and fibre density of the diet , with an increase in frequency of eating breakfast , and with a decrease in several physical activities , such as household activities , bicycling , walking and doing odd jobs . CONCLUSION Retirement was associated with an increase in weight and waist circumference among those with former active jobs , but not among those with former sedentary jobs . Retirement may bring opportunities for healthy changes in diet and physical activity , which could be used in health promotion programmes In the present study the relationship between the consumption of different beverage groups and body-weight status in 5 years of study participation in German adolescents was investigated . We used anthropometric and dietary data from 3 d weighed records of 244 subjects between 9 and 18 years of age participating in the Dortmund Nutritional and Anthropometric Longitudinally Design ed ( DONALD ) study . Only subjects with at least four out of six possible weighed dietary records were considered . A repeated- measures regression model ( PROC MIXED ) was used to analyse the effect of beverage consumption on body-weight status . BMI st and ard deviation scores ( BMI -SDS ) and body fat percentage ( % BF ) were chosen as the dependent variables . In boys , energetic beverage consumption was not associated with BMI -SDS or % BF , neither cross-sectionally nor prospect ively . In girls , baseline consumption of energetic beverages did not predict baseline BMI -SDS , baseline % BF , or change in either variable over the study period . However , an increase in energetic beverage consumption over the study period was associated with an increase in BMI -SDS ( + 0.070 SDS/MJ increase in energetic beverage consumption ; P = 0.01 ) . Separate consideration of regular soft drinks and fruit juices revealed that , in girls , BMI -SDS increased with increased fruit juice consumption ( + 0.096 SDS/MJ increase in fruit juice consumption ; P = 0.01 ) , and to a lesser extent with regular soft drink consumption ( + 0.055 SDS/MJ increase in regular soft drink consumption ; P = 0.08 ) . In conclusion , these results suggest that an increase in energetic beverage consumption may result in weight gain , at least in adolescent girls BACKGROUND The rising prevalence of obesity in children has been linked in part to the consumption of sugar-sweetened drinks . Our aim was to examine this relation . METHODS We enrolled 548 ethnically diverse schoolchildren ( age 11.7 years , SD 0.8 ) from public schools in four Massachusetts communities , and studied them prospect ively for 19 months from October , 1995 , to May , 1997 . We examined the association between baseline and change in consumption of sugar-sweetened drinks ( the independent variables ) , and difference in measures of obesity , with linear and logistic regression analyses adjusted for potentially confounding variables and clustering of results within schools . FINDINGS For each additional serving of sugar-sweetened drink consumed , both body mass index ( BMI ) ( mean 0.24 kg/m2 ; 95 % CI 0.10 - 0.39 ; p=0.03 ) and frequency of obesity ( odds ratio 1.60 ; 95 % CI 1.14 - 2.24 ; p=0.02 ) increased after adjustment for anthropometric , demographic , dietary , and lifestyle variables . Baseline consumption of sugar-sweetened drinks was also independently associated with change in BMI ( mean 0.18 kg/m2 for each daily serving ; 95 % CI 0.09 - 0.27 ; p=0.02 ) . INTERPRETATION Consumption of sugar-sweetened drinks is associated with obesity in children OBJECTIVE To determine whether an educational programme aim ed at discouraging students from drinking sugar-sweetened beverages could prevent excessive weight gain . DESIGN Forty-seven classes in twenty-two schools were r and omised as intervention or control . SUBJECTS Participants were 1140 , 9 - 12-year-old fourth grade rs ( 435 in the intervention group and 608 in the control group ) . Sugar-sweetened beverages and juice intake were measured through one 24 h recall at baseline and another at the end of the trial . The main outcome was the change in BMI ( BMI = weight (kg)/height ( m2 ) ) , measured at the beginning and at the end of the school year . Intention-to-treat analysis was performed taking into account the cluster ( classes ) effect . RESULTS A statistically significant decrease in the daily consumption of carbonated drinks in the intervention compared to control ( mean difference = -56 ml ; 95 % CI -119 , -7 ml ) was followed by a non-significant overall reduction in BMI , P = 0.33 . However , among those students overweight at baseline , the intervention group showed greater BMI reduction ( -0.4 kg/m2 compared with -0.2 kg/m2 in the control group ( P = 0.11 ) ) , and this difference was statistically significant among girls ( P = 0.009 ) . Fruit juice consumption was slightly increased in the intervention group ( P = 0.08 ) , but not among girls . CONCLUSION Decreasing sugar-sweetened beverages intake significantly reduced BMI among overweight children , and mainly among girls . Efforts to reduce energy intake through liquids need to emphasise overall sweetened beverages and addition of sugar on juices Objective To assess the long term effects of an obesity prevention programme in schools . Design Longitudinal results after a cluster r and omised controlled trial . Setting Schools in southwest Engl and . Participants Of the original sample of 644 children aged 7 - 11 , 511 children were tracked and measurements were obtained from 434 children three years after baseline . Intervention The intervention was conducted over one school year , with four sessions of focused education promoting a healthy diet and discouraging the consumption of carbonated drinks . Main outcome measures Anthropometric measures of height , weight , and waist circumference . Body mass index ( BMI ) converted to z scores ( SD scores ) and to centile values with growth reference curves . Waist circumference was also converted to z scores ( SD scores ) . Results At three years after baseline the age and sex specific BMI z scores ( SD scores ) had increased in the control group by 0.10 ( SD 0.53 ) but decreased in the intervention group by −0.01 ( SD 0.58 ) , with a mean difference of 0.10 ( 95 % confidence interval −0.00 to 0.21 , P=0.06 ) . The prevalence of overweight increased in both the intervention and control group at three years and the significant difference between the groups seen at 12 months was no longer evident . The BMI increased in the control group by 2.14 ( SD 1.64 ) and the intervention group by 1.88 ( SD 1.71 ) , with mean difference of 0.26 ( −0.07 to 0.58 , P= 0.12 ) . The waist circumference increased in both groups after three years with a mean difference of 0.09 ( −0.06 to 0.26 , P=0.25 ) . Conclusions These longitudinal results show that after a simple year long intervention the difference in prevalence of overweight in children seen at 12 months was not sustained at three years BACKGROUND Sugar-sweetened beverages are risk factors for type 2 diabetes ; however , the role of artificially sweetened beverages is unclear . OBJECTIVE The objective was to examine the associations of sugar- and artificially sweetened beverages with incident type 2 diabetes . DESIGN An analysis of healthy men ( n = 40,389 ) from the Health Professionals Follow-Up Study , a prospect i ve cohort study , was performed . Cumulatively averaged intakes of sugar-sweetened ( sodas , fruit punches , lemonades , fruit drinks ) and artificially sweetened ( diet sodas , diet drinks ) beverages from food-frequency question naires were tested for associations with type 2 diabetes by using Cox regression . RESULTS There were 2680 cases over 20 y of follow-up . After age adjustment , the hazard ratio ( HR ) for the comparison of the top with the bottom quartile of sugar-sweetened beverage intake was 1.25 ( 95 % CI : 1.11 , 1.39 ; P for trend < 0.01 ) . After adjustment for confounders , including multivitamins , family history , high triglycerides at baseline , high blood pressure , diuretics , pre-enrollment weight change , dieting , total energy , and body mass index , the HR was 1.24 ( 95 % CI : 1.09 , 1.40 ; P for trend < 0.01 ) . Intake of artificially sweetened beverages was significantly associated with type 2 diabetes in the age-adjusted analysis ( HR : 1.91 ; 95 % CI : 1.72 , 2.11 ; P for trend < 0.01 ) but not in the multivariate-adjusted analysis ( HR : 1.09 ; 95 % CI : 0.98 , 1.21 ; P for trend = 0.13 ) . The replacement of one serving of sugar-sweetened beverage with 1 cup ( ≈237 mL ) of coffee was associated with a risk reduction of 17 % . CONCLUSION Sugar-sweetened beverage consumption is associated with a significantly elevated risk of type 2 diabetes , whereas the association between artificially sweetened beverages and type 2 diabetes was largely explained by health status , pre-enrollment weight change , dieting , and body mass index BACKGROUND : Beverages are contributing an increased proportion of energy to the diet . Because they elicit a weak compensatory dietary response , they may increase risk of positive energy balance . OBJECTIVES : This study aim ed to document the differential effects of matched liquid and solid carbohydrate loads on diet and body weight . DESIGN : In a cross-over design , seven males and eight females consumed dietary carbohydrate loads of 1880 kJ/day as a liquid ( soda ) or solid ( jelly beans ) during two 4 week periods separated by a 4 week washout . Subjects were permitted to consume the loads however they chose . In addition to baseline measurements , diet records were obtained on r and om days throughout the study , body composition was measured weekly , physical activity was assessed before and after treatments and hunger was assessed during washout and midway through each treatment . RESULTS : Free-feeding energy intake during the solid period was significantly lower than intake prior to this period . Dietary energy compensation was precise ( 118 % ) . No decrease in free-feeding energy intake occurred during the liquid period . Total daily energy intake increased by an amount equal to the load result ing in dietary compensation of −17 % . Consequently , body weight and BMI increased significantly only during the liquid period . Physical activity and hunger were unchanged . CONCLUSIONS : This study indicates that liquid carbohydrate promotes positive energy balance , whereas a comparable solid carbohydrate elicits precise dietary compensation . Increased consumption of energy-yielding fluids may promote positive energy balance BACKGROUND Consumption of sugar-sweetened beverages may cause excessive weight gain . We aim ed to assess the effect on weight gain of an intervention that included the provision of noncaloric beverages at home for overweight and obese adolescents . METHODS We r and omly assigned 224 overweight and obese adolescents who regularly consumed sugar-sweetened beverages to experimental and control groups . The experimental group received a 1-year intervention design ed to decrease consumption of sugar-sweetened beverages , with follow-up for an additional year without intervention . We hypothesized that the experimental group would gain weight at a slower rate than the control group . RESULTS Retention rates were 97 % at 1 year and 93 % at 2 years . Reported consumption of sugar-sweetened beverages was similar at baseline in the experimental and control groups ( 1.7 servings per day ) , declined to nearly 0 in the experimental group at 1 year , and remained lower in the experimental group than in the control group at 2 years . The primary outcome , the change in mean body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) at 2 years , did not differ significantly between the two groups ( change in experimental group minus change in control group , -0.3 ; P=0.46 ) . At 1 year , however , there were significant between-group differences for changes in BMI ( -0.57 , P=0.045 ) and weight ( -1.9 kg , P=0.04 ) . We found evidence of effect modification according to ethnic group at 1 year ( P=0.04 ) and 2 years ( P=0.01 ) . In a prespecified analysis according to ethnic group , among Hispanic participants ( 27 in the experimental group and 19 in the control group ) , there was a significant between-group difference in the change in BMI at 1 year ( -1.79 , P=0.007 ) and 2 years ( -2.35 , P=0.01 ) , but not among non-Hispanic participants ( P>0.35 at years 1 and 2 ) . The change in body fat as a percentage of total weight did not differ significantly between groups at 2 years ( -0.5 % , P=0.40 ) . There were no adverse events related to study participation . CONCLUSIONS Among overweight and obese adolescents , the increase in BMI was smaller in the experimental group than in the control group after a 1-year intervention design ed to reduce consumption of sugar-sweetened beverages , but not at the 2-year follow-up ( the prespecified primary outcome ) . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; Clinical Trials.gov number , NCT00381160 . ) BACKGROUND Consumption of sugar-sweetened soda has been associated with an increased risk of cardiometabolic disease . The relation with cerebrovascular disease has not yet been closely examined . OBJECTIVE Our objective was to examine patterns of soda consumption and substitution of alternative beverages for soda in relation to stroke risk . DESIGN The Nurses ' Health Study , a prospect i ve cohort study of 84,085 women followed for 28 y ( 1980 - 2008 ) , and the Health Professionals Follow-Up Study , a prospect i ve cohort study of 43,371 men followed for 22 y ( 1986 - 2008 ) , provided data on soda consumption and incident stroke . RESULTS We documented 1416 strokes in men during 841,770 person-years of follow-up and 2938 strokes in women during 2,188,230 person-years of follow-up . The pooled RR of total stroke for ≥ 1 serving of sugar-sweetened soda/d , compared with none , was 1.16 ( 95 % CI : 1.00 , 1.34 ) . The pooled RR of total stroke for ≥ 1 serving of low-calorie soda/d , compared with none , was 1.16 ( 95 % CI : 1.05 , 1.28 ) . Compared with 1 serving of sugar-sweetened soda/d , 1 serving of decaffeinated coffee/d was associated with a 10 % ( 95 % CI : 1 % , 19 % ) lower risk of stroke and 1 serving of caffeinated coffee/d with a 9 % ( 95 % CI : 0 % , 17 % ) lower risk . Similar estimated reductions in risk were seen for substitution of caffeinated or decaffeinated coffee for low-calorie soda . CONCLUSIONS Greater consumption of sugar-sweetened and low-calorie sodas was associated with a significantly higher risk of stroke . This risk may be reduced by substituting alternative beverages for soda OBJECTIVE . The role of sugar-sweetened beverages ( SSBs ) in promoting obesity is controversial . Observational data link SSB consumption with excessive weight gain ; however , r and omized , controlled trials are lacking and necessary to resolve the debate . We conducted a pilot study to examine the effect of decreasing SSB consumption on body weight . METHODS . We r and omly assigned 103 adolescents aged 13 to 18 years who regularly consumed SSBs to intervention and control groups . The intervention , 25 weeks in duration , relied largely on home deliveries of noncaloric beverages to displace SSBs and thereby decrease consumption . Change in SSB consumption was the main process measure , and change in body mass index ( BMI ) was the primary end point . RESULTS . All of the r and omly assigned subjects completed the study . Consumption of SSBs decreased by 82 % in the intervention group and did not change in the control group . Change in BMI , adjusted for gender and age , was 0.07 ± 0.14 kg/m2 ( mean ± SE ) for the intervention group and 0.21 ± 0.15 kg/m2 for the control group . The net difference , −0.14 ± 0.21 kg/m2 , was not significant overall . However , baseline BMI was a significant effect modifier . Among the subjects in the upper baseline- BMI tertile , BMI change differed significantly between the intervention ( −0.63 ± 0.23 kg/m2 ) and control ( + 0.12 ± 0.26 kg/m2 ) groups , a net effect of −0.75 ± 0.34 kg/m2 . The interaction between weight change and baseline BMI was not attributable to baseline consumption of SSBs . CONCLUSIONS . A simple environmental intervention almost completely eliminated SSB consumption in a diverse group of adolescents . The beneficial effect on body weight of reducing SSB consumption increased with increasing baseline body weight , offering additional support for American Academy of Pediatrics guidelines to limit SSB consumption OBJECTIVE To examine prospect ively the association between beverage consumption ( fruit juice , fruit drinks , milk , soda , and diet soda ) and changes in weight and body mass index among preschool children . DESIGN A prospect i ve cohort study that collected dietary , anthropometric , and sociodemographic data .Subjects/ Setting The study population included 1,345 children age 2 to 5 years participating in the North Dakota Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) on two visits between 6 to 12 months apart . Statistical analyses We performed linear regression analyses to examine whether beverage consumption was associated with annual change in weight and body mass index . Intakes were measured as continuous ( oz/day ) and we also dichotomized fruit juice , fruit drinks , and milk at high intakes . RESULTS In multivariate regression analyses adjusted for age , sex , energy intake , change in height , and additional sociodemographic variables , weight change was not significantly related to intakes ( per ounce ) of fruit juice ( beta=0.01 lb/year , 95 % CI : -0.01 to 0.20 , P=.28 ) , fruit drinks ( beta=-0.03 lb/year , 95 % CI : -0.07 to 0.01 , P=.28 ) , milk ( beta=0.00 lb/year , 95 % CI : -0.02 to 0.02 , P=.86 ) , soda ( beta=-0.00 lb/year , 95 % CI : -0.08 to 0.08 , P=.95 ) , or diet soda ( beta=0.01 lb/year , 95 % CI : -0.11 to 0.13 , P=.82 ) . Findings remained null when we examined associations with body mass index and when fruit juice , fruit drinks , and milk were dichotomized at high intake levels in both analyses . CONCLUSIONS Our study does not show an association between beverage consumption and changes in weight or body mass index in this population of low-income preschool children in North Dakota Objective The present study evaluated weight loss and compliance outcomes for overweight adolescents assigned to one of two dietary interventions differing in the type of snacks allowed . Methods The study was a 12-week , controlled clinical trial , among otherwise healthy but overweight ( body mass index ≥95th percentile ) 11-year-old to 15-year-old girls who were r and omly assigned to either a 1,500 kcal/day free-snack program or a 1,500 kcal/day restricted-snack program . All subjects were counseled to consume three servings of dairy products per day , and were provided with a 500 mg calcium supplement as well . Subjects in the free-snack group could choose any 150-calorie item as one of their two daily snacks , including regular soda if desired ; however , subjects in the restricted-snack group were limited to diet soda . Results Thirty-two adolescent girls completed the 12-week intervention . Both diets were equally effective in achieving a modest amount of weight loss , and were equally acceptable to the subjects . Significant decreases in weight , body mass index , anthropometric measures , total cholesterol and triglycerides were observed . Conclusions A 1,500 kcal/day diet allowing for a free snack of 150 calories was equally as effective as a more restricted snack policy in achieving a modest amount of weight loss among overweight 11-year-old to 15-year-old girls . In addition , results suggest that some soda may be included in a teen weight control diet , as long as caloric intake is maintained at recommended levels , and care is taken to achieve adequate intake of essential nutrients . Calcium intake among subjects was low at baseline , and , although it increased during the study ( due to supplementation ) , further efforts to increase consumption of naturally calcium-rich and calcium-fortified foods and beverages are needed The authors analyzed data from a prospect i ve , community-based cohort to assess the risk of incident type 2 diabetes mellitus associated with coffee and sweetened beverage consumption . They included 12,204 nondiabetic , middle-aged men and women in the Atherosclerosis Risk in Communities ( ARIC ) Study ( 1987 - 1999 ) . Consumption of each beverage was assessed by food frequency question naire and classified into categories of cups per day . They found an inverse association , after adjusting for potential confounders , between increased coffee consumption and risk of type 2 diabetes mellitus in men ( for > or = 4 cups ( > or = 0.95 liter)/day compared with almost never : hazard ratio = 0.77 , p(trend ) = 0.02 ) with no significant association in women ( hazard ratio = 0.89 , p(trend ) = 0.32 ) using a combination of self-report of physician-diagnosed diabetes , diabetes treatment , and a fasting or nonfasting blood glucose test . When self-reported diabetes or diabetes treatment alone was used , a stronger and significant inverse association was seen in men and women . Sweetened beverage consumption ( men : hazard ratio = 1.03 , p(trend ) = 0.94 ; women : hazard ratio = 1.01 , p(trend ) = 0.58 ) showed no consistent association with the incidence of type 2 diabetes mellitus . In summary , increased coffee consumption was significantly associated with a decreased risk of diagnosed type 2 diabetes mellitus in community-based US adults OBJECTIVE The increase in consumption of sugar-added beverages over recent decades may be partly responsible for the obesity epidemic among U.S. adolescents . Our aim was to evaluate the relationship between BMI changes and intakes of sugar-added beverages , milk , fruit juices , and diet soda . RESEARCH METHODS AND PROCEDURES Our prospect i ve cohort study included > 10,000 boys and girls participating in the U.S. Growing Up Today Study . The participants were 9 to 14 years old in 1996 and completed question naires in 1996 , 1997 , and 1998 . We analyzed change in BMI ( kilograms per meter squared ) over two 1-year periods among children who completed annual food frequency question naires assessing typical past year intakes . We studied beverage intakes during the year corresponding to each BMI change , and in separate models , we studied 1-year changes in beverage intakes , adjusting for prior year intakes . Models included all beverages simultaneously ; further models adjusted for total energy intake . RESULTS Consumption of sugar-added beverages was associated with small BMI gains during the corresponding year ( boys : + 0.03 kg/m2 per daily serving , p = 0.04 ; girls : + 0.02 kg/m2 , p = 0.096 ) . In models not assuming a linear dose-response trend , girls who drank 1 serving/d of sugar-added beverages gained more weight ( + 0.068 , p = 0.02 ) than girls drinking none , as did girls drinking 2 servings/d ( + 0.09 , p = 0.06 ) or 3 + servings/d ( + 0.08 , p = 0.06 ) . Analyses of year-to-year change in beverage intakes provided generally similar findings ; boys who increased consumption of sugar-added beverages from the prior year experienced weight gain ( + 0.04 kg/m2 per additional daily serving , p = 0.01 ) . Children who increased intakes by 2 or more servings/d from the prior year gained weight ( boys : + 0.14 , p = 0.01 ; girls + 0.10 , p = 0.046 ) . Further adjusting our models for total energy intake substantially reduced the estimated effects , which were no longer significant . DISCUSSION Consumption of sugar-added beverages may contribute to weight gain among adolescents , probably due to their contribution to total energy intake , because adjustment for calories greatly attenuated the estimated associations PURPOSE To determine whether a significant relationship exists between fat mass ( FM ) development and physical activity ( PA ) and /or sugar-sweetened drink ( SD ) consumption in healthy boys and girls aged 8 - 19 yr . METHODS A total of 105 males and 103 females were assessed during childhood and adolescence for a maximum of 7 yr and a median of 5 yr . Height was measured biannually . Fat-free mass ( FFM ) and FM were assessed annually by dual x-ray absorptiometry ( DXA ) . PA was evaluated two to three times annually using the PAQ-C/A. Energy intake and SD were assessed using a 24-h dietary intake question naire also completed two to three times per year . Years from peak height velocity were used as a biological maturity age indicator . Multilevel r and om effects models were used to test the relationship . RESULTS When controlling for maturation , FFM , and energy intake adjusted for SD , PA level was negatively related to FM development in males ( P<0.05 ) but not in females ( P>0.05 ) . In contrast , there was no relationship between SD and FM development of males or females ( P>0.05 ) . There was also no interaction effect between SD and PA ( P>0.05 ) with FM development . CONCLUSION This finding lends support to the idea that increasing PA in male youths aids in the control of FM development . Models employed showed no relationship between SD and FM in either gender The long-term effects of sucrose on appetite and mood remain unclear . Normal weight subjects compensate for sucrose added blind to the diet ( Reid et al. , 2007 ) . Overweight subjects , however , may differ . In a single-blind , between-subjects design , soft drinks ( 4x25cl per day ; 1800kJ sucrose sweetened versus 67kJ aspartame sweetened ) were added to the diet of overweight women ( n=53 , BMI 25 - 30 , age 20 - 55 ) for 4 weeks . A 7-day food diary gave measures of total energy , carbohydrate , protein , fat , and micronutrients . Mood and hunger were measured by ten single Likert scales rated daily at 11.00 , 14.00 , 16.00 , and 20.00 . Activity levels were measured by diary and pedometer . Baseline energy intake did not differ between groups . During the first week of the intervention energy intake increased slightly in the sucrose group , but not in the aspartame group , then decreased again , so by the final week intake again did not differ from the aspartame group . Compensation was not large enough to produce significant changes in the composition of the voluntary diet . There were no effects on hunger or mood . It is concluded that overweight women do not respond adversely to sucrose added blind to the diet , but compensate for it by reducing voluntary energy intake . Alternative explanations for the correlation between sugary soft drink intake and weight gain are discussed |
13,352 | 25,323,325 | Conclusions These data indicate that ineffectiveness of glucagon is unfrequent , not different from dextrose ; in addition , intranasal and injected glucagon are similarly effective .
In the case of failure , a second dose can be administered | Abstract Aims Glucagon is used as an emergency drug in hypoglycemia , mainly when the patient is unconscious .
A few studies report on ineffectiveness of glucagon in relieving hypoglycemia .
The present systematic review and meta- analysis evaluate the effectiveness of glucagon alone and in comparison with dextrose and the effectiveness of intranasal glucagon in comparison with injected glucagon . | Biosynthetic glucagon ( GL-G ) produced by recombinant DNA technology with transformed yeast strains is already available for clinical use . We studied the effects of 1 mg GL-G injection on plasma glucose level and hypoglycemic symptoms in 38 diabetic patients treated with insulin or oral hypoglycemic agents during spontaneous hypoglycemic episodes . In both intramuscularly and intravenously administered GL-G groups , plasma glucose significantly increased from 58.1 + /- 11.4 to 113.2 + /- 6.9 mg/dl ( i.m . , n = 17 , P < 0.01 ) and from 76.4 + /- 4.4 to 125.7 + /- 5.9 mg/dl ( i.v . , n = 15 , P < 0.01 ) , respectively 20 min after the administration and the symptoms due to hypoglycemia subsided promptly after the injection of GL-G in 27 cases . The hyperglycemic effect of intramuscularly injected GL-G was more potent and long-st and ing than when intravenously injected , particularly in insulin-dependent diabetic ( IDDM ) patients . Neither significant changes of antibody levels against yeast proteins nor serious adverse effects were observed after GL-G administration . Biosynthetic glucagon is safe and useful for the treatment of hypoglycemia developing in diabetic patients Abstract 1 mg . glucagon was given i.m . or i.v . to a hundred hypoglycaemic diabetics unable to take glucose by mouth . Within 15 minutes forty were either awake or sufficiently roused to take oral glucose ; only one of the remaining sixty responded to a second injection of glucagon given 15 minutes after the first . There was no difference between the effect of i.m . and i.v . glucagon . The fifty-nine glucagon-unresponsive patients were given 25 g. dextrose i.v . ; thirty-six were awake within 15 minutes and another four responded to a second injection of 25 g. The remaining nineteen were still unconscious despite an adequate level of glycaemia having been achieved ( mean 247 : range 179 - 350 mg . per 100 ml . ) . They were treated with i.v . mannitol , dextrose , and steroids OBJECTIVE : We sought to establish the frequency of receiving > 1 dose of epinephrine in children who present to the emergency department ( ED ) with food-related anaphylaxis . PATIENTS AND METHODS : We performed a medical chart review at Boston hospitals of all children presenting to the ED for food-related acute allergic reactions between January 1 , 2001 , and December 31 , 2006 . We focused on causative foods , clinical presentations , and emergency treatments . RESULTS : Through r and om sampling and appropriate weighting , the 605 review ed cases represented a study cohort of 1255 patients . These patients had a median age of 5.8 years ( 95 % confidence interval [ CI ] : 5.3–6.3 ) , and the cohort was 62 % male . A variety of foods provoked the allergic reactions , including peanuts ( 23 % ) , tree nuts ( 18 % ) , and milk ( 15 % ) . Approximately half ( 52 % [ 95 % CI : 48–57 ] ) of the children met diagnostic criteria for food-related anaphylaxis . Among those with anaphylaxis , 31 % received 1 dose and 3 % received > 1 dose of epinephrine before their arrival to the ED . In the ED , patients with anaphylaxis received antihistamines ( 59 % ) , corticosteroids ( 57 % ) , epinephrine ( 20 % ) . Over the course of their reaction , 44 % of patients with food-related anaphylaxis received epinephrine , and among this subset of patients , 12 % ( 95 % CI : 9–14 ) received > 1 dose . Risk factors for repeat epinephrine use included older age and transfer from an outside hospital . Most patients ( 88 % ) were discharged from the hospital . On ED discharge , 43 % were prescribed self-injectable epinephrine , and only 22 % were referred to an allergist . CONCLUSIONS : Among children with food-related anaphylaxis who received epinephrine , 12 % received a second dose . Results of this study support the recommendation that children at risk for food-related anaphylaxis carry 2 doses of epinephrine Hypoglycaemia remains a serious and much feared complication of insulin therapy . In this study , patients attending an accident and emergency department in hypoglycaemic coma were r and omized to treatment with either intravenous dextrose ( 25 g ) or intramuscular glucagon ( 1 mg ) , administered into the right thigh . Restoration of normal conscious level was slower after glucagon than dextrose ( 9.0 vs 3.0 min , P less than 0.01 ) , although the average duration of hypoglycaemic coma was 120 min . Two patients in the glucagon-treated group , who failed to show satisfactory recovery after 15 min , required additional treatment with intravenous dextrose . On question ing following recovery , all except two patients reported loss of awareness of the onset of hypoglycaemia Intramuscular glucagon is valuable in the treatment of severe hypoglycaemia outwith hospital and , although the slightly slower and less predictable recovery may appear to make it a less attractive option than intravenous dextrose in the accident and emergency department , this must be balanced against the advantages of ease of administration and a lower incidence of serious adverse effects OBJECTIVE Glucagon delivery in closed-loop control of type 1 diabetes is effective in minimizing hypoglycemia . However , high insulin concentration lowers the hyperglycemic effect of glucagon , and small doses of glucagon in this setting are ineffective . There are no studies clearly defining the relationship between insulin levels , subcutaneous glucagon , and blood glucose . RESEARCH DESIGN AND METHODS Using a euglycemic clamp technique in 11 subjects with type 1 diabetes , we examined endogenous glucose production ( EGP ) of glucagon ( 25 , 75 , 125 , and 175 μg ) at three insulin infusion rates ( 0.016 , 0.032 , and 0.05 units/kg/h ) in a r and omized , crossover study . Infused 6,6-dideuterated glucose was measured every 10 min , and EGP was determined using a vali date d glucoregulatory model . Area under the curve ( AUC ) for glucose production was the primary outcome , estimated over 60 min . RESULTS At low insulin levels , EGP rose proportionately with glucagon dose , from 5 ± 68 to 112 ± 152 mg/kg ( P = 0.038 linear trend ) , whereas at high levels , there was no increase in glucose output ( 19 ± 53 to 26 ± 38 mg/kg , P = NS ) . Peak glucagon serum levels and AUC correlated well with dose ( r2 = 0.63 , P < 0.001 ) , as did insulin levels with insulin infusion rates ( r2 = 0.59 , P < 0.001 ) . CONCLUSIONS EGP increases steeply with glucagon doses between 25 and 175 μg at lower insulin infusion rates . However , high insulin infusion rates prevent these doses of glucagon from significantly increasing glucose output and may reduce glucagon effectiveness in preventing hypoglycemia when used in the artificial pancreas BACKGROUND Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention . We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes . METHODS We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes , using Cox proportional-hazards models with adjustment for covariates measured at baseline and after r and omization . RESULTS During a median follow-up period of 5 years , 231 patients ( 2.1 % ) had at least one severe hypoglycemic episode ; 150 had been assigned to intensive glucose control ( 2.7 % of the 5571 patients in that group ) , and 81 had been assigned to st and ard glucose control ( 1.5 % of the 5569 patients in that group ) . The median times from the onset of severe hypoglycemia to the first major macrovascular event , the first major microvascular event , and death were 1.56 years ( interquartile range , 0.84 to 2.41 ) , 0.99 years ( interquartile range , 0.40 to 2.17 ) , and 1.05 years ( interquartile range , 0.34 to 2.41 ) , respectively . During follow-up , severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events ( hazard ratio , 2.88 ; 95 % confidence interval [ CI ] , 2.01 to 4.12 ) , major microvascular events ( hazard ratio , 1.81 ; 95 % CI , 1.19 to 2.74 ) , death from a cardiovascular cause ( hazard ratio , 2.68 ; 95 % CI , 1.72 to 4.19 ) , and death from any cause ( hazard ratio , 2.69 ; 95 % CI , 1.97 to 3.67 ) ( P<0.001 for all comparisons ) . Similar associations were apparent for a range of nonvascular outcomes , including respiratory , digestive , and skin conditions ( P<0.01 for all comparisons ) . No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death . CONCLUSIONS Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes . It is possible that severe hypoglycemia contributes to adverse outcomes , but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events . ( Funded by Servier and the National Health and Medical Research Council of Australia ; Clinical Trials.gov number , NCT00145925 . ) Summary The main therapeutic indication for glucagon is the treatment of hypoglycaemia in insulin overdosed Type 1 ( insulin-dependent ) diabetic patients . We have previously shown that an intranasal spray of 7.5 mg glucagon with deoxycholic acid as surfactant was able to correct an i.v . insulin-induced hypoglycaemia in diabetic patients . However , bioavailability and stability needed to be improved before intranasal glucagon could be introduced into clinical practice . This has now been achieved with a freeze-dried mixture of glucagon ( 1 mg ) and glycocholic acid ( 1 mg ) as a surfactant . Kinetics and efficacy have been controlled by ( 1 ) comparing subcutaneous and intranasal glucagon in 12 healthy non-hypoglycaemic subjects ; ( 2 ) testing intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by an i.v . bolus of insulin and ( 3 ) comparing subcutaneous and intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by adding extra subcutaneous regular insulin to their usual morning dosage . Our results show that 1 mg of intranasal glucagon is as effective as 1 mg of subcutaneous glucagon in terms of the rise in blood glucose . Differences in kinetics between the subcutaneous and the intranasal routes may be observed : intranasal glucagon initiates the blood glucose rise earlier than does the subcutaneous form but the effect of the latter is more sustained . Glycocholic acid appears to be a perfectly tolerated agent in acute conditions . The use of intranasal lyophylized glucagon , for the reversal of hypoglycaemia in Type 1 diabetes , seems to be a clinical ly relevant alternative to its parenteral equivalent and should now be ready to be introduced in the market To estimate the frequency and morbidity of insulin-induced hypoglycaemia , a retrospective survey was undertaken of the frequency of severe hypoglycaemia in 600 r and omly selected patients with insulin-treated diabetes who were attending a large diabetic outpatient clinic in a teaching hospital . The result ing morbidity ( hypoglycaemia-related injuries , convulsions , and road traffic accidents ) was ascertained in 302 patients . One hundred and seventy-five ( 29.2 % ) of the 600 patients reported a total of 964 episodes of severe hypoglycaemia in the preceding year , giving an overall frequency for the group of 1.60 episodes patient-1year-1 . The frequency of severe hypoglycaemia which was documented in 544 Type 1 ( ketosis prone ) diabetic patients was double that observed in a subgroup of 56 Type 2 diabetic patients who were being treated with insulin ( 1.70 vs 0.73 episodes patient-1year-1 ) . In the subset of 302 patients , those who had experienced severe hypoglycaemia had greater morbidity associated with an estimated rate of injury of 0.04 injuries person-1year-1 . Twenty ( 6.6 % ) patients reported a total of 37 convulsions associated with hypoglycaemia , 5 of which had occurred in the preceding year ( 0.02 convulsions person-1year-1 ) . Five patients reported road traffic accidents in the preceding year which had been caused by hypoglycaemia . The only reliable predictors of severe hypoglycaemia were a history of previous severe hypoglycaemia ( p < 0.001 ) , a history of hypoglycaemia-related injury ( p < 0.001 ) or convulsion ( p < 0.001 ) , and the duration of insulin therapy ( p < 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Summary The aim of the present study was to compare intranasal glucagon with subcutaneous glucagon as a treatment of insulin-induced hypoglycaemia in 11 children , 7–12 years old , with Type 1 ( insulin-dependent ) diabetes mellitus . Hypoglycaemia ( 1.6±0.1 vs 1.8±0.2 mmol/l ) was induced twice in each child by continuous insulin and variable glucose infusions . One milligram of intranasal glucagon or 0.5 mg of subcutaneous glucagon was given in a r and omized order . At 15 min after the administrations of either intranasal or subcutaneous glucagon , the blood glucose concentration increased by 1.5±0.2 mmol/l or 1.7±0.2 mmol/l above the glucose nadir , respectively . After nasal administration , the maximal rise in blood glucose was seen after 25 min . Subcutaneous injections induced higher and more sustained plasma glucagon concentrations but the children suffered more often from nausea than when they were treated intranasally . In conclusion , treatment with intranasal glucagon seems to be efficient and results in a rapid correction of insulin-induced hypoglycaemia with few side-effects Intranasal glucagon can raise blood glucose levels in healthy subjects . The aims of this study were to 7 ) compare the hyperglycemic effect of intranasal and intramuscular glucagon in healthy subjects and type I ( insulin-dependent ) diabetes patients during euglycemic conditions and 2 ) test the efficacy of intranasal and intramuscular glucagon in counteracting hypoglycemic episodes in insulin-treated diabetic patients . Intranasal glucagon raised blood glucose levels in both healthy subjects and type I diabetic patients , the effect of intramuscular glucagon being similar for the first 30 min and higher thereafter . Intranasal glucagon was also quicker acting than oral glucose in healthy subjects . Intranasal glucagon raised blood glucose levels in patients with hypoglycemic episodes , although less effectively than intramuscular glucagon . These data indicate intranasal glucagon as a possible emergency remedy for self-medication in insulin-treated patients prone to hypoglycemic episodes Background : Congenital hyperinsulinism ( CHI ) is characterized by severe hypoglycemia caused by dysregulated insulin secretion . The long-term outcome is dependent on prevention of hypoglycemic episodes to avoid the high risk of permanent brain damage . Severe cases are usually resistant to diazoxide or nifedipine . In addition , somatostatin analogues are ineffective in a subgroup of patients to achieve stable euglycemia . In these infants the only remaining long-term option has been subtotal pancreatectomy with high risk of diabetes mellitus . Intravenous infusions of glucagon are used as immediate treatment to stabilize euglycemia in affected newborns . The rationale of this treatment comes from the observation of an increased glycogen content of the liver when glycogenolysis is inhibited by insulin . Objective : To review the efficacy and safety of long-term subcutaneous glucagon infusion as a potential therapeutic option for blood glucose stabilization in infants with severe CHI without the need of additional intravenous glucose or immediate surgical intervention . Method : Retrospective review of 9 children with CHI who received continuous subcutaneous infusion of glucagon for weeks or months . Glucagon was added to octreotide to replace octreotide-induced suppression of endogenous glucagon secretion , thereby liberating glucose by stimulation of hepatic glycogenolysis . In 3 cases , a stabilized formulation of glucagon was used to prevent glucagon crystallization that frequently occurs in smaller volumes . Results : Introduction of glucagon allowed the reduction or discontinuation of central glucose infusion in all children studied . In 2 patients , glucagon was introduced due to recurrent hypoglycemia despite subtotal pancreatectomy . Six out of 9 children were discharged home on this treatment , which their parents were able to continue without further symptomatic hypoglycemia , convulsions or unconsciousness . In 3 children , subcutaneous glucagon was continuously administered for 1–4 years leading to stable euglycemia . However , 2 children with diffuse type still required subtotal pancreatectomy . As a possible side effect , 2 children developed erythema necrolyticum , which resolved after discontinuation of the glucagon infusion . This has been described before in glucagonoma . Conclusion : In this retrospective series , combination therapy of low-dose octreotide and subcutaneous glucagon infusion has been effective in preventing hypoglycemic episodes in severe CHI . We propose this may serve as a therapeutic option in place of high rates of glucose infusion through a central venous catheter and as an alternative to subtotal pancreatectomy in diffuse type of CHI OBJECTIVE Children with type 1 diabetes are frequently difficult to manage during times of gastroenteritis or poor oral intake of carbohydrates because of mild or impending hypoglycemia . The present study describes the effective use of small doses of subcutaneous glucagon in these children . RESEARCH DESIGN AND METHODS We analyzed 33 episodes of impending or mild hypoglycemia in 28 children ( ages 6.6 + /- 0.7 years ) . All were healthy except for type 1 diabetes and an episode of gastroenteritis . Using a st and ard U-100 insulin syringe , children ages < or = 2 years received two " units " ( 20 microg ) of glucagon subcutaneously and those ages > 2 years received one unit/year of age up to 15 units ( 150 microg ) . If the blood glucose did not increase within 30 min , the initial dosage was doubled and given at that time . We used patients ' self-glucose monitoring devices , aqueous glucagon , st and ard insulin syringes , and frequent phone contact with a physician and /or a diabetes nurse educator in this study . RESULTS Blood glucose was 3.44 + /- 0.15 mmol/l before and 8.11 + /- 0.72 mmol/l 30 min after glucagon . In 14 children , relative hypoglycemia recurred , requiring retreatment ( 3.48 + /- 0.18 to 6.94 + /- 0.72 mmol/l ) . In four children , a third dose was required . The glucagon was well tolerated In 28 of the 33 episodes of impending hypoglycemia , the children remained at home and fully recovered . Five children were taken to their local hospital because of concerns of dehydration or fever , but none for hypoglycemia . CONCLUSIONS Mini-dose glucagon rescue , using subcutaneous injections , is effective in managing children with type 1 diabetes during episodes of impending hypoglycemia due to gastroenteritis or poor oral intake of carbohydrate INTRODUCTION By introducing an intensified insulin treatment regime to patients with insulin-dependent diabetes mellitus ( IDDM ) , the frequency of long-term complications that the patient will experience has been shown to decrease . The price is an increase in the frequency of severe and mild hypoglycaemic events . Therefore , constant monitoring of these patients is necessary . HYPOTHESIS This study compares the time until full recovery of IDDM patients with severe hypoglycaemia after treatment with either intravenous glucose or intramuscular glucagon . METHODS 14 patients with IDDM with severe hypoglycaemia requiring treatment by the medical staff was r and omised to treatment either with 50 ml of 50 % glucose intravenously or intramuscular 1 mg glucagon . The time to recovery was recorded . Plasma glucose was measured at fixed intervals to achieve a glycaemia profile . Demographic data were acquired through patient interviews following recovery . RESULTS Recovery time between the two groups was significantly different statistically . Recovery time ranged for 1 to 3 minutes for those receiving glucose intravenously and 8 to 21 minutes for those receiving intramuscular glucagon . Characteristic glycaemia profiles were identified and differences were present between the two groups with a greater fluctuating pattern for the glucose group compared to the steadily increasing pattern seen after glucagon treatment . Alcohol was believed to be involved in 8 out of the 14 cases , and thereby , is the major confounding factor in this study . CONCLUSION Intramuscularly administered glucagon is a safe and reliable alternative to intravenous glucose infusion . The fluctuating glycemia pattern seen after glucose treatment indicates a low risk for secondary hypoglycaemia . However , further studies are necessary to support this assertion Glucagon in solution with a surfactant ( deoxycholic acid 1 % w/v ) was administered by intranasal spray to 6 healthy fasting subjects and 6 insulin-dependent diabetics with insulin-induced hypoglycaemia . In the normal subjects , intranasal glucagon increased plasma glucose levels , with a dose-response effect . In the diabetic patients , plasma glucose levels showed a mean increase of 100 % above nadir values in approximately 26 min in response to 7.5 mg intranasal glucagon ; hypoglycaemic symptoms were relieved within about 7 min . These results suggest that intranasal glucagon is effective and may represent an alternative to parenteral glucagon or glucose or to oral sugar as the first-line treatment of hypoglycaemic episodes in insulin-dependent diabetics STUDY OBJECTIVE This study evaluated the efficacy of glucagon for prehospital therapy of hypoglycemia in patients without IV access . DESIGN Prospect i ve clinical trial . SETTING Prehospital in a busy , urban emergency medical services system . TYPE OF PARTICIPANTS Fifty consecutive patients presenting with documented hypoglycemia ( ChemStrip BG less than or equal to 80 mg/dL ) and symptoms of decreased level of consciousness , syncope , or seizure were enrolled . MEASURES AND MAIN RESULTS Data collected included pretreatment ( ChemStrip BG ) and post-treatment serum glucose ( hospital assay ) as well as assessment of level of consciousness by a quantitative measure , the Glasgow Coma Score , and by a qualitative scale ( 0 to 3 ) . The mean pretreatment blood glucose of 33.2 + /- 23.3 mg/dL increased after treatment to 133.3 + /- 57.3 mg/dL. Qualitative level of consciousness increased from a mean of 1.26 + /- .96 to 2.42 + /- .94 and Glasgow Coma Score increased from a mean of 9.0 + /- 4.19 to 13.04 + /- 3.68 . The mean time until response was 8.8 minutes in those who responded to both level of consciousness criteria 82 % ( 41 of 50 ) . Glucagon administered for hypoglycemia result ed in a glucose increase in 98 % ( 49 of 50 ) with headache as the only side effect noted in 4 % ( two of 50 ) of patients ( P less than .0001 ) . CONCLUSION Glucagon is safe and effective therapy for hypoglycemia in the prehospital setting |
13,353 | 19,493,363 | The review confirmed that both the st and ard recommended doses of PZQ ( single 40 mg/kg oral dose ) and metrifonate ( 3x7.5 - 10 mg/kg oral doses administered fortnightly ) are efficacious and safe in treating urinary schistosomiasis , but there is no study comparing these two regimens head-to-head . | Guidelines recommend praziquantel ( PZQ ) for the treatment and control of schistosomiasis , with no real alternative .
Metrifonate was still widely used against Schistosoma haematobium in the 1990s , and then withdrawn .
Experimental studies and clinical trials suggest that artemisinin compounds are active against S. haematobium . | A r and omized single blind stratified study involving 153 patients with mixed S. mansoni and S. haematobium infection showed that 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one ( praziquantel , EMBAY 8440 , Biltricide ) is effective in giving high cure rates in each infection separately , 66 % ( 64 patients ) and 77 % ( 94 patients ) , respectively . The complete clearance of both infections ( i.e. , no eggs whether dead or alive ) 6 months after treatment was 29 % ( 43 patients ) . The side effects of the drug were minimal and transient , the most common being gastrointestinal ones . The assessment of the objective tolerability by clinical , haematological and biochemical tests showed also that the drug was very safe . It is thus concluded that the drug is a promising useful tool in the control of schistosomiasis in general and the treatment of the individual The shortage of available information on the impact of low doses of praziquantel was remedied by a trial of 0 , 10 , 20 , 30 and 40 mg kg-1 against double infections of Schistosoma haematobium and S. mansoni in a rural area of Zimbabwe . No significant differences were found in egg reduction between 20 - 40 mg kg-1 for S. haematobium and between 30 - 40 mg kg-1 for S. mansoni . It is suggested that morbidity control can be achieved with lower dosages of praziquantel than currently recommended Relationships of S. haematobium , hookworm and malarial infections to growth 6 months after metrifonate treatment were studied in Kenyan primary school children in an area where poor growth , S. haematobium and hookworm were common and malaria was endemic . All children with light-moderate S. haematobium infections ( 1 - 500 eggs/10 ml adj ) in 4 schools were examined ( Exam 1 ) , allocated at r and om to either placebo ( MIP , n = 198 ) or metrifonate treatment ( MIT , n = 201 ) groups , treated , and examined again 6 months later ( Exam 2 ) . An additional 19 heavily infected children ( HIT group greater than 500 eggs/10 ml adj ) were treated immediately after Exam 1 and also followed . The MIT and HIT groups exhibited more rapid growth between Exam 1 and 2 than did the placebo group . The MIT group gained significantly ( P less than 0.001 ) more than the MIP group in weight ( 0.8 kg ) , percent weight for age ( 2.3 percentage points ) , weight for height squared ( 0.04 units ) , arm circumference ( 0.4 cm ) , percent arm circumference for age ( 1.7 percentage points ) and in triceps and subscapular skinfold thicknesses . In addition , the placebo group showed statistically significant decreases between exams in percentage weight for age , percent arm circumference for age , both skinfold thicknesses for age and no significant increase in percent height for age while the MIT group exhibited highly significant increases in all anthropometric parameters . ( ABSTRACT TRUNCATED AT 250 WORDS Praziquantel administered in a single oral dose of 30 mg kg-1 to subjects infected with Schistosoma haematobium produced minimal side effects and was more effective than established regimes of niridazole and metrifonate . Praziquantel should prove a major tool in schistosomiasis control programmes Abstract The efficacy and tolerability of oral artesunate for the treatment of urinary schistosomiasis was assessed among schoolchildren aged 5–18 years in Adim community , Nigeria . Overall , 500 children , r and omly selected from those attending the Presbyterian primary school , were each invited to provide two consecutive urine sample s. Using st and ard parasitological procedures , Schistosoma haematobium ova were found in the sample s from 145 ( 29.0 % ) of the subjects . Most ( 87 ) of the infected subjects were then treated orally with artesunate , using two doses , each of 6 mg/kg , given 2 weeks apart . When the treated children were re-examined 4 weeks after the second dose of artesunate , 61 ( 70.1 % ) appeared egg-negative and were therefore considered cured . Post-treatment , the geometric mean egg count ( GMEC ) for the treated subjects who were not cured was significantly lower than the pre-treatment GMEC for all the treated subjects , with log10[(eggs/10 ml urine ) + 1 ] values of 0.9 v. 1.75 ( t = 4.45 ; P < 0.05 ) . The cure ' rate ' for the subjects aged ≥ 10 years was slightly higher than that among the younger subjects . It was lowest for the heavier subjects ( 70 % for those weighing 41–50 kg ) and highest ( 79 % ) for the subjects who weighed 31–40 kg . The artesunate was well tolerated . This observation of a therapeutic effect of artesunate against S. haematobium in Nigeria confirms recent observations from Senegal . In the Adim community at least , it would be more cost-effective to treat urinary schistosomiasis with artesunate than with praziquantel . The wide-spread use of artesunate against schistosomiasis has to be considered carefully , however , if it is not to compromise the efficacy of the drug as an antimalarial , by increasing the risk of resistance developing in local Plasmodium The effectiveness of the new schistosomicide praziquantel was assessed in African schoolchildren infected with Schistosoma haematobium . They were stratified according to the severity of their infection and were then r and omly allocated to treatment with two single-dose regimens ( 30 and 40 mg/kg ) and a split regimen of two doses of 20 mg/kg given four hours apart . All three regimens were highly effective and produced few side effects . Children who initially had very high pretreatment egg loads showed a poorer therapeutic response at all dose levels , and further investigations are necessary to find the optimum dose . Because of its effectiveness in a single dose and lack of toxicity , praziquantel may prove to be the ideal schistosomicide Artemether is an efficacious antimalarial drug that also displays antischistosomal properties . Laboratory studies have found that artemether curtails the development of adult worms of Schistosoma japonicum , S. mansoni and S. haematobium , and thus prevents morbidity . These findings have been confirmed in clinical trials for the former two parasites ; administered orally once every 2 - 3 weeks , artemether significantly reduced the incidence and intensity of patent infections . Here , we present the first r and omized , double-blind , placebo-controlled trial of artemether against S. haematobium , done in a highly endemic area of Côte d'Ivoire . Urine specimens from 440 schoolchildren were examined over 4 consecutive days , followed by two systematic praziquantel treatments 4 weeks apart . S. haematobium-negative children were r and omized to receive 6 mg/kg artemether ( N = 161 ) or placebo ( N = 161 ) . Medication was administered orally for a total of six doses once every 4 weeks . Adverse events were assessed 72 hours after medication , and perceived illness episodes were monitored throughout the study period . Incidence and intensity of S. haematobium infections , and microhematuria and macrohematuria were assessed 3 weeks after the final dosing . We also monitored malaria parasitemia and treated positive cases with sulfadoxine-pyrimethamine ( SP ) . Oral artemether was well tolerated . The incidence of patent S. haematobium infections in artemether recipients was significantly lower than in placebo recipients ( 49 % versus 65 % , protective efficacy : 0.25 , 95 % CI : 0.08 - 0.38 , P = 0.007 ) . The geometric mean infection intensity in the artemether group was less than half that of the placebo recipients ( 3.4 versus 7.4 eggs/10 mL urine , P < 0.001 ) . Heavy S. haematobium infections , microhematuria and macrohematuria , and the incidence of malaria parasitemia were all significantly lower in artemether recipients . In conclusion , previous findings of efficacy of artemether against S. japonicum and S. mansoni were confirmed for S. haematobium , although the protective efficacy was considerably lower . These findings enlarge the scope and potential of artemether and further contribute to discussion s of its role as an additional tool for integrated schistosomiasis control Recently , artemisinin derivatives have been shown to be efficacious in chemoprophylaxis of and chemotherapy for Schistosoma japonicum and S. mansoni infections . Therefore , a double-blind , r and omized , placebo-controlled study was carried out to investigate the efficacy and tolerability of artesunate plus placebo and the combination of artesunate and praziquantel in the treatment of S. haematobium infections in Gabon . The 300 infected schoolchildren included in the study were r and omized to receive artesunate plus placebo ( n=90 ) , praziquantel plus placebo ( n=90 ) , artesunate and praziquantel ( n=90 ) , or only placebo ( n=30 ) . End points were efficacy , assessed as cure on day 56 , and tolerability . All treatment regimens were well tolerated . The praziquantel plus placebo-treated group attained a cure rate of 73 % , artesunate plus placebo a rate of 27 % , the combination of artesunate and praziquantel a rate of 81 % , and placebo alone a rate of 20 % . In summary , earlier findings of efficacy of artemisinin derivitives against S. mansoni and S. japonicum could not be confirmed in S. haematobium infections Quantitative parasitological assessment and quantitative analysis of proteinuria , hematuria , and leukocyturia were carried out in 182 Sudanese schoolboys with mixed urinary and intestinal schistosomiasis . Pathological proteinuria was found in 73 % of patients ( median = 380 , 95 % confidence limits = 200 to 500 mg/liter ) . The median protein/creatinine ratio was 0.54 . SDS polyacrylamide gel electrophoresis showed an excretion of albumin , transferrin , and IgG consistent with a postrenal pattern of proteinuria . Pathological erythrocyturia occurred in 84 % of patients ( median = 255 , 95 % CL = 95 to 629 cells/microliter ) and leukocyturia in 77 % of patients ( median = 148 , 95 % CL = 93 to 246 cells/microliter ) . Phase contrast microscopy revealed intact erythrocytes , suggestive of postrenal hemorrhage . Proteinuria , erythrocyturia , and leukocyturia correlated significantly with the ova excretion in the urine , but not with egg excretion in the stool . Oxamniquine reduced ova excretion in the stool but did not influence pathological urine findings . In patients treated effectively with Praziquantel or Metrifonate , pathological PU , EU , and LU decreased markedly 1 month post treatment . PU in severely proteinuric patients reached physiological values 5 months post therapy . We suggest that the proteinuria , erythrocyturia , and leukocyturia in mixed schistosomiasis were of postrenal origin A field trial was conducted in Sudan to evaluate the acceptability and efficacy of praziquantel given to schoolchildren aged 7 - 11 years who were all infected with both Schistosoma mansoni and S. haematobium . Two dosage regimes were compared , a single dose of 40 mg/kg bodyweight , and a divided dose 2 X 20 mg/kg given 4 - 6 h apart . When interviewed 24 h after treatment , 80 % of the children complained of drug-induced abdominal pain , diarrhoea , nausea or vomiting . However none of the side-effects persisted beyond the day of treatment . More children complained of side-effects from the divided dose than from the single dose . The cure rate in the divided-dose group was slightly better than in the single-dose group but the differences were not significant at any follow-up , nor when results were expressed in terms of cumulative failures . The initial cure rates were 66.3 % and 61.8 % at 1 month , and 73.2 % and 64.7 % at 3 months for the divided and single doses respectively . After 12 months there had apparently been considerable reinfection with S. mansoni and 73 % of the children were passing eggs . Reinfection with S. haematobium was negligible The impact of albendazole ( 400 mg ) and praziquantel ( 40 mg/kg body weight ) treatment of schoolchildren was compared with placebo according to the presence of anaemia ( haemoglobin concentration < 11 . 0 g/dl ) and heavy ( > 5000 epg ) or light ( < 5000 epg ) hookworm egg load . The study was conducted in rural Tanga . Medication was administered in September 1994 and children were followed-up in January 1995 . Overall , anthelminthic treatment reduced the fall in haemoglobin concentration compared with that observed in the placebo group ( - 0.11 g/dl vs. - 0.35 g/dl ; P = 0.02 ) . Anthelminthic treatment was of greatest benefit to the 9 % of children with both anaemia and heavy hookworm egg load ( + 0.67 g/dl vs. - 0.67 g/dl ) and was also of significant benefit to the 38 % of children with anaemia and light hookworm egg load ( + 0.07 g/dl vs. - 0.21 g/dl ) . It was of no significant benefit to children who were not anaemic . This study suggests that single-dose anthelminthic treatment distributed in schools in this area achieves haematological benefits in nearly half of children infected with S. haematobium and geohelminths ( 37 % of total population ) Summary In a r and omized double-blind study , the percentage egg reduction and cure rate after the st and ard schedule of metrifonate treatment ofSchistosoma haematobium ( 3 doses of 7.5 mg·kg−1 at two-weekly intervals ; A ) and an abbreviated regimen ( 3 doses of 5 mg·kg−1 in one day ; B ) were compared in five villages in Somalia.300 patients who were excreting 20 or more eggs ofS. haematobium in 10 ml urine were recruited . The patients were classified according to their home villages and were then , r and omly allocated to treatment A or B. They had similar ages , weights and egg output . Each patient received 3 doses of metrifonate and 2 doses of identical appearing placebo . Group A received metrifonate on the 1st , 4th and 5th dosing occasions and placebo on the 2nd and 3rd times . Group B received metrifonate on the 1st , 2nd and 3rd dosing times and placebo on the 4th and 5th times . Two hundred and one patients were followed up from 1 to 6 months . The remaining 99 ( 33 % ) patients either did not complete treatment or were lost during follow up . Egg reduction in the groups 1 , 2 , 3 and 6 months after treatment were 97 , 97 , 95 and 93 % in Group A and 96 , 96 , 94 and 92 % in Group B ( NS ) . Corresponding cure rates for Group A were 52 , 50 , 48 and 44 % , and in Group B they were 47 , 48 , 43 and 40 % ( NS ) . Seven patients from Group A and 9 from Group B complained of minor side-effects . Thus , under field conditions abbreviated regimen of metrifonate 5 mg·kg−1 3-times in one day could have as much efficacy and safety as the st and ard schedule of 3 doses of 7.5 mg·kg−1 at two-weekly intervals To determine the effect of targeted field administration of oral chemotherapeutic agents on the prevalence , intensity , and morbidity of Schistosoma haematobium infections , we initiated a long-term school-based program in the Msambweni area of Kwale District , Coast Province , Kenya . Prior to treatment , 69 % of the children examined ( ages 4 - 21 , n = 2,628 ) were infected ; 34 % had moderate or heavy infections ( greater than 100 eggs/10 ml urine ) . Infected individuals were r and omized to receive , during one year , either metrifonate ( 10 mg/kg x 3 doses ) or praziquantel , ( 40 mg/kg x 1 dose ) . At the end of the first year , prevalence of infection fell to 19 % ; only 2 % of the pupils remained in the moderately and heavily infected groups . Corresponding decreases in the prevalence of hematuria ( 54 % in 1984 vs. 16 % in 1985 ) and proteinuria ( 56 % in 1984 vs. 26 % in 1985 ) were noted . These were associated with significant declines in bladder thickening and irregularities noted during ultrasound examinations , but not with decreases in hydronephrosis . There was no significant difference in the post-treatment prevalence or intensity of infection after treatment with metrifonate as compared with praziquantel . These results demonstrate that field-applied chemotherapy with either agent offers a practical strategy for the control of S. haematobium infection and its associated morbidity At present , anthelmintic therapy with praziquantel at a dose of 40 mg/kg of body weight is the recommended treatment for control of urinary tract morbidity caused by Schistosoma haematobium . Although this st and ard regimen is effective , drug cost may represent a significant barrier to implementation of large-scale schistosomiasis control programs in developing areas . Previous comparison trials have established that low-dose ( 20 - 30 mg/kg ) praziquantel regimens can effectively suppress the intensity of S. haematobium infection in endemic setting s. However , the efficacy of these low-dose regimens in controlling infection-related morbidity has not been determined in a r and omized field trial . The present r and om allocation study examined the relative efficacy of a 20 mg/kg dose versus a 40 mg/kg dose of praziquantel in control of hematuria and bladder and renal abnormalities associated with S. haematobium infection in an endemic area of Coast Province , Kenya . After a nine-month observation period , the results indicated an advantage to the st and ard 40 mg/kg praziquantel dose in terms of reduction of infection prevalence and hematuria after therapy ( P < 0.01 and P < 0.005 , respectively ) . However , the two treatment groups were equally effective in reducing structural urinary tract morbidity detected on ultrasound examination . We conclude that in certain setting s , a 20 mg/kg dose of praziquantel may be sufficient in providing control of morbidity due to urinary schistosomiasis in population -based treatment programs OBJECTIVES To determine the epidemiology of helminthic infections and the efficacy of parasite treatment among rural South African primary school children in the province of KwaZulu-Natal . To assess the South African government 's parasite control policy . METHODS The study recruited 268 school children , aged 8 to 10 , and r and omly allocated them into treatment and placebo groups ( treatment consisted of a single dose of albendazole ( 400 mg ) and praziquantel ( 40 mg/kg ) ) . Anthropometric measurements and the prevalence and intensity of helminth infections were taken at baseline ( prior to treatment ) and 16 weeks post treatment . Two weeks after treatment prevalence and intensity were again measured for an approximate 50 % sub- sample of the children to investigate efficacy of treatment . An analysis of the South African government 's policies concerning parasite control is assessed in the light of these epidemiological findings . RESULTS Low levels of both stunting and wasting were observed throughout the study ( approximately 10 % and 1 % , respectively ) , but did not vary significantly across either treatment group or time period ( P > 0.50 ) . At baseline the observed prevalences for the three main helminths found in this study among the treated children were Ascaris lumbricoides 29.5 % , Trichuris trichiura 51.9 % and Schistosoma haematobium 22.3 % . These prevalences declined significantly to 4.7 % ( P < 0.0005 ) , 38.0 % ( P < 0.03 ) , and 3.3 % ( P < 0.0002 ) , respectively , 16 weeks post treatment . The majority of infections observed at baseline were of light intensity , namely A. lumbricoides ( 50 % ) , T. trichiura ( 80 % ) and S. haematobium ( 100 % ) , and following treatment these levels were reduced significantly ( P < 0.0001 , P < 0.05 and P < 0.005 , respectively ) . The levels of both prevalence and intensity in the untreated group remained constant . The cure rates over the first two weeks of the study were found to be 94.4 % for A. lumbricoides , 40 % for T. trichiura and 72.2 % for S. haematobium . CONCLUSION The benefits of targeted , school-based treatment in reducing the prevalence and intensity of infection supports the South African government 's focus of using school-based interventions as part of an integrated parasite control programme . These strategies and programmes are consistent with recommendations of the World Health Organization ( WHO ) and The United Nations Children 's Fund ( UNICEF ) Alternative regimes for the treatment of Schistosoma haematobium infection were compared in two trials . Praziquantel at a dose of 40 mg kg-1 appeared to cure 63 % of a r and om sample of heavily infected subjects ; significantly more than the 18 % cured by three fortnightly doses of metrifonate at 10 mg kg-1 . However , praziquantel led to a greater incidence of mild , transient side-effects . A single dose of metrifonate was found to be an inadequate treatment in the same group of subjects as it left 53 % with an egg count of at least 100 ova/10 ml . A combination of 10 mg kg-1 of metrifonate and 25 mg kg-1 of niridazole had a similar effect to that of a single dose of metrifonate alone and it had more side-effects . Reduced doses of praziquantel had less effect on egg counts than the st and ard regime , but the difference was not significant in the case of 20 mg kg-1 . Although a combination of metrifonate and praziquantel , each at 10 mg kg-1 , had a greater effect than either constituent alone , the difference was not significant . Factors affecting the choice of drug for use in mass treatment of urinary schistosomiasis in The Gambia are discussed . The present findings suggest that the st and ard regime of praziquantel should be used or , if this is not possible , a three-dose metrifonate regime The relationships between S. haematobium , hookworm , malaria , hemoglobin level , splenomegaly , and hepatomegaly before and 8 months after treatment with a single dose of metrifonate or praziquantel were studied in Kenyan primary schoolchildren in an area where anemia , S. haematobium , and hookworm are common and malaria is holoendemic . Children with light to moderate S. haematobium infection were examined ( Exam 1 ) , assigned at r and om to groups receiving placebo ( PL , n = 104 ) , metrifonate ( MT , n = 103 , dose 10 mg/kg body weight ) or praziquantel ( PR , n = 105 , dose 40 mg/kg body weight ) , treated , and examined 8 months later ( Exam 2 ) . At Exam 2 , 62 % of the MT group still passed S. haematobium eggs vs. 13 % in the PR group . Egg reduction rates were substantial in both groups , but greater in the PR group ; geometric mean egg counts in both groups were very low . Prevalence and intensity in the PL group had not changed between exams . Hookworm egg counts were significantly reduced in the MT group ( 59 % egg reduction rate ) ; malarial infection had increased in all 3 groups , presumably due to the long rainy season between exams . Hookworm egg count was the most significant predictor of initial hemoglobin level , followed by S. haematobium egg count and presence of malarial infection . Treatment with a single dose of MT or PR can produce substantial decreases in S. haematobium infection 8 months later To assess the efficacy of low dose praziquantel regimens in comparison with st and ard 40 mg/kg dosing in the treatment of urinary schistosomiasis , a r and om allocation dose-finding trial was performed in children and adults from a Schistosoma haematobium endemic region in Coast Province , Kenya . Following an initial screening , 280 individuals with greater than or equal to 50 eggs/10 ml urine were r and omly assigned to receive either 10 , 20 , 30 , or 40 mg/kg of the drug in a single oral dose . Two to three months later , cure rates of 26 % , 68 % , 78 % , and 84 % were found for the 10 , 20 , 30 , and 40 mg/kg doses , respectively . The results of 10 mg/kg oral dosing were significantly worse than for all other doses in terms of cure rate and of post-treatment prevalence of morbidity . The 40 mg/kg dosing result ed in a significantly higher cure rate than the 20 mg/kg doses ; nevertheless , there was no significant difference between 20 mg/kg and 40 mg/kg doses in terms of mean post-treatment intensity of infection or post-treatment prevalence of hematuria or proteinuria . For large-scale control programs , oral 20 mg/kg praziquantel therapy for urinary schistosomiasis may prove as effective as the st and ard oral 40 mg/kg dosing for control of infection-associated morbidity and reduction of parasite transmission ABSTRACT In the present study we found that after a single oral dose of 1,800 mg of praziquantel , following a high-lipid diet and a high-carbohydrate diet , the maximum levels in plasma increased 243 and 515 % and the area under the plasma concentration curve from 0 to 8 h increased 180 and 271 % , respectively A double-blind controlled trial of 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a ] isoquinolin-4-one ( praziquantel , EMBAY 8440 , Biltricide ) in the treatment of vesical schistosomiasis has been carried out in 90 Nigerian schoolchildren of both sexes aged 9 - -16 years . Oral doses of 1 x 30 , 1 x 40 , and 2 x 20 mg/kg b.w . were assessed against placebo at 1 x 40 mg/kg , and the subjects followed up for up to twelve months after treatment . The results showed that the drug is very effective against S. haematobium infections and well tolerated . There were not significant differences between the three dosage groups , and the drug had no adverse haematological or biochemical effects . It is concluded that praziquantel widely meets the requirements necessary for use in large scale control of vesical schistosomiasis The optimal dose of interferon-alfa ( IFN ) for chronic myeloid leukemia ( CML ) is unknown . Retrospective analyses suggest that low doses are as effective as high doses , with less toxicity and fewer patients ab and oning the drug . The Dutch Hemato-Oncology Association ( HOVON ) and British Medical Research Council ( MRC ) cooperative groups jointly performed r and omized trials in newly diagnosed CML patients , comparing high-dose IFN ( 5 MIU/m(2 ) daily ) with low-dose ( 3 MIU , 5 times a week ) . Both arms allowed additional hydroxyurea to keep the white blood cell count lower than 5 x 10(9)/L. Quality of life data were collected in a subset of patients . Between 1993 and 2001 , 407 patients were r and omized . At a median follow-up of 53 months , there were no significant differences in overall survival ( odds ratio = 1.09 , 95 % confidence interval , 0.81 - 1.46 ) , progression-free survival , and complete hematologic or major cytogenetic responses . Fewer patients in the low-dose group ab and oned IFN for reasons other than transplant or progressive disease ( P = .002 , 58 % vs 72 % at 5 years ) . Quality of life data showed comparable results in both arms for most factors . There is no evidence of benefit for high-dose IFN compared with low-dose for the treatment of CML . Therefore , when IFN is combined with other drugs , low-dose IFN is advised , to minimize toxicity and costs THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard A double blind trial of three oral preparations given in single doses for the treatment of Schistosoma haematobium infection was carried out in schoolchildren ; selection was biased towards those who excreted large quantities of eggs . Praziquantel 40 mg/kg was the most effective drug giving a greater than 97 % reduction in egg output six months after treatment ; combined treatment with niridazole 25 mg/kg and metrifonate 10 mg/kg gave a reduction of greater than 92 % and metrifonate 10 mg/kg alone a reduction of greater than 86 % . Fewer children continued to have moderate to heavy infections ( excretion greater than 124 ova/10 ml urine ) six months after treatment with praziquantel ( 5 % ) and the combined regimen ( 7 % ) than with metrifonate ( 16 % ) . Though our findings show that praziquantel appears to be the most effective and convenient drug available for individuals with S haematobium infection , the combined regimen is a cheaper alternative for treatment where cost is important and parasitological cure not an essential objective In a controlled clinical trial , Tanzanian schoolchildren with urinary schistosomiasis , many of whom had coexisting hookworm infection , were r and omly allocated to one of three groups that were treated with doses of 7.5 , 10.0 , and 12.5 mg per kg of body weight , respectively , of metrifonate , orally , up to 3 times at 14-day intervals . No serious side effects were observed during or after the administration of single or repeated doses . A few hours after medication , plasma cholinesterase was almost completely inhibited , regardless of the dose given , while erythrocyte cholinesterase was almost completely inhibited , regardless of the dose given , while erythrocyte cholinesterase was inhibited down to 40 - 60 % of the pretreatment level , depending on the dose . Plasma cholinesterase was inhibited to a greater extent than erythrocyte cholinesterase but showed a more rapid recovery of activity . A moderate accumulation of unreactivated erythrocyte cholinesterase occurred at all dose levels with this regime . Four weeks after the last dose of drug , plasma cholinesterase activity was nearly normal in all the treated children . Erythrocyte cholinesterase activity returned to normal 8 - 15 weeks after the last dose . The therapeutic results confirmed the efficacy of metrifonate against Schistosoma haematobium . There was an additional though less striking effect against hookworm Praziquantel is the current mainstay for morbidity control of schistosomiasis . Artemisinin and its derivatives , widely used for the treatment of malaria , also display antischistosomal properties . The present study is an effort to assess the therapeutic efficacy of artesunate , an artemisinin derivative , in Schistosoma haematobium infections in a human population . The efficacy of artesunate and praziquantel were comparatively studied in primary schoolchildren from two villages , Lampsar ( n=180 ) and Makhana ( n=108 ) , located along the Lampsar river in the delta of the Senegal River Basin in Northern Senegal ( West Africa ) . In each village , half of the infected children were treated with a single oral dose of 40 mg/kg praziquantel and half with artesunate following the recommended malaria monotherapy regimen . For both drugs , cure and egg count reduction rates were , without apparent explanation , higher in Makhana than in Lampsar . In both villages , high and nearly comparable egg count reduction rates were obtained with both drugs at each follow-up after treatment ( 5 , 12 and 24 weeks ) in the heavy infected group of children ( > 50 eggs/10 ml of urine ) . No major adverse effects were observed . The results demonstrate that artesunate is effective against S. haematobium , but the results obtained with praziquantel were consistently better A double-blind placebo-controlled study of the concurrent administration of albendazole and praziquantel was conducted in>1500 children with high prevalences of geohelminths and schistosomiasis . The study sites were in China and the Philippines , including 2 strains of Schistosoma japonicum , and 2 different regions of Kenya , 1 each with endemic Schistosoma mansoni or Schistosoma haematobium . Neither medication affected the cure rate of the other . There was no difference between the side effect rate from albendazole or the double placebo . Praziquantel-treated children had more nausea , abdominal pain , and headache but these side effects were statistically more common in children with schistosomiasis , suggesting a strong influence of dying parasites . The subjects were followed for 6 months for changes in infection status , growth parameters , hemoglobin , and schistosomiasis morbidity . In all 4 sites , a significant 6-month increase in serum hemoglobin was observed in children who received praziquantel , strongly supporting population -based mass treatment The combined effects of praziquantel and artesunate in the treatment of urinary schistosomiasis were assessed among 312 r and omly selected schoolchildren aged 4 - 20 years in Adim community , Nigeria . In the preliminary screening , infection was confirmed in 327 ( 38.5 % ) of the 850 subjects screened . Infected subjects who reported for treatment were then divided into six treatment groups of 52 subjects each ; 44 subjects in each group completed their treatment regimens and su bmi tted their urine for post-treatment assessment . Praziquantel and artesunate were administered orally at 40 mg/kg and 4 mg/kg body weight , respectively . Adverse effects due to drug reactions were assessed 72 h after medication and all perceived episodes of illness were treated . Morbidity indicators were assessed 56 days after the final dose of the drug regimens . All treatment regimens were well tolerated . The cure rates were 72.7 % in the praziquantel plus placebo-treated group and 70.5 % in the artesunate plus placebo group , while the artesunate plus praziquantel group had the highest cure rate ( 88.6 % ) . Haematuria and proteinuria were extensively reduced after treatment with the three drug regimens . This study confirmed that the treatment of urinary schistosomiasis with the combination of praziquantel and artesunate is safe and more effective than treatment with either drug alone A study was performed to determine the efficacy of praziquantel ( PZQ ) against Schistosoma haematobium . Children ( n = 592 ) infected with S. haematobium received either a single treatment with PZQ ( 40 mg/kg ) or two or three treatments with PZQ at three-week intervals after the initial treatment and efficacy was monitored for nine weeks . Cure rates at three-weeks post-treatment were low ( < 50 % ) , suggesting either that worms are killed very slowly or , more likely , that eggs continue to be released from tissues after worm death . Interestingly , a single dose of PZQ showed high efficacy ( cure rate > 83 % and egg reduction rate > 98 % ) when assessed from six weeks post-treatment onward . There were no significant differences in cure rates or intensity of infection between the three cohorts at any point in the study , despite the different treatment regimens . Since children were in contact with transmission sites during the study period , the results suggest good efficacy of PZQ against all stages of S. haematobium , including the immature worms |
13,354 | 11,034,689 | CBT in a full or less intensive form is not significantly superior to CBT in a pure self-help form .
Augmentation of CBT with exposure therapy is not more effective than CBT alone . | BACKGROUND Bulimia nervosa and like syndromes , such as binge eating disorder , are common in young Western women .
A specific psychotherapy , cognitive behaviour therapy ( CBT ) has been developed for the treatment of bulimia nervosa .
Other psychotherapies , some from a different theroretical framework , some modifications of CBT are also used .
OBJECTIVES The review aims to evaluate the psychotherapeutic treatments for those with binge eating syndromes , that have been tested in r and omised controlled trials .
Specifically , CBT therapy is compared with waiting list or a non-treatment group , any other psychotherapy , CBT in a " pure self-help " form and CBT augmented by exposure and response therapy .
As well , the review aims to evaluate the evidence for the efficacy of other psychotherapies when compared to a no treatment control group and to evaluate the evidence for the efficacy of other psychotherapies when compared to a ' placebo ' therapy . | A controlled trial comparing family therapy with individual supportive therapy in anorexia nervosa and bulimia nervosa was undertaken . Eighty patients ( 57 with anorexia nervosa ; 23 with bulimia nervosa ) were first admitted to a specialized unit to restore their weight to normal . Before discharge , they were r and omly allocated to family therapy or the control treatment ( individual supportive therapy ) . After one year of psychological treatment , they were reassessed , using body weight , menstrual function , and ratings on the Morgan and Russell scales . Family therapy was found to be more effective than individual therapy in patients whose illness was not chronic and had begun before the age of 19 years . A more tentative finding was the greater value of individual supportive therapy in older patients . To our knowledge , this is the first controlled trial of family therapy in anorexia nervosa and clarifies the specific indications for this treatment Since the primary role of psychoeducation in eating disorders is to act as a foundation for other interventions , nutritional rehabilitation should use the same therapeutic principles as psychotherapy . This paper looks at the possibility that traditional psychoeducational results can be enhanced in patients with bulimia nervosa by a new nutritional rehabilitation programme focused on psychobiological reorganization of eating behaviour as opposed to the prescription of regular eating patterns . Forty women with purging-type bulimia nervosa were enrolled for a 24-week experimental period of cognitive-behavioural psychotherapy ( CBT ) and were r and omly and evenly divided into two groups to follow a psychobiological nutritional rehabilitation ( PNR ) and a traditional nutritional rehabilitation ( TNR ) programme respectively . The follow-up period averaged 6 months ; four subjects dropped out . The baselines of both groups were comparable with regard to key features , including binge and vomiting frequency , and carbohydrate and lipid intake . Both groups improved significantly over time , though improvements in bingeing and vomiting and lipid intake were greater in the PNR group ( p<0.001 ) , both at the end of the study and at the follow-up . This psychobiological approach to appetite and weight control may constitute a theoretical framework facilitating the application of cognitive-behavioural guidelines to both nutritional rehabilitation and psychotherapy Previous research on the treatment of out patients with bulimia nervosa has focused on two treatment strategies : ( 1 ) drug therapy , primarily using tricyclic antidepressants , and ( 2 ) psychotherapy , often employing behavioral and cognitive behavioral techniques . We report here the short-term treatment outcome of a 12-week comparison trial of bulimic out patients who were r and omly assigned to one of four treatment cells : ( 1 ) imipramine hydrochloride treatment , ( 2 ) placebo treatment , ( 3 ) imipramine treatment combined with intensive group psychotherapy , and ( 4 ) placebo treatment combined with intensive group psychotherapy . All three active treatment cells result ed in significant reductions in target-eating behaviors and in a significant improvement in mood relative to placebo treatment . However , the results also suggested that the amount of improvement obtained with the intensive group psychotherapy component was superior to that obtained with antidepressant treatment alone . The addition of antidepressant treatment to the intensive group psychotherapy component did not significantly improve outcome over intensive group psychotherapy combined with placebo treatment in terms of eating behavior , but did result in more improvement in the symptoms of depression and anxiety Fifteen women with bulimia nervosa were treated with a 4-month course of combined cognitive-behavioral , nutritional and antidepressant therapy ( 5 with amineptine and 10 with fluvoxamine ) . Patients were monitored before and after 1 , 2 and 4 months of therapy for body mass index ( BMI ) , for eating disorder symptoms by the Eating Disorder Inventory ( EDI ) and the Bulimic Investigation Test ( BITE ) , and for depression and anxiety by the Hamilton Rating Scale for Depression and for Anxiety ( HRS-D and -A ) . BITE symptoms and gravity improved significantly and equally in the two groups during the 4 months of therapy . Global EDI scores , depression and anxiety decreased but not significantly . BMI was normal before therapy and did not change during treatment The purpose of this study was to conduct an assessment of binge eating severity among obese persons . Two question naires were developed . A 16-item Binge Eating Scale was constructed describing both behavioral manifestations ( e.g. , eating large amounts of food ) and feeling/cognitions surrounding a binge episode ( e.g. , guilt , fear of being unable to stop eating ) . An 11-item Cognitive Factors Scale was developed measure two cognitive phenomena thought to be related to binge eating : the tendency to set unrealistic st and ards for a diet ( e.g. , eliminating " favorite foods " ) and low efficacy expectations for sustaining a diet . The results showed that the Binge Eating Scale successfully discriminated among persons judged by trained interviewers to have either no , moderate or severe binge eating problems . Significant correlation between the scales were obtained such that severe bingers tended to set up diets which were unrealistically strict while reporting low efficacy expectations to sustain a diet . The discussion highlighted the differences among obese persons on binge eating severity and emphasized the role of cognitions in the relapse of self control of eating OBJECTIVE This study investigated the efficacy of a stepped-care trial of brief group psychoeducation ( PE ) followed by individual cognitive-behavioral therapy ( CBT ) in the treatment of bulimia nervosa . METHOD Fifty-six subjects first completed PE and were then r and omly assigned to either a 16-week trial of CBT ( PE + CBT ) or to no further treatment follow-up ( PE-alone ) . RESULTS Compared to PE-alone , PE + CBT produced significantly greater reductions in the specific eating symptoms of binging and purging and significantly higher remission rates that were maintained over a 16-week follow-up . However , there were no differential treatment effects on measures of nonspecific psychopathology . Among PE + CBT subjects , remission in specific eating symptoms was associated with greatest improvements in non-specific psychopathology . The outcome of nonremitted PE + CBT subjects and PE-alone subjects was no different at posttreatment or follow-up . DISCUSSION These results provide limited support for offering individual CBT to subjects once they have completed an initial trial of group PE OBJECTIVE Both cognitive-behavioral therapy ( CBT ) and antidepressant medication have demonstrated efficacy in the treatment of bulimia nervosa . However , data concerning the long-term impact of such treatments have been limited . This study sought to determine if treatment with CBT and antidepressant medication was associated with better long-term outcome among women diagnosed with bulimia nervosa . METHOD Women ( N = 101 ) who completed a controlled treatment study of bulimia nervosa participated in follow-up assessment s approximately 10 years later . RESULTS Women who received treatment with CBT or antidepressant medication or both reported improved social adjustment at long-term follow-up compared with women r and omized to the placebo condition . DISCUSSION Treatments with demonstrated efficacy for short-term outcome appear to improve psychosocial function at long-term follow-up among women initially diagnosed with bulimia nervosa OBJECTIVE To evaluate the effects of adding exercise and maintenance to cognitive-behavior therapy ( CBT ) for binge eating disorder ( BED ) in obese women . METHOD One hundred fourteen obese female binge eaters were r and omized into four groups : CBT with exercise and maintenance , CBT with exercise , CBT with maintenance , and CBT only . RESULTS AND DISCUSSION Eighty-four women completed the 16-month study . Subjects who received CBT with exercise experienced significant reductions in binge eating frequency compared with subjects who received CBT only . The CBT with exercise and maintenance group had a 58 % abstinence rate at the end of the study period and an average reduction of 2.2 body mass index ( BMI ) units ( approximately 14 lb ) . BMI was significantly reduced in the subjects in both the exercise and maintenance conditions . The results suggest that adding exercise to CBT , and extending the duration of treatment , enhances outcome and contributes to reductions in binge eating and BMI OBJECTIVE This open clinical trial examined the efficacy of treating obese patients with binge eating disorder ( BED ) with phentermine and fluoxetine in the setting of cognitive-behavioral therapy ( CBT ) . METHOD Sixteen obese women received individual CBT along with phentermine/fluoxetine . Treatment goals included elimination of binge eating , weight loss , and reduced psychological distress . Following active treatment , patients were offered once-monthly maintenance treatment for 3 years . RESULTS Patients showed significant reduction in binge frequency , weight loss , and psychological distress at the end of active treatment , but regained most of the weight within 1 year . At 18-month follow-up , there was an ongoing reduction in binge eating for patients who continued maintenance . DISCUSSION Treatment produced comparable binge suppression and more weight loss than most reported studies of CBT alone . However , there is significant weight regain , particularly following medication discontinuation . This study does not support the long-term clinical utility of adding phentermine/fluoxetine to CBT for BED Evidence for the effectiveness of existing treatments of patients with eating disorders is weak . Here we describe and evaluate a method of treatment in a r and omized controlled trial . Sixteen patients , r and omly selected out of a group composed of 19 patients with anorexia nervosa and 13 with bulimia nervosa , were trained to eat and recognize satiety by using computer support . They rested in a warm room after eating , and their physical activity was restricted . The patients in the control group ( n = 16 ) received no treatment . Remission was defined by normal body weight ( anorexia ) , cessation of binge eating and purging ( bulimia ) , a normal psychiatric profile , normal laboratory test values , normal eating behavior , and resumption of social activities . Fourteen patients went into remission after a median of 14.4 months ( range 4.9–26.5 ) of treatment , but only one patient went into remission while waiting for treatment ( P = 0.0057 ) . Relapse is considered a major problem in patients who have been treated to remission . We therefore report results on a total of 168 patients who have entered our treatment program . The estimated rate of remission was 75 % , and estimated time to remission was 14.7 months ( quartile range 9.6 ≥ 32 ) . Six patients ( 7 % ) of 83 who were treated to remission relapsed , but the others ( 93 % ) have remained in remission for 12 months ( quartile range 6–36 ) . Because the risk of relapse is maximal in the first year after remission , we suggest that most patients treated with this method recover Objective : The aims of the paper are to determine whether nutritional counselling is associated with an improvement in bulimic symptomatology , whether this improvement is maintained during post-treatment follow-up , and whether the addition of fluoxetine 3 × 20 mg/day confers additional benefit . Method : Psychological , pharmacological and combined psychopharmacological treatments of bulimia nervosa were review ed briefly . Sixty-seven patients referred to specialist eating disorder services who fulfilled strict diagnostic criteria were treated with intensive nutritional counselling and r and omly assigned to either fluoxetine 3 × 20 mg/day or placebo . After a 1-week ‘ wash-out ’ , active treatment was given over 8 weeks , followed by post-treatment interviews at 12 and 20 weeks . Results : Both groups of patients improved significantly during treatment . In some respects , the fluoxetine group did slightly better as demonstrated by the items ‘ restraint ’ , ‘ weight concern ’ and ‘ shape concern ’ ( p<0.05 vs p<0.0001 ) on the Eating Disorder Examination ( EDE ) . Fluoxetine patients decreased their energy intake and lost a modest amount of weight . They went on to regain weight during the follow-up period , returning to levels higher than they were initially . These patients also appeared more likely to have a recurrence of symptoms , as shown by the fall in percentage of binge-free patients and by changes in the EDE . Conclusion : Nutritional counselling is an effective means of treating bulimia nervosa , with improvement maintained up to 3 months follow-up . The addition of fluoxetine may confer some benefit during active treatment , but its discontinuation may contribute to a higher rate of recurrence of symptoms post treatment . Of course , this study can not be extrapolated to the efficacy of fluoxetine when used as the only form of treatment in patients for whom intensive nutritional counselling or other structured psychological programs are not available In a crossover study , 11 bulimic patients divided into two groups of six and five patients underwent six sessions of exposure and response prevention of bingeing ( ERPB ) or exposure and response prevention of vomiting ( ERPV ) over 3 weeks . After a buffer period of 3 weeks , they were crossed over to six sessions of the other treatment . High drop-out rates , particularly during the ERPB phases , precluded full use of the crossover design . The two treatments yielded similar reduction in binge-vomit frequencies and in other between-session measures . Within-session measures , however , showed significant differences between the two treatments . ERPB was less time-consuming and led to greater reductions of urges to binge , anxiety , and liking of food . Overall improvement of patients in both groups was reasonable and further supports the usefulness of exposure techniques in the treatment of bulimic patients OBJECTIVE The study aims were to evaluate the prevalence and distribution of respective eating disorder behaviors ( DSM-IV criteria ) in a representative community-based sample . METHOD Data were obtained from 3,001 interviews of a r and omly selected sample of 4,200 individuals ' ( age > 15 years ) households in South Australia . RESULTS Ninety-six ( 3.2 % ) of respondents had regular current episodes of binge eating , 48 ( 1.6 % ) regularly fasted or used strict dieting , 24 ( 0.8 % ) purged . An estimated 8 ( 0.3 % ) had bulimia nervosa and 30 ( 1 % ) had binge eating disorder . Binge eating and dieting were most common in people who were in their early to mid thirties . Dieting and purging , but not regular binge eating , were more common in women than in men . Purging was most common in the 35 - 44 year age range . The only behavior significantly associated with ( increased ) weight was binge eating . Unmarried subjects were less likely to diet than married subjects . No significant differences in rates of these behaviors were found for household income . DISCUSSION Problematic eating disorder behaviors in older women and in men were more common than expected and merit further clinical and research attention A re analysis of treatment response and relapse was performed using survival analysis in a 12-week clinical trial of cognitive behavioral group psychotherapy for the treatment of bulimia nervosa . One hundred forty-three ( 143 ) bulimic women with high incidence of binge eating , self-induced vomiting , and /or laxative abuse were r and omly assigned to one of four possible treatment conditions that consisted of a combination of two factors : ( 1 ) emphasis on abstinence ( high and low ) , and ( 2 ) treatment intensity ( high and low ) . " Initial " and " maintained " response to treatment based on " total " and " near " abstinence criteria were determined using self-reported binge eating , vomiting , and laxative use data . Results suggest that an emphasis on abstinence appears important in achieving initial abstinence , whereas intensity of treatment may be important in maintaining abstinence OBJECTIVE The aim of this study was to evaluate the effectiveness of guided self-change for bulimia nervosa . METHOD Sixty-two patients with DSM-III-R-defined bulimia nervosa were r and omly assigned to 1 ) use of a self-care manual plus eight fortnightly sessions of cognitive behavior therapy ( guided self-change ) or 2 ) 16 sessions of weekly cognitive behavior therapy . RESULTS At the end of treatment and at follow-up an average of 43 weeks after the end of therapy , substantial improvements had been achieved in both groups on the main outcome measures : eating disorder symptoms according to experts ' ratings ( Eating Disorder Examination subscores on overeating , vomiting , dietary restraint , and shape and weight concerns ) , self-reports ( Bulimic Investigatory Test Edinburgh ) , and a 5-point severity scale . Also , improvement was seen on the subsidiary outcome measures : the Beck Depression Inventory , the Self-Concept Question naire , and knowledge of nutrition , weight , and shape . At follow-up , 71 % of the cognitive behavior therapy group had not binged or vomited during the week preceding . In the guided self-change group , 70 % had not binged and 61 % had not vomited during the week before follow-up . CONCLUSIONS Guided self-change incorporating use of a self-care manual offers an approach that can be as effective as st and ard cognitive behavior therapy in the long term and can considerably reduce the amount of therapist contact required In a comparison of nutritional management ( NM ) and stress management ( SM ) for treatment of bulimia nervosa , 55 female patients were r and omly assigned to either treatment . Therapy consisted of 15 sessions in a group over three months , by the end of which , patients under both treatment conditions showed a significant reduction in the frequency of binge eating and vomiting and a significant improvement in various psychopathological features such as body dissatisfaction and depression . All improvements were maintained over 12-month follow-up NM produced a more rapid improvement in general eating behaviour , a faster reduction in binge frequency and a higher abstinence rate from binge eating . SM led to greater positive changes in certain psychopathological features such as feelings of ineffectiveness , interpersonal distrust and anxiety . NM should be regarded as a necessary first intervention in all bulimic patients . Further psychological therapy , such as SM , is indicated as well for some patients , depending on their specific psychological difficulties Despite the major advances in the development of treatments for bulimia nervosa , drop-outs and a lack of engagement in treatment , continue to be problems . Recent studies suggest that the transtheoretical model of change may be applicable to bulimia nervosa . The aim of this study was to examine the roles of readiness to change and therapeutic alliance in determining engagement and outcome in the first phase of treatment . One hundred and twenty five consecutive female patients meeting DSM-IV criteria for bulimia nervosa took part in a r and omised controlled treatment trial . The first phase of the sequential treatment compared four sessions of either cognitive behavioural therapy ( CBT ) or motivational enhancement therapy ( MET ) in engaging patients in treatment and reducing symptoms . Patients in the action stage showed greater improvement in symptoms of binge eating than did patients in the contemplation stage . Higher pretreatment scores on action were also related to the development of a better therapeutic alliance ( as perceived by patients ) after four weeks . However , pretreatment stage of change did not predict who dropped out of treatment . There were no differences between MET and CBT in terms of reducing bulimic symptoms or in terms of developing a therapeutic alliance or increasing readiness to change . The results suggest that the transtheoretical model of change may have some validity in the treatment of bulimia nervosa although current measures of readiness to change may require modification . Overall , readiness to change is more strongly related to improvement and the development of a therapeutic alliance than the specific type of treatment Background : The treatment of binge eating disorder ( BED ) is still the object of debate . In the present study , the effectiveness of antidepressant drugs ( fluoxetine – FLX – 60 mg/day , fluvoxamine – FLV –300 mg/day ) , cognitive-behavioural therapy ( CBT ) and combined treatments ( CBT + FLX , CBT + FLV ) has been evaluated in a r and omized , clinical trial . Results at the end of the active treatment ( in the 24th week ) and 1-year follow-up outcomes have been evaluated . Methods : One hundred eight ( 44 M , 64 F ) BED patients were r and omly assigned to either CBT , FLX ( 60 mg/day ) , FLV ( 300 mg/day ) , CBT + FLX or CBT + FLV , for 24 weeks . At the beginning ( T0 ) , at the end ( T1 ) of treatment and after 1 year ( T2 ) , body mass index ( BMI ) and eating attitude and behaviours ( by EDE 12.0D ) were assessed . Results : At T1 , BMI and EDE scores were significantly reduced in CBT , CBT + FLX and CBT + FLV , but not in the FLX and FLV treatment groups . In the CBT + FLV group , a greater ( p < 0.05 ) reduction of EDE total scores was observed , when compared to CBT + FLX or CBT treatment groups . At T2 , BMI was significantly higher than at T1 , but still significantly lower than at T0 in the CBT , CBT + FLX and CBT + FLV groups , while EDE scores remained unchanged from T1 in all treatment groups . Conclusions : CBT was more effective than FLX or FLV in the treatment of BED . The addition of FLX to CBT does not seem to provide any clear advantage , while the addition of FLV could enhance the effects of CBT on eating behaviours . Modifications of eating behaviours are maintained at the 1-year follow-up , although the lost weight was partly regained OBJECTIVE This study evaluated an eating disorder intervention multimedia program modeled after self-help eating disorder treatment programs . It was hypothesized that women who completed the program would increase their body satisfaction and decrease their preoccupation with weight and frequency of disordered eating behaviors . METHOD Participants were 57 undergraduate females r and omly assigned to either the intervention or control group . Psychological functioning was assessed at baseline , at 3 months postintervention , and at 3 months follow-up . RESULTS Intervention group subjects significantly improved their scores on all psychological measures over time . When compared to the control group , however , only the intervention group 's improvements on the Body Shape Question naire were statistically significant . DISCUSSION This study has demonstrated that minimally effective eating disorder intervention programs can be delivered . A revised program that eliminates interface problems and increases the structure of the intervention is likely to be even better received and more effective OBJECTIVE The aim of this study was to discover clinical ly useful predictors of attrition and outcome in the treatment of bulimia nervosa with cognitive behavior therapy . METHOD Pretreatment , course of treatment , and outcome data were gathered on 194 women meeting the DSM-III-R criteria for bulimia nervosa who were treated with 18 sessions of manual-based cognitive behavior therapy in a three-site study . Differences between dropouts and nondropouts and between recovered and nonrecovered participants were first examined descriptively , and signal detection analyses were then used to determine clinical ly significant cutoff points predicting attrition and abstinence . RESULTS The dropouts were characterized by more severe bulimic cognitions and greater impulsivity , but it was not possible to identify clinical ly useful predictors . The participants with treatment failures were characterized by poor social adjustment and a lower body mass index , presumably indicating greater dietary restriction . However , early progress in therapy best predicted outcome . Signal detection analyses revealed that poor outcome was predicted by a reduction in purging of less than 70 % by treatment session 6 , allowing identification of a substantial proportion of prospect i ve failures . CONCLUSIONS A cutoff point based on reduction of purging by session 6 usefully differentiates patients who will and will not respond to cognitive behavior therapy for bulimia nervosa , potentially allowing early use of a second therapy OBJECTIVE This was an investigation of whether treatment with fluoxetine is useful for individuals with bulimia nervosa who do not respond to psychotherapy or relapse afterward . METHOD Twenty-two patients with bulimia nervosa who had not responded to , or had relapsed following , a course of cognitive behavior therapy or interpersonal psychotherapy were r and omly assigned to receive placebo ( N=9 ) or fluoxetine ( 60 mg/day , N=13 ) for 8 weeks . RESULTS The median frequency of binge eating in the previous 28 days declined from 22 to four episodes in the fluoxetine group but increased from 15 to 18 episodes in the placebo group . Similarly , purging frequency in the previous 28 days declined from 30 to six episodes in the fluoxetine group but increased from 15 to 38 episodes in the placebo group . CONCLUSIONS Fluoxetine may be a useful intervention for patients with bulimia nervosa who have not responded adequately to psychological treatment BACKGROUND Little is known about the relative course and outcome of bulimia nervosa and binge eating disorder . METHODS Two community-based cohorts were studied prospect ively over a 5-year year period . One comprised 102 participants with bulimia nervosa and the other 48 participants with binge eating disorder ( 21 % [ 9/42 ] of whom had comorbid obesity ) . All participants were female and aged between 16 and 35 years at recruitment . The assessment s were at 15-month intervals and addressed eating disorder features , general psychiatric symptoms , and social functioning . RESULTS Both cohorts showed marked initial improvement followed by gradual improvement thereafter . Between half and two thirds of the bulimia nervosa cohort had some form of eating disorder of clinical severity at each assessment point , although only a minority continued to meet diagnostic criteria for bulimia nervosa . Each year about a third remitted and a third relapsed . The outcome of the binge eating disorder cohort was better , with the proportion with any form of clinical eating disorder declining to 18 % ( 7 of 40 ) by the 5-year follow-up . The relapse rate was low among this cohort . There was little movement of participants across the 2 diagnostic categories and few sought treatment . Both groups gained weight , with 39 % of the binge eating disorder cohort ( 14 of 36 ) meeting criteria for obesity at 5-year follow-up . CONCLUSIONS These findings suggest that , among young women in the community , bulimia nervosa and binge eating disorder have a different course and outcome . Whereas the prognosis of those with bulimia nervosa was relatively poor , the great majority of those with binge eating disorder recovered A comparison of cognitive-behavior therapy alone , desipramine alone , and cognitive-behavior therapy combined with desipramine was made in the treatment of bulimia nervosa . The study was terminated early with an N of only 7 subjects per condition because of a high drop-out rate and lack of positive response in the desipramine alone group compared to the other two groups . By this time it was also apparent that at posttreatment and at 6 months follow-up no benefit was being realized from combining cognitive-behavior therapy with desipramine OBJECTIVE In this study , we examined the effects of an exercise intervention in the treatment of obese women with binge eating disorder ( BED ) . METHOD Subjects were r and omized to one of two 6-month treatment programs that included an identical exercise component ( n = 44 ) or to a delayed treatment control condition ( n = 33 ) . Exercise level , binge eating frequency , and depressive symptomatology were assessed pre- and posttreatment . RESULTS Women who received active treatment reported significantly greater increases in their weekly exercise frequency than did control subjects . At posttreatment , 81.4 % of subjects who had received treatment were abstinent from binge eating . Compared to women who were not abstinent at posttreatment , abstinent women evidence d significant changes in exercise frequency and caloric expenditure . However , weight loss and improvements in depressive symptomatology were not related to exercise participation . DISCUSSION These results suggest that exercise may be an important aspect of BED treatment and useful in promoting abstinence from binge eating A r and omized , placebo-controlled study was conducted examining the singular and combined effects of fluoxetine and a self-help manual on suppressing bulimic behaviors in women with bulimia nervosa . A total of 91 adult women with bulimia nervosa were r and omly assigned to one of four conditions : placebo only , fluoxetine only , placebo and a self-help manual , or fluoxetine and a self-help manual . Subjects were treated for 16 weeks . Primary outcome measures included self-reports of bulimic behaviors . Fluoxetine and a self-help manual were found to be effective in reducing the frequency of vomiting episodes and in improving the response rates for vomiting and binge-eating episodes . Furthermore , both factors were shown to be acting additively on the primary and secondary efficacy measures in this study . Results are discussed in relation to previous research and the implication s for treatment of bulimia nervosa |
13,355 | 30,517,165 | The cost-effectiveness of treatments of CRPC strongly depended on the willingness to pay per quality -adjusted life year gained/life-year saved throughout all included costs-effectiveness analyses and model-based economic evaluations . | BACKGROUND Treatment of metastatic prostate cancer is associated with high personal and economic burden .
Recently , new treatment options for castration-resistant prostate cancer became available with promising survival advantages .
However , cost-effectiveness of those new treatment options is sometimes ambiguous or given only under certain circumstances .
The aim of this study was to systematic ally review studies on the cost-effectiveness of treatments and costs of castration-resistant prostate cancer ( CRPC ) and metastasizing castration-resistant prostate cancer ( mCRPC ) on their method ological quality and the risk of bias . | PURPOSE To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a r and omized controlled trial . PATIENTS AND METHODS We r and omized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone ( 10 mg daily ) . Nonresponding patients on prednisone could receive mitoxantrone subsequently . The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients ( or complete loss of pain if initially 1 + ) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart . Secondary end points were a decrease of > or = 50 % in use of analgesic medication without an increase in pain , duration of response , and survival . Health-related quality of life was evaluated with a series of linear analog self- assessment scales ( LASA and the Prostate Cancer-Specific Quality -of-Life Instrument [ PROSQOLI ] ) , the core question naire of the European Organization for Research and Treatment of Cancer ( EORTC ) , and a disease-specific module . RESULTS Palliative response was observed in 23 of 80 patients ( 29 % ; 95 % confidence interval , 19 % to 40 % ) who received mitoxantrone plus prednisone , and in 10 of 81 patients ( 12 % ; 95 % confidence interval , 6 % to 22 % ) who received prednisone alone ( P = .01 ) . An additional seven patients in each group reduced analgesic medication > or = 50 % without an increase in pain . The duration of palliation was longer in patients who received chemotherapy ( median , 43 and 18 weeks ; P < .0001 , log-rank ) . Eleven of 50 patients r and omized to prednisone treatment responded after addition of mitoxantrone . There was no difference in overall survival . Treatment was well tolerated , except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone . Most responding patients had an improvement in quality -of-life scales and a decrease in serum prostate-specific antigen ( PSA ) level . CONCLUSION Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer PURPOSE Anti and rogen withdrawal ( AAWD ) results in a prostate-specific antigen ( PSA ) response ( decline in PSA level of > or = 50 % ) in 15 % to 30 % of and rogen-independent prostate cancer ( AiPCa ) patients . Thereafter , adrenal and rogen ablation with agents such as ketoconazole ( K ) is commonly utilized . The therapeutic effect of AAWD alone was compared with simultaneous AAWD and K therapy . PATIENTS AND METHODS AiPCa patients were r and omized to undergo AAWD alone ( n=132 ) , or together with K ( 400 mg orally [ p.o . ] tid ) and hydrocortisone ( 30 mg p.o . each morning , 10 mg p.o . each evening ; n=128 ) . Patients who developed progressive disease after AAWD alone were eligible for deferred treatment with K. RESULTS Eleven percent of patients undergoing AAWD alone had a PSA response , compared to 27 % of patients who underwent AAWD and simultaneous K ( P=.0002 ) . Objective responses were observed in 2 % of patients treated with AAWD alone compared to 20 % in patients treated with AAWD/K ( P=.02 ) . There was no difference in survival . PSA and objective responses were observed in 32 % and 7 % , respectively , of patients receiving deferred K , and were more common in patients with prior AAWD response . Treatment with K was well tolerated , and result ed in a decline in adrenal and rogen levels , which rose at the time of disease progression . CONCLUSION K has modest activity in AiPCa patients , while AAWD alone has minimal activity . Adrenal and rogen levels fall with treatment with K and then climb at the time of progression , suggesting that progressive disease while on K may be due to tachyphylaxis to the adrenolytic properties of Purpose Advanced prostate cancer ( PC ) is associated with substantial psychosocial morbidity . We sought to determine whether mindfulness-based cognitive therapy ( MBCT ) reduces distress in men with advanced PC . Methods Men with advanced PC ( proven metastatic and /or castration-resistant biochemical progression ) were r and omly assigned to an 8-week , group-based MBCT intervention delivered by telephone ( n = 94 ) or to minimally enhanced usual care ( n = 95 ) . Primary intervention outcomes were psychological distress , cancer-specific distress , and prostate-specific antigen anxiety . Mindfulness skills were assessed as potential mediators of effect . Participants were assessed at baseline and were followed up at 3 , 6 , and 9 months . Main statistical analyses were conducted on the basis of intention to treat . Results Fourteen MBCT groups were conducted in the intervention arm . Facilitator adherence ratings were high ( > 93 % ) . Using r and om-effects mixed-regression models , intention-to-treat analyses indicated no significant changes in intervention outcomes or in engagement with mindfulness for men in MBCT compared with those receiving minimally enhanced usual care . Per- protocol analyses also found no differences between arms in outcomes or engagement , with the exception of the mindfulness skill of observing , which increased over time for men in MBCT compared with usual care ( P = .032 ) . Conclusion MBCT in this format was not more effective than minimally enhanced usual care in reducing distress in men with advanced PC . Future intervention research for these men should consider approaches that map more closely to masculinity BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) Background : Patients who develop castration-resistant prostate cancer ( CRPCa ) typically continue on and rogen deprivation therapy ( ADT ) . Whether these patients need to remain on ADT has not been well studied . We conducted a multicenter r and omized trial to compare an intermittent versus continuous approach to ADT in CRPCa patients . Overall survival , health-related quality of life ( QOL ) , and cost were the main endpoints . Methods : CRPCa patients were r and omized 2:1 to intermittent or continuous luteinizing hormone-releasing hormone agonists ( LHRHa ) . Patients were followed with clinical assessment s , laboratory investigations , and QOL question naires ( EORTC QLQ-C30 or PROSQOLI ) every 2 months . If the serum testosterone rose above castrate levels ( 1.75 nmol/L ) , LHRHa were reinitiated . The study was design ed to close if > 50 % of patients needed to restart ADT in the intermittent arm . Results : Thirty-one patients were followed with a median follow-up of 26.8 months—18 in the intermittent arm and 13 in the continuous . Twelve of 18 patients on the intermittent arm were reinitiated on LHRHa at a median time of 17.9 months . There was no difference in overall or cancer-specific survival between the 2 arms . There was no statistically significant difference in QOL between the 2 arms at 0 and 12 months . The total mean costs at 24 months were significantly lower in the intermittent arm ( $ 3135 vs. $ 8253 Canadian dollars , P=0.0167 ) compared with the continuous . The main limitation of this study is the small sample size . Conclusions : We have observed that intermittent ADT in patients with CRPCa , using a testosterone of > 1.75 ngmol/L as a trigger to reinitiate LHRHa , results in a substantial cost savings with no negative impact on oncologic and QOL outcomes Background Prostate cancer ( PCa ) is the most common non-skin cancer among men in developed countries . Several novel treatments have been adopted by healthcare systems to manage PCa . Most of the observational studies and r and omized trials on PCa have concurrently evaluated fewer treatments over short follow-up . Further , preceding decision analytic models on PCa management have not evaluated various contemporary management options . Therefore , a contemporary decision analytic model was necessary to address limitations to the literature by synthesizing the evidence on novel treatments thereby forecasting short and long-term clinical outcomes . Objectives To develop and vali date a Markov Monte Carlo model for the contemporary clinical management of PCa , and to assess the clinical burden of the disease from diagnosis to end-of-life . Methods A Markov Monte Carlo model was developed to simulate the management of PCa in men 65 years and older from diagnosis to end-of-life . Health states modeled were : risk at diagnosis , active surveillance , active treatment , PCa recurrence , PCa recurrence free , metastatic castrate resistant prostate cancer , overall and PCa death . Treatment trajectories were based on state transition probabilities derived from the literature . Validation and sensitivity analyses assessed the accuracy and robustness of model predicted outcomes . Results Validation indicated model predicted rates were comparable to observed rates in the published literature . The simulated distribution of clinical outcomes for the base case was consistent with sensitivity analyses . Predicted rate of clinical outcomes and mortality varied across risk groups . Life expectancy and health adjusted life expectancy predicted for the simulated cohort was 20.9 years ( 95%CI 20.5–21.3 ) and 18.2 years ( 95 % CI 17.9–18.5 ) , respectively . Conclusion Study findings indicated contemporary management strategies improved survival and quality of life in patients with PCa . This model could be used to compare long-term outcomes and life expectancy conferred of PCa management paradigms Purpose Sipuleucel-T , the first FDA -approved autologous cellular immunotherapy for treatment of advanced prostate cancer , is manufactured by activating peripheral blood mononuclear cells , including antigen presenting cells ( APCs ) , with a fusion protein containing prostatic acid phosphatase . Analysis of data from three phase 3 trials was performed to immunologically characterize this therapy during the course of the three doses , and to relate the immunological responses to overall survival ( OS ) . Methods Sipuleucel-T product characteristics [ APC numbers , APC activation ( CD54 upregulation ) , and total nucleated cell ( TNC ) numbers ] were assessed in three r and omized , controlled phase 3 studies ( N = 737 ) . Antigen-specific cellular and humoral responses were assessed in a subset of subjects . The relationships between these parameters and OS were assessed . Results APC activation occurred in the first dose preparation [ 6.2-fold , ( 4.65 , 7.70 ) ; median ( 25th , 75th percentile ) ] and increased in the second [ 10.6-fold ( 7.83 , 13.65 ) ] and third [ 10.5-fold ( 7.89 , 13.65 ) ] dose preparations . Cytokines and chemokines associated with activated APCs were produced during the manufacture of each dose ; T-cell activation-associated cytokines were detected in the second and third dose preparations . Antigen-specific T cells were detectable after administration of the first sipuleucel-T dose . Cumulative APC activation , APC number , and TNC number correlated with OS ( P < 0.05 ) . Antigen-specific immune responses were observed in 78.8 % of monitored subjects and their presence correlated with OS ( P = 0.003 ) . ConclusionS ipuleucel-T broadly engages the immune system by activating APCs ex vivo and inducing long-lived immune responses in vivo . These data indicate antigen-specific immune activation as a mechanism by which sipuleucel-T prolongs OS PURPOSE To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer ( HRPC ) in the context of a previously published Canadian open-label , phase III , r and omized trial with palliative end points . PATIENTS AND METHODS The trial r and omized 161 patients to initial treatment with mitoxantrone and prednisone ( M + P ) or to prednisone alone ( P ) and showed better palliation with M + P. There was no significant difference in survival . A detailed retrospective chart review was performed of re sources used from r and omization until death of 114 of 161 patients enrolled at the three largest centers : these included hospital admissions , outpatient visits , investigations , therapies ( which included all chemotherapy and radiation ) , and palliative care . Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project , respectively . Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer ( EORTC ) QLQ-C30 global quality -of-life item measured every 3 weeks on trial to an estimate of utility , and extending the last known value through to death or last follow-up . RESULTS The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $ 27,300 ; P CDN $ 29,000 . The 95 % confidence intervals on the observed cost difference ranged from a saving of $ 9,200 for M + P ( with palliative benefit ) to an increased cost of $ 5,800 for M + P. The major proportion of cost ( M + P 53 % v P 66 % ; CDN $ 14,500 v $ 19,100 ) was for inpatient care . Initial M + P was consistently less expensive in whichever time period was used to compare costs . Cost-utility analysis showed M + P to be the preferred strategy with an upper 95 % confidence interval for the incremental cost-utility ratio of CDN $ 19,700 per quality -adjusted life-year ( QALY ) . CONCLUSION A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas . Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient BACKGROUND Sipuleucel-T , an autologous active cellular immunotherapy , has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer . METHODS In this double-blind , placebo-controlled , multicenter phase 3 trial , we r and omly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T ( 341 patients ) or placebo ( 171 patients ) administered intravenously every 2 weeks , for a total of three infusions . The primary end point was overall survival , analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen ( PSA ) and lactate dehydrogenase . RESULTS In the sipuleucel-T group , there was a relative reduction of 22 % in the risk of death as compared with the placebo group ( hazard ratio , 0.78 ; 95 % confidence interval [ CI ] , 0.61 to 0.98 ; P=0.03 ) . This reduction represented a 4.1-month improvement in median survival ( 25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group ) . The 36-month survival probability was 31.7 % in the sipuleucel-T group versus 23.0 % in the placebo group . The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test ( hazard ratio , 0.77 ; 95 % CI , 0.61 to 0.97 ; P=0.02 ) and after adjustment for use of docetaxel after the study therapy ( hazard ratio , 0.78 ; 95 % CI , 0.62 to 0.98 ; P=0.03 ) . The time to objective disease progression was similar in the two study groups . Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills , fever , and headache . CONCLUSIONS The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer . No effect on the time to disease progression was observed . ( Funded by Dendreon ; Clinical Trials.gov number , NCT00065442 . BACKGROUND There is evidence linking metformin to improved prostate cancer (PCa)-related outcomes . OBJECTIVE To evaluate treatment with metformin in patients with castration-resistant PCa ( CRPC ) and the effect of the treatment on progression-free survival ( PFS ) and PSA doubling time ( PSA DT ) . DESIGN , SETTING , AND PARTICIPANTS Forty-four men with progressive metastatic CRPC from 10 Swiss centers were included in this single-arm phase 2 trial between December 2010 and December 2011 . INTERVENTION Patients received metformin 1000 mg twice daily until disease progression . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was the absence of disease progression at 12 wk . Simon two-stage optimal design was applied . With a 5 % significance level and 90 % power , 44 patients were required to test PFS at 12 wk ≤ 15 % ( H0 ) compared with ≥ 35 % ( H1 ) . RESULTS AND LIMITATIONS Thirty-six percent of patients were progression-free at 12 wk , 9.1 % were progression-free at 24 wk , and in two patients a confirmed ≥ 50 % prostate-specific antigen ( PSA ) decline was demonstrated . In 23 patients ( 52.3 % ) we observed a prolongation of PSA DT after starting metformin . The homeostatic model assessment index fell by 26 % from baseline to 12 wk , indicating an improvement in insulin sensitivity . There was a significant change in insulin-like growth factor-1 and insulin-like growth factor binding protein 3 from baseline to 12 wk . Sample size and lack of a control arm are the limitations of this trial ; analyses are therefore exploratory . CONCLUSIONS Treatment with metformin is safe in nondiabetic patients , and it yields objective PSA responses and may induce disease stabilization . The activity of metformin in PCa , along with its low cost , favorable toxicity profile , and positive effect on metabolic parameters , suggests that further investigation of metformin as therapy for patients with PCa is of interest . PATIENT SUMMARY In this trial we assessed the use of the diabetes mellitus drug metformin in patients with advanced prostate cancer . We found disease stabilization and prolongation of prostate-specific antigen doubling time in some patients as well as effects on metabolic parameters . TRIAL REGISTRATION This study is registered with Clinical Trials.gov with the identifier NCT01243385 . PREVIOUS PRESENTATION The study was presented at ESMO 2012 ( abstract 1460 ) Objective . To obtain estimates of direct health care costs for prostate cancer ( PC ) from diagnosis to death to inform state transition models . Methods . A stratified r and om sample of PC patients residing in 3 geographically diverse regions of Ontario , Canada , and diagnosed in 1993–1994 , 1997–1998 , and 2001–2002 , was selected from the Ontario Cancer Registry . We retrieved patients ’ pathology reports to identify referring physicians and contacted surviving patients and next of kin of deceased patients for informed consent . We review ed clinic charts to obtain data required to allocate each patient ’s observation time to 11 PC-specific health states . We linked these data to health care administrative data bases to calculate re source use and costs ( Canadian dollars , 2008 ) per health state . A multivariable mixed-effects model determined predictors of costs . Results . The final sample numbered 829 patients . In the regression model , total direct costs increased with age , comorbidity , and Gleason score ( all P < 0.0001 ) . Radical prostatectomy was the most costly primary treatment health state ( $ 4676 per 100 days ) . Radical prostatectomy , hormone-refractory metastatic disease ( $ 6398 per 100 days ) , and final ( predeath ) ( $ 13,739 per 100 days ) health states were significantly more costly ( P < 0.05 ) than nontreated nonmetastatic PC ( $ 3440 per 100 days ) , whereas the postprostatectomy ( $ 732 per 100 days ) and postradiation ( $ 1556 per 100 days ) states cost significantly less ( P < 0.0001 ) . Conclusions . This study used an innovative but labor-intensive approach linking chart and administrative data to estimate health care costs . Research ers should weigh the potential benefits of this method against what is involved in implementation . Modifications in methodology may achieve similar gains with less outlay in individual studies . However , we believe that this is a promising approach for research ers wishing to advance the quality of costing in state transition modeling Objective : To compare the efficacy of diethylstilboestrol ( DES ) with bicalutamide in the treatment of hormone refractory prostate cancer in relation to its effect on prostate-specific antigen ( PSA ) and survival . Methods : Patients on LHRH analogues for prostate carcinoma with evidence of biochemical or clinical progression were r and omized into one of the treatment arms ( n = 58 ) . The first group ( group A , n = 26 ) received 1 mg of DES with 75 mg of aspirin per day in addition to the primary hormonal treatment . The second group ( group B , n = 32 ) received bicalutamide at a dose of 50 mg/day in addition to the primary treatment . Patients were followed up every 3 months with their PSA being checked and were also monitored for any clinical progression and adverse effects as a result of treatment . Any adverse event occurring after patients were started on treatment was attributed to the drug and patients were clinical ly assessed at each visit . Failure of treatment was defined as a 50 % or greater increase in PSA after commencing treatment . Once r and omized , all patients were followed up for survival regardless of failure of second-line hormonal manipulation . Results : The mean age of the patients was 76.7 years ( 60–88 , SD 7.4 ) in group A and 76 years ( 67–86 , SD 6.9 ) in group B. Twelve patients in each group had metastatic disease . The median follow-up periods for both groups were 24 months ( range 6–48 in group A , range 3–54 in group B ) . 65 % of the patients in group A ( 17/26 ) and 43.5 % ( 14/32 ) in group B had a fall in their PSA levels ( p = 0.08 , Fisher ’s exact test ) with 23 % ( 6/26 ) and 31 % ( 10/32 ) having a > 50 % response respectively ( p = 0.34 , Fisher ’s exact test ) . Mean PSA nadir in those who responded were 20.6 ng/ml ( range 1.6–59.4 ) and 7.41 ng/ml ( range 0.1–42.6 ) in groups A and B respectively . The median duration of response was 9 months ( 3–18 months ) for group A and 12 months ( 3–18 months ) for group B. Seven patients in group A and 6 in group B experienced adverse events . Three of the 7 in the group A experienced cardiovascular related adverse effects ( 1 congestive cardiac failure , 1 pulmonary embolism and 1 stroke ) . At the end of the study period , 14 ( 54 % ) of group A patients were alive and 12 ( 46 % ) were dead . In group B , 15 ( 47 % ) were alive , 16 ( 50 % ) were dead and 1 ( 3 % ) lost to follow-up . At the completion of the study , 3 patients in each group were still on treatment . Conclusion : Low-dose DES and 50 mg of bicalutamide per day are equally effective in hormone refractory prostate carcinoma with respect to biochemical response , although DES has more severe adverse effects . This is a small sample and larger multicentre trials are needed to give us a definite conclusion BACKGROUND Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced , hormone-refractory prostate cancer , but it does not improve survival . We compared such treatment with docetaxel plus prednisone in men with this disease . METHODS From March 2000 through June 2002 , 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were r and omly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks , 75 mg of docetaxel per square meter every three weeks , or 30 mg of docetaxel per square meter weekly for five of every six weeks . The primary end point was overall survival . Secondary end points were pain , prostate-specific antigen ( PSA ) levels , and the quality of life . All statistical comparisons were against mitoxantrone . RESULTS As compared with the men in the mitoxantrone group , men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 ( 95 percent confidence interval , 0.62 to 0.94 ; P=0.009 by the stratified log-rank test ) and those given weekly docetaxel had a hazard ratio for death of 0.91 ( 95 percent confidence interval , 0.75 to 1.11 ; P=0.36 ) . The median survival was 16.5 months in the mitoxantrone group , 18.9 months in the group given docetaxel every 3 weeks , and 17.4 months in the group given weekly docetaxel . Among these three groups , 32 percent , 45 percent , and 48 percent of men , respectively , had at least a 50 percent decrease in the serum PSA level ( P<0.001 for both comparisons with mitoxantrone ) ; 22 percent , 35 percent ( P=0.01 ) , and 31 percent ( P=0.08 ) had predefined reductions in pain ; and 13 percent , 22 percent ( P=0.009 ) , and 23 percent ( P=0.005 ) had improvements in the quality of life . Adverse events were also more common in the groups that received docetaxel . CONCLUSIONS When given with prednisone , treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain , serum PSA level , and quality of life , as compared with mitoxantrone plus prednisone There are limited data available regarding the cost of care in patients with and rogen independent prostate carcinoma ( AIPC ) , and there are no data on the impact of direct nonmedical and indirect costs ( DNM/IC ) . This lack of data , along with the feasibility of collecting DNM/IC , was examined in patients with AIPC who took part in a r and omized trial using a newly developed question naire , the Collection of Indirect and Nonmedical Direct Costs ( COIN ) form PURPOSE We estimated the cost-effectiveness of zoledronic acid vs placebo for decreasing skeletal complications in men with prostate cancer . MATERIAL S AND METHODS We performed a cost-effectiveness analysis alongside a multinational clinical trial of zoledronic acid . Cost estimation was based on prospect ively collected re source use data for 85.3 % of enrolled patients . Cost-effectiveness ratios were based on within-trial data on clinical outcomes , quality of life and study medication cost . RESULTS Patients receiving zoledronic acid experienced fewer hospital days during a mean followup of 9 months ( average 5.6 vs 8.0 days ; p = 0.1910 ) . Mean direct costs excluding study medication were US dollars 5365 for patients receiving zoledronic acid and US dollars 5689 for patients receiving placebo , a difference of US dollars 324 ( 95 % CI US dollars 1781 to US dollars 1146 ) . The global average cost of zoledronic acid plus its administration during the trial was US dollars 5677 ( US dollars 450 per dose ) . The nominal cost per skeletal complication avoided was US dollars 112300 ( 95 % CI US dollars 6900 to US dollars 48700 ) and the cost per additional patient free of skeletal complications was US dollars 51400 ( 95 % CI US dollars 26900 to US dollars 243700 ) . Nominal within-trial cost per quality adjusted life-year was US dollars 159200 , which varied widely in sensitivity analyses . CONCLUSIONS The nominal base case estimate of the cost per quality adjusted life-year for zoledronic acid in the prevention of skeletal complications of prostate cancer is consistent with that of bisphosphonates in breast cancer . However , the cost-effectiveness ratios for bisphosphonates are higher than commonly cited thresholds for conferring cost-effectiveness BACKGROUND To address the rising concern about oncology drug costs , the American Society of Clinical Oncology ( ASCO ) and the National Comprehensive Cancer Network ( NCCN ) recently developed unique tools to help providers and patients make informed decisions about the value of an anticancer regimen . The ASCO Value Framework ( AVF ) allows users to generate a net health benefit ( NHB ) score along with drug acquisition costs for oncology regimens that have been compared in a prospect i ve r and omized clinical trial . In contrast , the NCCN Evidence Blocks ( NEB ) derives ratings from an expert panel assessment in the categories of efficacy , safety , quality and consistency of evidence , and affordability . OBJECTIVE To compare the results of the AVF and NEB by applying each tool to the same clinical scenarios . METHODS We evaluated 2 regimens using the AVF and NEB scores : ( 1 ) enzalutamide for treatment of metastatic castration-resistant prostate cancer and ( 2 ) nivolumab versus docetaxel in treatment of advanced squamous and nonsquamous non-small cell lung cancer ( NSCLC ) . RESULTS Enzalutamide generated a total NHB score of 44.8 ( range 0 - 180 ) for use before chemotherapy and 70.8 for use after chemotherapy with a monthly cost of $ 8,495 in the AVF . The NEB scored enzalutamide 4 ( very effective ) for efficacy , 4 ( occasionally toxic ) for safety , and 2 ( expensive ) for affordability in the no visceral metastases block . It scored 3 ( moderately effective ) for efficacy , 4 for safety , and 2 for affordability in the visceral metastases block . Nivolumab in advanced nonsquamous NSCLC scored 36.0 and 73.2 in advanced squamous NSCLC , with a monthly cost of $ 7,010 in the AVF . The NEB gave nivolumab a score of 4 for efficacy and safety and 1 ( very expensive ) for affordability in the NEB in advanced nonsquamous and advanced squamous NSCLC . CONCLUSIONS The AVF and NEB are novel tools that take different approaches in assessing the value of an oncology treatment regimen . From this study , it is clear that the findings generated by these tools are distinct . The AVF provides a summary score for treatments across all clinical benefit and toxicity categories , whereas the NEB provides component scores for treatment efficacy , safety , quality and consistency of evidence , and affordability . Both tools are novel and come with their own challenges . DISCLOSURES No outside funding supported this study . Shah-Manek is also employed by Ipsos Healthcare , a consulting firm . The authors have no conflicting interests to report . Study concept and design were contributed by Shah-Manek and Ignoffo . Galanto and Nguyen collected the data , and data interpretation was performed by all the authors . All the authors contributed to writing the manuscript , which was revised primarily by Shah-Manek , along with Galanto , Nguyen , and Ignoffo . This research was previously presented as a poster and podium presentation at the Academy of Managed Care Pharmacy Nexus 2016 held October 3 - 6 in National Harbor , Maryl and |
13,356 | 21,074,681 | Adding tobacco status as a vital sign result ed in an increase in some clinical guideline recommended actions , particularly documentation of smoking status .
There was insufficient evidence to quantify the effect of an EMR on changes in patient smoking behaviors . | CONTEXT The exp and ed use of electronic medical records ( EMRs ) may provide an opportunity to increase the use and impact of clinical guidelines to promote tobacco-cessation treatment in primary care setting s. The objective of this systematic review is to evaluate the evidence for such an effect . | The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . OBJECTIVE To test the effectiveness of a care coordination program for telephone counseling in raising referral and treatment rates for smoking cessation . STUDY DESIGN A demonstration project implementing a smoking cessation care coordination program offering telephone counseling and medication management to patients referred from primary care . METHODS The study was performed at 18 Veterans Health Administration ( VA ) sites in California . Participants were VA patients receiving primary care . We r and omly allocated 10 of 18 sites to receive the Telephone Care Coordination Program , which included simple 2-click referral , proactive care coordination , medication management , and 5 follow-up telephone calls . Each patient received a 30- to 45-minute counseling session from the California Smokers ' Helpline . Patients at control sites received usual care . RESULTS During 10 months , we received 2965 referrals . We were unable to reach 1156 patients ( 39 % ) , despite at least 3 attempts . We excluded 73 patients ( 3 % ) , and 391 patients ( 13 % ) were not interested . We connected the remaining 1345 patients ( 45 % ) to the Helpline . At 6-month followup , 335 patients ( 11 % of all referrals and 25 % of participating patients ) were abstinent . Providers at intervention sites reported referring many more patients to telephone counseling than providers at control sites ( 15.6 vs 0.7 in the prior month ) . CONCLUSIONS The program generated a large number of referrals ; almost half of the patients referred were connected with the Helpline . Long-term abstinence was excellent . These results suggest that managed care organizations may be able to improve tobacco control by implementing a similar system of care coordination AIMS To establish whether proactively identifying all smokers in primary care population s and offering smoking cessation support is effective in increasing long-term abstinence from smoking . DESIGN Cluster r and omized controlled trial . SETTING Twenty-four general practice s in Nottinghamshire , r and omized by practice to active or control intervention . PARTICIPANTS All adult patients registered with the practice s who returned a question naire confirming that they were current smokers ( n = 6856 ) . INTERVENTION Participants were offered smoking cessation support by letter and those interested in receiving it were contacted and referred into National Health Service ( NHS ) stop smoking services if required . MEASUREMENTS Vali date d abstinence from smoking , use of smoking cessation services and number of quit attempts in continuing smokers at 6 months . FINDINGS Smokers in the intervention group were more likely than controls to report that they had used local cessation services during the study period [ 16.6 % and 8.9 % , respectively , adjusted odds ratio ( OR ) 2.09 , 95 % confidence interval ( CI ) 1.57 - 2.78 ] , and continuing smokers ( in the intervention group ) were more likely to have made a quit attempt in the last 6 months ( 37.4 % and 33.3 % , respectively , adjusted OR 1.23 , 95 % CI 1.01 - 1.51 ) . Vali date d point prevalence abstinence from smoking at 6 months was higher in the intervention than the control groups ( 3.5 % and 2.5 % , respectively ) but the difference was not statistically significant ( adjusted OR controlling for covariates : 1.64 , 95 % CI 0.92 - 2.89 ) . CONCLUSIONS Proactively identifying smokers who want to quit in primary care population s , and referring them to a cessation service , increased contacts with cessation services and the number of quit attempts . We were unable to detect a significant effect on long-term cessation rates , but the study was not powered to detect the kind of difference that might be expected Background : Strategies to improve smoking cessation counseling in clinical setting s are critical to supporting smokers ’ attempts to quit . This study evaluates the impact of adding 2 smoking-related vital sign questions in an electronic medical records system on identification , assessment , and counseling for patients who smoke : “ Current smoker ? ” and “ Plan to quit ? ” Methods : Baseline data and data after intervention were collected through record review of 899 r and omly selected patient visits across 3 outpatient clinics . Results : From before to after intervention , identification of smokers increased 18 % ( from 71 % to 84 % ; P < .001 ) , and assessment for a plan to quit increased 100 % ( from 25.5 % to 51 % ; P < .005 ) . Among all smokers , cessation counseling increased 26 % ( from 23.6 % to 29.8 % ; P = .41 ) . Significantly more smokers who received the assessment for a plan to quit received cessation counseling ( 46 % vs. 14 % , P < .001 ) . Regression analysis showed that patients receiving an assessment for plan to quit were 80 % more likely to receive cessation counseling ( OR 0.209 ; 95 % CI , 0.095–0.456 ) . Conclusions : Physician-documented counseling rates are significantly higher when patients are asked about smoking and assessed for a plan to quit . Two questions that ask about smoking status and assess plans to quit may provide prompts to increase the likelihood that patients who smoke receive cessation counseling 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 BACKGROUND To improve the documentation and treatment of tobacco use in primary care , we developed and implemented a 3-part electronic health record enhancement : (1)smoking status icons , ( 2 ) tobacco treatment reminders , and ( 3 ) a Tobacco Smart Form that facilitated the ordering of medication and fax and e-mail counseling referrals . METHODS We performed a cluster-r and omized controlled trial of the enhancement in 26 primary care practice s between December 19 , 2006 , and September 30 , 2007 . The primary outcome was the proportion of documented smokers who made contact with a smoking cessation counselor . Secondary outcomes included coded smoking status documentation and medication prescribing . RESULTS During the 9-month study period , 132 630 patients made 315 962 visits to study practice s. Coded documentation of smoking status increased from 37 % of patients to 54 % ( + 17 % ) in intervention practice s and from 35 % of patients to 46 % ( + 11 % ) in control practice s ( P < .001 for the difference in differences ) . Among the 9589 patients who were documented smokers at the start of the study , more patients in the intervention practice s were recorded as nonsmokers by the end of the study ( 5.3 % vs 1.9 % in control practice s ; P < .001 ) . Among 12 207 documented smokers , more patients in the intervention practice s made contact with a cessation counselor ( 3.9 % vs 0.3 % in control practice s ; P < .001 ) . Smokers in the intervention practice s were no more likely to be prescribed smoking cessation medication ( 2 % vs 2 % in control practice s ; P = .40 ) . CONCLUSION This electronic health record-based intervention improved smoking status documentation and increased counseling assistance to smokers but not the prescription of cessation medication The electronic health record ( EHR ) may be an effective tool to help clinicians address tobacco use more consistently . To evaluate the impact of EHR-generated practice feedback on rates of referral to a state-level tobacco quitline , we conducted a cluster r and omized clinical trial ( feedback versus no feedback ) within 19 primary care clinics in Oregon . Intervention clinics received provider-specific monthly feedback reports generated from EHR data . The reports rated provider performance in asking , advising , assessing , and assisting with tobacco cessation compared with a clinic average and an achievable benchmark of care . During 12 months of follow-up , EHR-documented rates of advising , assessing , and assisting were significantly improved in the intervention clinics compared with the control clinics ( p<.001 ) . A higher case-mix index and presence of a clinic champion were associated with higher rates of referral to a state-level quitline . EHR-generated provider feedback improved documentation of assistance with tobacco cessation . Connecting physician offices to a state-level quitline was feasible and well accepted BACKGROUND Lack of interest has been cited as a reason not to offer cessation assistance to smokers , but research suggests that smokers accept treatments offered proactively . This study assessed acceptability , utilization , and effectiveness of free smoking cessation treatment among diverse primary care patients . METHOD Medical assistants invited 4174 adult smokers to participate . Enrollees ( 1869 ) self-selected or were assigned to receive free nicotine patch therapy alone or in combination with the Committed Quitters(R ) program , and for some , individual counseling . RESULTS In nearly 68 % of cases , patients accepted a treatment invitation ; 77 % of eligible smokers enrolled ; 85 % of these picked up free patches . Given a choice of treatments , 75 % of participants elected a psychosocial treatment in addition to patch therapy . Thirteen percent of treatment initiators achieved biochemically confirmed 7-day point-prevalence abstinence at 1 year , with no significant treatment effects . Minority patients showed greater initial interest but less utilization did than White patients . CONCLUSIONS Free , readily accessible smoking cessation treatment offered in primary care setting s was accepted and used by the majority of unselected smokers of diverse racial/ethnic origins . Psychosocial treatment components did not significantly increase abstinence rates . Barriers , rather than lack of interest , may keep minority smokers from using cessation treatments PURPOSE We undertook a study to assess the impact of comparative feedback vs general reminders on practice -based referrals to a tobacco cessation quit line and estimated costs for projected quit responses . METHODS We conducted a group-r and omized clinical trial comparing the impact of 6 quarterly ( 18 months ) feedback reports ( intervention ) with that of general reminders ( control ) on practice -based clinician referrals to a quit-line service . Feedback reports were based on an Achievable Benchmark of Care approach using baseline practice , clinician , and patient survey responses , and referrals per quarter . Comparable quit responses and costs were estimated . RESULTS Three hundred eight clinicians participated ( 171 family medicine , 88 internal medicine , 49 obstetrics-gynecology ) from 87 primary care practice s in Michigan . After 18 months , there were more referrals from the intervention than from the control practice s ( 484 vs 220 ; P < .001 ) . Practice facsimile ( fax ) referrals ( 84 % , n = 595 ) exceeded telephone referrals ( 16 % , n = 109 ) , but telephone referrals result ed in greater likelihood of enrollment ( 77 % telephone vs 44 % fax , P < .001 ) . The estimated number of smokers who quit based on the level of services utilized by referred smokers was 66 in the feedback and 36 in the gentle reminder practice s. CONCLUSION Providing comparative feedback on clinician referrals to a quit-line service had a modest impact with limited increased costs |
13,357 | 26,731,178 | Conclusion There is low level of evidence supporting the use of low-dose aspirin for the prevention of preeclampsia and SGA neonates in multiple gestations | Objective The objective of this study was to estimate the effect of low-dose aspirin in multiple gestations to prevent preeclampsia and small for gestational age ( SGA ) neonates . | OBJECTIVE This study was undertaken to compare rates and severity of gestational hypertension and preeclampsia , as well as perinatal outcomes when these complications develop , between women with twin gestations and those with singleton gestations . STUDY DESIGN This was a secondary analysis of prospect i ve data from women with twin ( n = 684 ) and singleton ( n = 2946 ) gestations enrolled in two separate multicenter trials of low-dose aspirin for prevention of preeclampsia . End points were rates of gestational hypertension , rates of preeclampsia , and perinatal outcomes among women with hypertensive disorders . RESULTS Women with twin gestations had higher rates of gestational hypertension ( relative risk , 2.04 ; 95 % confidence interval , 1.60 - 2.59 ) and preeclampsia ( relative risk , 2 . 62 ; 95 % confidence interval , 2.03 - 3.38 ) . In addition , women with gestational hypertension during twin gestations had higher rates of preterm delivery at both < 37 weeks ' gestation ( 51.1 % vs 5.9 % ; P < . 0001 ) and < 35 weeks ' gestation ( 18.2 % vs 1.6 % ; P < .0001 ) and also had higher rates of small-for-gestational-age infants ( 14.8 % vs 7 . 0 % ; P = .04 ) . Moreover , when outcomes associated with preeclampsia were compared , women with twin gestations had significantly higher rates of preterm delivery at < 37 weeks ' gestation ( 66.7 % vs 19.6 % ; P < .0001 ) , preterm delivery at < 35 weeks ' gestation ( 34.5 % vs 6.3 % ; P < .0001 ) , and abruptio placentae ( 4.7 % vs 0.7 % ; P = .07 ) . In contrast , among women with twin pregnancies , those who remained normotensive had more adverse neonatal outcomes than did those in whom hypertensive complications developed . CONCLUSIONS Rates for both gestational hypertension and preeclampsia are significantly higher among women with twin gestations than among those with singleton gestations . Moreover , women with twin pregnancies and hypertensive complications have higher rates of adverse neonatal outcomes than do those with singleton pregnancies PROBLEM : Effectiveness of early administered low‐dose aspirin in prevention of pregnancy‐induced hypertension ( PIH ) and fetal growth retardation in twin pregnancies was investigated in a r and omized placebo controlled , double‐blind trial in 47 twin pregnancies The National Institute of Child Health and Human Development conducts and supports research on all stages of human development from preconception to adulthood in order to better underst and the health of children , youths , adults , families , and communities . Health and human development information is made easily available on the site with a simple A to Z list , along with clinical trials and health education campaign information . Links to clinical trials , news releases , publications , and related web sites are also available , as well as information on research being conducted at present and supported by the National Institute of Child Health and Human Development OBJECTIVE To review the effect of assisted reproductive technology ( ART ) on perinatal outcomes , to provide guidelines to optimize obstetrical management and counselling of Canadian women using ART , and to identify areas specific to birth outcomes and ART requiring further research . OPTIONS Perinatal outcomes of ART pregnancies in subfertile women are compared with those of spontaneously conceived pregnancies . Perinatal outcomes are compared between different types of ART . OUTCOMES This guideline discusses the adverse outcomes that have been recorded in association with ART , including obstetrical complications , adverse perinatal outcomes , multiple gestations , structural congenital abnormalities , chromosomal abnormalities , imprinting disorders , and childhood cancer . EVIDENCE The Cochrane Library and MEDLINE were search ed for English- language articles from 1990 to February 2005 , relating to assisted reproduction and perinatal outcomes . Search terms included assisted reproduction , assisted reproductive technology , ovulation induction , intracytoplasmic sperm injection ( ICSI ) , embryo transfer , and in vitro fertilization ( IVF ) . Additional publications were identified from the bibliographies of these articles as well as the Science Citation Index . Studies assessing gamete intrafallopian transfer ( GIFT ) and zygote intrafallopian transfer ( ZIFT ) were excluded since they are rarely used in Canada . All study types were review ed . R and omized controlled trials were considered evidence of the highest quality , followed by cohort studies . Key studies and supporting data for each recommendation are summarized with evaluative comments and referenced . VALUES The evidence collected was review ed by the Genetics Committee and the Reproductive Endocrinology Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada ( SOGC ) and quantified using the Evaluation of Evidence Guidelines developed by the Canadian Task Force on the Periodic Health Examination . BENEFITS , HARMS , AND COSTS The type and magnitude of benefits , harms , and costs expected for patients from guideline implementation . This guideline has been review ed by the Genetics Committee and the Reproductive Endocrinology and Infertility Committee , and approved by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada and the Board of the Canadian Fertility and And rology Society . RECOMMENDATIONS 1 . Spontaneous pregnancies in untreated infertile women may be at higher risk for obstetrical complications and perinatal mortality than spontaneous pregnancies in fertile women . Further research is required to clarify the contribution of infertility itself to adverse obstetrical and perinatal outcomes . ( II-2A ) 2 . All men with severe oligozoospermia or azoospermia should be offered genetic/ clinical counselling for informed consent and offered karyotyping for chromosomal abnormalities before attempting IVF-ICSI . They should be made aware of the availability of tests for Y chromosome microdeletion . Some patients may consider the option of donor insemination . ( II-3B ) 3 . Couples exploring IVF-ICSI when the man has obstructive azoospermia should be offered genetic/ clinical counselling for informed consent and offered genetic testing for alterations in genes associated with cystic fibrosis ( CF ) before attempting IVF-ICSI . ( II-2A ) 4 . Pregnancies achieved by ovarian stimulation with gonadotropins and intrauterine insemination are at higher risk for perinatal complications , and close surveillance during pregnancy should be considered . It remains unclear if these increased risks are attributable to the underlying infertility , characteristics of the infertile couple , or use of assisted reproductive techniques . Multiple gestations remain a significant risk of gonadotropin treatment . ( II-2A ) 5 . Pregnancies achieved by IVF with or without ICSI are at higher risk for obstetrical and perinatal complications than spontaneous pregnancies , and close surveillance during pregnancy should be considered . It remains unclear if these increased risks are attributable to the underlying infertility , characteristics of the infertile couple , or use of assisted reproductive techniques . ( II-2A ) 6 . Women undergoing ART should be informed about the increased rate of obstetrical interventions such as induced labour and elective Caesarean delivery . ( II-2A ) 7 . Couples suffering from infertility who are exploring treatment options should be made aware of the psychosocial implication s of ART . Further research into the psychosocial impact of ART is needed . ( II-2A ) 8 . Singleton pregnancies achieved by assisted reproduction are at higher risk than spontaneous pregnancies for adverse perinatal outcomes , including perinatal mortality , preterm delivery , and low birth weight , and close surveillance during pregnancy should be available as needed . ( II-2A ) 9 . A significant risk of ART is multiple pregnancies . Infertile couples need to be informed of the increased risks of multifetal pregnancies . Although dichorionic twins are most common , the incidence of monochorionic twins is also increased . Risks of multiple pregnancies include higher rates of perinatal mortality , preterm birth , low birth weight , gestational hypertension , placental abruption , and placenta previa . Perinatal mortality in assisted conception twin pregnancies appears to be lower than in spontaneously conceived twin pregnancies . ( II-2A ) 10 . When multifetal reduction is being considered for high-order multiple pregnancies , psychosocial counselling should be readily available . Careful surveillance for fetal growth problems should be undertaken after multifetal reduction . ( II-2A ) 11 . To reduce the risks of multiple pregnancies associated with ART and to optimize pregnancy rates , national guidelines should be developed on the number of embryos replaced according to characteristics such as patient 's age and grade of embryos . ( II-2A ) 12 . Further epidemiologic and basic science research is needed to help determine the etiology and extent of the increased risks to childhood and long-term growth and development associated with ART . ( II-2A ) 13 . Discussion of options for prenatal screening for congenital structural abnormalities in pregnancies achieved by ART is recommended , including appropriate use of biochemical and sonographic screening . ( II-2A ) 14 . Further epidemiologic and basic science research is needed to help determine the etiology and extent of the increased risks of congenital abnormalities associated with ART . ( II-2A ) 15 . Couples considering IVF-ICSI for male-factor infertility should receive information , and if necessary formal genetic counselling , about the increased risk of de novo chromosomal abnormalities ( mainly sex chromosomal anomalies ) associated with their condition . Prenatal diagnosis by chorionic villus sampling ( CVS ) or amniocentesis should be offered to these couples if they conceive . ( II-2A ) 16 . Further epidemiologic and basic science research is needed to help determine the etiology and extent of the increased risks of chromosomal abnormalities associated with ART . ( II-2A ) 17 . Discussion of options for prenatal screening and testing for aneuploidy in pregnancies achieved by ART , adapted for maternal age and number of fetuses , is recommended , including appropriate use of biochemical and sonographic screening . ( II-2A ) 18 . The precise risks of imprinting and childhood cancer from ART remain unclear but can not be ignored . Further clinical research , including long-term follow-up , is urgently required to evaluate the prevalence of imprinting disorders and cancers associated with ART . ( II-2A ) 19 . The clinical application of preimplantation genetic diagnosis must balance the benefits of avoiding disease transmission with the medical risks and financial burden of in vitro fertilization . Further ethical discussion and clinical research is required to evaluate appropriate indications for preimplantation genetic diagnosis . ( III-B ) |
13,358 | 14,971,252 | The systemic antibiotics were uniformly beneficial in providing an improvement in AL when used as adjuncts to scaling and root planing ( SRP ) and were consistently beneficial , although of borderline significance , when used as adjuncts to SRP plus surgery or as a st and alone therapy .
5 .
When examining the effects of individual or combinations of antibiotics , it was found that there were statistically significant improvements in AL for tetracycline , metronidazole , and an effect of borderline statistical significance for the combination of amoxicillin plus metronidazole .
6 .
Improvements in mean AL were consistent for both chronic and aggressive periodontitis subjects , although the aggressive periodontitis patients benefited more from the antibiotics .
REVIEW ERS ' CONCLUSIONS 1 .
The use of systemically administered adjunctive antibiotics with and without SRP and /or surgery appeared to provide a greater clinical improvement in AL than therapies not employing these agents .
2 .
Due to a lack of sufficient sample size for many of the antibiotics tested , it is difficult to provide guidance as to the more effective ones | BACKGROUND Periodontal diseases are infections and thus systemically administered antibiotics are often employed as adjuncts for their control .
There are conflicting reports as to whether these agents provide a therapeutic benefit .
RATIONALE The purpose of this systematic review is to determine whether systemically administered antibiotics improve a primary clinical outcome measure , periodontal attachment level change .
FOCUSED QUESTION In patients with periodontitis , what is the effect of systemically administered antibiotics as compared to controls on clinical measures of attachment level ? | A sample of mentally retarded adolescents with moderate periodontal disease was given conventional treatment with and without adjunctive metronidazole therapy following consent of guardians . Antibiotics or placebo tables were taken 1 week following prophylaxis in a double blind clinical trial . Six months after the baseline examinations , there were no significant differences between the treatment and control groups in the mean attachment level or the proportions of microorganisms in subgingival pockets Sixteen patients diagnosed as having juvenile periodontitis were r and omly placed into one of two treatment groups . Group I received local and systemic tetracycline ( TTC ) , while Group II received no antibiotics . Osseous defects were grafted with allogeneic freeze-dried bone ( FDBA ) mixed with TTC powder ( Group Ia ) or FDBA alone ( Group IIa ) . Contralateral defects were debrided only in both Groups ( Ib and IIb ) . Direct reentry evaluation of 104 measurement sites demonstrated significantly greater bone fill ( mean = 2.8 mm ) and resolution of osseous defects ( mean = 72.7 % ) in the TTC/FDBA-treated group ( Ia ) as compared to the TTC plus debridement only ( Ib ) or no TTC-treated groups ( IIa and IIb ) . The results of this study indicate that of the modes of treatment investigated , the combination of local and systemic tetracycline coupled with freeze-dried bone allografts was the treatment of choice for defects associated with juvenile periodontitis The aim of the present study was to analyze the effect of systemic antimicrobial therapy and mechanical plaque control in patients with recurrent periodontal disease . 9 patients volunteered for the combined therapy . At a baseline examination they were r and omly distributed into 2 groups , one given tetracycline therapy for 2 weeks and the other metronidazole therapy for 1 week . A mechanical plaque control program comprising oral hygiene training , professional cleaning of all teeth and subgingival debridement at diseased sites was carried out at the baseline examination and at all recall visits , i.e. once every month during the first 6 months and then after 9 , 12 , and 18 months . The results demonstrated clinical ly and microbiologically that a combination of an initial antimicrobial and a continuous systematic mechanical plaque control program may be a valuable therapeutic approach in a strictly selected group of refractory patients . Recurrent periodontal lesions which still displayed severe inflammation despite renewed conventional therapy showed a marked reduction in probing depths , bleeding and suppuration from the pockets , and further , a reduced presence of spirochetes and motile rods during the trial . The results indicate that the level and longevity of success is also related to whether or not self-performed oral hygiene measures are sufficiently carried out . No superior effect of the combined program could be observed in cooperating patients receiving tetracycline as compared with those given metronidazole Periodontitis , a common cause of tooth loss in adult population s , is an inflammatory response to the overgrowth of anaerobic organisms such as spirochetes and bacteroides and , in some cases , micro-aerophilic organisms in the subgingival plaque . In the present investigation , using a double-blind clinical design , we sought to determine whether 1 week of metronidazole treatment plus debridement of the tooth surfaces was superior to 1 week of placebo treatment plus debridement ( positive control ) in reducing the subsequent amount of periodontal surgery given to the patients . Thirty-nine patients were r and omly assigned to either the metronidazole or placebo ( positive control ) groups . All patients were given the necessary scaling and root planing and were unsupervised in their usage of the medication . After the completion of this treatment , they were reexamined and it was found that the metronidazole regimen caused a significant reduction in surgical needs of about 5 teeth per patient compared to the positive control ( difference before and after treatment 8.3 + /- 6.8 teeth metronidazole versus 2.9 + /- 4.8 positive control , P = 0.007 ) . The difference between groups was maintained during the 2 to 3 years ' recall period . Metronidazole had a significant effect on the site specific reduction of spirochetes : 90 % of the sites in the metronidazole group versus 64 % in the positive-control group had a decrease in the percentage of spirochetes ( P less than 0.05 ) . We conclude that systemic metronidazole given 250 mg tid for 7 days in conjunction with debridement of the tooth surfaces can significantly reduce the need for periodontal surgery compared to the st and ard regimen which included only debridement BACKGROUND / AIMS The aim of this short-term open parallel longitudinal clinical study was to compare the clinical and microbiological efficacy of 2 different antibiotic regimes in the treatment of acute periodontal abscesses . METHOD After patient selection , a clinical examination was carried out recording the following variables : pain , edema , redness , swelling , bleeding on probing , suppuration , tooth mobility , lymphadenopathy , and probing pocket depth . Microbiological sample s were taken from the lesion and the patient was r and omly assigned to one of two antibiotic regimes : azithromycin or amoxicillin/clavulanate . Clinical variables were recorded , and microbiological sample s were taken , at 3 - 5 days , 10 - 12 days and 30 days . Additional mechanical treatment ( debridement and scaling ) was performed in the third visit ( 10 - 12 days ) . Blood and urine sample s were collected at baseline and after 10 - 12 days . Microbiological sample s were processed by anaerobic culturing , and isolated periodontal pathogens were tested for antibiotic susceptibility by means of the spiral gradient endpoint methodology . RESULTS 15 patients took azithromycin , and 14 amoxicillin/clavulanate . Subjective clinical variables demonstrated statistically significant improvements with both antibiotic regimes , which lasted for at least 1 month ( p<0.01 ) . Objective clinical variables also showed clear improvements , being statistically significant after 30 days with probing pocket depth in the azithromycin group ( p<0.01 ) . Microbiologically , short-term reductions were detected with both antibiotics , however fast recolonization occurred after the third visit . No significant differences were found between both treatment regimes . Antibiotic susceptibilities demonstrated no resistances for amoxicillin/clavulanate , while 2 - 3 strains of each studied pathogen were resistant to azithromycin . CONCLUSIONS However , both antibiotic regimes were effective in the short-term treatment of periodontal abscesses in periodontitis patients AIM To determine whether adjunctive metronidazole therapy would compensate for the poorer treatment response to scaling and root planing reported in smokers . METHOD A single-blind , r and omised clinical trial of 28 smokers and 56 non-smokers , stratified for periodontitis disease severity and r and omly allocated to 3 treatment groups : ( 1 ) Scaling and root planing using an ultrasonic scaler with local anaesthesia ( SRP ) , ( 2 ) SRP+ metronidazole tabs 200 mg tds for 7 days , ( 3 ) SRP + 2 subgingival applications of 25 % metronidazole gel . Probing depths ( PD ) and attachment levels ( AL ) were recorded with a Florida probe at baseline , 2 months and 6 months post treatment by a single examiner who was unaware of the treatment modality . Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance . RESULTS Reductions in probing depth at 6 months were significantly less ( p < 0.001 ) in the smokers ( mean 1.23 mm , 95 % confidence intervals = 1.05 to 1.40 mm ) than in the non-smokers ( 1.92 , 1.75 to 2.09 mm ) . Attachment level gains were approximately 0.55 mm and there was no statistically significant difference between smokers and non-smokers . There were no differences in any clinical measure in response to the three treatment regimens at 2 or 6 months for either smokers or non-smokers . A reduction in the proportion of spirochaetes was observed at 6 months which was less in smokers than in non-smokers ( p = 0.034 ) . Multiple linear regression analysis on probing depth at 6 months demonstrated that smoking was a significant explanatory factor ( p < 0.001 ) for poor treatment outcome , whilst the presence or absence of adjunctive metronidazole was not ( p = 0.620 ) . CONCLUSION This study confirms that smokers have a poorer treatment response to SRP , regardless of the application of either systemic or locally applied adjunctive metronidazole The present investigation was performed to study the effect of long-term , low dosage tetracycline therapy on advanced periodontal disease in humans . 14 volunteers participated in the trial . Each of the participants had at least 4 pairs of diseased sites around contralateral premolars and incisors with deep pockets and advanced bone loss . The trial extended over a 50-week period and was design ed as a double-blind split-mouth study . A Baseline examination included assessment s of oral hygiene , gingival conditions , probing depth , attachment level and analysis of the composition of the subgingival microbiota in sample s obtained from 8 selected diseased sites . All participants received oral hygiene instruction . In each patient 2 quadrants of the mouth , chosen at r and om , were treated by scaling and root planing . The 2 remaining quadrants were left unscaled . Following the Baseline examination the patients were r and omly distributed into 2 groups of 7 members each . In one of the groups the patients received tetracycline on a daily basis during a 50-week period . The participants of the control group received placebo . Reexaminations were performed 2 , 10 , 20 , 30 and 50 weeks after the Baseline examination . The findings demonstrated that in patients with advanced periodontal disease long-term tetracycline therapy in the absence of scaling result ed in the establishment of a subgingival microbiota almost devoid of motile bacteria and in markedly reduced signs of gingivitis , probing depth and attachment loss . In fact , the alterations observed as a result of tetracycline administration to patients with excellent self-performed plaque control were similar to those obtained by conventional scaling and root planing in the control group BACKGROUND The prevailing concept is that little or no clear benefit is derived from antibiotic therapy in chronic periodontitis . Studies to determine the effect of metronidazole plus amoxicillin ( M+A ) on adult periodontitis are question able because st and ard design for clinical trials was usually not used . In addition , there is no information about the effect of M+A as the sole therapy for periodontitis . METHODS A r and omized , triple-blind , controlled clinical trial was used to determine the effect of systemic administration of M+A , as the sole therapy , in progressive adult periodontitis . Forty-six subjects with moderate to advanced adult periodontitis who showed > or = 2 mm attachment loss in at least 2 sites in the previous 2 months were entered in the study . Subjects were r and omly distributed to a group who received 21 tablets of metronidazole 250 mg plus amoxicillin 500 mg , or to a group receiving a placebo ( 1 tablet every 8 hours for 1 week ) . Patients were examined every 2 months for 12 months . The M+A or placebo regimen was repeated at 4 and 8 months . No effort was made to change the oral habits of patients and they received no additional therapy . Differences between groups were assessed using the Mann-Whitney U test . The differences at every 2-month interval within each group were assessed using the ANOVA test . RESULTS Seven subjects ab and oned the study ; at 12 months the M+A group had 20 subjects and the placebo group 19 . There were no significant differences in the clinical parameters at baseline between the 2 groups . After 2 months and thereafter , the M+A group showed significant clinical improvement while the placebo group showed a progressive deterioration of periodontal status . At 12 months compared to baseline , subjects of the M+A group showed : 1 ) a significant overall mean attachment gain of 0.43 mm ( P = 0.005 ) ; 2 ) a significant decrease of active sites ( P < or = 0.03 ) ; 3 ) a significant increase of sites gaining attachment level ( P < or = 0.01 ) ; 4 ) a significant reduction of pocket depth ( P < or = 0.00006 ) ; and 5 ) a significant decrease in percentage of bleeding on probing sites ( BOP ) ( P < or = 0.0005 ) . Significant differences between both groups at all 2-month evaluations were found in overall mean attachment level ( P < or = 0.000004 ) , in percent of active sites ( P < or = 0.03 ) , and in percent of BOP sites ( P < or = 0.02 ) . Sites exhibiting > or = 2 mm of attachment loss in 2 successive or alternate evaluations , and periodontal abscess were noticed only in the placebo group . CONCLUSIONS A 1-week course of systemic M+A every 4 months , as the only therapy , arrests the progression of adult periodontitis and significantly improves the clinical parameters of the disease Abstract . The healing process following periodontal surgery for advanced adult periodontitis is described . Of the various indicators , tooth mobility ( TM ) is considered , and its relation to surgical treatment and the time lapse from the flap surgery is quantitatively modeled by non-parametric regression . Mobility is measured by an electronic apparatus , which also automatically performs the modeling . A new statistical method for TM prediction is demonstrated , and its quality is estimated . We show that the quality at the first step of prediction is approximately 0.7 . This indicates that the prediction method is able to model the effect of surgery on the healing process , although the r and om scattering of TM data recorded in the examined group is relatively large . The influence of periodontal surgery on TM , alone and in combination with systemic metronidazole , is quantitatively characterized in two groups of 12 patients each . In the test group , which received metronidazole , TM decreased significantly 1 week postoperatively , compared to the control group without the antibiotic . The gingival fluid flow rate ( GFFR ) and the percentage of spirochete morphotypes detected by darkfield microscopy exhibited a similar dependence . Significant differences in TM , GFFR and the percentage of spirochetes between the two groups were observed over a period of several weeks . Probing depths ( PD ) in both groups at 2 and 12 months after surgery did not reveal any category with pockets deeper than 4 mm . A gain of clinical attachment level of more than 2 mm ( CAL ) was observed at measurements of 16.7 % and 10.6 % on the test and control groups , respectively , 1 year after surgery Abstract The present investigation was performed to test the hypothesis that the persistence of inflammatory periodontal disease in human subjects is incompatible with the elimination of the anaerobic segments of the subgingival microbiota . 16 human subjects participated in the trial . They were selected on the basis of advanced periodontal disease which had produced at least 4 pairs of contra lateral teeth with advanced disease . At the Baseline examination the diseased sites were characterized by assessment of plaque , gingivitis , probing depth and attachment level . In addition , the composition of the subgingival microbiota was determined . One pair of sites was subjected to biopsy . In the tissue sample s the size of the inflammatory cell infiltrate was assessed . Following the Baseline examination the patients were r and omly distributed into 2 treatment groups , test and control . The patients of the test group received metronidazole for 3 periods of 2 weeks each , separated by intervals of 8 weeks . In addition , all patients received detailed oral hygiene instruction and a series of subgingival scalings involving 2 quadrants of the dentition , either the right or the left jaw quadrants , Reexaminations were performed 2 , 10 , 20 , 30 and 50 weeks after the Baseline examination . Biopsies from the predetermined sites were obtained at the reexaminations performed 2,20 and 50 weeks after the initiation of the therapy . The results demonstrated that the elimination of metronidazole sensitive bacteria from the subgingival microbiota result ed in the disappearance of clinical and histopathological signs of periodontal disease . Metronidazole has a unique bactericidal range against anaerobic bacteria . The present findings , therefore , emphasize the central role played by the anaerobic segments of the subgingival plaque for the maintenance of the inflammatory component of periodontal disease BACKGROUND Although the use of systemic antibiotics has been studied in patients with generalized aggressive periodontitis ( formerly rapidly progressive periodontitis ) , the use of adjunctive tetracycline fibers in these patients has not been reported . The purpose of the present study was to compare the clinical response of local versus systemic antibiotic treatment as adjuncts to scaling and root planing in patients with GAgP. METHODS After initial therapy and full-mouth scaling and root planing ( SRP ) , 30 patients were r and omly assigned to 1 of 2 antibiotic treatment groups . Probing depth ( PD ) , clinical attachment level ( CAL ) , and bleeding on probing ( BOP ) were recorded with an automated probe prior to SRP at baseline ( BL ) and 15 , 30 , 41 , and 54 weeks later . Three months after SRP , the patients were treated with amoxicillin/clavulanic acid ( 500 mg tid ; SRP + AUG group ) or with local tetracycline fiber in pockets with PD > or = 5 mm ( SRP + TCF group ) . RESULTS In both treatment groups , PD decreased significantly from BL to week 54 ( 6.2+/-1.5 mm to 4.7+/-1.4 mm for SRP + TCF and 6.5+/-1.4 mm to 4.2+/-0.6 mm for SRP + AUG ) . However , there was no statistically significant difference between the 2 groups in pocket reduction . Similarly , in both treatment groups , there were small but significant gains in CAL from BL to week 54 ( 12.0+/-1.8 mm to 11.3+/-1.8 mm for SRP + TCF and 12.3+/-1.5 mm to 11.2+/-1.2 mm for SRP + AUG ) . The difference in CAL gain between the 2 groups was not statistically significant . At the final examination , both groups showed significant PD reduction and CAL gain ( P < 0.001 ) compared to BL . The frequency and percentage of bleeding sites decreased significantly in both groups . At week 54 , this decrease was significantly greater in the SRP + AUG group ( 31.67 % for SRP + TCF versus 3.85 % for SRP + AUG ) . CONCLUSIONS These results indicate that the local delivery of tetracycline by a fiber or the systemic administration of amoxicillin/clavulanic acid given 3 months after scaling and root planing produced similar clinical outcomes over the 9-month observation period BACKGROUND AND AIM Several studies have reported adjunctive benefits to scaling and root planing ( SRP ) of systemic amoxycillin and metronidazole in the treatment of periodontal diseases . To date no comparisons have been made of these antimicrobials alone or in combination . The aim of this study was to compare the adjunctive benefits to SRP of amoxycillin and metronidazole alone and combined . METHODS 66 subjects < 46 years of age with advanced chronic periodontal disease participated in this r and omised , double blind , 4 parallel treatment group design ed study . All subjects received quadrant SRP and then were prescribed amoxycillin capsules ( 250 mg ) and metronidazole tablets ( 200 mg ) ( AM ) or lactate capsules and metronidazole ( PM ) or amoxycillin and calcium lactate tablets ( AP ) or lactate and calcium lactate ( PP ) . All medication was 3 of each per day for 7 days . Subgingival plaque sample s were obtained and probing depth ( PD ) , loss of attachment ( LOA ) , bleeding on probing ( BOP ) , suppuration ( SUPP ) and plaque ( DEP ) were recorded pre-treatment , 1 , 3 and 6 months post-treatment . RESULTS Final group sizes were : AM=15 , PM=16 , AP=16 and PP=15 . PD improved in all groups . Treatment effects were highly significantly different and always greatest in the AM and least in the PP groups . Benefits of PM and AP over PP were also noted . LOA improved in all groups and showed the same highly significant treatment differences , again favouring AM . BOP improved in all groups , particularly in AM compared to the other groups . SUPP improved in all groups and was virtually eradicated in AM with differences among treatments highly significant . DEP changed little in any group and there were no significant differences among groups . Microbiological data showed significant differences in favour of AM compared to PP and PM for total aerobes and anaerobes at 1 month . P. intermedia counts were always lower in active groups compared to PP and reached significance for AM and AP at 1 month and AM and PM at 3 months . CONCLUSION The significant differences among treatment groups and the overall trend in the data , in line with other studies , support the considerable adjunctive benefits to SRP of amoxycillin and metronidazole combined in the treatment of advanced chronic periodontal disease Previous reports have suggested that active progression of periodontitis may be correlated with increased collagenolytic activity , and that improved clinical conditions after tetracycline treatment may be explained by inhibition of host collagenase . Eighty-two patients with a recent history of periodontal abscesses and /or loss of gingival attachment level ( GAL ) despite active periodontal therapy were enrolled in a double-blind , r and omized , placebo-controlled trial . Clinical measurements , sampling of gingival crevicular fluid ( GCF ) and subgingival scaling were performed every 2 months . If any site exhibited greater than 2 mm loss of GAL or a periodontal abscess , patients were administered either 100 mg doxycycline per day for 3 weeks or placebo . During 12 months of monitoring , 55 patients exhibited recurrent active disease and were then r and omly assigned to either the doxycycline ( n = 30 ) or placebo ( n = 25 ) groups . Analysis of active collagenase and latent collagenase in GCF sample s were determined by functional assays and quantitated after SDS-PAGE and fluorography . Collagenase activities were assayed at sites exhibiting active destruction ( study site ) , at sites with pocket depth comparable to the study site but without active destruction , and at healthy sites . Clinical measurements of GAL and collagenase activity were made at intervals between 1 wk and 7 months after completion of the drug regime . Within 7 months , 15 out of 19 patients on placebo exhibited recurrent disease compared to 13 out of 29 patients on doxycycline . Collagenase activity exhibited large variations among patients and was analyzed as presence or absence of active collagenase with a logistic model . ( ABSTRACT TRUNCATED AT 250 WORDS 82 patients with a recent history of periodontal abscesses and /or loss of gingival attachment ( GAL ) despite active periodontal therapy were enrolled in a double-blind , r and omized , placebo-controlled trial . Clinical measurements and subgingival scaling were performed every 2 months . If any site exhibited greater than or equal to 2 mm loss of GAL or a periodontal abscess , patients were administered either 100 mg Doxycycline per day for 3 weeks or placebo . During 12 months of monitoring , 55 patients exhibited recurrent active disease and were then r and omly assigned to either the Doxycycline or placebo groups . Clinical measurements of GAL and microbiological culture of subgingival bacteria were made at intervals between 1 week and 7 months after completion of the drug regime . Within 7 months , 15 out of 19 patients on placebo exhibited recurrent disease compared to 13 out of 29 patients on Doxycycline , a relative risk reduction of 43 % ( p less than 0.05 ) for Doxycycline compared to placebo . Minimal inhibitory concentrations of Doxycycline for subgingival plaque sample s from active sites ranged between 25 - 100 micrograms/ml , which are several fold higher than reported crevicular fluid concentrations for this drug . However gingival crevicular fluid collagenase was inhibited in vitro at concentrations of 5 - 10 micrograms/ml Doxycycline . These data indicate that Doxycycline provides significant risk reduction of recurrent periodontitis in patients with active disease This study was design ed to evaluate the clinical significance of antibiotic therapy combined with guided tissue regeneration ( GTR ) therapy with a collagen membrane . The subjects were 20 adults diagnosed with periodontitis ( 20 intrabony periodontal defects ) . Ten patients were treated with GTR alone ( control group ) and the other 10 patients were treated with a combination of GTR and antibiotics ( antibiotic group ) . In the antibiotic group , minocycline ointment was applied locally before GTR therapy , and doxycycline and amoxyline were systemically administered after GTR therapy . Clinical manifestations , the presence or absence of exposed membrane , and microbiological findings were assessed 1 month before , immediately after , and 2 weeks , 6 weeks , and 3 months after GTR therapy . The results showed no significant differences in reduction of probing depth , probing attachment gain ( PAG ) , or the ratio of PAG to intraoperative depth of the intrabony defect ( vertical relative attachment gain ) between the antibiotic group and the control group before and 3 months after GTR therapy . A DNA probe test and specific enzymatic activity test revealed no significant differences in the improvement and the rate of bacterial negativity before , and 6 weeks and 3 months after , GTR therapy . These findings indicate that antibiotic therapy is not clinical ly beneficial when combined with GTR therapy with a collagen membrane In a study of the efficacy of modified Widman flap surgery and scaling and root planning accompanied by 1 of 4 systemic adjunctive agents , Augmentin , tetracycline , ibuprofen or placebo , it was observed that subjects differed in their response to therapy . The difference was only partially accounted for by the adjunctive agent employed . The purpose of the present investigation was to examine clinical and microbiological features in subjects who showed different levels of attachment change post-therapy . 40 subjects were subset into 3 groups based on mean attachment level change post-therapy . 10 poor response subjects showed mean attachment loss ; 19 moderate response subjects showed mean attachment gain between 0.02 - 0.5 mm and 11 good response subjects showed a mean gain of attachment > 0.5 mm . Clinical parameters were measured at 6 sites per tooth both pre- and post-therapy . Microbiological sample s were taken from the mesial aspect of each tooth and evaluated individually for their content of 14 subgingival taxa using a colony lift method and DNA probes . % of sites colonized by each species was computed for each subject both pre- and post-therapy . Significant differences were observed among treatment response groups for mean probing pocket depth , attachment level and % of sites with plaque pre-therapy . The poor response subjects had the lowest mean probing pocket depth and attachment level , but the highest plaque levels . Post-therapy , the poor response group exhibited the greatest degree of gingival inflammation as assessed by gingival redness and bleeding on probing . ( ABSTRACT TRUNCATED AT 250 WORDS The present study describes selected clinical and microbiological results obtained by treatment with local ( Elyzol ) and systemic ( Flagyl ) use of metronidazole alone and /or mechanical subgingival debridement in early onset periodontitis ( EOP ) . Twelve patients , with lesions not distributed as in classical localized juvenile periodontitis , were included . They were r and omly divided into local and systemic treatment groups each comprising 6 individuals , in each of whom 4 sites ( one site/quadrant ) with a probing depth of > or = 5 mm were selected and treated with separate treatment modalities . The overall treatment design provided 6 different test groups . Groups of quadrants received 1 ) scaling and root planing 2 ) local metronidazole treatment 3 ) systemic metronidazole treatment 4 ) local metronidazole combined with scaling and root planing 5 ) systemic metronidazole combined with scaling and root planing 6 ) No treatment . The microbiological and clinical effects of treatment modalities were monitored over 42 days . The results demonstrated reductions in mean counts of obligate anaerobic and capnophilic microorganisms coupled with significant improvements in mean clinical measurements ( gingivitis , probing depth , attachment level ) in all groups , except the untreated . Scaling and root planing provided an initial clinical improvement with a selective reduction of periodontopathogens ( 92.6 % obligate anaerobes , 42.9 % capnophilic microorganisms ) , whereas the combination of local or systemic metronidazole with scaling and root planing were found superior in reducing capnophilic bacteria ( 93.7 % and 93.4 % , respectively ) . It is of critical importance to have a treatment rationale for EOP , since bacterial differences exist in the etiological subforms of periodontitis . Microbial testing may be justified before prescribing the adjunctive antibiotic and selecting the mode of delivery for the successful clinical management of EOP Periodontal disease is a common infection-induced inflammatory disease among individuals suffering from diabetes mellitus . The purpose of this study was to assess the effects of treatment of periodontal disease on the level of metabolic control of diabetes . A total of 113 Native Americans ( 81 females and 32 males ) suffering from periodontal disease and non-insulin dependent diabetes mellitus ( NIDDM ) were r and omized into 5 treatment groups . Periodontal treatment included ultrasonic scaling and curettage combined with one of the following antimicrobial regimens : 1 ) topical water and systemic doxycycline , 100 mg for 2 weeks ; 2 ) topical 0.12 % chlorhexidine ( CHX ) and systemic doxycycline , 100 mg for 2 weeks ; 3 ) topical povidone-iodine and systemic doxycycline , 100 mg for 2 weeks ; 4 ) topical 0.12 % CHX and placebo ; and 5 ) topical water and placebo ( control group ) . Assessment s were performed prior to and at 3 and 6 months after treatment and included probing depth ( PD ) , clinical attachment level ( CAL ) , detection of Porphyromonas gingivalis in subgingival plaque and determination of serum glucose and glycated hemoglobin ( HbA1c ) . After treatment all study groups showed clinical and microbial improvement . The doxycycline-treated groups showed the greatest reduction in probing depth and subgingival Porphyromonas gingivalis compared to the control group . In addition , all 3 groups receiving systemic doxycycline showed , at 3 months , significant reductions ( P < or = 0.04 ) in mean HbA1c reaching nearly 10 % from the pretreatment value . Effective treatment of periodontal infection and reduction of periodontal inflammation is associated with a reduction in level of glycated hemoglobin . Control of periodontal infections should thus be an important part of the overall management of diabetes mellitus patients The effect of metronidazole was assessed in 20 subjects with untreated periodontitis , in a double-blind trial . Subjects received a 1-week course of drug or placebo immediately after baseline examination , and were reassessed 1 month and 3 months later . A 0.25 N constant force probe and darkfield microscopy were used . At 1 month , a difference was observed between the deepest individual pockets in experimental and control groups , with regard to change in probing depth and the proportions of non-motile organisms . At 3 months , differences were observed in 1 - 3 mm baseline pockets , where a greater proportion of control pockets increased in probing depth , and in 4 - 6 mm pockets , where a greater proportion of baseline bleeding pockets had ceased to bleed in the experimental group . The differences were of limited clinical significance when compared to studies where metronidazole was used as an adjunct to other therapy , and the results were equivocal with regard to the specific plaque hypothesis , since inhibition of connective tissue attachment loss was not unambiguously demonstrable A r and omized , double-blind , clinical study was done to assess the microbiological and clinical effects of metronidazole plus amoxicillin ( M+A ) as the only therapy in 46 patients with moderate to advanced progressive adult periodontitis . Patients were included in the study after at least 2 sites showed > or = 2 mm clinical attachment loss . Bleeding on probing , probing depth , and clinical attachment level were measured using on automated probe . The percentage of surfaces with plaque was recorded at day 0 , and at 2 and 4 months after therapy . No effort was made to change the oral hygiene habits of patients . Identification of Actinobacillus actinomycetemcomitans , Porphyromonas gingivalis , and Prevotella intermedia was assessed utilizing DNA technology at day 0 and 2 months after therapy . Twenty-three patients received metronidazole 250 mg plus amoxicillin 500 mg , 3 times/day for a week and 23 a placebo . Two patients in the placebo group were dropped at 2 months because they had taken antibiotics for medical reasons . Statistical analyses of differences between groups was done using the Mann-Whitney test , and the differences within each group were tested with ANOVA . There were no significant changes in surfaces with plaque in either group after therapy . The percentage of bleeding sites decreased significantly from baseline to 2 and 4 months in the M+A group ( P = 0.001 ) , and increased in the placebo group . Differences in bleeding on probing between groups were significant at 2 ( P = 0.018 ) , and 4 months ( P = 0.005 ) . The mean attachment level values at 2 and 4 months post-therapy improved significantly in the M+A group compared to the placebo group ( P = 0.001 ) . Treatment with M+A result ed in a significant mean reduction in probing depth at 2 and 4 months compared to baseline values ( P = 0.001 ) . The M+A group showed a significant reduction of sites with high levels of Pg ( P = 0.001 ) at 2 months compared with baseline values , and there was a significant reduction of sites with Pg and Pi in the M+A group compared with the placebo group . The results showed that a combined M+A treatment as the only therapy changes the proportion of some subgingival microorganisms and allows a significant improvement in clinical conditions BACKGROUND Regenerative treatment with enamel matrix proteins has been shown to promote healing in intrabony defects . However , up to now various postoperative antibiotic regimens have been used in combination with enamel matrix proteins and therefore it can not be excluded that the results may also be attributable to the effect of the antibiotic treatment . The aim of this r and omized , controlled , blinded , clinical investigation was to determine the effect of postsurgical administration of antibiotics on the healing of intrabony periodontal defects treated with enamel matrix proteins . METHODS Thirty-four patients each of whom exhibited one deep intrabony defect were r and omly treated with either enamel matrix proteins plus antibiotics ( test : EMD + AB ) or with enamel matrix proteins alone ( control : EMD ) . The antibiotic regimen consisted of a combination of 3 x 375 mg amoxicillin and 3 x 250 mg metronidazole daily for 7 days . The following parameters were recorded at baseline and at 1 year by the same calibrated and blinded investigator : plaque index ( PI ) , gingival index ( GI ) , bleeding on probing ( BOP ) , probing depth ( PD ) , gingival recession ( GR ) , and clinical attachment level ( CAL ) . Power analysis to determine superiority of antibiotic treatment showed that the available sample size would yield 85 % power to detect a 1 mm difference . RESULTS No statistically significant differences in any of the investigated parameters between the 2 groups were observed at baseline . No serious adverse events such as allergic reactions or abscesses after any of the treatments were observed during the entire study period . The results have shown that in the EMD + AB group the PD decreased from 9.1 + /- 1.5 mm to 4.5 + /- 1.1 mm ( P<0.0001 ) and the CAL changed from 11.0 + /- 1.6 mm to 7.5 + /- 1.4 mm ( P<0.0001 ) . In the EMD group the PD decreased from 9.0 + /- 1.7 mm to 4.3 + /- 1.7 mm ( P < 0.0001 ) and the CAL changed from 10.6 + /- 1.6 mm to 7.3 + /- 1.5 mm ( P < 0.0001 ) . There were no significant differences in any of the investigated parameters between the 2 groups . CONCLUSIONS It can be concluded that the systemic administration of amoxicillin and metronidazole adjacent to the use of EMD for the surgical treatment of intrabony periodontal defects does not produce statistically superior PD reduction and CAL gain when compared to treatment with EMD alone . Hence , the present results do not support the routine administration of amoxicillin and metronidazole following regenerative treatment with EMD Two previous double-blind studies have shown that 1 week of metronidazole , plus scaling and root planing , can significantly reduce the number of teeth per patient that require periodontal surgery , when compared to a positive-control treatment that consisted of 1 week of placebo treatment plus scaling and root planing . The only difference between the two studies was that in one , metronidazole or placebo tablets were taken at the beginning of the debridement procedures , while in the other , the tablets were taken after all debridement was completed . This article describes the results obtained by combining the data from both studies and using an analysis of variance to identify the effects of medication and those of the study protocol . There was an average reduction in surgical needs of about 7.1 teeth per patient using metronidazole compared to 2.4 teeth in the positive-control group ( P = 0.004 ) . In the deep pockets , there was a significant protocol effect because there were additional improvements associated with using the medications after the debridement was completed The present clinical trial was performed to study the effect of systemic administration of metronidazole and amoxicillin as an adjunct to mechanical therapy in patients with advanced periodontal disease . 16 individuals , 10 female and 6 male , aged 35 - 58 years , with advanced periodontal disease were recruited . A baseline examination included assessment of clinical , radiographical , microbiological and histopathological characteristics of periodontal disease . The 16 patients were r and omly distributed into 2 different sample s of 8 subjects each . One sample of subjects received during the first 2 weeks of active periodontal therapy , antibiotics administered via the systemic route ( metronidazole and amoxicillin ) . During the corresponding period , the 2nd sample of subjects received a placebo drug ( placebo sample ) . In each of the 16 patients , 2 quadrants ( 1 in the maxilla and 1 in the m and ible ) were exposed to non-surgical subgingival scaling and root planing . The contralateral quadrants were left without subgingival instrumentation . Thus , 4 different treatment groups were formed ; group 1 : antibiotic therapy but no scaling , group 2 : antibiotic therapy plus scaling , group 3 : placebo therapy but no scaling , group 4 : placebo therapy plus scaling . Re-examinations regarding the clinical parameters were performed , sample s of the subgingival microbiota harvested and 1 soft tissue biopsy from 1 scaled and 1 non-scaled quadrant obtained 2 months and 12 months after the completion of active therapy . The teeth included in groups 1 and 3 were following the 12-month examination exposed to non-surgical periodontal therapy , and subsequently exited from the study . Groups 2 and 4 were also re-examined 24 months after baseline . The findings demonstrated that in patients with advanced periodontal disease , systemic administration of metronidazole plus amoxicillin result ed in ( i ) an improvement of the periodontal conditions , ( ii ) elimination/suppression of putative periodontal pathogens such as A. actinomycetemcomitans , P. gingivalis , P. intermedia and ( iii ) reduction of the size of the inflammatory lesion . The antibiotic regimen alone , however , was less effective than mechanical therapy with respect to reduction of BoP - positive sites , probing pocket depth reduction , probing attachment gain . The combined mechanical and systemic antibiotic therapy ( group 2 ) was more effective than mechanical therapy alone in terms of improvement of clinical and microbiological features of periodontal disease The purpose of the present investigation was to assess the effects of periodontal surgery and 4 systemically administered agents , Augmentin , tetracycline , ibuprofen or a placebo on clinical and microbiological parameters of periodontal disease . 98 subjects were monitored at 2-month intervals at 6 sites per tooth for clinical parameters . Subgingival plaque sample s were taken from the mesial surface of each tooth at each visit and evaluated for their content of 14 subgingival species using DNA probes and a colony lift method . 40 subjects who exhibited loss of attachment > 2.5 mm at 1 or more sites during longitudinal monitoring were treated using modified Widman flap surgery at sites with probing pocket depth > 4 mm , subgingival scaling at all other sites and were r and omly assigned 1 of the 4 agents . Treatment was completed within 30 days during which time the subject took the assigned agent . Overall , subjects exhibited a mean attachment level " gain " of 0.34 + /- 0.10 mm ( SEM ) and a mean pocket depth reduction of 0.62 + /- 0.09 mm 10 + /- 4 months post-therapy . However , certain subjects in each treatment group showed a poor response . Subjects receiving antibiotics exhibited significantly more attachment level " gain " ( 0.57 + /- 0.15 mm , SEM ) than subjects receiving either ibuprofen or a placebo ( 0.02 + /- 0.10 ) . The differences between Augmentin and tetracycline groups were not significant , nor were the differences between ibuprofen and placebo . 10 months post-therapy , there was a reduction in the number of sites colonized in any subject group by detectable levels ( 10(3 ) ) of P. gingivalis . Species showing similar reductions were B. forsythus , P. intermedia and P. micros . Subjects receiving systemically administered antibiotics had a significant increase in the proportion of sites colonized by C. ochracea coupled with a greater decrease in the number of sites colonized by P. gingivalis , B. forsythus , P. intermedia and P. micros post-therapy than subjects not receiving antibiotics . The results of this investigation indicate that adjunctive systemic antibiotics increase periodontal attachment " gain " and decrease the levels of some suspected periodontal pathogens in subjects with evidence of current disease progression The purpose of this study was to assay the concentration of metronidazole in gingival fluid , to correlate clinical and microbiologic parameters of periodontal disease to each other and to the gingival fluid concentration of the drug . Ten subjects with a minimum of two contralateral pairs of periodontal pockets of greater than or equal to 5 mm were utilized . One side of the mouth was selected to serve as the root-planed site while the other was left untreated . On day 0 , plaque and bleeding-time indexes and probing depths were recorded . Subgingival plaque was analyzed using phase contrast microscopy . When root planing was completed , the subjects were prescribed either metronidazole or placebo three times daily for seven days . Within 24 hours of the last dose , and thereafter at intervals of 1 , 2 and 3 weeks , fluid sample s were assayed for metronidazole . Clinical and bacterial data were likewise recorded . The results indicate that root planing with metronidazole appears to be more effective in promoting periodontal health than root planing alone . Concentrations of metronidazole ranging from 5 to 20 micrograms/ml were detectable in fluid sample s obtained within 24 hours of administration of the last dose . No discernible levels could be found in sample s taken at the longer intervals This double-blind cross-over study was undertaken to assess the effect of systemically administered metronidazole when used as an adjunct to periodontal surgery for the treatment of moderate and advanced periodontitis . The effect of metronidazole was compared with that of placebo in patients undergoing modified Widman flap procedures in two areas of the same jaw which could be matched for type of tooth and severity of the periodontal disease . Clinical and microbiological parameters were examined prior to surgery and then 7 days , 1 month , and 3 to 6 months , postoperatively . The clinical parameters recorded were pocket depth ( PD ) , Sulcus Bleeding Index ( SBI ) , probing attachment level ( PAL ) , and patients ' preference and pain score . Subgingival plaque sample s were studied with dark-field microscopy for differential bacterial count . Pocket depths and SBIs were reduced significantly at all stages , in both groups . Probing attachment levels increased at 7 days , to significant levels only in the metronidazole group , subsequently PALs decreased in both groups with no significant differences between the groups . Although the differential bacterial count altered markedly in both groups at all times , only the straight rod count at 1 month was significantly ( P less than 0.05 ) lower in the metronidazole group . Metronidazole with surgery did not exert a significantly greater beneficial effect than placebo with surgery AIM The purpose of the present investigation was to determine the percentage and identity of antibiotic-resistant species in subgingival plaque and saliva sample s from chronic periodontitis patients treated by scaling and root planing followed by orally administered amoxicillin or metronidazole . METHOD In all , 20 chronic periodontitis patients were selected for study . After clinical and microbiological monitoring , subjects were r and omly assigned to receive either orally administered amoxicillin at the dosage of 500 mg , 3 times daily for 14 days or orally administered metronidazole at the dosage of 250 mg , 3 times daily for 14 days . For the antibiotic resistance determinations , subgingival plaque sample s were taken from six posterior teeth at baseline , and 90 days ; and from two r and omly selected teeth at 3 , 7 and 14 days during and after antibiotic administration . Sample s were plated on enriched blood agar plates with or without either 2 micro g/mL metronidazole or 2 micro g/mL amoxicillin . Colonies were counted at 7 days . Significant differences in percentage of resistant organisms over time were determined by the Quade test . Microbial growth was washed from antibiotic-containing media and the identity of species determined using checkerboard DNA-DNA hybridization . Data were compared with those obtained in a previous study from subjects receiving SRP only or SRP followed by 14 days of orally administered doxycycline . The level of doxycycline used to determine antibiotic resistance in that study was 4 micro g/mL. RESULTS The mean percentage of resistant isolates increased during antibiotic administration and returned to baseline levels by 90 days post therapy . The mean percentages ( + /- SEM ) of isolates resistant to 2 micro g/mL metronidazole were 53 + /- 9 , 65 + /- 9 , 79 + /- 4 and 69 + /- 7 at baseline , 3 , 7 and 14 days during antibiotic administration , and 57 + /- 4 , 64 + /- 5 , 62 + /- 7 and 47 + /- 6 at 3 , 7 , 14 and 90 days after antibiotic administration . At the same time points , the percentage of resistant isolates to amoxicillin was 0.5 + /- 0.2 , 22 + /- 12 , 14 + /- 5 and 37 + /- 11 during , and 31 + /- 11 , 8 + /- 3 , 3 + /- 2 and 3 + /- 0.6 after , administration . Antibiotic-resistant isolates of resistant species detected during or after therapy were also detected prior to therapy . The most prevalent resistant species in the metronidazole-treated group were : A. naeslundii 1 , S. constellatus , A. naeslundii 2 , S. mitis , S. oralis , A. odontolyticus , S. sanguis , and in the amoxicillin-treated group : S. constellatus , P. nigrescens , E. saburreum , A. naeslundii 1 , S. oralis , P. melaninogenica and P. intermedia . CONCLUSIONS Systemic antibiotic administration transiently increased the percentage of resistant subgingival species , but a major component of subgingival plaque remained sensitive to the agents during their administration . Antibiotic-resistant isolates of resistant species could be detected in sample s both prior to and after therapy . However , % antibiotic-resistant isolates returned to baseline levels 90 days after antibiotic administration BACKGROUND Periodontitis consists of a mixture of diseases , most of which respond favorably to traditional mechanical therapy . It is now recognized that advanced periodontitis does not always respond to conventional management with scaling , periodontal surgery , and oral hygiene measures . However , various types of antibiotics given systemically or locally improve the success rate of periodontal therapy . In short-term studies , it has been shown that metronidazole , when systemically administered after debridement , result ed in treatment benefits including less need for surgical intervention . METHODS In this double-blind study , we evaluated periodontal treatment involving initial non-surgical treatment , systemic administration of metronidazole for 1 week , and then follow-ups for scaling and root planing every 6 months , for 5 years . The study population consisted of 64 subjects ( 37 smokers and 27 non-smokers ) , mean age 36.3 ( + /-3.0 SD ) years , with severe periodontal disease . After initial scaling and root planing , patients were r and omly assigned to the intervention or placebo groups : 400 mg metronidazole or a placebo administered at 8-hour intervals for 1 week . The participants underwent an extensive clinical periodontal examination . Gingival crevicular fluid ( GCF ) was analyzed for spirochetes and granulocytes . Sample s were cultured for Actinobacillus actinomycetemcomitans ( A.a . ) , Porphyromonas gingivalis ( Pg . ) , and Prevotella intermedia ( Pi . ) . RESULTS The number of patients infected with A.a . , Pg . , Pi . , and spirochetes decreased during the study . Most patients who harbored spirochetes at the end of the study had these microorganisms at the beginning . Smokers responded less favorably to periodontal therapy than non-smokers . Non-smoking patients who required only non-surgical therapy in the intervention group showed statistically significant improvement in the clinical parameters after 5 years . Patients with complete healing , defined as the absence of inflamed sites > or = 5 mm , after 5 years were found only in the intervention group . The patients considered healthy after 5 years were the same patients found to be healthy after 6 months . CONCLUSIONS Decisive factors in the sustained long-term improvement of patients who respond satisfactorily to treatment are probably initial scaling and root planing ; a brief course of metronidazole ; and regular follow-up examinations at 6-month intervals for oral hygiene and scaling and root planing Several studies have indicated that the combination of metronidazole and spiramycin is synergistic against anaerobic bacteria and may be effective against oral infections . The present study sought to determine the efficacy and safety of a commercial preparation of these two antibiotics ( Rodogyl ) when used adjunctively in the treatment of advanced periodontal disease . In a double-blind parallel r and omized trial , 56 patients ( mean age = 44 years ) with advanced periodontitis ( 50 of whom completed the study ) were assigned to either the Rodogyl or placebo group . Both groups were thoroughly scaled and root planned for approximately 6 hours , with one group receiving Rodogyl for 2 weeks and the other a placebo . No other therapy was received during the study period . Two sites in each patient with probing depths of at least 7 mm were selected for study . Plaque level ( P1I ) , gingival inflammation ( GI ) , probing depth ( PD ) , and attachment level ( AL ) were measured at baseline , 14 days , 1 month , and then at monthly intervals up to 6 months . Subgingival bacteria were monitored with dark-field microscopy . The development of resistant bacteria , as well as side effects to the medications , was also monitored . The Rodogyl group exhibited a greater gain in AL ( 0.67 mm ) from the 2-month interval until the end of the study . Although this difference was statistically significant ( P less than 0.05 ) , it was not necessarily of biologic significance . There was a significantly greater decline in the proportion of spirochetes in the Rodogyl group at the 14-day interval , and this difference remained significant ( P less than 0.05 ) at all study intervals . No difference in the proportion of motile organisms was observed . ( ABSTRACT TRUNCATED AT 250 WORDS In a previous study , a double-blind between subject comparison of the effects of metronidazole and placebo tablets was completed over 22 weeks in 45 subjects with chronic periodontal disease ranging in severity from moderate ( PI = 2.0 - 3.9 ) to high ( PI = 4.0 - 6.0 ) . The results showed a significantly greater reduction in the mean probing depth of pockets with the use of metronidazole , but this reduction was apparent only in subjects with severe periodontal disease ( PI = 4.0 - 6.0 ) . 3 years later , 28 subjects attended . All groups still showed statistically significant improvements in all parameters when compared with those at the first visit . However , when compared with those at the end of the trial , there were statistically significant increases in gingival bleeding and calculus scores . An increase in plaque levels was also observed but this was not statistically significant . When subjects with moderate and severe periodontal disease were grouped together , there were no significant differences in any of the parameters between test and control groups . Moreover , the significantly greater reductions in mean probing depth of pockets , achieved with the use of metronidazole in the severe group at the end of the trial , had disappeared after 3 years . However , in subjects with mild disease , statistically significant reductions in pocket probing depth , not originally apparent , were observed 3 years later The one-year results of a regenerative procedure in patients treated with or without antibiotics are presented . Exp and ed polytetrafluoroethylene ( ePTFE ) was placed over m and ibular molar Class II furcation invasions and retained for four weeks . The patients in group 1 received no antibiotics ; patients in group 2 received amoxicillin/clavulanate potassium during the first 10 post-operative days . The initial differences in tested microorganisms and post-surgical inflammation indicated that the use of the antibiotic might enhance the long-term outcome . After one year , the reduction in mean probing depth of the furcation invasions was 2.0 + /- 1.2 mm for group 1 and 1.8 + /- 1.1 mm for group 2 . An overall gain of 0.8 mm of clinical attachment was found . Twenty-two of the 24 sites were re-entered . Wide individual variations were found but the changes between pre-treatment and one-year data for any of 6 linear measurements of hard tissue l and marks did not differ between groups or between pre-treatment and re-entry . A combination of an overall loss of 0.4 mm alveolar bone at the crest and 0.3 mm gain of bone at the bottom of the furcation defects was found . Volumetric analysis indicated an average 32 % bone fill for both groups , ranging from a decrease in defect volume by 84 % ( gain ) to an increase of the size of the furcation invasion by 66 % ( loss ) . A decrease in defect volume > 30 % was found at 7 sites from each group . The antibiotic may have controlled initial inflammation , but 12 months later it had no direct effect on bone regeneration or soft tissue attachment It has long been question ed whether antibiotics , used as a supplement to traditional therapy , provide any lasting benefit in the treatment of chronic periodontitis . This study was design ed to evaluate Spiramycin as an adjunct to scaling and root planing in the treatment of advanced chronic periodontitis . In total , 193 patients with advanced periodontitis were recruited in seven centres using selection criteria previously described . After undergoing thorough scaling and root planing , all patients r and omly received either Spiramycin , 1,500,000 international units , twice per day ( IU , bid ) for 14 days ( 96 patients ) , or a visually-identical placebo capsule ( 97 patients ) . The clinical parameters measured were plaque index , crevicular fluid level , probing depths , bleeding on probing and attachment level changes . Data was recorded at baseline , two- , eight- , 12- and 24-weeks visits . A total of 189 patients completed the study ( 96 placebo , 93 Spiramycin ) . Statistically significant differences in probing depth , favoring Spiramycin , were seen at two weeks ( p < 0.0125 ) , eight weeks ( p < 0.0020 ) , 12 weeks ( p < 0.0032 ) and 24 weeks ( p < 0.0075 ) . Spiramycin also produced a significant improvement in attachment level at 12 weeks ( p < 0.0146 ) . All other clinical parameters showed no difference between drug and placebo . This study shows that Spiramycin , as an adjunct to thorough scaling and root planing , provides a statistically significant improvement in probing depths for up to 24 weeks when compared with scaling and root planing alone . Both longer studies and microbiologic evaluations are necessary to determine whether a more lasting benefit is possible A double-blind clinical trial of oral penicillin as an adjunct to conventional treatment of localized juvenile periodontitis ( JP ) was conducted . Sixteen subjects with JP were paired on the basis of general similarity of disease , and within each pair the persons were assigned r and omly , one to a placebo group and one to a penicillin group . Neither patients nor therapist/examiner were aware of whether placebo or penicillin was being taken . All subjects received an initial scaling and root planing of all teeth and flap surgery of all affected sites . Every 12 weeks after surgery through Week 62 of the study , root planing and oral hygiene instructions were repeated . Phenoxymethyl penicillin ( 250 mg qid ) or placebo was started the day of surgery and each recall visit and lasted for 10 days . Clinical measurements were made at the beginning of the study and at each recall visit . In both groups there was a significant decrease in plaque scores , gingival inflammation , gingival bleeding and probeable depths for all sites and for affected sites . Similarly there was a significant increase in attachment level and radiographic bone height , and a total elimination of suppuration . The favorable changes were apparent at the first postsurgical recall ( Week 26 of the study ) and remained essentially the same through Week 62 . The magnitude of change in these parameters was similar to that reported by others for treatment regimes including tetracycline therapy . However , there were no differences in any parameters between the placebo and penicillin groups . Half of the subjects ( 4 in each group ) were continued in the study for another 9 months ( Week 98 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND In the last few years knowledge about periodontal infections has increased enormously , nevertheless practitioners are still seeking guidelines for suitable treatment concepts . METHODS The aim of this study was to examine the effect of doxycycline , metronidazole , and clindamycin used adjunctively in a 2-step nonsurgical procedure in patients with rapidly progressive periodontitis ( RPP ) . The first step included scaling , root planing , and polishing ( SRP ) in each quadrant using 4 to 5 visits . The second step included full-mouth enhanced root planing ( RP ) and wound dressing in 1 or 2 visits after SRP and the beginning of antibiotic therapy . Forty-eight patients ( mean age 32.4 years ) with generalized RPP , with an average of 16 sites with probing depths ( PD ) deeper than 8 mm , and high counts of Porphyromonas gingivalis were r and omly assigned to 4 different groups : group 1 ( doxycycline ) n = 12 , group 2 ( metronidazole ) n = 15 , group 3 ( clindamycin ) n = 11 , and group 4 ( control group ; no antibiotic treatment ) n = 10 . Clinical evaluations , including plaque index ( PI ) , sulcus bleeding index ( SBI ) , probing depth ( PD ) , clinical attachment level ( CAL ) , and bacteriological and crevicular cell sampling , were done at baseline ( BL ) , 3 weeks after SRP , and 6 and 24 months after RP . RESULTS After the first step ( SRP ) , we observed an improvement of PI and SBI in all 4 groups , but did not see any statistically significant PD reduction 3 weeks after SRP compared to baseline . However , 6 and 24 months after the second step ( RP ) we observed a significantly greater reduction of PD in groups 2 and 3 and a significantly greater CAL gain in comparison to groups 1 and 4 . After 24 months , the attachment level gain in group 1 and group 4 was less than 1.5 mm , and less than 1.0 mm in PD site categories 6 to 9 mm and > 9 mm . PI showed no significant difference between the groups throughout the period after SRP until 24 months , compared to 3 weeks after SRP . SBI decreased most in the metronidazole and clindamycin groups . P. gingivalis and Actinobacillus actinomycetemcomitans were almost completely eradicated in these 2 groups 24 months after RP . In addition , the phagocytotic capacity of crevicular polymorphonuclear neutrophils was increased in groups 2 and 3 after the second step . CONCLUSIONS The present results show that metronidazole and clindamycin are effective antibiotics when used adjunctively in a 2-step nonsurgical procedure of scaling and root planing in RPP patients The present study was undertaken to compare the efficacy of two antibiotics , spiramycin and tetracycline , with a placebo when used adjunctively with scaling and root planing in the treatment of advanced adult chronic periodontitis . This was a double-blind , parallel , r and omized trial with one factor ( drug ) at three levels . Ninety-six patients ( mean age 46 + /- 1 ) were r and omly assigned into one of three groups . All groups were scaled and root planed with each respective group receiving either spiramycin , tetracycline , or a placebo for 2 weeks . Two sites with probing depth of at least 7 mm were evaluated and the following clinical parameters were measured at baseline , 2 , 8 , 12 , and 24 weeks : plaque index , bleeding on probing , crevicular fluid , probing depth , and change in the attachment level . The changes in the subgingival bacteria were monitored also using a differential staining technique . Seventy-nine patients completed the study . At the end of 24 weeks , although all three groups had shown clinical improvement when compared to the baseline data , there were no significant intergroup differences in any of the clinical parameters measured . While the proportion of spirochetes were significantly decreased ( P less than 0.05 ) at 2- and 8-week intervals in both tetracycline and spiramycin groups ( 26 % to 0.04 % and 28 % to 0.04 % , respectively ) , compared to the placebo group ( 30 % to 7 % ) , only in the spiramycin group was the proportion of spirochetes significantly lower than the placebo group at the 24-week interval ( 3 % and 11 % , respectively ) . At week 24 , the proportion of spirochetes in the tetracycline group had rebounded to 7 % , which was not significantly different from the placebo group . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Bacterial contamination of membrane material negatively affects healing after guided tissue regeneration ( GTR ) procedures ; conversely , flap connective tissue integration on barrier material improves the clinical outcomes . The objective of this study was to evaluate the effect of topical application of antibiotics on : 1 ) clinical outcomes of GTR surgical procedures using titanium reinforced exp and ed polytetrafluoroethylene ( ePTFE ) periodontal membrane ; 2 ) bacterial colonization of membrane material ; and 3 ) flap connective tissue-membrane integration . METHODS Fifty-six deep interproximal bony defects were treated with GTR surgical procedures using titanium reinforced ePTFE periodontal membranes . Patients were r and omly assigned to 1 of the 2 antimicrobial treatment groups : the test group received weekly topical application of 25 % metronidazole gel and the control group received systemic antibiotics ( amoxicillin plus clavulanic acid 1 g/day for 14 days ) . Clinical outcomes were assessed at 1 year ; the amount of bacterial contamination and connective tissue integration on membrane material was evaluated at time of membrane removal by means of a morphological ( SEM ) method . RESULTS No statistically significant difference was found between test and control groups in terms of clinical attachment ( CAL ) gain ( baseline CAL - 12 months CAL ; P = 0.2 ) and probing depth ( PD ) reduction ( baseline PD - 12 months PD ; P = 0.6 ) . A greater increase in gingival recession ( REC ) ( 12 months REC - baseline REC ) was found in the test group compared to the control group ( P = 0.003 ) . The SEM analysis revealed no statistically significant ( t test ) difference between test and control groups in the number of fields positive to integrated connective tissue ( P = 0.82 ) , while the number of fields positive to bacteria was statistically higher ( P < 0.001 ) in the control group . CONCLUSIONS Local antibiotic administration is more effective than systemic use in preventing membrane contamination , but it does not improve clinical outcomes due to an interference of the vehicle ( gel ) with gingival tissues which may reduce the potential benefits derived from better control of the bacterial load In a previous study , subjects receiving either adjunctive tetracycline or Augmentin showed , on average , more attachment level gain 10 months post-therapy than subjects receiving either Ibuprofen or a placebo , although some subjects in each treatment group showed loss of attachment post-therapy . Since differences in treatment response might have been due to differences in the subgingival microbiota , the response to different therapies in subjects with different pre-therapy subgingival microbiotas was evaluated . 29 subjects exhibiting loss of attachment > 2.5 mm at 1 or more sites during longitudinal monitoring were treated by modified Widman flap surgery at deep sites , subgingival scaling at all other sites and were r and omly assigned one of the following agents : Augmentin , tetracycline , ibuprofen or a placebo . Treatment was completed within 30 days , during which time the subject took the assigned agent . Subgingival plaque sample s were taken from the mesial surface of each tooth at each visit and evaluated for their content of 14 subgingival species including P. gingivalis , P. nigrescens , P. intermedia and B. forsythus using DNA probes . 18 subjects with mean counts > 10(5 ) of 2 or more of these 4 species comprised the high test species group ; 11 subjects with mean counts > 10(5 ) of 0 or 1 of the species , the low test species group . Because this was a post-hoc analysis , the number of subjects in some of the treatment/test species groups was small . However , the 8 high test species subjects who received tetracycline showed the most attachment level gain ( 0.83 + /- 0.20 mm ) , while the 3 tetracycline-treated , low test species subjects showed minimal gain ( 0.05 + /- 0.28 mm ) 10 months post-therapy . Low test species subjects receiving Augmentin ( n = 2 ) showed a mean gain in attachment of 0.67 ( + /- 0.59 ) mm . The mean % of sites showing either attachment gain or loss > or = 2 mm was computed for each treatment/test species group . High test species subjects receiving tetracycline exhibited the best ratio of gaining to losing sites ( 16.2 ) , followed by low test species subjects receiving Augmentin ( 14.1 ) . Periodontal pockets < 7 mm pre-therapy in low test species subjects treated with Augmentin and high test species subjects treated with tetracycline showed attachment gain more frequently than attachment loss . The greatest proportion of gaining sites was seen at pockets > 6 mm , particularly in subjects receiving adjunctive tetracycline . Overall , the data indicated that a gain in mean attachment level post-therapy was significantly associated ( p < 0.001 ) with an increase in C. ochracea accompanied by a decrease in B. forsythus , P. gingivalis , P. intermedia and P. nigrescens . The 4 test species were decreased more in subjects receiving tetracycline . In contrast , Augmentin appeared to be effective in decreasing the % sites colonized by A. actinomycetemcomitans and in increasing the proportion of sites colonized by C. ochracea . Knowledge of the baseline microbiota should improve the choice of an appropriate adjunctive antibiotic for periodontal therapy The effect of adjunctive systemic metronidazole was studied in patients with moderate and advanced periodontitis recalcitrant to comprehensive non-surgical treatment . The material originated from a r and omly selected part of the population aged 31 to 40 years . After non-surgical treatment of 149 patients , 98 with persisting pathological pockets greater than or equal to 5 mm ( 52 men and 46 women ) became the subjects for the study . Clinical parameters were registered and pocket contents subjected to laboratory analysis . The subjects were r and omized into two groups according to a code list known only by the manufacturer and the statistician . The test group took three 400 mg metronidazole tablets daily for 1 week and the control group took placebo tablets . Re assessment 6 months later showed statistically significant clinical improvement , with a reduction in the number of sites greater than or equal to 5 mm in both test and control groups . Complete healing , with no pockets greater than or equal to 5 mm , was noted in 30 % of the test group and 9 % of the control group . The difference is statistically significant and shows the supplementary effect of adjunctive metronidazole in non-surgical treatment of moderate and advanced periodontitis 48 adult patients with untreated periodontitis harboring subgingival Actinobacillus actinomycetemcomitans and /or Porphyromonas gingivalis as assessed by PCR were r and omly assigned to receive full-mouth scaling alone ( control ) or scaling with systemic metronidazole plus amoxicillin and supragingival irrigation with chlorhexidine digluconate ( test ) . In patients harboring A. actinomycetemcomitans intraorally at baseline , the adjunctive antimicrobial therapy result ed in a significantly higher incidence of probing attachment level ( PAL ) gain of 2 mm or more compared to scaling alone over 12 months ( p<0.05 ) . In addition , suppression of A. actinomycetemcomitans in subgingival plaque below detectable levels was associated with an increased incidence of PAL gain . In contrast , patients initially harboring P. gingivalis but not A. actinomycetemcomitans in the oral cavity showed a significantly higher incidence of PAL loss following adjunctive antimicrobial therapy compared to scaling alone ( p<0.05 ) . When the presence of pathogens at baseline was disregarded in the analysis , adjunctive antimicrobial therapy did not significantly enhance clinical treatment outcome . The results indicated that adults with untreated periodontitis harboring A. actinomycetemcomitans may benefit from the adjunctive antimicrobial therapy for a minimum of 12 months , whereas , the regimen may adversely affect the clinical treatment outcome of patients harboring P. gingivalis but not A. actinomycetemcomitans The objective of this study was to test the efficacy of scaling and root planing with or without adjunctive tetracycline therapy in the treatment of periodonitis in humans . The presence of plaque , gingival inflammation , probing depths and attachment levels was assessed for all teeth in 12 patients with chronic , advanced periodontitis . After an initial examination all patients were given detailed oral hygiene instructions . The teeth in one-half of each arch were then scaled and root planed . The teeth in the contralateral half were not treated . Six patients were given tetracycline ( 1 gm/day ) during the first and second weeks and the seventh and eighth weeks of the trial . The study thus included four different treatment groups : 1 ) no treatment , 2 ) scaling and root planing alone , 3 ) tetracycline administration alone , and 4 ) scaling and root planing combined with tetracycline administration . All patients were reexamined at 8 and 25 weeks subsequent to the initiation of therapy . Both PlI and GI scores decreased significantly in all groups . The GI scores were significantly lower in the scaled and root planed areas as compared to the contralateral sides at both the 8- and 25-week examinations . The PlI score was lower in the scaled and root planed areas only at the 25-week interval . The gingival probing depths were reduced in all groups . A significantly greater decrease in probing depth , however , was noted in scaled and root planed areas . There was a trend to gain of attachment in the treated areas but the magnitude of the gain was very small . The findings of the trail also revealed that the administration of tetracycline had only a minor effect on the parameters examined Twenty-seven patients with a recent history of periodontal abscesses and /or loss of gingival attachment level ( GAL ) despite active periodontal therapy were enrolled in a double-blind , r and omized , placebo-controlled trial . Clinical measurements and subgingival scaling were performed every 2 months . When a site exhibited greater than or equal to 2 mm loss of GAL or a periodontal abscess , patients were administered either doxycycline at a dosage of 200 mg to start and 100 mg per day for 3 weeks , or a placebo . Clinical measurements of GAL and microbial analysis of subgingival plaque at study and control sites were made at the time of active disease and at intervals of 1 week and 7 months after completion of the drug regime . Plaque sample s were screened for the presence of Actinobacillus actinomycetemcomitans ( Aa ) , Porphyromonas gingivalis ( Pg ) , Bacteroides intermedius ( Bi ) , Eikenella corrodens ( Ec ) and Fusobacterium nucleatum ( Fn ) by indirect immunofluorescence antibody technique and for spirochetes ( Sp ) using Ryu 's stain . Based on presence or absence analysis of the sum scores of the 6 pathogens , both the placebo ( n = 10 ) and the doxycycline groups ( n = 17 ) exhibited similar scores at the time of detection of active disease ( mean placebo = 2.38 + /- 0.32 ; mean doxycycline = 2.95 + /- 0.27 ; P = 0.18 ) . One week after treatment , the probability of detection was unchanged in the placebo group ( mean placebo = 3.14 + /- 0.47 ) , but was significantly reduced in the doxycycline group ( mean doxycycline = 1.77 + /- 0.26 ; P = 0.0002 ) . Study ( active ) sites exhibited scores 2 to 3 times higher than control ( inactive ) sites before doxycycline treatment . ( ABSTRACT TRUNCATED AT 250 WORDS This study was design ed to compare both clinical and microbiological changes during the treatment of advanced periodontal disease with mechanical debridement , with or without the adjunctive use of either spiramycin or tetracycline . The study , which included 96 patients with advanced periodontitis , was performed as a controlled double-blind parallel r and omized trial . All patients received thorough scaling and root planing as well as adjunctive placebo or spiramycin or tetracycline . Probing depth measurements , attachment level changes , plaque level , gingival crevicular fluid , bleeding on probing and microbiological evaluation were carried out at baseline , 2- , 8- , 12- and 24-week visits . Seventy-nine patients ( 24 placebo , 27 tetracycline and 28 spiramycin ) completed the study . At 24 weeks there were no intergroup differences in the improvement of any of the clinical parameters . Spiramycin was the only antibiotic which produced a significantly greater decrease in the proportion of spirochaetes than the placebo group at the 24-week visit . It was concluded that mechanical debridement alone was sufficient in decreasing the subgingival bacteria to a level which would result in the return to periodontal health . The study was not long enough to determine whether or not the difference in spirochaete level was an indication that the spiramycin group would have maintained the benefits of treatment for a longer time Treponema denticola , Porphyromonas gingivalis , and Bacteroides forsythus each possesses an enzyme(s ) that hydrolyzes the synthetic substrate benzoyl-DL-arginine-naphthylamide ( BANA ) . The presence of these organisms in a subgingival plaque sample can be determined by the ability of the plaque to hydrolyze BANA . In the present study , we describe the usefulness of the BANA test at various stages of a clinical trial of the efficacy of metronidazole in the treatment of periodontal disease . A BANA-positive test was significantly associated with high levels and proportions of spirochetes in the plaque , so that it provided information comparable with that which could be obtained by a microscopic examination of the plaque . Patients with such anaerobic spirochetal infections were r and omly assigned to a group receiving either metronidazole or placebo ( 250 mg , three times a day ) for one week and whose teeth were scaled and root-planed . The advantages of the decision that metronidazole be used were apparent from the comparison with the results obtained in the patients who received only the scaling and root planing . The initially BANA-positive teeth in the patients treated with metronidazole , scaling , and root planing gained attachment and exhibited a significant reduction in the need for periodontal surgery , when compared with the BANA-positive teeth in the patients who received only placebo , scaling , and root planing . After the conclusion of this therapy , those teeth with persistent BANA-positive plaques had significantly higher proportions and levels of spirochetes than did the teeth with BANA-negative plaques . A tooth site which tested BANA-positive after the initial therapy lost significantly more attachment in the year following active treatment than did a tooth site that tested BANA-negative , i.e. , a mean difference of 0.48 mm per year . The ability of the BANA test to detect an anaerobic infection due to the BANA-positive species and possibly to predict future attachment loss indicates that this test may be helpful in the management of the periodontally diseased patient The objective of this study was to compare the efficacy of a systemic antibiotic ( doxycycline ) and a non-steroidal anti-inflammatory drug ( ibuprofen ) , administered either separately or combined , as an adjunctive treatment of scaling/root planing ( SRP ) . Thirty-two subjects diagnosed with generalized moderate adult periodontitis and having at least 2 teeth with > or = 5 mm probing depth were r and omly divided into 4 groups . Each group was treated with oral doxycycline and /or ibuprofen for 6 weeks as follows : group 1 , doxycycline 200 mg the first day followed by 100 mg per day ; group 2 , ibuprofen 800 mg per day ; group 3 , doxycycline plus ibuprofen scheduled as in groups 1 and 2 ; group 4 , one placebo capsule/day ( control ) . A split mouth design was utilized in each subject such that half of the teeth received one session of scaling/root planing ( SRP ) , while the other half received no SRP . Plaque index ( PI ) , gingival index ( GI ) , probing depth ( PD ) , and clinical attachment level ( CAL ) using a customized acrylic stent were recorded at baseline and at 3 , 6 , 12 , and 24 weeks following SRP . Analysis using ANOVA and Student t-test showed statistical significance ( P < or = 0.05 ) from baseline data in : 1 ) gains of 0.4 mm and 0.5 mm of CAL for groups 1 and 3 , respectively ; 2 ) reduction of 0.7 mm PD for group 3 ; 3 ) reduction of 0.4 and 0.1 GI scores for groups 1 and 3 , respectively ; and 4 ) gain of 0.5 mm CAL and reductions of 0.4 mm PD and 0.2 GI score for the SRP group when compared to the no SRP group at 24 weeks . It may be concluded that the adjunctive use of systemic doxycycline alone or in combination with ibuprofen results in a statistically significant , yet modest clinical , improvement beyond that obtained by scaling/root planing BACKGROUND , AIMS The aim of this double-blind , parallel study was to evaluate the adjunctive effects of systemically administered amoxicillin and metronidazole in a group of adult periodontitis patients who also received supra- and subgingival debridement . METHODS 49 patients with a diagnosis of generalised severe periodontitis participated in the study . R and om assignment result ed in 26 patients in the placebo ( P ) group with a mean age of 40 years and 23 patients in the test ( T ) group which had a mean age of 45 years . Clinical measurements and microbiological assessment s were taken at baseline and 3 months after completion of initial periodontal therapy with additional placebo or antibiotic treatment . Patients received coded study medication of either 375 mg amoxicillin in combination with 250 mg metronidazole or identical placebo tablets , every 8 hours for the following 7 days . RESULTS At baseline , no statistically significant differences between groups were found for any of the clinical parameters . Except for the plaque , there was a significantly larger change in the bleeding , probing pocket depth ( PPD ) and clinical attachment level ( CAL ) in the T-group as compared to the P-group after therapy . The greatest reduction in PPD was found at sites with initial PPD of > or = 7 mm , 2.5 mm in the P-group and 3.2 mm in the T-group . The improvement in CAL was most pronounced in the PPD category > or = 7 mm and amounted to 1.5 mm and 2.0 mm in the P- and T-groups , respectively . No significant decrease was found in the number of patients positive for any of the test species in the P-group . The number of patients positive for Porphyromonas gingivalis , Bacteroides forsythus and Prevotella intermedia in the T-group showed a significant decrease . After therapy there was a significant difference between the P- and the T- group in the remaining number of patients positive for P. gingivalis , B. forsythus and Peptostreptococcus micros . 4 subgroups were created on the basis of the initial microbiological status for P. gingivalis positive ( Pg-pos ) and negative patients ( Pg-neg ) in the P- and the T-groups . The difference in reduction of PPD between Pg-pos and Pg-neg patients was particularly evident with respect to the changes in % of sites with a probing pocket depth > or = 5 mm . This % decreased from 45 % at baseline to 23 % after treatment in the Pg-pos placebo subgroup and decreased from 46 % to 11 % in the Pg-pos test subgroup ( p < or = 0.005 ) . In contrast , the changes in the proportions of sites with a probing pocket depth > or = 5 mm in the Pg-neg placebo and Pg-neg test subgroup were similar , from 43 % at baseline to 18 % after treatment versus 40 % to 12 % respectively . CONCLUSIONS This study has shown that systemic usage of metronidazole and amoxicillin , when used in conjunction with initial periodontal treatment in adult periodontitis patients , achieves significantly better clinical and microbiological results than initial periodontal treatment alone . Moreover , this research suggests that especially patients diagnosed with P. gingivalis benefit from antibiotic treatment The purpose of this study was to conduct a direct comparison of two dose regimens of minocycline to determine 1 ) whether they achieved crevicular fluid concentrations in a therapeutic range ; and 2 ) the frequency of side effects . In a double-blind design , 30 patients divided into 2 groups were given either 100 mg minocycline or 200 mg minocycline per day for an 8-day period . The concentration of minocycline in the gingival clevicular fluid ( GCF ) at 8 days was 4.77 micrograms/ml for the 100 mg a day group and 5.97 micrograms/ml for the 200 mg a day group and at 15 days was 4.30 micrograms/ml for the 100 mg a day group and 4.17 micrograms/ml for the 200 mg a day group . There was no significant difference in the antibiotic concentration in the gingival crevicular fluid between the 2 groups . Reported adverse experiences to the minocycline were greater in the 200 mg a day group . Short-term changes in periodontal health as measured by plaque index , gingival index , pocket depth , and bleeding upon probing showed improvements in all parameters over the 15 day period . There were no significant differences in these parameters between the 100 mg a day and 200 mg a day group . At 8 days reduced levels of Porphyromonas gingivalis and Prevotella intermedia were achieved but they were not eliminated from infected subgingival sites in either group . Achieving bacteriostatic concentrations of GCF , fewer side effects , and the potential for better compliance suggests that a single daily dose of 100 mg minocycline should now be investigated for its efficacy in managing periodontal infections manifesting as periodontitis The present study describes results on selected clinical and microbiological parameters obtained by treatment with local ( Elyzol ) and systemic ( Flagyl ) use of metronidazole alone and /or mechanical subgingival debridement in adult periodontitis . Patients were r and omly divided into local and systemic treatment groups each comprising 5 individuals in each of whom 4 sites ( one site/ quadrant ) with a probing depth of > or = 5 mm were selected and treated with separate treatment modalities . The overall treatment design provided 6 different test groups . Groups of quadrants received : ( 1 ) scaling and root planing ; ( 2 ) local metronidazole treatment ; ( 3 ) systemic metronidazole treatment ; ( 4 ) local metronidazole combined with scaling and root planing ; ( 5 ) systemic metronidazole combined with scaling and root planing ; ( 6 ) no treatment . The microbiological and clinical effects of treatment modalities were monitored over a period of 42 days . All treatments result ed in clinical improvements ( gingivitis , probing pocket depth , attachment level ) except for the untreated group . Parallel to the clinical changes , all treatments reduced the number of total bacteria and proportions of obligately anaerobic microorganisms . Although both of the combined treatment groups responded to therapy with better resolution of infection that the pure mechanical and pure metronidazole treatments , local metronidazole in combination with scaling and root planing seems to be more effective in terms of producing both clinical and microbial improvements The systemic use of a single antibiotic was compared to that of a sequential antibiotic regimen in the treatment of A. actinomycetemcomitans and /or P. gingivalis-associated periodontitis . Eleven patients with recurrent/progressive periodontitis and demonstrating subgingival infection with A.a . and /or P.g . were selected . Six patients received oral administration of doxycycline ( Do ) , 200 mg the first day and 100 mg for 4 days thereafter , and then amoxicillin/clavulanate potassium ( Au ) , 500 mg 3 times daily for 5 days . The other 5 patients received only doxycycline for 10 days . Eight sites with > or = 5 mm probe depth per patient were selected , of which 4 received root planing at time 0 . Clinical measurements ( GI and PI , probing pocket depth , probing attachment level , and bleeding upon probing/suppuration ) and microbial infection levels ( 2 sites/patient as per DNA probe ) for A.a . and P.g . were recorded at 0 , 4 , 12 , and 25 weeks . Clinical data were subjected to statistical analysis of variance and t-tests for significance . The Do + Au groups produced significant reduction in probing pocket depth ( PPD ) at 4 , 12 , and 25 weeks ( 1.1 , 1.3 , and 1.1 mm , respectively ) . The Do group produced significant reduction in PPD only at 4 and 12 weeks ( 0.8 and 0.8 mm ) ; the Do + Au group produced significant gain of 0.8 mm in probing attachment level at 4 and 12 weeks ; and the Do + Au group in conjunction with root planing produced the most sustained reduction in PPD and gain in PAL . These findings suggest that the sequential use of multiple antibiotic agents may offer greater promise as an adjunctive treatment approach for the management of recurrent and /or progressive periodontitis than a single antibiotic regimen The aim of this study was to assess the clinical and microbiologic effects of the combination of amoxicillin and metronidazole therapy as an adjunct to mechanical treatment in the management of localized juvenile periodontitis . Twenty-five localized juvenile periodontitis ( LJP ) patients from a Brazilian population were r and omly allocated into an experimental group receiving mechanical treatment and antibiotics , and a control group receiving mechanical treatment and placebo . Clinical and radiographic assessment s , as well as microbiologic sampling for Actinobacillus actinomycetemcomitans , were performed at baseline and one year after the end of the treatment . At the termination of the study A. actinomycetemcomitans could be isolated from the oral cavity of all patients in the control group who harbored the bacterium at baseline and in 4 out of 8 patients in the experimental group . Both treatment modalities result ed in significant benefit on an individual basis . The experimental group , however , displayed better results than did the control group regarding gingival index ( GI ) , probing depth ( PD ) , clinical attachment level ( CAL ) , and radiographic analysis of crestal alveolar bone mass , but not with respect to plaque index ( PI ) . No serious adverse effects of the antibiotic treatment were observed in the present study Systemic doxycycline is one of the more common antimicrobial agents used in the treatment of periodontal infections and yet little is known of its effect on subgingival plaque composition during and after its administration . The purpose of the present investigation was to evaluate changes in subgingival plaque composition during and after 14 days of doxycycline administration . 20 subjects with adult periodontitis were r and omly assigned to test ( n = 10 ) and control ( n = 10 ) groups . The subjects received full mouth clinical assessment of pocket depth , attachment level , BOP , gingival redness , suppuration and plaque accumulation at baseline and 90 days . All subjects received full mouth SRP at baseline and , additionally , the test group received 100 mg doxycycline daily for 14 days . Subgingival plaque sample s were taken from the mesial surface of up to 28 teeth in each subject at baseline and 90 days . In addition , plaque sample s were taken from 2 r and omly selected teeth at 3 , 7 and 14 days during and after antibiotic administration . Control subjects were sample d at the same time points . Counts of 40 subgingival species were determined using checkerboard DNA-DNA hybridization and fluorescent detection . Significance of differences between test and control groups was determined at each time point using the Mann Whitney test . Significance of changes over time within test and control groups was determined using the Quade test . A modest but significant reduction in mean pocket depth from baseline to 90 days occurred in both test and control groups . A significant decrease in the % of sites with gingival redness occurred in the test group . There were no significant differences in proportions between test and control groups for 33 of the test species at any time point . Test subjects exhibited lower proportions of 4 Actinomyces species and an increase in 3 Streptococcus species during antibiotic administration . After cessation of doxycycline , Actinomyces sp. increased while Streptococcus sp. returned to baseline proportions . The relationship between these 2 genera appeared to be reciprocal ; an increase in one was accompanied by a decrease in the other . Periodontal pathogens including B. forsythus , P. gingivalis , T. denticola and A. actinomycetemcomitans were not significantly altered by oral administration of doxycycline using conventional therapeutic dosage The aim of the study was to evaluate the adjunctive effect of systemic tetracycline ( 250 mg qds for 14 days ) in sequential root planing and surgical phases of treatment in a r and omised , double-blind controlled trial . 38 patients who were under 26 years of age , in good general health and with localised ( 15 test/15 control ) or generalised ( 4 test/4 control ) early onset periodontitis completed the non-surgical phase . Data were analysed by ANOVA using baseline covariates and transformations where appropriate . Improvements in probing depth , probing attachment level and bleeding on probing were significantly better in the group treated with adjunctive tetracycline , at 3 months post-treatment . 26 patients ( 13 test/13 control ) subsequently completed the surgical phase ( modified Widman flap surgery with adjunctive tetracycline or placebo as before ) and were re-examined at 6 months and 12 months . In the test group , 58 % of the originally affected teeth required surgery compared to 75 % in the control group . Surgery produced further reductions in mean probing depths but no further gains in probing attachment . There were no further statistically significant differences between test and control groups for any of the clinical measures , although the tetracycline group appeared to maintain an advantage . In conclusion , systemically administered tetracycline is a useful adjunct in the management of early onset periodontitis , particularly in non-surgical treatment BACKGROUND / AIMS The aim of the study was to investigate the clinical and microbiological effects of azithromycin as an adjunct to the non-surgical treatment of periodontitis in adults . Azithromycin is an antibiotic which is taken up by phagocytes and is released over long periods in inflamed tissue but requires a total of only three doses of 500 mg to produce its therapeutic effect . METHOD 46 patients were treated in a double-blind placebo-controlled study with assessment s at weeks 0 , 1 , 2 , 3 , 6 , 10 and 22 . Throughout the trial measurements were made of plaque , gingival bleeding , calculus , probing pocket depths and bleeding on probing . Microbiological sampling was carried out from a selected pocket > or=6 mm at each visit . The regime employed consisted of OHI , scaling and root planing at weeks 0 , 1 and 2 with reinforcement of OHI and minimal scaling at weeks 6 , 10 and 22 . Patients were r and omly assigned to receive either azithromycin , ( A ) , or placebo capsules , ( C ) , 500 mg , 1x daily for 3 days at week 2 . 44 patients completed the study . Mean pocket depths were analysed using analysis of covariance in 3 groups with initial pocket depth values of 1 - 3 mm , 4 - 5 mm and > or=6 mm . RESULTS The results of the microbiology have been reported in a separate paper . The clinical data showed that by week 22 a lower % of pockets initially > 5 mm deep remained above that level in the 23 patients taking azithromycin ( A ) , than the 21 taking the placebo ( C ) , ( A , 5.6 % ; C , 23.3 % ) . Also at week 22 , for pockets initially 4 mm or more , the test group had fewer pockets > 3 mm deep ( A , 26.1 % ; C , 44.3 % ) , fewer failing to improve in probing depth ( A , 6.6 % ; C , 21.6 % ) and fewer continuing to bleed on probing ( A , 46.9 % ; C , 55.6 % ) when compared with the control group . Pocket depths initially 4 - 5 mm or 6 - 9 mm analysed by analysis of covariance showed lower mean pocket depths in the patients on azithromycin , at weeks 6 , 10 and 22 , ( pockets initially 4 - 5 mm , p<0.001 on all occasions , pockets initially 6 - 9 mm , p<0.001 , week 6 ; p < 0.003 , week 10 ; p<0.001 , week 22 ) . CONCLUSIONS Azithromycin may be a useful adjunct in the treatment of adult periodontitis , particularly where deep pockets are present AIM The current investigation evaluated changes in levels and proportions of 40 bacterial species in subgingival plaque sample s during , immediately after and up to 1 year after metronidazole or amoxicillin therapy combined with SRP . METHOD After baseline clinical and microbiological monitoring , 17 adult periodontitis subjects received full mouth SRP and 14 days systemic administration of either metronidazole ( 250 mg , TID , n=8 ) or amoxicillin ( 500 mg , TID , n=9 ) . Clinical measurements including % of sites with plaque , gingival redness , bleeding on probing and suppuration , pocket depth ( PD ) and attachment level ( AL ) were made at baseline , 90 , 180 and 360 days . Subgingival plaque sample s were taken from the mesial surface of all teeth in each subject at baseline , 90 , 180 and 360 days and from 2 r and omly selected posterior teeth at 3 , 7 , and 14 days during and after antibiotic administration . Counts of 40 subgingival species were determined using checkerboard DNA-DNA hybridization . Significance of differences over time was determined using the Quade test and between groups using ANCOVA . RESULTS Mean PD was reduced from 3.22+/-0.12 at baseline to 2.81+/-0.16 ( p<0.01 ) at 360 days and from 3.38+/-0.23 mm to 2.80+/-0.14 mm ( p<0.01 ) in the amoxicillin and metronidazole treated subjects respectively . Corresponding values for mean AL were 3.21+/-0.30 to 2.76+/-0.32 ( p<0.05 ) and 3.23+/-0.28 mm to 2.94+/-0.23 mm ( p<0.01 ) . Levels and proportions of Bacteroides forsythus , Porphyromonas gingivalis and Treponema denticola were markedly reduced during antibiotic administration and were lower than baseline levels at 360 days . Counts ( x10(5 ) , + /-SEM ) of B. forsythus fell from baseline levels of 0.66+/-0.16 to 0.04+/-0.02 , 0.13+/-0.04 , 0.10+/-0.03 and 0.42+/-0.19 in the amoxicillin group at 14 , 90 , 180 and 360 days respectively ( p<0.001 ) . Corresponding values for metronidazole treated subjects were : 1.69+/-0.28 to 0.02+/-0.01 , 0.20+/-0.08 , 0.22+/-0.06 and 0.22+/-0.08 ( p<0.001 ) . Counts of Campylobacter species , Eubacterium nodatum , Fusobacterium nucleatum subspecies , F. periodonticum and Prevotella nigrescens were also detected at lower mean levels during and immediately after therapy , but gradually increased after withdrawal of the antibiotics . Members of the genera Actinomyces , Streptococcus and Capnocytophaga were minimally affected by metronidazole . However , amoxicillin decreased the counts and proportions of Actinomyces species during and after therapy . CONCLUSIONS The data suggest that metronidazole and amoxicillin are useful in rapidly lowering counts of putative periodontal pathogens , but must be accompanied by other procedures to bring about periodontal stability The efficacy of metronidazole and doxycycline in preventing recurrent periodontitis was studied in 23 patients . After treatment in the previous 7 months with either bimonthly scaling and 3 weeks of systemic doxycycline ( 11 subjects ) or scaling and placebo ( 12 subjects ) , patients were monitored for recurrent periodontitis and were scaled every 2 months . When either a periodontal abscess or greater than 2 mm loss of gingival attachment was observed , metronidazole was administered ( 250 mg every 8 hours ) for 10 days . In the placebo plus metronidazole group , 5 patients ( 42 % ) exhibited recurrent periodontitis after the metronidazole regimen compared with only one ( 9 % ) in the doxycycline plus metronidazole group ( P less than 0.096 ) . Subgingival plaque sample s at study and healthy control sites were screened for the presence of Actinobacillus actinomycetemcomitans , Porphyromonas gingivalis , Prevotella intermedia , Eikenella corrodens , and Fusobacterium nucleatum by immunofluorescence and for spirochetes using Ryu 's stain . Presence/absence analysis of the sum of scores of the 6 individual pathogens demonstrated large reductions ( P less than 0.005 ) in the frequency of detection of pathogens in the former doxycycline compared with the placebo plus metronidazole group at both study and control sites before and one month after metronidazole . By 7 months after metronidazole , there was no detectable difference between groups . These results indicate that prevention of recurrent periodontitis with metronidazole may be enhanced by previous treatment with doxycycline A considerable amount of circumstantial evidence indicates that most forms of periodontitis are due to the presence or dominance of a finite number of bacterial species in the subgingival plaque . Almost all of the putative pathogens are anaerobic species , indicating that most forms of periodontitis could be diagnosed as anaerobic infections . In this double-blind investigation , patients with elevated proportions or levels of spirochetes in 2 or more plaque sample s , i.e. , 60 % spirochetes , were r and omly assigned to receive either metronidazole , 250 mg 3 x a day for 1 week , or placebo ( positive-control ) after the completion of all debridement procedures . When the patients were re-examined 4 to 6 weeks later , the patients in the metronidazole group ( n = 15 ) exhibited a highly significant ( p less than 0.01 ) reduction in probing depth and apparent gain in attachment levels relative to the patients ( n = 18 ) in the positive-control group about those teeth that initially had probing depths of 4 to 6 mm . This pattern was also observed about teeth that initially had probing depths greater than or equal to 7 mm . This reduction in probing depths and apparent gain in attachment was associated with a significant reduction in the need for periodontal surgery in the metronidazole-treated patients ( difference 8.4 teeth per patient ) compared to the positive-control patients ( 2.6 teeth per patient ) . These clinical improvements in the metronidazole group were associated with significantly lower proportions of spirochetes , selenomonads , motile rods , and P. intermedius , and a significantly higher proportion of cocci in the plaques . These findings indicate that systemic metronidazole , when given after all the root surface debridement is completed , leads to additional treatment benefits , including a reduced need for surgery , beyond that which can be achieved by debridement alone A r and omized , double-blind , placebo-controlled study on the immediate clinical and microbiological efficacy of doxycycline ( 100 mg for 14 days ) was carried out to determine the benefit of adjunctive medication in 16 patients with localized juvenile periodontitis . Measurements of gingival fluid flow , probing depths , bleeding on probing and suppuration were determined at 2 periodontal sites with and 2 without radiographic attachment loss , at weeks 0 , 1 , 3 and 8 . Subgingival bacterial sample s were taken with curettes from the same sites . Spirochaetes were search ed for by dark-field microscopy . Actinobacillus actinomycetemcomitans , pigmented and non-pigmented Bacteroides spp . , Capnocytophaga , Fusobacterium and Actinomyces spp . were cultured on various selective and non-selective media . Bacterial species found at least in 50 % of the patients and comprising on average 5 % or more of the cultivable flora were included in the analysis . Neither short-term clinical nor microbiological efficacy beyond that of a course of mechanical debridement alone was found by using systemic medication with doxycycline in patients with localized juvenile periodontitis This study determined the microbial composition of the apical parts of the exp and ed polytetrafluoroethylene membrane surfaces facing the gingiva and the tooth in guided tissue regeneration . Microbial and clinical features of 2-to-3 wall periodontal bony defects treated with membranes with and without concomitant use of systemic Augmentin therapy were also determined . 18 patients with 18 study sites participated . 9 patients received systemic 500 mg Augmentin 1 h prior to surgery , and 500 mg TID for 8 days thereafter . 9 patients received no systemic antimicrobial therapy . Microbiological examination was performed 1 h prior to surgery , at the time of membrane removal at week 6 , and at 6 months post-surgery . Microbial morphotypes , total viable counts , and the occurrence of selected microbial species were determined by phase-contrast microscopy , selective and non-selective culture , and DNA probes . Study sites were examined for probing pocket depths and attachment levels . At baseline , no microbial or clinical parameter showed statistical differences between groups . At 6 months , the Augmentin group demonstrated a significantly higher ( P = 0.032 ; Student t-test ) mean probing attachment gain ( 36.5 % of potential gain to the cemento-enamel junction ) than the 9 control patients ( 22.4 % of potential gain ) . At the time of removal , membranes in the Augmentin group showed significantly fewer organisms than membranes in the control group ( 52.2 x 10(6 ) versus 488.6 x 10(6 ) ) . Sites free of pathogens on the membrane surface toward the tooth gained the most clinical attachment , even in the presence of various pathogens on the gingiva-facing membrane surface . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of the present study was to evaluate the effect of non-surgical periodontal therapy with the adjunct of a selected antibiotic in subjects diagnosed with refractory periodontal disease . 21 subjects were selected for the study ; all had a history of periodontal surgery , tetracycline therapy , and regular maintenance by a periodontist . When disease activity was detected , a bacterial sample was taken and a whole plaque susceptibility test was performed . Before the outcome of the susceptibility test the subjects were assigned to either antibiotic or placebo therapy . All subjects received scaling and rootplaning prior to antibiotic or placebo therapy . Based on the susceptibility test , subjects in the antibiotic group were treated either with Augmentin or clindamycin . The results demonstrated that in subjects with refractory periodontal disease there was no significant difference ( N.S. ) in the proportion of sites losing attachment before and after treatment ( 11.3 % and 12.4 % , respectively ) over a 2-year post therapy observation period . However , the proportion of sites showing gain of attachment increased from 0.9 % before therapy to 5.1 % ( p = 0.029 ) following selective antibiotic therapy when combined with scaling and rootplaning . The remainder of sites showed no change between pre- and post-therapy monitoring periods . The progression of attachment loss in the active sites could not be completely stopped over the entire 2-year period . After 12 - 15 months following therapy , there was a tendency towards new loss of attachment and an increase of pocket depth . However , all 4 subjects treated with placebo drug demonstrated continuous deterioration and had to be retreated . Although the proportion of sites losing attachment decreased from 5.1 % to 2.3 % ( N.S. ) , the proportion of sites gaining attachment also decreased from 2.0 % to 1.0 % ( N.S. ) . The results suggest that scaling and rootplaning together with selected antibiotic therapy repeated every 12 - 15 months may be beneficial for these subjects although it may not completely stop progressive attachment loss The aims of this study were to evaluate the clinical and microbiological effects of initial periodontal therapy ( IT ) and to determine the additional effects of systemic amoxicillin ( Flemoxin Solutab ) 375 mg TID plus metronidazole 250 mg TID therapy , in patients with adult Actinobacillus actinomycetemcomitans (Aa)-associated periodontitis in conjunction with either Porphyromonas gingivalis ( Pg ) , Bacteroides forsythus ( Bf ) and /or Prevotella intermedia ( Pi ) . In addition the adverse effects of the antimicrobial therapy were also documented . A total of 22 patients were enrolled . The deepest , bleeding pocket in each quadrant was selected and at these 4 experimental sites clinical measurements and microbiological testing was carried out at baseline , after ( IT ) , i.e. , 21 weeks after baseline , and after antimicrobial therapy ( AM ) , i.e. , 35 weeks after baseline . At baseline , the mean plaque index ( PI ) amounted 0.5 , 0.1 after IT and 0.3 after systemic AM . The mean bleeding index decreased from 1.6 to 1.2 after IT and a further decrease to 0.7 after AM was noted . Suppuration was completely eliminated after AM . The mean change of probing pocket depth ( PPD ) after IT amounted 1.4 mm and was further reduced with an additional mean change of 1.1 mm after medication . Clinical attachment gain was 1.1 mm after IT and an additional 0.9 mm was observed after AM . One of the 22 Aa positive patients and 4 of 17 Pg positive patients became negative for these species after IT . The number of patients with detectable Pi decreased from 16 to 10 after IT . After AM , in comparison to baseline , suppression below detection level for Aa was achieved in 19 out of 22 , for Pg in 9 out of 17 , for Bf in 13 out of 14 , and for Pi in 11 out of 16 patients . By contrast , higher frequencies of Peptostreptococcus micros and Fusobacterium nucleatum were found after AM . On the basis of the microbiological results the study group was separated into 2 subgroups : group A consisted of subjects who had no detectable levels of Aa , Pg , Bf and < 5 % of Pi after AM . Group B consisted of those who still showed presence of one of these 3 species and /or > or = 5 % levels of Pi . After AM , group B had significantly higher PI , BI , PPD and CAL scores then group A. It is concluded that group A showed low plaque scores and no detectable periodontal pathogens . This microbiological condition has been associated with a long-term stable periodontium Objective : To compare clinical and microbiological responses following non-surgical treatment of moderate to advanced adult periodontitis using subgingival scaling with and without adjunctive topical or systemic metronidazole . Design : A single blind r and omised clinical trial of 90 subjects , stratified for periodontitis disease severity and smoking status , divided into three treatment groups : 1 . Subgingival scaling using ultrasonic scalers and local anaesthesia ; 2 . Subgingival scaling using ultrasonic scalers and local anaesthesia plus seven days of systemic metronidazole ( 200 mg tds ) ; 3 . Subgingival scaling using ultrasonic scalers and local anaesthesia plus two applications of 25 % metronidazole gel one week apart in all sites with probing depths more than 4 mm . Evaluations were made before treatment , and 8 weeks and 24 weeks post treatment . Main outcome measures : Probing depths , probing attachment levels and bleeding on probing were measured using a Florida probe . Bacterial morphotypes were evaluated with darkfield microscopy . Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance . Results : 84 subjects completed the trial and the three treatment groups did not differ at baseline for any clinical parameter . Mean probing depths were reduced following treatment by greater than 1.6 mm ( Group 1 = 1.68 mm , Group 2 = 1.62 mm , Group 3 = 1.74 mm at six months post treatment ) but no significant differences were detected between treatment groups at any time point . Similarly , no significant differences were detectable between treatments for changes in mean probing attachment levels , bleeding on probing , plaque scores or proportions of bacterial morphotypes . Conclusions : This study does not support the routine use of adjunctive metronidazole in the non-surgical treatment of |
13,359 | 27,895,779 | Treatment with mTOR inhibitors in general was well tolerated in patients with metastatic disease .
The predominant toxicities were grade 1 and 2 .
The phase 1 trials included in this review demonstrated that mTOR inhibitor treatments are feasible and safe . | The aim of the present systematic review was to analyze the potential impact of mammalian target of rapamycin ( mTOR ) inhibitors on the treatment of cervical squamous cell carcinoma ( CSCC ) . | Background : Bevacizumab and temsirolimus are active agents in gynecologic tumors . Temsirolimus attenuates upregulation of HIF-1α levels , a resistance mechanism for antiangiogenics , and targets the PI3-kinase/AKT/mTOR axis , commonly aberrant in these tumors Patients and Methods : We analyzed safety and responses in 41 patients with gynecologic cancers treated as part of a Phase I study of bevacizumab and temsirolimus . Results : Median age of the 41 women was 60 years ( range , 33 - 80 years ) ; median number of prior systemic therapies was 4 ( 1 - 11 ) . Grade 3 or 4 treatment-related toxicities included : thrombocytopenia ( 10 % ) , mucositis ( 2 % ) , hypertension ( 2 % ) , hypercholesterolemia ( 2 % ) , fatigue ( 7 % ) , elevated aspartate aminotransferase ( 2 % ) , and neutropenia ( 2 % ) . Twenty-nine patients ( 71 % ) experienced no treatment-related toxicity greater than grade 2 . Full FDA -approved doses of both drugs ( bevacizumab 15mg/kg IV Q3weeks and temsirolimus 25 mg IV weekly ) were administered without dose-limiting toxicity . Eight patients ( 20 % ) achieved stable disease ( SD ) ≥ 6 months and 7 patients ( 17 % ) , a partial response ( PR ) [ total = 15/41 patients ( 37 % ) ] . Eight of 13 patients ( 62 % ) with high- grade serous histology ( ovarian or primary peritoneal ) achieved SD ≥ 6 months/PR . Conclusion : Bevacizumab and temsirolimus was well tolerated . Thirty-seven percent of heavily-pretreated patients achieved SD ≥ 6 months/PR , suggesting that this combination warrants further study Background : Two strategies to interrogate the insulin growth factor 1 receptor ( IGF-1R ) pathway were investigated : vertical inhibition with dalotuzumab and MK-2206 or ridaforolimus to potentiate PI3 K pathway targeting and horizontal cross-talk inhibition with dalotuzumab and MK-0752 to exert effects against cellular proliferation , angiogenesis , and stem cell propagation . Methods : A phase I , multi-cohort dose escalation study was conducted in patients with advanced solid tumours . Patients received dalotuzumab ( 10 mg kg–1 ) and escalating doses of MK-2206 ( 90–200 mg ) or escalating doses of dalotuzumab ( 7.5–10 mg kg–1 ) and MK-0752 ( 1800 mg ) weekly . Upon maximum tolerated dose determination , patients with low-RAS signature , high-IGF1 expression ovarian cancer were r and omised to dalotuzumab/MK-2206 versus dalotuzumab/ridaforolimus , whereas patients with high IGF1/low IGF2 expression colorectal cancer received dalotuzumab/MK-0752 . Results : A total of 47 patients were enrolled : 29 in part A ( 18 in the dalotuzumab/MK-2206 arm and 11 in the dalotuzumab/MK-0752 arm ) and 18 in part B ( 6 in each arm ) . Dose-limiting toxicities ( DLTs ) for dalotuzumab/MK-2206 included grade 4 neutropenia and grade 3 serum sickness-like reaction , maculopapular rash , and gastrointestinal inflammation . For dalotuzumab/MK-0752 , DLTs included grade 3 dehydration , rash , and diarrhoea . Seven patients remained on study for > 4 cycles . Conclusions : Dalotuzumab/MK-2206 and dalotuzumab/MK-0752 combinations were tolerable . Further developments of prospect ively vali date d predictive biomarkers to aid in patient selection for anti-IGF-1R therapies are needed Concanavalin A ( Con A ) , a mannose or glucose specific legume lectin , is well known for its anti-proliferative and cytotoxic effect on different types of cancer cells , through its binding to the membrane receptors leading to a major stimulus for the induction of distinct metabolic responses . Recently it has been also been proved that , Con A induces autophagy in hepatoma cells through internalization and mitochondria mediated pathway involving a mitochondrial interacting protein named Bcl2/E1B-19kDa protein-interacting protein 3 ( BNIP3 ) . Through this current endeavor , we propose a membrane associated pathway involved in Con A induced autophagy , taking Human cervical cancer ( HeLa ) cell as a cancer model . Here , we deciphered the role of membrane mediated phosphatidylinositol 3 kinase (PI3K)/Akt/mTOR ( mammalian target of rapamycin ) and MEK/Extracellular signal-regulated kinases ( ERK ) pathway in Con A induced autophagy in HeLa cells . Subsequently , we found that Con A treatment suppresses the PI3K/Akt/mTOR and up regulates the MEK/ERK pathway leading to the activation of autophagy . This study will further help us to underst and the mechanism behind the autophagic pathway induced by Con A and simultaneously it will strengthen its effective use as a prospect i ve cancer chemo-therapeutic Cisplatin‐based chemoradiation ( CRT ) is the st and ard treatment for patients with locally advanced cervical cancer . Epidermal growth factor receptor ( EGFR ) is frequently overexpressed in cervical cancer , and EGFR inhibition itself has antitumor effects and potentiates CRT . Results of a previous phase 1 trial of the EGFR inhibitor erlotinib combined with cisplatin‐based CRT ( E + CRT ) recommended a phase 2 erlotinib dose of 150 mg/day Background : We conducted a phase I study in patients with advanced solid tumours to identify the recommended dose , assess pharmacokinetics ( PK ) , pharmacodynamic activity and pre clinical antitumour efficacy of the combination of sirolimus and gemcitabine . Methods : Nineteen patients were treated with sirolimus 2 or 5 mg daily and gemcitabine 800 or 1000 mg m−2 on days 1 and 8 . Dose escalation depended on dose-limiting toxicity ( DLT ) rate during the first 3-week period . Paired skin biopsies were evaluated for phosphorylated S6 ( pS6 ) as marker of mTOR ( mammalian target of rapamycin ) inhibition . Pharmacokinetics and pre clinical evaluation of efficacy using two different sarcoma cell lines and leiomyosarcoma xenografts were also conducted . Results : Three DLTs were observed : grade 3 transaminitis , grade 3 thrombocytopenia and grade 4 thrombocytopenia . Common treatment-related adverse events included anaemia , neutropenia , thrombocytopenia and transaminitis . Pharmacodynamic analyses demonstrated mTOR inhibition with sirolimus 5 mg and PK showed no influence of sirolimus concentrations on gemcitabine clearance . In vitro and in vivo studies suggested mTOR pathway hyperactivation by gemcitabine that was reversed by sirolimus . Tumour growth in leiomyosarcoma xenografts was dramatically inhibited by the treatment . Conclusions : Recommended dose was sirolimus 5 mg per 24 h plus gemcitabine 800 mg m−2 . Antitumour activity in pre clinical sarcoma models and mTOR signalling inhibition were observed . A phase II study is currently ongoing BACKGROUND Everolimus ( RAD001 ) is an orally administered inhibitor of the mammalian target of rapamycin ( mTOR ) , a therapeutic target for metastatic renal cell carcinoma . We did a phase III , r and omised , double-blind , placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factor-targeted therapy . METHODS Patients with metastatic renal cell carcinoma which had progressed on sunitinib , sorafenib , or both , were r and omly assigned in a two to one ratio to receive everolimus 10 mg once daily ( n=272 ) or placebo ( n=138 ) , in conjunction with best supportive care . R and omisation was done central ly via an interactive voice response system using a vali date d computer system , and was stratified by Memorial Sloan-Kettering Cancer Center prognostic score and previous anticancer therapy , with a permuted block size of six . The primary endpoint was progression-free survival , assessed via a blinded , independent central review . The study was design ed to be terminated after 290 events of progression . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00410124 . FINDINGS All r and omised patients were included in efficacy analyses . The results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was thus halted early after 191 progression events had been observed ( 101 [ 37 % ] events in the everolimus group , 90 [ 65 % ] in the placebo group ; hazard ratio 0.30 , 95 % CI 0.22 - 0.40 , p<0.0001 ; median progression-free survival 4.0 [ 95 % CI 3.7 - 5.5 ] vs 1.9 [ 1.8 - 1.9 ] months ) . Stomatitis ( 107 [ 40 % ] patients in the everolimus group vs 11 [ 8 % ] in the placebo group ) , rash ( 66 [ 25 % ] vs six [ 4 % ] ) , and fatigue ( 53 [ 20 % ] vs 22 [ 16 % ] ) were the most commonly reported adverse events , but were mostly mild or moderate in severity . Pneumonitis ( any grade ) was detected in 22 ( 8 % ) patients in the everolimus group , of whom eight had pneumonitis of grade 3 severity . INTERPRETATION Treatment with everolimus prolongs progression-free survival relative to placebo in patients with metastatic renal cell carcinoma that had progressed on other targeted therapies BACKGROUND We performed a single institution , phase I study of sirolimus and bevacizumab , in order to determine the dose limiting toxicity ( DLT ) and recommended phase II doses . PATIENTS AND METHODS Eligible patients had previously treated advanced malignancies and were enrolled in three cohorts . Sirolimus 90 mg PO weekly ( 45 mg on days 1 and 2 ) was combined with bevacizumab 7.5mg/kg ( cohort # 1 ) or bevacizumab 15 mg/kg ( cohort # 2 ) IV q3weeks . Sirolimus 4 mg PO daily was combined with bevacizumab 15 mg/kg IV q3weeks ( cohort # 3 ) . RESULTS Twenty-eight patients enrolled . The most common tumour types were colorectal ( 21 % ) , head/neck ( 14 % ) , and renal cell ( 11 % ) . No DLTs were observed in cohorts # 1 ( 4 patients ) and # 2 ( 12 patients ) , while two DLTs ( grade 3 confusion and grade 3 fatigue ) were observed in the first six patients in cohort # 3 ( 12 patients ) . The most common grade 3 toxicities were fatigue ( 18 % ) , hypertension ( 14 % ) and anorexia ( 11 % ) . There were no responses , but one patient has had stable disease for 78 weeks . CONCLUSIONS The combination of sirolimus and bevacizumab at full doses is tolerable in the majority of patients . The availability and cost of sirolimus compared with other mTOR inhibitors make this an attractive agent to combine with bevacizumab This study is to investigate the antitumor activity of ophiopogonin B ( OP-B ) . MTT assay , flow cytometric analysis , acridine orange staining , Lyso-Tracker Red staining and HeLa-GFP-LC3 transfect cells assay were used to detect the proliferation activity , apoptosis and autophagy of HeLa cells . The results showed that OP-B exerted potent antiproliferative activity on HeLa cells , the cell growth inhibition effect of OP-B was not due to apoptosis and OP-B could induce autophagy of HeLa cells . OP-B also induced the protein expression up-regulation of Beclin-1 and promoted LC3 I transformation LC3 II , which were representative proteins of autophagy . Furthermore , 3-MA , an inhibitor of autophagy , not only inhibited OP-B-mediated autophagy but also almost completely reversed the antiproliferative effect of OP-B , suggesting that the growth inhibition effect of OP-B was autophagy dependent . Western blotting demonstrated that OP-B inhibited the phosphorylation of Akt and its ' downstream vital protein , such as mTOR and p70S6 K . In addition , OP-B also induced the protein expression up-regulation of PTEN , which is a negative regulation protein for Akt/mTOR signaling pathway . However , OP-B did not affect the protein expression of total Akt . Collectively , the antitumor effects of OP-B were autophagy-dependent via repression Akt/mTOR signaling pathway . Therefore , OP-B is a prospect i ve inhibitor of Akt/mTOR and may be used as an alternative compound to treat cervical carcinoma Purpose : This phase I , first-in-human study evaluated the safety , maximum-tolerated dose ( MTD ) , pharmacokinetics , pharmacodynamics , and preliminary efficacy of SAR245409 , an inhibitor of pan-Class I phosphoinositide 3-kinase ( PI3 K ) and mTOR , administered orally once or twice daily in patients with advanced solid tumors . Experimental Design : Eighty-three patients received SAR245409 . Doses ranged from 15 to 120 mg twice daily , and 70 to 100 mg once daily . A 3 + 3 dose-escalation design was used to determine the MTD . Patients were evaluated for adverse events and response . Assessment s included pharmacokinetic , pharmacodynamic impact of SAR245409 on PI3 K pathway signaling in hair sheath cells , skin and tumor , and characterization of tumor molecular alterations . Results : The MTDs were 50 mg twice daily and 90 mg once daily . The most frequent treatment-related adverse events were nausea ( 36.1 % ) , diarrhea ( 21.7 % ) , vomiting ( 19.3 % ) , and decreased appetite ( 16.9 % ) . The most frequent treatment-related grade 3/4 adverse events were increases in alanine aminotransferase ( 6.0 % ) and aspartate aminotransferase ( 4.8 % ) . SAR245409 had a relatively short plasma half-life ( 2.96–7.52 hours ) . At MTDs , once- and twice-daily regimens yielded similar mean steady-state plasma exposure . A reduction in PI3 K and mTORC1/mTORC2 pathway signaling was observed in serial hair sheath cells , skin , and tumor sample s. Best response was stable disease in 48 % of evaluable patients ; seven patients had minor tumor regression . Twelve patients with stable disease were treated for ≥16 weeks . No trend was observed correlating tumor molecular alteration with antitumor activity . Conclusion : SAR245409 had a manageable safety profile , demonstrated reduced PI3 K and mTORC1/mTORC2 pathway signaling and was associated with clinical ly relevant stable disease . Clin Cancer Res ; 20(9 ) ; 2445–56 . © 2014 AACR OBJECTIVE Disseminated gynecologic cancers are usually fatal due to chemoresistance . Recently , rationally developed , targeted agents are entering the early clinical trials setting . We assessed patients with metastatic gynecologic cancers in a dedicated phase I clinical trials clinic in order to determine their outcome . METHODS We review ed records for 89 consecutive patients with gynecologic cancers referred to the Phase I Clinical Trials Program , 85 ( 96 % ) of whom were treated on > or = 1 trial . RESULTS Cancer diagnoses were ovarian ( N=43 ) , uterine ( N=19 ) , cervix ( N=17 ) , and other . Median age was 58 years ; median number of prior cytotoxic regimens , five . Two patients ( 2.4 % ) achieved a CR ; four ( 4.7 % ) , a PR ; and eight ( 9.4 % ) , SD > or = 6 months ( total CR/PR/SD > or = 6 months=16.5 % ) for the first phase I trial . Twenty-five patients enrolled on a second trial and three , on a third ( N=113 trials total ) . Combining response data for all trials , of the 85 patients , two achieved CR ( 2.4 % ) , nine achieved PR ( 10.6 % ) , and 12 ( 14 % ) had SD for > or = 6 months . One-year survival was 30 % ( 95 % CI , 21 % to 44 % ) . There was no difference in time-to-treatment failure ( TTF ) on phase I versus the patient 's last st and ard treatment . CONCLUSION Twenty-three of 85 patients ( 27 % ) with advanced , heavily pretreated , gynecologic cancers achieved CR/PR/SD > or = 6 months on a phase I trial , and overall TTF on phase I was comparable to that of last conventional therapy , suggesting that participation in a phase I trial is a reasonable option for these patients PURPOSE To identify the optimal regimen and dosage of the oral mammalian target of rapamycin inhibitor everolimus ( RAD001 ) . METHODS We performed a dose-escalation study in advanced cancer patients administering oral everolimus 5 to 30 mg/wk , with pharmacokinetic ( PK ) and pharmacodynamic ( PD ) studies . PD data prompted investigation of 50 and 70 mg weekly and daily dosing at 5 and 10 mg . RESULTS Ninety-two patients were treated . Dose-limiting toxicity was seen in one patient each at 50 mg/wk ( stomatitis and fatigue ) and 10 mg/d ( hyperglycemia ) ; hence , the maximum-tolerated dose was not reached . S6 kinase 1 activity in peripheral-blood mononuclear cells was inhibited for at least 7 days at doses > or= 20 mg/wk . Area under the curve increased proportional to dose , but maximum serum concentration increased less than proportionally at doses > or= 20 mg/wk . Terminal half-life was 30 hours ( range , 26 to 38 hours ) . Partial responses were observed in four patients , and 12 patients remained progression free for > or= 6 months , including five of 10 patients with renal cell carcinoma . CONCLUSION Everolimus was satisfactorily tolerated at dosages up to 70 mg/wk and 10 mg/d with predictable PK . Antitumor activity and PD in tumors require further clinical investigation . Doses of 20 mg/wk and 5 mg/d are recommended as appropriate starting doses for these studies Purpose : Liposomal doxorubicin ( D ) and bevacizumab ( A ) are active single agents in gynecologic and breast malignancies which share a resistance mechanism : upregulation of hypoxia inducible factor ( HIF-1α ) . We , therefore , added temsirolimus ( T ) , which inhibits HIF-1α , to D and A ( DAT ) . Trial objectives were assessment of safety , preliminary efficacy , and identification of biological response correlates . Patients and Methods : Cycle length was 21 days , with IV D , A , and T on day 1 ; T on days 8 and 15 ( 3 + 3 dose-escalation design with expansion cohorts ) . Mutational assays for PIK3CA , BRAF , KRAS , and immunhistochemistry for PTEN loss were conducted . Results : This article details 74 patients with gynecologic and breast malignancies who received at least one dose of drug on study . Median patient age : 52 ( 27–79 ) ; prior regimens : 4 ( 1–11 ) . Responses : 1 ( 1.4 % ) complete response ( CR ) , 14 ( 18.9 % ) partial responses ( PR ) , and 13 ( 17.6 % ) with stable disease ( SD ) ≥ 6 months ( total = 37.9 % ) . The most common grade 1 toxicities were fatigue ( 27 % ) and anemia ( 20.2 % ) . Notable grade 3/4 toxicities : thrombocytopenia ( 9.5 % ) , mucositis ( 6.7 % ) , and bowel perforation ( 2.7 % ) . PIK3CA mutations or PTEN loss were identified in 25 of 59 ( 42.3 % ) of tested patients . Among these , nine ( 36 % ) achieved CR/PR and four ( 16 % ) had SD ≥ 6 months ( CR+PR+SD ≥ 6 months = 52 % ) . Conclusions : DAT is well tolerated with manageable side effects . Responses observed warrant further evaluation . Mutational analyses were notable for a high percentage of responders with phosphoinositide-3-kinase pathway aberrations . Clin Cancer Res ; 17(21 ) ; 6840–6 . © 2011 AACR OBJECTIVE The mTOR inhibitor , temsirolimus , has clinical activity in the treatment of gynecologic malignancies , particularly endometrial cancer . We sought to determine the tolerability of the combination of weekly topotecan with weekly temsirolimus . METHODS Women with a history of advanced or recurrent gynecologic malignancy refractory to curative therapy were enrolled . A starting dose of 1mg/m(2 ) of intravenous topotecan days 1 , 8 and 15 was combined with 25 mg temsirolimus days 1 , 8 , 15 and 22 of a 28 day cycle . Patients with and without prior pelvic radiotherapy ( RT ) were dose-escalated in separate cohorts . RESULTS Fifteen patients were treated on study . Forty-three cycles were administered , with between 1 and 7 cycles received per patient . Patient characteristics included ovarian cancer ( n=7 ) , endometrial cancer ( n=3 ) , uterine carcinosarcoma ( n=3 ) , and cervical cancer ( n=2 ) ; performance status 0 ( n=10 ) and 1 ( n=5 ) ; prior chemotherapy regimens one ( n=8 ) , two ( n=4 ) , and three ( n=3 ) . Dose-limiting toxicity included asymptomatic neutropenia and thrombocytopenia . Four patients without prior pelvic RT were successfully treated with 1mg/m(2 ) topotecan with 25 mg temsirolimus , days 1 , 8 , and 15 of a 28 day cycle . The combination was not tolerated in patients with a history of pelvic RT . CONCLUSIONS Dose-limiting toxicity for the combination of temsirolimus with topotecan was myelosuppression . The regimen may be safe in women who have not previously received radiation , but full doses of each agent could not be administered in combination |
13,360 | 28,592,324 | Conclusion FNB-combined SNB provides superior pain relief and less morphine consumption within the first 24 h compared FNB-combined LIA in total knee arthroplasty .
In addition , there were fewer side effects associated with SNB . | Background This meta- analysis aim ed to perform a meta- analysis to evaluate the efficiency and safety between local infiltration analgesia ( LIA ) and sciatic nerve block ( SNB ) when combined with femoral nerve block ( FNB ) after total knee arthroplasty ( TKA ) . | Background Several previous surveys have estimated the rate of major complications that occur after regional anesthesia . However , because of the increase in the use of regional anesthesia in recent years and because of the introduction of new techniques , re appraisal of the incidence and the characteristics of major complications is useful . Methods All French anesthesiologists were invited to participate in this 10-month prospect i ve survey based on ( 1 ) voluntary reporting of major complications related to regional anesthesia occurring during the study period using a telephone hotline service available 24 h a day and managed by three experts , and ( 2 ) voluntary reporting of the number and type of regional anesthesia procedures performed using pocket booklets . The service was free of charge for participants . Results The participants ( n = 487 ) reported 56 major complications in 158,083 regional anesthesia procedures performed ( 3.5/10,000 ) . Four deaths were reported . Cardiac arrest occurred after spinal anesthesia ( n = 10 ; 2.7/10,000 ) and posterior lumbar plexus block ( n = 1 ; 80/10,000 ) . Systemic local anesthetic toxicity consisted of seizures only , without cardiac toxicity . Lidocaine spinal anesthesia was associated with more neurologic complications than bupivacaine spinal anesthesia ( 14.4/10,000 vs. 2.2/10,000 ) . Most neurologic complications were transient . Among 12 that occurred after peripheral nerve blocks , 9 occurred in patients in whom a nerve stimulator had been used . Conclusion This prospect i ve survey based on a free hotline permanent telephone service allowed us to estimate the incidence of major complications related to regional anesthesia and to provide a detailed analysis of these complications Background and purpose — The local infiltration analgesia ( LIA ) technique has been widely used to reduce opioid requirements and to improve postoperative mobilization following total hip arthroplasty ( THA ) . However , the evidence for the efficacy of LIA in THA is not yet clear . We determined whether single-shot LIA in addition to a multimodal analgesic regimen would reduce acute postoperative pain and opioid requirements after THA . Patients and methods — 116 patients undergoing primary THA under spinal anesthesia were included in this r and omized , double-blind , placebo-controlled trial . All patients received oral opioid-sparing multimodal analgesia : etoricoxib , acetaminophen , and glucocorticoid . The patients were r and omized to receive either 150 mL ropivacaine ( 2 mg/mL ) and 0.5 mL epinephrine ( 1 mg/mL ) or 150 mL 0.9 % saline . Rescue analgesic consisted of morphine and oxycodone as needed . The primary endpoint was pain during mobilization in the recovery unit . Secondary endpoints were pain during mobilization on the day after surgery and total postoperative opioid requirements on the first postoperative day . Results — The levels of pain during mobilization — both in the recovery unit and on the day after surgery— and consumption of opioids on the first postoperative day were similar in the 2 groups . Interpretation — LIA did not provide any extra analgesic effect after THA over and above that from the multimodal analgesic regimen used in this study Background and purpose Pain after total knee arthroplasty ( TKA ) is usually severe , and epidural analgesia or femoral nerve block has been considered to be an effective pain treatment . Recently , local infiltration analgesia ( LIA ) has become increasingly popular but the outcome of this method regarding the analgesic effect has not been fully evaluated . We compared local infiltration analgesia and femoral block with regard to analgesia and morphine dem and during the first 24 h after TKA . Methods 40 patients undergoing TKA under spinal anesthesia were r and omized to receive femoral nerve block ( group F ) or peri- and intraarticular infiltration analgesia ( group LIA ) with a mixture containing ropivacaine , ketorolac , and epinephrine . All patients had access to intravenous patient-controlled analgesia ( PCA ) with morphine postoperatively . Pain intensity at rest and upon movement was assessed on a numeric rating scale ( 0–10 ) on an hourly basis over 24 h if the patients were awake . Results The average pain at rest was marginally lower with LIA ( 1.6 ) than with femoral block ( 2.2 ) . Total morphine consumption per kg was similar between the 2 groups . Ancillary analysis revealed that 1 of 20 patients in the LIA group reported a pain intensity of > 7 upon movement , as compared to 7 out of 19 in the femoral block group ( p = 0.04 ) . Interpretation Both LIA and femoral block provide good analgesia after TKA . LIA may be considered to be superior to femoral block since it is cheaper and easier to perform Local infiltration anesthesia ( LIA ) with anesthetics , steroids , NSAIDS , and epinephrine has been shown to be effective in reducing total knee arthroplasty ( TKA ) postoperative pain . This systematic review explores the functional outcomes of r and omized control trials that have compared the use of LIA with and without steroids during TKA . Five studies with 412 patients met the inclusion criteria , 228 received local infiltration anesthesia with steroids ( LIAS ) and 184 received local infiltration anesthesia without steroids ( LIAWS ) . The use of LIAS in management of postoperative TKA pain has been shown to decrease the length of hospital stay , time required to achieve straight leg raise , and pro-inflammatory signals in patients . Although there is no overwhelming data to suggest LIAS improves postoperative TKA pain , current literature does support its effectiveness in producing other favorable surgical outcomes Peripheral nerve blocks appear to provide effective analgesia for patients undergoing total knee arthroplasty . Although the literature supports the use of femoral nerve block , addition of sciatic nerve block is controversial . In this study we investigated the value of sciatic nerve block and an alternative technique of posterior capsule local anesthetic infiltration analgesia . 100 patients were prospect ively r and omized into three groups . Group 1 : sciatic nerve block ; Group 2 : posterior local anesthetic infiltration ; Group 3 : control . All patients received a femoral nerve block and spinal anesthesia . There were no differences in pain scores between groups . Sciatic nerve block provided a brief clinical ly insignificant opioid sparing effect . We conclude that sciatic nerve block and posterior local anesthetic infiltration do not provide significant analgesic benefits We evaluated the efficacy of periarticular infiltration of corticosteroid , opioid , and a local anesthetic by comparing pain scores , knee flexion , and quadriceps function on the day of surgery , first postoperative day , day of discharge , and 2 and 4 weeks after surgery between the infiltrated and the noninfiltrated knee in 40 patients undergoing simultaneous bilateral computer-assisted total knee arthroplasty who were r and omized to receive the injection in the right or left knee . In comparison to the noninfiltrated side , the infiltrated knee showed significantly lower pain scores , significantly greater active flexion up to 4 weeks , and superior quadriceps recovery up to 2 weeks after surgery . This simple and inexpensive technique can significantly reduce pain and hasten functional recovery in the first month after total knee arthroplasty Purpose The purpose s of this study were to compare the pain score , systemic opioid consumption , and range of motion ( ROM ) between the group where the use of continuous femoral nerve block ( CFNB ) was discontinued on postoperative day 3 ( POD 3 ) and the group where it was discontinued on POD 7 within an established clinical pathway for postoperative recovery after total knee arthroplasty ( TKA ) and to assess the treatment-related side effects and complications , as well as the functional status of these two groups of patients at 2 years after surgery . Methods This prospect i ve , r and omized , double-blinded trial compared the analgesic efficacy and the functional outcomes between group A ( n = 30 ) where continuous femoral nerve block was performed until POD 3 ( discontinued prior to the initiation of range of motion ( ROM ) exercises ) and group B ( n = 33 ) , where the continuous femoral nerve block was performed until POD 7 ( discontinued during the ROM exercise ) after TKA . Results The resting pain scores of group B were lower than those of group A but there was no significant difference between the two groups ( n.s . , P = 0.387 ) . However , the peak pain scores during ROM exercise , beginning on POD3 through to POD14 , were significantly lower in group B than in group A ( P = 0.001 ) . The cumulative morphine IV-PCA requirements through the POD 2 were similar in the two groups ( n.s . , P = 0.811 ) . However , the cumulative oral oxycodone consumption during hospitalization was significantly lower in group B than in group A , P < 0.0001 . Group B showed significantly greater satisfaction with their method of analgesia than group A ( P = 0.001 ) . Group A scored 2.0 ( 2.0–3.0 ) , whereas group B scored 1.0 ( 1.0–2.0 ) . At 2 years , there was no significant difference in the functional outcomes ( the knee flexion and extension angle , the Knee Society Score , and WOMAC pain , stiffness , and function scale ) . Conclusion The study group who received 7-day continuous femoral nerve block after TKA showed superior analgesia and higher patient satisfaction during the hospital stay than those given 3-day continuous femoral nerve block . Despite the additional time , effort and cost to place and manage continuous femoral nerve catheters , the 7-day continuous femoral nerve block can be recommended as an effective and safe regional component of a multimodal analgesia strategy after TKA.Level of evidence II Numerous postoperative pain protocol s exist for patients undergoing total knee arthroplasty ( TKA ) . We compared the length of stay , early range of motion ( ROM ) , and pain scores of a control group with a femoral nerve block to those of a group with femoral nerve block and local infiltration analgesia following TKA . In a consecutive series of patients undergoing primary TKA at a Veteran 's Administration hospital , 40 patients ( 40 TKAs ) who had local infiltration analgesia were compared to a historical group of 43 patients ( 43 TKAs ) who had a long-acting femoral nerve block without local infiltration analgesia . Local infiltration analgesia consisted of intraoperative injection of 150 mL of 300 mg ropivacaine , 30 mg ketorolac , and 500 μg epinephrine using 50 mL into each of 3 areas : ( 1 ) posterior capsule , ( 2 ) medial and lateral capsule , and ( 3 ) anterior capsule and subcutaneous tissues . A 17-gauge intra-articular catheter was used to inject an additional 100 mg of ropivacaine on postoperative day 1 . The control group had a single-shot femoral nerve block using 150 mg of ropivacaine with epinephrine . Mean length of stay for the local infiltration analgesia group compared to controls was 3.2±1.4 days vs 3.8±1.6 days , respectively ( P=.03 ) . No significant differences existed in average ROM ( 6 weeks ) , discharge hematocrit , transfusions , and temperature . Mean pain scores were lower in the local infiltration analgesia group on postoperative day 1 ( P=.04 ) , but not on postoperative day 2 or 3 . Maximum visual analog scale scores ( P<.01 ) were reduced in the local infiltration analgesia group . Our early experience with local infiltration analgesia demonstrated a significantly reduced length of stay due to decreased postoperative pain Background Although femoral nerve block provides good analgesia after total knee arthroplasty ( TKA ) , residual posterior knee pain may decrease patient satisfaction . We compared the efficacy of periarticular infiltration analgesia ( PIA ) and sciatic nerve block ( SNB ) for posterior knee pain . Methods Forty-nine patients scheduled for TKA were prospect ively r and omized into the PIA group ( n = 25 ) or SNB group ( n = 24 ) and received general anesthesia with ultrasound-guided femoral nerve block ( FNB ) . In the PIA group , 60 ml 0.5 % ropivacaine and 0.3 mg epinephrine were injected intraoperatively into the periarticular soft tissue before inserting the components . In the SNB group , patients received ultrasound-guided SNB with 20 ml 0.375 % ropivacaine and periarticular infiltration with 20 ml normal saline and 0.3 mg epinephrine . We evaluated postoperative pain scores , posterior knee pain , frequency of rescue analgesics for 36 h , and performance time of PIA and SNB . Results Visual analogue pain scores at 12–24 h were significantly lower in the PIA group than in the SNB group ( p < 0.05 ) . The majority of patients had no posterior knee pain . There were no significant differences between the groups in frequency and time of first administration of rescue analgesics and in side effects . Time for performance of periarticular infiltration was significantly shorter than that for SNB ( p < 0.05 ) . The dose of intraoperative remifentanil was significantly lower in the SNB group than in the PIA group ( p < 0.001 ) . Conclusions The combination of FNB and PIA provides sufficient analgesia after TKA . The rapid and convenient periarticular infiltration technique could be a good alternative to SNB Background The use of femoral nerve block ( FNB ) combined with sciatic nerve block ( SNB ) after total knee arthroplasty ( TKA ) has recently become controversial . Local infiltration analgesia ( LIA ) has been reported to be effective for postoperative TKA pain control . We aim ed to assess whether LIA with continuous FNB is as effective as SNB combined with continuous FNB . Methods This was a prospect i ve , r and omized , single-center , observer-blinded , parallel group comparison trial of 34 American Society of Anesthesiologists ( ASA ) physical status 1–3 patients who underwent TKA and fulfilled the inclusion and exclusion criteria . Patients were r and omized into two groups : a periarticular LIA and FNB group ( group L , n = 17 ) , and an SNB and FNB group ( group S , n = 17 ) . In both groups , participants received FNB with 20 mL of 0.375 % ropivacaine , and 5 mL h−1 of 0.2 % ropivacaine after surgery . In group L , participants received 100-ml injections of 0.2 % ropivacaine and 0.5 mg epinephrine to the surgical region . In group S , participants received SNB with 20 ml of 0.375 % ropivacaine . After TKA , Numeric Rating Scale ( NRS ) scores for the first 24 h post-operation were compared via repeated- measures analysis of variance ( ANOVA ) as the primary outcome . Other outcome measures included NRS score changes within groups , area under the curve for the NRS scores , total analgesic dose , change in knee flexion and extension , pain control satisfaction , nausea and vomiting , and hospital stay duration . Results NRS score changes were greater in group L than in group S ( P < 0.01 , ANOVA ) and greater in group L than in group S at three postoperative time points : 3 h ( P < 0.01 ) , 6 h ( P < 0.01 ) , and 12 h ( P = 0.013 ; Mann – Whitney U test ) . Changes in the mean NRS score were observed in each group ( P < 0.01 , Friedman test ) . No significant differences were detected in the other outcome measures ( Mann – Whitney U , Wilcoxon signed-rank , and chi-squared tests ) . Conclusions Sciatic nerve block with femoral nerve block is superior to local anesthetic infiltration with femoral nerve block for postoperative pain control within 3–12 h of total knee arthroplasty . Trial registration Background and Objectives : The benefit of adding a sciatic nerve block to the femoral block to improve analgesia after total knee replacement is controversial . The aim of this study is to address this controversy in a prospect i ve , comparative , and r and omized study . Methods : Patients were allocated r and omly to receive a continuous femoral nerve block or continuous blocks of both the femoral and sciatic nerves . Stimulating catheters were used in all cases . A loading dose of 15 mL ropivacaine 0.75 % was injected into each catheter , followed by administration of ropivacaine 0.2 % ( 2 - 5 mL/h infusion via the femoral catheter ; bolus 10 mL repeated every 12 hours in the sciatic catheter ) . The primary outcome was visual analog scale ( VAS ) scores ( 0 = no pain , 100 mm = worst pain ) in postanesthesia care unit and in the 48-hour period after surgery . The secondary outcomes were amplitude of knee flexion , morphine consumption , and occurrence of postoperative nausea and vomiting ( PONV ) . Results : The VAS scores at rest were significantly higher when there was only continuous femoral nerve block than when there was both continuous femoral and sciatic nerve blocks . This difference progressively decreased and disappeared at 36 hours after surgery . The combined femoral and sciatic blocks decreased the morphine consumption by 81 % and significantly decreased the occurrence of PONV . Conclusion : During the 36 hours immediately after total knee replacement , the combination of continuous femoral and sciatic nerve blocks improves analgesia while decreasing morphine consumption and PONV Postoperative pain control after total knee arthroplasty ( TKA ) is a well-known clinical problem . Efforts to treat it with the use of local anesthesia have been made , but the results have been contradictive . In the late 1990s , an infiltrated solution of ropivacaine/ketorolac/adrenaline was shown to be effective for this purpose , and this technique has since spread over the world . The purpose of this study was to compare the local infiltration anesthesia technique with epidural anesthesia , which has been the most widely used technique in Sweden . Eighty-five patients received either local infiltration anesthesia or epidural anesthesia for postoperative pain relief . Postoperative morphine consumption , range of motion , walking ability , patient satisfaction , hospital stay , and time in the recovery room were measured . The groups were followed equally . The patients in the local infiltration anesthesia group were mobilized 24 hours earlier . On postoperative day one , 22 of 33 patients in the local infiltration anesthesia group could get in and out of bed without assistance . Only 1 of 31 patients in the epidural anesthesia group could manage this . On postoperative day two , 28 of 33 patients in the local infiltration anesthesia group could walk without assistance , compared to 5 of 31 in the epidural anesthesia group . Seventy-six percent of the local infiltration anesthesia patients were " very satisfied " with their postoperative pain control method , compared to 40 % of the epidural anesthesia patients .The local infiltration anesthesia technique is better for postoperative pain relief in TKA than epidural anesthesia . It offers equal pain relief , faster mobilization , and more satisfied patients . No negative side effects were seen during the study We conducted a prospect i ve r and omized controlled trial to test the null hypothesis that there is no difference between sciatic nerve block ( SNB ) and local infiltration of analgesia ( LIA ) regarding postoperative analgesia after total knee arthroplasty ( TKA ) , when administrated in addition to femoral nerve block ( FNB ) . Forty-six patients scheduled for TKA were r and omized into two groups : concomitant administration of FNB and SNB or FNB and LIA . Average pain scores during the first 21days after surgery were similar in the two groups and remained at low level . There was no significant difference in the need for adjuvant analgesics , patient satisfaction level , the time to achieve rehabilitation goals , and length of hospital stay . The LIA offers a potentially safer alternative to SNB as an adjunct to FNB |
13,361 | 26,990,451 | Low caloric DASH led to even more weight reduction when compared with other low-energy diets .
In addition , the effect was greater in overweight/obese participants and when compared with typical ( Western or population 's usual ) diets .
DASH diet is a good choice for weight management particularly for weight reduction in overweight and obese participants | BACKGROUND Dietary approaches to stop hypertension ( DASH ) diet is rich in foods that are proposed to be inversely associated with obesity .
Therefore , DASH might better affect body weight ; however , published data are conflicting .
OBJECTIVE To assess the effect of DASH on body weight and composition in adults . | BACKGROUND Although the Dietary Approaches to Stop Hypertension ( DASH ) diet is an accepted nonpharmacologic treatment for hypertension , little is known about what patient characteristics affect dietary adherence and what level of adherence is needed to reduce blood pressure ( BP ) . OBJECTIVE Our aim was to determine what factors predict dietary adherence and the extent to which dietary adherence is necessary to produce clinical ly meaningful BP reductions . DESIGN Ancillary study of the ENCORE ( Exercise and Nutrition Interventions for Cardiovascular Health ) trial -- a 16-week r and omized clinical trial of diet and exercise . PARTICIPANTS / SETTING Participants included 144 sedentary , overweight , or obese adults ( body mass index 25 to 39.9 ) with high BP ( systolic 130 to 159 mm Hg and /or diastolic 85 to 99 mm Hg ) . INTERVENTION Patients were r and omized to one of three groups : DASH diet alone , DASH diet plus weight management , and Usual Diet Controls . MAIN OUTCOMES MEASURES Our primary outcomes were a composite index of adherence to the DASH diet and clinic BP . STATISTICAL ANALYSES PERFORMED General linear models were used to compare treatment groups on post-treatment adherence to the DASH diet . Linear regression was used to examine potential predictors of post-treatment DASH adherence . Analysis of covariance was used to examine the relation of adherence to the DASH diet and BP . RESULTS Participants in the DASH diet plus weight management ( 16.1 systolic BP [ SBP ] ; 95 % CI 13.0 to 19.2 mm Hg and 9.9 diastolic BP [ DBP ] ; 95 % CI 8.1 to 11.6 mm Hg ) and DASH diet alone ( 11.2 SBP ; 95 % CI 8.1 to 14.3 mm Hg and 7.5 DBP ; 95 % CI 5.8 to 9.3 mm Hg ) groups showed significant reductions in BP in comparison with Usual Diet Controls participants ( 3.4 SBP ; 95 % CI 0.4 to 6.4 mm Hg and DBP 3.8 ; 95 % CI 2.2 to 5.5 mm Hg ) . Greater post-treatment consumption of DASH foods was noted in both the DASH diet alone ( mean = 6.20 ; 95 % CI 5.83 to 6.57 ) and DASH diet plus weight management groups ( mean = 6.23 ; 95 % CI 5.88 to 6.59 ) compared with Usual Diet Controls ( mean = 3.66 ; 95 % CI 3.30 to 4.01 ; P<0.0001 ) , and greater adherence to the DASH diet was associated with larger reductions in clinic SBP and DBP ( P ≤ 0.01 ) . Only ethnicity predicted dietary adherence , with African Americans less adherent to the DASH diet compared with whites ( 4.68 ; 95 % CI 4.34 to 5.03 vs 5.83 ; 95 % CI 5.50 to 6.11 ; P<0.001 ) . CONCLUSIONS Greater adherence to the DASH diet was associated with larger BP reductions independent of weight loss . African Americans were less likely to be adherent to the DASH dietary eating plan compared with whites , suggesting that culturally sensitive dietary strategies might be needed to improve adherence to the DASH diet High blood pressure increases the risks of stroke , dementia , and neurocognitive dysfunction . Although aerobic exercise and dietary modifications have been shown to reduce blood pressure , no r and omized trials have examined the effects of aerobic exercise combined with dietary modification on neurocognitive functioning in individuals with high blood pressure ( ie , prehypertension and stage 1 hypertension ) . As part of a larger investigation , 124 participants with elevated blood pressure ( systolic blood pressure 130 to 159 mm Hg or diastolic blood pressure 85 to 99 mm Hg ) who were sedentary and overweight or obese ( body mass index : 25 to 40 kg/m2 ) were r and omized to the Dietary Approaches to Stop Hypertension ( DASH ) diet alone , DASH combined with a behavioral weight management program including exercise and caloric restriction , or a usual diet control group . Participants completed a battery of neurocognitive tests of executive function-memory-learning and psychomotor speed at baseline and again after the 4-month intervention . Participants on the DASH diet combined with a behavioral weight management program exhibited greater improvements in executive function-memory-learning ( Cohen 's D=0.562 ; P=0.008 ) and psychomotor speed ( Cohen 's D=0.480 ; P=0.023 ) , and DASH diet alone participants exhibited better psychomotor speed ( Cohen 's D=0.440 ; P=0.036 ) compared with the usual diet control . Neurocognitive improvements appeared to be mediated by increased aerobic fitness and weight loss . Also , participants with greater intima-medial thickness and higher systolic blood pressure showed greater improvements in executive function-memory-learning in the group on the DASH diet combined with a behavioral weight management program . In conclusion , combining aerobic exercise with the DASH diet and caloric restriction improves neurocognitive function among sedentary and overweight/obese individuals with prehypertension and hypertension BACKGROUND The Dietary Approaches to Stop Hypertension ( DASH ) diet , which emphasizes fruits , vegetables , and low fat dairy products , significantly lowers blood pressure ( BP ) . We conducted a clinical trial to assess the BP response to the DASH diet with an antihypertensive medication , losartan , in participants with essential hypertension . METHODS A total of 55 hypertensive participants were r and omly assigned to 8 weeks of controlled feeding with either a control diet or the DASH diet . Within each diet arm , participants received losartan 50 mg daily or placebo for 4 weeks each , in double blind , r and omized , cross-over fashion . Twenty-four-hour ambulatory BP ( ABP ) was measured at the end of a 2-week run-in period ( baseline ) and after each 4-week intervention period . RESULTS There was no significant change in ABP during the placebo period on the control diet ( n = 28 ) ( -2.3 + /- 1.5/-1.6 + /- 1.0 mm Hg ) , but there was a significant reduction in systolic ABP ( -5.3 + /- 1.5 mm Hg , P < .05 ) and no change in DBP ( -2.5 + /- 1.0 mm Hg ) on the DASH diet ( n = 27 ) . Losartan significantly reduced ABP on the control diet ( -6.7 + /- 1.5/-3.7 + /- 1.0 mm Hg , P < .05 ) and to a greater extent on the DASH diet ( -11.7 + /- 1.5/-6.9 + /- 1.0 mm Hg , P < .05 versus basal and control diet ) particularly in African Americans . On the DASH diet , DeltaSBP on losartan was inversely related to basal plasma renin activity ( n = -0.53 , P = .004 ) . CONCLUSIONS The DASH diet enhances the ABP response to losartan in essential hypertension . This effect is particularly marked in African Americans OBJECTIVE High prevalence rates of prehypertension require nonpharmaceutical lifestyle interventions . The objective of this study was to assess the feasibility and initial efficacy of a primarily electronically delivered intervention for prehypertension . METHODS Twenty-three adults with prehypertension ( M age of 54.3 ; systolic blood pressure [ BP ] , 126.3 mmHg ; weight , 87.8 kg ; body mass index , 31.5 ; 6514 steps/day ) were r and omized to DASH 2 wellness only st and ard of care or to DASH 2 wellness plus . Both groups received instruction on the DASH eating plan , instructions to increase steps per day and use of a weight scale and pedometer , and information about social-cognitive theory-based self-regulation strategies . D2W plus also involved home blood pressure monitoring and monitoring steps per day , nutrition , and body weight . Through weekly newsletters , participants engaged in electronic reporting and goal setting and received feedback on progress . RESULTS D2W plus showed a larger increase in daily steps ( M = 2,900 ) than D2W only ( M = 636 ) ; a larger decrease in systolic BP ( mmHg ) , M = 15.1 versus M = 4.6 , and a larger decrease in weight ( in kg ) , M = 4.8 versus M = 1.5 . CONCLUSIONS Concentrating efforts not only toward adoption and initiation of innovative risk-reduction strategies but also toward the provision for long-term maintenance of a healthy lifestyle once initial changes have been accomplished is paramount . The D2W plus program could be adapted for such use in health care and other setting s for treating prehypertension Background —The Dietary Approaches to Stop Hypertension ( DASH ) diet is recommended in the 2005 US Dietary Guidelines . To underst and the potential benefits of DASH on coronary heart disease ( CHD ) , we applied the Framingham risk equations to calculate 10-year risk of developing CHD using data from the DASH trial . Methods and Results —In the DASH trial , 459 individuals with prehypertension or stage-1 hypertension not taking antihypertensive medication were r and omly assigned to 1 of 3 diets : control , fruits and vegetables ( F/V ) , or DASH ( rich in fruits , vegetables , low-fat dairy , and reduced in fats and cholesterol ) . Weight was held constant . Estimated 10-year CHD risk was the primary outcome of this secondary analysis . Among 436 participants with complete data , mean ( SD ) age was 44.7 ( 10.7 ) years , 51 % were male , and 60 % were African-American . Median 10-year CHD risk was 0.98 % at baseline and decreased in all groups . Compared with control , the relative risk ratio comparing 8-week with baseline 10-year CHD risk was 0.93 ( 95 % confidence interval , 0.85 to 1.02 ; P=0.12 ) for F/V and 0.82 ( 95 % confidence interval , 0.75 to 0.90 ; P<0.001 ) for DASH . Comparing DASH with F/V , the relative risk ratio was 0.89 ( 95 % confidence interval , 0.81 to 0.97 ; P=0.012 ) . With the exception of an interaction between dietary pattern and race suggesting a greater risk reduction in blacks than whites ( P for interaction=0.038 ) , results were similar across subgroups . Conclusions —Compared with control and F/V , the DASH diet reduced estimated 10-year CHD risk by 18 % and 11 % , respectively . In addition to reducing blood pressure , the DASH diet should substantially reduce the risk of CHD . Clinical Trial Registration —URL : http:// clinical trials.gov . Unique identifier : NCT00000544 Aims /hypothesisA diet low in saturated fatty acids and rich in wholegrains , vegetables and fruit is recommended in order to reduce the risk of obesity , cardiovascular disease and type 2 diabetes mellitus . However there is widespread interest in high-fat ( “ Atkins Diet ” ) and high-protein ( “ Zone Diet ” ) alternatives to the conventional high-carbohydrate , high-fibre approach . We report on a r and omised trial that compared these two alternative approaches with a conventional diet in overweight insulin-resistant women . Methods Ninety-six normoglycaemic , insulin-resistant women ( BMI > 27 kg/m2 ) were r and omised to one of three dietary interventions : a high-carbohydrate , high-fibre ( HC ) diet , the high-fat ( HF ) Atkins Diet , or the high-protein ( HP ) Zone Diet . The experimental approach was design ed to mimic what might be achieved in clinical practice : the recommendations involved advice concerning food choices and were not prescriptive in terms of total energy . There were supervised weight loss and weight maintenance phases ( 8 weeks each ) , but there was no contact between the research team and the participants during the final 8 weeks of the study . Outcome was assessed in terms of body composition and indicators of cardiovascular and diabetes risk . Results Body weight , waist circumference , triglycerides and insulin levels decreased with all three diets but , apart from insulin , the reductions were significantly greater in the HF and HP groups than in the HC group . These observations suggest that the popular diets reduced insulin resistance to a greater extent than the st and ard dietary advice did . When compared with the HC diet , the HF and HP diets were shown to produce significantly ( p<0.01 ) greater reductions in several parameters , including weight loss ( HF −2.8 kg , HF −2.7 kg ) , waist circumference ( HF −3.5 cm , HF −2.7 cm ) and triglycerides ( HF −0.30 mmol/l , HF −0.22 mmol/l ) . LDL cholesterol decreased in individuals on the HC and HP diets , but tended to fluctuate in those on the HF diet to the extent that overall levels were significantly lower in the HP group than in the HF group ( −0.28 mmol/l , 95 % CI 0.04–0.52 , p=0.02 ) . Of those on the HF diet , 25 % showed a > 10 % increase in LDL cholesterol , whereas this occurred in only 13 % of subjects on the HC diet and 3 % of those on the HP diet . Conclusions /interpretationIn routine practice a reduced-carbohydrate , higher protein diet may be the most appropriate overall approach to reducing the risk of cardiovascular disease and type 2 diabetes . To achieve similar benefits on a HC diet , it may be necessary to increase fibre-rich wholegrains , legumes , vegetables and fruits , and to reduce saturated fatty acids to a greater extent than appears to be achieved by implementing current guidelines . The HF approach appears successful for weight loss in the short term , but lipid levels should be monitored . The potential deleterious effects of the diet in the long term remain a concern BACKGROUND Dietary energy density ( ED ) reductions are associated with energy intake ( EI ) reductions . Little is known about influences on body weight ( BW ) . OBJECTIVES We examined the effects of behavioral interventions on ED values and explored how 6-mo ED changes relate to BW . DESIGN Prehypertensive and hypertensive persons were r and omly assigned to 1 of 3 groups : the established group received an 18-session intervention implementing well-established hypertension recommendations ( eg , weight loss , sodium reduction , and physical activity ) , the established+Dietary Approaches to Stop Hypertension ( DASH ) group received an 18-session intervention also implementing the DASH diet , and the advice group received 1 session on these topics . Two 24-h dietary recalls were collected ( n=658 ) . RESULTS Each group had significant declines in EI , ED , and BW . The established and established+DASH groups had the greatest EI and BW reductions . The established+DASH group had the greatest ED reduction and the greatest increase in the weight of food consumed . When groups were combined and analyzed by ED change tertiles , participants in the highest tertile ( ie , largest ED reduction ) lost more weight ( 5.9 kg ) than did those in the middle ( 4.0 kg ) or lowest ( 2.4 kg ) tertile . Participants in the highest and middle tertiles increased the weight of food they consumed ( 300 and 80 g/d , respectively ) but decreased their EI ( 500 and 250 kcal/d ) . Conversely , those in the lowest tertile decreased the weight of food consumed ( 100 g/d ) , with little change in EI . The highest and middle tertiles had favorable changes in fruit , vegetable , vitamin , and mineral intakes . CONCLUSION Both large and modest ED reductions were associated with weight loss and improved diet quality BACKGROUND Effects of diet on blood lipids are best known in white men , and effects of type of carbohydrate on triacylglycerol concentrations are not well defined . OBJECTIVE Our goal was to determine the effects of diet on plasma lipids , focusing on subgroups by sex , race , and baseline lipid concentrations . DESIGN This was a r and omized controlled outpatient feeding trial conducted in 4 field centers . The subjects were 436 participants of the Dietary Approaches to Stop Hypertension ( DASH ) Trial [ mean age : 44.6 y ; 60 % African American ; baseline total cholesterol : < or = 6.7 mmol/L ( < or = 260 mg/dL ) ] . The intervention consisted of 8 wk of a control diet , a diet increased in fruit and vegetables , or a diet increased in fruit , vegetables , and low-fat dairy products and reduced in saturated fat , total fat , and cholesterol ( DASH diet ) , during which time subjects remained weight stable . The main outcome measures were fasting total cholesterol , LDL cholesterol , HDL cholesterol , and triacylglycerol . RESULTS Relative to the control diet , the DASH diet result ed in lower total ( -0.35 mmol/L , or -13.7 mg/dL ) , LDL- ( -0.28 mmol/L , or -10.7 mg/dL ) , and HDL- ( -0.09 mmol/L , or -3.7 mg/dL ) cholesterol concentrations ( all P < 0.0001 ) , without significant effects on triacylglycerol . The net reductions in total and LDL cholesterol in men were greater than those in women by 0.27 mmol/L , or 10.3 mg/dL ( P = 0.052 ) , and by 0.29 mmol/L , or 11.2 mg/dL ( P < 0.02 ) , respectively . Changes in lipids did not differ significantly by race or baseline lipid concentrations , except for HDL , which decreased more in participants with higher baseline HDL-cholesterol concentrations than in those with lower baseline HDL-cholesterol concentrations . The fruit and vegetable diet produced few significant lipid changes . CONCLUSIONS The DASH diet is likely to reduce coronary heart disease risk . The possible opposing effect on coronary heart disease risk of HDL reduction needs further study BACKGROUND Weight loss reduces blood pressure , and the Dietary Approaches to Stop Hypertension ( DASH ) diet has also been shown to lower blood pressure . OBJECTIVE Our goal was to assess the effect on blood pressure of 2 weight-reduction diets : a low-fat diet ( LF diet ) and a moderate-sodium , high-potassium , high-calcium , low-fat DASH diet ( WELL diet ) . DESIGN After baseline measurements , 63 men were r and omly assigned to either the WELL or the LF diet for 12 wk , and both diet groups undertook 0.5 h of moderate physical activity on most days of the week . RESULTS Fifty-four men completed the study . Their mean ( + /-SD ) age was 47.9 + /- 9.3 y ( WELL diet , n = 27 ; LF diet , n = 27 ) , and their mean baseline home systolic and diastolic blood pressures were 129.4 + /- 11.3 and 80.6 + /- 8.6 mm Hg , respectively . Body weight decreased by 4.9 + /- 0.6 kg ( + /-SEM ) in the WELL group and by 4.6 + /- 0.6 kg in the LF group ( P < 0.001 for both ) . There was a greater decrease in blood pressure in the WELL group than in the LF group [ between-group difference ( week 12 -baseline ) in both SBP ( 5.5 + /- 1.9 mm Hg ; P = 0.006 ) and DBP ( 4.4 + /- 1.2 mm Hg ; P = 0.001 ) ] . CONCLUSIONS For a comparable 5-kg weight loss , a diet high in low-fat dairy products , vegetables , and fruit ( the WELL diet ) result ed in a greater decrease in blood pressure than did the LF diet . This dietary approach to achieving weight reduction may confer an additional benefit in reducing blood pressure in those who are overweight BACKGROUND Estimating energy requirements is a frequent task in clinical studies . OBJECTIVE We examined weight patterns of participants enrolled in a clinical trial and evaluated factors that may affect weight stabilization . The Harris-Benedict equation and the FAO/WHO equation , used in conjunction with physical activity levels estimated with the 7-d Physical Activity Recall , were compared for estimating energy expenditure . DESIGN This was a multicenter , r and omized controlled feeding trial with participants of the Dietary Approaches to Stop Hypertension Trial . For 11 wk , the amount of food participants received was adjusted to maintain their body weights as close to their initial weights as possible . Change-point regression techniques were used to identify weight-stable periods . Factors related to achieving weight stabilization were examined with logistic regression . RESULTS A stable weight was achieved by 86 % of the 448 participants during the run-in period and by 78 % during the intervention period . Energy intake averaged 11 + /- 2.4 MJ/d ( 2628 + /- 578 kcal/d ) , with most participants ( n = 270 ) requiring 9 - 13 MJ/d ( 2100 - 3100 kcal/d ) . The difference between predicted and observed intakes was highest at high estimated energy intakes , mainly because of high and probably incorrect estimates of the activity factor . Participants with lower energy intakes tended to need less adjustment of their energy intakes to maintain a stable weight than did participants with higher energy intakes . CONCLUSIONS Weight stabilization is not affected by diet composition , sex , race , age , or baseline weight . Either the Harris-Benedict equation or the FAO/WHO equation can be used to estimate energy needs . Activity factors > 1.7 often lead to overestimation of energy needs A diet rich in fruits , vegetables , and low-fat dairy foods has been shown to lower blood pressure ( BP ) when all foods are provided . We compared the effect on BP ( measured at home ) of 2 different self-selected diets : a low-sodium , high-potassium diet , rich in fruit and vegetables ( LNAHK ) and a high-calcium diet rich in low-fat dairy foods ( HC ) with a moderate-sodium , high-potassium , high-calcium DASH-type diet , high in fruits , vegetables and low-fat dairy foods ( OD ) . Subjects were r and omly allocated to 2 test diets for 4 wk , the OD and either LNAHK or HC diet , each preceded by a 2 wk control diet ( CD ) . The changes in BP between the preceding CD period and the test diet period ( LNAHK or HC ) were compared with the change between the CD and the OD periods . Of the 56 men and 38 women that completed the OD period , 43 completed the LNAHK diet period and 48 the HC diet period . The mean age was 55.6 + /- 9.9 ( + /-SD ) years . There was a fall in systolic pressure between and the CD and OD [ -1.8 + /- 0.5 mm Hg ( P < 0.001 ) ] . Compared with OD , systolic and diastolic BPs fell during the LNAHK diet period [ -3.5 + /- 1.0 ( P < 0.001 ) and -1.9 + /- 0.7 ( P < 0.05 ) mmHg , respectively ] and increased during the HC diet period [ + 3.1 + /- 0.9 ( P < 0.01 ) and + 0.8 + /- 0.6 ( P = 0.15 ) mm Hg , respectively ] . A self-selected low-sodium , high-potassium diet result ed in a greater fall in BP than a multifaceted OD , confirming the beneficial effect of dietary intervention on BP in a community setting BACKGROUND Although increased consumption of dietary fiber and grain products is widely recommended to maintain healthy body weight , little is known about the relation of whole grains to body weight and long-term weight changes . OBJECTIVE We examined the associations between the intakes of dietary fiber and whole- or refined-grain products and weight gain over time . DESIGN In a prospect i ve cohort study , 74,091 US female nurses , aged 38 - 63 y in 1984 and free of known cardiovascular disease , cancer , and diabetes at baseline , were followed from 1984 to 1996 ; their dietary habits were assessed in 1984 , 1986 , 1990 , and 1994 with vali date d food-frequency question naires . Using multiple models to adjust for covariates , we calculated average weight , body mass index ( BMI ; in kg/m(2 ) ) , long-term weight changes , and the odds ratio of developing obesity ( BMI > or = 30 ) according to change in dietary intake . RESULTS Women who consumed more whole grains consistently weighed less than did women who consumed less whole grains ( P for trend < 0.0001 ) . Over 12 y , those with the greatest increase in intake of dietary fiber gained an average of 1.52 kg less than did those with the smallest increase in intake of dietary fiber ( P for trend < 0.0001 ) independent of body weight at baseline , age , and changes in covariate status . Women in the highest quintile of dietary fiber intake had a 49 % lower risk of major weight gain than did women in the highest quintile ( OR = 0.51 ; 95 % CI : 0.39 , 0.67 ; P < 0.0001 for trend ) . CONCLUSION Weight gain was inversely associated with the intake of high-fiber , whole-grain foods but positively related to the intake of refined-grain foods , which indicated the importance of distinguishing whole-grain products from refined-grain products to aid in weight control Hypertension is one of the leading causes of morbidity and mortality in Brazil . Diet may play an important role in reducing blood pressure ( BP ) , as has been shown for diets high in fruits , vegetables and low-fat dairy products and low in salt ( Dietary Approaches to Stop Hypertension (DASH)-Na ) . A low-glycaemic index Brazilian diet combined with the principles of the DASH-Na diet was evaluated in a r and omised study of 206 individuals who were followed for 6 months . In the control group ( CG ) , counselling was based on st and ard care and mainly focused on salt intake reduction . An intention-to-treat analysis showed that , after 6 months , systolic BP was reduced by 14·4 mmHg and diastolic BP by 9·7 mmHg in the experimental group ( EG ) , compared with 6·7 and 4·6 mmHg , respectively , in the CG . After adjusting for body weight , BP at baseline and age , these changes were 12·1 and 7·9 mmHg , respectively . Urinary Na excretion was also reduced by 43·4 mEq/24 h in the EG . Food intake was modified accordingly during the intervention with an increase in the consumption of vegetables ( 2·97 - 5·85 frequency of consumption measured in three non-consecutive days ) , fruits ( 4·09 - 7·18 ) , beans ( 1·94 - 3·13 ) and fish ( 1·80 - 2·74 ) by the EG . The present study showed the feasibility of a Brazilian dietary approach to treating hypertension by reducing urinary Na excretion and BP , changes that may have a great impact on public health and promote the benefits of controlling hypertension BACKGROUND There is a paucity of data describing the sustained benefits of lifestyle interventions on health behaviors and blood pressure ( BP ) . METHODS We examined the persistence of changes in health habits and BP in the ENCORE study , a trial in which 144 overweight individuals with above-normal BP were r and omized to one of the following 16-week interventions : Dietary Approaches to Stop Hypertension ( DASH ) diet alone ( DASH-A ) , DASH diet plus a behavioral weight management intervention ( DASH-WM ) , or Usual Care . Follow-up assessment s were conducted 8 months after the end of treatment . RESULTS At 16 weeks , systolic BP was reduced by 16.1 ( 95 % confidence interval ( CI ) = 13.0 - 19.2 ) mm Hg in the DASH-WM group , 11.2 ( 95 % CI = 8.1 - 14.3 ) mm Hg in the DASH-A group , and 3.4 ( 95 % CI = 0.4 - 6.4 ) mm Hg in the Usual Care group . A decrease in BP persisted for 8 months , with systolic BP lower than baseline by 11.7 ( 95 % CI = 8.1 - 15.3 ) mm Hg in the DASH-WM group , 9.5 ( 95 % CI = 6.7 - 12.1 ) mm Hg in the DASH-A group , and 3.9 ( 95 % CI = 0.5 - 7.3 ) mm Hg in the Usual Care group ( P < 0.001 for active treatments vs. Usual Care ) . DASH-WM subjects lost 8.7 kg during the intervention and remained 6.3 kg lighter on follow-up examination . Changes in diet content were sustained in both DASH intervention groups . Among those who participated in DASH-WM , however , caloric intake was no longer lower , and only 21 % reported still exercising regularly 8 months after completing the intervention . CONCLUSIONS Changes in dietary habits , weight , and BP persisted for 8 months after completion of the 16-week ENCORE program , with some attenuation of the benefits . Additional research is needed to identify effective methods to promote long-term maintenance of the benefits of lifestyle modification programs . CLINICAL TRIAL REGISTRATION Clinical trials.gov identifier : NCT00571844 OBJECTIVE Examine the acceptability of sodium-reduced research diets . DESIGN R and omized crossover trial of three sodium levels for 30 days each among participants r and omly assigned to one of two dietary patterns . PARTICIPANTS / SETTING Three hundred fifty-four adults with prehypertension or stage 1 hypertension who were participants in the Dietary Approaches to Stop Hypertension ( DASH-Sodium ) outpatient feeding trial . INTERVENTION Participants received their assigned diet ( control or DASH , rich in fruits , vegetables , and low-fat dairy products ) , each at three levels of sodium ( higher , intermediate , and lower ) corresponding to 3,500 , 2,300 , and 1,200 mg/day ( 150 , 100 , and 50 mmol/day ) per 2,100 kcal . MAIN OUTCOME MEASURES Nine-item question naire on liking and willingness to continue the assigned diet and its level of saltiness using a nine-point scale , ranging from one to nine . STATISTICAL ANALYSES PERFORMED Generalized estimating equations to test participant ratings as a function of sodium level and diet while adjusting for site , feeding cohort , carryover effects , and ratings during run-in . RESULTS Overall , participants rated the saltiness of the intermediate level sodium as most acceptable ( DASH group : 5.5 for intermediate vs 4.5 and 4.4 for higher and lower sodium ; control group : 5.7 for intermediate vs 4.9 and 4.7 for higher and lower sodium ) and rated liking and willing to continue the DASH diet more than the control diet by about one point ( ratings range from 5.6 to 6.6 for DASH diet and 5.2 to 6.1 for control diet ) . Small race differences were observed in sodium and diet acceptability . CONCLUSIONS Both the intermediate and lower sodium levels of each diet are at least as acceptable as the higher sodium level in persons with or at risk for hypertension OBJECTIVE : To examine the changes in intake of fruits and vegetables in relation to risk of obesity and weight gain among middle-aged women . DESIGN : Prospect i ve cohort study with 12 y of follow-up conducted in the Nurses ' Health Study .SUBJECTS : A total of 74 063 female nurses aged 38–63 y , who were free of cardiovascular disease , cancer , and diabetes at baseline in 1984 . MEASUREMENTS : Dietary information was collected using a vali date d food frequency question naire , and body weight and height were self-reported . RESULTS : During the 12-y follow-up , participants tended to gain weight with aging , but those with the largest increase in fruit and vegetable intake had a 24 % of lower risk of becoming obese ( BMI ≥30 kg/m2 ) compared with those who had the largest decrease in intake after adjustment for age , physical activity , smoking , total energy intake , and other lifestyle variables ( relative risk ( RR ) , 0.76 ; 95 % confidence interval ( CI ) , 0.69–0.86 ; P for trend < 0.0001 ) . For major weight gain ( ≥25 kg ) , women with the largest increase in intake of fruits and vegetables had a 28 % lower risk compared to those in the other extreme group ( RR , 0.72 ; 95 % CI , 0.55–0.93 ; P=0.01 ) . Similar results were observed for changes in intake of fruits and vegetables when analyzed separately . CONCLUSIONS : Our findings suggest that increasing intake of fruits and vegetables may reduce long-term risk of obesity and weight gain among middle-aged women Background / Objectives : The current study was performed to investigate the effects of the Dietary Approaches to Stop Hypertension ( DASH ) eating plan on pregnancy outcomes in pregnant women with gestational diabetes mellitus (GDM).Subjects/ Methods : This r and omized controlled clinical trial was performed among 52 women diagnosed with GDM . Participants were r and omly assigned to consume either the control ( n=26 ) or the DASH diet ( n=26 ) for 4 weeks . The control diet was design ed to contain 45–55 % carbohydrates , 15–20 % protein and 25–30 % total fat . The DASH diet was rich in fruits , vegetables , whole grains and low-fat dairy products , and contained lower amounts of saturated fats , cholesterol and refined grains with a total of 2400 mg/day sodium . The numbers of women who commenced insulin therapy after dietary intervention , the mode of delivery and prevalence of polyhydramnios were assessed . The length , weight and head circumference of infants were measured during the first 24 h after birth . Results : Whereas 46.2 % of women in the DASH diet needed to have a cesarean section , this percentage for the control group was 80.8 % ( P=0.01 ) . The percentage of those who needed to commence insulin therapy after intervention was also significantly different between the two groups ( 23 % for DASH vs 73 % for control group , P<0.0001 ) . Infants born to mothers on the DASH diet had significantly lower weight ( 3222.7 vs 3818.8 g , P<0.0001 ) , head circumference ( 34.2 vs 35.1 cm , P=0.01 ) and ponderal index ( 2.50 vs 2.87 kg/m3 , P<0.0001 ) compared with those born to mothers on the control diet . Conclusions : In conclusion , consumption of DASH diet for 4 weeks among pregnant women with GDM result ed in improved pregnancy outcomes OBJECTIVE To determine the effects of the Dietary Approaches to Stop Hypertension ( DASH ) eating pattern on cardiometabolic risks in type 2 diabetic patients . RESEARCH DESIGN AND METHODS A r and omized crossover clinical trial was undertaken in 31 type 2 diabetic patients . For 8 weeks , participants were r and omly assigned to a control diet or the DASH eating pattern . RESULTS After following the DASH eating pattern , body weight ( P = 0.007 ) and waist circumference ( P = 0.002 ) reduced significantly . Fasting blood glucose levels and A1C decreased after adoption of the DASH diet ( −29.4 ± 6.3 mg/dl ; P = 0.04 and −1.7 ± 0.1 % ; P = 0.04 , respectively ) . After the DASH diet , the mean change for HDL cholesterol levels was higher ( 4.3 ± 0.9 mg/dl ; P = 0.001 ) and LDL cholesterol was reduced ( −17.2 ± 3.5 mg/dl ; P = 0.02 ) . Additionally , DASH had beneficial effects on systolic ( −13.6 ± 3.5 vs. −3.1 ± 2.7 mmHg ; P = 0.02 ) and diastolic blood pressure ( −9.5 ± 2.6 vs. −0.7 ± 3.3 mmHg ; P = 0.04 ) . CONCLUSIONS Among diabetic patients , the DASH diet had beneficial effects on cardiometabolic risks Abstract — Evidence suggests that obesity may raise blood pressure ( BP ) through oxidative stress – sensitive mechanisms and that the Dietary Approaches to Stop Hypertension combination diet ( DASH-CD ) may decrease BP by enhancing antioxidant capacity . To address this question , 12 obese patients with high-normal – to – stage 1 hypertension ( hypertensives ) and 12 lean normotensives were studied on their usual diets and after following the DASH-CD and a low-antioxidant diet in r and om sequence for 4 weeks each . Acute oxidative stress was induced by a 4-hour infusion of intralipid and heparin . Ferric-reducing activity of plasma ( FRAP ) and plasma F2-isoprostanes were measured as biomarkers of antioxidant capacity and oxidative stress , respectively . BP was lower in obese hypertensives on the DASH-CD than on the usual and low-antioxidant diets ( −8.1±1.5/−7.4±1.6 mm Hg , P < 0.05 ) . BP did not change significantly in lean normotensives after 4 weeks on the DASH-CD but tended to rise on the low-antioxidant diet . FRAP on usual diets was higher in lean subjects than in obese subjects . FRAP increased in obese but not lean volunteers on the DASH-CD compared with usual diet , and the group difference disappeared . F2-isoprostanes increased from baseline during intralipid and heparin in both groups on the low-antioxidant diet but not in obese hypertensives on the DASH-CD . Among free-living obese hypertensives , the DASH-CD raises antioxidant capacity , lowers BP , and reduces oxidative stress induced by acute hyperlipidemia . The findings are consistent with evidence that elevated BP in obese subjects may reflect an imbalance between antioxidant capacity and oxidative stress that is improved by the DASH-CD Endothelial dysfunction has been recognized as a pathophysiologic mechanism in the progression of heart failure ( HF ) . However , little attention has been given to the ability of dietary approaches to improve endothelial function . This study examined the effects of the Dietary Approaches to Stop Hypertension ( DASH ) diet on endothelial function , exercise capacity , and quality of life in patients with chronic symptomatic ( stage C ) HF . Forty-eight patients were r and omized to follow the DASH diet ( n = 24 ) or the general HF dietary recommendations ( n = 24 ) . Endothelial function was assessed by measuring large and small arterial elasticity ( LAE and SAE ) at rest . Exercise capacity ( measured with the 6-minute walk test ) and quality of life ( measured with the Minnesota Living with Heart Failure Question naire ) at baseline and 3 months were also evaluated . Patients were older adults with an average HF duration of 5 years . LAE at 1 month improved significantly in the DASH diet group ( P < 0.01 ) . Overall LAE and SAE scores at 3 months also improved ; however , the net changes were not statistically significant . The DASH group had better exercise capacity ( 292 m vs 197 m ; P = 0.018 ) and quality of life scores ( 21 vs 39 ; P = 0.006 ) over time , while sodium intake levels at 1 , 2 , and 3 months were comparable between the groups . Adhering to the DASH diet improved arterial compliance initially and improved exercise capacity and quality of life scores at 3 months . The DASH diet may be an important adjunctive therapy for patients with symptomatic H Use of the DASH ( Dietary Approaches to Stop Hypertension ) diet , which is rich in fruits , vegetables , and low-fat dairy foods , significantly lowers blood pressure . Among the 459 participants in the DASH Trial , 72 had stage 1 isolated systolic hypertension ( ISH ) ( systolic blood pressure , 140 to 159 mm Hg ; diastolic blood pressure , < 90 mm Hg ) . We examined the blood pressure response in these 72 participants to determine whether the DASH diet is an effective treatment for stage 1 ISH . After a 3-week run-in period on a typical American ( control ) diet , participants were r and omly assigned for 8 weeks to 1 of 3 diets : a continuation of the control diet ( n=25 ) , a diet rich in fruits and vegetables ( n=24 ) , or the DASH diet ( n=23 ) . Sodium content was the same in the 3 diets , and caloric intake was adjusted during the trial to prevent weight change . Blood pressure was measured at baseline and at the end of the 8-week intervention period with st and ard sphygmomanometry . Use of the DASH diet significantly lowered systolic blood pressure compared with the control diet ( −11.2 mm Hg ; 95 % confidence interval , −6.1 to −16.2 mm Hg;P < 0.001 ) and the fruits/vegetables diet ( −8.0 mm Hg ; 95 % confidence interval , −2.5 to −13.4 mm Hg;P < 0.01 ) . Overall , blood pressure in the DASH group fell from 146/85 to 134/82 mm Hg . Similar results were observed with 24-hour ambulatory blood pressure measurements . In the DASH diet group , 18 of 23 participants ( 78 % ) reduced their systolic blood pressure to < 140 mm Hg , compared with 24 % and 50 % in the control and fruits/vegetables groups , respectively . Our results indicate that the DASH diet , which is rich in fruits , vegetables , and low-fat dairy foods , is effective as first-line therapy in stage 1 ISH Complementary medicine advocates the use of a multifactorial approach to address the varied aspects of hypertension . The aim of this study was to compare the blood pressure ( BP ) effect and medication use of a novel Comprehensive Approach to Lowering Measured Blood Pressure ( CALM-BP ) , based on complementary medicine principles , with the st and ard recommended Dietary Approach to Stop Hypertension ( DASH ) . A total of 113 patients treated with antihypertensive drugs were r and omly assigned to either CALM-BP treatment ( consisting of rice diet , walks , yoga , relaxation and stress management ) or to a DASH+exercise control group ( consisting of DASH and walks ) . Ambulatory 24-h and home BP were monitored over a 16-week programme , followed by 6 months of maintenance period . Medications were reduced if systolic BP dropped below 110 mm Hg accompanied by symptoms . In addition to BP reduction , medications were reduced because of symptomatic hypotension in 70.7 % of the CALM-BP group compared with 32.7 % in the DASH group , P<0.0001 . After 6 months , medication status was not altered in the majority of individuals . Significant reductions in body mass index , cholesterol and improved quality -of-life scores were observed only in the CALM-BP group . Lifestyle and diet modifications based on complementary medicine principles are highly effective with respect to BP control , medication use and cardiovascular risk factors The mechanism underlying blood pressure ( BP ) reduction in the high fruits and vegetables arm of the Dietary Approaches to Stop Hypertension ( DASH ) study is unknown but may include potassium , magnesium and fibre . This study was design ed to separate minerals and fibre from other components of DASH on BP in abdominally obese individuals with metabolic syndrome with pre-hypertension to stage 1 hypertension ( obese hypertensives ) . A total of 15 obese hypertensives and 15 lean normotensives were studied on a st and ardized usual diet , r and omized to DASH or usual diet supplemented with potassium , magnesium and fibre to match DASH , then crossed over to the complementary diet . All diets were 3 weeks long , isocaloric and matched for sodium and calcium . In obese hypertensives , BP was lower after 3 weeks on DASH than usual diet ( −7.6±1.4/−5.3±1.4 mm Hg , P<0.001/0.02 ) and usual diet supplemented ( −6.2±1.4/−3.7±1.4 P<0.005/0.06 ) , whereas BP was not significantly different on usual and supplemented diets . BP values were not different among the three diets in lean normotensives . Small artery elasticity was lower in obese hypertensives than in lean normotensives on the usual and supplemented diets ( P<0.02 ) . This index of endothelial function improved in obese hypertensives ( P<0.02 ) but not lean normotensives on DASH , and was no longer different from values in lean normotensives ( P>0.50 ) . DASH is more effective than potassium , magnesium and fibre supplements for lowering BP in obese hypertensives , which suggest that high fruits and vegetables DASH lowers BP and improves endothelial function in this group by nutritional factors in addition to potassium , magnesium and fibre OBJECTIVE To determine the effects of dietary patterns on blood pressure in subgroups . METHODS Dietary Approaches to Stop Hypertension ( DASH ) was a r and omized controlled feeding study conducted at 4 academic medical centers . Participants were 459 adults with untreated systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg . For 3 weeks , participants were fed a " control " diet . They were then r and omized to 8 weeks of ( 1 ) control diet ; ( 2 ) a diet rich in fruits and vegetables ; or ( 3 ) a combination diet rich in fruits , vegetables , and low-fat dairy foods , and reduced in saturated fat , total fat , and cholesterol ( the DASH combination diet ) . Weight and salt intake were held constant . Change in diastolic blood pressure was the primary outcome variable , and systolic blood pressure a secondary outcome . Subgroups analyzed included race , sex , age , body mass index , years of education , income , physical activity , alcohol intake , and hypertension status . RESULTS The combination diet significantly lowered systolic blood pressure in all subgroups ( P<.008 ) , and significantly lowered diastolic blood pressure ( P<.01 ) in all but 2 subgroups . The fruits- and -vegetables diet also reduced blood pressure in the same subgroups , but to a lesser extent . The combination diet lowered systolic blood pressure significantly more in African Americans ( 6.8 mm Hg ) than in whites ( 3.0 mm Hg ) , and in hypertensive subjects ( 11.4 mm Hg ) than in nonhypertensive subjects ( 3.4 mm Hg ) ( P<.05 for both interactions ) . CONCLUSIONS The DASH combination diet , without sodium reduction or weight loss , significantly lowered blood pressure in virtually all subgroups examined , and was particularly effective in African Americans and those with hypertension . The DASH combination diet may be an effective strategy for preventing and treating hypertension in a broad cross section of the population , including segments of the population at highest risk for blood pressure-related cardiovascular disease The impact of resistance training has not been thoroughly examined in overweight older adults undergoing weight loss . Subjects ( n = 27 ) were overweight and obese ( BMI 31.7 ± 3.6 kg/m2 ) older ( age 67 ± 4 years ) adults and were r and omized into either a 10-week Dietary Approaches to Stop Hypertension for weight loss diet ( DASH , n = 12 ) or DASH plus moderate intensity resistance training ( DASH-RT , n = 15 ) . Outcomes included weight loss , total body and mid-thigh composition , muscle and physical function . There were no significant weight loss differences between the DASH-RT and DASH groups ( −3.6 ± 0.8 vs. −2.0 ± 0.9 % , p = 0.137 ) . The DASH-RT group had a greater reduction in body fat than the DASH group ( −4.1 ± 0.9 vs. −0.2 ± 1.0 kg , p = 0.005 ) . The DASH-RT group had greater changes in lean mass ( + 0.8 ± 0.4 vs. −1.4 ± 0.4 kg , p = 0.002 ) and strength ( + 60 ± 18 vs. −5 ± 9 N , p = 0.008 ) than the DASH group . There were favorable changes in mid-thigh composition variables in the DASH-RT group that were different than the lack of changes observed in the DASH group , except for intermuscular adipose tissue . Both groups experienced decreases in 400-m walk times showed ( DASH −36 ± 11 s , DASH-RT −40 ± 7 s ) with no differences between groups . Moderate intensity resistance training during weight loss appears to improve fat mass and thigh composition , but weight loss only does not . However , global measures of physical functioning may improve with a weight loss-only program Background Dietary Approaches to Stop Hypertension ( DASH ) has been shown to successfully reduce systolic ( SBP ) and diastolic blood pressure ( DBP ) when evaluated in clinical ly controlled environments but there is a lack of information regarding the efficacy of the original DASH diet when it is applied in a free-living environment . Purpose To provide descriptive data as to the changes in blood pressure individuals could expect to achieve when following the DASH diet in a free-living environment for 4-weeks with no additional behavioral modifications . Methods Twenty , pre- and stage 1 hypertensive participants were r and omly split into 2 groups ; DASH ( males N = 5 , females N = 5 , age = 38.5 ± 10.8 ) and control ( males N = 7 , females N = 3 , age = 38.1 ± 11.1 ) . The DASH group was instructed on how to follow the DASH diet on their own for 4-weeks while the control group continued their normal diet . SBP , DBP , body weight , 3-day food diaries and physical activity recall question naire data were collected pre and post intervention using a traditional person-to-person instructional technique . Results Two-way ANOVA demonstrated that there was a significant group ( DASH , control ) by time ( pre , post ) interaction for SBP ( P = 0.003 ) and no significant effects for DBP . The interaction was due to a significant reduction ( P < 0.001 ) in SBP in the DASH group ( pre : 141.3 ± 11.3 mmHg vs. post : 130.7 ± 9.1 mmHg ) over the course of the intervention with no change in SBP in the control group ( pre : 133.5 ± 6.6 mmHg vs. post : 131.9 ± 8.9 mmHg ) . Pearson 's correlation analyses revealed that changes in potential moderators of blood pressure including body weight , BMI , sodium intake and total kilocalories were each not associated with changes in SBP ( r ≤ 0.14 , P ≥ 0.5 ) or DBP ( r < 0.10 , P ≥ 0.6 ) pre- to post-treatment . Chi-square demonstrated no significant differences in the number of participants per group ( n = 4 DASH , n = 1 control ) who indicated increasing physical activity during the intervention . Conclusion DASH diet followed in a free-living environment significantly reduced SBP but not DBP . However , the changes in SBP and DBP were very similar to those noted in controlled clinical feeding evaluations of the DASH diet . Presently , none of the potential moderators of blood pressure that were assessed were independently associated with the observed changes in blood pressure which may be due to our small sample size or the possibility that it is the combined change in multiple factors that lead to reductions in blood pressure when following the DASH diet BACKGROUND Although dietary factors are suspected to be important determinants of coronary heart disease ( CHD ) risk , the direct evidence is relatively sparse . METHODS The Adventist Health Study is a prospect i ve cohort investigation of 31,208 non-Hispanic white California Seventh-Day Adventists . Extensive dietary information was obtained at baseline , along with the values of traditional coronary risk factors . These were related to risk of definite fatal CHD or definite nonfatal myocardial infa rct ion . RESULTS Subjects who consumed nuts frequently ( more than four times per week ) experienced substantially fewer definite fatal CHD events ( relative risk , 0.52 ; 95 % confidence interval [ CI ] , 0.36 to 0.76 ) and definite nonfatal myocardial infa rct ions ( relative risk , 0.49 ; 95 % CI , 0.28 to 0.85 ) , when compared with those who consumed nuts less than once per week . These findings persisted on covariate adjustment and were seen in almost all of 16 different subgroups of the population . Subjects who usually consumed whole wheat bread also experienced lower rates of definite nonfatal myocardial infa rct ion ( relative risk , 0.56 ; 95 % CI , 0.35 to 0.89 ) and definite fatal CHD ( relative risk , 0.89 ; 95 % CI , 0.60 to 1.33 ) when compared with those who usually ate white bread . Men who ate beef at least three times each week had a higher risk of definite fatal CHD ( relative risk , 2.31 ; 95 % CI , 1.11 to 4.78 ) , but this effect was not seen in women or for the nonfatal myocardial infa rct ion end point . CONCLUSION Our data strongly suggest that the frequent consumption of nuts may protect against risk of CHD events . The favorable fatty acid profile of many nuts is one possible explanation for such an effect To determine the impact of dietary patterns on the control of hypertension we studied the subgroup of 133 participants with systolic blood pressure ( BP ) of 140 to 159 mm Hg and /or diastolic BP of 90 to 95 mm Hg enrolled in the Dietary Approaches to Stop Hypertension ( DASH ) study . Participants were fed a control diet for a 3-week period and were then r and omized to receive for 8 weeks either the control diet ; a diet rich in fruits and vegetables , but otherwise similar to control ; or a combination diet rich in fruits , vegetables , and low-fat dairy products , including whole grains , fish , poultry , and nuts , and reduced in fats , red meats , sweets , and sugar-containing beverages . Sodium intake and body weight were held constant throughout the study . The combination diet significantly reduced systolic BP ( -11.4 mm Hg , P < .001 ) and diastolic BP ( -5.5 mm Hg , P < .001 ) . The fruits- and -vegetables diet also significantly reduced systolic BP ( -7.2 mm Hg , P < .001 ) and diastolic BP ( -2.8 mm Hg , P = .013 ) . The combination diet produced significantly greater BP effects ( P < .05 ) than the fruits- and -vegetables diet . Blood pressure changes were evident within 2 weeks of starting the intervention feeding . After the 8-week intervention period , 70 % of participants eating the combination diet had a normal BP ( systolic BP < 140 and diastolic BP < 90 mm Hg ) compared with 45 % on the fruits- and -vegetables diet and 23 % on the control diet . In patients with hypertension , the DASH combination diet effectively lowers BP and may be useful in achieving control of Stage 1 hypertension BACKGROUND Despite the popularity of the low-carbohydrate , high-protein , high-fat ( Atkins ) diet , no r and omized , controlled trials have evaluated its efficacy . METHODS We conducted a one-year , multicenter , controlled trial involving 63 obese men and women who were r and omly assigned to either a low-carbohydrate , high-protein , high-fat diet or a low-calorie , high-carbohydrate , low-fat ( conventional ) diet . Professional contact was minimal to replicate the approach used by most dieters . RESULTS Subjects on the low-carbohydrate diet had lost more weight than subjects on the conventional diet at 3 months ( mean [ + /-SD ] , -6.8+/-5.0 vs. -2.7+/-3.7 percent of body weight ; P=0.001 ) and 6 months ( -7.0+/-6.5 vs. -3.2+/-5.6 percent of body weight , P=0.02 ) , but the difference at 12 months was not significant ( -4.4+/-6.7 vs. -2.5+/-6.3 percent of body weight , P=0.26 ) . After three months , no significant differences were found between the groups in total or low-density lipoprotein cholesterol concentrations . The increase in high-density lipoprotein cholesterol concentrations and the decrease in triglyceride concentrations were greater among subjects on the low-carbohydrate diet than among those on the conventional diet throughout most of the study . Both diets significantly decreased diastolic blood pressure and the insulin response to an oral glucose load . CONCLUSIONS The low-carbohydrate diet produced a greater weight loss ( absolute difference , approximately 4 percent ) than did the conventional diet for the first six months , but the differences were not significant at one year . The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease . Adherence was poor and attrition was high in both groups . Longer and larger studies are required to determine the long-term safety and efficacy of low-carbohydrate , high-protein , high-fat diets Background : A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol . To our knowledge , no studies have evaluated a low – saturated fatty acid ( SFA ) ( < 7 % calories ) diet that contains lean beef . Objective : We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ ie , Dietary Approaches to Stop Hypertension ( DASH ) : 28 g beef/d ; Beef in an Optimal Lean Diet ( BOLD ) : 113 g beef/d ; and Beef in an Optimal Lean Diet plus additional protein ( BOLD+ ) : 153 g beef/d ] compared with that of a healthy American diet ( HAD ) . Design : Thirty-six hypercholesterolemic participants ( with LDL-cholesterol concentrations > 2.8 mmol/L ) were r and omly assigned to consume each of the 4 diets ( HAD : 33 % total fat , 12 % SFA , 17 % protein , and 20 g beef/d ) , DASH ( 27 % total fat , 6 % SFA , 18 % protein , and 28 g beef/d ) , BOLD ( 28 % total fat , 6 % SFA , 19 % protein , and 113 g beef/d ) , and BOLD+ ( 28 % total fat , 6 % SFA , 27 % protein , and 153 g beef/d ) for 5 wk . Results : There was a decrease in total cholesterol ( TC ) and LDL-cholesterol concentrations ( P < 0.05 ) after consumption of the DASH ( −0.49 ± 0.11 and −0.37 ± 0.09 mmol/L , respectively ) , BOLD ( −0.48 ± 0.10 and −0.35 ± 0.9 mmol/L , respectively ) , and BOLD+ ( −0.50 ± 0.10 and −0.345 ± 0.09 mmol/L , respectively ) diets compared with after consumption of the HAD ( −0.22 ± 0.10 and −0.14 ± 0.10 mmol/L , respectively ) . Apolipoprotein A-I , C-III , and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD , and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD ( P < 0.05 for both ) . LDL cholesterol and TC decreased after consumption of the DASH , BOLD , and BOLD+ diets when the baseline C-reactive protein ( CRP ) concentration was < 1 mg/L ; LDL cholesterol and TC decreased when baseline CRP concentration was > 1 mg/L with the BOLD and BOLD+ diets . Conclusions : Low-SFA , heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease ( CVD ) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern . These results , in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets , which were greater with the BOLD+ diet , provide support for including lean beef in a heart-healthy dietary pattern . This trial was registered at clinical trials.gov as NCT00937898 National guidelines for the prevention and treatment of hypertension recommend sodium reduction , weight loss , the Dietary Approach to Stop Hypertension ( DASH ) diet , and regular aerobic exercise . However , no trial has assessed the efficacy of simultaneously implementing all of these recommendations . The objective of this study was to determine the effects on blood pressure and other cardiovascular disease risk factors of a comprehensive lifestyle intervention . We conducted a r and omized controlled trial of 44 hypertensive , overweight adults on a single blood pressure medication . Participants were r and omized to a lifestyle or control group . For 9 weeks , the lifestyle group was fed a hypocaloric version of the DASH diet that provided 100 mmol/d of sodium . This group also participated in a supervised , moderate-intensity exercise program 3 times per week . The control group received no intervention . Outcomes were ambulatory blood pressure , serum lipids , weight , and fitness . At the end of the intervention , mean weight loss in the lifestyle group , net of control , was 4.9 kilograms . In the lifestyle group mean net reductions in 24-hour ambulatory systolic and diastolic blood pressures were 9.5 mm Hg ( P<0.001 ) and 5.3 mm Hg ( P<0.002 ) , respectively . Corresponding changes in daytime systolic and diastolic blood pressures were 12.1 mm Hg ( P<0.001 ) and 6.6 mm Hg ( P<0.001 ) . The lifestyle group experienced mean reductions in total cholesterol ( -25 mg/dL , P<0.001 ) , low-density lipoprotein cholesterol ( -18 mg/dL , P=0.005 ) , high-density lipoprotein cholesterol ( -5 mg/dL , P<0.001 ) , net of control . In conclusion , among hypertensive overweight adults already on antihypertensive medication , a comprehensive lifestyle intervention can substantially lower blood pressure and improve blood pressure control Background — Although trials of lifestyle interventions generally focus on cardiovascular disease risk factors rather than hard clinical outcomes , 10-year coronary heart disease ( CHD ) risk can be estimated from the Framingham risk equations . Our objectives were to study the effect of 2 multicomponent lifestyle interventions on estimated CHD risk relative to advice alone and to evaluate whether differences can be observed in the effects of the lifestyle interventions among subgroups defined by baseline variables . Methods and Results — A total of 810 healthy adults with untreated prehypertension or stage I hypertension were r and omized to 1 of 3 intervention groups : An “ advice-only ” group , an “ established ” group that used established lifestyle recommendations for blood pressure control ( sodium reduction , weight loss , and increased physical activity ) , or an “ established-plus-DASH ” group that combined established lifestyle recommendations with the DASH ( Dietary Approaches to Stop Hypertension ) diet . The primary outcome was 10-year CHD risk , estimated from follow-up data collected at 6 months . A secondary outcome was 10-year CHD risk at 18 months . Of the 810 participants , 62 % were women and 34 % were black . Mean age was 50 years , mean systolic/diastolic blood pressure was 135/85 mm Hg , and median baseline Framingham risk was 1.9 % . The relative risk ratio comparing 6-month to baseline Framingham risk was 0.86 ( 95 % confidence interval 0.81 to 0.91 , P<0.001 ) in the established group and 0.88 ( 95 % confidence interval 0.83 to 0.94 , P<0.001 ) in the established-plus-DASH group relative to advice alone . Results were virtually identical in sensitivity analyses , in each major subgroup , and at 18 months . Conclusions — The observed reductions of 12 % to 14 % in estimated CHD risk are substantial and , if achieved , should have important public health benefits BACKGROUND It is known that obesity , sodium intake , and alcohol consumption factors influence blood pressure . In this clinical trial , Dietary Approaches to Stop Hypertension , we assessed the effects of dietary patterns on blood pressure . METHODS We enrolled 459 adults with systolic blood pressures of less than 160 mm Hg and diastolic blood pressures of 80 to 95 mm Hg . For three weeks , the subjects were fed a control diet that was low in fruits , vegetables , and dairy products , with a fat content typical of the average diet in the United States . They were then r and omly assigned to receive for eight weeks the control diet , a diet rich in fruits and vegetables , or a " combination " diet rich in fruits , vegetables , and low-fat dairy products and with reduced saturated and total fat . Sodium intake and body weight were maintained at constant levels . RESULTS At base line , the mean ( + /-SD ) systolic and diastolic blood pressures were 131.3+/-10.8 mm Hg and 84.7+/-4.7 mm Hg , respectively . The combination diet reduced systolic and diastolic blood pressure by 5.5 and 3.0 mm Hg more , respectively , than the control diet ( P<0.001 for each ) ; the fruits- and -vegetables diet reduced systolic blood pressure by 2.8 mm Hg more ( P<0.001 ) and diastolic blood pressure by 1.1 mm Hg more than the control diet ( P=0.07 ) . Among the 133 subjects with hypertension ( systolic pressure , > or = 140 mm Hg ; diastolic pressure , > or = 90 mm Hg ; or both ) , the combination diet reduced systolic and diastolic blood pressure by 11.4 and 5.5 mm Hg more , respectively , than the control diet ( P<0.001 for each ) ; among the 326 subjects without hypertension , the corresponding reductions were 3.5 mm Hg ( P<0.001 ) and 2.1 mm Hg ( P=0.003 ) . CONCLUSIONS A diet rich in fruits , vegetables , and low-fat dairy foods and with reduced saturated and total fat can substantially lower blood pressure . This diet offers an additional nutritional approach to preventing and treating hypertension Background The clinical significance of glycemic index ( GI ) and glycemic load ( GL ) is inconclusive . Objective This study was conducted to examine the association of GI and GL with clinical cardiovascular disease ( CVD ) risk factors including body weight , blood pressure ( BP ) , serum lipids , fasting glucose , insulin and homocysteine over time among the PREMIER participants . Design PREMIER was an 18-month r and omized lifestyle intervention trial , conducted from 2000 to 2002 , design ed to help participants reduce BP by following the Dietary Approaches to Stop Hypertension ( DASH ) dietary pattern , losing weight , reducing sodium and increasing physical activity . GI and GL were estimated from 24 h diet recall data at baseline , 6 and 18 months after intervention . PROC MIXED model was used to examine the association of changes in GI or GL with changes in CVD risk factors . Results A total of 756 r and omized participants , 62 % females and 34 % African Americans and who averaged 50.0±0.3 years old and 95.3±0.7 kg , were included in this report . Neither GI nor GL changes was associated with changes in any risk factors at 6 months . At 18 months , however , the GI change was significantly and positively associated with total cholesterol ( TC ) change only ( p<0.05 , β=23.80±12.11 mg/dL or 0.62±0.31 mmol/L ) with a significant age interaction . The GL change was significantly associated with TC ( p=0.02 , β=0.28±0.15 mg/dL or 0.01±0.00 mmol/L ) positively and with low density lipoprotein cholesterol ( LDL-C ) changes negatively ( p=0.03 , β=−0.01±0.00 mg/dL or −0.00±0.00 mmol/L ) , and significant age interactions were observed for both . Conclusions GI and GL was associated with TC and LDL-C after controlling for energy , fat and fiber intake and other potential confounders and the associations were modified by age . Further investigation into this relationship is important because of its potential clinical impact A DASH ( dietary approaches to stop hypertension ) dietary pattern rich in fruits and vegetables and low-fat dairy products with increased dietary protein provided primarily from plant protein sources decreases blood pressure . No studies , however , have evaluated the effects of a DASH-like diet with increased dietary protein from lean beef on blood pressure and vascular health . The aim of this study was to study the effect of DASH-like diets that provided different amounts of protein from lean beef ( DASH 28 g beef per day ; beef in an optimal lean diet ( BOLD ) 113 g beef per day ; beef in an optimal lean diet plus additional protein ( BOLD+ ) 153 g beef per day ) on blood pressure , endothelial function and vascular reactivity versus a healthy American diet ( HAD ) . Using a r and omized , crossover study design , 36 normotensive participants ( systolic blood pressure ( SBP ) , 116±3.6 mm Hg ) were fed four isocaloric diets , : HAD ( 33 % total fat , 12 % saturated fatty acids ( SFA ) , 17 % protein ( PRO ) , 20 g beef per day ) , DASH ( 27 % total fat , 6 % SFA , 18 % PRO , 28 g beef per day ) , BOLD ( 28 % total fat , 6 % SFA , 19 % PRO , 113 g beef per day ) and BOLD+ ( 28 % total fat , 6 % SFA , 27 % PRO , 153 g beef per day ) , for 5 weeks . SBP decreased ( P<0.05 ) in subjects on the BOLD+ diet ( 111.4±1.9 mm Hg ) versus HAD ( 115.7±1.9 ) . There were no significant effects of the DASH and BOLD diets on SBP . Augmentation index ( AI ) was significantly reduced in participants on the BOLD diet ( −4.1 % ) . There were no significant effects of the dietary treatments on diastolic blood pressure or endothelial function ( as measured by peripheral arterial tonometry ) . A moderate protein DASH-like diet including lean beef decreased SBP in normotensive individuals . The inclusion of lean beef in a heart healthy diet also reduced peripheral vascular constriction Abstract Objective : To examine the relation between nut consumption and risk of coronary heart disease in a cohort of women from the Nurses ' Health Study . Design : Prospect i ve cohort study . Setting : Nurses ' Health Study . Subjects : 86 016 women from 34 to 59 years of age without previously diagnosed coronary heart disease , stroke , or cancer at baseline in 1980 . Main outcome measures : Major coronary heart disease including non-fatal myocardial infa rct ion and fatal coronary heart disease . Results : 1255 major coronary disease events ( 861 cases of non-fatal myocardial infa rct ion and 394 cases of fatal coronary heart disease ) occurred during 14 years of follow up . After adjusting for age , smoking , and other known risk factors for coronary heart disease , women who ate more than five units of nuts ( one unit equivalent to 1 oz of nuts ) a week ( frequent consumption ) had a significantly lower risk of total coronary heart disease ( relative risk 0.65 , 95 % confidence interval 0.47 to 0.89 , P for trend=0.0009 ) than women who never ate nuts or who ate less than one unit a month ( rare consumption ) . The magnitude of risk reduction was similar for both fatal coronary heart disease ( 0.61 , 0.35 to 1.05 , P for trend=0.007 ) and non-fatal myocardial infa rct ion ( 0.68 , 0.47 to 1.00 , P for trend=0.04 ) . Further adjustment for intakes of dietary fats , fibre , vegetables , and fruits did not alter these results . The inverse association persisted in subgroups stratified by levels of smoking , use of alcohol , use of multivitamin and vitamin E supplements , body mass index , exercise , and intake of vegetables or fruits . Conclusions : Frequent nut consumption was associated with a reduced risk of both fatal coronary heart disease and non-fatal myocardial infa rct ion . These data , and those from other epidemiological and clinical studies , support a role for nuts in reducing the risk of coronary heart disease Despite widely publicized hypertension treatment guidelines for physicians and lifestyle recommendations for patients , blood pressure control rates remain low . In community-based primary care clinics , we performed a nested , 2 × 2 r and omized , controlled trial of physician intervention versus control and /or patient intervention versus control . Physician intervention included internet-based training , self-monitoring , and quarterly feedback reports . Patient intervention included 20 weekly group sessions followed by 12 monthly telephone counseling contacts and focused on weight loss , Dietary Approaches to Stop Hypertension dietary pattern , exercise , and reduced sodium intake . The primary outcome was change in systolic blood pressure at 6 months . Eight primary care practice s ( 32 physicians ) were r and omized to physician intervention or control groups . Within those practice s , 574 patients were r and omized to patient intervention or control groups . Patient mean age was 60 years , 61 % were women , and 37 % were black . Blood pressure data were available for 91 % of patients at 6 months . The main effect of physician intervention on systolic blood pressure at 6 months , adjusted for baseline pressure , was 0.3 mm Hg ( 95 % CI : −1.5 to 2.2 ; P=0.72 ) . The main effect of the patient intervention was −2.6 mm Hg ( 95 % CI : −4.4 to −0.7 ; P=0.01 ) . The interaction of the 2 interventions was significant ( P=0.03 ) ; the largest impact was observed with the combination of physician and patient intervention ( −9.7±12.7 mm Hg ) . Differences between treatment groups did not persist at 18 months . Combined physician and patient interventions lowers blood pressure ; future research should focus on enhancing effectiveness and sustainability of these interventions Salt induces oxidative stress in salt-sensitive ( SS ) animals and man . It is not known whether in SS subjects the low-sodium dietary approaches to stop hypertension ( LS-DASH ) reduces oxidative stress more than DASH , which is high in antioxidants . To assess the effects of DASH and LS-DASH on oxidative stress , 19 volunteers were studied after 3 weeks of a st and ardized usual low fruits and vegetables diet ( ULFV ) , followed by 3 weeks on DASH ( both diets ∼120 mmol Na+ per day ) , then 3 weeks on LS-DASH ( 60 mmol Na+ per day ) . SS was defined as systolic blood pressure ⩾5 mm Hg lower on LS-DASH than DASH . In SS subjects ( N=9 ) , systolic blood pressure was lower on LS-DASH ( 111.0±2.0 mm Hg ) than DASH ( 118.0±2.2 , P<0.01 ) and ULFV ( 122.3±2.7 , P=0.002 ) . In salt-resistant ( SR ) volunteers ( N=10 ) , systolic blood pressure was lower on DASH ( 113.0±1.6 ) than ULFV ( 119.0±1.8 , P<0.05 ) but not LS-DASH ( 115.7±1.8 ) . Urine F2-isoprostanes , a marker of oxidative stress , were lower in SS subjects on LS-DASH ( 1.69±0.24 ) than ULFV ( 3.09±0.50 , P<0.05 ) and marginally lower than DASH ( 2.46±0.44 , P<0.20 ) . F2-isoprostanes were not different among the three diets in SR volunteers ( 2.18±0.29 , 2.06±0.29 , 2.27±0.53 , respectively ) . Aortic augmentation index , a measure of vascular stiffness , was lower in SS subjects on LS-DASH than either DASH or ULFV , and lower on DASH than ULFV in SR volunteers . In SS but not SR subjects , LS-DASH is associated with lower values for F2-isoprostanes and the aortic augmentation index . The results suggest that LS-DASH decreases oxidative stress , improves vascular function and lowers blood pressure in SS but not SR volunteers Background Increased lipoprotein(a ) [ Lp(a ) ] levels are associated with atherosclerotic cardiovascular disease . Studies of dietary interventions on changes in Lp(a ) are sparse . We aim ed to compare the effects of three healthy dietary interventions differing in macronutrient content on Lp(a ) concentration . Methods Secondary analysis of a r and omized , 3-period crossover feeding study including 155 ( 89 blacks ; 66 whites ) individuals . Participants were given DASH-type healthy diets rich in carbohydrates [ Carb ] , in protein [ Prot ] or in unsaturated fat [ Unsat Fat ] for 6 weeks each . Plasma Lp(a ) concentration was assessed at baseline and after each diet . Results Compared to baseline , all interventional diets increased mean Lp(a ) by 2 to 5 mg/dl . Unsat Fat increased Lp(a ) less than Prot with a difference of 1.0 mg/dl ( 95 % CI , −0.5 , 2.5 ; p = 0.196 ) in whites and 3.7 mg/dl ( 95 % CI , 2.4 , 5.0 ; p<0.001 ) in blacks ( p-value between races = 0.008 ) ; Unsat Fat increased Lp(a ) less than Carb with a difference of −0.6 mg/dl , 95 % CI , −2.1 , 0.9 ; p = 0.441 ) in whites and −1.5 mg/dl ( 95 % CI , −0.2 , −2.8 ; p = 0.021 ) in blacks ( p-value between races = 0.354 ) . Prot increased Lp(a ) more than Carb with a difference of 0.4 mg/dl ( 95 % CI , −1.1 , 1.9 ; p = 0.597 ) in whites and 2.2 mg/dl ( 95%CI , 0.9 , 3.5 ; p = 0.001 ) in blacks ( p-value between races = 0.082 ) . Conclusion Diets high in unsaturated fat increased Lp(a ) levels less than diets rich in carbohydrate or protein with greater changes in blacks than whites . Our results suggest that substitutions with dietary mono- and polyunsaturated fatty acids in healthy diets may be preferable over protein or carbohydrates with regards to Lp(a ) . Trial Registration Clinical trials.gov BACKGROUND The effect of dietary composition on blood pressure is a subject of public health importance . We studied the effect of different levels of dietary sodium , in conjunction with the Dietary Approaches to Stop Hypertension ( DASH ) diet , which is rich in vegetables , fruits , and low-fat dairy products , in persons with and in those without hypertension . METHODS A total of 412 participants were r and omly assigned to eat either a control diet typical of intake in the United States or the DASH diet . Within the assigned diet , participants ate foods with high , intermediate , and low levels of sodium for 30 consecutive days each , in r and om order . RESULTS Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg ( P<0.001 ) during the control diet and by 1.3 mm Hg ( P=0.03 ) during the DASH diet . Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet ( P<0.001 ) and 1.7 mm Hg during the DASH diet ( P<0.01 ) . The effects of sodium were observed in participants with and in those without hypertension , blacks and those of other races , and women and men . The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level ; and the difference was greater with high sodium levels than with low ones . As compared with the control diet with a high sodium level , the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension , and 11.5 mm Hg lower in participants with hypertension . CONCLUSIONS The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially , with greater effects in combination than singly . Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods Low-sodium Dietary Approaches to Stop Hypertension ( DASH ) diets are base producing but restrict red meat without clear justification . We hypothesized that a vitality diet ( VD ) , a low-sodium DASH-type diet with a low dietary acid load containing 6 servings of 100 g cooked lean red meat per week , would be more effective in reducing blood pressure ( BP ) compared with a higher acid load reference healthy diet ( RHD ) based on general dietary guidelines to reduce fat intake and increase intake of breads and cereals . A r and omized , parallel dietary intervention study was conducted to compare the BP-lowering effect of these 2 diets in postmenopausal women with high/normal BP . Women were r and omly assigned to follow either VD or RHD for 14 weeks . Home BP was measured daily with an automated BP monitor under st and ard conditions . Of 111 women commencing the study , 95 completed ( 46 VD , 49 RHD ) . Systolic BP ( SBP ) throughout the intervention was lower in the VD group compared to the RHD group ( repeated- measures analysis of variance time by diet , P = .04 ) , such that at the end of the study , the VD had a fall of SBP by 5.6 + /- 1.3 mm Hg ( mean + /- SEM ) compared with a fall of 2.7 + /- 1.0 mm Hg in the RHD ( group difference , P = .08 ) . When only those taking antihypertensive medications were assessed , the VD ( n = 17 ) had a significant fall of 6.5 + /- 2.5 mm Hg SBP ( P = .02 ) and 4.6 + /- 1.4 mm Hg diastolic BP ( P = .005 ) after 14 weeks , and their BP was lower than that of the RHD group ( n = 18 ) throughout the study ( P < .05 ) . We concluded that a low-sodium DASH diet with a low dietary acid load , which also included lean red meat on most days of the week , was effective in reducing BP in older women , particularly in those taking antihypertensive medications Background : Population s eating mainly vegetarian diets have lower blood pressure levels than those eating omnivorous diets . Epidemiologic findings suggest that eating fruits and vegetables lowers blood pressure A r and omised , parallel- design dietary intervention study was conducted in women ( aged 45 - 75 years ) with prehypertension or stage 1 hypertension . The aim was to compare the effects on bone turnover of a low-Na base-producing ( LNAB ) Dietary Approaches to Stop Hypertension (DASH)-type diet ( including six serves lean red meat/week ) with a high-carbohydrate low-fat ( HCLF ) diet with a higher acid load ( both > 800 mg dietary Ca/d ) . Fasting serum bone markers ( baseline and week 14 ) and 24 h urinary electrolyte excretion ( baseline , weeks 4 , 8 , 12 and 14 ) were measured . After the intervention period , the LNAB group ( n 46 ) had a fall of 26 ( sem 6 ) % ( P < 0.0001 ) in urinary Na , an increase in K excretion ( 6.8 ( sem 3.6 ) mmol/d ; P = 0.07 ) and , compared with the HCLF group ( n 49 ) , a greater reduction in urinary Ca excretion by 0.7 ( sem 0.3 ) mmol/d . Serum 25-hydroxyvitamin D , intact parathyroid hormone and osteocalcin did not change , and both groups had a similar increase of 23 ( sem 5 ) % ( P < 0.0001 ) in C-terminal telopeptide of type I collagen . The HCLF group had an 11 ( sem 4 ) % increase ( P = 0.003 ) in N-terminal propeptide , type I procollagen , which could indicate an increased rate of bone turnover . The fall in urinary Ca with the lower-Na lower-acid load diet is likely to have long-term beneficial effects on bone . As bone resorption was not different between the two dietary patterns with relatively high Ca intake , the effect on bone health of a dietary pattern with a lower acid load warrants further study on a lower Ca intake Identifying dietary modifications that potentiate the blood pressure (BP)-lowering effects of antihypertensive medications and that are practical for free-living people may assist in achieving BP reduction goals . We assessed whether two dietary patterns were effective in lowering BP in persons on antihypertensive therapy and in those not on therapy . Ninety-four participants ( 38/56 females/males ) , aged 55·6 ( SD 9·9 ) years , consumed two 4-week dietary regimens in r and om order ( Dietary Approaches to Stop Hypertension (DASH)-type diet and low- Na high-K ( LNAHK ) diet ) with a control diet before each phase . Seated home BP was measured daily for the last 2 weeks in each phase . Participants were grouped based on antihypertensive drug therapy . The LNAHK diet produced a greater fall in systolic BP ( SBP ) in those on antihypertensive therapy ( -6·2 ( SD 6·0 ) mmHg ) than in those not on antihypertensive therapy ( -2·8 ( SD 4·0 ) mmHg ) ( P = 0·036 ) , and this was greatest for those on renin-angiotensin system ( RAS ) blocker therapy ( -9·5 ( SD 6·4 ) mmHg ) ( interaction P = 0·007 ) . The fall in SBP on the DASH-type diet , in those on therapy ( overall -1·1 ( SD 6·2 ) mmHg ; renin-angiotensin blocker therapy -4·2 ( SD 4·7 ) mmHg ) , was not as marked as that observed on the LNAHK diet . Dietary modifications are an important part of all hypertension management regimens , and a low-Na and high-K diet enhances the BP-lowering effect of antihypertensive medications , particularly those targeting the RAS BACKGROUND Although the DASH ( Dietary Approaches to Stop Hypertension ) diet has been shown to lower blood pressure ( BP ) in short-term feeding studies , it has not been shown to lower BP among free-living individuals , nor has it been shown to alter cardiovascular biomarkers of risk . OBJECTIVE To compare the DASH diet alone or combined with a weight management program with usual diet controls among participants with prehypertension or stage 1 hypertension ( systolic BP , 130 - 159 mm Hg ; or diastolic BP , 85 - 99 mm Hg ) . DESIGN AND SETTING R and omized , controlled trial in a tertiary care medical center with assessment s at baseline and 4 months . Enrollment began October 29 , 2003 , and ended July 28 , 2008 . PARTICIPANTS Overweight or obese , unmedicated out patients with high BP ( N = 144 ) . INTERVENTIONS Usual diet controls , DASH diet alone , and DASH diet plus weight management . OUTCOME MEASURES The main outcome measure is BP measured in the clinic and by ambulatory BP monitoring . Secondary outcomes included pulse wave velocity , flow-mediated dilation of the brachial artery , baroreflex sensitivity , and left ventricular mass . RESULTS Clinic-measured BP was reduced by 16.1/9.9 mm Hg ( DASH plus weight management ) ; 11.2/7.5 mm ( DASH alone ) ; and 3.4/3.8 mm ( usual diet controls ) ( P < .001 ) . A similar pattern was observed for ambulatory BP ( P < .05 ) . Greater improvement was noted for DASH plus weight management compared with DASH alone for pulse wave velocity , baroreflex sensitivity , and left ventricular mass ( all P < .05 ) . CONCLUSION For overweight or obese persons with above-normal BP , the addition of exercise and weight loss to the DASH diet result ed in even larger BP reductions , greater improvements in vascular and autonomic function , and reduced left ventricular mass . CLINICAL TRIAL REGISTRATION clinical trials.gov Identifier : NCT00571844 Recommendations for control of high blood pressure ( BP ) emphasize lifestyle modification , including weight loss , reduced sodium intake , increased physical activity , and limited alcohol consumption . The Dietary Approaches to Stop Hypertension ( DASH ) dietary pattern also lowers BP . The PREMIER r and omized trial tested multicomponent lifestyle interventions on BP in demographic and clinical subgroups . Participants with above-optimal BP through stage 1 hypertension were r and omized to an Advice Only group or one of two behavioural interventions that implement established recommendations ( Est ) or established recommendations plus DASH diet ( Est plus DASH ) . The primary outcome was change in systolic BP at 6 months . The study population was 810 individuals with an average age of 50 years , 62 % women , 34 % African American ( AA ) , 95 % overweight/obese , and 38 % hypertensive . Participants in all the three groups made lifestyle changes . Mean net reductions in systolic ( S ) BP in the Est intervention were 1.2 mmHg in AA women , 6.0 in AA men , 4.5 in non-AA women , and 4.2 in non-AA men . The mean effects of the Est Plus DASH intervention were 2.1 , 4.6 , 4.2 , and 5.7 mmHg in the four race – sex subgroups , respectively . BP changes were consistently greater in hypertensives than in nonhypertensives , although interaction tests were nonsignificant . The Est intervention caused statistically significant BP reductions in individuals over and under age 50 . The Est Plus DASH intervention lowered BP in both age groups , and significantly more so in older individuals . In conclusion , diverse groups of people can adopt multiple lifestyle changes that can lead to improved BP control and reduced CVD risk Although gestational diabetes mellitus ( GDM ) is associated with an increased risk of maternal and neonatal morbidity , there is no consensus as to the optimal approach of nutritional management in these patients . The present study was design ed to assess the effect of the Dietary Approaches to Stop Hypertension ( DASH ) eating plan on glucose tolerance and lipid profiles of pregnant women with GDM . The present r and omised controlled clinical trial was performed among thirty-four women diagnosed with GDM at 24 - 28 weeks of gestation . Subjects were r and omly assigned to consume either the control diet ( n 17 ) or the DASH eating pattern ( n 17 ) for 4 weeks . The control diet was design ed to contain 45 - 55 % carbohydrates , 15 - 20 % protein and 25 - 30 % total fat . The macronutrient composition of the DASH diet was similar to the control diet ; however , the DASH diet was rich in fruits , vegetables , whole grains and low-fat dairy products , and contained lower amounts of saturated fats , cholesterol and refined grains with a total of 2400 mg Na/d . Fasting blood sample s were taken at baseline and after 4 weeks of intervention to measure fasting plasma glucose , glycated Hb ( HbA1c ) and lipid profiles . Participants underwent a 3 h oral glucose tolerance tests and blood sample s were collected at 60 , 120 and 180 min to measure plasma glucose levels . Adherence to the DASH eating pattern , compared with the control diet , result ed in improved glucose tolerance such that plasma glucose levels reduced at 60 ( 21·86 v. 20·45 mmol/l , Pgroup = 0·02 ) , 120 ( 22·3 v. 0·2 mmol/l , Pgroup = 0·001 ) and 180 min ( 21·7 v. 0·22 mmol/l , Pgroup = 0·002 ) after the glucose load . Decreased HbA1c levels ( 20·2 v. 0·05 % , Pgroup = 0·001 ) was also seen in the DASH group compared with the control group . Mean changes for serum total ( 20·42 v. 0·31 mmol/l , Pgroup = 0·01 ) and LDL-cholesterol ( 20·47 v. 0·22 mmol/l , Pgroup = 0·005 ) , TAG ( 20·17 v. 0·34 mmol/l , Pgroup = 0·01 ) and total : HDL-cholesterol ratio ( 20·6 ( SD 0·9 ) v. 0·3 ( SD 0·8 ) , Pgroup = 0·008 ) were significantly different between the two diets . Additionally , consumption of the DASH diet favourably influenced systolic blood pressure ( 22·6 v. 1·7 mmHg , Pgroup = 0·001 ) . Mean changes of fasting plasma glucose ( 20·29 v. 0·15 mmol/l , Pgroup = 0·09 ) were nonsignificant comparing the DASH diet with the control diet . In conclusion , consumption of the DASH eating pattern for 4 weeks among pregnant women with GDM result ed in beneficial effects on glucose tolerance and lipid profiles compared with the control diet Hypertensive patients often have an unfavorable lipid and glucose profile . The main goal of dietary treatment for these patients is to achieve adequate control of blood pressure and reducing cardiovascular morbidity and mortality . The aim of this study was to evaluate whether the Brazilian Dietary Approach to Break Hypertension ( BRADA ) based on Dietary Approaches to Stop Hypertension but with both low sodium and glycemic index foods could reduce lipid and glycemic profiles in hypertensive patients who were seeing primary health care providers in a low-income region of Brazil . A r and omized study of 206 individuals were followed up for the duration of 6 months . The experimental group received orientation and planned monthly menus from the BRADA diet . In the control group , counseling was based on st and ard care and mainly focused on salt intake reduction . Differences in all biochemical parameters were compared at the baseline and at the 6-month follow-up period . The mean age was 60.1 ( ±12.9 ) years old , and 156 subjects ( 119 females ) completed the study . An intention-to-treat analysis showed that both groups reduced fasting plasma glucose , glycated hemoglobin , total cholesterol , and low-density lipoprotein cholesterol concentrations ; however , statistically significant between-group differences were found for these parameters . The mean difference in fasting glucose was -7.0 ( P < .01 ) , -0.2 for HbA1c ( P < .01 ) , -28.6 for TC ( P < .01 ) , and -23.8 for LDL-c ( P < .01 ) for the experimental group compared with the control group . This study showed the efficacy of the BRADA diet to treat hypertension on biochemical parameters tested in a primary health care service setting Objective To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals . Design R and omized controlled trial . Setting Research studies unit . Participants Overweight hypertensive patients , receiving one or two antihypertensive drugs , were recruited by advertising , and allocated r and omly to a usual care group ( controls ; n = 118 ) or a lifestyle modification group ( programme group ; n = 123 ) . Intervention A 4-month programme of weight loss , a low-sodium ‘ Dietary Approaches to Stop Hypertension’-type diet with added fish , physical activity and moderation of alcohol intake . After 4 months , if mean 24-h ambulatory blood pressure ( ABP ) was less than 135/85 mmHg , antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun . Main outcome measures Antihypertensive drug requirements , ABP , weight , waist girth at 4 months and 1-year follow-up . Results Ninety control group and 102 programme group participants completed the study . Mean 24-h ABP changed after 4 months by −1.0/−0.3 ± 0.5/0.4 mmHg in controls and −4.1/−2.1 ± 0.7/0.5 mmHg with the lifestyle programme ( P < 0.01 ) . At follow-up , changes in the two groups were not significantly different ( 4.1/1.3 ± 1.1/1.0 mmHg in controls ; 2.5/−0.1 ± 1.1/0.8 mmHg in the programme group ; P = 0.73 ) . At 4 months , drug withdrawal differed significantly between the groups ( P = 0.038 ) in men ( control 44 % ; programme 66 % ) but not in women ( 65 and 64 % , respectively ; P = 0.964 ) . At follow-up , sex-related differences were not significant , and 41 % in the control group and 43 % in the programme group maintained drug-withdrawal status . With the programme , net weight loss was 3.3 kg ( P < 0.001 ) at 4 months and 3.0 kg ( P < 0.001 ) at follow-up ; respective net decreases in waist girth were 3.3 cm ( P < 0.001 ) and 3.5 cm ( P < 0.001 ) . Conclusions A 4-month multifactorial lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term . Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk BACKGROUND & AIMS To compare the acute effects of three fatty meals with different fat quality on postpr and ial thermogenesis , substrate oxidation and satiety . METHODS Twenty-nine healthy men aged between 18 and 30 years participated in a r and omised crossover trial comparing the thermogenic effects of three isocaloric meals : high in polyunsaturated fatty acids from walnuts , high in monounsaturated fatty acids from olive oil , and high in saturated fatty acids from fat-rich dairy products . Indirect calorimetry was used to determine resting metabolic rate , respiratory quotient , 5-h postpr and ial energy expenditure and substrate oxidation . Satiety was estimated by using visual analogue scales and measuring caloric intake in a subsequent ad libitum meal . RESULTS Five-h postpr and ial thermogenesis was higher by 28 % after the high-polyunsaturated meal ( p=0.039 ) and by 23 % higher after the high-monounsaturated meal ( p=0.035 ) compared with the high-saturated meal . Fat oxidation rates increased nonsignificantly after the two meals rich in unsaturated fatty acids and decreased nonsignificantly after the high-saturated fatty acid meal . Postpr and ial respiratory quotient , protein and carbohydrate oxidation , and satiety measures were similar among meals . CONCLUSIONS Fat quality determined the thermogenic response to a fatty meal but had no clear effects on substrate oxidation or satiety BACKGROUND Fruit and vegetable consumption might prevent weight gain through their low energy density and high dietary fiber content . OBJECTIVE We assessed the association between the baseline consumption of fruit and vegetables and weight change in participants from 10 European countries participating in the European Prospect i ve Investigation into Cancer and Nutrition study . DESIGN Diet was assessed at baseline in 373,803 participants by using country-specific vali date d question naires . Weight was measured at baseline and self-reported at follow-up in most centers . Associations between baseline fruit and vegetable intakes ( per 100 g/d ) and weight change ( g/y ) after a mean follow-up of 5 y were assessed by using linear mixed-models , with age , sex , total energy intake , and other potential confounders controlled for . RESULTS After exclusion of subjects with chronic diseases at baseline and subjects who were likely to misreport energy intakes , baseline fruit and vegetable intakes were not associated with weight change overall . However , baseline fruit and vegetable intakes were inversely associated with weight change in men and women who quit smoking during follow-up . We observed weak positive associations between vegetable intake and weight change in women who were overweight , were former smokers , or had high prudent dietary pattern scores and weak inverse associations between fruit intake and weight change in women who were > 50 y of age , were of normal weight , were never smokers , or had low prudent dietary pattern scores . CONCLUSIONS In this large study , higher baseline fruit and vegetable intakes , while maintaining total energy intakes constant , did not substantially influence midterm weight change overall but could help to reduce risk of weight gain in persons who stop smoking . The interactions observed in women deserve additional attention Racial differences in potassium ( K ) intake and urinary K excretion may contribute to the higher BP observed in black compared with white individuals . Although black individuals typically consume less dietary K than white individuals , the lower urinary K excretion observed in black individuals may reflect more than differences in intake . In this study , data from the Dietary Approaches to Stop Hypertension ( DASH ) trial ( 413 white and black participants ) were used to evaluate urinary K excretion in black and white individuals with similar K intake . At screening , mean urinary K excretion was higher in white than black individuals ( mean Delta = 645 mg/d for white minus black individuals , adjusted for age , gender , and weight ; P < 0.001 ) . After a 3-wk run-in period during which all participants received a low-K control diet , a significant racial difference remained ( mean Delta = 201 mg/d , adjusted for age , gender , and caloric intake ; P < 0.001 ) . Participants were then r and omly assigned to continue the control diet or switch to a high-K diet ( either a high fruit/vegetable diet or the DASH diet ) for 8 wk . At the end of intervention , the mean difference in urinary K in white compared with black individuals after adjustment for age , gender , and caloric intake was -6 mg/d ( P = 0.95 ) in the control group , 163 mg/d in the fruits/vegetables group ( P = 0.39 ) , and 903 mg/d in the DASH group ( P < 0.001 ) . Racial differences in urinary K excretion seem to reflect more than intake differences ; further studies are needed to underst and their potential impact on clinical outcomes OBJECTIVE —To determine the effects of soy consumption on markers of inflammation and endothelial function in postmenopausal women with the metabolic syndrome . RESEARCH DESIGN AND METHODS —This r and omized cross-over clinical trial included 42 postmenopausal women with the metabolic syndrome . Participants were r and omly assigned to consume a control diet ( Dietary Approaches to Stop Hypertension [ DASH ] ) , soy protein diet , or soy nut diet , each for 8 weeks . Red meat in the DASH diet ( one serving/day ) was replaced by soy protein in the soy protein diet and by soy nut in the soy nut diet . RESULTS —For nitric oxide levels , the difference from the control diet was 9.8 % ( P < 0.01 ) on the soy nut and −1.7 % ( P = 0.10 ) on the soy protein diets . The difference from the control diet for serum E-selectin was −11.4 % ( P < 0.01 ) on the soy nut consumption and −4.7 % ( P = 0.19 ) on the soy protein diet . Soy nut consumption reduced interleukin-18 compared with the control diet ( difference from the control diet : −9.2 % , P < 0.01 ) , but soy protein did not ( difference from the control diet : −4.6 % , P = 0.14 ) . For C-reactive protein , the difference from the control diet was −8.9 % ( P < 0.01 ) on the soy nut diet and −1.6 % ( P < 0.01 ) on the soy protein diet . CONCLUSIONS —Short-term soy nut consumption reduced some markers of inflammation and increased plasma nitric oxide levels in postmenopausal women with the metabolic syndrome People taking antipsychotic medications are at increased risk for obesity , diabetes , and early mortality . Few weight loss interventions have targeted this population . Thirty-six individuals were r and omized to an evidence -based 12-week weight loss intervention ( PREMIER with DASH diet , n = 18 ) or to usual care ( n = 18 ) in this feasibility trial . Average attendance was 8.6 of 12 sessions . Intent-to-treat analyses of covariance , adjusted for baseline weight , showed significant changes in weight : Mean weight in intervention participants declined from 213.3 to 206.6 pounds , while control participants ’ weight was unchanged . It is possible to recruit , assess , intervene with , and retain participants taking antipsychotic medications in a dietary and exercise lifestyle change trial . Participants reported high levels of satisfaction with the intervention Lifestyle modifications , such as weight loss , sodium restriction , and limiting alcohol consumption , are important components of the initial treatment of hypertensive patients . The Dietary Approaches to Stop Hypertension ( DASH ) study investigated the effects of dietary patterns on blood pressure in individuals with diastolic blood pressure between 80 - 95 mmHg . Two different dietary patterns were tested in this feeding study . A diet enriched in fruits and vegetables and a diet enriched in fruits , vegetables , and low-fat dairy products and low in total and saturated fat ( combination diet ) were compared with a control diet . Dietary intake was adjusted so that participants did not lose weight , and all study diets had comparable sodium intake ( approximately 3 grams/day ) . All meals were provided for 459 participants for an 11-week period . Those r and omized to the combination diet ( n = 151 ) had a significant change in systolic ( -5.5 mmHg ; p < 0.001 ) and diastolic blood pressure ( -3.0 mmHg ; p < 0.001 ) after subtracting the response to the control diet ( n = 154 ) . The fruits- and -vegetables diet ( n = 154 ) produced a significant but lesser decrease in blood pressure ( systolic , -2.8 mmHg ; p < 0.001 and diastolic , -1.1 mmHg ; p = 0.07 ) . Hypertensive individuals and African Americans had particularly favorable responses with blood pressure reductions , which were significantly greater than other subgroups . The combination diet was well-accepted and adherence to the diet was high ( > 90 % ) for all participants . The DASH combination diet is an effective lifestyle modification for lowering blood pressure in patients with high-normal or Stage 1 hypertension A diet rich in fruits , vegetables and low-fat dairy products , and reduced in saturated fat , total fat and cholesterol ( the ‘ DASH ’ diet ) significantly lowers blood pressure ( BP ) . Previous studies have documented that certain therapies that lower BP increase plasma renin activity ( PRA ) . Using data from the Dietary Approaches to Stop Hypertension ( DASH ) trial , we assessed the effects of dietary patterns on PRA and determined the relationship of change in PRA with change in BP on each diet . After eating a control diet for 3 weeks , participants were then r and omized to receive for 8 weeks : the control diet , a diet rich in fruits and vegetables ( F/V ) , or the DASH diet . Baseline and follow-up levels of PRA were available in 381 participants . Compared with the control diet , the DASH diet increased PRA by 0.37 ng ml−1 h−1 ( P=0.01 ) . In multivariable linear regression analyses , there was an inverse association of PRA change with systolic BP change on the control diet ( slope=−0.35 , P=0.001 ) , but PRA did not differ by BP change on the F/V diet ( slope=−0.002 , P=0.98 ) or DASH diet ( slope=−0.08 , P=0.32 ) . These data suggest that a blunted counter-regulatory response of the renin – angiotensin system is associated with the BP-lowering effect of the F/V and DASH diets BACKGROUND Previous studies that reported an association of dietary Na(+ ) intake with metabolic syndrome were limited by the use of imprecise measures of obesity , Na(+ ) intake , or exclusion of multiethnic population s. The effect of dietary K(+ ) intake on obesity is less well described . OBJECTIVE We hypothesized that high dietary Na(+ ) and low K(+ ) , based on the ratio of urinary Na(+ ) to K(+ ) ( U[Na(+)]/[K(+ ) ] ) in a first-void morning urinary sample , is independently associated with total body fat . DESIGN In a prospect i ve population -based cohort , 2782 participants in the community-dwelling , probability- sample d , multiethnic Dallas Heart Study were analyzed . The primary outcome established a priori was total-body percentage fat ( TBPF ) measured by dual-energy X-ray absorptiometry . The main predictor was U[Na(+)]/[K(+ ) ] . Robust linear regression was used to explore an independent association between U[Na(+)]/[K(+ ) ] and TBPF . The analyses were stratified by sex and race after their effect modifications were analyzed . RESULTS Of the cohort , 55.4 % were female , 49.8 % African American , 30.8 % white , 17.2 % Hispanic , and 2.2 % other races . The mean ( ±SD ) age was 44 ± 10 y , BMI ( in kg/m(2 ) ) was 30 ± 7 , TBPF was 32 ± 10 % , and U[Na(+)]/[K(+ ) ] was 4.2 ± 2.6 ; 12 % had diabetes . In the unadjusted and adjusted models , TBPF increased by 0.75 ( 95 % CI : 0.25 , 1.25 ) and 0.43 ( 0.15 , 0.72 ) , respectively ( P = 0.003 for both ) , for every 3-unit increase in U[Na(+)]/[K(+ ) ] . A statistically significant interaction was found between race and U[Na(+ ) ] /[K(+ ) ] , so that the non-African American races had a higher TBPF than did the African Americans per unit increase in U[Na(+)]/[K(+ ) ] ( P-interaction < 0.0001 for both ) . No interaction was found between sex and U[Na(+)]/[K(+ ) ] . CONCLUSIONS The ratio of dietary Na(+ ) to K(+ ) intake may be independently associated with TBPF , and this association may be more pronounced in non-African Americans . Future studies should explore whether easily measured spot U[Na(+)]/[K(+ ) ] can be used to monitor dietary patterns and guide strategies for obesity management OBJECTIVES The STRIDE study assessed whether a lifestyle intervention , tailored for individuals with serious mental illnesses , reduced weight and diabetes risk . The authors hypothesized that the STRIDE intervention would be more effective than usual care in reducing weight and improving glucose metabolism . METHOD The study design was a multisite , parallel two-arm r and omized controlled trial in community setting s and an integrated health plan . Participants who met inclusion criteria were ≥18 years old , were taking antipsychotic agents for ≥30 days , and had a body mass index ≥27 . Exclusions were significant cognitive impairment , pregnancy/breastfeeding , recent psychiatric hospitalization , bariatric surgery , cancer , heart attack , or stroke . The intervention emphasized moderate caloric reduction , the DASH ( Dietary Approaches to Stop Hypertension ) diet , and physical activity . Blinded staff collected data at baseline , 6 months , and 12 months . RESULTS Participants ( men , N=56 ; women , N=144 ; mean age=47.2 years [ SD=10.6 ] ) were r and omly assigned to usual care ( N=96 ) or a 6-month weekly group intervention plus six monthly maintenance sessions ( N=104 ) . A total of 181 participants ( 90.5 % ) completed 6-month assessment s , and 170 ( 85 % ) completed 12-month assessment s , without differential attrition . Participants attended 14.5 of 24 sessions over 6 months . Intent-to-treat analyses revealed that intervention participants lost 4.4 kg more than control participants from baseline to 6 months ( 95 % CI=-6.96 kg to -1.78 kg ) and 2.6 kg more than control participants from baseline to 12 months ( 95 % CI=-5.14 kg to -0.07 kg ) . At 12 months , fasting glucose levels in the control group had increased from 106.0 mg/dL to 109.5 mg/dL and decreased in the intervention group from 106.3 mg/dL to 100.4 mg/dL. No serious adverse events were study -related ; medical hospitalizations were reduced in the intervention group ( 6.7 % ) compared with the control group ( 18.8 % ) . CONCLUSIONS Individuals taking antipsychotic medications can lose weight and improve fasting glucose levels . Increasing reach of the intervention is an important future step Epidemiological and metabolic studies have shown that regular nut consumption may protect against risk of heart disease and diabetes . None has investigated the effect of adding nuts to a self-selected habitual diet ( containing little or no nuts ) on dietary patterns . The present study evaluated the impact of long-term almond supplementation in healthy men ( n 43 ) and women ( n 38 ) aged 25 - 70 years on nutrient profile and nutrient displacement . All subjects were followed for 1 year . During the first 6 months , subjects followed their habitual diets ; in the second 6 months , subjects added almonds to their diets . Diets were assessed by seven r and om 24 h telephone diet recalls during each diet period . On average , the almond supplement was 52 g/d ( about forty-two nuts ) containing 1286 kJ. When subjects changed from their habitual diet to the almond-supplemented diet , the intakes of MUFA , PUFA , fibre , vegetable protein , alpha-tocopherol , Cu and Mg significantly ( P<0.05 ) increased by 42 , 24 , 12 , 19 , 66 , 15 and 23 % respectively ; the intakes of trans fatty acids , animal protein , Na , cholesterol and sugars significantly ( P<0.05 ) decreased by 14 , 9 , 21 , 17 and 13 % respectively . These spontaneous nutrient changes closely match the dietary recommendations to prevent cardiovascular and other chronic diseases . Displacement estimates for total energy , total protein , total fat , SFA , MUFA , PUFA , total fibre , Ca , Fe , Mg , P , K , Zn and alpha-tocopherol ranged from 16 to 98 % ; the estimates for total food weight , carbohydrate , sugars and Se were > 245 % . A daily supplement of almonds can induce favourable nutrient modifications for chronic disease prevention to an individual 's habitual diet AIMS To evaluate the effectiveness of Dietary Approaches to Stop Hypertension ( DASH ) by one-off dietary counselling on reducing cardiovascular risk factors among Chinese Grade 1 hypertensive patients in primary care . METHODS AND RESULTS A parallel-group , r and omized controlled trial ( ChiCTR-TRC-13003014 ) was conducted among patients ( 40 - 70 years old ) newly diagnosed with Grade 1 hypertension in primary care setting s in Hong Kong . Subjects were r and omized to usual care ( st and ard education , control ) ( n = 275 ) , or usual care plus DASH-based dietary counselling ( intervention ) ( n = 281 ) . The study endpoints included blood pressure ( BP ) , lipid profile , and body mass index ( BMI ) at 6- and 12-months . Outcome data were available for 504 ( 90.6 % ) and 485 ( 87.2 % ) patients at 6 and 12 months , respectively . Blood pressure levels reduced in both groups at follow-ups . However , the intervention group did not show a significantly greater reduction in either systolic BP ( -0.7 mmHg , 95%CI -3.0 - 1.5 at 6-month ; -0.1 mmHg , 95%CI -2.4 - 2.2 at 12-month ) or diastolic BP ( -1.0 mmHg , 95%CI -2.7 - 0.7 at 6-month ; -1.1 mmHg , 95%CI -2.9 - 0.6 at 12-month ) , when compared with the control group . The improvements in lipid profile and BMI were observed among all subjects , yet no significant differences were detected between intervention and control groups . CONCLUSION The DASH diet by one-off dietitian counselling which resembled the common primary care practice might confer no added long-term benefits on top of physician 's usual care in optimizing cardiovascular risk factors . Physicians may still practice st and ard usual care , yet further explorations on different DASH delivery models are warranted to inform best clinical practice OBJECTIVE To describe the nutrient and food composition of the diets tested in the Optimal Macronutrient Intake Trial to Prevent Heart Disease ( OmniHeart ) . DESIGN Two center , r and omized , three-period crossover , controlled feeding trial that tested the effects of three healthful diet patterns on blood pressure , serum lipid levels , and estimated cardiovascular risk . SUBJECTS/ SETTING One hundred sixty-four participants with prehypertension and hypertension . During the 19 weeks of feeding , participants were required to consume only food prepared as part of the trial . INTERVENTION The OmniHeart trial studied three diet patterns that differed in macronutrient composition : a carbohydrate-rich diet similar to the Dietary Approaches to Stop Hypertension diet ( 58 % carbohydrate , 15 % protein , and 27 % fat ) , a higher protein diet that had 10 % more protein and 10 % less carbohydrate ( 48 % carbohydrate , 25 % protein , and 27 % fat ) , and a higher unsaturated fat diet that had 10 % more unsaturated fat and 10 % less carbohydrate ( 48 % carbohydrate , 15 % protein , and 37 % fat ) . Each diet contained 6 % saturated fat and 100 to 200 mg cholesterol . Sodium was 2,300 mg at the 2,100 kcal energy level and was indexed across energy levels . Calcium , magnesium , and potassium were consistent with recommendations for the Dietary Approaches to Stop Hypertension diet and also indexed to energy levels . Each diet pattern met the major nutrient recommendations set by the Dietary Guidelines for Americans 2005 . The 10 % protein increase in the higher protein diet emphasized plant protein ; however , meat and dairy food sources were also increased somewhat . Olive oil , canola oil , and olive oil spread were used liberally to achieve the unsaturated fat content of the higher unsaturated fat diet . The 10 % reduction in carbohydrate in the higher protein diet and the higher unsaturated fat diet was achieved by replacing some fruits with vegetables , reducing sweets , and using smaller portions of grain products . All three diets reduced blood pressure , total and low-density lipoprotein cholesterol levels , and estimated coronary heart disease risk . CONCLUSIONS The OmniHeart diet patterns offer substantial flexibility in macronutrient intake that should make it easier to eat a heart-healthy diet and reduce cardiovascular disease risk UNLABELLED This study was design ed to assess the effects of Dietary Approaches to Stop Hypertension ( DASH ) eating plan on insulin resistance and serum hs-CRP in overweight and obese women with PCOS . This r and omized controlled clinical trial was done on 48 women diagnosed with PCOS . Subjects were r and omly assigned to consume either the control ( n=24 ) or the DASH eating pattern ( n=24 ) for 8 weeks . The DASH diet consisted of 52 % carbohydrates , 18 % proteins , and 30 % total fats . It was design ed to be rich in fruits , vegetables , whole grains , and low-fat dairy products and low in saturated fats , cholesterol , refined grains , and sweets . Sodium content of the DASH diet was design ed to be less than 2 400 mg/day . The control diet was also design ed to contain 52 % carbohydrates , 18 % protein , and 30 % total fat . Fasting blood sample s were taken at baseline and after 8 weeks intervention to measure -insulin resistance and serum hs-CRP levels . -Adherence to the DASH eating pattern , compared to the -control diet , result ed in a significant reduction of serum insulin levels ( -1.88 vs. 2.89 μIU/ml , p=0.03 ) , HOMA-IR score ( -0.45 vs. 0.80 ; p=0.01 ) , and serum hs-CRP levels ( -763.29 vs. 665.95 ng/ml , p=0.009 ) . Additionally , a significant reduction in waist ( -5.2 vs. -2.1 cm ; p=0.003 ) and hip circumference ( -5.9 vs. -1 cm ; p<0.0001 ) was also seen in the DASH group compared with the control group . In conclusion , consumption of the DASH eating pattern for 8 weeks in overweight and obese women with PCOS result ed in the improvement of insulin resistance , serum hs-CRP levels , and abdominal fat accumulation . CLINICAL TRIAL REGISTRATION NUMBER www.i rct .ir : I RCT 201304235623N6 Background The DASH ( Dietary Approaches to Stop Hypertension ) diet is a carbohydrate-rich , reduced-fat diet that lowers blood pressure ( BP ) and LDL-cholesterol . Whether partial replacement of some carbohydrate ( C ) with either protein ( P ) or unsaturated fat ( U ) can further improve these and other cardiovascular ( CVD ) risk factors is unknown . Methods OmniHeart is a r and omized , three-period , crossover feeding study design ed to compare the effects on BP and blood lipids of a carbohydrate-rich diet ( CARB , similar to the DASH diet ) with a diet rich in protein ( PROT , predominantly from nonmeat sources ) and a diet rich in unsaturated fat ( UNSAT , predominantly monounsaturated ) . Throughout feeding ( run in and the three intervention periods ) , participants are provided with all of their meals that meet the nutrient profile of their assigned diet . Calorie intake is adjusted to maintain weight . The target sample size is 160 ( 50 % African-American ) . Participants are adults , aged 30 or older , with prehypertension or Stage 1 hypertension ( systolic BP 120–159 or diastolic BP 80–99 mmHg ) . The primary outcome variables are systolic BP and LDL-cholesterol . Secondary outcomes are diastolic BP , HDL-cholesterol , and triglycerides . Other outcome variables are total cholesterol , apolipoproteins VLDL-apoB , VLDL-apoCIII , apolipoprotein B , non-HDL cholesterol , and lipoprotein(a ) , and insulin resistance , as measured by Homeostasis Model Assessment ( HOMA ) . Conclusions OMNI-Heart should advance our fundamental knowledge of the effects of diet on both traditional and emerging risk factors , and , in the process , guide policy makers , health care providers and the general public on the relative benefits of carbohydrate , protein , and unsaturated fat as a means to reduce CVD risk Abstract —We evaluated the effect on serum lipids of sodium intake in 2 diets . Participants were r and omly assigned to a typical American control diet or the Dietary Approaches to Stop Hypertension ( DASH ) diet , each prepared with 3 levels of sodium ( targeted at 50 , 100 , and 150 mmol/d per 2100 kcal ) . The DASH diet is increased in fruits , vegetables , and low-fat dairy products and is reduced in saturated and total fat . Within assigned diet , participants ate each sodium level for 30 days . The order of sodium intake was r and om . Participants were 390 adults , age 22 years or older , with blood pressure of 120 to 159 mm Hg systolic and 80 to 95 mm Hg diastolic . Serum lipids were measured at baseline and at the end of each sodium period . Within each diet , sodium intake did not significantly affect serum total cholesterol , LDL cholesterol , HDL cholesterol , or triglycerides . On the control diet , the ratio of total cholesterol-to-HDL cholesterol increased by 2 % from 4.53 on higher sodium to 4.63 on lower sodium intake ( P = 0.04 ) . On the DASH diet , sodium intake did not affect this ratio . There was no dose-response of sodium intake on serum lipids or the cholesterol ratio in either diet . At each sodium level , total cholesterol , LDL cholesterol , and HDL cholesterol were lower on the DASH diet versus the typical American diet . There were no significant interactions between the effects of sodium and the DASH diet on serum lipids . In conclusion , changes in dietary sodium intake over the range of 50 to 150 mmol/d did not affect blood lipid concentrations PURPOSE To describe PREMIER , a r and omized trial to determine the effects of multi-component lifestyle interventions on blood pressure ( BP ) . METHODS Participants with above optimal BP through stage 1 hypertension were r and omized to : 1 ) a behavioral lifestyle ( BLS ) intervention that implements established recommendations , 2 ) a BLS intervention that implements established recommendations plus the DASH diet , or 3 ) an advice only st and ard of care group . The two BLS interventions consist of group and individual counseling sessions for 18 months . The primary outcome is systolic BP at 6 months . Additional outcomes include diastolic BP and homocysteine at 6 months ; systolic and diastolic BP at 18 months ; fasting lipids , glucose and insulin at 6 and 18 months ; and effects in subgroup . CONCLUSION Results from the PREMIER trial will provide scientific rationale for implementing multi-component behavioral lifestyle intervention programs to control BP and prevent CVD CONTEXT Weight loss , sodium reduction , increased physical activity , and limited alcohol intake are established recommendations that reduce blood pressure ( BP ) . The Dietary Approaches to Stop Hypertension ( DASH ) diet also lowers BP . To date , no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations . OBJECTIVE To determine the effect on BP of 2 multicomponent , behavioral interventions . DESIGN , SETTING , AND PARTICIPANTS R and omized trial with enrollment at 4 clinical centers ( January 2000-June 2001 ) among 810 adults ( mean [ SD ] age , 50 [ 8.9 ] years ; 62 % women ; 34 % African American ) with above-optimal BP , including stage 1 hypertension ( 120 - 159 mm Hg systolic and 80 - 95 mm Hg diastolic ) , and who were not taking antihypertensive medications . INTERVENTION Participants were r and omized to one of 3 intervention groups : ( 1 ) " established , " a behavioral intervention that implemented established recommendations ( n = 268 ) ; ( 2 ) " established plus DASH,"which also implemented the DASH diet ( n = 269 ) ; and ( 3 ) an " advice only " comparison group ( n = 273 ) . MAIN OUTCOME MEASURES Blood pressure measurement and hypertension status at 6 months . RESULTS Both behavioral interventions significantly reduced weight , improved fitness , and lowered sodium intake . The established plus DASH intervention also increased fruit , vegetable , and dairy intake . Across the groups , gradients in BP and hypertensive status were evident . After subtracting change in advice only , the mean net reduction in systolic BP was 3.7 mm Hg ( P<.001 ) in the established group and 4.3 mm Hg ( P<.001 ) in the established plus DASH group ; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg ( P = .43 ) . Compared with the baseline hypertension prevalence of 38 % , the prevalence at 6 months was 26 % in the advice only group , 17 % in the established group ( P = .01 compared with the advice only group ) , and 12 % in the established plus DASH group ( P<.001 compared with the advice only group ; P = .12 compared with the established group ) . The prevalence of optimal BP ( < 120 mm Hg systolic and < 80 mm Hg diastolic ) was 19 % in the advice only group , 30 % in the established group ( P = .005 compared with the advice only group ) , and 35 % in the established plus DASH group ( P<.001 compared with the advice only group ; P = .24 compared with the established group ) . CONCLUSION Individuals with above-optimal BP , including stage 1 hypertension , can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk Context Can adults make sustained changes in unhealthy lifestyle behaviors ? Content In this multicenter trial , 810 adult volunteers with prehypertension or stage 1 hypertension were r and omly assigned to a multicomponent behavioral intervention group , a group combining the behavioral intervention plus the Dietary Approaches to Stop Hypertension ( DASH ) diet , or an advice only group . At 18 months , participants in both behavioral intervention groups had less hypertension , more weight loss , and better reduction in sodium and fat intake than those receiving advice only . The participants in the DASH diet group also increased their intake of fruits , vegetables , and fiber . Implication s Motivated adults can sustain several lifestyle changes over 18 months , which might reduce their risk for cardiovascular disease . The Editors The public health burden of chronic diseases related to suboptimal diet and physical inactivity is enormous . It has been estimated that these lifestyle factors contribute to approximately 20 % of deaths in the United States ( 1 ) . Incidence of atherosclerotic cardiovascular disease , overweight and obesity , elevated blood pressure and lipid levels , diabetes , osteoporosis , and cancer is increased by unhealthy lifestyles ( 2 - 8 ) . Multiple lifestyle factors , such as physical inactivity ; excessive intake of calories , sodium , saturated fat , and cholesterol ; and inadequate intake of fruits , vegetables , and low-fat dairy products , are etiologically related to the development of these diseases ( 4 , 5 , 8 - 10 ) . To reduce the burden of chronic disease , increased physical activity and changes in diet are needed , yet few intervention studies have attempted to achieve many lifestyle changes simultaneously . The PREMIER r and omized trial tested the effects of 2 multicomponent behavioral interventions on blood pressure ( 11 ) . Both interventions promoted increased physical activity , weight loss , and reduced sodium intake , each of which is recommended by the 2005 Dietary Guidelines Scientific Advisory Committee ( 12 ) . One intervention also added the Dietary Approaches to Stop Hypertension ( DASH ) diet ( 13 ) . This diet , which is high in fruits , vegetables , and low-fat dairy products and low in saturated fat , total fat , and cholesterol , meets each of the major nutrient recommendations that were established by the Institute of Medicine ( 14 - 18 ) . We report the effects of the PREMIER interventions on lifestyle changes and blood pressure status at 18 months . The main results of PREMIER , namely change in blood pressure at 6 months , were reported previously ( 11 ) . Methods The PREMIER study design and rationale ( 19 ) and intervention methods ( 11 ) have been described previously . The institutional review boards at each clinical center ; an external protocol review committee appointed by the National Heart , Lung , and Blood Institute ( NHLBI ) ; and the NHLBI review ed and approved the protocol ( available at www.kpchr.org/public/premier/intervention/default.asp ) . The NHLBI also appointed a data and safety monitoring board to monitor the trial . Each participant provided written informed consent . The trial was conducted from January 2000 through November 2002 . Study Participants Participants were generally healthy adults , age 25 years or older , who had prehypertension or stage 1 hypertension and met the Joint National Committee VI ( JNC VI ) criteria for a 6-month trial of nonpharmacologic therapy ( 2 ) . Targeted recruitment methods were used to ensure adequate representation of clinical ly important subgroups , in particular , African-American persons . Specific methods varied from site to site but included direct mailings , radio and newspaper advertisements , and networking within the local African-American communities . Eligibility criteria included not taking antihypertensive medication and having a systolic blood pressure of 120 to 159 mm Hg and a diastolic blood pressure of 80 to 95 mm Hg , based on the average of 3 screening visits . Persons with prehypertension ( systolic blood pressure of 120 to 139 mm Hg or diastolic blood pressure of 80 to 89 mm Hg ) were included because of the excess risk for cardiovascular disease in those with blood pressure within this range ( 20 ) . Major exclusion criteria were a body mass index less than 18.5 kg/mg2 or greater than 45.0 kg/m2 , use of antihypertensive drugs or other drugs that affect blood pressure , JNC VI risk category C ( target organ damage or diabetes ) , use of prescription weight loss medications , previous cardiovascular event , congestive heart failure , angina , cancer , and consumption of more than 21 alcoholic drinks per week . Trial Conduct Eligible participants were r and omly assigned , with equal probability , to 1 of 3 groups : an advice only comparison group ( advice only ) ; an intervention group that targeted established , guideline -recommended lifestyle recommendations ( established ) ( 2 ) ; or an intervention group targeting the established recommendations and adding the DASH dietary pattern ( established plus DASH ) ( 13 ) . Computer-generated treatment assignments were stratified by clinic and hypertension status and were assigned in blocks of varying sizes to provide balance over time . The actual assignments were administered by using a password-protected , Web-based application developed by the coordinating center and accessible only by authorized individuals . All clinic measurement staff were blinded to treatment assignment , and all intervention staff were blinded to clinic measurements . Hypertension was defined by using the JNC VI criteria for hypertension treatment : an average systolic blood pressure of 140 mm Hg , a diastolic blood pressure greater than 90 mm Hg , or use of antihypertensive medication . Normal blood pressure was defined as systolic blood pressure less than 120 mm Hg , diastolic blood pressure less than 80 mm Hg , and no use of antihypertensive medication ( 21 ) ( Figure ) . Intervention was provided by master 's degreelevel counselors ( dietitians and health educators trained in behavioral methods ) . The counselors were central ly trained before the start of the study , attended annual 3-day training sessions , and participated in monthly conference calls . Figure . Flow diagram of enrollment , measurements , and visit completion . Advice Only Group Participants in the advice group received advice to follow the National High Blood Pressure Education Program lifestyle recommendations for blood pressure control ( 2 ) . Lifestyle recommendations included reducing weight ( if overweight ) , following a reduced-sodium diet , engaging in regular moderate-intensity physical activity , and eating a heart-healthy diet , including the DASH diet . This advice was provided in two 30-minute individual sessions , 1 immediately after r and om assignment and 1 after the 6-month data collection visit . A PREMIER counselor review ed the guidelines with the participant and provided printed educational material s and information about community re sources . This intervention did not include advice to keep a food or exercise diary . Behavioral Interventions in the Established and Established plus DASH Groups Participant goals for the established and established plus DASH groups included weight loss of at least 6.8 kg ( 15 lb ) for those with a body mass index of 25 kg/m2 or greater , at least 180 minutes per week of moderate-intensity physical activity , no more than 100 mmol per day of dietary sodium , and alcohol consumption of no more than 30 mL ( 1 oz ) per day ( 2 drinks ) for men and 15 mL ( 0.5 ) oz per day ( 1 drink ) for women . Participants assigned to the established plus DASH group ( but not those in the established group ) also received counseling on the DASH diet , with goals for increased consumption of fruits and vegetables ( 9 to 12 servings/d ) and low-fat dairy products ( 2 to 3 servings/d ) and reduced consumption of saturated fat ( 7 % of energy ) and total fat ( 25 % of energy ) . The intervention format , contact pattern , and behavior change strategies for the established and established plus DASH groups were identical . During the first 6 months , participants in both behavioral intervention groups attended 14 group sessions and 4 individual sessions ; during months 7 to 18 , they attended monthly group sessions supplemented with 3 individual counseling sessions . Throughout the trial , participants in the established and established plus DASH groups ( but not those in the advice group ) kept food diaries , monitored dietary calorie and sodium intakes , and recorded minutes of physical activity . Self-monitoring was used to provide individualized feedback , reinforcement , problem solving , and support . Social support for initial behavior changes and maintenance of change was provided during the group sessions . More detailed descriptions of the behavorial intervention methods are available ( 22 ) . Measurements Blood pressure was assessed twice at each measurement , and systolic and diastolic blood pressures were calculated by using the mean of all available measurements ( 4 sets before r and om assignment , 3 sets at 6 and 18 months , and 1 set at 3 and 12 months ) . For 4 participants who were started on antihypertensive drug therapy between the 12- and 18-month visits , we obtained an official set of blood pressure measurements before initiation of therapy and used these as our 18-month blood pressure values for analysis . A similar procedure was used to obtain the 6-month blood pressure value for the 1 participant who began taking antihypertensive drugs between the 3- and 6-month visits . Two 24-hour dietary recalls , 1 obtained on a weekday and the other obtained on a weekend , were collected at baseline and at 6 and 18 months by telephone interview ( 23 ) . Intakes of nutrients and food groups were calculated by using the Nutrition Data System for Research , version NDS-R 1998 ( University of Minnesota , Minneapolis , Minnesota ) . Urinary excretion of sodium ( reflecting salt intake ) and potassium ( reflecting fruit and vegetable intake ) was obtained from 24-hour urinary collection s at baseline This study evaluated the effect of adding fruit or oats to the diet of free-living women on energy consumption and body weight . Fruit and oat cookies had the same amount of fiber and total calories ( approximately 200 kcal ) , but differed in energy density . We analyzed data from a clinical trial conducted in a primary care unit in Rio de Janeiro , Brazil . Forty-nine women , ages ranging from 30 to 50 years , with body mass index ( BMI ) > 25 kg/m2 , were r and omly chosen to add three apples ( 0.63 kcal/g energy density ) or three pears ( 0.64 kcal/g energy density ) or three oat cookies ( 3.7 kcal/g energy density ) to their usual diet for 10 weeks . Fiber composition was similar ( approximately 6 g ) . Statistical analysis of the repeated measures of dietary composition and body weight were analyzed using mixed model procedures . Results showed a significant decrease in the energy density during the follow-up ( -1.23 kcal/g , p<0.04 , and -1.29 kcal/g , p<0.05 ) for apples and pears , respectively , compared to the oat group . The energy intake also decreased significantly ( -25.05 and -19.66 kcal/day ) for the apple and pear group , respectively , but showed a small increase ( + 0.93 ) for the oat group . Apples and pears were also associated ( p<0.001 ) with weight reduction ( -0.93 kg for the apple and -0.84 for the pear group ) , whereas weight was unchanged ( + 0.21 ; p=0.35 ) in the oat group . Results suggest that energy densities of fruits , independent of their fiber amount can reduce energy consumption and body weight over time Participants in controlled feeding studies must consume all study foods and abstain from all other foods . In outpatient studies in which adherence may be compromised by free-living conditions , promoting , documenting , and monitoring dietary adherence are necessary . In the Dietary Approaches to Stop Hypertension ( DASH ) trial , a thorough participant screening process , an orientation session , and a run-in feeding period before r and omization aided in the selection of participants who would most likely adhere to the dem and s of the study protocol . Throughout the feeding period , various educational and motivational techniques were used to encourage DASH participants to adhere to the dietary protocol . Both objective and subjective methods documented excellent participant adherence . Daily monitoring of individual adherence was based on meal attendance , body weight measurements , and daily diaries . Urinary sodium , potassium , phosphorus , and urea nitrogen values and an anonymous post study survey were used to evaluate adherence at the end of the study . Most DASH participants adhered to the feeding regimen by consuming only study foods and no other foods . When adherence lapsed , participants generally cited the lack of menu variety as a reason . Successful participant adherence to the constraints of an outpatient controlled feeding study is possible with carefully selected participants and a variety of adherence-promoting strategies incorporated into the study protocol Few studies exist regarding the effects of the Dietary Approaches to Stop Hypertension ( DASH ) diet on novel cardiovascular risk factors among type 2 diabetic patients . We evaluated the effects of the DASH eating pattern on C-reactive protein ( CRP ) level , coagulation abnormalities , and hepatic function tests in type 2 diabetic patients . In this r and omized , crossover clinical trial , 31 type 2 diabetic patients consumed a control diet or the DASH diet for 8 wk . The DASH diet was rich in fruits , vegetables , whole grains , and low-fat dairy products and low in saturated fat , total fat , cholesterol , refined grains , and sweets , with a total of 2400 mg/d sodium . The control diet was a st and ard diet for diabetic patients . There was a 4-wk washout between the 2 trial phases . The main outcome measures were CRP level , coagulation indices , and hepatic function tests . The mean percent change for plasma CRP level was -26.9 ± 3.5 % after the DASH diet period and -5.1 ± 3.8 % after the control diet period ( P = 0.02 ) . Decreases in both alanine aminotransferase and aspartate aminotransferase levels were greater after consuming the DASH diet compared with the control diet ( -14.8 ± 3.0 % vs -6.6 ± 3.4 % ; P = 0.001 ; -29.4 ± 3.7 % vs -5.9 ± 1.4 % ; P = 0.001 , respectively ) . The decrease in the plasma fibrinogen level during the DASH diet period ( -11.4 ± 3.6 % ) was greater than that during the control diet ( 0.5 ± 3.4 % ) ( P = 0.03 ) . Among diabetic patients , the DASH diet can play an important role in reducing inflammation , plasma levels of fibrinogen , and liver aminotransferases . Future longer term studies are recommended OBJECTIVES Determine whether self-efficacy independently predicted weight loss in a behavioral intervention and explore factors that influence the path between self-efficacy and weight change . DESIGN Secondary analysis of the PREMIER trial , a r and omized controlled trial testing effects of lifestyle interventions on blood pressure . SETTING Four academic medical centers . PARTICIPANTS PREMIER recruited adults ( n = 810 ) with pre-hypertension/stage 1 hypertension , not currently receiving medication . This analysis excluded participants in the control arm , result ing in n = 537 . INTERVENTIONS Participants were r and omly assigned to 1 of 3 groups : advice only , established lifestyle recommendations , or established lifestyle recommendations plus Dietary Approaches to Stop Hypertension dietary pattern . MAIN OUTCOME MEASURES Self-efficacy ( dietary self-efficacy [ DSE ] , exercise self-efficacy [ ESE ] ) , dietary intake , fitness . ANALYSIS Pearson correlations , 1-way analysis of variance , mediation analyses . RESULTS Despite an overall decrease in DSE/ESE , change in DSE/ESE significantly predicted weight change at 6 ( β = -.21 , P < .01 ; β = -.19 , P < .01 , respectively ) and 18 months ( β = -.19 , P < .01 ; β = -.35 , P < .01 ) . Change in percent calories from fat partially mediated the DSE/weight change relationship at 6 months . Change in fitness partially mediated the ESE/weight change relationship at 18 months . CONCLUSIONS AND IMPLICATION S Changes in DSE/ESE were not associated with behavior change as hypothesized . Additional research is needed to identify mediators between self-efficacy and adoption of behaviors that influence weight loss Although epidemiologic data show a direct relation between dietary sodium intake and blood pressure at the population level ( 1 , 2 ) , some experts question the universality of the findings and oppose public health recommendations to decrease sodium intake in the general population ( 3 ) . Certainly , results from reports on the relationship between sodium and blood pressure among major subgroups vary considerably . Several studies suggest that African Americans and older adults have heightened salt sensitivity ( greater blood pressure response to sodium intake ) ( 4 - 6 ) . Some evidence also indicates increased salt sensitivity in women ( 7 ) , although other studies do not support this cl aim ( 4 , 5 ) . The association of sodium intake with cardiovascular morbidity and mortality varies by overweight status ( 8) , perhaps reflecting a differential effect of sodium on blood pressure in overweight persons . Finally , higher dietary intakes of potassium and calcium have been shown to blunt the pressor effects of dietary sodium ( 9 , 10 ) . Dietary factors other than sodium also directly affect blood pressure , and these effects also appear to vary across subgroups . In the Dietary Approaches to Stop Hypertension ( DASH ) Trial , for example , a diet that had reduced total and saturated fat and was rich in fruits , vegetables , and low-fat dairy foods ( the DASH diet ) substantially decreased blood pressure compared with a more typical U.S. diet , in the absence of weight change and at sodium intakes approximating current U.S. consumption ( 11 , 12 ) . These effects persisted across all subgroups and were especially pronounced among hypertensive persons , African Americans , and persons who did not drink alcohol ( 13 ) . The DASH-Sodium Trial examined the effects of reduced sodium intake in the context of the DASH diet and a more typical U.S. diet ( 14 ) . In that study , highly significant decreases in blood pressure were observed with decreased sodium intake in participants following either diet , and the DASH diet decreased blood pressure at sodium intakes well below the current U.S. average . These results were observed overall and in subgroups defined by ethnicity , sex , and hypertension status ( 15 ) . We report on more detailed subgroup analyses from the DASH-Sodium Trial , including results for subgroups defined by age , obesity , waist circumference , alcohol intake , and baseline sodium intake . We also report the results of multivariate analyses that demonstrate how these effects vary across subgroups defined jointly by age , ethnicity , sex , and hypertension status . Methods Study Design The DASH-Sodium Trial was a multicenter , r and omized feeding trial comparing the effects on blood pressure of three levels of sodium intake and two dietary patterns . The 412 participants were 22 years of age or older and had systolic blood pressures of 120 to 159 mm Hg and diastolic blood pressures of 80 to 95 mm Hg ( 15 ) . The three levels of sodium intake ( lower , intermediate , and higher ) varied according to energy intake in a ratio of 1:2:3 ; target intakes were 50 , 100 , and 150 mmol/d , respectively , for a 2100-kcal diet . The dietary patterns were a control diet , typical of what many Americans eat , and the DASH diet , which emphasizes fruits , vegetables , and low-fat dairy foods ; includes whole grains , poultry , fish , and nuts ; and is reduced in fats , red meat , sweets , and sugar-containing beverages ( 11 , 14 ) . Participants were recruited in four separate feeding cohorts and were r and omly assigned to one of the two dietary patterns by using a parallel-group design . They then ate their assigned diet for three consecutive 30-day intervention feeding periods , during which sodium intake varied among the three levels by a r and omly assigned sequence ( Figure ) . Participants ate the control diet at the higher sodium intake during a 2-week run-in period . During the three intervention periods , participants received all their food in the context of the study and were asked not to eat any non study food . Individual energy intake was adjusted to keep body weight stable . Figure . Design of the Dietary Approaches to Stop Hypertension (DASH)-Sodium Trial . Exclusion criteria were heart disease , renal insufficiency , poorly controlled hyperlipidemia or diabetes mellitus , diabetes requiring insulin , special dietary requirements , intake of more than 14 alcoholic drinks/wk , or use of antihypertensive drugs or other medications that would affect blood pressure or nutrient metabolism . The study was approved by the human subjects committees of the clinical centers and coordinating center , and participants gave informed consent . Measurement Protocol Trained staff measured blood pressure at each of three screening visits , on 2 days during the run-in period , and on 5 of the last 9 days of each intervention feeding period . Interim blood pressures were assessed once during each of the first 3 weeks of each intervention feeding period . During screening and the last week of each intervention feeding period , a 24-hour urine collection was obtained . Height and weight were measured , and body mass index was calculated . Baseline physical activity was measured by using a 7-day physical activity recall interview ( 16 ) . Information on education level , income , alcohol consumption , and family history was obtained by using a question naire . Baseline blood pressure was defined as the average of the five preintervention blood pressures . End-of-feeding blood pressures were defined as the average of the five blood pressures at the end of each 30-day intervention feeding period . If no end-of-feeding blood pressure values were available ( 49 of 1236 possible cases ) , interim ( n = 9 ) or screening ( n = 40 ) blood pressures were used to impute end-of-feeding blood pressures . Definitions of Subgroups Ethnicity was categorized as African American versus other ( primarily non-Hispanic white ) . Participants were considered hypertensive if their untreated baseline systolic blood pressure was 140 mm Hg or greater and their diastolic blood pressure was 90 mm Hg or greater . ( Use of antihypertensive agents was an exclusion criterion [ 17 ] . ) Obesity was defined as body mass index of 30 kg/m2 or greater , and high-risk waist circumference was defined as greater than 102 cm in men and greater than 88 cm in women ( 18 ) . Age , physical activity , baseline alcohol intake , baseline 24-hour urinary sodium level , and family income were dichotomized at the approximate median . Level of education was dichotomized as high school or less versus more than high school . Statistical Analysis The data were analyzed on an intention-to-treat basis . Given the differential effects of sodium on blood pressure observed in previous analyses among participants eating the DASH diet versus the control diet ( 15 ) and because power for subgroup analyses is more limited than for overall analysis , we focused our comparisons on the maximum contrasts ( higher versus lower sodium intake with the control diet , DASH diet versus control diet at the higher sodium intake , and the combined effect of DASH diet and lower sodium intake versus control diet and higher sodium intake ) . We used generalized estimating equations ( 19 ) to fit linear models that predicted baseline and end-of-feeding blood pressures as a function of diet ( DASH vs. control ) , sodium level , and subgroup indicators . Different ways of modeling the dietsodium effects and their interactions with the subgroup indicators were used to test specific hypotheses . In particular , two-way interactions of the various dietsodium effects with ethnicity , sex , hypertension status , and age were analyzed to determine the incremental effect on blood pressure in each of these subgroups while controlling for the main and incremental effects of the other subgroups . This model allowed us to estimate various diet-sodium contrasts for each of the 16 subgroups defined by hypertension status , ethnicity , sex , and age . A second set of models examined subgroup variables in a bivariate manner and did not assume simple additivity of subgroup effects . Finally , unadjusted subgroup analyses included main effects and interactions for a single subgroup indicator . All analyses were performed by using the xtgee procedure in Stata software , version 5 ( Stata Corp. , College Station , Texas ) ( 20 ) and included adjustment for baseline blood pressure , site , feeding cohort , and carryover effects . An exchangeable covariance matrix was assumed for the repeated measurements for each participant . Unless otherwise stated , a P value less than 0.05 was significant , and all confidence intervals are 95 % confidence intervals . Because subgroup analyses were planned to interpret and eluci date the overall study results , they are not adjusted for multiple comparisons . Results Of the 412 participants who underwent r and omization , 390 ( 95 % ) completed the 12-week intervention feeding period . Adherence to the study diets seemed excellent , and body weight remained stable over time ( 15 ) . Table 1 shows baseline characteristics of the 412 participants . Mean urinary sodium excretion at screening was 155 mmol/d , a value higher than that found while participants ate higher-sodium diets ( 142 mmol/d ) . Table 1 . Characteristics of Study Sample Several key subgroups were highly interrelated . Women made up 70 % of African-American participants but only 39 % of non-African-American participants . Women were more likely to be hypertensive than were men . The percentage of both men and women with hypertension increased sharply with age among non-African-American participants ( 21 % of those 45 years of age vs. 47 % of those > 45 years of age ) but was equally high among older and younger African Americans ( 43 % of those 45 years of age vs. 45 % of those > 45 years of age ) . These correlations highlight the potential for confounding in our results and , hence , the importance of the multivariate-adjusted analyses . Effects of the DASH Diet Table 2 shows the effect on systolic blood pressure of the DASH diet compared with the control diet |
13,362 | 29,239,785 | This systematic review confirms the existence of cytokines abnormalities in schizophrenia disease .
Immune imbalances such as increased levels of some cytokines ( either at protein level or at mRNA expression ) , cytokine mRNAs , as well as cytokine gene polymorphisms have been reported with a large support in schizophrenia .
These findings provide a strong evidence of a concomitant process of inflammatory activity in schizophrenia illness course | INTRODUCTION Schizophrenia is a multifactorial psychiatric disease with complex interactions among the brain and the immune system .
A psycho-immune relationship underling schizophrenia is supported by several studies and integrates a specific area of knowledge - psychoneuroimmunology . | BACKGROUND Childhood trauma is associated with higher risk for mental disorders , including psychosis . Heightened sensitivity to social stress may be a mechanism . This virtual reality study tested the effect of childhood trauma on level of paranoid ideations and distress in response to social stress , in interaction with psychosis liability and level of social stress exposure . METHOD Seventy-five individuals with higher psychosis liability ( 55 with recent onset psychotic disorder and 20 at ultra-high risk for psychosis ) and 95 individuals with lower psychosis liability ( 42 siblings and 53 controls ) were exposed to a virtual café in five experiments with 0 - 3 social stressors ( crowded , other ethnicity and hostility ) . Paranoid ideation was measured after each experiment . Subjective distress was self-rated before and after experiments . Multilevel r and om regression analyses were used to test main effects of childhood trauma and interaction effects . RESULTS Childhood trauma was more prevalent in individuals with higher psychosis liability , and was associated with higher level of ( sub clinical ) psychotic and affective symptoms . Individuals with a history of childhood trauma responded with more subjective distress to virtual social stress exposures . The effects of childhood trauma on paranoia and subjective distress were significantly stronger when the number of virtual environmental stressors increased . Higher psychosis liability increased the effect of childhood trauma on peak subjective distress and stress reactivity during experiments . CONCLUSIONS Childhood trauma is associated with heightened social stress sensitivity and may contribute to psychotic and affective dysregulation later in life , through a sensitized paranoid and stress response to social stressors The aim of this study was to look into the balance of pro-inflammatory ( TNF-α , IL-6 ) and anti-inflammatory ( TGF-β ) cytokines and their association with stress , alterations in HPA axis activity and the disease severity in acute psychosis . Socio-demographic and clinical details were collected from 41 in- patients with a diagnosis of Acute and Transient Psychotic Disorder . Holmes and Rahe Stress Scale for stress in the preceding year , and Brief Psychiatric Rating Scale at baseline and follow up ( 4 - 12 weeks ) for psychopathology were applied . IL-6 , TNF-α ( pro-inflammatory ) , TGF-β ( anti-inflammatory ) and Cortisol ( morning and afternoon values ) were measured at baseline and follow up . A total of 30 out of 41 cases recruited had follow up data available . The levels of IL-6 ( p<0.001 ) , TNF-α ( p<0.001 ) and TGF-β ( p<0.001 ) at baseline were all found to be significantly elevated compared to 42 age and gender matched healthy controls . There was a significant increase in the levels of TNF-α ( p=0.020 ) and morning levels of cortisol ( p=0.009 ) and a significant decrease in the levels of TGF-β ( p=0.004 ) and afternoon levels of cortisol ( p=0.043 ) from baseline to follow up . This study showed that there was an increased level of both pro and anti-inflammatory cytokines at baseline and a prolonged pro - inflammatory compared to anti - inflammatory response which warrants larger prospect i ve studies and comparative studies to patients with schizophrenia and bipolar disorders OBJECTIVE Many studies have implicated prenatal infection in the etiology of schizophrenia . Cytokines , a family of soluble polypeptides , are critically important in the immune response to infection and in other inflammatory processes . The goal of this study was to determine whether second-trimester levels of four cytokines-interleukin-8 ( IL-8 ) , interleukin-1beta ( IL-1beta ) , interleukin-6 ( IL-6 ) , and tumor necrosis factor-alpha (TNF-alpha)-are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects . METHOD The authors conducted a nested case-control study of maternal serum cytokine levels in a large birth cohort , born 1959 - 1967 . Cases ( N=59 ) were subjects diagnosed with schizophrenia spectrum disorders ( mostly schizophrenia and schizoaffective disorder ) who had available second-trimester maternal serum sample s. Comparison subjects ( N=105 ) were members of the birth cohort , had not been diagnosed with a schizophrenia spectrum disorder or major affective disorder , and were matched to subjects with schizophrenia for date of birth , gender , length of time in the cohort , and availability of maternal sera . Maternal second-trimester serum levels of IL-8 , IL-1beta , IL-6 , and TNF-alpha were determined by s and wich enzyme-linked immunosorbent assay . RESULTS The second-trimester IL-8 levels in mothers of offspring with schizophrenia spectrum disorders were significantly higher than those of the mothers of comparison subjects . There were no differences between subjects with schizophrenia and comparison subjects with respect to maternal levels of IL-1beta , IL-6 , or TNF-alpha . CONCLUSIONS Using prospect ively collected prenatal sera in a large and well-characterized birth cohort , the authors have documented a significant association between maternal IL-8 level during the second trimester and risk of schizophrenia spectrum disorders in the offspring . These findings provide further support for a substantive role of in utero infection or inflammation in the etiology of schizophrenia . Moreover , these results may have important implication s for elucidating the mechanisms by which disrupted fetal development raises the risk of this disorder IMPORTANCE Longitudinal studies have linked the systemic inflammatory markers interleukin 6 ( IL-6 ) and C-reactive protein ( CRP ) with the risk of developing heart disease and diabetes mellitus , which are common comorbidities for depression and psychosis . Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression , first-episode psychosis , and acute psychotic relapse ; however , the direction of the association has been unclear . OBJECTIVE To test the hypothesis that higher serum levels of IL-6 and CRP in childhood would increase future risks for depression and psychosis . DESIGN , SETTING , AND PARTICIPANTS The Avon Longitudinal Study of Parents and Children (ALSPAC)is a prospect i ve general population birth cohort study based in Avon County , Engl and . We have studied a sub sample of approximately 4500 individuals from the cohort with data on childhood IL-6 and CRP levels and later psychiatric assessment s. MEASUREMENT OF EXPOSURE Levels of IL-6 and CRP were measured in nonfasting blood sample s obtained in participants at age 9 years . MAIN OUTCOMES AND MEASURES Participants were assessed at age 18 years . Depression was measured using the Clinical Interview Schedule-Revised ( CIS-R ) and Mood and Feelings Question naire ( MFQ ) , thus allowing internal replication ; psychotic experiences ( PEs ) and psychotic disorder were measured by a semistructured interview . RESULTS After adjusting for sex , age , body mass index , ethnicity , social class , past psychological and behavioral problems , and maternal postpartum depression , participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed ( CIS-R ) at age 18 years ( adjusted odds ratio [ OR ] , 1.55 ; 95 % CI , 1.13 - 2.14 ) . Results using the MFQ were similar . Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline ( adjusted OR , 1.81 ; 95 % CI , 1.01 - 3.28 ; and adjusted OR , 2.40 ; 95 % CI , 0.88 - 6.22 , respectively ) . Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner . CONCLUSIONS AND RELEVANCE Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood . Inflammatory pathways may provide important new intervention and prevention targets for these disorders . Inflammation might explain the high comorbidity between heart disease , diabetes mellitus , depression , and schizophrenia Findings to date provide evidence that altered membrane structure and function are present in patients with either first-episode or chronic schizophrenia , suggesting defects in phospholipid metabolism and cell signaling in schizophrenia . The purpose of this investigation is to test whether decreased membrane polyunsaturated fatty acids ( PUFAs ) were associated with an increased secretion of proinflammatory cytokines . Thus , we measured interleukin 6 ( IL-6 ) and interleukin 10 ( IL-10 ) in cerebrospinal fluid ( CSF ) of patients with chronic schizophrenia as well as PUFAs of red blood cell ( RBC ) membranes from the same individuals . A significant and inverse correlation was found between CSF IL-6 ( not IL-10 ) and RBC membrane PUFAs levels in both haloperidol-treated and medication-free patients with schizophrenia . Specifically , such an association was found in the n-6 ( 18:2 , 20:4 , and 22:4 ) and , to a lesser extent , the n-3 fatty acids . Taken together , the present findings suggest that decreased membrane PUFAs may be related to an immune disturbance in schizophrenia , possibly result ing from an increased phospholipase A2 activity mediated through the proinflammatory cytokines An overactivation of the Th1 activity in schizophrenia had been described . Interleukin-12 ( IL-12 ) , a proinflammatory cytokine , plays a key role in the regulation of the Th1 response . The aims of this study were to investigate the effect of first and second generation antipsychotic drugs on IL-12 production during the acute phase of the illness and its association with clinical features . Participants comprised 56 drug-naïve first episode psychotic patients and 28 healthy volunteers . Patients were initially r and omly assigned to risperidone ( n=16 ) , olanzapine ( n=20 ) or haloperidol ( n=20 ) ; subject were maintained on the same medication throughout the study . Clinical assessment s were conducted at baseline and at 6 weeks . IL-12 plasma levels were assessed at baseline and after 6 weeks of antipsychotic treatment . IL-12 haplotypes were also analysed . Patients showed higher IL-12 plasma levels at baseline compared with controls , and had a significant increase in IL-12 plasma level after 6 weeks of antipsychotic treatment . No significant differences in IL-12 level increase were found among the three antipsychotic treatments . IL-12 plasma levels at week 6 were not significantly associated with the severity of psychopathology at week 6 . Thus , patients with a first episode of psychosis have inflammatory-like immunological function during early phases of the illness that it is independent of the antipsychotic treatment used An increasing body of evidence suggests a role for the immune system in the pathogenesis of schizophrenia . The information concerning the effects of antipsychotics on cytokine profiles are limited and often controversial in particular regarding novel antipsychotics . The authors first investigated the production of various cytokines [ interleukin (IL)-2 , IL-4 , IL-10 , interferon (INF)-gamma ] in drug-free ( n = 12 ) and drug-naive ( n = 3 ) schizophrenic patients and in healthy controls ( n = 33 ) and then the modifications of cytokines values during a 3-month period of treatment with risperidone . In the baseline condition , the production of IL-2 and INF-gamma was significantly higher ( P = .023 and .026 , respectively ) in patients than in controls . In the same patients , the use of risperidone was associated with augmented IL-10 ( a suppressor of Type I cytokines ) and decreased INF-gamma production . This modification suggests that clinical improvement is associated with a reduction in the inflammatory-like situation present in not currently treated schizophrenic patients BACKGROUND Some but not all antipsychotics have been shown to modulate plasma cytokine levels in schizophrenia patients . Thus far , the most consistent finding has been the increase in plasma levels of soluble interleukin (IL)-2 receptor ( sIL-2R ) associated with clozapine treatment . Quetiapine is a second-generation antipsychotic with a pharmacological profile similar to that of clozapine , but its immunomodulatory effects have not been investigated in schizophrenia yet . The purpose of this exploratory study was to examine the changes in plasma levels of sIL-2R in schizophrenia during quetiapine treatment and association with psychopathology . METHODS Participants were 29 schizophrenia-spectrum disorder patients ( DSM-IV criteria ) , and 28 healthy controls . Patients had a comorbid substance use disorder ( cannabis > alcohol > cocaine ) , since quetiapine is increasingly used in this population of dual diagnosis . No participant suffered from infection or overt inflammatory diseases . On baseline , patients taking mostly second-generation antipsychotics were switched to quetiapine for a 12-week open-label trial . Five patients were drop-outs . Mean dose of quetiapine for trial completers ( n=24 ) was 466.6mg±227.3 . Psychiatric variables were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia . Plasma sIL-2R levels were assessed at baseline , weeks 6 and 12 in patients , and in healthy controls , using s and wich immunoassay . Plasma IL-6 and IL-1 receptor antagonist ( IL-1RA ) were measured for comparison purpose s. RESULTS On baseline , plasma sIL-2R , IL-6 and IL-1RA levels were higher in dual-diagnosis patients , compared to controls . Plasma sIL-2R further increased after quetiapine treatment ( p=0.037 ) , while plasma IL-6 and IL-1RA did not change . Clinical improvements were observed in positive , negative and depressive symptoms , and substance abuse severity ( all p<0.01 ) . Interestingly , changes in sIL-2R levels during treatment were inversely correlated with changes in positive symptoms ( r=-0.524 ; p=0.009 ) . That is , increases in sIL-2R levels were associated with reductions in positive symptoms . CONCLUSION These data show that quetiapine elevates , like clozapine , sIL-2R levels in schizophrenia . Furthermore , the results suggest that sIL-2R alterations in schizophrenia rely on complex interplays between antipsychotics and the positive symptoms of the disorder . Future r and omized controlled trials involving larger sample s of schizophrenia patients are warranted to determine whether changes in plasma sIL-2R are quetiapine-related |
13,363 | 17,443,603 | There is currently no evidence to support the use of CFTR gene transfer reagents as a treatment for lung disease in people with cystic fibrosis . | BACKGROUND Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator ( CFTR ) , and is characterised by chronic lung infection result ing in inflammation and progressive lung damage that results in a reduced life expectancy .
OBJECTIVES To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes , and to assess any adverse effects . | Gene transfer is an attractive option to treat the basic defect in cystic fibrosis . In a double-blind , placebo-controlled , rising-dose tolerance study in the nasal epithelium , we tested the safety and efficacy of a cationic liposome [ p-ethyl-dimyristoylphosphadityl choline ( EDMPC ) cholesterol ] complexed with an expression plasmid containing hCFTR cDNA . Eleven adult CF patients were studied in a protocol that allowed comparisons within individual subjects : vector and placebo were sprayed into alternate nostrils at intervals over 7 h. After dosing , vector-specific DNA was present in nasal lavage of all subjects for up to 10 days . There were no adverse events . The vector-treated epithelium did not exhibit a significant increase in CFTR-mediated Cl- conductance from baseline and was not different from the placebo-treated nostril : mean deltaCFTR Cl- conductance , mV + /- SEM , -1.6+/-0.4 vs -0.6+/-0.4 , respectively . CFTR-mediated Cl- conductance increased toward normal during repetitive nasal potential difference measurements over the 3 days before dosing which influenced the postdosing calculations . No vector-specific mRNA was detected in the nasal epithelial scrape biopsies , although endogenous CFTR mRNA was detected in all subjects . We conclude that the lipid-DNA complex is safe , but did not produce consistent evidence of gene transfer to the nasal epithelium by physiologic or molecular measures STUDY OBJECTIVES The primary objective was to determine the safety and tolerability of repeated doses of aerosolized adeno-associated serotype 2 vector containing cystic fibrosis transmembrane conductance regulator ( CFTR ) complementary DNA ( cDNA ) [ tgAAVCF ] , an adeno-associated virus ( AAV ) vector encoding the complete human CFTR cDNA . Secondary objectives included evaluation of pulmonary function assessed by spirometry , lung abnormalities by high-resolution CT ( H RCT ) , airway cytokines , vector shedding , serum neutralizing antibody to AAV serotype 2 ( AAV2 ) , and gene transfer and expression in a subset of subjects undergoing bronchoscopy with bronchial brushings . DESIGN R and omized , double-blind , placebo-controlled , phase II trial . SETTING Eight cystic fibrosis ( CF ) centers in the United States . SUBJECTS CF patients with mild lung disease , defined as FEV(1 ) > or = 60 % predicted . INTERVENTIONS Subjects were r and omized to inhale three aerosolized doses of 1 x 10(13 ) deoxyribonuclease-resistant particles of tgAAVCF or matching placebo at 30-day intervals using the Pari LC Plus nebulizer ( PARI ; Richmond , VA ) . MEASUREMENTS AND RESULTS Of 42 subjects r and omized , 20 subjects received at least one dose of tgAAVCF and 17 subjects received placebo . No difference in the pattern of adverse events or laboratory abnormalities was noted between the two treatment groups . Improvements in induced-sputum interleukin-8 ( p = 0.03 ) and FEV(1 ) ( p = 0.04 ) were observed at day 14 and day 30 , respectively , in the group receiving tgAAVCF when compared to those receiving placebo . No significant differences in H RCT scans were noted . Vector shedding in sputum was observed at low levels up to 90 days after the third dose of vector . All subjects receiving tgAAVCF exhibited an increase ( by at least fourfold ) in serum AAV2-neutralizing antibodies and detectable levels in BAL fluid from five of six treated subjects undergoing BAL . Gene transfer but not gene expression was detected in a subset of six tgAAVCF subjects who underwent bronchoscopy . CONCLUSIONS Repeat doses of aerosolized tgAAVCF were safe and well tolerated , and result ed in encouraging trends in improvement in pulmonary function in patients with CF and mild lung disease Cationic lipids show promise as vectors for transfer of CFTR cDNA to airway epithelia of patients with cystic fibrosis ( CF ) . However , previous studies have not compared the effect of DNA-lipid to DNA alone . Recently , we developed a formulation of plasmid encoding CFTR ( pCF1-CFTR ) and cationic lipid ( GL-67:DOPE ) that generated greater gene transfer in mouse lung than previously described DNA-lipid vectors . Therefore , we tested the hypothesis that DNA-lipid complexes were more effective than DNA alone at transferring CFTR cDNA to airway epithelia in vivo . We administered complexes of DNA-lipid to one nostril and DNA alone to the other nostril in a r and omized , double-blind study . Electrophysiologic measurements showed that DNA-lipid complexes partially corrected the Cl- transport defect . Importantly , the pCF1-CFTR plasmid alone was at least as effective as complexes of DNA with lipid . Measurements of vector-specific CFTR transcripts also showed gene transfer with both DNA-lipid and DNA alone . These results indicate that nonviral vectors can transfer CFTR cDNA to airway epithelia and at least partially restore the Cl- transport defect characteristic of CF . However , improvements in the overall efficacy of gene transfer are required to develop a treatment for CF We sought to evaluate the ability of an E1(- ) , E3(- ) adenovirus ( Ad ) vector ( Ad(GV)CFTR.10 ) to transfer the normal human cystic fibrosis transmembrane conductance regulator ( CFTR ) cDNA to the airway epithelium of individuals with cystic fibrosis ( CF ) . We administered Ad(GV)CFTR.10 at doses of 3 x 10(6 ) to 2 x 10(9 ) plaque-forming units over 9 months by endobronchial spray to 7 pairs of individuals with CF . Each 3-month cycle , we measured vector-derived versus endogenous CFTR mRNA in airway epithelial cells prior to therapy , as well as 3 and 30 days after therapy . The data demonstrate that ( a ) this strategy appears to be safe ; ( b ) after the first administration , vector-derived CFTR cDNA expression in the CF airway epithelium is dose-dependent , with greater than 5 % endogenous CFTR mRNA levels at the higher vector doses ; ( c ) expression is transient , lasting less than 30 days ; ( d ) expression can be achieved with a second administration , but only at intermediate doses , and no expression is observed with the third administration ; and ( e ) the progressive lack of expression with repetitive administration does not closely correlate with induction of systemic anti-Ad neutralizing antibodies . The major advantage of an Ad vector is that it can deliver sufficient levels of CFTR cDNA to the airway epithelium so that CFTR expression protects the lungs from the respiratory manifestations of CF . However , this impressive level of expression is linked to the challenging fact that expression is limited in time . Although this can be initially overcome by repetitive administration , unknown mechanisms eventually limit this strategy , and further repetitive administration does not lead to repetitive expression Cystic fibrosis ( CF ) , an autosomal recessive disorder result ing from mutations in the cystic fibrosis trans-membrane conductance regulator ( CFTR ) gene , is the most common lethal genetic illness in the Caucasian population . Gene transfer to airway epithelium , using adenoviruses containing normal CFTR cDNA , leads to transient production of CFTR mRNA and , in some studies , to correction of the airway epithelial ion transport defect caused by dysfunctional CFTR . Inflammatory responses to the adenoviral vector have been reported , particularly at high viral titers . We evaluated the effects of adenovirus-mediated CFTR gene transfer to airway epithelium in 36 subjects with CF ( 34 individuals , 2 of whom received two separate doses of vector ) , 20 by lobar instillation and 16 by aerosol administration . Doses ranged from 8 x 10(6 ) to 2.5 x 10(10 ) infective units ( IU ) , in 0.5-log increments . After lobar administration of low doses there were occasional reports of cough , low- grade temperature , and myalgias . At the highest lobar dose ( 2.5 x 10(9 ) IU ) two of three patients had transient myalgias , fever , and increased sputum production with obvious infiltrates on CT scan . After aerosol administration there were no significant systemic symptoms until the 2.5 x 10(10 ) IU dose , when both patients experienced myalgias and fever that resolved within 24 hr . There were no infiltrates seen on chest CT scans in any of the patients in the aerosol administration group . There were no consistent changes in pulmonary function tests or any significant rise in serum IgG or neutralizing antibodies in patients from either group . Serum , sputum , and nasal cytokines , measured before and after vector administration , showed no correlation with adenoviral dose . Gene transfer to lung cells was inefficient and expression was transient . Cells infected with the vector included mononuclear inflammatory cells as well as cuboidal and columnar epithelial cells . In summary , we found no consistent immune response , no evidence of viral shedding , and no consistent change in pulmonary function in response to adenovirus-mediated CFTR gene transfer . At higher doses there was a mild , nonspecific inflammatory response , as evidence d by fevers and myalgias . Overall , vector administration was tolerated but transfer of CFTR cDNA was inefficient and transgene expression was transient for the doses and method of administration used here The major cause of mortality in patients with cystic fibrosis ( CF ) is lung disease . Expression of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene product in the airways is a potential treatment . Clinical studies in which the CFTR cDNA was delivered to the respiratory epithelia of CF patients have result ed in modest , transient gene expression . It seems likely that repeated administration of the gene transfer vector will be required for long-term gene expression . We have undertaken a double-blinded study in which multiple doses of a DNA/liposome formulation were delivered to the nasal epithelium of CF patients . Ten subjects received plasmid DNA expressing the CFTR cDNA complexed with DC-Chol/DOPE cationic liposomes , whilst two subjects received placebo . Each subject received three doses , administered 4 weeks apart . There was no evidence of inflammation , toxicity or an immune response towards the DNA/liposomes or the expressed CFTR . Nasal epithelial cells were collected 4 days after each dose for a series of efficacy assays including quantitation of vector-specific DNA and mRNA , immunohistochemistry of CFTR protein , bacterial adherence , and detection of halide efflux ex vivo . Airway ion transport was also assessed in vivo by repeated nasal potential difference ( PD ) measurements . On average , six of the treated subjects were positive for CFTR gene transfer after each dose . All subjects positive for CFTR function were also positive for plasmid DNA , plasmid-derived mRNA and CFTR protein . The efficacy measures suggest that unlike high doses of recombinant adenoviral vectors , DNA/liposomes can be successfully re-administered without apparent loss of efficacy Previous studies have demonstrated that delivery of a recombinant adeno-associated virus ( AAV ) vector encoding the complete human cystic fibrosis transmembrane regulator ( CFTR ) cDNA ( tgAAVCF ) to the nose , sinus , and lungs of subjects with cystic fibrosis ( CF ) was safe and well tolerated . In a small r and omized , double-blind study of three doses of aerosolized tgAAVCF or placebo at 30-day intervals , encouraging but non-significant trends in pulmonary function and induced sputum interleukin 8 ( IL-8 ) levels were seen at early time points . This larger study was conducted to verify these trends . One hundred and two subjects aged 12 years and older with mild-to-moderate cystic fibrosis ( forced expiratory flow in 1 sec [FEV1]:60 % predicted ) were r and omized to two aerosolized doses of 1x10(13)DNase-resistant particles of tgAAVCF ( n=51 ) or matching placebo ( n=51 ) administered 30 days apart . Although tgAAVCF was well tolerated , the study did not meet its primary efficacy end point of statistically significant improvement in FEV1 30 days after initial administration of tgAAVCF compared with placebo . There were no significant differences in spirometric lung function over time , induced sputum biologic markers , or days of antibiotic use in either treatment group . Thus repeated doses of aerosolized tgAAVCF were safe and well tolerated , but did not result in significant improvement in lung function over time . Because gene transfer is the simplest , most basic way to correct the underlying genetic defect that leads to disease in CF , further research is warranted to develop an effective gene transfer agent for the treatment of CF BACKGROUND We and others have previously reported significant changes in chloride transport after cationic-lipid-mediated transfer of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene to the nasal epithelium of patients with cystic fibrosis . We studied the safety and efficacy of this gene transfer to the lungs and nose of patients with cystic fibrosis in a double-blind placebo-controlled trial . METHODS Eight patients with cystic fibrosis were r and omly assigned DNA-lipid complex ( active ) by nebulisation into the lungs followed 1 week later by administration to the nose . Eight control patients followed the same protocol but with the lipid alone ( placebo ) . Safety was assessed clinical ly , by radiography , by pulmonary function , by induced sputum , and by histological analysis . Efficacy was assessed by analysis of vector-specific CFTR DNA and mRNA , in-vivo potential difference , epifluorescence assay of chloride efflux , and bacterial adherence . FINDINGS Seven of the eight patients receiving the active complex reported mild influenza-like symptoms that resolved within 36 h. Six of eight patients in both the active and placebo groups reported mild airway symptoms over a period of 12 h following pulmonary administration . No specific treatment was required for either event . Pulmonary administration result ed in a significant ( p<0.05 ) degree of correction of the chloride abnormality in the patients receiving active treatment but not in those on placebo when assessed by in-vivo potential difference and chloride efflux . Bacterial adherence was also reduced . We detected no alterations in the sodium transport abnormality . A similar pattern occurred following nasal administration . INTERPRETATION Cationic-lipid-mediated CFTR gene transfer can significantly influence the underlying chloride defect in the lungs of patients with cystic fibrosis In cystic fibrosis ( CF ) , mutation of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene results in defective transepithelial ion transport , leading to life shortening inflammatory lung disease . Before lung studies , we tested the safety and efficacy of gene delivery to the nasal epithelium of CF patients using pCMV-CFTR – DOTAP cationic liposome complex . A single dose of 400 μg pCMV-CFTR:2.4 mg DOTAP was administered in a r and omised , double-blinded fashion to the nasal epithelium of eight CF patients , with a further eight receiving buffer only . Patients were monitored for signs and symptoms for 2 weeks before treatment and 4 weeks after treatment . Inflammatory cells were quantified in a nasal biopsy taken 3 days after treatment . There was no evidence for excess nasal inflammation , circulating inflammatory markers or other adverse events ascribable to active treatment . Gene transfer and expression were assayed by the polymerase chain reaction . Transgene DNA was detected in seven of the eight treated patients up to 28 days after treatment and vector derived CFTR mRNA in two of the seven patients at + 3 and + 7 days . Transepithelial ion transport was assayed before and after treatment by nasal potential difference during drug perfusion and by SPQ fluorescence halide ion conductance . Partial , sustained correction of CFTR-related functional changes toward normal values were detected in two treated patients . The level of gene transfer and functional correction were comparable to those reported previously using adenoviral vectors or another DNA – liposome complex , but here were sustained and uncompromised by false positives . These results justify further studies with pCMV-CFTR – DOTAP aim ed at treating CF lung disease BACKGROUND Cystic fibrosis is a monogenic disease that deranges multiple systems of ion transport in the airways , culminating in chronic infection and destruction of the lung . The introduction of a normal copy of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene into the airway epithelium through gene transfer is an attractive approach to correcting the underlying defects in patients with cystic fibrosis . We tested the feasibility of gene therapy using adenoviral vectors in the nasal epithelium of such patients . METHODS An adenoviral vector containing the normal CFTR complementary DNA in four logarithmically increasing doses ( estimated multiplicity of infection , 1 , 10 , 100 , and 1000 ) , or vehicle alone , was administered in a r and omized , blinded fashion to the nasal epithelium of 12 patients with cystic fibrosis . Gene transfer was quantitated by molecular techniques that detected the expression of CFTR messenger RNA and by functional measurements of transepithelial potential differences ( PDs ) to assess abnormalities of ion transport specific to cystic fibrosis . The safety of this treatment was monitored by nasal lavage and biopsy to assess inflammation and vector replication . RESULTS The adenoviral vector was detected in nasal-lavage fluid by culture , the polymerase chain reaction ( PCR ) , or both in a dose-dependent fashion for up to eight days after vector administration . There was molecular evidence of gene transfer by reverse-transcriptase PCR assays or in situ hybridization in five of six patients treated at the two highest doses . However , the percentage of epithelial cells transfected by the vector was very low ( < 1 percent ) , and measurement of PD across the epithelium revealed no significant restoration of chloride transport or normalization of sodium transport . At the lower doses of vector , there were no toxic effects . However , at the highest dose there was mucosal inflammation in two of three patients . CONCLUSIONS In patients with cystic fibrosis , adenoviral-vector-mediated transfer of the CFTR gene did not correct functional defects in nasal epithelium , and local inflammatory responses limited the dose of adenovirus that could be administered to overcome the inefficiency of gene transfer Cystic fibrosis ( CF ) is a common , serious , inherited disease . The major cause of mortality in CF is lung disease , due to the failure of airway epithelial cells to express a functional product of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene . A potential treatment for CF lung disease is the expression of CFTR in the airways following gene transfer . We have undertaken a double-blinded , placebo-controlled , clinical study of the transfer of the CFTR cDNA to the nasal epithelium of 12 CF patients . Cationic liposomes complexed with plasmid containing the human CFTR cDNA were administered to eight patients , whilst four patients received placebo . Biopsies of the nasal epithelium taken 7 days after dosing were normal . No significant changes in clinical parameters were observed . Functional expression of CFTR assessed by in vivo nasal potential difference measurements showed transient correction of the CF chloride transport abnormality in two patients ( 15 days after dosing in one patient ) . Fluorescence microscopy demonstrated CFTR function ex vivo in cells from nasal brushings . In total , evidence of functional CFTR gene transfer was obtained in six out of the eight treated patients . These results provide proof of concept for liposome-mediated CF gene transfer A third-generation adenoviral vector containing recombinant human cystic fibrosis transmembrane conductance regulator ( CFTR ) gene was delivered by bronchoscope in escalating doses to the conducting airway of 11 volunteers with cystic fibrosis . Assessment s of dose-limiting toxicity ( DLT ) , efficiency of gene transfer , and cell-mediated and humoral immune responses to vector administration were performed . DLT , manifest by flulike symptoms and transient radiographic infiltrates , was seen at 2.1 x 10(11 ) total viral particles . A highly specific assay for gene transfer was developed using in situ hybridization with an oligoprobe against unique vector sequence . Detectable gene transfer was observed in harvested bronchial epithelial cells ( < 1 % ) 4 days after vector instillation , which diminished to undetectable levels by day 43 . Adenovirus-specific cell-mediated T cells were induced in most subjects , although only mild increases in systemic humoral immune response were observed . These results demonstrate that gene transfer to epithelium of the lower respiratory tract can be achieved in humans with adenoviral vectors but that efficiency is low and of short duration in the native CF airway tgAAVCF , an adeno-associated cystic fibrosis transmembrane conductance regulator ( CFTR ) viral vector/gene construct , was administered to 23 patients in a Phase II , double-blind , r and omized , placebo-controlled clinical trial . For each patient , a dose of 100,000 replication units of tgAAVCF was administered to one maxillary sinus , while the contralateral maxillary sinus received a placebo treatment , thereby establishing an inpatient control . Neither the primary efficacy endpoint , defined as the rate of relapse of clinical ly defined , endoscopically diagnosed recurrent sinusitis , nor several secondary endpoints ( sinus transepithelial potential difference [ TEPD ] , histopathology , sinus fluid interleukin [IL]-8 measurements ) achieved statistical significance when comparing treated to control sinuses within patients . One secondary endpoint , measurements of the anti-inflammatory cytokine IL-10 in sinus fluid , was significantly ( p < 0.03 ) increased in the tgAAVCF-treated sinus relative to the placebo-treated sinus at day 90 after vector instillation . The tgAAVCF administration was well tolerated , without adverse respiratory events , and there was no evidence of enhanced inflammation in sinus histopathology or alterations in serum-neutralizing antibody titer to adeno-associated virus ( AAV ) capsid protein after vector administration . In summary , this Phase II trial confirms the safety of tgAAVCF but provides little support of its efficacy in the within-patient controlled sinus study . Various potentially confounding factors are discussed Cystic fibrosis ( CF ) is a common autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator gene . Recombinant adenoviruses have shown promise as vectors for transfer of CF transmembrane conductance regulator cDNA to airway epithelia and correction of the Cl- transport defect . However , because adenovirus-mediated gene transfer is transient , use of adenovirus as a vector for treatment of CF would require repeated administration . Therefore , we evaluated repeat administration of an adenovirus vector to the nasal epithelium of patients with CF with five escalating doses of up to 10(10 ) infectious units . There were no detectable adverse affects . All subjects were initially seropositive but developed additional humoral immune responses . The vector partially corrected the defect in airway epithelial Cl- transport in some subjects , although there was variability between subjects and there was less correction with subsequent administration , perhaps because the immune response limited gene transfer . Future work must focus on vectors with increased efficiency and with the ability to evade host defenses BACKGROUND Assessing the biological activity and clinical efficacy of gene therapy is critically important in cystic fibrosis ( CF ) . It is widely accepted that clinical testing using surrogate markers including pulmonary function will be useful in assessing clinical efficacy . One problem with pulmonary surrogate markers of CF disease is the large number of patients and length of time required to demonstrate clinical efficacy . An alternative to pulmonary testing of new CF treatments is use of the maxillary sinuses as a surrogate model of CF lung disease . Using CF sinusitis as a surrogate model for testing clinical efficacy of new treatments is attractive because CF upper respiratory disease is similar to the lower respiratory disease with respect to electrophysiology and microbiology . METHODS Sinusitis recurrence in untreated sinuses was analyzed during a prospect i ve , r and omized , unblinded , dose-escalation , within-subjects , phase I clinical trial of the adeno-associated virus mediated cystic fibrosis transmembrane conductance regulator ( AAV-CFTR ) gene transfer . RESULTS Clinical symptoms combined with sinus endoscopy proved useful in the diagnosis of unilateral and bilateral sinusitis recurrence . Sinusitis recurred at a rate of 45 % during one month of follow-up . IL-8 concentration rose in sinus fluids from affected sinuses . Bacterial cultures and increased sinus leukocytes corroborated recurrent sinusitis . Sinus CT scans were also useful in diagnosing recurrent sinusitis in this surrogate model of CF infectious exacerbations . CONCLUSIONS CF sinusitis as a surrogate for lung disease is particularly well-suited for phase II clinical trials of gene transfer agents , with the potential for measuring clinical efficacy in relatively small numbers of patients over relatively short periods of time OBJECTIVE The host immune response and low vector efficiency have been key impediments to effective cystic fibrosis transmembrane regulator ( CFTR ) gene transfer for cystic fibrosis ( CF ) . An adeno-associated virus vector ( AAV-CFTR ) was used in a phase I dose-escalation study to transfer CFTR cDNA into respiratory epithelial cells of the maxillary sinus of 10 CF patients . STUDY DESIGN A prospect i ve , r and omized , unblinded , dose-escalation , within-subjects , phase I clinical trial of AAV-CFTR was conducted . PATIENTS Ten patients with previous bilateral maxillary antrostomies were treated . MAIN OUTCOME MEASURES Safety , gene transfer as measured by semiquantitative polymerase chain reaction ( PCR ) , and sinus transepithelial potential difference ( TEPD ) were measured . RESULTS The highest level of gene transfer was observed in the range of 0.1 - 1 AAV-CFTR vector copy per cell in biopsy specimens obtained 2 weeks after treatment . When tested , persistence was observed in one patient for 41 days and in another for 10 weeks . Dose-dependent changes in TEPD responses to pharmacologic intervention were observed following treatments . Little or no inflammatory or immune responses were observed . CONCLUSION AAV-CFTR administration to the maxillary sinus results in successful , dose-dependent gene transfer to the maxillary sinus and alterations in sinus TEPD suggestive of a functional effect , with little or no cytopathic or host immune response . Further study is warranted for AAV vectors as they may prove useful for CFTR gene transfer and other in vivo gene transfer therapies . A prospect i ve , r and omized , double-blind , placebo-controlled , within-subjects , phase II clinical trial of the effect AAV-CFTR on clinical recurrence of sinusitis will determine the clinical efficacy of AAV gene therapy for CF |
13,364 | 23,846,573 | We found evidence of variation in the way that administration costs were measured , and that this affected the magnitude of costs reported , which could then influence cost effectiveness .
Conclusions Our findings suggested that manufacturers of biologic medicines should pay attention to formulation issues and their impact on administration costs , because these affect the total costs of healthcare delivery and cost effectiveness | Background The acquisition costs of biologic drugs are often considered to be relatively high compared with those of nonbiologics .
However , the total costs of delivering these drugs also depend on the cost of administration .
Ignoring drug administration costs may distort re source allocation decisions because these affect cost effectiveness .
Objectives The objectives of this systematic review were to develop a framework of drug administration costs that considers both the costs of physical administration and the associated proximal costs ; and , as a case example , to use this framework to evaluate administration costs for biologics within the UK National Health Service ( NHS ) . | The aim of this study was to assess the lifetime cost effectiveness of recombinant activated factor VII vs placebo as adjunctive therapy for control of bleeding in patients with severe blunt trauma in the UK . We developed a cost‐effectiveness model based on patient level data from a 30‐day international , r and omised , placebo‐controlled Phase II trial . The data were supplemented with secondary data from UK sources to estimate lifetime costs and benefits . The model produced a baseline estimate of the incremental cost per life year gained with recombinant activated factor VII relative to placebo of £ 12 613 . The incremental cost per quality adjusted life year gained was £ 18 825 . These estimates are sensitive to the choice of discount rate and health state utility values used . Preliminary results suggest that relative to placebo , recombinant activated factor VII may be a cost‐effective therapy to the UK National Health Service Fifteen anaesthetists were observed while providing anaesthesia for 15 pairs of adult cardiac surgical operations , using conventional methods for one of each pair and a new drug administration system design ed to reduce error for the other . Aspects of each method were rated by users on 10‐cm visual analogue scales ( 10 being best ) . The new system was rated more favourably than conventional methods in terms of safety ( median [ range ] = 8.1 [ 6.8–9.7 ] vs. 7.1 [ 2.6–9.3 ] cm ; p = 0.001 ) and usability ( 8.5 [ 5.9–9.4 ] vs. 7.5 [ 3.2–9.8 ] cm ; p = 0.027 ) . The new system saved preparation time both before anaesthesia ( median [ range ] = 180 [ 32–480 ] vs. 360 [ 120–600 ] s ; p = 0.013 ) and during anaesthesia ( 10 [ 2–38 ] vs. 12 [ 10–60 ] s ; p = 0.009 ) . Prefilled syringes for the new system increased costs by € 23.00 per anaesthetic ( p = 0.041 ) , but this increase is likely to be offset by the potential of the new system to decrease costly iatrogenic harm by preventing drug error Oral capecitabine ( Xeloda ® ) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer . Oxaliplatin-based therapy is becoming st and ard for Dukes ' C colon cancer in patients suitable for combination therapy , but is not yet approved by the UK National Institute for Health and Clinical Excellence ( NICE ) in the adjuvant setting . Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin ( 5-FU/LV ) , with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival . We assessed the cost-effectiveness of adjuvant capecitabine from payer ( UK National Health Service ( NHS ) ) and societal perspectives . We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality -adjusted life months ( QALMs ) . Acquisition costs were higher for capecitabine than 5-FU/LV , but higher 5-FU/LV administration costs result ed in 57 % lower chemotherapy costs for capecitabine . Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations ( cost savings £ 3653 ) . Societal costs , including patient travel/time costs , were reduced by > 75 % with capecitabine vs 5-FU/LV ( cost savings £ 1318 ) , with lifetime gain in QALMs of 9 months . Medical re source utilisation is significantly decreased with capecitabine vs 5-FU/LV , with cost savings to the NHS and society . Capecitabine is also projected to increase life expectancy vs 5-FU/LV . Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes ' C colon cancer . This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK OBJECTIVE To determine the cost of achieving pregnancy with different gonadotropin preparations . DESIGN Cost-minimization analysis of a prospect i ve r and omized clinical trial . SETTING Twenty-two centers in six countries . PATIENT(S ) Women 18 to 36 years of age with infertility for more than 1 year who were undergoing IVF or ICSI . INTERVENTION(S ) Highly purified hMG or recombinant FSH . RESULT ( S ) Mean cost of achieving an ongoing pregnancy . The mean cost per patient treatment cycle was estimated to be pound 2423 with highly purified hMG ( 95 % CI , pound 2356 to pound 2495 ) and pound 2745 with recombinant FSH ( 95 % CI , pound 2658 to pound 2830 ) . The ongoing pregnancy rate was 22 % with highly purified hMG and 19 % with recombinant FSH . The cost per ongoing pregnancy was pound 10781 with highly purified hMG ( 95 % CI , pound 9056 to pound 12919 ) and pound 14284 with recombinant FSH ( 95 % CI , pound 11883 to pound 17891 ) . CONCLUSION ( S ) Highly purified hMG and recombinant FSH are equally effective , but highly purified hMG is less expensive per cycle . Using highly purified hMG instead of recombinant FSH would translate into a 13 % increase in the number of cycles that could be offered This study was design ed to assess the cost-effectiveness of erlotinib compared with docetaxel in the second-line management of advanced non-small-cell lung cancer ( NSCLC ) within the UK National Health Service ( NHS ) . A health-state transition model , based on two r and omized phase III studies of erlotinib or docetaxel versus best supportive care , was used to estimate total direct costs , quality -adjusted life years ( QALYs ) and the subsequent net monetary benefit . Erlotinib was associated with a reduction in total costs ( £ 13 730 versus £ 13 956 ) and improved outcomes ( total QALYs of 0.238 versus 0.206 ) compared with docetaxel . Sensitivity analyses demonstrated the robustness of this analysis . In summary , erlotinib appeared to generate similar overall survival , an increase in QALYs and a small reduction in total NHS costs compared with docetaxel , due to lower adverse event and drug administration costs . Consequently , from a health economics perspective for the treatment of relapsed stage III - IV NSCLC patients in the UK , erlotinib has advantages over docetaxel The National Institute for Health and Clinical Excellence ( NICE ) issues m and atory guidance on health technologies to the UK NHS , based on clinical evidence , cost-effectiveness and other considerations . However , the exact factors considered , their relative importance and tradeoffs between them are not made explicit . Previous research modelled NICE decisions as a binary choice ( accept/reject ) dependent on cost-effectiveness , amongst other variables . This paper proposes and tests an alternative model of decision-making that may better represent the " yes , but ... " nature of many NICE decisions . Decisions were categorised as " recommended for routine use " , " recommended for restricted use " or " not recommended " . The NICE appraisal process was modelled as a single decision between the three categories . Multinomial logistic regression techniques were used to evaluate the impact of : quantity/ quality of clinical evidence ; cost-effectiveness ; decision date ; existence of alternative treatments ; budget impact ; technology type . Results suggest that interventions supported by more r and omised trials are more likely to be recommended and endorsed for routine use . Higher cost-effectiveness ratios increased the likelihood of interventions being rejected rather than recommended for restricted use but did not significantly affect the decision between routine and restricted use . Pharmaceuticals , interventions appraised early in the NICE programme and those with more systematic review s were also less likely to be rejected , while patient group su bmi ssions made a recommendation for routine rather than restricted use more likely . The presence of factors affecting the decision between routine and restricted use but not that between routine use and rejection suggests that modelling these three outcomes reflects NICE decision-making more closely than binary-choice analyses OBJECTIVES To estimate the cost-effectiveness of temsirolimus compared to interferon-alpha for first line treatment of patients with advanced , poor prognosis renal cell carcinoma , from the perspective of the UK National Health Service . METHODS A decision-analytic model was developed to estimate the cost-effectiveness of temsirolimus . The clinical effectiveness of temsirolimus compared with interferon-alpha and the utility values ( using EQ-5D tariffs ) were taken from a recent phase III r and omized clinical trial . Cost data were obtained from published literature and based on current UK practice . The effect of parameter uncertainty on cost-effectiveness was explored through extensive one-way and probabilistic sensitivity analyses . RESULTS Compared to interferon-alpha , temsirolimus treatment result ed in an incremental cost per QALY gained of pound94,632 ; based on an estimated mean gain of 0.24 quality -adjusted life years ( QALYs ) per patient , at a mean additional cost of pound22,331 ( inflated to 2007/8 ) . The cost per QALY for patient subgroups ranged from pound74,369 to pound154,752 . The probability that temsirolimus is cost-effective compared to interferon-alpha at a willingness to pay threshold of pound30,000 per QALY for all patient groups is expected to be close to zero . The cost per QALY was sensitive to the clinical effectiveness parameters , health state utilities , drug costs and the cost of administration of temsirolimus . CONCLUSIONS Temsirolimus has been shown to be clinical ly effective compared to interferon-alpha offering additional health benefits , however , with a cost per QALY in excess of pound90,000 , it may not be regarded as a cost-effective use of re sources in some health care setting |
13,365 | 31,335,677 | The meta- analysis showed that other than its urate-lowering effect , febuxostat presented a reno-protective effect in CKD patients . | BACKGROUND / OBJECTIVE Hyperuricemia has been proven to be an independent risk factor for chronic kidney disease ( CKD ) .
However , the role of hyperuricemia in the progression of CKD remains unclear .
Thus , we performed a systematic review and meta- analysis to evaluate the efficacy and safety of febuxostat , a first line urate-lowering agent , in CKD patients with hyperuricemia . | The kidney is one of the organs most prominently affected by aging . This can be seen by a loss of renal mass which is caused by a decrease in the number of nephrons result ing in hyperfiltration , hypertrophy and elevations in glomerular pressure . The factors influencing aging of the kidney are not fully eluci date d. Epidemiological , experimental and interventional studies result ed in inconsistent results and have not firmly established whether uric acid levels affect progression of Chronic Kidney Disease ( CKD ) . Therefore , we analyzed whether uric acid levels predict the progression of CKD in the Mild to Moderate Kidney Disease Study comprising at baseline 227 Caucasian patients aged 18 - 65 years with primary non-diabetic CKD of various degrees of renal impairment . Of them , 177 completed a prospect i ve follow-up of 7 years . Primary endpoint was progression of CKD defined as doubling of baseline serum creatinine and /or terminal renal failure . Patients who reached a progression endpoint ( n = 6 5 ) were significantly older , had higher baseline serum creatinine and protein excretion rates as well as lower Glomerular Filtration Rate ( GFR ) . Uric acid levels were only higher in patients with progression of disease when patients with uric acid-lowering drugs were excluded from the analysis . Cox regression analysis revealed that increasing uric acid levels predict disease progression only when the analysis was not adjusted for baseline kidney function parameters . As soon as we adjusted the analysis for GFR and proteinuria this association completely vanished . In summary , our prospect i ve 7 year follow-up study in patients with non-diabetic primary CKD did not support uric acid as an independent predictor for CKD progression Background : Endothelial dysfunction is an important risk factor for cardiovascular diseases to occur in end-stage renal disease patients . Febuxostat , being a novel xanthine oxidase inhibitor , is apparently having a beneficial role in improving the endothelial dysfunction ; however , data among hemodialysis patients are still limited . Methods : A prospect i ve , placebo-controlled , block-r and omized , double-blinded study was carried out to evaluate the effect of oral febuxostat on the endothelial dysfunction in hemodialysis patients . Fifty-seven eligible hemodialysis patients were r and omly assigned to either the drug group ( 40 mg thrice weekly ) or the placebo group . Serum Asymmetric dimethylarginine ( ADMA ) , Serum uric acid ( UA ) , and serum high sensitivity C-reactive protein ( hsCRP ) were measured at baseline and at the end of a 2-month study . Serum alanine aminotransferase ( ALT ) , serum aspartate aminotransferase ( AST ) , and the occurrence of pancytopenia were tested as safety parameters at baseline and at the end of study . Results : Serum UA significantly decreased from 7.5 ± 0.8 to 5.1 ± 1.2 mg/dL in the febuxostat group , while it did not change significantly in the placebo group . Treatment with febuxostat result ed in a significant decrease in the serum ADMA level from 1.027 ± 0.116 to 0.944 ± 0.104 µmol/L and the serum hsCRP level from 12.5 ± 1.65 to 12.1 ± 1.70 mg/L. Testing of serum ALT , serum AST , and pancytopenia revealed no significant difference in both groups . Conclusion : Febuxostat appears to improve hyperuricemia and endothelial dysfunction and ameliorate inflammation in hemodialysis patients with no safety concerns Introduction The purpose of this study was to compare urate-lowering ( UL ) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate ( sUA ) ≥ 8.0 mg/dL in a six-month trial . Methods Subjects ( n = 2,269 ) were r and omized to febuxostat 40 mg or 80 mg , or allopurinol 300 mg ( 200 mg in moderate renal impairment ) . Endpoints included the proportion of all subjects with sUA < 6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA < 6.0 mg/dL. Safety assessment s included blinded adjudication of each cardiovascular ( CV ) adverse event ( AE ) and death . Results Comorbidities included : renal impairment ( 65 % ) ; obesity ( 64 % ) ; hyperlipidemia ( 42 % ) ; and hypertension ( 53 % ) . In febuxostat 40 mg , febuxostat 80 mg , and allopurinol groups , primary endpoint was achieved in 45 % , 67 % , and 42 % , respectively . Febuxostat 40 mg UL was statistically non-inferior to allopurinol , but febuxostat 80 mg was superior to both ( P < 0.001 ) . Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg ( 72 % ; P < 0.001 ) compared with febuxostat 40 mg ( 50 % ) or allopurinol ( 42 % ) , but febuxostat 40 mg showed greater efficacy than allopurinol ( P = 0.021 ) . Rates of AEs did not differ across treatment groups . Adjudicated ( APTC ) CV event rates were 0.0 % for febuxostat 40 mg and 0.4 % for both febuxostat 80 mg and allopurinol . One death occurred in each febuxostat group and three in the allopurinol group . Conclusions Urate-lowering efficacy of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol ( 300/200 mg ) , which were comparable . In subjects with mild/moderate renal impairment , both febuxostat doses were more efficacious than allopurinol and equally safe . At the doses tested , safety of febuxostat and allopurinol was comparable . Clinical Trial Registration The aim of the present study was to determine the influence of severe renal dysfunction ( estimated glomerular filtration rate < 30 ml/min/1.73 m2 , including hemodialysis ) on the pharmacokinetics and therapeutic effects of febuxostat using a population pharmacokinetic analysis . This study recruited patients with hyperuricemia who were initially treated with allopurinol , but were switched to febuxostat , and it consists of 2 sub- studies : a pharmacokinetic study ( 26 patients ) and retrospective efficacy evaluation study ( 51 patients ) . The demographic and clinical data of patients were collected from electronic medical records . Plasma febuxostat concentrations were obtained at each hospital visit . Population pharmacokinetic modeling was performed with NONMEM version 7.2 . A total of 128 plasma febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis . The data were best described by a 1-compartment model with first order absorption . Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat , whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution . The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment . No serious adverse event associated with febuxostat was observed irrespective of renal function . The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat . These results suggest that febuxostat is tolerated well by patients with severe renal impairment Background Hyperuricemia is associated with the onset of chronic kidney disease ( CKD ) and renal disease progression . Febuxostat , a novel , non-purine , selective xanthine oxidase inhibitor , has been reported to have a stronger effect on hyperuricemia than conventional therapy with allopurinol . However , few data are available regarding the clinical effect of febuxostat in patients with CKD . Methods A prospect i ve , r and omized , open-label , parallel-group trial was conducted in hyperuricemic patients with stage 3 CKD . Patients were r and omly assigned to treatment with febuxostat ( n = 21 ) or to continue conventional therapy ( n = 19 ) . Treatment was continued for 12 weeks . The efficacy of febuxostat was determined by monitoring serum uric acid ( UA ) levels , blood pressures , renal function , and urinary protein levels . In addition , urinary liver-type fatty acid-binding protein ( L-FABP ) , urinary albumin , urinary beta 2 microglobulin ( β2MG ) , and serum high sensitivity C-reactive protein were measured before and 12 weeks after febuxostat was added to the treatment . Results Febuxostat result ed in a significantly greater reduction in serum UA ( −2.2 mg/dL ) than conventional therapy ( −0.3 mg/dL , P < 0.001 ) . Serum creatinine and estimated glomerular filtration rate changed little during the study period in each group . However , treatment with febuxostat for 12 weeks reduced the urinary levels of L-FABP , albumin , and β2MG , whereas the levels of these markers did not change in the control group . Conclusion Febuxostat reduced serum UA levels more effectively than conventional therapy and might have a renoprotective effect in hyperuricemic patients with CKD . Further studies should clarify whether febuxostat prevents the progression of renal disease and improves the prognosis of CKD BACKGROUND Hyperuricemia is associated strongly with the development of hypertension , renal disease , and progression . Allopurinol decreases serum uric acid levels by inhibiting the enzyme xanthine oxidase . We hypothesized that administrating allopurinol to decrease serum uric acid levels to the normal range in hyperuricemic patients with chronic kidney disease may be of benefit in decreasing blood pressure and slowing the rate of renal disease progression in these patients . METHODS We conducted a prospect i ve , r and omized , controlled trial of 54 hyperuricemic patients with chronic kidney disease . Patients were r and omly assigned to treatment with allopurinol , 100 to 300 mg/d , or to continue the usual therapy for 12 months . Clinical , hematologic , and biochemical parameters were measured at baseline and 3 , 6 , and 12 months of treatment . We define our study end points as : ( 1 ) stable kidney function with less than 40 % increase in serum creatinine level , ( 2 ) impaired renal function with creatinine level increase greater than 40 % of baseline value , ( 3 ) initiation of dialysis therapy , and ( 4 ) death . RESULTS One patient in the treatment group dropped out because of skin allergy to allopurinol . Serum uric acid levels were significantly decreased in subjects treated with allopurinol , from 9.75 + /- 1.18 mg/dL ( 0.58 + /- 0.07 mmol/L ) to 5.88 + /- 1.01 mg/dL ( 0.35 + /- 0.06 mmol/L ; P < 0.001 ) . There were no significant differences in systolic or diastolic blood pressure at the end of the study comparing the 2 groups . There was a trend toward a lower serum creatinine level in the treatment group compared with controls after 12 months of therapy , although it did not reach statistical significance ( P = 0.08 ) . Overall , 4 of 25 patients ( 16 % ) in the allopurinol group reached the combined end points of significant deterioration in renal function and dialysis dependence compared with 12 of 26 patients ( 46.1 % ) in the control group ( P = 0.015 ) . CONCLUSION Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate chronic kidney disease . Its use is safe and helps preserve kidney function during 12 months of therapy compared with controls . Results of this study need to be confirmed with an additional prospect i ve trial involving a larger cohort of patients to determine the long-term efficacy of allopurinol therapy and in specific chronic kidney disease sub population Recent epidemiologic studies suggest that uric acid predicts the development of new-onset kidney disease , but it is unclear whether uric acid is an independent risk factor . In this study , data from 21,475 healthy volunteers who were followed prospect ively for a median of 7 yr were analyzed to examine the association between uric acid level and incident kidney disease ( estimated GFR [ eGFR ] < 60 ml/min per 1.73 m(2 ) ) . After adjustment for baseline eGFR , a slightly elevated uric acid level ( 7.0 to 8.9 mg/dl ) was associated with a nearly doubled risk for incident kidney disease ( odds ratio 1.74 ; 95 % confidence interval 1.45 to 2.09 ) , and an elevated uric acid ( > or = 9.0 mg/dl ) was associated with a tripled risk ( odds ratio 3.12 ; 95 % confidence interval 2.29 to 4.25 ) . These increases in risk remained significant even after adjustment for baseline eGFR , gender , age , antihypertensive drugs , and components of the metabolic syndrome ( waist circumference , HDL cholesterol , blood glucose , triglycerides , and BP ) . In a fully adjusted spline model , the risk for incident kidney disease increased roughly linearly with uric acid level to a level of approximately 6 to 7 mg/dl in women and 7 to 8 mg/dl in men ; above these levels , the associated risk increased rapidly . In conclusion , elevated levels of uric acid independently increase the risk for new-onset kidney disease Background : In observational studies , higher uric acid levels are associated with metabolic syndrome , diabetes , and kidney disease . Objective : The objective of this study is to examine whether reduction of plasma uric acid with febuxostat , a xanthine oxido reductase inhibitor , impacts adipose tissue oxidative stress , adipokines , and markers of systemic inflammation or kidney fibrosis . Design : This was a double-blinded r and omized controlled trial . Setting : Academic university setting was used . Patients : Overweight or obese adults with hyperuricemia and type 2 diabetic nephropathy were included . Measurements : Adipose tissue thiobarbituric acid reducing substances ( TBARS ) and adiponectin concentrations and urinary transforming growth factor – β ( TGF-β ) were primary endpoints . Plasma C-reactive protein , high molecular weight – adiponectin , interleukin–6 , tumor necrosis factor – α , and TBARS and albuminuria were among predefined secondary endpoints . Methods : Participants were r and omly assigned to febuxostat ( n = 40 ) or matching placebo ( n = 40 ) and followed for 24 weeks . Results : Baseline plasma uric acid levels were 426 ± 83 µmol/L ; 95 % completed the study . Estimated glomerular filtration rate ( eGFR ) declined from 54 ± 17 mL/min/1.73 m2 at baseline to 51 ± 17 mL/min/1.73 m2 at 24 weeks ( P = .05 ) . In separate mixed-effects models , compared with placebo , febuxostat reduced uric acid by 50 % ( P < .001 ) but had no significant effects on subcutaneous adipose tissue TBARS ( −7.4 % , 95 % confidence interval [ CI ] , 57.4%-101.4 % ) or adiponectin ( 6.7 % , 95 % CI , 26.0%-53.8 % ) levels or urinary TGF-β/creatinine ratio ( 18.0 % , 95 % CI , 10.0%-54.8 % ) or secondary endpoints . Limitations : Relatively modest sample size and short duration of follow-up . Conclusions : In this population with progressive diabetic nephropathy , febuxostat effectively reduced plasma uric acid . However , no detectable effects were observed for the prespecified primary or secondary endpoints . Trial Registration : The study was registered in clinical trials.gov ( NCT01350388 ) BACKGROUND The NU-FLASH trial demonstrated that febuxostat was more effective for hyperuricemia than allopurinol . This time , we compared these medications in patients with chronic kidney disease ( CKD ) from the NU-FLASH trial . METHODS AND RESULTS In the NU-FLASH trial , 141 cardiac surgery patients with hyperuricemia were r and omized to a febuxostat group or an allopurinol group . This study analyzed 109 patients with an estimated glomerular filtration rate ( eGFR ) ≤60 mL/min/1.73 m(2 ) , and also analyzed 87 patients with stage 3 CKD . The primary endpoint was the serum uric acid level . Secondary endpoints included serum creatinine , urinary albumin , cystatin-C , oxidized low-density lipoprotein , eicosapentaenoic acid/arachidonic acid ratio , total cholesterol , triglycerides , low-density lipoprotein , high-density lipoprotein , and high-sensitivity C-reactive protein . Among patients with an eGFR≤60 mL/min/1.73 m(2 ) , uric acid levels were significantly lower in the febuxostat group than the allopurinol group from 1 month of treatment onward . The serum creatinine , urinary albumin , cystatin-C , oxidized low-density lipoprotein , eicosapentaenoic acid/arachidonic acid ratio , and high-sensitivity C-reactive protein were also significantly lower in the febuxostat group . Similar results were obtained in the patients with stage 3 CKD . CONCLUSION In cardiac surgery patients with renal dysfunction , febuxostat reduced uric acid earlier than allopurinol , had a stronger renoprotective effect than allopurinol , and also had superior antioxidant and anti-inflammatory effects Endothelial dysfunction is often found in both hyperuricemia and hemodialysis patients . Recent studies have shown that treating hyperuricemia with allopurinol improves endothelial dysfunction . This study is performed to assess the effect of febuxostat on endothelial dysfunction in hemodialysis patients with hyperuricemia . We r and omly assigned 53 hemodialysis patients with hyperuricemia to a febuxostat ( 10 mg daily ) group and a control group and measured flow-mediated dilation , serum uric acid ( UA ) levels , systolic and diastolic blood pressure , malondialdehyde-modified low-density lipoprotein ( MDA-LDL ) , and highly sensitive C-reactive protein ( hsCRP ) at baseline and at the end of a 4-week study period . Flow-mediated dilation increased from 5.3 % ± 2.4 % to 8.9 % ± 3.6 % in the febuxostat group but did not change significantly in the control group . Treatment with febuxostat result ed in a significant decrease in serum UA level and a significant decrease in MDA-LDL compared with baseline , but no significant difference was observed in hsCRP level or blood pressure . No significant differences were observed in the control group . Febuxostat improved endothelial dysfunction and reduced serum UA levels and oxidative stress in hemodialysis patients with hyperuricemia BACKGROUND Hyperuricemia is a putative risk factor for the progression of chronic kidney disease ( CKD ) . We hypothesized that control of asymptomatic hyperuricemia may slow disease progression in CKD . STUDY DESIGN This was a single-center , double-blind , r and omized , parallel-group , placebo-controlled study . SETTING & PARTICIPANTS Eligible participants were adults from Eastern India aged 18 to 65 years with CKD stages 3 and 4 , with asymptomatic hyperuricemia . INTERVENTION The intervention group received febuxostat , 40 mg , once daily for 6 months , while the placebo group received placebo ; both groups were followed up for 6 months . OUTCOMES The primary outcome was the proportion of patients showing a > 10 % decline in estimated glomerular filtration rate ( eGFR ) from baseline in the febuxostat and placebo groups . Secondary outcomes included changes in eGFRs in the 2 groups from baseline and at the end of the study period . RESULTS 45 patients in the febuxostat group and 48 in the placebo group were analyzed . Mean eGFR in the febuxostat group showed a nonsignificant increase from 31.5±13.6 ( SD ) to 34.7±18.1mL/min/1.73m(2 ) at 6 months . With placebo , mean eGFR decreased from a baseline of 32.6±11.6 to 28.2±11.5mL/min/1.73m(2 ) ( P=0.003 ) . The difference between groups was 6.5 ( 95 % CI , 0.08 - 12.81 ) mL/min/1.73m(2 ) at 6 months ( P=0.05 ) . 17 of 45 ( 38 % ) participants in the febuxostat group had a > 10 % decline in eGFR over baseline compared with 26 of 48 ( 54 % ) from the placebo group ( P<0.004 ) . LIMITATIONS Limitations of this study included small numbers of patients and short follow-up , and ∼10 % of the r and omly assigned population dropped out prior to completion . CONCLUSIONS Febuxostat slowed the decline in eGFR in CKD stages 3 and 4 compared to placebo BACKGROUND Despite recent evidence , the role of uric acid as a causal factor in the pathogenesis and progression of kidney disease remains controversial , partly because of the inclusion in epidemiologic studies of patients with hypertension , diabetes , and /or proteinuria . STUDY DESIGN Prospect i ve observational cohort . SETTING & PARTICIPANTS 900 healthy normotensive adult blood donors ( 153 women , 747 men ) evaluated at baseline and after 5 years . PREDICTOR Serum uric acid level . OUTCOMES Decrease in estimated glomerular filtration rate ( eGFR ) > 10 mL/min/1.73 m(2 ) , computed using the Modification of Diet in Renal Disease ( MDRD ) Study equation , with secondary analyses examining similar decreases using the Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI ) and Cockcroft-Gault equations . RESULTS During a median follow-up of 59 months , eGFR decreased from 97 + /- 16 to 88 + /- 14 mL/min/1.73 m(2 ) . Higher serum uric acid levels were associated with a greater likelihood of eGFR decrease in both women and men ( HR , 1.13 [ 95 % CI , 1.04 - 1.39 ] per each 1-mg/dL increase in uric acid level ) ; in multivariable analyses adjusting for age , sex , body mass index , blood glucose level , total cholesterol level , mean blood pressure , urine albumin-creatinine ratio , and serum triglyceride level , the association remained highly significant ( HR , 1.28 [ 95 % CI , 1.12 - 1.48 ] ) . Results were similar using different estimating equations and when the association was examined in sex-specific subgroups . LIMITATIONS Analyses were based on a single baseline uric acid measurement . Women are underrepresented . CONCLUSIONS In healthy normotensive individuals , serum uric acid level is an independent risk factor for decreased kidney function Background Febuxostat immediate release ( IR ) , a xanthine oxidase inhibitor , is indicated for the management of hyperuricemia in patients with gout by lowering urate levels . An extended release ( XR ) formulation of febuxostat was developed to provide equal or superior efficacy on urate lowering compared with the IR formulation and potentially lower the risk of treatment-initiated gout flares due to an altered pattern of drug exposure . The present study evaluated the efficacy and safety of febuxostat XR and IR formulations in patients with gout and moderate renal impairment ( estimated glomerular filtrate rate ≥ 30 and < 60 ml/min ) . Methods This was an exploratory , 3-month , phase II , multicenter , placebo-controlled , double-blind proof-of-concept study . Patients ( n = 189 ) were r and omized 1:1:1:1:1 to receive placebo or febuxostat IR 40 mg , XR 40 mg , IR 80 mg , or XR 80 mg once daily . Endpoints included : proportion of patients with serum uric acid ( sUA ) < 5.0 mg/dl at month 3 ( primary endpoint ) , proportion of patients with sUA < 6.0 mg/dl at month 3 , and proportion of patients with ≥ 1 gout flare requiring treatment over 3 months . Results At month 3 , all febuxostat treatment groups were associated with greater proportions of patients achieving sUA < 5.0 mg/dl ( p < 0.05 vs placebo ) . A greater proportion of patients receiving XR 40 mg achieved sUA < 5.0 mg/dl versus those receiving IR 40 mg ( p = 0.034 ) ; proportions were similar in the IR 80 mg and XR 80 mg groups . Higher proportions of febuxostat-treated patients achieved sUA < 6.0 mg/dl at month 3 ( p < 0.05 vs placebo ) and experienced ≥ 1 gout flare ( significant for all comparisons , except XR 40 mg ) . Incidences of treatment-related adverse events were low across all treatment groups ; the majority were mild or moderate with no apparent trends correlating with IR or XR doses . The most common treatment-emergent adverse event was hypertension . One death ( unrelated to the study drug ) was reported . Conclusions These exploratory data demonstrate that febuxostat ( XR and IR ) formulations were effective and well tolerated in patients with gout and moderate renal impairment . Trial registration Clinical Trials.gov , NCT02128490 Registered on 29 April 2014 Background To compare the safety and efficacy of benzbromarone and febuxostat in hyperuricemia patients with estimated glomerular filtration rate ( eGFR ) 20–60 mL/min/1.73 m2 . Methods This study was a single-centered , parallel-grouped , r and omized clinical trial ( RCT ) . We r and omly assigned hyperuricemia participants with eGFR 20–60 mL/min/1.73 m2 into benzbromarone and febuxostat treatment group . Drugs were adjusted by titration from small doses . Results Seventy-three eligible participants enrolled , 66 subjects ( 33 in each group ) were included finally for analysis . When compared to baseline , serum uric acid ( SUA ) decreased significantly after treatment in both groups , but no differences were detected among all the follow-up points . After 12-month treatment , eGFR did not have significant change in both groups . In the benzbromarone group , kidney stones in one case increased in quantity . In the febuxostat group , kidney stones in one case became smaller in size and in two cases vanished completely . Both drugs did not increase myocardial enzymes significantly after the treatment . In addition , hemoglobin increased significantly in the two groups ( p < 0.05 ) . Conclusions Benzbromarone and febuxostat could reduce SUA and maintain renal function in chronic kidney disease ( CKD ) patients with eGFR 20–60 mL/min/1.73 m2 . Urate-lowering therapy with benzbromarone or febuxostat could increase serum hemoglobin level and potentially improve anemia Introduction : Hyperuricemia is associated with chronic kidney disease ( CKD ) progression and poor cardiovascular outcomes . We studied the effect of febuxostat on estimated glomerular filtration rate ( eGFR ) , proteinuria and monitored the safety profile of the medication . Material and Methods : This is a prospect i ve open-label , r and omized study in CKD stage 3 and 4 patients with diabetic nephropathy and asymptomatic hyperuricemia . Patients were r and omized into febuxostat 40 mg daily and no treatment group using block r and omization method and were followed up for 6 months . Their usual care for diabetes mellitus , hypertension and dyslipidemia were continued in the study . Blood and urine investigations were monitored at baseline , 3 months and 6 months . Results : The eGFR in febuxostat group was stabilized at 6 months with no significant reduction [ 26.2 ( IQR 14.30 ) at baseline to 26.3 ( IQR 15.2 ) ml/min/1.73 m2 ] . Whereas , there was a significant reduction of the eGFR in no treatment group from 28.2 ( IQR 17.9 ) to 27.6 ( IQR 19.3 ) ml/min/1.73 m2 ( p value < 0.01 ) . We found the HbA1c ( glycosylated hemoglobin ) was significantly increased in febuxostat group from 7.2 ± 0.5 % at baseline to 7.6 ± 1.4 at 6 months ( p value 0.04 ) but no significant change of HbA1c in the no treatment group . Proteinuria level was unchanged in both groups . The commonest adverse event was joint pain . Conclusions : Febuxostat was able to preserve eGFR in CKD patients with diabetic nephropathy and this effect was beyond glycemic control . Increment of HbA1c level in febuxostat group needs further larger trials RATIONALE & OBJECTIVE Epidemiologic and clinical studies have suggested that urate-lowering therapy may slow the progression of chronic kidney disease ( CKD ) . However , definitive evidence is lacking . STUDY DESIGN R and omized , double-blind , placebo-controlled trial . SETTING & PARTICIPANTS 467 patients with stage 3 CKD and asymptomatic hyperuricemia at 55 medical institutions in Japan . INTERVENTION Participants were r and omly assigned in a 1:1 ratio to receive febuxostat or placebo for 108 weeks . OUTCOMES The primary end point was the slope ( in mL/min/1.73m2 per year ) of estimated glomerular filtration rate ( eGFR ) . Secondary end points included changes in eGFRs and serum uric acid levels at 24 , 48 , 72 , and 108 weeks of follow-up and the event of doubling of serum creatinine level or initiation of dialysis therapy . RESULTS Of 443 patients who were r and omly assigned , 219 and 222 assigned to febuxostat and placebo , respectively , were included in the analysis . There was no significant difference in mean eGFR slope between the febuxostat ( 0.23±5.26mL/min/1.73m2 per year ) and placebo ( -0.47±4.48mL/min/1.73m2 per year ) groups ( difference , 0.70 ; 95 % CI , -0.21 to 1.62 ; P=0.1 ) . Subgroup analysis demonstrated a significant benefit from febuxostat in patients without proteinuria ( P=0.005 ) and for whom serum creatinine concentration was lower than the median ( P=0.009 ) . The incidence of gouty arthritis was significantly lower ( P=0.007 ) in the febuxostat group ( 0.91 % ) than in the placebo group ( 5.86 % ) . Adverse events specific to febuxostat were not observed . LIMITATIONS GFR was estimated rather than measured , and patients with stages 4 and 5 CKD were excluded . CONCLUSIONS Compared to placebo , febuxostat did not mitigate the decline in kidney function among patients with stage 3 CKD and asymptomatic hyperuricemia . FUNDING Funded by Teijin Pharma Limited . TRIAL REGISTRATION Registered at the UMIN ( University Hospital Medical Information Network ) Clinical Trials Registry with study number UMIN000008343 BACKGROUND Hyperuricemia is prevalent in patients with chronic kidney disease ( CKD ) ; however , data are limited about the relationship of uric acid levels with long-term outcomes in this patient population . STUDY DESIGN Cohort study . SETTING & PARTICIPANTS The Modification of Diet in Renal Disease ( MDRD ) Study was a r and omized controlled trial ( N = 840 ) conducted from 1989 to 1993 to examine the effects of strict blood pressure control and dietary protein restriction on progression of stages 3 to 4 CKD . This analysis included 838 patients . PREDICTOR Uric acid level . OUTCOMES & MEASUREMENTS The study evaluated the association of baseline uric acid levels with all-cause mortality , cardiovascular disease ( CVD ) mortality , and kidney failure . RESULTS Mean age was 52 + /- 12 ( SD ) years , glomerular filtration rate was 33 + /- 12 mL/min/1.73 m(2 ) , and uric acid level was 7.63 + /- 1.66 mg/dL. During a median follow-up of 10 years , 208 ( 25 % ) participants died of any cause , 127 ( 15 % ) died of CVD , and 553 ( 66 % ) reached kidney failure . In multivariate models , the highest tertile of uric acid was associated with increased risk of all-cause mortality ( hazard ratio [ HR ] , 1.57 ; 95 % confidence interval [ CI ] , 1.07 to 2.32 ) , a trend toward CVD mortality ( HR , 1.47 ; 95 % CI , 0.90 to 2.39 ) , and no association with kidney failure ( HR , 1.20 ; 95 % CI , 0.95 to 1.51 ) compared with the lowest tertile . In continuous analyses , a 1-mg/dL greater uric acid level was associated with 17 % increased risk of all-cause mortality ( HR , 1.17 ; 95 % CI , 1.05 to 1.30 ) and 16 % increased risk of CVD mortality ( HR , 1.16 ; 95 % CI , 1.01 to 1.33 ) , but was not associated with kidney failure ( HR , 1.02 ; 95 % CI , 0.97 to 1.07 ) . LIMITATIONS Primary analyses were based on a single measurement of uric acid . Results are generalizable primarily to relatively young white patients with predominantly nondiabetic CKD . CONCLUSIONS In patients with stages 3 to 4 CKD , hyperuricemia appears to be an independent risk factor for all-cause and CVD mortality , but not kidney failure |
13,366 | 31,363,365 | In conclusion , analysis of the pooled data revealed that panobinostat-containing regimens were effective and tolerable for patients with RRMM .
Furthermore , lenalidomide-refractory patients may derive greater benefits from these regimens . | Multiple myeloma ( MM ) remains incurable primarily due to relapse .
Histone deacetylase inhibitors ( HDACis ) have shown potential application for the treatment of relapsed/refractory multiple myeloma ( RRMM ) . | BACKGROUND Histone deacetylase ( HDAC ) inhibitors are an important new class of therapeutics for treating multiple myeloma . Ricolinostat ( ACY-1215 ) is the first oral selective HDAC6 inhibitor with reduced class I HDAC activity to be studied clinical ly . Motivated by findings from pre clinical studies showing potent synergistic activity with ricolinostat and lenalidomide , our goal was to assess the safety and preliminary activity of the combination of ricolinostat with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma . METHODS In this multicentre phase 1b trial , we recruited patients aged 18 years or older with previously treated relapsed or refractory multiple myeloma from five cancer centres in the USA . Inclusion criteria included a Karnofsky Performance Status score of at least 70 , measureable disease , adequate bone marrow reserve , adequate hepatic function , and a creatinine clearance of at least 50 mL per min . Exclusion criteria included previous exposure to HDAC inhibitors ; previous allogeneic stem-cell transplantation ; previous autologous stem-cell transplantation within 12 weeks of baseline ; active systemic infection ; malignancy within the last 5 years ; known or suspected HIV , hepatitis B , or hepatitis C infection ; a QTc Fridericia of more than 480 ms ; and substantial cardiovascular , gastrointestinal , psychiatric , or other medical disorders . We gave escalating doses ( from 40 - 240 mg once daily to 160 mg twice daily ) of oral ricolinostat according to a st and ard 3 + 3 design according to three different regimens on days 1 - 21 with a conventional 28 day schedule of oral lenalidomide ( from 15 mg [ in one cohort ] to 25 mg [ in all other cohorts ] once daily ) and oral dexamethasone ( 40 mg weekly ) . Primary outcomes were dose-limiting toxicities , the maximum tolerated dose of ricolinostat in this combination , and the dose and schedule of ricolinostat recommended for further phase 2 investigation . Secondary outcomes were the pharmacokinetics and pharmacodynamics of ricolinostat in this combination and the preliminary anti-tumour activity of this treatment . The trial is closed to accrual and is registered at Clinical Trials.gov , number NCT01583283 . FINDINGS Between July 12 , 2012 , and Aug 20 , 2015 , we enrolled 38 patients . We observed two dose-limiting toxicities with ricolinostat 160 mg twice daily : one ( 2 % ) grade 3 syncope and one ( 2 % ) grade 3 myalgia event in different cohorts . A maximum tolerated dose was not reached . We chose ricolinostat 160 mg once daily on days 1 - 21 of a 28 day cycle as the recommended dose for future phase 2 studies in combination with lenalidomide 25 mg and dexamethasone 40 mg . The most common adverse events were fatigue ( grade 1 - 2 in 14 [ 37 % ] patients ; grade 3 in seven [ 18 % ] ) and diarrhoea ( grade 1 - 2 in 15 [ 39 % ] patients ; grade 3 in two [ 5 % ] ) . Our pharmacodynamic studies showed that at clinical ly relevant doses , ricolinostat selectively inhibits HDAC6 while retaining a low and tolerable level of class I HDAC inhibition . The pharmacokinetics of ricolinostat and lenalidomide were not affected by co-administration . In a preliminary assessment of antitumour activity , 21 ( 55 % [ 95 % CI 38 - 71 ] ) of 38 patients had an overall response . INTERPRETATION The findings from this study provide preliminary evidence that ricolinostat is a safe and well tolerated selective HDAC6 inhibitor , which might partner well with lenalidomide and dexamethasone to enhance their efficacy in relapsed or refractory multiple myeloma . FUNDING Acetylon Pharmaceuticals BACKGROUND We aim ed to assess efficacy and tolerability of vorinostat in combination with bortezomib for treatment of patients with relapsed or refractory multiple myeloma . METHODS In our r and omised , double-blind , placebo-controlled , phase 3 trial , we enrolled adults ( ≥18 years ) at 174 university hospitals in 31 countries worldwide . Eligible patients had to have non-refractory multiple myeloma that previously responded to treatment ( one to three regimens ) but were currently progressing , ECOG performance statuses of 2 or less , and no continuing toxic effects from previous treatment . We excluded patients with known resistance to bortezomib . We r and omly allocated patients ( 1:1 ) using an interactive voice response system to receive 21 day cycles of bortezomib ( 1·3 mg/m(2 ) intravenously on days 1 , 4 , 8 , and 11 ) in combination with oral vorinostat ( 400 mg ) or matching placebo once-daily on days 1 - 14 . We stratified patients by baseline tumour stage ( International Staging System stage 1 or stage ≥2 ) , previous bone-marrow transplantation ( yes or no ) , and number of previous regimens ( 1 or ≥2 ) . The primary endpoint was progression-free survival ( PFS ) in the intention-to-treat population . We assessed adverse events in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number 00773747 . FINDINGS Between Dec 24 , 2008 , and Sept 8 , 2011 , we r and omly allocated 317 eligible patients to the vorinostat group ( 315 of whom received at least one dose ) and 320 to the placebo group ( all of whom received at least one dose ) . Median PFS was 7·63 months ( 95 % CI 6·87 - 8·40 ) in the vorinostat group and 6·83 months ( 5·67 - 7·73 ) in the placebo group ( hazard ratio [ HR ] 0·77 , 95 % CI 0·64 - 0·94 ; p=0·0100 ) . 312 ( 99 % ) of 315 patients in the vorinostat group and 315 ( 98 % ) of 320 patients in the placebo group had adverse events ( 300 [ 95 % ] adverse events in the vorinostat group and 282 [ 88 % ] in the control group were regarded as related to treatment ) . The most common grade 3 - 4 adverse events were thrombocytopenia ( 143 [ 45 % ] patients in the vorinostat group vs 77 [ 24 % ] patients in the placebo group ) , neutropenia ( 89 [ 28 % ] vs 80 [ 25 % ] ) , and anaemia ( 53 [ 17 % ] vs 40 [ 13 % ] ) . INTERPRETATION Although the combination of vorinostat and bortezomib prolonged PFS relative to bortezomib and placebo , the clinical relevance of the difference in PFS between the two groups is not clear . Different treatment schedules of bortezomib and vorinostat might improve tolerability and enhance activity . FUNDING Merck Micro‐ Abstract We evaluated the combination of pegylated liposomal doxorubicin , bortezomib and vorinostat in 32 patients with relapsed/refractory multiple myeloma in a phase I study . The maximum tolerated dose of vorinostat with PLD/bortezomib was 400 mg on days 4 to 11 . Clinical activity was seen including in bortezomib‐refractory patients . However , hematologic , constitutional and gastrointestinal toxicity was common . Introduction / Background : Deacetylase inhibitors have synergistic activity in combination with proteasome inhibitors and anthracyclines in pre clinical models of multiple myeloma ( MM ) . We therefore evaluated the safety and efficacy of the deacetylase inhibitor vorinostat in combination with pegylated liposomal doxorubicin ( PLD ) and bortezomib in relapsed/refractory MM . Patients and Methods : Thirty‐two patients were treated with PLD and bortezomib in combination with escalating doses of vorinostat on days 4 to 11 or 1 to 14 . Results : The maximum tolerated dose of vorinostat was 400 mg on days 4 to 11 . Neutropenia and thrombocytopenia attributable to protocol therapy were seen in 59 % and 94 % of patients , of which 37 % and 47 % were of grade 3 or higher severity , respectively . Constitutional and gastrointestinal adverse events of all grade s were common , the majority of which were less than grade 3 in severity . The overall response rate ( partial response rate or better ) was 65 % and the clinical benefit rate ( minimal response rate or better ) 74 % . The overall response rate was 83 % , 71 % , and 45 % for patients with bortezomib‐naive , ‐sensitive , and ‐refractory MM , respectively . The median progression‐free survival was 13.9 months and the 3‐year overall survival 77 % . Whole blood proteasome activity assays demonstrated a potential impact of vorinostat on the chymotryptic‐like activity of the proteasome . Conclusion : Further evaluation of PLD , bortezomib , and deacetylase inhibitor combinations is warranted , with special attention directed toward strategies to improve tolerability BACKGROUND Panobinostat is a potent oral pan-deacetylase inhibitor that in pre clinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone . We aim ed to compare panobinostat , bortezomib , and dexamethasone with placebo , bortezomib , and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma . METHODS PANORAMA1 is a multicentre , r and omised , placebo-controlled , double-blind phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma who have received between one and three previous treatment regimens . Patients were r and omly assigned ( 1:1 ) via an interactive web-based and voice response system , stratified by number of previous treatment lines and by previous use of bortezomib , to receive 21 day cycles of placebo or panobinostat ( 20 mg ; on days 1 , 3 , 5 , 8 , 10 , 12 , orally ) , both in combination with bortezomib ( 1·3 mg/m(2 ) on days 1 , 4 , 8 , 11 , intravenously ) and dexamethasone ( 20 mg on days 1 , 2 , 4 , 5 , 8 , 9 , 11 , 12 , orally ) . Patients , physicians , and the investigators who did the data analysis were masked to treatment allocation ; crossover was not permitted . The primary endpoint was progression-free survival ( in accordance with modified European Group for Blood and Marrow Transplantation criteria and based on investigators ' assessment ) and was analysed by intention to treat . The study is ongoing , but no longer recruiting , and is registered at Clinical Trials.gov , number NCT01023308 . FINDINGS 768 patients were enrolled between Jan 21 , 2010 , and Feb 29 , 2012 , with 387 r and omly assigned to panobinostat , bortezomib , and dexamethasone and 381 to placebo , bortezomib , and dexamethasone . Median follow-up was 6·47 months ( IQR 1·81 - 13·47 ) in the panobinostat group and 5·59 months ( 2·14 - 11·30 ) in the placebo group . Median progression-free survival was significantly longer in the panobinostat group than in the placebo group ( 11·99 months [ 95 % CI 10·33 - 12·94 ] vs 8·08 months [ 7·56 - 9·23 ] ; hazard ratio [ HR ] 0·63 , 95 % CI 0·52 - 0·76 ; p<0·0001 ) . Overall survival data are not yet mature , although at the time of this analysis , median overall survival was 33·64 months ( 95 % CI 31·34-not estimable ) for the panobinostat group and 30·39 months ( 26·87-not estimable ) for the placebo group ( HR 0·87 , 95 % CI 0·69 - 1·10 ; p=0·26 ) . The proportion of patients achieving an overall response did not differ between treatment groups ( 235 [ 60·7 % , 95 % CI 55·7 - 65·6 ] for panobinostat vs 208 [ 54·6 % , 49·4 - 59·7 ] for placebo ; p=0·09 ) ; however , the proportion of patients with a complete or near complete response was significantly higher in the panobinostat group than in the placebo group ( 107 [ 27·6 % , 95 % CI 23·2 - 32·4 ] vs 60 [ 15·7 % , 12·2 - 19·8 ] ; p=0·00006 ) . Minimal responses were noted in 23 ( 6 % ) patients in the panobinostat group and in 42 ( 11 % ) in the placebo group . Median duration of response ( partial response or better ) was 13·14 months ( 95 % CI 11·76 - 14·92 ) in the panobinostat group and 10·87 months ( 9·23 - 11·76 ) in the placebo group , and median time to response ( partial response or better ) was 1·51 months ( 1·41 - 1·64 ) in the panobinostat group and 2·00 months ( 1·61 - 2·79 ) in the placebo group . Serious adverse events were reported in 228 ( 60 % ) of 381 patients in the panobinostat group and 157 ( 42 % ) of 377 patients in the placebo group . Common grade 3 - 4 laboratory abnormalities and adverse events ( irrespective of association with study drug ) included thrombocytopenia ( 256 [ 67 % ] in the panobinostat group vs 118 [ 31 % ] in the placebo group ) , lymphopenia ( 202 [ 53 % ] vs 150 [ 40 % ] ) , diarrhoea ( 97 [ 26 % ] vs 30 [ 8 % ] ) , asthenia or fatigue ( 91 [ 24 % ] vs 45 [ 12 % ] ) , and peripheral neuropathy ( 67 [ 18 % ] vs 55 [ 15 % ] ) . INTERPRETATION Our results suggest that panobinostat could be a useful addition to the treatment armamentarium for patients with relapsed or relapsed and refractory multiple myeloma . Longer follow up will be necessary to determine whether there is any effect on overall survival . FUNDING Novartis Pharmaceuticals Panobinostat is an oral pan-deacetylase inhibitor that synergizes with bortezomib to inhibit both the aggresome and proteasome pathways in pre clinical studies . PANORAMA 2 is a phase 2 trial of panobinostat in combination with bortezomib and dexamethasone to treat patients with relapsed and bortezomib-refractory multiple myeloma ( with ≥2 prior lines of therapy , including an immunomodulatory drug , and patients who had progressed on or within 60 days of the last bortezomib-based therapy ) . Fifty-five heavily pretreated patients were enrolled ( median , 4 prior regimens , including a median of 2 prior bortezomib-containing regimens ) . The overall response rate was 34.5 % ( 1 near-complete response and 18 partial responses ) . An additional 10 patients achieved minimal response , for a clinical benefit rate of 52.7 % . Median exposure and progression-free survival were 4.6 and 5.4 months , respectively . In patients who achieved a response , median time to response was 1.4 months , and median duration of response was 6.0 months . Common grade 3/4 adverse events , regardless of study drug relationship , included thrombocytopenia ( 63.6 % ) , fatigue ( 20.0 % ) , and diarrhea ( 20.0 % ) . Only 1 patient had grade 3 peripheral neuropathy . Panobinostat , when combined with bortezomib and dexamethasone , can recapture responses in heavily pretreated , bortezomib-refractory multiple myeloma patients . This trial was registered at www . clinical trials.gov as # NCT01083602 Purpose : Vorinostat , a histone deacetylase inhibitor , enhances cell death by the proteasome inhibitor bortezomib in vitro . We sought to test the combination clinical ly . Experimental Design : A phase I trial evaluated sequential dose escalation of bortezomib at 1 to 1.3 mg/m2 i.v . on days 1 , 4 , 8 , and 11 and vorinostat at 100 to 500 mg orally daily for 8 days of each 21-day cycle in relapsed/refractory multiple myeloma patients . Vorinostat pharmacokinetics and dynamics were assessed . Results : Twenty-three patients were treated . Patients had received a median of 7 prior regimens ( range , 3 - 13 ) , including autologous transplantation in 20 , thalidomide in all 23 , lenalidomide in 17 , and bortezomib in 19 , 9 of whom were bortezomib-refractory . Two patients receiving 500 mg vorinostat had prolonged QT interval and fatigue as dose-limiting toxicities . The most common grade > 3 toxicities were myelo-suppression ( n = 13 ) , fatigue ( n = 11 ) , and diarrhea ( n = 5 ) . There were no drug-related deaths . Overall response rate was 42 % , including three partial responses among nine bortezomib refractory patients . Vorinostat pharmacokinetics were nonlinear . Serum Cmax reached a plateau above 400 mg . Pharmacodynamic changes in CD-138 + bone marrow cells before and on day 11 showed no correlation between protein levels of NF-κB , IκB , acetylated tubulin , and p21CIP1 and clinical response . Conclusions : The maximum tolerated dose of vorinostat in our study was 400 mg daily for 8 days every 21 days , with bortezomib administered at a dose of 1.3 mg/m2 on days 1 , 4 , 8 , and 11 . The promising antimyeloma activity of the regimen in refractory patients merits further evaluation . ( Clin Cancer Res 2009;15(16):5250–7 Purpose : Histone deacetylase ( HDAC ) inhibition improves the efficacy of proteasome inhibition for multiple myeloma but adds substantial toxicity . Pre clinical models suggest that the observed synergy is due to the role of HDAC6 in mediating resistance to proteasome inhibition via the aggresome/autophagy pathway of protein degradation . Experimental Design : We conducted a phase I/II trial of the HDAC6-selective inhibitor ricolinostat to define the safety , preliminary efficacy , and recommended phase II dose in combination with st and ard proteasome inhibitor therapy . Patients with relapsed or refractory multiple myeloma received oral ricolinostat on days 1–5 and 8–12 of each 21-day cycle . Results : Single-agent ricolinostat therapy result ed in neither significant toxicity nor clinical responses . Combination therapy with bortezomib and dexamethasone was well-tolerated during dose escalation but led to dose-limiting diarrhea in an expansion cohort at a ricolinostat dose of 160 mg twice daily . Combination therapy at a ricolinostat dose of 160 mg daily in a second expansion cohort was well tolerated , with less severe hematologic , gastrointestinal , and constitutional toxicities compared with published data on nonselective HDAC inhibitors . The overall response rate in combination with daily ricolinostat at ≥160 mg was 37 % . The response rate to combination therapy among bortezomib-refractory patients was 14 % . Sample s taken during therapy showed dose-dependent increases of acetylated tubulin in peripheral blood lymphocytes . Conclusions : At the recommended phase II dose of ricolinostat of 160 mg daily , the combination with bortezomib and dexamethasone is safe , well-tolerated , and active , suggesting that selective inhibition of HDAC6 is a promising approach to multiple myeloma therapy . Clin Cancer Res ; 23(13 ) ; 3307–15 . © 2017 AACR Panobinostat is a histone deacetylase inhibitor that has shown synergistic pre clinical anti-myeloma activity when combined with other agents , recently exhibiting synergy with the alkylating agent melphalan ( Sanchez et al. , Leuk Res 35(3):373–379 , 2011 ) . This phase 1/2 trial investigated the safety and efficacy of panobinostat in combination with melphalan for relapsed/refractory multiple myeloma patients . There were four different trial treatment schedules due to tolerability issues , with the final treatment schedule ( treatment schedule D ) consisting of panobinostat ( 15 or 20 mg ) and melphalan ( 0.05 or 0.10 mg/kg ) , both administered on days 1 , 3 , and 5 of a 28-day cycle . A total of 40 patients were enrolled ; 3 in treatment schedule A , 9 in schedule B , 7 in schedule C , and finally 21 schedule D. Patients had been treated with a median of four regimens ( range , 1–16 ) and two prior bortezomib-containing regimens ( range , 0–9 ) . Maximum-tolerated dose was established at 20 mg panobinostat and 0.05 mg/kg melphalan in treatment schedule D. Overall , 3 patients ( 7.5 % ) achieved ≥partial response ( two very good PRs and one PR ) while 23 exhibited stable disease and 14 showed progressive disease . All three responders were enrolled in cohort 2 of treatment schedule B ( panobinostat 20 mg thrice weekly continuously with melphalan 0.05 mg/kg on days 1 , 3 , and 5 ) . Neutropenia and thrombocytopenia were common , with 30.8 and 23.1 % of patients exhibiting ≥ grade 3 , respectively . Panobinostat + melphalan appears to have tolerability issues in a dosing regimen capable of producing a response . Care must be taken to balance tolerability and efficacy with this combination Clinical trials of vorinostat , a Class I/II histone deacetylase inhibitor , in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma . This phase IIb , open‐label , single‐institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide‐refractory patients . Patients were considered lenalidomide‐refractory if they had no clinical response PURPOSE Despite advancements , prognosis for patients with relapsed/refractory multiple myeloma ( MM ) is poor , and novel therapies are needed . Panobinostat is a potent deacetylase inhibitor that elicits synergistic effects on MM cells in combination with bortezomib . This phase Ib study sought to determine the maximum-tolerated dose ( MTD ) of panobinostat plus bortezomib in patients with relapsed or relapsed and refractory MM . PATIENTS AND METHODS In the dose-escalation phase ( n = 47 ) , panobinostat was administered orally thrice weekly every week in combination with bortezomib ( 21-day cycles ) . After MTD determination , patients were evaluated in an expansion phase ( n = 15 ) that incorporated a 1-week treatment holiday of panobinostat , with dexamethasone added in cycle 2 . Additional assessment s included safety , pharmacokinetics , and efficacy per International Myeloma Working Group criteria . RESULTS The MTD was established at panobinostat 20 mg plus bortezomib 1.3 mg/m(2 ) . Grade 3 or 4 adverse events ( AEs ) included thrombocytopenia ( 85.1 % ) , neutropenia ( 63.8 % ) , and asthenia ( 29.8 % ) in the escalation phase , and thrombocytopenia ( 66.7 % ) , neutropenia ( 46.7 % ) , and fatigue ( 20.0 % ) in the expansion phase . At MTD in the escalation phase , eight patients ( 47.1 % ) discontinued therapy as a result of AEs , whereas five patients ( 33.3 % ) discontinued treatment in the expansion phase . Expansion phase patients demonstrated greater median treatment duration . Overall response rate ( ORR ) was 73.3 % in the expansion phase and 52.9 % at the escalation phase MTD . Among bortezomib-refractory patients , the ORR was 26.3 % , and 42.1 % of patients had ≥ minimal response . CONCLUSION The MTD of panobinostat plus bortezomib was determined and demonstrated activity in patients with relapsed or relapsed/refractory MM , including bortezomib-refractory patients . A phase II/III clinical trial program ( Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma [ PANORAMA ] ) has been initiated BACKGROUND Panobinostat ( a pan histone deacetylase inhibitor ) is approved in combination with bortezomib and dexamethasone for patients with relapsed multiple myeloma who have received two or more previous lines of therapy . We aim ed to improve the safety of this combination and investigate efficacy by incorporating low-dose thalidomide , using sub-cutaneous weekly bortezomib , and determining the maximum tolerated dose of panobinostat in this regimen . METHODS We did a phase 1/2 , multicentre , open-label trial ( MUK six ) at four hospitals in the UK , enrolling patients with relapsed , or relapsed and refractory , multiple myeloma aged at least 18 years , with an Eastern Cooperative Oncology Group performance status of 2 or less who had previously received 1 - 4 lines of therapy . Exclusion criteria included any antimyeloma treatment within 28 days of study drugs ( except dexamethasone 160 mg > 48 h before treatment ) . We used a rolling six escalation design to determine the maximum tolerated dose of panobinostat , and allocated patients to receive subcutaneous bortezomib 1·3 mg/m2 , and oral thalidomide 100 mg , dexamethasone 20 mg , and panobinostat 10 , 15 , or 20 mg ( escalated to 20 mg according to the escalation schedule ) . Treatment was given during a 21-day cycle ( bortezomib on days 1 and 8 ; thalidomide every day ; dexamethasone on days 1 , 2 , 8 , and 9 ; and panobinostat on days 1 , 3 , 5 , 8 , 10 , and 12 ) for 16 cycles in the absence of disease progression or unacceptable toxicity . Patients were permitted to come off study for autologous stem cell transplantation . The primary objective was to determine the maximum tolerated dose and recommended dose of panobinostat , and to estimate the proportion of patients with an overall response that was equal to a partial response or greater within 16 cycles of treatment at the recommended panobinostat dose in the modified intention-to-treat population . We assessed safety in all patients who received a trial drug ( ie , bortezomib , thalidomide , dexamethasone , or panobinostat ) . This trial is registered at Clinical Trials.gov , number NCT02145715 , and with the IS RCT N registry , number IS RCT N59395590 and is closed to recruitment . FINDINGS Between Jan 31 , 2013 , and Oct 30 , 2014 , we enrolled 57 eligible patients who received at least one dose of trial medication or any drug . One dose-limiting toxicity was reported ( grade 3 hyponatremia at the 20 mg dose ) , therefore the maximum tolerated dose was not reached , and 20 mg was deemed to be the recommended dose . 46 patients were treated with panobinostat 20 mg ( the intention-to-treat population ) . 42 patients ( 91 % , 80 % CI 83·4 - 96·2 ) of 46 achieved the primary endpoint of an overall response that was equal to a partial response or greater . Most adverse events were grade 1 - 2 with few occurrences of grade 3 - 4 diarrhoea or fatigue . The most common adverse events of grade 3 or worse in the safety population ( n=57 ) were reduced neutrophil count ( 15 [ 26 % ] ) , hypophosphatemia ( 11 [ 19 % ] ) , and decreased platelet count ( 8 [ 14 % ] ) . 46 serious adverse events were reported in 27 patients ; of 14 suspected to be related to the trial medication , seven ( 50 % ) were gastrointestinal disorders . INTERPRETATION Panobinostat 20 mg in combination with bortezomib , thalidomide , and dexamethasone is an efficacious and well tolerated regimen for patients with relapsed multiple myeloma . FUNDING Novartis and Myeloma UK On October 6 , 2006 , the U.S. Food and Drug Administration granted regular approval to vorinostat ( Zolinza(R ) ; Merck & Co. , Inc. , Whitehouse Station , NJ ) , a histone deacetylase inhibitor , for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma ( CTCL ) in patients with progressive , persistent , or recurrent disease on or following two systemic therapies . The pivotal study supporting approval was a single-arm open-label phase II trial that enrolled 74 patients with stage IB and higher CTCL who had failed two systemic therapies ( one of which must have contained bexarotene ) . Patients received vorinostat at a dose of 400 mg orally once daily , which could be reduced for toxicity to 300 mg daily or 300 mg 5 days a week . The median age of patients was 61 years . Sixty-one patients ( 82 % ) had stage IIB or higher CTCL and 30 patients ( 41 % ) had Sézary syndrome . The median duration of protocol treatment was 118 days . The primary efficacy endpoint was objective response assessed by the Severity-Weighted Assessment Tool . The objective response rate was 30 % ( 95 % confidence interval [ CI ] , 19.7%-41.5 % ) , the estimated median response duration was 168 days , and the median time to tumor progression was 202 days . An additional single-center study enrolled 33 patients with similar baseline and demographic features as the pivotal trial . Thirteen of the 33 received vorinostat ( 400 mg/day ) . The response rate in these 13 patients was 31 % ( 95 % CI , 9.1%-61.4 % ) . The most common clinical adverse events ( AEs ) of any grade were diarrhea ( 52 % ) , fatigue ( 52 % ) , nausea ( 41 % ) , and anorexia ( 24 % ) . Grade 3 or 4 clinical AEs included fatigue ( 4 % ) and pulmonary embolism ( 5 % ) . Hematologic laboratory abnormalities included thrombocytopenia ( 26 % ) and anemia ( 14 % ) . Chemistry laboratory abnormalities included increased creatinine ( 16 % ) , increased serum glucose ( 69 % ) , and proteinuria ( 51 % ) . Most abnormalities were National Cancer Institute Common Terminology Criteria for Adverse Events grade 1 or 2 . Grade 3 or greater chemistry abnormalities included hyperglycemia , hypertriglyceridemia , and hyperuricemia , hypoglycemia , hypokalemia , hyponatremia , hyperkalemia , hypercholesterolemia , hypophosphatemia , and increased creatinine UNLABELLED Pre clinical studies have shown that targeted combination therapy consisting of vorinostat and bortezomib has antitumor activity in multiple myeloma ( MM ) . We examined this drug combination in advanced relapsing and /or refractory MM patients ( n = 34 ) . Although the maximum tolerated dose was not reached , the study found this combination regimen generally well tolerated and clinical ly active in relapsed and /or refractory MM patients . BACKGROUND Development of targeted therapies for MM has improved response rates and increased patient survival , but ultimately the disease becomes refractory and progresses . Vorinostat combined with bortezomib has demonstrated synergistic antiproliferative and proapoptotic activity in pre clinical models of MM . The objectives of this study were to determine the maximum tolerated dose for vorinostat with bortezomib in patients with advanced MM and to evaluate the clinical benefit of this new drug combination . PATIENTS AND METHODS Patients ≥ 18 years old with relapsed and /or refractory MM were enrolled into escalating dose cohorts of vorinostat and bortezomib combination therapy . Thirty-four patients were enrolled and were evaluable for safety and efficacy analyses . RESULTS All patients reported adverse events , 89 % of which were mild to moderate in severity . Thirteen patients experienced 29 serious adverse events , 12 ( 41 % ) of which were considered drug-related . The maximum tolerated dose was not reached . Partial responses were observed in 9 ( 27 % ) patients . Minimal responses were observed in 2 additional patients ( 6 % ) , and another 20 patients ( 59 % ) experienced disease stabilization . CONCLUSION Vorinostat with bortezomib is generally well-tolerated and has clinical activity in patients with relapsed and /or refractory MM . Response rates were similar in patients previously exposed to bortezomib and patients who were naive to bortezomib therapy Abstract The combination of melphalan , prednisone and thalidomide ( MPT ) has demonstrated efficacy and acceptable toxicity in newly diagnosed and relapsed/refractory patients with multiple myeloma ( MM ) . Panobinostat is a potent oral pan-deacetylase inhibitor ( pan-DACi ) . In pre clinical and clinical studies , panobinostat showed good anti-myeloma activity in combination with several agents . This phase II study evaluated the combination of a fixed dose of MPT with escalating doses of panobinostat ( three times weekly for 3 weeks , followed by a 9-day rest period ) in relapsed/refractory MM . We used a two-stage design to determine whether the combination was safe and effective . At least a partial response was observed in 38.5 % of patients . The maximum tolerated dose of panobinostat in combination with MPT could not be determined due to the high rate of dose-limiting toxicities experienced with panobinostat at doses of 10 and 15 mg . The most common grade 3/4 adverse events were neutropenia ( 71 % ) and thrombocytopenia ( 35.5 % ) . In conclusion , MPT in combination with panobinostat three times weekly for 3 weeks followed by a 9-day rest period is not well tolerated in patients with relapsed/refractory MM . Future studies should evaluate alternative dose schedules of panobinostat The purpose of this study was to assess the safety and efficacy of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma . Patients with multiple myeloma who had relapsed after at least one prior treatment were eligible to participate . In the dose escalation part of the study a st and ard 3 + 3 design was used to determine the maximum tolerated dose of four planned dose levels of the combination of carfilzomib and panobinostat . Panobinostat was administered on days 1 , 3 , 5 , 15 , 17 , and 19 . Carfilzomib was administered on days 1 , 2 , 8 , 9 , 15 , and 16 of each 28-day cycle . Treatment was continued until progression or intolerable toxicity . Forty-four patients were accrued into the trial , 13 in the phase I part and 31 in the phase II part of the study . The median age of the patients was 66 years and the median number of prior therapies was five . The expansion dose was established as 30 mg panobinostat , 20/45 mg/m2 carfilzomib . The overall response rate was 67 % for all patients , 67 % for patients refractory to prior proteasome inhibitor treatment and 75 % for patients refractory to prior immune modulating drug treatment . At a median follow up of 17 months , median progression-free survival was 7.7 months , median time to progression was 7.7 months , and median overall survival had not been reached . The regimen was well tolerated , although there were several panobinostat dose reductions . In conclusion , the combination of panobinostat and carfilzomib is feasible and effective in patients with relapsed/refractory multiple myeloma . ( Trial registered at Clinical Trials.gov : NCT01496118 |
13,367 | 32,187,708 | The findings support the effectiveness of character strengths-based intervention on improving the psychological well-being of patients with chronic illnesses .
IMPACT This rigorous review provided current evidence on using character strengths-based intervention to improve the psychological well-being of patients with chronic illnesses .
character strengths-based intervention provides a creative approach for patients because it may help improve their well-being , happiness , self-esteem and self-efficacy , as well as reduce depression and mental symptoms . | AIMS To identify and evaluate available evidence on the effectiveness of character strengths-based intervention on the psychological well-being of patients with chronic illnesses . | OBJECTIVE Little is known about positive emotion communication ( PEC ) in end-of-life care . This study aims to identify types and patterns of PEC among hospice nurses , caregivers , and patients . METHODS A coding system based on positive psychology theory was applied as a secondary analysis to audio recordings of hospice nurse home visits with cancer patients and family caregivers , collected as part of a prospect i ve longitudinal study . Eighty recordings ( 4 visits from 20 triads ) were coded for humor , connection , praise , positive focus , gratitude , taking joy/savoring , and perfunctory statements . RESULTS Descriptive statistics revealed the greatest proportion of PEC was made by nurses . Humor was most frequently used across all speakers . Cluster analysis revealed four PEC visit types : Savor/Take Joy ; Humor ; Perfunctory ; and Other-focused Expressions of Positive Emotions . Linear mixed effect regression was used to estimate the trajectory of PEC over time , but no significant change was found . CONCLUSION We found that positive emotions are common in nurse , caregiver and patient communication at end-of-life and do not decline closer to death . PRACTICE IMPLICATION This study is among the first to explore PEC at end-of-life , and offers a way to bring strengths-based approaches into end of life communication research This study prospect ively examined psychological strengths targeted in U.S. Army training programs as predictors of psychiatric diagnosis in active duty soldiers . At baseline , the cohort ( 140,584 soldiers ) was without psychiatric disorder . Soldiers were then followed for 2 yr and classified as healthy , or acquiring a psychiatric diagnosis ( adjustment disorder , anxiety disorder , depression , or post-traumatic stress disorder ) , or being prescribed psychotropic medication without a psychiatric diagnosis . Soldiers who remained healthy reported significantly higher strengths scores at baseline , compared with soldiers who were diagnosed with a psychiatric disorder . In addition , soldiers in the worst strengths decile were twice as likely to develop a psychiatric disorder , compared with soldiers in the top 50 % on baseline strengths . Strengths afforded the greatest protection against depression . Offering tailored resilience training programs could help the Army steel vulnerable soldiers against the challenges of life , military training , and combat Background Linkage to and retention in care for US persons living with HIV ( PLWH ) after release from jail usually declines . We know of no rigorously evaluated behavioral interventions that can improve this . We hypothesized that a strengths-based case management intervention that we developed for PLWH leaving jail would increase linkage/retention in care ( indicated by receipt of laboratory draws ) and a suppressed HIV viral load ( VL ) in the year following release . Methods and findings We conducted a quasi-experimental feasibility study of our intervention for PLWH jailed in Atlanta . We recruited 113 PLWH in jail starting in 2014 . “ SUCCESS ” ( Sustained , Unbroken Connection to Care , Entry Services , and Suppression ) began in jail and continued post-release . Subjects who started the intervention but subsequently began long-term incarcerations were excluded from further analysis . Persons who were retained in the intervention group were compared to contemporaneously incarcerated PLWH who did not receive the intervention . Identities were su bmi tted to an enhanced HIV/AIDS reporting system ( eHARS ) at the state health department to capture all laboratories drawn . Both community engagement and care upon jail return were assessed equally . For 44 intervention participants released to Atlanta , 50 % of care occurred on subsequent jail stays , as documented with EventFlow software . Forty-five receiving usual services only were recruited for comparison . By examining records of jail reentries , half of participants and 60 % of controls recidivated ( range : 1–8 returns ) . All but 6 participants in the intervention and 9 subjects in the comparison arm had ≥1 laboratory recorded in eHARS post-release . Among the intervention group , 52 % were retained in care ( i.e. , had two laboratory studies , > = 3 months apart ) , versus 40 % among the comparison group ( OR = 1.60 , 95 % CI ( 0.71 , 3.81 ) ) . Both arms showed improved viral load suppression . Conclusions There was a trend towards increased retention for PLWH released from jail after SUCCESS , compared to usual services . Measuring linkage at all venues , including jail-based clinics , fully captured engagement for this frequently recidivating population . Trial registration Clinical Trials.gov Positive psychology has flourished in the last 5 years . The authors review recent developments in the field , including books , meetings , courses , and conferences . They also discuss the newly created classification of character strengths and virtues , a positive complement to the various editions of the Diagnostic and Statistical Manual of Mental Disorders ( e. g. , American Psychiatric Association , 1994 ) , and present some cross-cultural findings that suggest a surprising ubiquity of strengths and virtues . Finally , the authors focus on psychological interventions that increase individual happiness . In a 6-group , r and om-assignment , placebo-controlled Internet study , the authors tested 5 purported happiness interventions and 1 plausible control exercise . They found that 3 of the interventions lastingly increased happiness and decreased depressive symptoms . Positive interventions can supplement traditional interventions that relieve suffering and may someday be the practical legacy of positive psychology This study assessed the effects of a psychological group intervention based on positive psychology in women with breast cancer . 175 women were r and omly assigned either to an experimental group , receiving the 14-session intervention ( n = 87 ) , or to a waitlist group ( n = 88 ) that did not receive any type of intervention . For treatment , a group intervention was applied , based on improving psychological strengths and enhancing positive psychology-based styles of coping . Strength-related outcomes , self-esteem , well-being , and happiness were assessed before and after the intervention . The experimental group showed higher scores on all of the study variables after the intervention . Participants reported improved self-esteem , emotional intelligence-related abilities , resilience , and optimism , as well as positive affectivity , well-being , and happiness . The results show a beneficial effect of this psychological intervention based on positive psychology on female breast cancer patients ' psychological health The effect of a grateful outlook on psychological and physical well-being was examined . In Studies 1 and 2 , participants were r and omly assigned to 1 of 3 experimental conditions ( hassles , gratitude listing , and either neutral life events or social comparison ) ; they then kept weekly ( Study 1 ) or daily ( Study 2 ) records of their moods , coping behaviors , health behaviors , physical symptoms , and overall life appraisal s. In a 3rd study , persons with neuromuscular disease were r and omly assigned to either the gratitude condition or to a control condition . The gratitude-outlook groups exhibited heightened well-being across several , though not all , of the outcome measures across the 3 studies , relative to the comparison groups . The effect on positive affect appeared to be the most robust finding . Results suggest that a conscious focus on blessings may have emotional and interpersonal benefits Recent years have seen an increasing interest in research in positive psychology interventions . There is broad evidence for their effectiveness in increasing well-being and ameliorating depression . Intentional activities that focus on those character strengths , which are most typical for a person ( i.e. , signature strengths , SS ) and encourage their usage in a new way have been identified as highly effective . The current study aims at comparing an intervention aim ed at using SS with one on using individual low scoring ( or lesser ) strengths in a r and omized placebo-controlled trial . A total of 375 adults were r and omly assigned to one of the two intervention conditions [ i.e. , using five signature vs. five lesser strengths ( LS ) in a new way ] or a placebo control condition ( i.e. , early memories ) . We measured happiness and depressive symptoms at five time points ( i.e. , pre- and post-test , 1- , 3- , and 6-months follow-ups ) and character strengths at pre-test . The main findings are that ( 1 ) there were increases in happiness for up to 3 months and decreases in depressive symptoms in the short term in both intervention conditions ; ( 2 ) participants found working with strengths equally rewarding ( enjoyment and benefit ) in both conditions ; ( 3 ) those participants that reported generally higher levels of strengths benefitted more from working on LS rather than SS and those with comparatively lower levels of strengths tended to benefit more from working on SS ; and ( 4 ) deviations from an average profile derived from a large sample of German-speakers completing the Values-in-Action Inventory of Strengths were associated with greater benefit from the interventions in the SS-condition . We conclude that working on character strengths is effective for increasing happiness and discuss how these interventions could be tailored to the individual for promoting their effectiveness PURPOSE New approaches to chronic disease management emphasize the need to improve the delivery of primary care services to meet the needs of chronically ill patients . This study ( 1 ) assessed whether chronic disease management differed among 4 models of primary health care delivery and ( 2 ) identified which practice organizational factors were independently associated with high- quality care . METHODS We undertook a cross-sectional survey with nested qualitative case studies ( 2 practice s per model ) in 137 r and omly selected primary care practice s from 4 delivery models in Ontario Canada : fee for service , capitation , blended payment , and community health centers ( CHCs ) . Practice and clinician surveys were based on the Primary Care Assessment Tool . A chart audit assessed evidence -based care delivery for patients with diabetes , congestive heart failure , and coronary artery disease . Intermediate outcomes were calculated for patients with diabetes and hypertension . Multiple linear regression identified those organizational factors independently associated with chronic disease management . RESULTS Chronic disease management was superior in CHCs . Clinicians in CHCs found it easier than those in the other models to promote high- quality care through longer consultations and interprofessional collaboration . Across the whole sample and independent of model , high- quality chronic disease management was associated with the presence of a nurse-practitioner . It was also associated with lower patient-family physician ratios and when practice s had 4 or fewer full-time-equivalent family physicians . CONCLUSIONS The study adds to the literature supporting the value of nurse-practitioners within primary care teams and vali date s the contributions of Ontario ’s CHCs . Our observation that quality of care decreased in larger , busier practice s suggests that moves toward larger practice s and greater patient-physician ratios may have unanticipated negative effects on processes of care quality Abstract Objective : To investigate the feasibility and effectiveness of conducting two positive psychology interventions to improve mood and self-concept with survivors of traumatic brain injury ( TBI ) , within a neuro-rehabilitation hospital . Method and procedures : Ten patients with brain injury were r and omly allocated to an intervention and control group . The efficacy of the first intervention , ‘ three positive things in life ’ was measured via Seligman ’s Authentic Happiness Index ( AHI ) , at base-line , directly following the intervention and at the end of the 12-week group programme . The second intervention , the ‘ Value in Action ( VIA ) signature strengths intervention ’ was measured by the Head Injury Semantic Differential Scale ( HISDS ) at baseline and at the end of the group . Results : Compared to baseline and control group scores , the AHI index showed an increase in the intervention group ’s happiness following the intervention and at the end of the 12-week programme , albeit the latter increase was non-significant . The HISDS showed non-significant improvement in self-concept and reduction in polarization of the self in the present , future and past in the second intervention . Anecdotal evidence revealed a clear improved mood following the interventions . Conclusion : This study shows promising results for the effectiveness of Positive Psychology interventions and methods to improve feasibility when applying this treatment within a hospital setting OBJECTIVE Seligman , Steen , Park , and Peterson ( 2005 ) suggested that positive psychology interventions ( PPIs ) contain specific , powerful , therapeutic ingredients that effect greater increases in happiness and reductions in depression than a placebo control . This study reexamined the three PPIs that Seligman et al. found to be most effective when delivered over the internet . METHOD Three PPIs and a placebo control , identical with the interventions used by Seligman et al. , were examined in a web-based , r and omized assignment design . RESULTS Mixed- design analysis of variance and multilevel modeling showed that all interventions , including the placebo , led to significant increases in happiness and reductions in depression . The effects of PPIs were indistinguishable from those of the placebo control . CONCLUSION Using web-based delivery , both PPIs and theoretically neutral placebos can increase happiness and reduce depression in self-selected population s. Possible explanations include that non-specific factors common to most therapeutic treatments are responsible for the observed changes , or that cultural or other context -related variables operate to account for the divergent findings OBJECTIVE The objective of this study was to develop and evaluate a low-cost , strengths-based group intervention led jointly by peer counselors and professional counselors to foster recovery among adults with serious mental illnesses . METHODS Cohort 1 included development of material s and a feasibility pilot , with participants recruited from community mental health centers ( CMHCs ) . Cohorts 2 and 3 included a small r and omized controlled trial with participants recruited from members of a not-for-profit , integrated health plan . Cohorts 4 and 5 involved evaluation of the most appropriate length for the intervention with a pre-post design that allowed intervention length to vary between 12 and 18 sessions ; participants and peer leaders were recruited from two CMHCs ( N=82 ) . RESULTS Participants were very satisfied with the recovery-focused group intervention , preferred a greater number of weekly sessions ( 17 or 18 sessions ) , and reported improved outcomes across multiple domains . CONCLUSIONS Using peer-developed material s and a combination of peer and professional counselors as group leaders is feasible to offer and valuable to participants . Outcomes measures suggest that the intervention has potential to facilitate recovery in multiple domains OBJECTIVE Mental health treatment approaches based on character strengths can be used to complement the traditional focus on functional impairment . The study tested use of a character strengths-based intervention to enhance the self-esteem and self-efficacy of psychiatrically hospitalized youths . METHODS Eighty-one hospitalized adolescents were r and omly assigned to intervention or comparison groups . The intervention used the Values in Action Inventory of Strengths for Youth to discover character strengths and incorporate them into coping skills . Self-efficacy and self-esteem were measured at baseline , postintervention , two weeks , and three months . RESULTS Self-esteem and self-efficacy initially increased in both groups , but only the intervention group showed sustained improvement . The intervention was associated with increased self-efficacy at two weeks and increased self-efficacy and self-esteem at three months . CONCLUSIONS A brief , easily administered character strengths-based intervention may be an adjunctive tool in the treatment of psychiatrically hospitalized youths |
13,368 | 32,192,946 | The highest reduction in the odds of exacerbation was associated with patients achieving 80 % or more adherence , and the odds also reduced among those with 50 % or more adherence , whereas a substantial increase in exacerbation was associated with discontinuation of therapy | OBJECTIVE To assess the association between adherence levels and severe asthma exacerbation . | The importance of adherence to antihypertensive treatments for the prevention of cardiovascular disease has not been well eluci date d. This study evaluated the effect of antihypertensive medication adherence on specific cardiovascular disease mortality ( ischemic heart disease [ IHD ] , cerebral hemorrhage , and cerebral infa rct ion ) . Our study used data from a 3 % sample cohort that was r and omly extracted from enrollees of Korean National Health Insurance . Study subjects were aged ≥20 years , were diagnosed with hypertension , and started newly prescribed antihypertensive medication in 2003 to 2004 . Adherence to antihypertensive medication was estimated as the cumulative medication adherence . Subjects were divided into good ( cumulative medication adherence , ≥80 % ) , intermediate ( cumulative medication adherence , 50%–80 % ) , and poor ( cumulative medication adherence , < 50 % ) adherence groups . We used time-dependent Cox proportional hazards models to evaluate the association between medication adherence and health outcomes . Among 33 728 eligible subjects , 670 ( 1.99 % ) died of coronary heart disease or stroke during follow-up . Patients with poor medication adherence had worse mortality from IHD ( hazard ratio , 1.64 ; 95 % confidence interval , 1.16–2.31 ; P for trend=0.005 ) , cerebral hemorrhage ( hazard ratio , 2.19 ; 95 % confidence interval , 1.28–3.77 ; P for trend=0.004 ) , and cerebral infa rct ion ( hazard ratio , 1.92 ; 95 % confidence interval , 1.25–2.96 ; P for trend=0.003 ) than those with good adherence . The estimated hazard ratios of hospitalization for cardiovascular disease were consistent with the mortality end point . Poor medication adherence was associated with higher mortality and a greater risk of hospitalization for specific cardiovascular diseases , emphasizing the importance of a monitoring system and strategies to improve medication adherence in clinical practice ABSTRACT Introduction : This study was aim ed at evaluating whether once-daily regimens ( od-r ) show benefits in adherence when compared to twice-daily ( td-r ) . Methods : Prospect i ve , multicenter , 6-month follow-up study with two visits . The main objective was to compare adherence assessed by the electronic prescription refill rate ( EPRR ) and by the 10-item Test of Adherence to Inhalers ( TAI ) in patients with od-r and td-r . Suboptimal adherence was defined as TAI < 50 or EPRR ≤ 80 % . The effect of suboptimal adherence on meaningful clinical outcomes and the concordance between EPRR and TAI were also examined . Results : One hundred and ninety-seven patients ( 47.3 ± 15.9 years , 65 % women ) were included and 180 completed the study . TAI score was < 50 in 29.8 % od-r patients and 46.9 % in td-r ( p = 0.01 ) and EPRR was ≤80 % in 22.6 % and 37.5 % respectively ( p = 0.02 ) . The correlation between the two methods was moderate ( rho = 0.548 ; p < 0.001 ) . There were no significant differences in FEV1 ( % ) , symptoms or exacerbations between patients with optimal and suboptimal adherence . During follow-up , five patients ( 6 % ) with o-dr and 17 patients ( 17.7 % ) with t-dr suffered an exacerbation ( p = 0.013 ) . At visit two , 13.1 % of the patients with o-dr and 31.3 % with t-dr had uncontrolled asthma ( p = 0.003 ) , although more patients with o-dr were receiving inhaled corticosteroids in the high-dose stratum ( 25.8 % vs. 11.5 % ; p = 0.001 ) . Conclusion : Mean adherence rates were greater with od-r than with td-r , but we did not observe an effect on clinical outcomes OBJECTIVES The primary aims of the study were to : ( a ) describe the trajectories of adherence to daily inhaled corticosteroid ( ICS ) medication for a year in economically disadvantaged , African-American youth with asthma based on growth curve modeling ; and ( b ) test the relationship of treatment adherence to symptom control , quick-relief medication , and healthcare utilization . METHODS This prospect i ve study measured adherence to daily ICS treatment using electronic monitoring in 92 children and adolescents with moderate to severe asthma for 9 - 12 months and assessed clinical outcomes , including asthma-related symptoms , quick-relief medication , and healthcare utilization . RESULTS Youth showed a decrement in treatment adherence to less than half of prescribed corticosteroid treatment over the course of the study , which related to increased healthcare utilization ( p < .04 ) , but not to asthma symptoms or albuterol use . CONCLUSION Economically disadvantaged youth with asthma demonstrate high rates of chronic nonadherence that warrant identification and intervention to reduce asthma-related healthcare utilization The assessment of compliance is critical in the evaluation of the effectiveness of a new therapeutic agent . Fifteen patients with transfusion-dependent beta-thalassemia , many of whom had previously demonstrated erratic compliance with deferoxamine , were enrolled in a clinical trial of a new oral iron chelator , 1,2-dimethyl-3-hydroxypyrid-4-one ( L1 ) . Their compliance with this medication was estimated by several existing methods and the novel Medication Event Monitoring System ( MEMS ) . Overall compliance as assessed by the MEMS was 78.5 + /- 13.0 % of prescribed doses taken , significantly lower than the corresponding rates calculated by pill counts and diaries ( 91.5 + /- 9.2 % and 94.1 + /- 4.3 % , respectively ) . However , several serious problems were encountered with the MEMS , mostly in the form of incorrect use of the device by the patients . Disclosure of the nature of the MEMS and the compliance monitoring process did not alter the rate of adherence with L1 therapy . Compliance as determined by pill counts did not differ between the 1st and 2nd 6-month periods . Although not reaching statistical significance , a trend towards better L1 compliance occurred in those patients in whom serum ferritin levels decreased . Patients who filled at least 50 % of their diaries had significantly better compliance by pill counts than those who completed less than 50 % of their diaries ( 95.9 + /- 4.1 % and 86.5 + /- 11.1 % , respectively ) . Steady-state L1 trough concentrations and 24-hour urinary iron excretion did not correlate with L1 compliance . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Patients who adhere to medications experience better outcomes than their nonadherent counterparts . However , these observations may be confounded by patient behaviors . The level of adherence necessary for patients to derive benefit and whether adherence to all agents is important for diseases that require multiple drugs remain unclear . This study quantifies the relationship between medication adherence and post-myocardial infa rct ion ( MI ) adverse coronary events . METHODS This is a secondary analysis of the r and omized MI FREEE trial . Patients who received full prescription coverage were classified as adherent ( proportion of days covered ≥80 % ) or not based upon achieved adherence in the 6 months after r and omization . First major vascular event or revascularization rates were compared using multivariable Cox models adjusting for comorbidity and health-seeking behavior . RESULTS Compared with patients r and omized to usual care , full coverage patients adherent to statin , β-blocker , or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were significantly less likely to experience the study 's primary outcome ( hazard ratio [ HR ] range 0.64 - 0.81 ) . In contrast , nonadherent patients derived no benefit ( HR range 0.98 - 1.04 , P ≤ .01 for the difference in HRs between adherent and nonadherent patients ) . Partially adherent patients had no reduction in clinical outcomes for any of the drugs evaluated , although their achieved adherence was higher than that among controls . CONCLUSION Achieving high levels of adherence to each and all guideline -recommended post-MI secondary prevention medication is associated with improved event-free survival . Lower levels of adherence appear less protective BACKGROUND Unmeasured confounders and selection bias can significantly influence the results of retrospective observational analyses of asthma therapy . OBJECTIVE To evaluate the efficacy of oral montelukast and inhaled fluticasone propionate in a r and omized , prospect i ve 12-month " real-world " observational analysis of children with mild persistent asthma . METHODS Children ( n = 104 ) between 6 and 15 years of age with mild asthma as determined by forced expiratory volume in 1 second , symptoms , and evaluation by an experienced pediatric allergist or pulmonologist , who were not currently receiving controller therapy , were r and omly assigned to fluticasone or montelukast on an alternating basis . Subjects were asked to complete a question naire at 6 and 12 months ; otherwise , medical care was identical to that of similar managed care patients . Outcome parameters were evaluated after 12 months by cl aims data base analysis . An acute asthma attack requiring emergent care was the primary outcome parameter . Measures of adherence , symptoms , and asthma control , as measured by the pediatric Asthma Therapy Assessment Question naire , were secondary outcome parameters . RESULTS Demographics , spirometry , symptoms at enrollment , emergent care visits , asthma hospitalizations , routine office visits , and symptoms at study completion were not significantly different between study groups . Adherence , as evaluated by the number of controller fills , was significantly ( P = 0.0003 ) better for montelukast ( 7.65 + /- 3.01 ) than fluticasone ( 5.46 + /- 3.01 ) . Similar numbers of subjects in each study group required beta-agonists and oral prednisone . CONCLUSIONS These results suggest that oral montelukast and inhaled fluticasone have similar real-world efficacies in the treatment of children with mild asthma , possibly as a result of the significantly better adherence with oral montelukast therapy compared with inhaled fluticasone BACKGROUND Being able to identify patients at risk of exacerbations is useful as it enables re sources to be targeted at these patients . AIMS To test the theoretically-derived prediction that the frequency of non-asthma related visits to the general practitioner ( GP ) predicts exacerbations . METHODS Clinical and demographic data and both self-report and prescription-based adherence data were obtained from 166 patients diagnosed with asthma attending a GP clinic , all of whom were prescribed inhaled corticosteroids ( ICS ) . Asthma exacerbations ( treated by the GP or in hospital ) and non-asthma visits and symptoms were assessed from notes for the subsequent 5 years . RESULTS Exacerbations correlated with non-asthma visits ( 0.35 ) , severity as measured by BTS step ( 0.28 ) , and with prescription-based adherence ( 0.28 ) . Asthma severity correlated with non-asthma visits ( 0.35 ) . Receiver operating curves showed that ≥2 non-asthma visits per year provided 79 % sensitivity and 58 % specificity for detecting ≥3 exacerbations over 5 years . Poor adherence predicted outcomes only for patients with high levels of non-asthma visits ( ≥3 ) and only for those reporting regular-but-less ICS use but not symptom-directed ICS use . CONCLUSIONS Non-asthma visits are a good predictor of asthma exacerbations , particular in non-adherent patients . These results are consistent with a mechanism where exacerbations result from a combination of r and om oscillating specific and non-specific inflammatory processes . It is important to consider the total patient rather than just the lung when managing patients with asthma BACKGROUND Information comparing subjective and objective measurements of adherence to study medications and the effects of adherence on treatment-related differences in asthma clinical trials are limited . OBJECTIVE We sought to compare subjective and objective measurements of children 's adherence to inhaled corticosteroids or placebo and to determine whether adherence to study medications modified treatment-related differences in outcomes . METHODS In an ancillary study conducted in 3 of 8 Childhood Asthma Management Program Clinical Centers , adherence was assessed by using self-reported and objective data in 5- to 12-year-old children with mild or moderate asthma who were r and omly assigned to 200 μg of inhaled budesonide twice per day ( n = 84 ) or placebo ( n = 56 ) for 4 years . The κ statistic was used to evaluate agreement between self-reported adherence ( daily diary cards ) and objective ly measured adherence ( number of doses left in study inhalers ) . Multivariable analyses were used to determine whether adherence to study treatment modified treatment-related differences in outcomes . RESULTS Adherence of less than 80 % was seen in 75 % of 140 children when adherence was measured objective ly but only in 6 % of children when measured by means of self-report . There was poor agreement between objective and subjective measurements of adherence of at least 80 % ( κ = 0.00 ; 95 % CI , -0.05 to 0.04 ) ; self-reported adherence over the 4-year period generally overestimated objective ly measured adherence ( 93.6 % vs 60.8 % , P < .0001 ) . There was little evidence to indicate that adherence modified treatment-related differences in outcomes . CONCLUSION Research ers should use objective rather than self-reported adherence data to identify clinical trial participants with low levels of adherence to study treatment A Nebulizer Chronolog , a portable device that houses a st and ard nebulizer canister , was used in a unique method to measure compliance with aerosolized medication . Each actuation is tabulated to within 4 minutes of the actual time of usage and can subsequently be displayed in a day-hour-minute format . Of the 19 patients studied for 12 weeks with a cromolyn-like agent , appropriate usage four times a day ranged from 4.3 % to 94.8 % . Underusage exceeded overusage and ranged from 5.2 % to 95 % of the study days . Younger subjects and male subjects were less likely to use the aerosol appropriately . Patients failed to write the truth in their diaries with overreporting of appropriate usage more than 50 % of the times . Lack of compliance with aerosolized medication represents an important medical issue for the physicians caring for patients with asthma . The Nebulizer Chronolog elicits new insight into the disparity between reported and observed compliance OBJECTIVE To determine the feasibility of using the Medication Event Monitoring System ( MEMS ) to estimate medication compliance in patients with schizophrenia or schizoaffective disorder . SUBJECTS AND SETTING Fourteen of 35 consecutive patients admitted to a psychiatric inpatient hospital with schizophrenia or schizoaffective disorder who met eligibility requirements and gave informed consent . INTERVENTION After r and om assignment to either risperidone or typical antipsychotic treatment , medication upon discharge from hospital was dispensed in a bottle with a MEMS cap which recorded the number of bottle openings and the date and time of each opening . The first 6 patients were asked to return monthly for data downloading . The next 8 were asked to return weekly during the first month and every 2 weeks thereafter ; they were also paid $ 5 for returning each bottle . OUTCOME MEASURES MEMS data collected over a 6-month period and hospital readmission data . RESULTS Patient medication compliance data were collected from 10 ( 71 % ) of 14 patients during the first month , from 7 ( 58 % ) of 12 ( 2 patients dropped out ) during the second and from 5 ( 45 % ) of 11 ( a third patient dropped out ) during months 3 - 6 . Mean compliance rates were 63 % for the first month and ranged from 56 % to 45 % over the next 5 . First-month compliance rates were significantly lower for those who were subsequently readmitted to hospital ( n = 7 ) than for those who were not ( p < 0.01 ) . CONCLUSIONS Electronic monitoring devices can be used to estimate compliance with medication regimens in patients with severe schizophrenic disorders , but there are method ological improvements that can be made to increase data recovery and compliance , and these are discussed |
13,369 | 24,339,912 | Weak to moderate correlations were observed between IL-1β , IL-6 , TNF-α levels , and different degrees of cognitive impairment .
Different types of chemotherapy treatments might lead to varying presentations and severities of cytokine-induced cognitive impairment . | OBJECTIVES While various clinical and pharmacological determinants for chemotherapy-associated cognitive impairment have been identified , conflicting evidence suggests that cytokines might play an intermediary role .
The objective of this systematic review was to evaluate the current evidence pertaining to the associations among chemotherapy , cytokines induction and cognitive impairment in cancer patients . | Testosterone has immune-modulating properties , and current in vitro evidence suggests that testosterone may suppress the expression of the proinflammatory cytokines TNFalpha , IL-1beta , and IL-6 and potentiate the expression of the antiinflammatory cytokine IL-10 . We report a r and omized , single-blind , placebo-controlled , crossover study of testosterone replacement ( Sustanon 100 ) vs. placebo in 27 men ( age , 62 + /- 9 yr ) with symptomatic and rogen deficiency ( total testosterone , 4.4 + /- 1.2 nmol/liter ; bioavailable testosterone , 2.4 + /- 1.1 nmol/liter ) . Compared with placebo , testosterone induced reductions in TNFalpha ( -3.1 + /- 8.3 vs. 1.3 + /- 5.2 pg/ml ; P = 0.01 ) and IL-1beta ( -0.14 + /- 0.32 vs. 0.18 + /- 0.55 pg/ml ; P = 0.08 ) and an increase in IL-10 ( 0.33 + /- 1.8 vs. -1.1 + /- 3.0 pg/ml ; P = 0.01 ) ; the reductions of TNFalpha and IL-1beta were positively correlated ( r(S ) = 0.588 ; P = 0.003 ) . In addition , a significant reduction in total cholesterol was recorded with testosterone therapy ( -0.25 + /- 0.4 vs. -0.004 + /- 0.4 mmol/liter ; P = 0.04 ) . In conclusion , testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol . Twenty of these men had established coronary disease , and because total cholesterol is a cardiovascular risk factor , and proinflammatory cytokines mediate the development and complications associated with atheromatous plaque , these properties may have particular relevance in men with overt vascular disease Post-chemotherapy treated cancer patients frequently report cognitive difficulties . The biology of this phenomenon is poorly understood , with uncertainty about possible direct toxic effects on the brain , secondary effects from systemic inflammation , host factors/genetic predisposition to cognitive complaints , or hormonal changes influencing cognitive function . To eluci date possible mechanisms associated with post-treatment cognitive dysfunction among breast cancer survivors , in 2007 we established a prospect i ve , longitudinal , observational cohort study of early stage breast cancer patients , recruited at the end of initial treatments ( primary treatment exposure included surgery , ± radiation , ± chemotherapy ) , and prior to the initiation of adjuvant endocrine therapy . We assessed cognitive complaints , neuropsychological ( NP ) test performance , markers of inflammation , and brain imaging at baseline , 6 months and 12 months after enrollment . In this analysis of data from the first 93 patients enrolled in the cohort study , we focus on the relationship of circulating levels of proinflammatory cytokines to cerebral functioning and chemotherapy exposure . Among the proinflammatory cytokines tested ( IL-1 ra , sTNF-RII , CRP , and IL-6 ) at baseline , only sTNF-RII was increased among chemotherapy exposed patients , with a significant decline in the year after treatment ( p=0.003 ) . Higher baseline sTNF-RII in chemotherapy patients was significantly associated with increased memory complaints . In chemotherapy exposed patients , the longitudinal decline in sTNF-RII was significantly correlated with fewer memory complaints over 12 months ( r=-0.34 , p=0.04 ) . Higher baseline sTNF-RII was also associated with relatively diminished brain metabolism in the inferior frontal cortex ( r=-0.55 , p=0.02 ) , as well as relatively increased inferior frontal metabolism after 1 year , in chemotherapy-exposed subjects . These preliminary findings suggest that post-chemotherapy increases in TNF-α may be playing an important role in the manifestations of cognitive complaints in breast cancer survivors BACKGROUND Neuropsychological examinations have shown an elevated risk for cognitive impairment 2 years after therapy in breast cancer patients r and omized to receive adjuvant high-dose cyclophosphamide , thiotepa , carboplatin ( CTC ) chemotherapy compared with a non-treated control group of stage I breast cancer patients . Patients r and omized to receive st and ard-dose fluorouracil , epirubicin , cyclophosphamide ( FEC ) chemotherapy showed no elevated risk compared with controls . However , breast cancer patients treated with conventional cyclophosphamide , methotrexate , 5-fluorouracil ( CMF ) chemotherapy showed a higher risk of cognitive impairment . The present study was design ed to obtain a greater insight into these long-term neuropsychological sequelae following chemotherapy and their course in time . PATIENTS AND METHODS At 4 years post-therapy , 22 of the original 34 CTC patients , 23 of 36 FEC patients , 31 of 39 CMF patients and 27 of 34 control patients were re-examined with neuropsychological tests . RESULTS Improvement in performance was observed in all chemotherapy groups , whereas in the control group there was a slight deterioration in test results . A differential attrition was observed among the groups , with a relatively high percentage of initially cognitively impaired patients from the CTC group dropping out due to factors related to disease progression . CONCLUSIONS The results suggest that cognitive dysfunction following adjuvant chemotherapy in breast cancer patients may be transient . Additional studies are needed to investigate the differential attrition of patients with cognitive impairment 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 BACKGROUND Flu-like symptoms are common , early transient side effects of paclitaxel chemotherapy . We hypothesized that these symptoms may be due to release of inflammatory cytokines in response to treatment . The objective of this study was to assess changes in plasma levels of interleukin (IL)-1beta , IL-6 , IL-8 , IL-10 , IL-12 , and TNF-alpha during chemotherapy and to correlate these changes with musculoskeletal symptoms . METHODS Ninety patients with breast cancer were included ; 70 patients received single agent paclitaxel either weekly or every 3 weeks and 20 received FAC ( 5-FU , doxorubicin , cyclophosphamide ) chemotherapy . Fifteen healthy volunteers were included as controls . Cytokines and symptoms were measured before starting therapy , on day 3 and on the last day of one treatment cycle . RESULTS At baseline , all subjects had measurable levels of IL-8 but only 49 % had IL-12 , 45 % had IL-10 , 32 % had IL-6 , and 21 % had IL-1beta or TNF-alpha in their plasma . There was no difference in baseline cytokine levels between cancer patients and the healthy volunteers . Schedule-dependent transient changes in the levels of 3 cytokines were observed in the paclitaxel treated patients . In the every 3-week paclitaxel group , IL-6 and IL-8 increased whereas in the weekly paclitaxel group IL-10 increased significantly compared to baseline . Fatigue and flu-like symptoms were also worse on day 3 . In the weekly paclitaxel group , increase in IL-10 level correlated positively with joint pain ( p=0.003 ) . In the every 3-week paclitaxel group , increase in IL-8 level correlated positively with flu-like symptom ( p=0.008 ) . In the FAC-treated group and among the healthy volunteers none of these cytokines increased significantly . CONCLUSIONS Weekly paclitaxel induces transient increase in IL-10 levels whereas every 3-week higher dose treatments induce IL-8 and IL-6 in the plasma . These changes correlate with joint pain and flu-like symptoms Purpose : Clinical studies indicate that up to 70 % of patients with cancer who receive chemotherapy experience cognitive impairment . The present study used a prospect i ve longitudinal design to assess short- and long-term effects of commonly used anticancer drugs on cognitive performance in a mouse model . Experimental Design : Normal mice received three weekly injections of a combination of methotrexate + 5-fluorouracil ( CHEMO group ) or an equal volume of saline ( SAL group ) . Cognitive tests , measuring different aspects of learning and memory , were administered before treatment , immediately after treatment , and three months later . Structural MRI scanning was conducted at each stage of cognitive testing . Results : The CHEMO group exhibited deficits on cognitive tasks acquired pretreatment [ spatial memory , nonmatching-to- sample ( NMTS ) learning , and delayed NMTS ] , as well as impaired new learning on two tasks ( conditional associative learning , discrimination learning ) introduced posttreatment . Consistent with clinical evidence , cognitive deficits were pronounced on tests that are sensitive to hippocampal and frontal lobe dysfunction , but the CHEMO group 's poor performance on the discrimination learning problem suggests that impairment is more widespread than previously thought . Cognitive deficits persisted for at least three months after treatment but some recovery was noted , particularly on tests thought to be under frontal lobe control . The MRI tests did not detect brain changes that could be attributed to treatment . Conclusions : Chemotherapeutic agents can have adverse effects on information acquired pretreatment as well as new learning and memory and , despite some recovery , impairment is long lasting . Clin Cancer Res ; 18(11 ) ; 3112–21 . © 2012 AACR 9008 Background : Cognitive complaints ( CC ) are common in BCS , and are associated with adjuvant chemotherapy ( CTx ) . The biology of these symptoms is poorly understood , enduring in 25 % of BCS . We tested the hypothesis that CTx-induced alterations in TNF inflammatory signaling might underlie observed cerebral dysfunction . METHODS We enrolled 93 BCS in a prospect i ve observational study within 1 month of completing primary treatment ( surgery , radiation , chemotherapy ) , prior to initiating endocrine therapy . At entry , 6 and 12 months later , BCS completed self-report measures of CC and a 2 hr neuropsychological ( NP ) battery and had blood drawn for markers of proinflammatory cytokine activity : IL-6 , IL-1 receptor antagonist , soluble TNF receptor type 2 ( sTNFr2 ) , and C reactive protein . A subset of BCS ( n=14 ) had brain FDG-PET scans at entry and 12 mos . Multivariate models and ANOVA were used to examine relationships of cytokine activity with CC and CTx , controlling for covariates . RESULTS 53 % of BCS sample had received CTx . At entry , sTNFr2 was the only cytokine measure that was significantly elevated in CTx patients compared with non-CTx ( p=0.005 ) , and its level declined significantly by 12 months to a level similar to non CTx group ( p = 0.003 ) . CTx was also associated with increased CC at entry ( p=0.05 ) , controlling for time since CTx , age , IQ and BMI . CC were significantly associated with sTNFr2 ( p=0.05 ) at entry . Entry CC predicted subsequent NP test abnormalities at 6 months . PET scan sub study showed : among CTx patients , higher levels of sTNFr2 correlated with lower levels of baseline metabolism in left inferior frontal gyrus , including Broca 's area ( p=0.002 ) . Entry sTNFr2 levels correlated with increases over 1 year in Broca 's area for the CTx group ( r=0.75 , p=0.02 ) , suggesting greater recovery of function in this area . CONCLUSIONS Relationships between sTNFr2 and CC and brain metabolism in BCS are consistent with animal studies that show increased peripheral and brain TNF after CTx , and suggest CTx-induced TNF might represent a biological target for pharmacologic remediation of " chemobrain . " FUNDING NCI R01 CA 109650 and the BCRF The effects of sleep deprivation on cognitive performance psychological variables related to cognitive performance were studied in 44 college students . Participants completed the Watson-Glaser Critical Thinking Appraisal after either 24 hours of sleep deprivation or approximately 8 hours of sleep . After completing the cognitive task , the participants completed 2 question naires , one assessing self-reported effort , concentration , and estimated performance , the other assessing off-task cognitions . As expected , sleep-deprived participants performed significantly worse than the nondeprived participants on the cognitive task . However , the sleep-deprived participants rated their concentration and effort higher than the nondeprived participants did . In addition , the sleep-deprived participants rated their estimated performance significantly higher than the nondeprived participants did . The findings indicate that college students are not aware of the extent to which sleep deprivation negatively affects their ability to complete cognitive tasks BACKGROUND Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma . We aim ed to test this hypothesis using previously unpublished data from eight European , Canadian , and US case-control studies of the International Lymphoma Epidemiology Consortium ( InterLymph ) . METHODS We selected 12 single-nucleotide polymorphisms for analysis , on the basis of previous functional or association data , in nine genes that have important roles in lymphoid development , Th1/Th2 balance , and proinflammatory or anti-inflammatory pathways ( IL1A , IL1RN , IL1B , IL2 , IL6 , IL10 , TNF , LTA , and CARD15 ) . Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls , and were assessed in a pooled analysis by use of a r and om-effects logistic regression model . FINDINGS The tumour necrosis factor ( TNF ) -308G-->A polymorphism was associated with increased risk of non-Hodgkin lymphoma ( p for trend=0.005 ) , particularly for diffuse large B-cell lymphoma , the main histological subtype ( odds ratio 1.29 [ 95 % CI 1.10 - 1.51 ] for GA and 1.65 [ 1.16 - 2.34 ] for AA , p for trend < 0.0001 ) , but not for follicular lymphoma . The interleukin 10 ( IL10 ) -3575T-->A polymorphism was also associated with increased risk of non-Hodgkin lymphoma ( p for trend=0.02 ) , again particularly for diffuse large B-cell lymphoma ( p for trend=0.006 ) . For individuals homozygous for the TNF -308A allele and carrying at least one IL10 -3575A allele , risk of diffuse large B-cell lymphoma doubled ( 2.13 [ 1.37 - 3.32 ] , p=0.00083 ) . INTERPRETATION Common polymorphisms in TNF and IL10 , key cytokines for the inflammatory response and Th1/Th2 balance , could be susceptibility loci for non-Hodgkin lymphoma . Moreover , our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer 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 BACKGROUND A diagnosis of breast cancer and treatment are psychologically stressful events , particularly over the first year after diagnosis . Women undergo many dem and ing and anxiety-arousing treatments such as surgery , radiation and chemotherapy . Psychosocial interventions that promote psychosocial adaptation to these challenges may modulate physiological processes ( neuroendocrine and immune ) that are relevant for health outcomes in breast cancer patients . METHODS Women with Stages 1 - 3 breast cancer recruited 4 - 8 weeks after surgery were r and omized to either a 10-week group-based cognitive behavioral stress management ( CBSM ) intervention or a 1-day psychoeducational control group and completed question naires and late afternoon blood sample s at study entry and 6 and 12 months after assignment to experimental condition . RESULTS Of 128 women initially providing psychosocial question naire and blood sample s at study entry , 97 provided complete data for anxiety measures and cortisol analysis at all time points , and immune assays were run on a subset of 85 of these women . Those assigned to a 10-week group-based CBSM intervention evidence d better psychosocial adaptation ( lower reported cancer-specific anxiety and interviewer-rated general anxiety symptoms ) and physiological adaptation ( lower cortisol , greater Th1 cytokine [ interleukin-2 and interferon-gamma ] production and IL-2:IL-4 ratio ) after their adjuvant treatment compared to those in the control group . Effects on psychosocial adaptation indicators and cortisol appeared to hold across the entire 12-month observation period . Th1 cytokine regulation changes held only over the initial 6-month period . CONCLUSIONS This intervention may have facilitated a " recovery or maintenance " of Th1 cytokine regulation during or after the adjuvant therapy period . Behavioral interventions that address dysregulated neuroendocrine function could play a clinical ly significant role in optimizing host immunologic resistance during a vulnerable period |
13,370 | 26,446,159 | Conclusion The present study supports the conclusion of Gwaltney ’s previous meta- analysis showing that PROMs administered on paper are quantitatively comparable with measures administered on an electronic device .
It also confirms the ISPOR Taskforce´s conclusion that quantitative equivalence studies are not required for migrations with minor change only . | Objective To conduct a systematic review and meta- analysis of the equivalence between electronic and paper administration of patient reported outcome measures ( PROMs ) in studies conducted subsequent to those included in Gwaltney et al ’s 2008 review . | PURPOSE The purpose of this study was to evaluate a computerized touch-screen version of the asthma-specific quality -of-life ( cA-QOL ) question naire against the conventional paper- and -pencil version ( pA-QOL ) for equivalence , time for completion , user preference , and ease of use . METHODS A total of 261 patients were recruited . A r and omized cross-over design was used . Patients in group A completed the cA-QOL first while waiting to see a physician , and completed the pA-QOL version after seeing the physician . Patients allocated in group B completed these question naires in the reverse order . The patients were asked questions about user preference and ease of use of the cA-QOL . The time taken to complete both versions of the question naire was measured . RESULTS Weighted kappa coefficients of all items showed almost perfect agreement . The time required to complete the pA-QOL is faster than the time for cA-QOL . The patients who preferred the cA-QOL were 37.5 % , while those who preferred the pA-QOL were 29.9 % . Most patients reported that the cA-QOL was " easy " or " very easy " to complete . CONCLUSION The cA-QOL is the computerized equivalent of the pA-QOL . The findings herein demonstrate that the cA-QOL can be helpful to nurses in busy practice s for assessing , collecting , and evaluating their patients ' health related quality of life Aims In this study we evaluated indicators of the feasibility , reliability , and validity of the Child Health Question naire-Child Form ( CHQ-CF ) . We compared the results in a subgroup of adolescents who completed the st and ard paper version of the CHQ-CF with the results in another subgroup of adolescents who completed an internet version , i.e. , an online , web-based CHQ-CF question naire . Methods Under supervision at school , 1,071 adolescents were r and omized to complete the CHQ-CF and items on chronic conditions by a paper question naire or by an internet administered question naire . Results The participation rate was 87 % ; age range 13–7 years . The internet administration result ed in fewer missing answers . All but one multi-item scale showed internal consistency reliability ( Cronbach ’s α > 0.70 ) . All scales clearly discriminated between adolescents with no , a few , or many self-reported chronic conditions . The paper administration result ed in statistically significant , higher scores on 4 of 10 CHQ-CF scales compared with the internet administration ( P < 0.05 ) , but Cohen ’s effect sizes d were ≤0.21 . Mode of administration interacted significantly with age ( P < 0.05 ) on four CHQ-CF scales , but Cohen ’s effect sizes for these differences were also ≤0.21 . Conclusion This study supports the feasibility , internal consistency reliability of the scales , and construct validity of the CHQ-CF administered by either a paper question naire or online question naire . Given Cohen ’s suggested guidelines for the interpretation of effect sizes , i.e. , 0.20–.50 indicates a small effect , differences in CHQ-CF scale scores between paper and internet administration can be considered as negligible or small Purpose To test the impact of method of administration ( MOA ) on the measurement characteristics of items developed in the Patient-Reported Outcomes Measurement Information System ( PROMIS ) . Methods Two non-overlapping parallel 8-item forms from each of three PROMIS domains ( physical function , fatigue , and depression ) were completed by 923 adults ( age 18–89 ) with chronic obstructive pulmonary disease , depression , or rheumatoid arthritis . In a r and omized cross-over design , subjects answered one form by interactive voice response ( IVR ) technology , paper question naire ( PQ ) , personal digital assistant ( PDA ) , or personal computer ( PC ) on the Internet , and a second form by PC , in the same administration . Structural invariance , equivalence of item responses , and measurement precision were evaluated using confirmatory factor analysis and item response theory methods . Results Multigroup confirmatory factor analysis supported equivalence of factor structure across MOA . Analyses by item response theory found no differences in item location parameters and strongly supported the equivalence of scores across MOA . Conclusions We found no statistically or clinical ly significant differences in score levels in IVR , PQ , or PDA administration as compared to PC . Availability of large item response theory-calibrated PROMIS item banks allowed for innovations in study design and analysis BACKGROUND The feasibility and validity of Web-based assessment s in Parkinson 's disease is unknown . The objectives of this study were to develop and to compare home Web-based assessment s with office-based assessment s. METHODS We tested feasibility and validity using a longitudinal , r and omized crossover design . Patients were assessed at baseline and after 6 and 12 weeks using both assessment s including the Unified Parkinson 's Disease Rating Scale , the Unified Dyskinesia Rating scale , timed tests , and quality -of life and Non-Motor Symptoms question naires . RESULTS Forty-two patients were included ( 22 men , 20 women ; mean age , 64.7 ± 9.0 years ) . Only 2 patients ( 5 % ) dropped out . The mean intraclass correlation coefficient between Web- and office-based assessment s ranged from 0.67 ( first visit ) to 0.75 ( last visit ) and 0.81 and 0.82 for doctor- and patient-administered scales , respectively . No differences in responsiveness ( P = 0.63 ) , and data precision ( P = 0.11 ) were found , but Web-based assessment s had fewer missing values ( P = 0.01 ) . CONCLUSIONS Web-based assessment s offer a feasible format for assessing PD-related impairment from home Background When evaluating hearing rehabilitation , it is reasonable to use self-report question naires as outcome measure . Question naires used in audiological research are developed and vali date d for the paper- and -pencil format . As computer and Internet use is increasing , st and ardized question naires used in the audiological context should be evaluated to determine the viability of the online administration format . The aim of this study was to compare administration of question naires online versus paper- and pencil of four st and ardised question naires used in hearing research and clinic . We included the Hearing H and icap Inventory for the Elderly ( HHIE ) , the International Outcome Inventory for Hearing Aids ( IOI-HA ) , Satisfaction with Amplification in Daily Life ( SADL ) , and the Hospital Anxiety and Depression Scale ( HADS ) . Methods A cross-over design was used by r and omly letting the participants complete the question naires either online or on paper . After 3 weeks the participants filled out the same question naires again but in the other format . A total of 65 hearing-aid users were recruited from a hearing clinic to participate on a voluntary basis and of these 53 completed both versions of the question naires . Results A significant main effect of format was found on the HHIE ( p < 0.001 ) , with participants reporting higher scores on the online format than in the paper format . There was no interaction effect . For the other question naires were no significant main or interaction effects of format . Significant correlations between the two ways of presenting the measures was found for all question naires ( p<0.05 ) . The results from reliability tests showed Cronbachs α ’s above .70 for all four question naires and differences in Cronbachs α between administration formats were negligible . Conclusions For three of the four included question naires the participants ’ scores remained consistent across administrations and formats . For the fourth included question naire ( HHIE ) a significant difference of format with a small effect size was found . The relevance of the difference in scores between the formats depends on which context the question naire is used in . On balance , it is recommended that the administration format remain stable across assessment points BACKGROUND Sexual dysfunction is a symptom of major depression , as well as a common complication of treatment with many classes of antidepressants . Nonetheless , the various forms of sexual dysfunction continue to be underreported in clinical practice , despite the availability of vali date d scales such as the Changes in Sexual Functioning Question naire ( CSFQ ) . The current study was design ed to evaluate the validity of obtaining CSFQ data using interactive voice response ( IVR ) technology . METHOD Sexually active , healthy male volunteers ( N = 99 ; mean age of 31 years ) were r and omly assigned to 3 weeks of double-blind , parallel-group treatment with paroxetine ( 20 mg/day ) ; CP-448,187 ( 3 mg/day ) ; or placebo . Patients completed both paper- and -pencil and IVR versions of the 14-item CSFQ at baseline and on treatment days 8 , 15 , and 21 . Additional IVR assessment s were obtained at days 2 , 4 , and 6 , permitting assessment of changes between office visits . This study was conducted between March and May 2001 . RESULTS The overall correlation between the paper and IVR CSFQ total score was r = 0.96 ( p < .0001 ) . Similarly , high correlations were found between paper and IVR assessment methods on the individual CSFQ subscales : pleasure ( r = 0.88 ) , frequency ( r = 0.88 ) , interest ( r = 0.93 ) , arousal ( r = 0.89 ) , and orgasm ( r = 0.92 ; p < .0001 for all comparisons ) . Both assessment methods were able to detect a statistically significant between-group difference in sexual functioning by day 8 , which remained significant throughout the remainder of the study . Both assessment methods found SSRI-related sexual dysfunction to include significant effects on all CSFQ domains . Assessment s using IVR collected from subjects at home on days 2 , 4 , and 6 identified onset of sexual dysfunction by day 4 , before it was detected during scheduled office visits . CONCLUSION Interactive voice response assessment of sexual dysfunction on the CSFQ was found to be highly correlated with previously vali date d paper- and -pencil assessment . Interactive voice response provides a valid , easy-to-administer alternative method for obtaining systematic data on the impact of antidepressant treatment on sexual functioning . More frequent assessment by IVR enables more precise evaluation of symptom onset Background Augmenting vali date d paper versions of existing outcome measures with an equivalent online version may offer substantial research advantages ( cost , rapidity and reliability ) . However , equivalence of online and paper question naires can not be assumed , nor can acceptability to respondents . The aim was to test whether online and written versions of the Rol and Morris Disability Question naire ( RMDQ ) , a st and ard measure of functional disability in back pain , are equivalent at both group and individual levels to establish whether they can be used interchangeably . Methods This is a within- participants equivalence study . 167 participants with back pain fully completed both the paper and online versions of the RMDQ in r and om order . Participants were recruited from a chiropractic clinic and patient support groups in Southern Engl and . Limits of equivalence were pre-defined as 0.5 RMDQ points , the Bl and -Altman range was calculated , and participants ' comments were examined using content analysis . Results The mean score difference was 0.03 ( SD = 1.43 ) , with the 95 % Confidence Interval falling entirely within our limits of equivalence ( -0.19 to 0.25 ) . The Bl and -Altman range was -2.77 to 2.83 RMDQ points . Participants identified unique advantages and disadvantages associated with each version of the RMDQ . Conclusions The group and individual level data suggest that online and paper versions of the RMDQ are equivalent and can be used interchangeably . The Bl and -Altman range appears to reflect the known measurement properties of the RMDQ . Furthermore , participants ' comments confirmed the potential value to be had from offering them the choice of completing the RMDQ online or on paper Background To compare data based on touch screen to data based on traditional paper versions of question naires frequently used to examine patient reported outcomes in knee osteoarthritis patients and to examine the impact of patient characteristics on this comparison Methods Participants were recruited from an ongoing trial ( http:// Clinical Trials . Gov Identifier : NCT00655941 ) . 20 female participants , mean age 67 ( SD 7 ) , completed KOOS , VAS pain , function and patient global , SF-36 , Physical Activity Scale , painDETECT , and the ADL Taxonomy . Patients were r and omly assigned to one of two subgroups , completing either the paper or touch screen version first . Mean , mean differences ( 95 % CI ) , median , median differences and Intraclass Correlation Coefficients ( ICCs ) were calculated for all question naires . Results ICCs between data based on computerized and paper versions ranged from 0.86 to 0.99 . Analysis revealed a statistically significant difference between versions of the ADL Taxonomy , but not for the remaining question naires . Age , computer experience or education-level had no significant impact on the results . The computerized question naires were reported to be easier to use . Conclusion The computerized question naires gave comparable results to answers given on paper . Patient characteristics did not influence results and implementation was feasible Background In clinical and research practice linked to prostate cancer treatment , frequent monitoring of patient health-related quality of life ( HRQOL ) is essential . Practical and analytic limitations of paper question naire data capture may be overcome with the use of self-administered personal digital assistant ( PDA ) data collection . The objective of this study was to assess the reliability , validity , and feasibility of using PDA in place of paper versions of the International Prostate Symptom Score ( IPSS ) , the Patient Oriented Prostate Cancer Utility Survey ( PORPUS ) , and the International Index of Erectile Function-5 ( IIEF-5 ) in a prostate cancer clinic setting . Methods 152 participants were r and omly assigned to one of three conditions : 1 ) paper followed by PDA survey ; 2 ) PDA followed by paper survey ; or 3 ) PDA followed by PDA survey . Evaluation included an assessment of data quality ( internal consistency , test-retest reliability , response correlation , completeness of data ) , and feasibility ( participation rates , time to completion , preference and difficultly/ease of using PDA ) . Results Internal consistency was similar for both PDA and paper applications . Test-retest reliability was confirmed for PDA repeated administration . Data from paper and PDA question naires were strongly correlated . Lower missed item rates were found in PDA administration . 82.8 % of participants preferred using the PDA or had no preference . Mean difficulty/ease ratings indicated that participants found the PDA easy to use . Age did not significantly correlate with preference or difficulty . Conclusion The results confirm the adaptability of the IPSS , IIEF-5 , and the PORPUS to PDA administration . Similarly , the findings of this study support the feasibility of using PDA technology for HRQOL serial data capture in the prostate cancer patient population Use of Internet versions of question naires may have several advantages in clinical and epidemiological research , but we know little about if Internet versions differ with respect to validity and reliability . We aim ed to compare Internet- and pen- and -paper versions of short form-36 ( SF-36 ) with respect to test – retest reliability and internal consistency . Women referred to mammography ( n = 782 ) were r and omised to receive either a paper version with a prepaid return envelope or a guideline on how to fill in the Internet version . A subgroup was asked to answer the question naire once again in the alternative version . Test – retest reliability was assessed by the intra-class correlation coefficient . Internal consistency was calculated as Cronbach 's alpha . The between-version test – retest reliability for the eight subscales were between 0.63 and 0.92 . Cronbach 's alpha for the two versions were all between 0.75 and 0.93 with minor differences between the Internet- and the pen- and -paper version . We found little or no evidence of a difference in test – retest reliability and internal consistency when we compared an Internet- and a pen- and -paper version of SF-36 Background When large scale trials are investigating the effects of interventions on appetite , it is paramount to efficiently monitor large amounts of human data . The original h and -held Electronic Appetite Ratings System ( EARS ) was design ed to facilitate the administering and data management of visual analogue scales ( VAS ) of subjective appetite sensations . The purpose of this study was to vali date a novel h and -held method ( EARS II ( HP ® iPAQ ) ) against the st and ard Pen and Paper ( P&P ) method and the previously vali date d EARS . Methods Twelve participants ( 5 male , 7 female , aged 18 - 40 ) were involved in a fully repeated measures design . Participants were r and omly assigned in a crossover design , to either high fat ( > 48 % fat ) or low fat ( < 28 % fat ) meal days , one week apart and completed ratings using the three data capture methods ordered according to Latin Square . The first set of appetite sensations was completed in a fasted state , immediately before a fixed breakfast . Thereafter , appetite sensations were completed every thirty minutes for 4h . An ad libitum lunch was provided immediately before completing a final set of appetite sensations . Results Repeated measures ANOVAs were conducted for ratings of hunger , fullness and desire to eat . There were no significant differences between P&P compared with either EARS or EARS II ( p > 0.05 ) . Correlation coefficients between P&P and EARS II , controlling for age and gender , were performed on Area Under the Curve ratings . R2 for Hunger ( 0.89 ) , Fullness ( 0.96 ) and Desire to Eat ( 0.95 ) were statistically significant ( p < 0.05 ) . Conclusions EARS II was sensitive to the impact of a meal and recovery of appetite during the postpr and ial period and is therefore an effective device for monitoring appetite sensations . This study provides evidence and support for further validation of the novel EARS II method for monitoring appetite sensations during large scale studies . The added versatility means that future uses of the system provides the potential to monitor a range of other behavioural and physiological measures often important in clinical and free living trials . This study was registered as a clinical trial by Current Controlled Trials ( Registration Number - IS RCT N47291569 ) This study examines whether the Internet-based question naire is psychometrically equivalent to the paper-based question naire . A r and om sample of 2,400 teachers in Taiwan was divided into experimental and control groups . The experimental group was invited to complete the electronic form of the Chinese version of Center for Epidemiologic Studies Depression Scale ( CES-D ) placed on the Internet , whereas the control group was invited to complete the paper-based CES-D , which they received by mail . The multi sample invariance approach , derived from structural equation modeling ( SEM ) , was applied to analyze the collected data . The analytical results show that the two groups have equivalent factor structures in the CES-D. That is , the items in CES-D function equivalently in the two groups . Then the e quality of latent mean test was performed . The latent means of " depressed mood , " " positive affect , " and " interpersonal problems " in CES-D are not significantly different between these two groups . However , the difference in the " somatic symptoms " latent means between these two groups is statistically significant at alpha = 0.01 . But the Cohen 's d statistics indicates that such differences in latent means do not apparently lead to a meaningful effect size in practice . Both CES-D question naires exhibit equal validity , reliability , and factor structures and exhibit a little difference in latent means . Therefore , the Internet-based question naire represents a promising alternative to the paper-based question naire This study compared results from Internet and written question naires about respiratory symptoms in order to find out if both forms of the survey yielded the same answers . One thous and seventy-one students , ages 13 to 17 , were asked to complete either an Internet or a written question naire . The demographic characteristics of the participants equalled those of the general Dutch adolescent population . Participants were r and omly assigned to fill out an electronic or written question naire . In addition to eight items from the International Study of Asthma and Allergies in Childhood ( ISAAC ) question naire , two items on doctor visits ( medical attention ) regarding asthma or allergic disease during the past 12 months were included . The participation rate was 87 % . The Internet version of the question naire showed fewer missing answers than the written version , but this was not statistically significant . The respiratory items did not show statistically significant score differences between the Internet and written modes of administration , and there was no visible trend for higher respectively lower scores by either mode of question naire administration . From these results , we conclude that respiratory question naires may be provided to adolescents electronically rather than on paper , since both approaches yielded equal results . To generalize these findings , we recommend repeated studies in other setting Background The majority of Internet-mediated studies use measures developed as paper- and -pencil measures or face-to-face-delivered material . Previous research suggests that the equivalence between online and offline measures must be demonstrated rather than assumed . Objective The objective of this study was to explore the equivalence 4 measures completed in an online or offline setting . Methods A sample of students ( n = 1969 ) was r and omly assigned to complete 4 popular scales ( the SF-12v2 , the Hospital Anxiety and Depression Scale ( HADS ) , the Fatigue Symptom Inventory , and a single-item fatigue measure ) either online or by mail survey ( pencil and paper ) . The response rate was 52.51 % ( n = 1034 ) and comparable between the online and offline groups . Results Significant differences were noted in fatigue levels between the online and offline group ( P = .01 ) as measured by the Fatigue Symptom Inventory , with the online sample demonstrating higher levels of fatigue . Equivalency was noted for the SF-12v2 , the Hospital Anxiety and Depression Scale , and the single-item fatigue measure . Internal consistency was high except for the SF-12v2 . The SF-12v2 may not be an ideal measure to use for remote administration . Conclusions Equivalency of the Hospital Anxiety and Depression Scale ( HADS ) and the Physical Component Score and Mental Component Score of the SF-12v2 for online and offline data were demonstrated . Equivalency was not demonstrated for the Fatigue Symptom Inventory . Explanations for the difference in fatigue score between the online and offline sample s are unclear . Research that seeks to match sample s and control for extraneous online and offline variables is called for , along with exploration of factors that may mediate the completion of question naires or alter the respondents ’ relationship with the same , to enhance progress in this area Purpose To evaluate the equivalence of electronic and paper versions of the Psoriasis Symptom Inventory and to examine measurement properties of the electronic version . Methods In a prospect i ve , r and omized , crossover , non-interventional study in adult subjects ( age ≥18 years ) with plaque psoriasis conducted over a period of 15 days , subjects were r and omized to two groups , completing either the paper or electronic Psoriasis Symptom Inventory daily for 7 consecutive days followed by the alternate version . Equivalence was assessed by the intraclass correlation coefficient ( ICC ) between both administration modes . Differences in scores were also tested using paired Student ’s t test . Measurement properties included internal consistency reliability , test – retest reliability , and convergent and discriminant validity between the Psoriasis Symptom Inventory and ( 1 ) disease-specific ( Dermatology Life Quality Index ) and ( 2 ) general health ( SF-36v2 ) status . Results Eighty subjects [ 74 % ( 59/80 ) moderate-to-severe psoriasis ; 26 % ( 21/80 ) mild psoriasis receiving systemic treatment ] were enrolled from 8 sites in the USA . The two modes were highly concordant for both total ( ICC = 0.97 ) and individual item scores ( ICC range = 0.93–0.97 ) . Response bias testing showed no differences based on completion order with all ICC values > 0.91 . All mean score differences , except for one item ( “ flaking ” ) , were non-significant ( P > 0.05 ) . Minimum values for reliability ( > 0.70 ) and validity ( convergent , r ≥ 0.40 ) were exceeded for the electronic Psoriasis Symptom Inventory . Conclusions Equivalence between paper and electronic versions of the Psoriasis Symptom Inventory and strong measurement properties of the electronic mode indicated a successful migration from paper to electronic format of the Psoriasis Symptom Inventory Background : The Short Inflammatory Bowel Disease Question naire ( SIBDQ ) is a written , self‐administered instrument measuring quality of life in IBD . We assessed the validity of an interactive voice response system ( IVRS ) as a new mode of administering the SIBDQ . Methods : An IVRS was design ed using prerecorded questions to collect data via touchtone telephone . Subjects with Crohn 's disease ( CD ) or ulcerative colitis ( UC ) were r and omized into 2 groups with different orders of administration : written , self‐administered followed by IVRS ( S‐I ) or IVRS followed by written , self‐administered ( I‐S ) . Half of the S‐I group was also r and omized to receive a second IVRS . Sixty‐four subjects were studied : 30 in S‐I , 34 in I‐S. Results : The mean SIBDQ scores were not different between written and IVRS modes ( P = 0.26 ) with r = 0.93 . IVRS scores were lower in active than inactive CD ( 36.1 ± 9.6 versus 54.7 ± 8.6 , P < 0.001 ) and lower in active than inactive UC ( 40.8 ± 9.6 versus 59.8 ± 10.0 , P < 0.001 ) . Mean scores correlated highly with disease activity indices , and were not different between first and second IVRS administrations ( P = 0.85 ) with r = 0.92 . IVRS had excellent internal consistency ( Cronbach alpha = 0.90 ) . Conclusions : IVRS administration of the SIBDQ yields results similar to written self‐administration , with excellent procedural validity , test – retest reliability , and internal consistency . ( Inflamm Bowel Dis 2009 Background The use of the Internet to administer question naires has many potential advantages over the use of pen- and -paper administration . Yet it is important to vali date Internet administration , as most question naires were initially developed and vali date d for pen- and -paper delivery . While some have been vali date d for use over the Internet , these question naires have predominately been used amongst the healthy general population . To date , information is lacking on the validity of question naires administered over the Internet in patients with chronic diseases such as heart failure . Objectives To determine the validity of three heart failure question naires administered over the Internet compared to pen- and -paper administration in patients with heart failure . Methods We conducted a prospect i ve r and omized study using test-retest design comparing administration via the Internet to pen- and -paper administration for three heart failure question naires provided to patients recruited from a heart failure clinic in Toronto , Ontario , Canada : the Kansas City Cardiomyopathy Question naire ( KCCQ ) , the Minnesota Living with Heart Failure Question naire ( MLHFQ ) , and the Self-Care Heart Failure Index ( SCHFI ) . Results Of the 58 subjects enrolled , 34 completed all three question naires . The mean difference and confidence intervals for the summary scores of the KCCQ , MLHFQ , and SCHFI were 1.2 ( CI -1.5 to 4.0 , scale from 0 to 100 ) , 4.0 ( CI -1.98 to 10.04 , scale from 0 to 105 ) , and 10.1 ( CI 1.18 to 19.07 , scale from 66.7 to 300 ) , respectively . Conclusions Internet administration of the KCCQ appears to be equivalent to pen- and -paper administration . For the MLHFQ and SCHFI , we were unable to demonstrate equivalence . Further research is necessary to determine if the administration methods are equivalent for these instruments BACKGROUND The Western Ontario Rotator Cuff Index ( WORC ) is commonly used in orthopedic research to assess the effect of a rotator cuff injury . Questions in the WORC are presented in a visual analog scale format , which requires patients to place a pencil mark along a 10-cm line indicating their responses . The purpose of our study was to determine if a computerized version of a visual analog scale requiring patients drag a cursor along a line was comparable to data collected using the st and ard paper version of the WORC . MATERIAL S AND METHODS Administration of the WORC was r and omized , with the first version given in the waiting room before the office visit , and the second immediately after the office visit , to ensure the participant 's shoulder function had not significantly changed . RESULTS Thirty-five patients with rotator cuff injury completed the paper and computerized versions of the WORC . There was no significant difference in mean scores for the WORC between the paper ( 1040.3 ) and computerized versions ( 1021.2 , P = .488 ) . The intraclass correlation coefficient for the 2 versions was 0.94 . Similarly , there were no significant differences in scores between the subset of scores within the WORC ( Physical Activity , Work , Sports , Lifestyle , and Emotion , P > .05 ) , and each subset was highly correlated ( intraclass correlation coefficient > 0.80 ) . CONCLUSIONS There was no significant difference in scores for the WORC index when administered in a computerized format vs a paper format Objectives This study examined the measurement equivalence of the original paper-based vertical format of the EQ-5D visual analog scale ( EQ VAS ) with a touch-screen computer-based horizontal format . Methods A total of 314 subjects were administered two modes of the EQ VAS in a r and omized crossover design . One mode was the original paper-based 20 cm vertical EQ VAS ; the other mode was touch-screen-based . Measurement equivalence was assessed by testing the 95 % confidence interval of the mean differences from an equivalence threshold of −3 to + 3 points on the VAS and evaluating the intraclass correlation coefficient ( ICC ) . Results The adjusted mean ( SE ) EQ VAS score was 80.96 ( 0.87 ) on the paper and 79.59 ( 0.85 ) on the touch-screen . The mean ( CI ) difference between scores on the two formats was 1.37 with a confidence interval of 0.175–2.559 , wholly contained within the equivalence interval . The ICC was 0.75 , indicating acceptable agreement between the two modes . Almost a third ( 30.1 % ) of the respondents reported identical scores on both formats . Conclusion These results provide evidence for the measurement equivalence of this EQ VAS touch-screen administration mode with the original paper mode Purpose The objective of this study was to evaluate the measurement equivalence of an interactive voice response system ( IVRS ) version and the original paper-based version of the EORTC QLQ-C30 . Methods The QLQ-C30 is a cancer-specific , health-related quality of life question naire consisting of nine multi-item scales ( physical , role , emotional , cognitive and social functioning , fatigue , nausea/vomiting , pain , and quality of life ) and six single item measures ( dyspnea , insomnia , appetite loss , constipation , diarrhea , and financial problems ) . This study utilized a crossover design with subjects r and omly assigned to one of two assessment orders : ( 1 ) paper then IVRS or ( 2 ) IVRS then paper . Equivalence between the two administration modes was established by comparing the 95 % lower confidence interval ( CI ) of the intraclass correlation coefficients ( ICCs ) for each scale , with a critical value of 0.70 . Results The ICCs for the nine multi-item scales were all above 0.79 , ranging from 0.791 to 0.899 ( ICC 95 % lower CI range 0.726–0.865 ) and significantly different from our threshold reliability of 0.70 . The ICCs for the six single items ranged from 0.689 to 0.896 ( ICC 95 % lower CI range 0.611–0.888 ) . Two of the items , insomnia and appetite loss , were not statistically different from 0.70 . When considered together , the per- protocol analysis results support the equivalence of the paper and IVRS versions of the QLQ-C30 for 13 of the 15 scores . Conclusion This analysis provides evidence that the scores obtained from the IVRS version of the QLQ-C30 are equivalent to those obtained with the original paper version except for the insomnia and appetite loss items Background Self-report measures can guide clinical decisions and are useful when evaluating treatment outcomes . However , many clinicians do not use self-report measures systematic ally in their clinical practice . Internet-based question naires could facilitate administration , but the psychometric properties of the online version of an instrument should be explored before implementation . The recommendation from the International Test Commission is to test the psychometric properties of each question naire separately . Objective Our objective was to compare the psychometric properties of paper- and -pencil versions and Internet versions of two question naires measuring depressive symptoms . Methods The 87 participating patients were recruited from primary care and psychiatric care within the public health care system in Sweden . Participants completed the Beck Depression Inventory ( BDI-II ) and the Montgomery-Åsberg Depression Rating Scale — Self-rated ( MADRS-S ) , both on paper and on the Internet . The order was r and omized to control for order effects . Symptom severity in the sample ranged from mild to severe depressive symptoms . Results Psychometric properties of the two administration formats were mostly equivalent . The internal consistency was similar for the Internet and paper versions , and significant correlations were found between the formats for both MADRS-S ( r = .84 ) and the BDI-II ( r = .89 ) . Differences between paper and Internet total scores were not statistically significant for either question naire nor for the MADRS-S question dealing with suicidality ( item 9 ) when analyzed separately . The score on the BDI-II question about suicidality ( item 9 ) was significantly lower when administered via the Internet compared with the paper score , but the difference was small ( effect size , Cohen ’s [ d ] = 0.14 ) . There were significant main effects for order of administration on both question naires and significant interaction effects between format and order . This should not , however , pose a problem in clinical use as long as the administration format is not changed when repeated measurements are made . Conclusions The MADRS-S can be transferred to online use without affecting the psychometric properties in a clinical ly meaningful way . The full BDI-II also seems to retain its properties when transferred ; however , the item measuring suicidality in the Internet version needs further investigation since it was associated with a lower score in this study . The use of online question naires offers clinicians a more practical way of measuring depressive symptoms and has the potential to save re sources RATIONALE Recent guidelines focus on adjusting asthma treatment to the level of asthma control . The availability of a web-based asthma control question naire offers the possibility to assess asthma control without the need of outpatient clinic visits . The aim of this study was to evaluate the agreement between web-based and paper-based versions of the Asthma Control Test ( ACT ) and Childhood Asthma Control Test ( C-ACT ) , short-term reproducibility and satisfaction with both versions . METHODS One hundred seventy-three children with stable asthma and a normal lung function were r and omized to fill in a web-based or paper-based version of the C-ACT ( 4 - 11 years ) or ACT ( 12 - 18 years ) . According to a cross-over design , they completed the opposite version after 1 week . Reproducibility was evaluated by repeating the 2nd version ( web- or paper-based ) 7 days later . RESULTS Eighty-eight children filled in the C-ACT , 68 children filled in the ACT . Intraclass Correlation Coefficient ( ICC ) for web-based versus paper-based C-ACT was 0.81 ( 95 % confidence interval [ 95 % CI ] 0.72 - 0.87 ) . For ACT this was 0.84 ( 95 % CI 0.76 - 0.90 ) . For web-based and paper-based C-ACT the reproducibility ICC was 0.82 ( 95 % CI 0.67 - 0.90 ) and 0.75 ( 95 % CI 0.59 - 0.85 ) , respectively . The reproducibility ICC of the ACT for web- and paper-based versions was 0.93 ( 95 % CI 0.87 - 0.97 ) and 0.77 ( 95 % CI 0.59 - 0.88 ) , respectively . Eighty-six percent of patients preferred the web-based version . CONCLUSION The web-based version of the C-ACT and ACT is reproducible and comparable with the paper-based version in assessing asthma control . Most children and their parents prefer the web-based version The authors aim ed to evaluate the web and an Interactive Voice Response ( IVR ) phone service as vehicles in population -based infectious disease surveillance . Fourteen thous and subjects were r and omly selected from the Swedish population register and asked to prospect ively report all respiratory tract infections , including Influenza-like Illness ( ILI— clinical symptoms indicative of influenza but no laboratory confirmation ) , immediately as they occurred during a 36-week period starting October 2007 . Participants were classified as belonging to the web or IVR group based on their choice of technology for initial registration . In all , 1,297 individuals registered via IVR while 2,044 chose the web . The latter were more often young and well-educated than those registered via IVR . Overall , 52 % of the participants reported at least one infection episode . The risk of an infectious disease report was 14 % ( 95 % CI : 6 , 22 % ) higher in the web group than in the IVR group . For ILI the excess was 27 % ( 95 % CI : 11 , 47 % ) . After adjustments for socio-demographic factors , statistically non-significant excesses of 1 and 8 % remained , indicating trivial differences potentially attributable to the two reporting techniques . With attention to confounding , it should be possible to combine the web and IVR for simple reporting of infectious disease symptoms Objectives to verify the feasibility and reliability of the electronic version of Chinese SF-36 based on the Quality -of-Life-Recorder . Design A crossover r and omized controlled trial , comparing a paper-based and an electronic version of the Chinese SF-36 , was conducted . According to generated r and om numbers , interviewees were asked to fill out either the electronic version or the paper version first . The second version was filled in after a pause of at least 10 min . Setting s and participants One group of 100 medical students at the School of Medicine of Zhejiang University and the other group of 50 out patients at a clinic for general practice in Hangzhou City ( China ) were eventually recruited in this study . Results The acceptance of the electronic version was good ( 60 % of medical students and 84 % of out patients preferred the electronic version ) . At the level of eight-scale scores , the mean-difference for each scale ( except for general health ) between the two versions was less than 5 % . At the level of 36 questions , the percentage of “ exact agreement ” ranged within 64%–99 % ; the percentage of “ global agreement ” ranged within 72%–99 % ; 77 % of the kappa coefficients demonstrated “ good/excellent agreement ” and 23 % of the kappa coefficients demonstrated “ medium agreement ” . Conclusion This study , for the first time , can provide empirical basis for the confirmation of the feasibility and reliability of the electronic version of the Chinese SF-36 and may provide an impulse towards widespread deployment of the Quality -of-Life-Recorder in Chinese population OBJECTIVE Chronic pain is a common and costly syndrome which affects approximately one in three US adults . Factors such as shortened length of the medical visit , increased availability of technological approaches to care , and a more informed patient all suggest that a new paradigm is required for chronic pain management . Although much has been written about the use of electronic diaries in clinical trials , little has been presented about the use of these diaries in clinic practice and their potential for changing pain behavior . The intent of this preliminary study is to measure accessibility and usability of a software program design ed for use on a personal digital assistant and to discuss how the software program may impact clinic practice and patient behavior . METHODS We present the results of a preliminary , r and omized , comparison , crossover trial of 36 chronic pain patients who were asked to monitor their pain , mood , activity interference , medication use , and pain location on either a paper or electronic diary for 2 weeks . Patients in the electronic diary condition were able to observe changes in their ratings over time and view them on a secure web site . RESULTS No differences were found between paper and electronic tracking on pain descriptors , pain interference , mood , or helpfulness of medication . Similar to past findings , patients found the electronic diary easier to use ( P < 0.0001 ) and would continue using it ( P < 0.05 ) over paper if given the choice . Importantly , patients using the electronic diary reported more frequently that a provider suggested medication change ( P < 0.05 ) based on feedback from the electronic diary . One trend requiring further investigation is that electronic diary users reported that the diary enabled them and their doctor to make care adjustments according to changes in pain status . CONCLUSION This study goes beyond previous research on preference and data quality to investigate how the information provided may affect patient and physician perspectives toward pain management . Although not the initial intent of this study , findings indicate that electronic tracking may provide information which can affect management decisions . A follow-up study is ongoing to investigate these initial results . If found to be true , electronic monitoring may have broad implication s for health care , policy , and improvement in quality of care for chronic pain sufferers in the future Purpose The Social Difficulties Inventory ( SDI-21 ) assesses everyday problems experienced by cancer patients , including difficulties with self-care , work and relationships . Early development and psychometric evaluation studies have vali date d the SDI-21 for computer administration . However , several recent studies have administered the SDI-21 on paper . We sought to test the score equivalence of electronic and paper versions of the SDI-21 . Methods A r and omised two-arm crossover trial in a sample of cancer patients with varied diagnoses . Patients completed electronic ( via the internet ) and paper versions of the SDI-21 , with half r and omly assigned to complete the electronic version first ( n = 51 ) and half the paper version first ( n = 60 ) . Patients were asked to complete both versions at home , within 2 weeks . Analyses were performed for the SDI-21 summary score and three subscales . Results Score distributions and internal reliabilities for the paper and electronic versions were highly similar . There were no significant differences between mean summary or subscale scores for the two administration modes . All mean score differences ( all < 0.25 of a scale point ) were well below the SDI-21 ’s established minimally important differences , and all 95 % confidence intervals were narrow and included zero . Intraclass correlations between paper and electronic scores were uniformly high and significant ( all ≥0.85 ) and above the st and ard acceptable level of reliability . Conclusions Paper and electronic versions of the SDI-21 can be considered equivalent and used interchangeably . This is important because , despite the growth of electronic formats , paper versions are currently still necessary to ensure inclusive use of the SDI-21 with representative sample Introduction and hypothesisWe studied a web-based version of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Question naire ( PISQ-12 ) . Methods A r and omized crossover study in which subjects completed both a web-based and paper-based version of the PISQ-12 , with a 2-week separation between the completion of the two versions . Demographic data and question naire preferences were also assessed . Group 1 completed the web version first , and group 2 completed the paper version first . Results We recruited 52 women and 50 ( 96.2 % ) completed the study . Demographic data were similar for the two groups . There was no difference in total PISQ-12 score ( P = 0.41 ) and a high degree of correlation between versions ( r = 0.88 ) . Women preferred the web-based PISQ-12 ( 77.6 % ) over the paper-based version . Conclusion The web-based version of the PISQ-12 is a reliable alternative to the st and ard paper-based version and was preferred by women in this study regardless of age , race , and education BACKGROUND Guided self-management is an important component of asthma care . Most trials have evaluated paper-based strategies . The effectiveness of new communication technologies remains uncertain . OBJECTIVES To compare the feasibility and clinical outcomes of a st and ard paper-based asthma self-management strategy with web-based strategies . METHODS In a crossover trial , 21 patients using inhaled corticosteroids and long-acting B2-agonists ( mean [ SD ] age 29 [ 10 ] years ) were r and omly assigned to use a sequence of web-based and paper-based diary and action plan . Quality of life , asthma control , lung function , and airway inflammation were assessed using the Asthma Life Quality Question naire ( ALQ ) , Asthma Control Question naire ( ACQ-5 ) , Mini Asthma Quality of Life Question naire ( Mini AQLQ ) , and office spirometry . The ratio of forced expiratory volume in the first second of expiration ( FEV1 ) to peak expiratory flow ( PEF ) rate ( PiKo-1 ) and fraction of exhaled nitric oxide ( FE(NO ) ) were monitored . The main clinical outcomes were asthma control and FE(NO ) . Quality of data and adherence to monitoring tools were the main process outcomes . RESULTS Significant improvements were observed in the AQL and ACQ scores , although lung function did not change . FE(NO ) was significantly reduced only after a web-based strategy but a significant period effect occurred ( P = .006 ) . There were no differences in clinical outcomes between web-based and paper-based management . No intervention-related adverse effects were observed . Adherence seemed higher with the paper-based strategy ( P < .001 ) . However , paper data were unreliable when compared to automatic daily electronic FEV1/PEF records . Twelve patients were very interested in continuing self-management with the web-based approach compared with 2 in using paper tools ( P = .002 ) . CONCLUSIONS Web-based management was feasible , safe , and preferred by patients . Short-term outcomes were at least as good , and data quality was improved OBJECTIVE To assess the measurement equivalence of an interactive voice response ( IVR ) version of the EQ-5D with the original paper version . METHODS Subjects were r and omly assigned to : 1 ) paper then IVR , or 2 ) IVR then paper and asked to complete the question naire two days apart . The analyses tested mean differences ( repeated measures analysis of variance ) and reliability ( intraclass correlation coefficient [ ICC ] ) . Equivalence of the means was established if the 95 % confidence interval ( CI ) of the mean difference was within the minimally important difference interval : -0.035 to 0.035 for the EQ-5D index and -3 to 3 for the visual analog scale ( EQ VAS ) . ICC adequacy was tested by comparing the ICC 95 % lower CI with a critical value of 0.70 . RESULTS The analyses included 113 subjects for the index and 109 subjects for the EQ VAS . For the index , the adjusted means of the paper and IVR versions were 0.789 ± 0.016 and 0.798 ± 0 . 017 , respectively . The 95 % CI of the mean difference was -0.024 to 0.006 , within the equivalence interval . The ICC was 0.894 ( 95 % lower CI 0.857 ) , significantly greater than 0.70 . For the EQ VAS , the adjusted means were 71.94 ± 1.87 for paper and 74.63 ± 1.79 for IVR . The 95 % CI of the mean difference was -4.347 to -1.049 , partially within the equivalence interval . The ICC was 0.887 ( 95 % lower CI 0.840 ) , significantly greater than 0.70 . CONCLUSIONS The results provide evidence that the EQ-5D scores on the IVR version were sufficiently equivalent to those obtained on the paper version OBJECTIVES The primary aim was to assess the equivalence of an Internet-based chronic obstructive pulmonary disease- population screener ( COPD -PS ) relative to a vali date d paper- and -pencil version . A secondary aim was to compare groups based on known COPD risk factors , such as smoking status and gender . METHODS Using an online panel survey organization , participants were r and omized to internet or paper- and -pencil assessment where they completed the COPD -PS and other study forms . A subset of respondents also completed a test-retest reliability assessment . Finally , several thous and additional online respondents completed the COPD -PS for risk factor analyses . RESULTS A total of 1006 adults completed the r and omized study ( N = 504 online , N = 502 by mail ) . There were no differences between the arms in mean COPD -PS scores ( mean difference : 0.12 ; 95 % confidence interval : -0.14-+0.37 ; P = 0.365 ) . In the web arm , 106/504 ( 21.0 % ) exceeded the screening cut-off compared to 101/502 ( 20.1 % ) in the paper-administration arm ( difference in proportions : 0.9 % ; 95 % confidence interval : -4.1%-+5.9 % ; P = 0.720 ) . Subgroup analyses on a separate cohort of 3001 adults demonstrated hypothesized differences between groups defined by smoking status , presence of COPD , and shortness of breath . CONCLUSION The methods of administration that were evaluated in this study ( internet vs. paper and pencil ) result ed in no significant differences in COPD -PS mean scores . Furthermore , the predictive utility of the COPD -PS was not different between methods of administration , even after accounting for age and smoking status ABSTRACT Objective : Following the recent introduction of h and -held computers to be used by patients instead of conventional pencil- and -paper question naires , a validation study under ’ real-life ‚ conditions was conducted , in order to compare these two clinical instruments when used by chronic pain patients to describe their pain using visual and numerical rating scales . Method : Each of 200 chronic pain patients attending a single physician 's practice was given two pain question naires to complete , one on paper and one on a h and -held computer ; completion of these took place directly before and after consultation , in r and omised order . The questions asked in the two question naires were identical : present pain , average pain , worst pain and those of the painDETECT question naire ( the latter distinguishes characteristic symptoms of nociceptive pain ) . In accordance with st and ard practice , the paper question naire used numerical rating scales and the electronic one employed visual analogue scales , with or without a numerical indicator . Results : Nearly all patients ( 99 % ) of the study population ( 58 % female ; aged 57 ± 14 years ) completed both question naires . In spite of the expected substantial intra-individual scatter , overall results from the two question naire types were highly consistent . Only a few differences of potential statistical significance ( p < 5 % ) were observed , and none were found that would have led to different interpretations . No difference was seen between results from the electronic visual analogue scales with and without a numerical indicator . Conclusion : Under conditions of routine clinical practice , the h and -held computer question naire can give results equivalent to those obtained with the conventional paper question naire AIM To adapt the Asthma Quality of Life Question naire ( AQLQ(S ) ) , the Asthma Control Question naire ( ACQ ) and the Rhinoconjunctivitis Quality of Life Question naire ( RQLQ(S ) ) for a personal digital assistant ( Palm TX ) and to examine the validity of the electronic versions by comparing them with the original paper versions . METHODS 84 adults with asthma and 32 with rhinitis were r and omised to complete either the paper or the electronic version first . After 2h , they completed the other version . RESULTS 68 asthma and 27 rhinitis patients provided analysable data . For the AQLQ(S ) and RQLQ(S ) differences between paper and electronic were significant . Concordance between paper and electronic , evaluated using an intraclass correlation coefficient were : AQLQ=0.92 , ACQ=0.90 and RQLQ=0.85 . Concordance for the individual domains of the AQLQ and RQLQ ranged from 0.52 to 0.94 . These levels of concordance did not reach the a priori defined requirement for validity . CONCLUSIONS The significant bias between paper and electronic versions and only modest concordance provides evidence that patients may respond differently to question naires in different formats and show that different formats must not be used interchangeably OBJECTIVES The goal of this study was to provide recommended steps to assess measurement comparability using a crossover study design and to demonstrate these steps using a short patient-reported outcome ( PRO ) instrument as an example . METHODS The example PRO instrument was administered via paper , Web , interactive voice response system , and interview ; a r and omized crossover design was used to gather data across the multiple administration types . Participants completed the PRO instrument , demographic and health questions , and a short preference question naire . Evaluation included comparisons of the item-level responses and agreement , comparison of mean scale scores , score classifications , and questions design ed to collect usability and administration preference . Here the authors provide a four-step evaluation guide to evaluate measurement comparability and illustrate these steps using a case-finding tool . RESULTS In the example , item-level kappa statistics between the paper and the alternate versions ranged from good to excellent , intraclass correlation coefficient for mean scores were above 0.70 , and the rate of disagreement ranged from 2 % to 14 % . In addition , although participants had an administration preference , they reported few difficulties with the versions they were assigned . CONCLUSIONS The steps described in this article provide a guide for evaluating whether to combine scores across administration versions to simplify analyses and interpretation under a crossover design . The guide recommends the investigation of item-level responses , summary scores , and participant usability/preference when comparing versions , with each step providing unique information to support comprehensive evaluation and informed decisions regarding whether to combine data We compared the administration of the 9-item Patient Health Question naire ( PHQ-9 ) to assess depressive symptoms using interactive voice response ( IVR ) technology with the method of administration using paper- and -pencil . Data were collected from 51 veterans participating in an 8-week r and omized controlled trial of an illness management programme for heart failure . To counter possible bias in answering questions via IVR technology , the anchoring responses of the PHQ-9 question naire were reversed so that lower numbers corresponded to more severe depression . The mean for the pencil- and -paper administered PHQ-9 was 4.1 ( SD = 4.5 ) and the mean for IVR administration was 2.8 ( SD = 3.1 ) . The internal consistency ( Cronbach 's alpha ) of the PHQ-9 was 0.76 for IVR administration and 0.82 for paper administration . The intraclass correlation coefficient for the two modes of administration was 0.65 , indicating moderate agreement . IVR administration of the PHQ-9 produces similar results to pencil- and -paper administration , but the former is not as sensitive to higher levels of depressive symptom severity . This suggests that a lower threshold for probable depression is warranted when assessing depressive symptoms with IVR |
13,371 | 27,355,649 | This systematic review and meta- analysis suggests relatively small or neutral overall associations of butter with mortality , CVD , and diabetes . | BACKGROUND Dietary guidelines recommend avoiding foods high in saturated fat .
Yet , emerging evidence suggests cardiometabolic benefits of dairy products and dairy fat .
Evidence on the role of butter , with high saturated dairy fat content , for total mortality , cardiovascular disease , and type 2 diabetes remains unclear . | Background It is unknown whether individuals at high cardiovascular risk sustain a benefit in cardiovascular disease from increased olive oil consumption . The aim was to assess the association between total olive oil intake , its varieties ( extra virgin and common olive oil ) and the risk of cardiovascular disease and mortality in a Mediterranean population at high cardiovascular risk . Methods We included 7,216 men and women at high cardiovascular risk , aged 55 to 80 years , from the PREvención con DIeta MEDiterránea ( PREDIMED ) study , a multicenter , r and omized , controlled , clinical trial . Participants were r and omized to one of three interventions : Mediterranean Diets supplemented with nuts or extra-virgin olive oil , or a control low-fat diet . The present analysis was conducted as an observational prospect i ve cohort study . The median follow-up was 4.8 years . Cardiovascular disease ( stroke , myocardial infa rct ion and cardiovascular death ) and mortality were ascertained by medical records and National Death Index . Olive oil consumption was evaluated with vali date d food frequency question naires . Multivariate Cox proportional hazards and generalized estimating equations were used to assess the association between baseline and yearly repeated measurements of olive oil intake , cardiovascular disease and mortality . Results During follow-up , 277 cardiovascular events and 323 deaths occurred . Participants in the highest energy-adjusted tertile of baseline total olive oil and extra-virgin olive oil consumption had 35 % ( HR : 0.65 ; 95 % CI : 0.47 to 0.89 ) and 39 % ( HR : 0.61 ; 95 % CI : 0.44 to 0.85 ) cardiovascular disease risk reduction , respectively , compared to the reference . Higher baseline total olive oil consumption was associated with 48 % ( HR : 0.52 ; 95 % CI : 0.29 to 0.93 ) reduced risk of cardiovascular mortality . For each 10 g/d increase in extra-virgin olive oil consumption , cardiovascular disease and mortality risk decreased by 10 % and 7 % , respectively . No significant associations were found for cancer and all-cause mortality . The associations between cardiovascular events and extra virgin olive oil intake were significant in the Mediterranean diet intervention groups and not in the control group . Conclusions Olive oil consumption , specifically the extra-virgin variety , is associated with reduced risks of cardiovascular disease and mortality in individuals at high cardiovascular risk . Trial registration This study was registered at controlled-trials.com ( http://www.controlled-trials.com/IS RCT N35739639 ) . International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 35739639 . Registration date : 5 October 2005 Background Evidence regarding the role of dairy fat intake in cardiovascular disease ( CVD ) has been mixed and inconclusive . Most earlier studies have used self‐reported measures of dietary intake and focused on relatively racially homogeneous population s. Circulating biomarkers of dairy fat in a multiethnic cohort provide objective measures of dairy fat intake and facilitate conclusions relevant to population s with different diets and susceptibility to CVD . Methods and Results In a multiethnic cohort of 2837 US adults aged 45 to 84 years at baseline ( 2000–2002 ) , phospholipid fatty acids including 15:0 , 14:0 , and trans‐16:1n7 were measured using st and ardized methods , and the incidence of CVD prospect ively adjudicated . Self‐reported whole‐fat dairy and butter intakes had strongest associations with 15:0 , rather than 14:0 or trans‐16:1n7 . In multivariate models including demographics and lifestyle and dietary habits , each SD‐unit of 15:0 was associated with 19 % lower CVD risk ( hazard ratio [ 95 % CI ] 0.81 [ 0.68 to 0.98 ] ) and 26 % lower coronary heart disease ( CHD ) risk ( 0.74 [ 0.60 to 0.92 ] ) . Associations were strengthened after mutual adjustment for 14:0 and trans‐16:1n‐7 and were similar after adjustment for potential mediators . Plasma phospholipid 14:0 and trans‐16:1n‐7 were not significantly associated with incident CVD or CHD . All findings were similar in white , black , Hispanic , and Chinese American participants . Conclusion Plasma phospholipid 15:0 , a biomarker of dairy fat , was inversely associated with incident CVD and CHD , while no association was found with phospholipid 14:0 and trans‐16:1n‐7 . These findings support the need for further investigation of CVD effects of dairy fat , dairy‐specific fatty acids , and dairy products in general OBJECTIVE To examine associations between type 2 diabetes and fiber , glycemic load ( GL ) , dietary glycemic index ( GI ) , and fiber-rich foods . RESEARCH DESIGN AND METHODS This was a prospect i ve study of 36,787 men and women aged 40 - 69 years without diabetes . For all self-reported cases of diabetes at 4-year follow-up , confirmation of diagnosis was sought from medical practitioners . Case subjects were those who reported diabetes at follow-up and for whom there was no evidence that they did not have type 2 diabetes . Data were analyzed with logistic regression , adjusting for country of birth , physical activity , family history of diabetes , alcohol and energy intake , education , 5-year weight change , sex , and age . RESULTS Follow-up was completed by 31,641 ( 86 % ) participants , and 365 cases were identified . The odds ratio ( OR ) for the highest quartile of white bread intake compared with the lowest was 1.37 ( 95 % CI 1.04 - 1.81 ; P for trend = 0.001 ) . Intakes of carbohydrate ( OR per 200 g/day 0.58 , 0.36 - 0.95 ) , sugars ( OR per 100 g/day 0.61 , 0.47 - 0.79 ) , and magnesium ( OR per 500 mg/day 0.62 , 0.43 - 0.90 ) were inversely associated with incidence of diabetes , whereas intake of starch ( OR per 100 g/day 1.47 , 1.06 - 2.05 ) and dietary GI ( OR per 10 units 1.32 , 1.05 - 1.66 ) were positively associated with diabetes . These relationships were attenuated after adjustment for BMI and waist-to-hip ratio . CONCLUSIONS Reducing dietary GI while maintaining a high carbohydrate intake may reduce the risk of type 2 diabetes . One way to achieve this would be to substitute white bread with low-GI breads Summary Background Conflicting evidence exists regarding the association between saturated fatty acids ( SFAs ) and type 2 diabetes . In this longitudinal case-cohort study , we aim ed to investigate the prospect i ve associations between objective ly measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants . Methods The EPIC-InterAct case-cohort study includes 12 403 people with incident type 2 diabetes and a representative subcohort of 16 154 individuals who were selected from a cohort of 340 234 European participants with 3·99 million person-years of follow-up ( the EPIC study ) . Incident type 2 diabetes was ascertained until Dec 31 , 2007 , by a review of several sources of evidence . Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids ( mol% ) ; sample s from people with type 2 diabetes and subcohort participants were processed in a r and om order by centre , and laboratory staff were masked to participant characteristics . We estimated country-specific hazard ratios ( HRs ) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression , which is weighted for case-cohort sampling , and pooled our findings using r and om-effects meta- analysis . Findings SFAs accounted for 46 % of total plasma phospholipid fatty acids . In adjusted analyses , different individual SFAs were associated with incident type 2 diabetes in opposing directions . Even-chain SFAs that were measured ( 14:0 [ myristic acid ] , 16:0 [ palmitic acid ] , and 18:0 [ stearic acid ] ) were positively associated with incident type 2 diabetes ( HR [ 95 % CI ] per SD difference : myristic acid 1·15 [ 95 % CI 1·09–1·22 ] , palmitic acid 1·26 [ 1·15–1·37 ] , and stearic acid 1·06 [ 1·00–1·13 ] ) . By contrast , measured odd-chain SFAs ( 15:0 [ pentadecanoic acid ] and 17:0 [ heptadecanoic acid ] ) were inversely associated with incident type 2 diabetes ( HR [ 95 % CI ] per 1 SD difference : 0·79 [ 0·73–0·85 ] for pentadecanoic acid and 0·67 [ 0·63–0·71 ] for heptadecanoic acid ) , as were measured longer-chain SFAs ( 20:0 [ arachidic acid ] , 22:0 [ behenic acid ] , 23:0 [ tricosanoic acid ] , and 24:0 [ lignoceric acid ] ) , with HRs ranging from 0·72 to 0·81 ( 95 % CIs ranging between 0·61 and 0·92 ) . Our findings were robust to a range of sensitivity analyses . Interpretation Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions , which suggests that SFAs are not homogeneous in their effects . Our findings emphasise the importance of the recognition of subtypes of these fatty acids . An improved underst and ing of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed . Funding EU FP6 programme , Medical Research Council Epidemiology Unit , Medical Research Council Human Nutrition Research , and Cambridge Lipidomics Biomarker Research Initiative Using lipidomic method ologies the impact that meal lipid composition and metabolic syndrome ( MetS ) exerts on the postpr and ial chylomicron triacylglycerol ( TAG ) response was examined . Males ( 9 control ; 11 MetS ) participated in a r and omised crossover trial ingesting two high fat breakfast meals composed of either dairy-based foods or vegetable oil-based foods . The postpr and ial lipidomic molecular composition of the TAG in the chylomicron-rich ( CM ) fraction was analysed with t and em mass spectrometry coupled with liquid chromatography to profile CM TAG species and targeted TAG regioisomers . Postpr and ial CM TAG concentrations were significantly lower after the dairy-based foods compared with the vegetable oil-based foods for both control and MetS subjects . The CM TAG response to the ingested meals involved both significant and differential depletion of TAG species containing shorter- and medium-chain fatty acids ( FA ) and enrichment of TAG molecular species containing C16 and C18 saturated , monounsaturated and diunsaturated FA . Furthermore , there were significant changes in the TAG species between the food TAG and CM TAG and between the 3- and 5-h postpr and ial sample s for the CM TAG regioisomers . Unexpectedly , the postpr and ial CM TAG concentration and CM TAG lipidomic responses did not differ between the control and MetS subjects . Lipidomic analysing of CM TAG molecular species revealed dynamic changes in the molecular species of CM TAG during the postpr and ial phase suggesting either preferential CM TAG species formation and /or clearance Background / Objectives : Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes ( T2D ) risk , but studies on foods high in fat per unit weight are sparse . We assessed whether the intake of vegetable oil , butter , margarine , nuts and seeds and cakes and cookies is related to incident T2D.Subjects/ Methods : A case-cohort study was conducted , nested within eight countries of the European Prospect i ve Investigation into Cancer ( EPIC ) , with 12 403 incident T2D cases and a subcohort of 16 835 people , identified from a cohort of 340 234 people . Diet was assessed at baseline ( 1991–1999 ) by country-specific question naires . Country-specific hazard ratios ( HRs ) across four categories of fatty foods ( nonconsumers and tertiles among consumers ) were combined with r and om-effects meta- analysis . Results : After adjustment not including body mass index ( BMI ) , nonconsumers of butter , nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption . Among consumers , cakes and cookies were inversely related to T2D ( HRs across increasing tertiles 1.14 , 1.00 and 0.92 , respectively ; P-trend < 0.0001 ) . All these associations attenuated upon adjustment for BMI , except the higher risk of nonconsumers of cakes and cookies ( HR 1.57 ) . Higher consumption of margarine became positively associated after BMI adjustment ( HRs across increasing consumption tertiles : 0.93 , 1.00 and 1.12 ; P-trend 0.03 ) . Within consumers , vegetable oil , butter and nuts and seeds were unrelated to T2D . Conclusions : Fatty foods were generally not associated with T2D , apart from weak positive association for margarine . The higher risk among nonconsumers of cakes and cookies needs further explanation IMPORTANCE Epidemiologic studies have suggested that higher intake of added sugar is associated with cardiovascular disease ( CVD ) risk factors . Few prospect i ve studies have examined the association of added sugar intake with CVD mortality . OBJECTIVE To examine time trends of added sugar consumption as percentage of daily calories in the United States and investigate the association of this consumption with CVD mortality . DESIGN , SETTING , AND PARTICIPANTS National Health and Nutrition Examination Survey ( NHANES , 1988 - 1994 [ III ] , 1999 - 2004 , and 2005 - 2010 [ n = 31,147 ] ) for the time trend analysis and NHANES III Linked Mortality cohort ( 1988 - 2006 [ n = 11 733 ] ) , a prospect i ve cohort of a nationally representative sample of US adults for the association study . MAIN OUTCOMES AND MEASURES Cardiovascular disease mortality . RESULTS Among US adults , the adjusted mean percentage of daily calories from added sugar increased from 15.7 % ( 95 % CI , 15.0%-16.4 % ) in 1988 - 1994 to 16.8 % ( 16.0%-17.7 % ; P = .02 ) in 1999 - 2004 and decreased to 14.9 % ( 14.2%-15.5 % ; P < .001 ) in 2005 - 2010 . Most adults consumed 10 % or more of calories from added sugar ( 71.4 % ) and approximately 10 % consumed 25 % or more in 2005 - 2010 . During a median follow-up period of 14.6 years , we documented 831 CVD deaths during 163,039 person-years . Age- , sex- , and race/ethnicity-adjusted hazard ratios ( HRs ) of CVD mortality across quintiles of the percentage of daily calories consumed from added sugar were 1.00 ( reference ) , 1.09 ( 95 % CI , 1.05 - 1.13 ) , 1.23 ( 1.12 - 1.34 ) , 1.49 ( 1.24 - 1.78 ) , and 2.43 ( 1.63 - 3.62 ; P < .001 ) , respectively . After additional adjustment for sociodemographic , behavioral , and clinical characteristics , HRs were 1.00 ( reference ) , 1.07 ( 1.02 - 1.12 ) , 1.18 ( 1.06 - 1.31 ) , 1.38 ( 1.11 - 1.70 ) , and 2.03 ( 1.26 - 3.27 ; P = .004 ) , respectively . Adjusted HRs were 1.30 ( 95 % CI , 1.09 - 1.55 ) and 2.75 ( 1.40 - 5.42 ; P = .004 ) , respectively , comparing participants who consumed 10.0 % to 24.9 % or 25.0 % or more calories from added sugar with those who consumed less than 10.0 % of calories from added sugar . These findings were largely consistent across age group , sex , race/ethnicity ( except among non-Hispanic blacks ) , educational attainment , physical activity , health eating index , and body mass index . CONCLUSIONS AND RELEVANCE Most US adults consume more added sugar than is recommended for a healthy diet . We observed a significant relationship between added sugar consumption and increased risk for CVD mortality Epidemiological studies conducted thus far have mainly used a single-nutrient approach which may not be sufficient in detecting diet-cancer relationships . The aim of the study was to examine the association of a food pattern based on explained variations in fatty acid intake by means of reduced rank regression with breast cancer risk . Study participants were female subjects ( n 15,351 ) of the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Potsdam Study free of cancer at baseline and with complete dietary and outcome information followed for an average of 6.0 years . Among those , 137 incident cases of invasive breast cancer were identified . We identified a food pattern characterized by low consumption of bread , and fruit juices , and high consumption of processed meat , fish , butter and other animal fats , and margarine explaining > 42 % of total variation in fatty acid intake ( SFA , MUFA , n-3 PUFA , n-6 PUFA ) . Intake of all four fatty acid fractions was positively associated with the pattern score . Adherence to this food pattern adjusted for covariates was associated with a two-fold risk ( hazard ratio 2.00 ; 95 % CI 1.30 , 3.09 ) of breast cancer comparing extreme tertiles of the pattern score . There was no evidence of effect modification by menopausal status , overweight status and use of hormone replacement therapy , respectively . In conclusion , a food pattern characterized by high-fat food choices was significantly associated with increased risk of breast cancer . Given that the food pattern was high in all fatty acid fractions , we found evidence for total dietary fat rather than for specific fatty acids to be associated with breast cancer risk OBJECTIVE Studies examining the association of dairy consumption with incident CHD have yielded inconsistent results . The current prospect i ve study examined the association between dairy consumption and CHD in a population -based sample of older community-dwelling adults . DESIGN Baseline CHD risk factors were assessed and an FFQ was self-administered . Participants were followed for morbidity and mortality with periodic clinic visits and annual mailed question naires for an average of 16?2 years , with a 96 % follow-up rate for fatal and non-fatal CHD . SETTING Community . SUBJECTS Participants were 751 men and 1008 women aged 50–93 years who attended a clinic visit in 1984–1987 . RESULTS At baseline the mean age was 70.6 ( SD 9.8 ) years for men and 70.1 ( SD 9.3 ) years for women . Participants who developed CHD during follow-up were significantly older ( P < 0.001 ) , had higher BMI ( P = 0.035 ) and higher total cholesterol ( P = 0.050 ) , and were more likely to be male ( P < 0.001 ) , diabetic ( P = 0.011 ) and hypertensive ( P < 0.001 ) , than those who did not develop CHD . Multivariate regression analyses adjusting for age , BMI , diabetes , hypertension , LDL-cholesterol and oestrogen use ( in women ) indicated that women who consumed low-fat cheese ‘ sometimes/often ’ and women who consumed non-fat milk ‘ sometimes/often ’ had an increased risk of incident CHD ( hazard ratio 52.32 ; 95 % CI 1.57 , 3.41 ) and CHD ( hazard ratio 51.48 ; 95 % CI 1.02 , 2.16 ) compared with women who ‘ never/rarely ’ ate these dairy products . CONCLUSIONS Woman with higher intake of low-fat cheese and non-fat milk seem to have a higher risk of incident CHD . This needs further investigation considering recent evidence of cardiovascular benefits from certain dairy fat OBJECTIVE Oxidative stress plays a major role in the pathogenesis and progression of diabetes . Among various functional foods with an antioxidant effect , probiotic foods have been reported to repress oxidative stress . The objective of this clinical trial was to assess the effects of probiotic and conventional yogurt on blood glucose and antioxidant status in type 2 diabetic patients . METHODS Sixty-four patients with type 2 diabetes mellitus , 30 to 60 y old , were assigned to two groups in this r and omized , double-blind , controlled clinical trial . The patients in the intervention group consumed 300 g/d of probiotic yogurt containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 and those in the control group consumed 300 g/d of conventional yogurt for 6 wk . Fasting blood sample s , 24-h dietary recalls , and anthropometric measurements were collected at the baseline and at the end of the trial . RESULTS Probiotic yogurt significantly decreased fasting blood glucose ( P < 0.01 ) and hemoglobin A1c ( P < 0.05 ) and increased erythrocyte superoxide dismutase and glutathione peroxidase activities and total antioxidant status ( P < 0.05 ) compared with the control group . In addition , the serum malondialdehyde concentration significantly decreased compared with the baseline value in both groups ( P < 0.05 ) . No significant changes from baseline were shown in insulin concentration and erythrocyte catalase activity within either group ( P > 0.05 ) . CONCLUSION The consumption of probiotic yogurt improved fasting blood glucose and antioxidant status in type 2 diabetic patients . These results suggest that probiotic yogurt is a promising agent for diabetes management BACKGROUND Plasma phospholipid concentrations of trans-palmitoleic acid ( trans-16:1n-7 ) , a biomarker of dairy fat intake , are inversely associated with incident type 2 diabetes in 2 US cohorts . OBJECTIVE The objective was to investigate whether the intake of trans-16:1n-7 in particular , or dairy fat in general , is associated with glucose tolerance and key factors determining glucose tolerance . DESIGN A cross-sectional investigation was undertaken in 17 men and women with nonalcoholic fatty liver disease and 15 body mass index ( BMI ) - and age-matched controls . The concentrations of trans-16:1n-7 and 2 other biomarkers of dairy fat intake , 15:0 and 17:0 , were measured in plasma phospholipids and free fatty acids ( FFAs ) . Liver fat was estimated by computed tomography-derived liver-spleen ratio . Intravenous-glucose-tolerance tests and oral-glucose-tolerance test ( OGTT ) and hyperinsulinemic-euglycemic clamps were performed to assess β-cell function and hepatic and systemic insulin sensitivity . RESULTS In multivariate analyses adjusted for age , sex , and BMI , phospholipid 17:0 , phospholipid trans-16:1n-7 , FFA 15:0 , and FFA 17:0 were inversely associated with fasting plasma glucose , the area under the curve for glucose during an OGTT , and liver fat . Phospholipid trans-16:1n-7 was also positively associated with hepatic and systemic insulin sensitivity . None of the biomarkers were associated with β-cell function . The associations between dairy fat intake and glucose tolerance were attenuated by adjusting for insulin sensitivity or liver fat , but strengthened by adjusting for β-cell function . CONCLUSION Although we can not rule out reverse causation , these data support the hypothesis that dairy fat improves glucose tolerance , possibly through a mechanism involving improved hepatic and systemic insulin sensitivity and reduced liver fat Assessment of eating habits ( EH ) through closed questions could be an alternative tool to assess diet as a predictor of weight change in epidemiological studies . The aim was to assess the association between baseline EH and the risk of weight gain or becoming overweight/obese in a Spanish dynamic prospect i ve cohort ( the Seguimiento Universidad de Navarra Project ) of 10 509 participants . The baseline question naire included ten short questions with two possible answers : yes or no. We calculated a baseline EH score , categorised in quartiles , positively weighting answers on more fruit , vegetables , fish and fibre and less meat , sweets and pastries , fat , butter , fatty meats and added sugar in drinks . Reducing the consumption of meat or fat and removing fat from meat were significantly associated with lower weight gain . The partial correlation coefficient between EH score and weight change was - 0·033 ( P = 0·001 ) . We observed 1063 cases of incident overweight/obesity among 7217 participants without overweight/obesity at baseline . Trying to eat more fruit , fish or fibre and less meat was inversely significantly associated with incident overweight/obesity . Those participants in the upper quartile of the score were at a 38 % ( adjusted OR 0·62 ; 95 % CI 0·48 , 0·81 ) lower risk of developing overweight/obesity during the follow-up compared with those in the lower quartile . However , the receiver-operating characteristic curves for the model with and without the EH score were material ly identical . Despite the apparent significant inverse association , this score had a low predictive value for future weight gain and for incident overweight/obesity in a Mediterranean population , although some EH were independently and positively associated with weight gain OBJECTIVE To determine whether responses to simple dietary questions are associated with specific causes of death . DESIGN Self-reported frequency intakes of various classes of foods and data on confounding factors were collected at the baseline survey . Death notifications up to 31 December 1997 were ascertained from the Office for National Statistics . Relative risk ( RR ) of death and 95 % confidence intervals ( CI ) associated with baseline dietary factors were calculated by Cox regression . SETTING Prospect i ve follow-up study based on five UK general practice s. SUBJECTS Data were used from 11,090 men and women aged 35 - 64 years ( 81 % of the eligible patient population ) who responded to a postal question naire in 1989 . RESULTS After 9 years of follow-up , 598 deaths were recorded , 514 of these among the 10,522 subjects with no previous history of angina . All-cause mortality was positively associated with age , smoking and low social class , as expected . Among the dietary variables , all-cause mortality was significantly reduced in participants who reported relatively high consumption of vegetables , puddings , cakes , biscuits and sweets , fresh or frozen red meat ( but not processed meat ) , among those who reported using polyunsaturated spreads and among moderate alcohol drinkers . These associations were broadly similar for deaths from ischaemic heart disease ( IHD ) , cancer and all other causes combined , and were not greatly attenuated by adjusting for potential confounding factors including social class . CONCLUSIONS Responses to simple questions about nutrition were associated with mortality . These findings must be interpreted with caution since residual confounding by dietary and lifestyle factors may underlie the associations BACKGROUND Because of differences in processing and nutrients , brown rice and white rice may have different effects on risk of type 2 diabetes mellitus . We examined white and brown rice consumption in relation to type 2 diabetes risk prospect ively in the Health Professionals Follow-up Study and the Nurses ' Health Study I and II . METHODS We prospect ively ascertained and up date d diet , lifestyle practice s , and disease status among 39,765 men and 157,463 women in these cohorts . RESULTS After multivariate adjustment for age and other lifestyle and dietary risk factors , higher intake of white rice ( > or = 5 servings per week vs < 1 per month ) was associated with a higher risk of type 2 diabetes : pooled relative risk ( 95 % confidence interval [ CI ] ) , 1.17 ( 1.02 - 1.36 ) . In contrast , high brown rice intake ( > or = 2 servings per week vs < 1 per month ) was associated with a lower risk of type 2 diabetes : pooled relative risk , 0.89 ( 95 % CI , 0.81 - 0.97 ) . We estimated that replacing 50 g/d ( cooked , equivalent to one-third serving per day ) intake of white rice with the same amount of brown rice was associated with a 16 % ( 95 % CI , 9%-21 % ) lower risk of type 2 diabetes , whereas the same replacement with whole grains as a group was associated with a 36 % ( 30%-42 % ) lower diabetes risk [ corrected ] . CONCLUSIONS Substitution of whole grains , including brown rice , for white rice may lower risk of type 2 diabetes . These data support the recommendation that most carbohydrate intake should come from whole grains rather than refined grains to help prevent type 2 diabetes Aims /hypothesisThus far , it is unclear whether lifestyle recommendations for people with diabetes should be different from those for the general public . We investigated whether the associations between lifestyle factors and mortality risk differ between individuals with and without diabetes . Methods Within the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) , a cohort was formed of 6,384 persons with diabetes and 258,911 EPIC participants without known diabetes . Joint Cox proportional hazard regression models of people with and without diabetes were built for the following lifestyle factors in relation to overall mortality risk : BMI , waist/height ratio , 26 food groups , alcohol consumption , leisure-time physical activity , smoking . Likelihood ratio tests for heterogeneity assessed statistical differences in regression coefficients . Results Multivariable adjusted mortality risk among individuals with diabetes compared with those without was increased , with an HR of 1.62 ( 95 % CI 1.51 , 1.75 ) . Intake of fruit , legumes , nuts , seeds , pasta , poultry and vegetable oil was related to a lower mortality risk , and intake of butter and margarine was related to an increased mortality risk . These associations were significantly different in magnitude from those in diabetes-free individuals , but directions were similar . No differences between people with and without diabetes were detected for the other lifestyle factors . Conclusions /interpretationDiabetes status did not substantially influence the associations between lifestyle and mortality risk . People with diabetes may benefit more from a healthy diet , but the directions of association were similar . Thus , our study suggests that lifestyle advice with respect to mortality for patients with diabetes should not differ from recommendations for the general population BACKGROUND Dairy consumption is linked to a lower risk of type 2 diabetes , but constituents responsible for this relation are not established . Emerging evidence suggests that trans-palmitoleate ( trans 16:1n-7 ) , a fatty acid in dairy and also partially hydrogenated oils , may be associated with a more favorable metabolic profile and less incident diabetes . OBJECTIVE We investigated the association of trans-palmitoleate with metabolic risk and incident diabetes in a multiethnic US cohort . DESIGN Phospholipid fatty acids and metabolic risk factors were measured in 2000 - 2002 among 2617 adults in the Multi-Ethnic Study of Atherosclerosis ( MESA ) , a cohort of white , black , Hispanic , and Chinese Americans . In 2281 participants free of baseline diabetes , we also prospect ively assessed the risk of new-onset diabetes ( 205 cases ) from baseline to 2005 - 2007 . RESULTS trans-Palmitoleate concentrations correlated positively with self-reported consumption of whole-fat dairy , butter , margarine , and baked desserts and with other circulating biomarkers of both dairy fat and partially hydrogenated oil consumption , which suggested mixed dietary sources . After multivariable adjustment , trans-palmitoleate concentrations were associated with higher LDL cholesterol ( quintile 5 compared with quintile 1 : + 6.4 % ; P-trend = 0.005 ) , lower triglycerides ( -19.1 % ; P-trend < 0.001 ) , lower fasting insulin ( -9.1 % ; P-trend = 0.002 ) , and lower systolic blood pressure ( -2.4 mm Hg ; P-trend = 0.01 ) . In prospect i ve analyses , trans-palmitoleate was independently associated with lower incident diabetes ( P-trend = 0.02 ) , including a 48 % lower risk in quintile 5 compared with quintile 1 ( HR : 0.52 ; 95 % CI : 0.32 , 0.85 ) . All findings were similar between men and women and between different race-ethnic subgroups . CONCLUSIONS Circulating trans-palmitoleate is associated with higher LDL cholesterol but also with lower triglycerides , fasting insulin , blood pressure , and incident diabetes in a multiethnic US cohort . Our findings support the need for further experimental and dietary intervention studies that target circulating trans-palmitoleate . The MESA trial was registered at clinical trials.gov as NCT00005487 Dietary medium chain fatty acids ( MCFA ) and linoleic acid follow different metabolic routes , and linoleic acid activates PPAR receptors . Both these mechanisms may modify lipoprotein and fatty acid metabolism after dietary intervention . Our objective was to investigate how dietary MCFA and linoleic acid supplementation and body fat distribution affect the fasting lipoprotein subclass profile , lipoprotein kinetics , and postpr and ial fatty acid kinetics . In a r and omized double blind cross-over trial , 12 male subjects ( age 51±7 years ; BMI 28.5±0.8 kg/m2 ) , were divided into 2 groups according to waist-hip ratio . They were supplemented with 60 grams/day MCFA ( mainly C8:0 , C10:0 ) or linoleic acid for three weeks , with a wash-out period of six weeks in between . Lipoprotein subclasses were measured using HPLC . Lipoprotein and fatty acid metabolism were studied using a combination of several stable isotope tracers . Lipoprotein and tracer data were analyzed using computational modeling . Lipoprotein subclass concentrations in the VLDL and LDL range were significantly higher after MCFA than after linoleic acid intervention . In addition , LDL subclass concentrations were higher in lower body obese individuals . Differences in VLDL metabolism were found to occur in lipoprotein lipolysis and uptake , not production ; MCFAs were elongated intensively , in contrast to linoleic acid . Dietary MCFA supplementation led to a less favorable lipoprotein profile than linoleic acid supplementation . These differences were not due to elevated VLDL production , but rather to lower lipolysis and uptake rates Background — The PREDIMED ( Prevención con Dieta Mediterránea ) r and omized primary prevention trial showed that a Mediterranean diet enriched with either extravirgin olive oil or mixed nuts reduces the incidence of stroke , myocardial infa rct ion , and cardiovascular mortality . We assessed the effect of these diets on the incidence of atrial fibrillation in the PREDIMED trial . Methods and Results — Participants were r and omly assigned to 1 of 3 diets : Mediterranean diet supplemented with extravirgin olive oil , Mediterranean diet supplemented with mixed nuts , or advice to follow a low-fat diet ( control group ) . Incident atrial fibrillation was adjudicated during follow-up by an events committee blinded to dietary group allocation . Among 6705 participants without prevalent atrial fibrillation at r and omization , we observed 72 new cases of atrial fibrillation in the Mediterranean diet with extravirgin olive oil group , 82 in the Mediterranean diet with mixed nuts group , and 92 in the control group after median follow-up of 4.7 years . The Mediterranean diet with extravirgin olive oil significantly reduced the risk of atrial fibrillation ( hazard ratio , 0.62 ; 95 % confidence interval , 0.45–0.85 compared with the control group ) . No effect was found for the Mediterranean diet with nuts ( hazard ratio , 0.89 ; 95 % confidence interval , 0.65–1.20 ) . Conclusions — In the absence of proven interventions for the primary prevention of atrial fibrillation , this post hoc analysis of the PREDIMED trial suggests that extravirgin olive oil in the context of a Mediterranean dietary pattern may reduce the risk of atrial fibrillation . Clinical Trial Registration — URL : http://www.controlled-trials.com . Unique identifier : IS RCT N35739639 |
13,372 | 27,512,052 | The reduction in office BP was more pronounced in hypertensive compared to normotensive individuals ( p < 0.01 ) , when using larger muscle groups ( p < 0.05 ) and when participants were recovering in the supine position ( p < 0.01 ) .
Conclusion A single bout of resistance exercise can have a BP-lowering effect that last for up to 24 hours .
Supine recovery and the use of larger muscle groups result ed in greater BP reductions after resistance exercise | Background Current exercise guidelines recommend aerobic types of exercises on most days of the week , supplemented with dynamic resistance exercise twice weekly .
Whereas the blood pressure (BP)-lowering effects of a single session of aerobic exercise have been well studied , less is known about the hypotensive effect of a single bout of resistance exercise .
Objectives To evaluate the transient effect of resistance exercise on BP by means of meta-analytic techniques . | PURPOSE To test the association between exercise mode and the recovery pattern of baroreflex sensitivity ( BRS ) after exercise . METHODS The study population included healthy male subjects ( N = 12 , age : 31 + /- 3 yr ) . Four different interventions were performed in a r and omized order : 1 ) aerobic exercise session on a bicycle ergometer , 2 ) light resistance exercise session , 3 ) heavy resistance exercise session , and 4 ) control intervention with no exercise . All interventions lasted 40 min . R-R intervals and continuous blood pressure were measured before ( 10 min ) and 30 - 180 min after the interventions . BRSLF was calculated by the transfer function method from the low-frequency b and ( LF , 0.04 - 0.15 Hz ) of the R-R intervals and systolic blood pressure spectra . RESULTS BRSLF had blunted until 30 min after aerobic and light resistance exercise ( 11.1 + /- 4.3 and 10.0 + /- 3.6 vs 17.5 + /- 7.0 ms.mm Hg(-1 ) , P = 0.002 for both , compared with the control intervention , respectively ) . However , BRSLF was significantly blunted until 60 min after heavy resistance exercise ( 9.3 + /- 2.3 vs 15.1 + /- 4.7 ms.mm Hg(-1 ) , P = 0.005 , compared with the control intervention ) . The high-frequency power of R-R intervals ( 0.15 - 0.4 Hz ) was significantly reduced , and the LF power of systolic blood pressure oscillation was significantly augmented 30 min after heavy resistance exercise ( P < 0.01 for both ) , whereas both indices were restored to the control level by 30 min after aerobic and light resistance exercise . CONCLUSION BRS after acute exercise is associated with exercise intensity , showing relatively rapid recovery after aerobic and light resistance exercise and delayed recovery after heavy resistance exercise . The delayed BRS pattern after heavy resistance exercise is regulated by delicate interplay between the withdrawal of vagal outflow and the probably increased sympathetic vasomotor tone documented by measurements of heart rate and blood pressure variability Decreased central arterial compliance is an emerging risk factor for cardiovascular disease . Resistance training is associated with reductions in the elastic properties of central arteries . Currently , it is not known whether this reduction is from one bout of resistance exercise or from an adaptation to multiple bouts of resistance training . Sixteen healthy sedentary or recreationally active adults ( 11 men and 5 women , age 27 + /- 1 yr ) were studied under parallel experimental conditions on 2 separate days . The order of experiments was r and omized between resistance exercise ( 9 resistance exercises at 75 % of 1 repetition maximum ) and sham control ( seated rest in the exercise room ) . Baseline hemodynamic values were not different between the two experimental conditions . Carotid arterial compliance ( via simultaneous B-mode ultrasound and applanation tonometry ) decreased and beta-stiffness index increased ( P < 0.01 ) immediately and 30 min after resistance exercise . Immediately after resistance exercise , carotid systolic blood pressure increased ( P < 0.01 ) , although no changes were observed in brachial systolic blood pressure at any time points . These measures returned to baseline values within 60 min after the completion of resistance exercise . No significant changes in these variables were observed during the sham control condition . These results indicate that one bout of resistance exercise acutely decreases central arterial compliance , but this effect is sustained for < 60 min after the completion of resistance exercise The occurrence of post-exercise hypotension after resistance exercise is controversial , and its mechanisms are unknown . To evaluate the effect of different resistance exercise intensities on post-exercise blood pressure ( BP ) , and hemodynamic and autonomic mechanisms , 17 normotensives underwent three experimental sessions : control ( C—40 min of rest ) , low- ( E40%—40 % of 1 repetition maximum , RM ) , and high-intensity ( E80%—80 % of 1 RM ) resistance exercises . Before and after interventions , BP , heart rate ( HR ) , and cardiac output ( CO ) were measured . Autonomic regulation was evaluated by normalized low- ( LFR – Rnu ) and high-frequency ( HFR – Rnu ) components of the R – R variability . In comparison with pre-exercise , systolic BP decreased similarly in the E40 % and E80 % ( −6 ± 1 and −8 ± 1 mmHg , P < 0.05 ) . Diastolic BP decreased in the E40 % , increased in the C , and did not change in the E80 % . CO decreased similarly in all the sessions ( −0.4 ± 0.2 l/min , P < 0.05 ) , while systemic vascular resistance ( SVR ) increased in the C , did not change in the E40 % , and increased in the E80 % . Stroke volume decreased , while HR increased after both exercises , and these changes were greater in the E80 % ( −11 ± 2 vs. −17 ± 2 ml/beat , and + 17 ± 2 vs. + 21 ± 2 bpm , P < 0.05 ) . LFR – Rnu increased , while ln HFR – Rnu decreased in both exercise sessions . In conclusion : Low- and high-intensity resistance exercises cause systolic post-exercise hypotension ; however , only low-intensity exercise decreases diastolic BP . BP fall is due to CO decrease that is not compensated by SVR increase . BP fall is accompanied by HR increase due to an increase in sympathetic modulation to the heart Abstract Post-exercise hypotension is an important event for blood pressure regulation , especially in hypertensive individuals . Although post-exercise hypotension is a well-known phenomenon , the mechanism responsible is still unclear . The kallikrein-kinin system is involved in blood pressure control , but its role in post-exercise hypotension has not yet been investigated . Thus , the purpose of this study was to investigate the involvement of the vasodilators bradykinin and des-Arg9-BK and kallikrein activity in post-exercise hypotension promoted by 35 min of cycle ergometer ( CE ) or circuit weight-training ( CWT ) bouts in normotensive and hypertensive individuals . A significant decrease in mean arterial pressure at 45 and 60 min after CE and 45 min after CWT was observed in normotensive individuals . Hypertensive values of mean arterial pressure were significantly reduced at 45 and 60 min after CE and at 60 min after CWT . Before exercise , plasma bradykinin concentrations and kallikrein activity were higher in hypertensive compared to normotensive volunteers . Kinin levels increased in the groups evaluated at the end of the training period and 60 min post-exercise . These data suggest that the kallikrein-kinin system may be involved in post-exercise hypotension in normotensive and hypertensive individuals subjected to CE and CWT bouts Post-exercise hypotension ( PEH ) , the reduction of blood pressure ( BP ) after a single bout of exercise , is of great clinical relevance . As the magnitude of this phenomenon seems to be dependent on pre-exercise BP values and chronic exercise training in hypertensive individuals leads to BP reduction ; PEH could be attenuated in this context . Therefore , the aim of the present study was to investigate whether PEH remains constant after resistance exercise training . Fifteen hypertensive individuals ( 46±8 years ; 88±16 kg ; 30±6 % body fat ; 150±13/93±5 mm Hg systolic/diastolic BP , SBP/DBP ) were withdrawn from medication and performed 12 weeks of moderate-intensity resistance training . Parameters of cardiovascular function were evaluated before and after the training period . Before the training program , hypertensive volunteers showed significant PEH . After an acute moderate-intensity resistance exercise session with three sets of 12 repetitions ( 60 % of one repetition maximum ) and a total of seven exercises , BP was reduced post-exercise ( 45–60 min ) by an average of aproximately −22 mm Hg for SBP , −8 mm Hg for DBP and −13 mm Hg for mean arterial pressure ( P<0.05 ) . However , this acute hypotensive effect did not occur after the 12 weeks of training ( P>0.05 ) . In conclusion , our data demonstrate that PEH , following an acute exercise session , can indeed be attenuated after 12 weeks of training in hypertensive stage 1 patients not using antihypertensive medication Objective To investigate the blood pressure ( BP ) responses to cardiovascular stress test after a combined exercise circuit session at moderate intensity . Method Twenty individuals ( 10 male/10 fem ; 33.4± 6.9 years ; 70.2± 15.8 kg ; 170.4± 11.5 cm ; 22.3± 6.8 % body fat ) were r and omized in a different days to control session with no exercise or exercise session consisting of 3 laps of the following circuit : knee extension , bench press , knee flexion , rowing in the prone position , squats , shoulder press , and 5 min of aerobic exercise at 75 - 85 % of age-predicted maximum heart rate and /or 13 on the Borg Rating of Perceived Exertion [ scale of 6 to 20 ] . The sets of resistance exercise consisted of 15 repetitions at ~50 % of the estimated 1 repetition maximum test . Systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) were measured at rest and during 1h of recovery in both experimental sessions . After that , blood pressure reactivity ( BPR ) was evaluated using the Cold Pressor Test . Results During 1h of exercise recovery , there was a reduction in SBP ( 3 - 6 mmHg ) and DBP ( 2 - 5 mmHg ) in relation to pre-session rest ( p<0.01 ) , while this reduction was not observed in the control session . A decline in BPR ( 4 - 7 mmHg ; p<0.01 ) was observed 1h post-exercise session , but not in the control session . Post-exercise reductions in SBP and DBP were significantly correlated with BPR reductions ( r=0.50 - 0.45 ; p<0.05 ) . Conclusion A combined exercise circuit session at moderate intensity promoted subsequent post-exercise hypotension and acutely attenuated BPR in response to a cardiovascular stress test . In addition , the post-exercise BP reduction was correlated with BPR attenuation in healthy adults of both genders This study examined cardiovascular responses as a function of time following exercise in which participants were exposed to a laboratory stressor . Ninety ( 42 women ) young ( 18 - 35 years old ) nonsmoking normotensive participants engaged in 30 min of high and low intensity ( 75 - 80 % and 50 - 55 % VO(2 ) max ) aerobic exercise and a sedentary control condition . Participants were r and omly assigned to a laboratory stressor 5 , 30 , or 60 min following the exercise bout . Results indicate that low and high intensity exercise significantly reduce heart rate ( HR ) and systolic and diastolic blood pressure reactivity and HR recovery values . An inverse relationship between intensity of exercise and subsequent cardiovascular reactivity was found . These findings suggest attenuated stress responses following acute exercise depend both on exercise intensity and the time of exposure to psychological stress following exercise Purpose To investigate the blood pressure responses during recovery after two protocol s of circuit resistance exercises ( CRE ) with different rest intervals ( RI ) . Methods Eleven normotensive males ( aged 19.5 ± 1.0 yrs , height 172.8 ± 5.7 cm and weight 65.1 ± 8.1 kg ) performed two CRE with RI of 30 ( RI30s ) and 40 ( RI40s ) seconds between the exercises r and omly , as well as a control session without exercise . The protocol s consisted of 3 circuits of 6 exercises with 10 repetitions maximum ( 10RM ) and 2 minute rest between circuits , followed by an 80 minute recovery period . Measurements were taken before exercise and at each 10 min of post-exercise recovery . The Analysis of Variance ( ANOVA ) with Repeated Measures ( group × time ) was used to analyze data , followed by post-hoc Bonferroni test , for P≤0.05 . Results Post-exercise hypotension of systolic blood pressure was observed after both CRE with RI30s and RI40s ( at R40 , R50 , R60 , R70 and R80 ) , whereas diastolic blood pressure did not differ from that measured at rest . In all measured moments , there was no significant difference between exercise trials in post-exercise levels of systolic and diastolic blood pressure . Conclusion CRE with RI30s and RI40s between the exercises can lead to occurrence of PEH similarly in magnitude and duration . Our findings suggest a potentially positive health benefit of strength training PURPOSE The purpose of this investigation was to examine selected psychobiological responses to acute bouts of resistance exercise ( RE ) of different intensities . METHODS Eighty-four participants were classified as experienced or inexperienced and then r and omly assigned to three conditions : 1 ) 50 % of one repetition maximum(1RM ) , 2 ) 80 % 1RM , or 3 ) control condition . RE consisted of performing three sets of four exercises between 12 to 20 reps in the 50 % 1RM condition and four to eight reps in the 80 % 1RM condition . Dependent variables consisted of state anxiety ( SA ) , mood states ( POMS ) , systolic BP ( SBP ) , diastolic BP ( DBP ) , and heart rate ( HR ) . These variables were assessed before as well as 1 , 20 , 60 , 120 , and 180-min following the conditions . Data were analyzed with a 2 ( experience ) x 3 ( conditions ) x 6 ( trials ) mixed model ANOVA and Tukey post-hoc tests . RESULTS Results indicated that SA decreased significantly ( P < 0.05 ) 180 min following the 50 % 1RM condition . A significant decrease ( P < 0.05 ) in vigor occurred immediately following the 50 % IRM condition and persisted for 20 min . SBP increased significantly ( P < 0.05 ) immediately following the 80 % 1RM condition . HR increased significantly ( P < 0.05 ) following both RE conditions . No significant differences were found between the experienced or inexperienced participants . CONCLUSIONS An acute bout of RE at 50 % 1RM is associated with an immediate reduction in vigor followed by a significant decrease in SA that emerged 180 min following exercise PURPOSE The heritability of the response to exercise training in resting blood pressure ( BP ) and heart rate ( HR ) was assessed in 482 Caucasian individuals comprising 98 families participating in the HERITAGE Family Study . METHODS All individuals were sedentary at the baseline visit ( time 1 measurement ) . After completing a 20-wk exercise-training program , subjects were measured again ( time 2 ) . A familial correlation model was used to assess the heritability ( genetic plus familial environmental ) of the response in resting systolic BP ( SBP ) , diastolic BP ( DBP ) , and HR , computed as the difference between the two measurement times . This response was adjusted for the effects of baseline levels and age within sex and generation groups . Analyses were conducted separately in a sub sample of families in which at least one family member was considered to have elevated BP ( 95th percentile ; SBP > or = 135 or DBP > or = 80 ) . RESULTS Several novel findings emerged from this study . First , the SBP and HR response may be influenced by genetic factors . The maximal heritabilities were 20 % ( SBP ) and 36 % ( HR ) in the elevated BP , 18 % and 24 % in the complete , and not significant in the normotensive sample s. For DBP , there were cohort effects ( significant sibling and spouse but not parent-offspring correlations ) in the complete and normotensive sample s that may be due to generation-specific environmental influences . CONCLUSION The trainability of SBP and HR in families with elevated BP appears to be determined in part by genetic factors , whereas DBP trainability may be more a function of environmental effects Concurrent training is recommended for health improvement , but its acute effects on cardiovascular function are not well established . This study analyzed hemodynamics and autonomic modulation after a single session of aerobic ( A ) , resistance ( R ) , and concurrent ( A + R ) exercises . Twenty healthy subjects r and omly underwent four sessions : control ( C:30 min of rest ) , aerobic ( A:30 min , cycle ergometer , 75 % of VO2 peak ) , resistance ( R:6 exercises , 3 sets , 20 repetitions , 50 % of 1 RM ) , and concurrent ( AR : A + R ) . Before and after the interventions , blood pressure ( BP ) , heart rate ( HR ) , cardiac output ( CO ) , and HR variability were measured . Systolic BP decreased after all the exercises , and the greatest decreases were observed after the A and AR sessions ( −13 ± 1 and −11 ± 1 mmHg , respectively , P < 0.05 ) . Diastolic BP decreased similarly after all the exercises , and this decrease lasted longer after the A session . CO also decreased similarly after the exercises , while systemic vascular resistance increased after the R and AR sessions in the recovery period ( + 4.0 ± 1.7 and + 6.3 ± 1.9 U , respectively , P < 0.05 ) . Stroke volume decreased , while HR increased after the exercises , and the greatest responses were observed after the AR session ( SV , A = −14.6 ± 3.6 , R = −22.4 ± 3.5 and AR = −23.4 ± 2.4 ml ; HR , A = + 13 ± 2 , R = + 15 ± 2 vs. AR = + 20 ± 2 bpm , P < 0.05 ) . Cardiac sympathovagal balance increased after the exercises , and the greatest increase was observed after the AR session ( A = + 0.7 ± 0.8 , R = + 1.0 ± 0.8 vs. AR = + 1.2 ± 0.8 , P < 0.05 ) . In conclusion , the association of aerobic and resistance exercises in the same training session did not potentiate post-exercise hypotension , and increased cardiac sympathetic activation during the recovery period Abstract Mota , MR , de Oliveira , RJ , Dutra , MT , Pardono , E , Terra , DF , Lima , RM , Simões , HG , and da Silva , FM . Acute and chronic effects of resistive exercise on blood pressure in hypertensive elderly women . J Strength Cond Res 27(12 ) : 3475–3480 , 2013—The purpose of this study was to investigate postexercise hypotension ( PEH ) during a 4-month period of resistance training in hypertensive elderly women . Sixty-four women were divided into 2 groups : an experimental group ( EG ) , which performed resistance training , and a control group ( CG ) that did not practice any exercise . The EG carried out the following steps : ( a ) 3 weeks of exercise adaptation and 1 repetition maximum ( 1RM ) test ( month 1 ) ; ( b ) resistance exercise at 60 % 1RM ( month 2 ) ; ( c ) resistance exercise at 70 % 1RM ( month 3 ) ; ( d ) resistance exercise at 80 % 1RM ( month 4 ) ; and ( e ) PEH analyses at the end of each month . Measurements of systolic ( SBP ) and diastolic blood pressure ( DBP ) were calculated each 5 minutes during a 20-minute resting period before the sessions and each 15 minutes during 1 hour of post-session recovery . Analysis of covariance for repeated measures showed a reduction in SBP of about 14 mm Hg ( p ⩽ 0.05 ) and in DBP of 3.6 mm Hg ( p ⩽ 0.05 ) between resting values after the training period . In the EG group , SBP showed acute PEH during months 2 and 3 , whereas DBP showed acute PEH during months 2 and 4 . The CG did not show acute PEH or variations during the 4-month period . Postexercise hypotension occurrence and chronic reduction of resting blood pressure observed in the EG may have a protective effect on the cardiovascular system of the study participants Background Post-exercise hypotension has been extensively described under laboratory conditions . However , studies investigating the persistence of this post-exercise decrease in blood pressure for longer periods have produced controversial results . The present investigation was conducted to verify the effect of a single bout of exercise on ambulatory blood pressure and to identify potential factors that might influence this post-exercise ambulatory blood pressure fall . Design The study was a r and omized controlled clinical trial . Methods Thirty normotensive and 23 hypertensive subjects were su bmi tted to two ambulatory blood pressure monitorings ( using the SpaceLabs 90207 , SpaceLabs , Redmond , Washington , USA ) , which were performed after 45 min of seated rest ( control session ) or cycling exercise at 50 % peak oxygen uptake ( exercise session ) . Results Normotensive subjects demonstrated a lower 24 h blood pressure level in the exercise session . Hypertensive patients showed no significant difference in ambulatory blood pressure level between the two experimental sessions . Further data analysis revealed that approximately 65 % of the subjects in both groups experienced a fall in blood pressure after exercise . Moreover , in the normotensive subjects , this blood pressure fall was significantly and positively correlated with clinic and ambulatory blood pressure , and negatively correlated with weight and body mass index . The blood pressure response to exercise was also greater in women . In the hypertensive patients , the post-exercise blood pressure decrease was significantly and positively correlated with clinic and ambulatory blood pressure as well as with the peak oxygen uptake , and negatively correlated with age and body mass index . Conclusions The post-exercise ambulatory blood pressure fall observed in normotensive and hypertensive humans depends on individual characteristics . Moreover , in both normotensive and hypertensive humans , post-exercise ambulatory hypotension is greater in subjects with a higher initial blood pressure level Abstract Neto , GR , Sousa , MSC , Costa , PB , Salles , BF , Novaes , GS , and Novaes , JS . Hypotensive effects of resistance exercises with blood flow restriction . J Strength Cond Res 29(4 ) : 1064–1070 , 2015—The effects of low-intensity resistance exercise ( RE ) combined with blood flow restriction ( BFR ) on blood pressure ( BP ) are an important factor to be considered because of the acute responses imposed by training . The aim of this study was to compare the hypotensive effect of RE performed with and without BFR in normotensive young subjects . After 1 repetition maximum ( 1RM ) tests , 24 men ( 21.79 ± 3.21 years ; 1.72 ± 0.06 m ; 69.49 ± 9.80 kg ) performed the following 4 experimental protocol s in a r and omized order : ( a ) high-intensity RE at 80 % of 1RM ( HI ) , ( b ) low-intensity RE at 20 % of 1RM ( LI ) , ( c ) low-intensity RE at 20 % of 1RM combined with partial BFR ( LI + BFR ) , and ( d ) control . Analysis of systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) was conducted over a 60-minute period . The 3 RE protocol s result ed in hypotensive SBP ( HI = −3.8 % , LI = −3.3 % , LI + BFR = −5.5 % ) responses during the 60 minutes ( p ⩽ 0.05 ) . The LI + BFR protocol promoted hypotensive ( −11.5 % ) responses in DBP during the 60 minutes ( p ⩽ 0.05 ) , and both the HI and LI + BFR protocol s result ed in mean blood pressure ( MBP ) hypotension between 30 ( −7.0 % , −7.7 % ) and 60 minutes ( −3.6 % , −8.8 % ) , respectively . In conclusion , postexercise hypotension may occur after all 3 exercise protocol s with greater reductions in SBP after HI and LI + BFR , in DBP after LI + BFR , and in MBP after HI and LI + BFR protocol Moderate- to high-intensity strength training is recommended for healthy adults . In young subjects , a single session of strength training decreases blood pressure , while heart rate and cardiac work remain elevated afterwards . However , these effects have not been clearly demonstrated in elderly subjects . To investigate this issue , 16 elderly subjects each underwent a Control and an Exercise ( 3 sets , 8 RM , 9 exercises ) session conducted in r and om order . Haemodynamic variables and heart rate variability were measured before and after the interventions . Systolic blood pressure did not change after the exercise session but did increase after the control session ( + 8.1±1.6 mm Hg , P≤0.05 ) . Diastolic blood pressure , as well as systemic vascular resistance increased similarly after both sessions . Cardiac output and stroke volume decreased , while heart rate , rate-pressure product and the low- to high-frequency ratio of heart rate variability increased only after the exercise session ( - 0.5±0.1 L/min , - 9.3±2.0 ml,+3.8±1.6 bpm , + 579.3±164.1 mmHg.bpm and + 0.71±0.34 , P≤0.05 ) . Ambulatory blood pressure was similar after both sessions , while heart rate and rate pressure product remained higher after the exercise session for up to 4.5 h. After a single session of strength training , cardiac sympathetic modulation and heart rate remain elevated in elderly subjects , keeping cardiac work elevated for a long period of time Abstract Prista , A , Macucule , CF , Queiroz , ACC , Silva Jr , ND , Cardoso Jr , CG , Tinucci , T , Damasceno , AAM , and Forjaz , CLM . A bout of resistance exercise following the 2007 AHA guidelines decreases asleep blood pressure in Mozambican men . J Strength Cond Res 27(3 ) : 786–792 , 2013—Hypertension is highly prevalent among African individuals and descendants , and in this ethnic group , asleep blood pressure is strongly associated with target organ damage . After its execution , a single bout of resistance exercise may decrease blood pressure in white individuals , but its effects are unknown in Africans . This study investigated the effects of a bout of resistance exercise , conducted in accordance with the 2007 American Heart Association ( AHA ) guidelines , on postexercise blood pressure in African subjects . Twenty-four Mozambican men ( 40 ± 2 years ) underwent , in a r and om order , 2 experimental sessions : control ( sitting resting ) and exercise [ 8 resistance exercises , 1 set , 10–15 repetitions , 30–40 % of 1 repetition maximum ( 1RM ) for upper-body muscles and 50–60 % of 1RM for lower-body muscles ] . Before and after the interventions , clinic blood pressure was measured . Ambulatory blood pressure was also evaluated after both sessions . Clinic systolic blood pressure did not change after both interventions , whereas diastolic blood pressure increased significantly and similarly after the control and the exercise sessions . Twenty-four-hour ( 127 ± 3 mm Hg vs. 130 ± 3 mm Hg and 78 ± 2 mm Hg vs. 81 ± 2 mm Hg , respectively , p < 0.05 ) and asleep ( 119 ± 4 mm Hg vs. 123 ± 4 mm Hg and 69 ± 3 mm Hg vs. 72 ± 3 mm Hg , respectively , p < 0.05 ) systolic and diastolic blood pressures were lower after the exercise than in the control session . These results show that in African men , a single bout of resistance exercise , conducted in accordance with 2007 AHA guidelines , decreased 24-hour and asleep blood pressures . These reductions might represent an important benefit for African individuals and descendants among whom target organ damage is mainly associated with ambulatory blood pressure levels Polito , MD and Farinatti , PTV . The effects of muscle mass and number of sets during resistance exercise on postexercise hypotension . J Strength Cond Res 23(8 ) : 2351 - 2357 , 2009-The effects of muscle mass and number of sets on postexercise hypotension ( PEH ) following resistance exercises are barely known . The aim of the study was to compare systolic blood pressure ( SBP ) , diastolic blood pressure , and mean arterial blood pressure ( MAP ) after biceps curl and leg extension with different number of sets . Twenty-four trained men ( 23 ± 1 year , 69 ± 4 kg , 173 ± 3 cm ) were r and omly assigned into control group , arm group , and leg group . On the first day , the 12 repetition maximum ( 12RM ) workload was determined for both experimental groups . In the remaining days , arm group and leg group performed , r and omly , 6 or 10 sets of 10 repetitions of the respective exercises at 12RM workload . Blood pressure was assessed before and every 10 minutes after the exercises for 1 hour . The 3-way analysis of variance identified a significant influence of the type of exercise ( p = 0.000001 ) , number of sets ( p = 0.007 ) , and postexercise period ( p = 0.009 ) on SBP and of the type of exercise ( p = 0.03 ) on MAP . No differences were found among the groups at rest . Postexercise hypotension was only observed for the leg group when 10 sets were performed . In this group , SBP was significantly ( p ≤ 0.05 ) lower than at rest during all the observation periods ( 120.6 ± 2.7 vs. 107.1 ± 3.2 to 113.4 ± 2.8 mm Hg ) and MAP was significantly lower than at rest only for the 30-minute assessment ( 90.3 ± 2.1 vs. 85.1 ± 1.5 mm Hg ) . It is therefore possible that the muscle mass activated during resistance exercise has an influence on PEH , especially in high-volume multiple-set training sessions Twenty-four mildly hypertensive sedentary men were r and omly assigned to one or two control conditions of health education or a treatment of a single bout of strength training . The men were rotated through the conditions until each man had participated in the treatment and both control conditions . Blood pressure was measured every 15 minutes for the 24-hour period following participation in each condition using an ambulatory blood pressure monitoring system . Compared to the control conditions , systolic blood pressure and blood pressure load were reduced for at least 1 hour after exercise , and diastolic blood pressure and blood pressure load were reduced for at least 3 minutes and 1 hour , respectively , after exercise |
13,373 | 21,633,956 | Although our findings suggest that therapeutic engagement appears to be considered an important construct to assess , they also reveal that there is little consensus in the definition of engagement employed .
It is concluded that further work is required to develop adequate measures of therapeutic engagement | This article reports a systematic review of engagement measures for psychosocial therapy . | The contribution to outcome of two group-process factors , group cohesion and group therapeutic alliance , was tested in the context of a r and omized , controlled treatment trial for borderline personality disorder . Group members from four time-limited groups of an experimental model of group psychotherapy completed measures of group cohesion and group alliance at prespecified intervals across the 30-session therapy . Outcome was measured in terms of psychiatric symptoms , social adaptation , and indicators of behavioral dysfunction . The results showed that cohesion and alliance were correlated significantly and separately contributed to outcome on most of the dependent measures . Stepwise regression analyses showed , however , that when compared with cohesion , alliance accounted for more outcome variance on the dependent measures . The clinical implication s of the findings and the limitations of the study are discussed BACKGROUND It is widely assumed that the outcome of correctional treatment largely depends on the patient 's treatment engagement ; however , evidence for this notion is scarce . AIM In this study , the Treatment Engagement Rating scale ( TER ) was used to investigate the relationship of a patient 's treatment engagement with premature treatment termination and treatment outcome , defined as reduction of the risk of reoffending . METHOD Employing a prospect i ve design , this study addressed the relationship of the behavioural treatment engagement of correctional out patients ( N = 138 ) with treatment non-completion and treatment outcome , respectively . RESULTS Treatment engagement as measured by the TER emerged as an accurate predictor of treatment non-completion ( area under the curve = 0.76 ; odds ratio = 4.1 ) and was also significantly correlated with treatment outcome ( rho = 0.41 ) . The prediction was more accurate for sex offenders than for violent offenders , for expulsion from the treatment than for dropout , and when treatment engagement was assessed closer to the end of the treatment . CONCLUSIONS The study provides evidence that the outcome of correctional treatment depends to a substantial degree on the behavioural efforts that the patients make for the treatment . Periodic assessment of treatment engagement in correctional treatment facilities would be useful , and the TER seems to be a practical , reliable and valid instrument for this purpose The relationship between the therapeutic alliance and treatment participation and drinking outcomes during and after treatment was evaluated among alcoholic outpatient and aftercare clients . In the outpatient sample , ratings of the working alliance , whether provided by the client or therapist , were significant predictors of treatment participation and drinking behavior during the treatment and 12-month posttreatment periods , after a variety of other sources of variance were controlled . Ratings of the alliance by the aftercare clients did not predict treatment participation or drinking outcomes . Therapists ratings of the alliance in the aftercare sample predicted only percentage of days abstinent during treatment and follow-up . The results document the independent contribution of the therapeutic alliance to treatment participation and outcomes among alcoholic out patients The bidirectional causal relationships between psychotherapy homework ( HW ) compliance and changes in depression were assessed in 2 groups of depressed out patients treated with cognitive-behavioral therapy using nonrecursive structural equation modeling techniques . The data were consistent with the hypothesis that HW compliance had a causal effect on changes in depression , and the magnitude of this effect was large . Patients who did the most HW improved much more than patients who did little or no HW . In contrast , depression severity did not appear to influence HW compliance . HW compliance did not appear to be a proxy for any other , unobserved ( 3rd ) variable , such as motivation . Although the causal effect of HW on depression was large , the correlation between HW and depression was small . Some possible explanations , along with suggestions for future studies , are proposed We present a brief measure of awareness of illness in schizophrenia and test whether awareness is related to perceived need for and adherence to outpatient psychiatric treatment . A prospect i ve design assessed treatment adherence , awareness of the signs and symptoms of schizophrenia , symptoms , neurocognitive status , and substance abuse at baseline and 6-month follow-up in 89 persons with schizophrenia . Results indicate that persons with greater awareness perceived greater need for outpatient treatment and evidence d better adherence to outpatient treatment when adherence and awareness were measured concurrently . Awareness was not related to adherence at 6-month follow-up . In addition , neurocognitive impairment was associated with lower overall adherence to treatment when reported by collaterals at baseline and 6-month follow-up . Neurocognitive impairment was , however , associated with higher self-reported adherence to medication , which suggests that neurocognitive status may bias adherence reporting in persons with schizophrenia OBJECTIVE The authors extend previous research on homework in psychotherapy by examining the relationship between homework compliance and therapeutic outcome among depressed older adult out patients ( N = 63 ) , addressing previous limitations by using session-by-session therapist ratings of homework compliance and including both interviewer ratings and patient self-reports of outcomes . METHODS Patients were participants in a r and omized clinical trial evaluating the efficacy of desipramine versus cognitive/behavioral therapy-alone ( C/B-Alone ) versus a combination of the two ( Combined ) . Given the current study 's focus on homework compliance , only patients assigned to conditions with assigned homework in the clinical trial ( i.e. , C/B-Alone and Combined conditions ) were included . RESULTS Results of hierarchical regression analyses indicated that homework compliance contributed significantly to posttreatment outcome as measured by both interviewer-administered and patient self-report measures of depression . A separate series of ANOVAs also found significant differences in pre-posttreatment change between patients scoring above and below the median of reported homework compliance . Findings were similar for patients in the C/B-Alone and Combined conditions . CONCLUSION The study 's results call for additional research on issues related to homework compliance with older adult patients This paper reports on the development and initial psychometric evaluation of the Treatment Adherence Survey-patient version ( TAS-P ) , a brief instrument design ed to assess patient adherence to Cognitive-Behavioral Therapy ( CBT ) and pharmacotherapy recommendations for OCD . Eighty individuals with Obsessive Compulsive Disorder ( OCD ) were administered the TAS-P as part of the intake interview of a prospect i ve , observational study of the course of OCD . Results demonstrated excellent test-retest reliability . Responses on the TAS-P were also significantly correlated with scores on a self-report measure of general treatment adherence and with data collected from a chart- review , demonstrating concurrent validity . Treatment adherence was not explained by demographic variables . However , participants who reported nonadherence to CBT recommendations had more severe OCD symptoms at the time of intake than those who did not endorse CBT nonadherence ( mean Y-BOCS = 23.27 + /- 7.5 versus 18.20 + /- 8.0 , respectively ) . Results suggest that the TAS-P is a promising instrument for assessing reasons for nonadherence to recommendations for CBT and pharmacotherapy interventions The purpose of this study was to examine the comparative efficacy of cognitive rehabilitation as an intervention for substance misuse . Patients with substance use disorders entering long-term residential care ( N = 160 ) were r and omly assigned to one of two conditions : ( a ) st and ard treatment plus computer-assisted cognitive rehabilitation ( CACR ) , which was design ed to improve cognitive performance in areas such as problem solving , attention , memory , and information processing speed ; and ( b ) an equally intensive attention control condition consisting of st and ard treatment plus a computer-assisted typing tutorial ( CATT ) . Participants were assessed at baseline , during treatment , at treatment completion , and 3- , 6- , 9- , and 12-month follow-up . Intent-to-treat analyses showed that , compared with those r and omized to CATT , patients who received CACR were significantly more engaged in treatment ( e.g. , higher ratings of positive participation by treatment staff , higher ratings of therapeutic alliance ) , more committed to treatment ( e.g. , longer stays in residence ) and reported better long-term outcomes ( e.g. , higher percentage of days abstinent after treatment ) . Mediational analyses revealed the positive comparative effect of CACR on abstinence during the year after treatment was mediated by treatment engagement and length of stay in residence |
13,374 | 28,653,747 | The narrative synthesis suggests that NSAIDs as well as corticosteroid and hyaluronate injections are effective treatments for TMD-joint pain .
The network meta- analysis showed that clonazepam and capsaicin reduced pain intensity in BMS , and the muscle relaxant cyclobenzaprine , for the TMD-muscle group .
In conclusion , based on a limited number of studies , evidence provided with network meta- analysis showed that clonazepam and capsaicin are effective in treatment of BMS and that the muscle relaxant cyclobenzaprine have a positive treatment effect for TMD-muscle pain . | This health technology assessment evaluated the efficacy of pharmacological treatment in patients with orofacial pain . | OBJECTIVES The aim of this study was to compare the effectiveness of using Ping On ointment and using petroleum jelly in the treatment of temporom and ibular joint ( TMJ ) and masticatory muscle pain , in order to establish the true efficacy of Ping On ointment . METHODS In this r and omized , double-blinded , placebo-controlled trial , 55 subjects with TMJ and /or masticatory pain ( Group I patients according to the Research Diagnostic Criteria for Temporom and ibular Disorder ( RDC/TMD ) received Ping On ointment for 4 weeks , or placebo for 4 weeks . Subjects were evaluated with st and ard measures of efficacy : pain intensity measured by visual analogue scale and maximal comfortable m and ibular opening , at baseline and again after 4 weeks of treatment . RESULTS Ping On ointment significantly reduced the symptoms of painful TMJs and /or masticatory muscles . Maximal comfortable m and ibular opening also improved in the Ping On ointment group compared with the placebo , but was not clinical ly significant . CONCLUSIONS This preliminary study suggests that topical application of Ping On ointment may be considered for further investigation as a potential first-line treatment modality , before prescribing analgesics , for the management of TMDs . It is topically applied , safe , reversible , and effective in managing TMDs and masticatory muscle pain A study of the effectiveness of physical therapy for patients with myofacial pain dysfunction syndrome was performed . Clinical evaluation of 120 patients revealed marked male preponderance , distribution according to age showed a great prevalence of the third decade , and most common chief complaints were pain and muscle tenderness . Patients were classified r and omly into three equal groups treated by muscle relaxant drugs , shortwave diathermy , and ultrasonic therapy , respectively . Regular follow-up was carried out for 6 to 12 months to assess patients ' responses to different forms of treatment . Evaluation revealed marked relief of symptoms by the use of physical therapy , and the best results were obtained by the use of ultrasonic therapy & NA ; Burning mouth syndrome ( stomatodynia ) is associated with changes of a neuropathic nature the main location of which , peripheral or central , remains unknown . A r and omised , double‐blind crossover design was used to investigate the effects of lingual nerve block on spontaneous burning pain and a possible correlation with the effects of topical clonazepam , the patient 's response to a psychological question naire , and the taste and heat thresholds . The spontaneous burning was measured with a visual analogue scale ( VAS ) just before and 15 min after injection . The decreases in VAS score after lidocaine or saline injection were not significantly different ( 2.7 ± 3.9 and 2.0 ± 2.6 , respectively ; n = 20 ) . However , two groups of patients could be identified : in a “ peripheral group ” ( n = 10 ) the VAS decrease due to lingual nerve injection was 4.3 ± 3.1 cm after lidocaine and 0.9 ± 0.3 cm after saline ( p = 0.02 ) . In a “ central group ” ( n = 7 ) , there were an increase in pain intensity score ( −0.8 ± 2.6 cm ) after lidocaine and a decrease ( 1.5 ± 3.0 cm ) after saline ( p = 0.15 ) . An increase in the hospital anxiety and depression ( HAD ) score and a decreased taste sensitivity and heat pain threshold of painful oral area were seen in patients compared with age‐ and ‐sex‐matched controls ( p < 0.05 ) . Topical clonazepam treatment tended to be more effective ( p = 0.07 ) and HAD score lower ( p < 0.03 ) in the peripheral than in the central group . These results suggest that the neuropathic disorder associated with stomatodynia may be predominantly peripheral , central or mixed depending on the individual . Topical application of clonazepam and HAD may serve as indicators of which mechanism is dominating Purpose Arthrocentesis ( AC ) is an acceptable treatment modality in the treatment of internal derangement ( ID ) pain . This study evaluated outcomes of AC on pain relief of ID pain with or without corticosteroids . Material s and Methods This single-blind clinical trial was conducted on 60 patients with ID pain who were r and omly assigned to 2 groups ( 30 in each group ) for AC . The AC of the upper joint space was then performed by using Ringer lactate under local anesthesia in both groups . In the second group , the procedure was followed by the administration of a single-dose intra-articular dexamethasone ( 8 mg ) . Assessment s were made at baseline ( T0 ) , 1 month ( T1 ) , and 6 months ( T6 ) after AC ; pain , maximum mouth opening , and joint sounds before and after treatment up to 6 months were evaluated . Pain severity was documented according to Visual Analogue Scale . Age , sex , and skeletal maxillom and ibular relationship were considered as variable factors , and irrigation with or without corticosteroids was a predictive factor of the study . Pain , click , and maximum mouth opening were other assessment outcomes of the study . Results Comparison of age , sex , and skeletal relationship did not show any significant differences between the 2 groups . Results did not demonstrate any difference for click between the 2 groups . Comparison of pain severity in T0 , T1 , and T2 between the 2 groups did not show any significant differences ( P < 0.05 ) . The repeat measure test revealed a significant change in T0 , T1 , and T2 for both groups ( P < 0.001 ) . MMO significantly changed between T0 and T1 and T0 and T6 in the 2 groups without any significant differences between them . Conclusions The AC is an effective procedure for a short-term reduction of pain in temporom and ibular disorder cases . It seems that AC using Ringer solution with or without corticosteroids may have the same effect on pain relief OBJECTIVES In a preliminary pilot study of 30 treatments in 26 patients with osteonecrosis of the jaws and chronic disabling facial pain , our specific aim was to determine whether , to what degree , and how safely therapy of hypofibrinolysis and thrombophilia would ameliorate the chronic pain associated with osteonecrosis of the m and ible and maxilla . STUDY DESIGN Thrombophilia was treated with Coumadin ( DuPont ) in 10 patients ; hypofibrinolysis was treated with Winstrol ( Sanofi-Winthrop ) in 20 patients , including 4 who had mixed thrombophilia and hypofibrinolysis and had previously been treated with Coumadin . The initial treatment period was targeted to be 4 months . Each patient was asked to keep a daily written pain-relief numeric rating score and side-effects diary and to provide a summary pain-relief numeric rating score and side effects compilation for the total treatment period . RESULTS There were 4 men and 22 women in the study group ; their mean age was 49 + /- 11 years . The mean onset of their osteonecrosis pain was at age 45 + /- 12 years , and the mean duration of their facial pain prior to therapy was 4.5 + /- 4.2 years . Ten patients had one or more thrombophilic traits ( there were two patients with protein C deficiency , five with resistance to activated protein C and /or the mutant Factor V Leiden gene , and four with high anticardiolipin antibodies ) . The 10 patients who were thrombophilic were treated with Coumadin ( the international normalized ratio was targeted to 2.5 - 3.0 ) for 22 + /- 9 weeks . By self-reported pain-relief numeric rating scores , 6 of the 10 patients with thrombophilia ( 60 % ) had > or = 40 % pain relief , 2 ( 20 % ) had no change , and 2 ( 20 % ) had increased pain ( 30 % and 80 % worse ) . Nine of the 10 patients with thrombophilia ( 90 % ) had no Coumadin-related side effects ; 1 patient ( 10 % ) stopped Coumadin therapy ( after 28 weeks ) because of nosebleeds . Winstrol ( 6 mg per day ) was used for 16 + /- 9 weeks in 20 patients with hypofibrinolysis , some of whom had one or more hypofibrinolytic traits ( 10 had high levels of plasminogen activator/inhibitor activity , usually accompanied by low stimulated tissue plasminogen activator activity ; 13 had high Lp[a ] lipoprotein ) . Of these 20 patients with hypofibrinolysis , 9 patients ( 45 % ) had > or = 40 % pain relief , 3 patients ( 15 % ) had 20 % to 30 % relief , 5 patients ( 25 % ) had no improvement , and 3 patients ( 15 % ) had increased pain ( 30 % worse , 60 % worse , and 70 % worse ) . Six of the 20 patients with hypofibrinolysis ( 30 % ) had no Winstrol-related side effects , while 14 ( 70 % ) had side effects that could be attributed to Winstrol , including weight gain , peripheral edema , increased facial and body hair , and acne -- all of which were reversed within 6 weeks of stopping Winstrol therapy . CONCLUSIONS We postulate that thrombophilia and hypofibrinolysis lead to impaired venous circulation and venous hypertension of the m and ible/maxilla with subsequent development of osteonecrosis and chronic facial pain . In many patients , facial pain can be ameliorated by treating the pathogenetic coagulation defects with Coumadin or Winstrol . Large , double-blind , placebo-controlled crossover studies will be required in the future to vali date these preliminary results and to determine whether pain relief with Coumadin or Winstrol justifies the risks and side effects associated with these medications , especially for long-term use , in osteonecrosis of the jaws INTRODUCTION Although a significant amount of evidence indicates the efficacy of some antidepressants in treating psychogenic pain and somatoform disorder , very few studies have investigated their possible therapeutic action in burning mouth syndrome ( BMS ) . The purpose of this 8-week , single-blind study was to provide preliminary data on the efficacy and tolerability of amisulpride and the selective serotonin reuptake inhibitors ( SSRIs ) paroxetine and sertraline for patients with BMS . METHOD Seventy-six patients with BMS ( diagnosed according to the criteria in the literature and integrating the Diagnostic Interview Schedule-Revised for a complete psychiatric assessment ) , with no possible local or systemic causes and without concurrent major depression , were r and omly assigned to receive amisulpride ( 50 mg/day ) , paroxetine ( 20 mg/day ) , or sertraline ( 50 mg/day ) . Efficacy assessment s included a visual analogue scale ( VAS ) for pain intensity , the Hamilton Rating Scale for Depression ( HAM-D ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , and the Clinical Global Impressions scale ( CGI ) . RESULTS All 3 treatment regimens result ed in a significant improvement from baseline in burning mouth symptoms at week 8 as demonstrated by the quantitative ( mean reduction in VAS , HAM-D , and HAM-A scores ) and qualitative ( percentage of responders ) analyses . Amisulpride showed a shorter response latency than the SSRIs . No serious adverse events were reported , and the incidence of side effects did not differ among the 3 groups . None of the patients who received amisulpride withdrew from the trial , whereas withdrawal from the trial occurred within the first week of treatment in 11.5 % of patients ( N = 3 ) treated with paroxetine and in 21.7 % of patients ( N = 5 ) treated with sertraline . CONCLUSION The data suggest that amisulpride and SSRIs may be effective treatments for BMS ; they are equally effective and equally well tolerated in the short-term treatment of BMS . Amisulpride is associated with better compliance within the first week of treatment and with a shorter response latency in comparison with SSRIs . This finding may indicate that amisulpride is especially useful at the beginning of drug therapy of BMS . Double-blind , placebo-controlled trials are needed to further document the efficacy of amisulpride and SSRIs in the treatment of BMS In a double-blind study , diclofenac sodium ( Voltaren ) , 50 mg two or three times a day , was compared with placebo in 32 patients with pain localized to the temporom and ibular joint ( TMJ ) . The patients were allocated into two equally large groups . A visual analog scale was used to estimate the pretreatment degree of pain . The treatment effect was assessed as the frequency of joint and muscle pain and by the patients ' own evaluation of improvement . The change in the clinical condition was assessed by tenderness to palpation of the TMJ and masticatory muscles and by m and ibular mobility . The frequency of TMJ pain showed a greater reduction in the diclofenac group than in the placebo group , and there was a significant reduction of daily TMJ pain in the diclofenac group . The diclofenac group also showed a significant decrease in tenderness to palpation of the masticatory muscles in comparison with the placebo group . The patients with short duration of pain showed the best response to diclofenac . There was no evidence in this study to prove that diclofenac should be used as a primary treatment of TMJ pain , but it could be used as a complement to other treatments of acute TMJ pain OBJECTIVE The purpose of this study was to evaluate the efficacy of the topical use of benzydamine hydrochloride 0.15 % oral mouthwashes in the control of burning mouth syndrome symptoms . STUDY DESIGN In this double-blind , r and omized , longitudinal investigation , each of 30 patients with burning mouth syndrome was assigned to one of 3 management modalities . Those in group A received an oral rinse solution of benzydamine hydrochloride 0.15 % 3 times a day for 4 weeks , those in group B received a placebo 3 times a day for 4 weeks , and those in group C did not receive any kind of treatment . A visual analog scale was used for evaluation of the symptoms ; a Kruskal-Wallis analysis of variance exact test was performed on the result ing data . RESULTS The findings of this investigation failed to reveal significant differences among the groups . CONCLUSIONS The clinical application of benzydamine hydrochloride oral rinses in the treatment of patients with burning mouth syndrome did not demonstrate significative efficacy in comparison with use of a placebo solution The aim of this study was to compare the effectiveness of dexamethasone administration following arthrocentesis of the temporom and ibular joint ( TMJ ) with a placebo ( saline ) . Twenty-eight participants with TMJ arthralgia were r and omly assigned to two groups of a parallel double-blind RCT . In both groups , an arthrocentesis procedure was carried out . In one group , the procedure was followed by the administration of a single-dose intra-articular dexamethasone . In the other group , saline was administered as a control . Follow-up visits were scheduled after 1 , 3 , and 24 weeks . During each visit , TMJ pain ( on a 100-mm VAS ) and jaw stiffness ( mouth opening in mm ) were scored . In the statistical analysis , generalized estimating equation ( GEE ) models showed no differences between the two study groups , although pain and jaw stiffness were both reduced over 24 weeks . In conclusion , intra-articular dexamethasone following arthrocentesis did not improve the procedure ’s effect in patients presenting with TMJ arthralgia ( Clinical Trials.gov number CT01275014 ) & NA ; The aim of this study was to determine the analgesic efficacy of a single dose intra‐articular injection ( i.a . ) of morphine in 53 patients with unilateral arthralgia/osteoarthritis of the temporom and ibular joint ( TMJ ) . This r and omized , double‐blind , parallel group , multicenter study included a screening visit , a treatment visit , and a follow‐up visit 1 week after treatment . Recordings of visual analog scales ( VAS ) pain intensity scores at maximum mouth opening ( main efficacy variable ) and at jaw rest were made directly before a 1‐ml i.a . injection into one TMJ of either 1.0 mg morphine – HCl , 0.1 mg morphine – HCl , or saline ( placebo ) . The pain intensity was also recorded at the follow‐up and in a diary 3 days before and 5 days after the injection . The VAS pain score at maximum mouth opening was considerably reduced 1–10 h after injection but without significant differences between groups . At the follow‐up , the median VAS pain score at maximal mouth opening was significantly lower in the 0.1‐mg morphine group than in the 1.0‐mg morphine group ( P<0.043 ) or the saline group ( P<0.021 ) . A significant increase in pain pressure threshold over the affected joint was seen in the 0.1‐mg morphine group compared with the saline group at the follow‐up but not 1 and 2 h post‐injection . The incidence of adverse events was small and did not differ between the treatment groups . In conclusion , one i.a . injection of 0.1 mg morphine significantly increased the pain pressure threshold and mouth opening ability , but evidence for the analgesic property of the locally applied opioid was inconclusive . No dose – effect relation and no significant short‐term analgesic property were seen . Although statistically significant , the magnitude of the reduced VAS pain intensity score was not clinical ly relevant at the 1‐week follow‐up OBJECTIVE This r and omized , double-blind , placebo-controlled clinical study aim ed at evaluating the effect of the systemic use of an herbal compound ( Catuama ) on the symptoms of burning mouth syndrome ( BMS ) . STUDY DESIGN Seventy-two patients with BMS were r and omly allocated into test ( n = 38 ) and control ( n = 34 ) groups . Patients were instructed to take 2 capsules each day for 8 weeks . They were reassessed at 4 , 8 , and 12 weeks after treatment onset using a faces scale ( FS ) and a visual numeric scale ( VNS ) . RESULTS Although both groups demonstrated a reduction in symptoms , the improvement observed in the test group was significantly greater than in the control group after 4 ( FS : P = .010 ) and 8 ( VNS : P = .03 ; FS : P < .001 ) weeks of treatment . This significant reduction was maintained 12 weeks after treatment onset ( FS , VNS : P = .001 ) . CONCLUSIONS The systemic administration of Catuama reduces the symptoms of BMS and may be a novel therapeutic strategy for the treatment of this disease The aim of this study was to evaluate the efficacy of injection of plasma rich in growth factors ( PRGF ) after temporom and ibular joint ( TMJ ) arthroscopy in patients with Wilkes stage IV internal derangement . Ninety-two patients were r and omized to two experimental groups : group A ( 42 joints ) received injections of PRGF , group B ( 50 joints ) received saline injections . Pain intensity on a visual analogue scale ( VAS ) and maximum mouth opening ( MMO , mm ) were measured before and after surgery and compared by analysis of variance ( ANOVA ) . The mean age of patients was 35.8 years ( range 17 - 67 years ) ; 86 were female . Significant reductions in pain were noted in both groups after surgery : VAS 7.9 preoperative and 1.4 at 24 months postoperative . Significantly better clinical results were achieved in group A than in group B only at 6 and 12 months postoperative ; no significant difference was noted at 18 or 24 months after the surgical intervention . MMO increased after surgery in both groups : 26.2 mm preoperative and 36.8 mm at 24 months postoperative . No significant differences in MMO were found when the two groups of patients were compared . In conclusion , the injection of PRGF does not add any significant improvement to clinical outcomes at 2 years after surgery in patients with advanced internal derangement of the TMJ Abstract A r and omized controlled trial was performed to compare the short-term effectiveness of botulinum toxin injections and physiatric treatment provided by means of Fascial Manipulation techniques in the management of myofascial pain of jaw muscles . Thirty patients with a Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) diagnosis of myofascial pain were r and omized to receive either single-session botulinum toxin injections ( Group A ) or multiple-session Fascial Manipulation ( Group B ) . Maximum pain levels ( VAS ratings ) and jaw range of motion in millimeters ( maximum mouth opening , protrusion , right and left laterotrusion ) were assessed at baseline , at the end of treatment , and at a three-month follow-up . Both treatment protocol s provided significant improvement over time for pain symptoms . The two treatments seem to be almost equally effective , Fascial Manipulation being slightly superior to reduce subjective pain perception , and botulinum toxin injections being slightly superior to increase jaw range of motion . Differences between the two treatment protocol s as to changes in the outcome parameters at the three-months follow-up were not relevant clinical ly . Findings from the present investigation are in line with literature data supporting the effectiveness of a wide spectrum of conservative treatment approaches to myofascial pain of the jaw muscles . Future studies on larger sample s over a longer follow-up span are needed on the way to identify tailored treatment strategies PURPOSE The main objective of our study was to evaluate the effectiveness of the injection of plasma rich in platelet-derived growth factors ( PRGF ) versus hyaluronic acid ( HA ) following arthroscopic surgery in patients diagnosed with internal derangement of the temporom and ibular joint ( TMJ ) with osteoarthritis ( OA ) . MATERIAL S AND METHODS A total of 100 patients were r and omised into two study groups . Group A ( n = 50 ) received an injection of PRGF , and Group B ( n = 50 ) received an injection of HA . The mean age was 35.5 years ( range 18 - 77 years ) , and 88 % of the patients were women . The pain intensity ( visual analogue scale ) and the extent of maximum mouth opening before and after the procedure were statistically analysed . RESULTS Better results were observed in the group treated with PRGF , with a significant reduction in pain at 18 months , compared with HA treatment . Regarding mouth opening , an increase was observed in both groups , with no significant difference . CONCLUSIONS The injection of PRGF following arthroscopy is more effective than the injection of HA with respect to pain in patients with advanced internal derangement of the TMJ OBJECTIVES The aim of this study was to evaluate the efficacy of aloe vera ( AV ) applied in combination with a tongue protector , comparing this with a placebo . METHODS A total of 75 patients with burning mouth syndrome ( BMS ) were divided into three groups r and omly : Group I ( tongue protector three times a day ) , Group II ( tongue protector and 0.5 ml AV at 70 % three times a day ) and Group III ( tongue protector and 0.5 ml placebo three times a day ) . Symptoms were evaluated by visual analogue scale ( VAS ) , while patient psychological profiles were assessed using the Hospital Anxiety-Depression scale and their quality of life using the Oral Health Impact Profile 49 ( OHIP-49 ) . Treatment continued for 3 months . RESULTS Visual analogue scale pain values improved for all three study groups but without statistically significant differences between the groups ( P = 0.210 ) . Regarding quality of life , no significant differences were found between groups with the exception of the OHIP-49 score for h and icap . The overall clinical improvement was greater for Group II , with a difference almost reaching significance . CONCLUSIONS The concomitant prescription of tongue protector and AV is effective for treating patients with BMS PURPOSE Chronic hyperactivity of the masticatory muscles is a common functional disorder associated with chronic facial pain and headache . The positive therapeutic effect of botulinum toxin type A on functional disorders and pain symptoms has been known in connection with the treatment of cervical dystonia . The purpose of this report is to assess whether the targeted reduction of masticatory muscular hyperactivity by local injection treatment with botulinum toxin type A can improve facial pain headache symptoms in the event that other treatment methods prove ineffective . MATERIAL S AND METHODS In an r and omized blinded placebo-controlled study , 90 patients ( 60 verum and 30 placebo ) with chronic facial pain were treated with botulinum toxin type A ( Botox ; Allergan , Ettlingen , Germany ) injections into masticatory muscles . RESULTS Ninety-one percent of patients who received botulinum toxin improved by a significant mean reduction of approximately 3.2 on a visual analog pain scale . By comparison with t test and chi(2 ) test , there was a significant difference compared with the placebo group ( P < .01 ) . CONCLUSIONS The local injection of botulinum toxin type A constitutes an innovative and adequately efficient treatment method for chronic facial pain associated with hyperactivity of the masticatory muscles . An improvement in the painful symptoms can be expected in up to 90 % of patients who do not respond to conservative treatment methods ABSTRACT The objective of this study was to determine the influence of medical and physical therapy on long-term treatment outcome in 72 patients with anterior disk displacement without reduction . Patients were treated solely with occlusal splints ( group I ) , with splints and supplementary medical therapy ( group II ) , with splints and physical therapy ( group III ) or with splints , medical , and physical therapy ( group IV ) . After therapy , the maintenance of improvement was objective ly and subjectively assessed with an extensive clinical examination and a postal question naire . The percentage of pain free patients after therapy was 76 % in group I , 88 % in group II , 43 % in group III , and 65 % in group IV . There was a statistically significant higher increase of maximum jaw opening after therapy in group II than in the control groups ( p<0.05 ) . The improvement in mouth opening came to 9.7 mm in group I , 14.5 mm in group II , 7.3 mm in group III , and 11.2 mm in group IV . Medical therapy seems to have a positive influence on the treatment outcome of patients with anterior disk displacement without reduction UNLABELLED The burning mouth syndrome ( BMS ) is a chronic condition characterized by oral burning pain in the absence of clinical abnormalities and without established therapy . OBJECTIVES The purpose of this study was to evaluate the effectiveness of alpha lipoic acid ( ALA ) in the management of BMS symptoms through a r and omized double-blind placebo-controlled trial . METHODS Thirty-eight patients ( 34 women and four men , median age 62.9 years , range 36 - 78 ) were included and 31 completed the study . The patients were r and omized into two cycles of treatment : one with alpha lipoic acid and one with placebo both administered in identical capsules . These cycles were separated by a washout period of 20 days . The oral symptoms and the treatment response were assessed using a 100-mm visual analog scale before and after each cycle and the global perceived effect score , using a 5-point scale after each treatment cycle . RESULTS The level of reduction on burning was significant for both treatments ( paired t-test : P < 0.05 ; rp = 0.011 ; ral < 0.001 ) . Considering the two cycles together , 22 patients reported at least some improvement after ALA use and 23 patients after placebo . CONCLUSIONS Comparison of the oral assessment scores of the two cycles failed to demonstrate the effectiveness of ALA over placebo ( t-test : P > 0.05 ; r = 0.75 ) Abstract Atypical odontalgia ( AO ) is an intraoral pain condition of currently unknown mechanisms . In 10 AO patients and 10 matched healthy controls , we examined the effect of intravenous infusion of an N‐methyl‐d‐aspartate ( NMDA ) receptor antagonist S‐ketamine and a μ‐opioid agonist fentanyl on spontaneous AO pain and on an acute intraoral nociceptive input evoked by topical application of capsaicin . The drugs were administered in a r and omized , placebo‐controlled , cross‐over manner . Furthermore , measures of intraoral sensitivity to mechanical and thermal quantitative sensory testing ( QST ) including temporal summation were compared between groups and sides . Both drugs failed to produce an analgesic effect on spontaneous AO pain , but fentanyl effectively reduced capsaicin‐evoked pain . AO patients showed increased sensitivity to capsaicin and heat pain , but no significant differences in cold and mechanical sensitivity compared with healthy controls . No side‐to‐side differences in QST measures were found in AO patients . The present study demonstrates that AO is unlikely to be primarily due to a persistent afferent barrage from the peripheral region . Furthermore , in contrast to studies on various neuropathic pain conditions , fentanyl and S‐ketamine in the present doses failed to attenuate AO pain BACKGROUND Treatment recommendations for patients with painful temporom and ibular disorders ( TMDs ) range from conservative treatments such as physiotherapy to aggressive and irreversible treatments such as restorative reconstruction and joint surgery . METHODS The authors r and omized 200 subjects diagnosed with TMD into three groups : usual conservative , dentist-prescribed self-care treatment without any intraoral splint appliance ( UT ) ; UT plus a conventional flat-plane hard acrylic splint ( HS ) ; and UT plus a soft vinyl ( a low-cost athletic mouth guard ) splint ( SS ) . Subjects completed question naires and clinical examinations at three , six and 12 months . RESULTS The authors observed no significant differences among the groups in TMD-related pain levels or other common signs and symptoms of TMD at baseline ( BL ) or at any follow-up . The changes from BL were comparable for all three groups . The authors did not note any significant differences at any follow-up for compliance with study protocol s or for occurrences of adverse effects from either splint type . For HS versus SS , there were significant differences in rates of splint use , but these differences were not accompanied by differences in either self-reported symptoms or in clinical findings . CONCLUSIONS All patients improved over time , and traditional splint therapy offered no benefit over the SS splint therapy . Neither splint therapy provided a greater benefit than did self-care treatment without splint therapy . CLINICAL IMPLICATION S These findings suggest that clinicians who treat patients with TMD should consider prescribing low-cost nonsplint self-care therapy for most patients PURPOSE To compare the effectiveness of 2 treatment protocol s providing 5 weekly temporom and ibular joint ( TMJ ) arthrocenteses immediately followed by injections of 2 different molecular weight hyaluronic acid ( HA ) drugs to manage symptoms in patients with inflammatory-degenerative TMJ disease . MATERIAL S AND METHODS Patients with a Research Diagnostic Criteria for Temporom and ibular Disorders diagnosis of osteoarthritis were r and omly assigned to 1 of 2 study groups receiving either low- or medium-molecular weight HA after arthrocentesis . The level of maximum pain at chewing was the primary outcome variable , and maximum pain at rest , subjective chewing efficiency , functional limitation , treatment tolerability , perceived treatment effectiveness , and jaw range-of-motion function in millimeters were the secondary outcomes . All variables were assessed and compared between groups at baseline , at the end of treatment , and 3 months later . RESULTS Forty subjects entered the study . At the end of the follow-up period , all the outcome variables improved in both groups of patients . A between-group comparison of changes over time showed that differences were not significant for any of the outcome variables , that is , pain at chewing ( F = 0.056 , P = .815 ) , pain at rest ( F = 0.383 , P = .541 ) , chewing efficiency ( F = 0.050 , P = .825 ) , functional limitation ( F = 0.268 , P = .609 ) , and mouth opening ( F = 0.003 , P = .954 ) . In addition , no between-group differences were shown for perceived treatment effectiveness and treatment tolerability . CONCLUSIONS Similar positive effectiveness was shown for 2 treatment protocol s for TMJ osteoarthritis ( ie , 5-session single-needle arthrocentesis plus low- or medium-molecular weight HA ) Introduction Three common haplotypes in the gene encoding catechol-O-methyltransferase ( COMT ) have been associated with pain modulation and the risk of developing chronic musculoskeletal pain , namely temporom and ibular disorder ( TMD ) . Haplotypes coding for higher enzymatic activity were correlated with lower pain perception . Rodent studies showed that COMT inhibition increases pain sensitivity through β2/3-adrenergic receptors . We hypothesized that the nonselective β-adrenergic antagonist propranolol will reduce clinical and experimental pain in TMD patients in a manner dependent on the individuals ' COMT diplotype . Methods Forty Caucasian female participants meeting the Research Diagnostic Criteria for TMD were genotyped for COMT polymorphisms and completed a r and omized , double-blind , placebo-controlled , two-period crossover pilot study . Each period consisted of a baseline assessment week followed by an intervention week ( propranolol or placebo ) . Changes in clinical pain ratings , psychological status , and responses to heat and pressure stimuli between baseline and intervention weeks were compared across periods . Results The number of patients reporting a reduction in pain intensity rating was greater during propranolol treatment ( P=0.014 ) compared with placebo . Propranolol significantly reduced a composite pain index ( P=0.02 ) but did not decrease other clinical and experimental pain ratings . When stratified by the COMT high activity haplotype , a beneficial effect of propranolol on pain perception was noted in patients not carrying this haplotype , a diminished benefit was observed in the heterozygotes , and no benefit was noted in the homozygotes . Conclusion COMT haplotypes may serve as genetic predictors of propranolol treatment outcome , identifying a subgroup of TMD patients who will benefit from propranolol therapy & NA ; The efficacy of amitriptyline was evaluated in 28 patients with chronic oral‐facial pain . Most of the patients had evidence of musculoskeletal pain while some had a history suggesting pain of neurogenic origin . Two patients had mixed elements of neurogenic and musculoskeletal pain . Amitriptyline was more effective than placebo in reducing pain after 4 weeks of treatment . No effect was found after only 1 week of drug administration in either dose range . When the patients were divided into depressed and non‐depressed groups based on their Hamilton depression scores , amitriptyline reduced pain in the depressed and in the non‐depressed groups as compared to placebo . Amitriptyline reduced the depression scores in the depressed group but had no effect on the depression scores in the non‐depressed group . Thus , pain reduction was not associated with a change in mood in the non‐depressed group . Amitriptyline had no effect on patients ' ratings of the intensity of experimental heat stimuli . We conclude that amitriptyline is effective in the treatment of chronic oral‐facial pain and that its efficacy is independent of its effects on depression . It appears that tricyclic antidepressants act in a fashion different from opiate drugs that alter the sensory discriminative component of pain PURPOSE Hyaluronic acid ( HA ) injections and occlusal splints have been suggested in the treatment of temporom and ibular joint ( TMJ ) derangements , but no sufficient data are available from controlled clinical trials comparing HA injection with another treatment modality . This study compared the effectiveness of a single HA injection , a double HA injection , and splint therapy for the treatment of TMJ disc displacement with reduction ( DDR ) . MATERIAL S AND METHODS A prospect i ve clinical trial was design ed . The study sample included patients with TMJ DDR . The primary predictor variable was treatment method . Patients were divided into 4 groups : control , single HA injection , double HA injection , and stabilization splint therapy . Patients were r and omly assigned to 1 of 3 treatment groups . The control group was self-selected . The primary outcome variable was pain at rest and during mastication . The secondary outcome variables were TMJ noise , quality of life , and level of jaw movements . Clinical symptoms and jaw movements were evaluated at baseline and at 6-month follow-up . Descriptive , comparative , correlation , and multivariate analyses were conducted . RESULTS The sample included 51 patients ( 66 TMJs ) 18 to 48 years old . All treatment groups showed significant improvement compared with baseline values for pain , TMJ noise , quality of life , and maximum mouth opening ( MMO ) at 6-month follow-up ( P < .05 ) . However , the 2 HA injection groups indicated superior improvement for pain , MMO , and quality of life compared with the stabilization splint group ( P < .05 ) . CONCLUSIONS The results of this study showed that HA injection and stabilization splinting are acceptably successful treatment modalities to alleviate the clinical signs and symptoms of TMJ DDR A double-blind pilot study was undertaken to test the administration of low doses of the long-acting benzodiazepine drug clonazepam in the management of chronic intractable temporom and ibular disorder/myofascial pain patients who were not responsive to occlusal splint , behavioral , and physical therapy . Clonazepam was selected for its long duration and its cholinergic/GABA-ergic/serotonergic , anxiolytic , muscle relaxant , and sedative properties . Clonazepam appears to be effective when compared to a placebo . However , caution must be observed with long-term administration of clonazepam because of potential side effects such as depression and liver dysfunction . Indiscriminate administration of clonazepam may be harmful to the patient Abstract The present investigation is a preliminary double-blind , controlled placebo , r and omized clinical trial with a six month follow-up period . The study aim ed to assess the efficacy of type A botulinum toxin ( Botox , Allergan , Inc. Irvine , CA ) to treat myofascial pain symptoms and to reduce muscle hyperactivity in bruxers . Twenty patients ( ten males , ten females ; age range 25 - 45 ) with a clinical diagnosis of bruxism and myofascial pain of the masticatory muscles were enrolled in a double-blind , controlled placebo , r and omized clinical trial , with a treatment group ( ten subjects treated with botulinum toxin injections- BTX-A ) and a control group ( ten subjects treated with saline placebo injections ) . A number of objective and subjective clinical parameters ( pain at rest and during chewing ; mastication efficiency ; maximum nonassisted and assisted mouth opening , protrusive and laterotrusive movements ; functional limitation during usual jaw movements ; subjective efficacy of the treatment ; tolerance of the treatment ) were assessed at baseline time and at one week , one month , and six months follow-up appointments . Descriptive analysis showed that improvements in both objective ( range of m and ibular movements ) and subjective ( pain at rest ; pain during chewing ) clinical outcome variables were higher in the Botox treated group than in the placebo treated subjects . Patients treated with BTX-A had a higher subjective improvement in their perception of treatment efficacy than the placebo subjects . Differences were not significant in some cases due to the small sample size . Results from the present study supported the efficacy of BTX-A to reduce myofascial pain symptoms in bruxers , and provided pilot data which need to be confirmed by further research using larger sample Abstract The aim of the study was to evaluate the analgesic effect of lidocaine in a double‐blind , controlled multi‐center study on patients with atypical odontalgia ( AO ) – a possible orofacial neuropathic pain condition . Thirty‐five consecutive AO patients ( range 31–81 years ) with a mean pain duration of 7.2 years ( range 1–30 years ) were recruited from four different orofacial pain clinics in Sweden . In a r and omized cross‐over design , 1.5 ml local anesthesia ( 20 mg/ml lidocaine and 12.5 μg/ml adrenaline ) or 1.5 ml saline ( 9 mg/ml NaCl solution ) ( placebo ) was injected to block the painful area . The VAS pain scores showed an overall effect of time ( ANOVA : P < 0.001 ) and treatment ( ANOVA : P = 0.018 ) with a significant interaction between the factors ( ANOVA : P < 0.001 ) . Overall , VAS pain relief was significantly greater at 15–120 min following the lidocaine injections compared to the placebo injections ( Tukey : P < 0.05 ) . All patients demonstrated significant disturbances in somatosensory function on the painful side compared to the non‐painful side as revealed by quantitative sensory tests , however , only one significant inverse correlation was found between percentage pain relief and the magnitude of brush‐evoked allodynia ( Spearman : P < 0.01 ) . In conclusion , AO patients experienced significant , but not complete , pain relief from administration of local anesthetics compared with placebo . The findings indicate that the spontaneous pain in AO patients only to some extent is dependent on peripheral afferent inputs and that sensitization of higher order neurons may be involved in the pathophysiology of AO In patients with myofascial pain , painful trigger points are often treated using dry needling and local anesthetic injections . However , the therapeutic effect of these treatments has been poorly quantified , and the mechanism underlying the effect is poorly understood . In a r and omized , double-blind , double-placebo clinical trial , a pressure algometer was used to measure pain-pressure thresholds in the masseter and temporalis muscles of 30 subjects aged 23 to 53 years with myofascial pain in the jaws , before and after a series of dry needling treatments , local anesthetic injections , and simulated dry needling and local anesthetic treatments ( treatment group A : Procaine + simulated dry needling ; treatment group B : dry needling + simulated local anesthetic ; control group C : simulated local anesthetic + simulated dry needling ) . Subjects rated pain intensity and unpleasantness using visual analogue scales , and the data were analyzed using analysis of variance . Pain pressure thresholds increased slightly after treatment , irrespective of the treatment modality . Pain intensity and unpleasantness scores decreased significantly at the end of treatment in all groups . There were no statistically significant between-group differences in pain pressure thresholds and visual analogue scale scores at the end of treatment . The findings suggest that the general improvement in pain symptoms was the result of nonspecific , placebo-related factors rather than a true treatment effect . Thus , the therapeutic value of dry needling and Procaine in the management of myofascial pain in the jaw muscles is question able & NA ; Evidence of an effect by botulinum toxins is still lacking for most pain conditions . In the present r and omized , placebo‐controlled , crossover multicenter study , the efficacy of botulinum toxin type A ( BTX‐A ) was investigated in patients with persistent myofascial temporom and ibular disorders ( TMD ) . Twenty‐one patients with myofascial TMD without adequate pain relief after conventional treatment participated . A total of 50 U of BTX‐A or isotonic saline ( control ) was r and omly injected into 3 st and ardized sites of the painful masseter muscles . Follow‐up was performed after 1 and 3 months , followed by a 1‐month washout period , after which crossover occurred . Pain intensity at rest was the primary outcome measure , while physical and emotional function , global improvement , side effects , and clinical measures were additional outcome measures . There was no main difference between drugs ( ANOVA ; P = .163 ) , but there was a significant time effect ( P < .001 ) , so BTX‐A reduced mean ( SD ) percent change of pain intensity by 30 ( 33 % ) after 1 month and by 23 ( 30 % ) after 3 months compared to 11 ( 40 % ) and 4 ( 33 % ) for saline . The number of patients who received a 30 % pain reduction was not significantly larger for BTX‐A than after saline at any follow‐up visit . The number needed to treat was 11 after 1 month and 7 after 3 months . There were no significant changes after treatment in any other outcome measures , with the exception of pain on palpation , which decreased 3 months after saline injection ( P < .05 ) . These results do not indicate a clinical relevant effect of BTX‐A in patients with persistent myofascial TMD pain . Botulinum toxin type A is not an effective adjunct to conventional treatment in persistent myofascial temporom and ibular disorders An account is given of a two-centre controlled clinical trial to assess the efficacy of dothiepin ( Prothiaden ) against placebo and a soft bite-guard in the treatment of psychogenic facial pain . The results confirm the superiority of the dothiepin to placebo in achieving pain relief , but show no benefit from the use of mechanical treatment . Short-term relapse of pain which occurred in the follow-up period was not associated with recurrence of psychiatric symptoms but appeared to be directly related to withdrawal of dothiepin PURPOSE To show whether an intra-articular ( IA ) infiltration of 1 mL sodium hyaluronate ( SH ) into the temporom and ibular joint ( TMJ ) would significantly reduce pain and improve joint function in Wilkes stage II disease , compared with the oral administration of a combination of methocarbamol and paracetamol . PATIENTS AND METHODS Forty-one patients with Wilkes stage II disease were selected and r and omly assigned to 2 groups . The experimental group received 1 IA infiltration of SH with assessment s at days 14 , 28 , 56 , and 84 . The control group was given 2 tablets of a combination of methocarbamol 380 mg and paracetamol 300 mg every 6 hours for 4 weeks , with assessment s at days 14 and 28 . RESULTS Forty-one patients were r and omized into the study ( SH : 20 patients , control drug : 21 patients ) . A statistically significant difference ( P < . 05 ) was detected in favor of the SH group from day 56 onward for TMJ pain at rest , from day 14 onward for pain on jaw opening , and at days 28 and 56 for pain on mastication . The TMJ function was statistically significantly ( P < .05 ) better in the test group at all follow-up visits . The global evaluation of efficacy by both , the patients and investigators , was better for the test group . No adverse reactions were detected with SH . CONCLUSIONS An IA infiltration of SH showed better efficacy in reducing pain and improving joint function in Wilkes stage II disease , compared with the oral administration of methocarbamol-paracetamol tablets Patients with chronic orofacial pain often report disturbances in sleep , leading to the hypothesis that nocturnal motor hyperactivity of the muscles of mastication may contribute to the nociceptive process . This hypothesis was tested in a controlled study to evaluate the relationship between sleep stages , patient self-report of pain in the orofacial region , and nocturnal masticatory muscle activity . Twenty subjects participating in a two-period , within-subject , crossover study received triazolam or placebo for 4 nights . Sleep , pain , and m and ibular range of motion were assessed at baseline , following the first period , and again following the second period ; a 3-day washout period separated the two treatments . Subjective report of sleep quality was significantly improved following triazolam in comparison to placebo as measured by category scales for sleep quality , restfulness , and sleep compared to usual . The amount of time spent in stage-2 sleep was also significantly increased by triazolam . No improvement was seen in pain as measured by palpation with an algometer , in scales for sensory intensity and the affective component of pain , or in daily pain diaries . Mean facial muscle electromyographic activity for 30-second epochs averaged over the entire period of sleep did not reveal any differences in muscle activity across the three conditions . These data indicate that improvements in sleep quality and alterations in sleep architecture do not affect nocturnal facial muscle activity or subsequent pain report in temporom and ibular patients , thereby failing to support the hypothesized relationship between sleep disturbances and chronic orofacial pain PURPOSE Among patients with Wilkes stage III and IV disease undergoing arthroscopic lysis and lavage , does the use of an intra-articular injection of sodium hyaluronate ( SH ) , when compared with Ringer lavage , result in better postoperative pain control and temporom and ibular joint ( TMJ ) function ? PATIENTS AND METHODS We design ed and implemented a r and omized , double-blind , pilot controlled clinical trial . The study sample was composed of patients with middle Wilkes stage ( late stage III and early stage IV ) disease . Subjects were r and omized to 1 of 2 treatment limbs . The treatment group received Ringer lactate plus an injection of 1 mL of SH after arthroscopy , whereas the control group was given Ringer lactate during arthroscopy . The primary outcome variables were pain and TMJ function measured by use of visual analog scales . Appropriate descriptive and bivariate statistics were computed . A P value less than .05 was considered statistically significant . RESULTS The study sample was composed of 40 patients with 20 subjects enrolled in both treatment groups . There were no statistically significant differences between the 2 groups in terms of demographics and preoperative variables . Postoperative analgesia was statistically significant in the treatment group with respect to the control group on the visits on days 14 and 84 . No statistically significant differences were observed between the 2 groups in the maximum interincisal opening and tolerance . CONCLUSIONS An intra-articular injection of SH after arthroscopic lysis and lavage is effective in reducing pain in patients with TMJ dysfunction , enhancing postsurgical recovery . The analgesic effect of treatment with SH is maintained in the long term AIMS To compare the relative effectiveness of a benzodiazepine ( clonazepam ) , a muscle relaxant ( cyclobenzaprine ) , and a placebo for the treatment of jaw pain upon awakening , when each is combined with the recommended nonpharmacological components of initial medical management . METHODS Forty-one subjects were recruited with a diagnosis of myofascial pain based on the Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) . All subjects were given education about TMD and a self-care program . Subjects were r and omized into 1 of 3 groups : clonazepam ( 0.5 mg/night ) , cyclobenzaprine ( 10 mg/night ) , or placebo . The primary outcome measure was the subjects ' average intensity of jaw pain upon awakening over the prior week . This was recorded with a visual analog scale at pretreatment and at the completion of the 3-week trial . A secondary outcome measure was sleep quality based on the Pittsburg Sleep Quality Index . RESULTS Within-group changes showed a statistically significant ( P < .001 ) decrease in jaw pain upon awakening for all 3 groups . Between-group differences demonstrated a statistically significant difference ( P < .016 ) between cyclobenzaprine and placebo , and between cyclobenzaprine and clonazepam . There was no significant effect on sleep quality in any group . CONCLUSION This study suggests that cyclobenzaprine is statistically superior to either placebo or clonazepam when added to self-care and education for the management of jaw pain upon awakening . Based on the subjects ' report of sleep quality , these medications failed to significantly improve sleep in the short term UNLABELLED Burning Mouth Syndrome ( BMS ) is a disease that manifests as burning in the tongue or in any area of the oral mucosa , in the absence of clinical ly verifiable injuries . OBJECTIVES To verify the efficacy of alpha lipoic acid ( ALA ) and gabapentin ( GABA ) , used individually and jointly , to reduce the burning in patients with burning mouth and establish a drug therapy for the BMS . STUDY DESIGN During April and May 2008 , we conducted a r and omized , double-blind , placebo-controlled trial in the Department of Clinical Stomatology , Faculty of Dentistry , Rosario , Argentina . The gathering of patients was between those ones with BMS who were treated in our service between March 2003 and March 2008 without complying with the applied treatments . The 120 patients were r and omly divided into 4 groups and were provided , by lot and in a blinded fashion , with four different treatment cycles consisting of the following drugs : Group A ( n = 20 ) 600 mg / day of alpha lipoic acid for two months , Group B ( n = 20 ) 300 mg / day of gabapentin for two months , Group C ( n = 20 ) a combination of both drugs for two months and Group D ( n = 60 ) 100 mg / day of cellulose starch for two months ( control group ) . RESULTS AND CONCLUSIONS all 120 patients completed the treatment . The best response was obtained with the combination of ALA + GABA , with a 70 % of the cases with reduced burning in this group and a 13.2 times greater chance of presenting positive changes for these patients than those taking placebo . The combined use of drugs that act at different levels of the nociceptive system can be useful for the treatment of this syndrome AIMS An 8-week parallel , placebo-controlled , double-blind trial evaluated the efficacy of the antidepressant trazodone in the treatment of chronic burning mouth pain . METHODS Thirty-seven carefully selected women aged 39 to 71 ( mean 58.6 years ) were r and omized to receive either 200 mg of trazodone or a placebo in a similar manner . Pain and pain-related symptoms were evaluated on a visual analogue scale and other measures at 0 , 2 , 4 , and 8 weeks . RESULTS There were no significant differences between the groups in treatment effects for pain or pain-related symptoms . Seven patients in the trazodone group and 2 in the placebo group failed to complete the trial because of side effects . The most common side effects were dizziness and drowsiness . CONCLUSION In this controlled trial , trazodone failed to relieve burning mouth pain Background Serotonin ( 5-HT ) mediates pain by peripheral 5-HT3-receptors . Results from a few studies indicate that intramuscular injections of 5-HT3-antagonists may reduce musculoskeletal pain . The aim of this study was to investigate if repeated intramuscular tender-point injections of the 5-HT3-antagonist granisetron alleviate pain in patients with myofascial temporom and ibular disorders ( M-TMD ) . Methods This prospect i ve , r and omized , controlled , double blind , parallel-arm trial ( RCT ) was carried out during at two centers in Stockholm , Sweden . The r and omization was performed by a research er who did not participate in data collection with an internet-based application ( www.r and omization.com ) . 40 patients with a diagnose of M-TMD according to the Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) were r and omized to receive repeated injections , one week apart , with either granisetron ( GRA ; 3 mg ) or isotonic saline as control ( CTR ) . Results The median weekly pain intensities decreased significantly at all follow-ups ( 1- , 2- , 6-months ) in the GRA-group ( Friedman test ; P < 0.05 ) , but not in the CTR-group ( Friedman-test ; P > 0.075 ) . The numbers needed to treat ( NNT ) were 4 at the 1- and 6-month follow-ups , and 3.3 at the 2-month follow-up in favor of granisetron . Conclusions Repeated intramuscular tender-point injections with granisetron provide a new pharmacological treatment possibility for myofascial pain patients with repeated intramuscular tender-point injections with the serotonin type 3 antagonist granisetron . It showed a clinical ly relevant pain reducing effect in the temporom and ibular region , both in a short- and long-term aspect . Trial registration European Clinical Trials Data base 2005 - 006042 - 41 as well as at Clinical Trials NCT02230371 Abstract This r and omized , double-blind study was design ed to evaluate the effectiveness of the topical cream Theraflex-TMJ ( NaBob/Rx , San Mateo , CA ) in patients with masseter muscle pain and temporom and ibular joint ( TMJ ) pain . Fifty-two subjects ( 5 males and 47 females ) were instructed to apply a cream over the afflicted masseter muscle(s ) or over the jaw joint(s ) twice daily for two weeks . Theraflex-TMJ cream was used by the experimental group , while a placebo cream was used by the control group . The means of pain ratings were calculated prior to the application of the cream ( baseline ) , after ten days of tx ( period 1 ) , and 15 days of tx ( period 2 ) days of treatment and five days after stopping the treatment ( follow-up ) . There was a significant decrease in reported pain levels from baseline in the experimental group for period 1 ( p<0.01 ) , period 2 ( p<0.001 ) , and follow-up ( p<0.01 ) . For the control group , no significant differences were found between the different time periods ( p>0.05 ) . There was evidence of minor side effects such as skin irritation and /or burning on the site of the application in two subjects in the experimental as well as two subjects in the control groups . The data strongly suggest that Theraflex-TMJ topical cream is safe and effective for reducing pain in the masseter muscle and the temporom and ibular joint The aim of the study was the evaluation of myorelaxant action of bee venom ( BV ) ointment compared to placebo . Parallel group , r and omized double blinded trial was performed . Experimental group patients were applying BV for 14 days , locally over masseter muscles , during 3-minute massage . Placebo group patients used vaseline for massage . Muscle tension was measured twice ( TON1 and TON2 ) in rest muscle tonus ( RMT ) and maximal muscle contraction ( MMC ) on both sides , right and left , with Easy Train Myo EMG ( Schwa-medico , Version 3.1 ) . Reduction of muscle tonus was statistically relevant in BV group and irrelevant in placebo group . VAS scale reduction was statistically relevant in both groups : BV and placebo . Physiotherapy is an effective method for myofascial pain treatment , but 0,0005 % BV ointment gets better relief in muscle tension reduction and analgesic effect . This trial is registered with Clinical trials.gov NCT02101632 Diffuse sclerosing osteomyelitis ( DSO ) of the m and ible is a chronic condition , the cause of which is not known . Jaw pain , occurring irregularly , is a typical symptom . The aim of the study was to assess the effectiveness of disodium clodronate for relieving pain in patients with DSO . Disodium clodronate is a bisphosphonate used to treat diseases of bone and calcium metabolism . Ten DSO patients experiencing pain received disodium clodronate or placebo intravenously on a r and omized double-blind basis . Both minimum ( 300 mg ) and maximum ( 900 mg ) doses were well tolerated . Disodium clodronate administration did not result in better immediate pain relief than placebo administration . However , 6 months after treatment there was a statistically significant difference in pain intensity between the groups , with the disodium clodronate group experiencing significantly less pain The purpose of this study was to compare the efficacy and the complications of intra-articular temporom and ibular joint ( TMJ ) injections in 40 patients with osteoarthritis of the TMJ . The subjects were r and omly divided into two groups , and the patients received either two intra-articular injections with sodium hyaluronate or two intra-articular injections with corticosteroids , 14 days apart . The effect of the treatment was evaluated 14 days , 1 and 6 months after the initial injection and was based on the following measurements : pain intensity , pain localization , joint sounds , m and ibular function and complications . Both groups of patients had less pain intensity at the 6-month follow-up , and there was significantly less pain intensity in the group of patients receiving sodium hyaluronate compared with corticosteroids ( P = 0.001 ) . A decrease in crepitation was seen in both groups . In the 20 subjects receiving sodium hyaluronate both the m and ibular vertical opening and protrusion increased significantly ( P < 0.000 ) . Lateral movement from the affected side increased both in subjects injected with sodium hyaluronate ( P = 0.024 ) , and those injected with corticosteroids ( P = 0.042 ) . In conclusion , this study confirms that injections in the TMJ with sodium hyaluronate or corticosteroids may reduce pain and improve function in patients with osteoarthritis . The injections were more effective in patients with only TMJ pain compared with patients suffering from both TMJ and myofascial pain . Injection with sodium hyaluronate was significantly more effective in decreasing pain intensity than corticosteroids . Temporary pain after injections may be observed OBJECTIVE To observe the clinical efficacy of livial on postmenopause women with burning mouth syndrome . METHODS Fifty six postmenopause women with burning mouth syndrome were r and omly divided into two groups , 26 patients were treated with livial as the treatment group , 30 patients were treated with oryzanol and vitamin E as the control . To evaluate the effect , all the patients were observed in 3 - 6 months after therapy . RESULTS The result showed that the total effective rate of the treatment group was 84.62 % after 3 months , 88.46 % after 6 months , and significantly higher than that in the control(P < 0.005 ) . CONCLUSION It is indicated that livial is safer and more effective than nylestriol in treatment with burning mouth syndrome The effects of iontophoretically applied dexamethasone in a lidocaine vehicle were compared with those of saline placebo in 53 patients with one of three diagnoses of painful temporom and ibular joint pathologic conditions : disk displacement with reduction , disk displacement without reduction , and osteoarthritis . Both dexamethasone and the saline placebo produced a significant reduction in pain scores from baseline levels after the first two of three treatments . There were no observed differences , however , in pain report or m and ibular range of motion between the dexamethasone and placebo groups . A trend for pain relief was noted in the subgroup that received dexamethasone with a diagnosis of osteoarthritis . Results may reflect varying degrees of inflammation or central nervous system hyperexcitability , or both , in this heterogeneous study sample . Potential confounding variables were lack of knowledge of actual drug penetration , the effects of electric current transmitted by the iontophoresor , and pain reduction caused by cyclic fluctuations in symptoms . These data suggest that iontophoretically applied dexamethasone is no more effective than saline placebo in providing pain relief in patients with temporom and ibular joint pain OBJECTIVES This study was carried out to compare intra-articular ozone gas injection and drug therapy as conservative treatment modalities for internal derangement of the temporom and ibular joint ( TMJ ) . STUDY DESIGN Sixty patients ( 49 female and 11 male ) with bilateral internal derangement of the TMJs , disc displacement with reduction , were included in this study . They were divided r and omly into 2 equal groups . The first group was treated by a direct injection of ozone gas into the superior joint space . Each joint received 2 mL ozone-oxygen mixture ( ozone gas concentration 10 μg/mL ) . The injections were repeated 2 times per week for 3 weeks . The second group received nonsteroidal antiinflammatory drugs and muscles relaxants . The clinical signs and symptoms before and after the treatment were assessed according to Helkimo 's clinical dysfunction index . RESULTS The results showed that 87 % of the patients who received ozone gas injections into the superior joint space ( n = 26 ) either completely recovered ( 37 % ; n = 11 ) or improved ( 50 % ; n = 15 ) . In the second group , 33 % of the patients who were treated with nonsteroidal antiinflammatory drugs and muscle relaxants ( n = 10 ) showed only an improvement in their clinical dysfunction indexes . CONCLUSIONS Based on the findings of the present study , we can consider that intra-articular ozone gas injection is a promising new treatment modality for internal derangement of the TMJ . However , further clinical and experimental studies are required to provide direct evidence for its mechanism of action and to substantiate our results AIMS To compare the effectiveness of adding cyclobenzaprine , tizanidine , or placebo to patient education and a self-care management program for patients with myofascial pain and specifically presenting with jaw pain upon awakening . METHODS Forty-five patients with a diagnosis of myofascial pain based on the guidelines of the American Academy of Orofacial Pain participated in this 3-week study . The subjects were r and omly assigned into one of three groups : placebo group , TZA group ( tizanidine 4 mg ) , or CYC group ( cyclobenzaprine 10 mg ) . Patients were evaluated for changes in pain intensity , frequency , and duration by using the modified Severity Symptoms Index and changes in sleep quality with the use of the Pittsburgh Sleep Quality Index . Data were analyzed by ANOVA and post-hoc or nonparametric statistical tests as appropriate . RESULTS All three groups had a reduction in pain symptoms and improvement of sleep quality based on a comparison of pretreatment and treatment scores . However , no significant differences among the groups were observed at the posttreatment evaluation . CONCLUSION The use of tizanidine or cyclobenzaprine in addition to self-care management and patient education was not more effective than placebo for the management of patients with myofascial jaw pain upon awakening OBJECTIVE The aim of this study was to investigate the effect of intra-articular sodium hyaluronate ( SH ) injections on the main components of plasminogen activator ( PA ) system in the synovial fluid of temporom and ibular joint ( TMJ ) osteoarthritis ( OA ) . STUDY DESIGN Forty patients diagnosed with TMJ OA and 20 healthy control subjects were included in this study . Synovial fluid was collected in the OA group and the healthy group at baseline . The OA patients were r and omly divided into 2 groups ( 20 patients for each group ) : One group received 5 injections of SH , and the other received 5 injections of physiologic saline solution in the upper joint space at weekly intervals . Synovial fluid was collected before and after treatment . Urokinase-type PA ( uPA ) , soluble uPA receptor ( suPAR ) and PA inhibitor 1 ( PAI-1 ) levels in synovial fluid were quantified by enzyme-linked immunosorbent assay . RESULTS The OA patients had significantly higher uPA activity and levels of uPA ( median 80.01 ng/L ) , suPAR ( median 7.54 ng/L ) , and PAI-1 ( median 54.9 ng/mL ) than the healthy control subjects ( median 20.47 ng/L uPA , 2.34 ng/L suPAR , and 19.9 ng/mL PAI-1 ; ( P < .05 ) . The uPA activity and levels of uPA , suPAR , and PAI-1 were significantly decreased after SH injections in TMJs of OA patients ( P < .05 ) , and there was no difference after saline injection . Visual analog pain score reduction correlated with changes in uPA and uPAR levels as well as uPA activity . CONCLUSION The effects of SH on PA system provide new insight into a possible underlying mechanism by which SH alleviates pain of patients with TMJ OA BACKGROUND AND OBJECTIVES Myofascial Pain Dysfunction Syndrome ( MPDS ) has been recognized as the most common , nontooth-related chronic orofacial pain condition that confronts dentists . A variety of therapies has been described in literature for its management . The present study is a prospect i ve study carried out to evaluate the efficacy of occlusal splint therapy and compare it with pharmacotherapy ( using analgesics and muscle relaxants ) in the management of Myofascial Pain Dysfunction Syndrome . MATERIAL S AND METHODS Forty patients in the age range of 17 - 55 years were included in the study and r and omly assigned to one of two equally sized groups , A and B. Group A patients received a combination of muscle relaxants and analgesics while Group B patients received soft occlusal splint therapy . All the patients were evaluated for GPI , VAS , maximum comfortable mouth opening , TMJ clicking and tenderness during rest and movement as well as for the number of tender muscles at the time of diagnosis , after the 1 st week of initiation of therapy and every month for three months of follow-up . RESULTS There was a progressive decrease in GPI scores , number of tender muscles , TMJ clicking and tenderness with various jaw movements and significant improvement in mouth opening in patients on occlusal splint therapy during the follow-up period as compared to the pharmacotherapy group . CONCLUSION Occlusal splint therapy has better long-term results in reducing the symptoms of MPDS . It has better patient compliance , fewer side effects , and is more cost-effective than pharmacotherapy ; hence , it can be chosen for the treatment of patients with MPDS OBJECTIVE To compare the treatment potential of glucosamine sulfate ( GS ) and ibuprofen in patients diagnosed with temporom and ibular joint ( TMJ ) osteoarthritis ( OA ) . METHODS Forty women and 5 men received either GS ( 500 mg tid ) or ibuprofen ( 400 mg tid ) for 90 days in a r and omized double blind study . ASSESSMENT TMJ pain with function , pain-free , and voluntary maximum mouth opening , Brief Pain Inventory ( BPI ) question naire and masticatory muscle tenderness were performed after a one week washout and at Day 90 . Acetaminophen ( 500 mg ) dispensed for breakthrough pain was counted every 30 days to Day 120 . RESULTS In total , 176 adults were interviewed , 45 ( 26 % ) qualified , 39 ( 87 % ) completed the study ( 21 GS , 18 ibuprofen ) . Four discontinued due to stomach upset ( 3 ibuprofen , one GS ) , one due to dizziness ( GS ) , one due to inadequate pain control ( ibuprofen ) . Within-group analysis revealed significant improvement compared to baseline of all variables in both treatment groups but no change in acetaminophen used . Fifteen GS ( 71 % ) and 11 ibuprofen ( 61 % ) improved , with positive clinical response taken as a 20 % decrease in primary outcome ( TMJ pain with function ) . The number of patients with positive clinical response was not statistically different between groups ( p = 0.73 ) . Between-group comparison revealed that patients taking GS had a significantly greater decrease in TMJ pain with function , effect of pain , and acetaminophen used between Day 90 and 120 compared with patients taking ibuprofen . CONCLUSION GS and ibuprofen reduce pain levels in patients with TMJ degenerative joint disease . In the subgroup that met the initial efficacy criteria , GS had a significantly greater influence in reducing pain produced during function and effect of pain with daily activities . GS has a carryover effect PURPOSE Arthrocentesis has been used for the management of patients with temporom and ibular joint ( TMJ ) pain , with good success . The additional use of hyaluronic acid ( HA ) or corticosteroid ( CS ) remains controversial . The purpose of this study was to compare HA , CS , and lactated Ringer solution ( LR ; placebo ) after arthrocentesis . MATERIAL S AND METHODS This was a prospect i ve multicenter double-blinded r and omized clinical trial . Consecutive patients presenting to the oral and maxillofacial departments at Emory University , the University of Pennsylvania , the University of California-Los Angeles , the University of Cincinnati , and the Oregon Health Sciences University were enrolled in the study . Patients were r and omized to HA , CS , or LR . All patients underwent arthrocentesis and then the instillation of HA , CS , or LR . Patients were evaluated clinical ly at 1 and 3 months . The primary outcome variable was pain at 1 month ( by visual analog scale ) . Secondary outcome variables were pain at 3 months and analgesic consumption . Univariate , bivariate , and multivariate statistics were computed , with a P value less than .05 considered significant . RESULTS One hundred two patients were enrolled in the study . Four were lost to follow-up , leaving 98 patients for the final analysis . The mean age of patients in the HA , CS , and LR groups was 39.6 , 44.3 , and 51.8 years , respectively ( P = .02 ) . There was no difference among groups in time to follow-up at 1 month ( P = .11 ) . The mean decrease in pain in the CS group was 19 % for right-side procedures ( P = .12 ) and 36 % for left-side procedures ( P = .02 ) . The mean decrease in pain in the HA group was 31 % for right-side procedures ( P = .01 ) and 34 % for left-side procedures ( P = .01 ) . The mean decrease in pain in the LR group was 43 % for right-side procedures ( P < .01 ) and 37 % for left-side procedures ( P < .01 ) . There was no difference in pain decrease among groups ( P = .55 ) . There was no difference in the use of narcotic ( P = .52 ) or nonsteroidal anti-inflammatory drugs ( P = .71 ) among groups . CONCLUSION Arthrocentesis alone is as efficacious as arthrocentesis with HA or CS in decreasing TMJ pain Summary Dental hygienist‐delivered pain self‐management training was superior to continuous oral contraceptive therapy for women with TMD pain ; focusing on menstrually‐related changes in symptoms did not increase its efficacy . ABSTRACT Mounting evidence supports the importance of hormonal fluctuations in temporom and ibular disorder ( TMD ) pain among women . Stabilizing influential hormones or having a plan and skills for coping with hormonally related increases in TMD pain , therefore , may be beneficial for women with TMD pain . This r and omized clinical trial evaluated the short‐ and long‐term efficacy of 3 interventions for women with TMD pain : ( 1 ) dental hygienist‐delivered pain self‐management training ( SMT ; n = 59 ) ; ( 2 ) the same dental hygienist‐delivered pain self‐management training , but with a focus on menstrual cycle‐related changes in pain and other symptoms ( targeted SMT , or TSMT ; n = 55 ) ; and ( 3 ) continuous oral contraceptive therapy ( 6‐month trial ) aim ed at stabilizing hormones believed to be influential in TMD pain ( COCT ; n = 57 ) . Study participants completed outcome ( pain , activity interference , depression ) and process ( pain beliefs , catastrophizing , coping effectiveness ) measures before r and omization , and 6 and 12 months later . Intent‐to‐treat analyses supported the benefits of the SMT and TSMT interventions relative to COCT . Targeting the self‐management treatment to menstrual cycle‐related symptoms did not increase the treatment ’s efficacy . The benefits of the self‐management interventions relative to COCT for pain and activity interference were statistically significant at 12 months , but not at 6 months , whereas the benefits for the process measures generally were apparent at both time points . COCT was associated with multiple adverse events ( none serious ) . The study provides further support for long‐term benefits of a safe , low‐intensity ( 2 in‐person sessions and 6 brief telephone contacts ) , dental hygienist‐delivered self‐management treatment for TMD pain OBJECTIVE The purpose of this study was to identify the appropriate treatment element for initial anterior disc displacement without reduction subjects . STUDY DESIGN Sixty-nine consecutive patients with temporom and ibular joint disc displacement without reduction confirmed on magnetic resonance images were r and omly divided into 3 experimental treatment groups . The treatment of group 1 consisted of short-term nonsteroidal anti-inflammatory drugs and self-care instructions ( palliative care group ) ; group 2 , nonsteroidal anti-inflammatory drugs , self-care instructions , and occlusal appliance and mobilization therapy ( physical medicine group ) ; and group 3 , no treatment ( control group ) . Outcomes were assessed by means of a 5-item question naire that evaluated ( 1 ) symptom improvement , ( 2 ) difficulty of treatment , and ( 3 ) satisfaction with treatment during the 8-week observation period . RESULTS Improvement scores in the palliative care group were significantly better than those in the physical medicine group or the no-treatment group . Satisfaction scores showed no significant difference among the 3 groups . Difficulty from treatment for the physical medicine group was significantly greater than that for other 2 groups . CONCLUSION These data suggest that palliative care would be more appropriate as the initial therapy to treat painful anterior disc displacement without reduction & NA ; Stomatodynia is characterised by a spontaneous burning pain in the oral mucosa without known cause or recognised treatment . The purpose of this double‐blind , r and omised , multicentre parallel group study was to evaluate the efficacy of the topical use of clonazepam . Forty‐eight patients ( 4 men and 44 women , aged 65±2.1 years ) were included , of whom 41 completed the study . The patients were instructed to suck a tablet of 1 mg of either clonazepam or placebo and hold their saliva near the pain sites in the mouth without swallowing for 3 min and then to spit . This protocol was repeated three times a day for 14 days . The intensity was evaluated by a 11‐point numerical scale before the first administration and then after 14 days . Two weeks after the beginning of treatment , the decrease in pain scores was 2.4±0.6 and 0.6±0.4 in the clonazepam and placebo group , respectively ( P=0.014 ) . Similar effects were obtained in an intent‐to‐treat analysis ( P=0.027 ) . The blood concentration of clonazepam was similar whether it was measured 14 days after sucking a tablet three times a day or during the 5 h that followed sucking a single tablet ( n=5 ) . It is hypothesised that clonazepam acts locally to disrupt the mechanism(s ) underlying stomatodynia AIMS To evaluate , in an open trial , the pharmacotherapeutic efficacy of tricyclic antidepressant ( TCA ) drugs and gabapentin in patients with persistent myofascial pain and to identify patient and pain characteristics that may predict treatment outcome . METHODS A stepped pharmacotherapeutic protocol was employed . All 42 patients having persistent facial pain with tenderness of regional muscles were first prescribed amitriptyline , but those with side effects were subsequently transferred to nortriptyline . In patients where no response to TCAs was observed , gabapentin was initiated . Outcome was assessed by employing prospect i ve diaries recording pain intensity measured with an 11-point ( 0 - 10 ) verbal pain scale ( VPS ) . Individual characteristics in these patients and their influence on drug response and outcome were analyzed ; specifically , patients treated with TCAs were compared with those subsequently treated with gabapentin . Chi-square and t tests were used to analyze the data . RESULTS A total of 23 patients responded to TCAs and continued on this regimen , while 19 were resistant to TCAs and were subsequently treated with gabapentin . Their mean ( ± SD ) VPS score at baseline was 6.5 ± 1.9 on an 11-point scale . In TCA-treated patients , 43 % showed ≥ 50 % reduction in pain intensity . This was achieved with a mean amitriptyline dose of 16 ± 1.1 mg/d and a mean nortriptyline dose of 25 ± 2.1 mg/d . Patients who did not respond to TCAs were characterized by a significantly higher age , more comorbid medical illness , and evidence of more regional pain spread ( P < .05 ) . In spite of not responding to TCAs , 36.8 % of this group showed ≥ 50 % reduction in pain intensity following gabapentin therapy at a mean daily dose of 973.7 ± 68.8 mg . Overall , a stepped approach employing TCAs and gabapentin result ed in 54.8 % of all treated patients reporting improvements of ≥ 50 % in VPS scores . CONCLUSION This study has demonstrated the good pharmacotherapeutic response of persistent myofascial pain , even in more severe cases . Not being a r and omized controlled trial , the results may be biased and should be interpreted with caution . Patients who do not respond to TCAs may be a distinct subgroup and this needs further investigation . The results also suggest that gabapentin , at a lower dose than previously reported , is a good alternative in TCA-resistant patients This r and omized , double-blind , placebo-controlled study was undertaken to evaluate the efficacy and tolerability of lamotrigine added to gabapentin , a tricyclic antidepressant , or a nonopioid analgesic in patients whose neuropathic pain was inadequately controlled with these medications . Patients with neuropathic pain from diabetic peripheral neuropathy , postherpetic neuralgia , traumatic/surgical nerve injury , incomplete spinal cord injury , trigeminal neuralgia , multiple sclerosis , or HIV-associated peripheral neuropathy , who had a mean weekly pain score > or = 4 on an 11-point numerical rating scale , were r and omized to receive a flexible dose of lamotrigine 200 , 300 , or 400 mg daily ( n=111 ) or placebo ( n=109 ) for up to 14 weeks ( including eight weeks of dose escalation ) in addition to their pre study regimen of gabapentin , a tricyclic antidepressant , or a nonopioid analgesic . No statistically significant difference in the mean change in pain-intensity score from baseline to Week 14 ( primary endpoint ) was detected between lamotrigine and placebo ( P=0.67 ) . Differences between lamotrigine and placebo were not statistically significant for secondary efficacy assessment s , including mean changes from baseline in the Short-Form McGill Pain Question naire , the Neuropathic Pain Scale , rescue medication use , and the percentages of patients rated as much improved or very much improved at the end of treatment on the Clinician Global Impression of Change scale and the Patient Global Impression of Change scale . Lamotrigine was generally well tolerated . Lamotrigine ( up to 400 mg/day ) added to gabapentin , a tricyclic antidepressant , or a nonopioid analgesic did not demonstrate efficacy as an adjunctive treatment of neuropathic pain but was generally safe and well tolerated PURPOSE This study was design ed to investigate the efficacy of arthrocentesis with and without injection of sodium hyaluronate ( SH ) into the upper joint space in the treatment of temporom and ibular joint ( TMJ ) internal derangements . PATIENTS AND METHODS Forty-one TMJs in 5 males and 26 females aged 14 to 53 years comprised the study material . The patients ' complaints were limited mouth opening , TMJ pain and tenderness , and joint noises during function . Patients were r and omly divided into 2 groups in which only arthrocentesis was performed in 1 group and arthrocentesis plus intra-articular injection of sodium hyaluronate was performed in the other group . Both groups contained patients with disc displacement with reduction and with closed lock . Clinical evaluation of the patients was done before the procedure , immediately after the procedure , on postoperative day 1 , and at 1 , 2 , 3 , 4 , 5 , 6 , 9 , 12 , 18 , and 24 months postoperatively . Intensity of TMJ pain , jaw function , and clicking sounds in the TMJ were assessed using visual analog scales . Maximal mouth opening and lateral jaw movements also were recorded at each follow-up visit . RESULTS Both techniques increased maximal mouth opening , lateral movements , and function , while reducing TMJ pain and noise . CONCLUSIONS Although patients benefitted from both techniques , arthrocentesis with injection of SH seemed to be superior to arthrocentesis alone Abstract Chronic masticatory myalgia ( CMM ) can be defined as constant pain in the masticatory muscles for more than 6 months and is influenced by the central nervous system . The antiepileptic agent gabapentin acts central ly and is used for managing different types of chronic pain conditions . The objective of this study was to evaluate the analgesic action of gabapentin on CMM . In this 12‐week r and omized controlled clinical trial 50 patients were r and omly allocated into two study groups : 25 received gabapentin and 25 received placebo . The outcome measures utilized were pain reported on a VAS ( VAS‐pain ) , Palpation Index ( PI ) and impact of CMM on daily functioning reported on a VAS ( VAS‐function ) . Thirty‐six patients completed the study . Gabapentin showed to be clinical ly and statistically superior to placebo in reducing pain reported by patients ( gabapentin = 51.04 % ; placebo = 24.30 % ; P = 0.037 ) , masticatory muscle hyperalgesia ( gabapentin = 67.03 % ; placebo = 14.37 % ; P = 0.001 ) and impact of CMM on daily functioning ( gabapentin = 57.70 % ; placebo = 16.92 % ; P = 0.022 ) . It can be concluded from this study that gabapentin is effective for the management of CMM ABSTRACT Previous studies have shown chondroitin sulfate and glucosamine hydrochloride have beneficial effects on symptoms of osteoarthritis of the knee . Our aim was to study the effect of a daily dose of 1500 mg of glucosamine hydrochloride ( GH ) and 1200 mg of chondroitin sulfate ( CS ) taken for twelve weeks on subjects diagnosed with capsulitis , disk displacement , disk dislocation , or painful osteoarthritis of the temporom and ibular joint ( TMJ ) . Forty-five subjects were enrolled in the study and were r and omly assigned to either an active medication group or a placebo group . Eleven subjects were lost from the study for various reasons , result ing in fourteen subjects remaining in the active medication group and twenty subjects remaining in the placebo group . Subjects taking CS-GH had improvements in their pain as measured by one index of the McGill Pain Question naire , in TMJ tenderness , in TMJ sounds , and in the number of daily over-the-counter medications needed . Subjects taking the placebo medication had improvements in their pains as measured by the visual analog scale and by four indices of the McGill Pain Question naire . Additional studies are required to evaluate the clinical effectiveness of CS-GH and to determine the exact mechanism by which CS-GH affects the articular cartilage of synovial joints PURPOSE To evaluate the effects of botulinum toxin-A in the treatment of patients who have myofascial pain with or without functional disc displacement . PATIENTS AND METHODS Twenty-four participants were r and omly assigned to the study by using Research Diagnostic Criteria for Temporom and ibular Disorders . All patients were informed about botulinum toxin-A , and were required to give informed consent . Before the injections , patients were asked to fill out a Biobehavioral Question naire to evaluate their pain and psychological status , and afterward , electromyography of the right and left masseter and anterior temporal muscles was recorded . Saline was injected into the masseter and anterior temporal muscles in the placebo group , and botulinum toxin-A was used in the study group . On days 14 and 28 , patients were asked to fill out a Biobehavioral Question naire again , and electromyography of the right and left masseter and anterior temporal muscles was recorded again . RESULTS The study group showed improvement in pain and psychological status . Although a decrease in the action potentials of the masseter muscles on day 14 was followed by an increase on day 28 , the reduction of pain scores and improvement in psychological status continued on day 28 . CONCLUSIONS The injection of botulinum toxin-A decreases the muscle action potential in 14 days . The patients also show improvement in pain and psychological status Temporom and ibular dysfunction ( TMD ) has been established as a therapeutic challenge in the plastic and maxillofacial clinics . The current treatment recommendations for TMD include resting the jaw , soft diet , and pain medication with nonsteroidal analgesic agents . If conservative and noninvasive techniques do not work , more invasive techniques may be considered . The main goal of this study was to assess the safety and clinical utility of intraarticular injection of sodium hyaluronate for the treatment of symptoms associated with internal derangement of the temporom and ibular joint ( TMJ ) . In this prospect i ve study , 40 TMJs of 33 patients who have TMD were treated with intraarticular sodium hyaluronate injections at weekly intervals for 3 weeks . Pre- and postinjection pain intensity , the presence of joint sounds , and interincisial distance were documented . The follow-up period was 12 months . There was a statistically significant reduction of pain intensity ( P < 0.01 ) and joint sound ( P < 0.05 ) in all patients . This study shows that intraarticular hyaluronic acid injection for the treatment of reducing and nonreducing disc displacement of TMJ is an effective and safe management Objective . Pharmaceuticals are among factors that might be associated with temporom and ibular disorders ( TMDs ) , but knowledge about their utilization is limited . The purpose was to systematic ally register the regular use of medication in general among TMD patients and matched controls to enable comparisons to be made . Material and Methods . Three hundred consecutive patients referred for diagnosis and treatment of TMDs and fulfilling the Research Diagnostic Criteria were examined prospect ively and any medication recorded . Matched controls were registered parallel in time . The pharmaceuticals used were categorized according to the Anatomical Therapeutic Chemical Classification System ( ATC ) . Results . Forty-four percent of the patients received a main diagnosis of “ muscle disorder ” , 39 % “ disk disorder ” , and 17 % “ joint disorder ” . Fifty-one percent of all patients used some medication on a regular basis compared to 36 % of the controls ( p<0.001 ) . The average number of ATC categories used among all patients was 0.9 and among controls 0.5 ( p<0.001 ) . Of the female patients with the diagnosis “ muscle disorder ” , 23 % used antidepressants ( N06A ) , 6 % tranquilizers ( N05B ) , and 7 % sleep medication or sedatives ( N05C ) significantly more frequently than controls . Of the female patients diagnosed with a “ joint disorder ” , 26 % used antidepressants ( N06A ) significantly more frequently than controls . All other ATC categories differed non-significantly . Conclusions . The results suggest that the use of pharmaceuticals differs between patients and controls . TMD patients , particularly women diagnosed with “ muscle ” or “ joint ” disorders , appear to use drugs for depression more frequently than ordinary dental patients The clinical results obtained with phloctaphenin in an " open " study comprising cases of real neuralgia and spinal radicular pain syndromes and in a " double-blind " study comparing the preparation with a placebo , and involving algico-vasomotor syndromes of the face , are reported . The results obtained confirm the antalgic power of phloctaphenin for by the third day , subacute or chronic pain syndromes already presented a significant improvement in simptomatology , while in algico-vasomotor syndromes of the face , the treatment proved effective in eliminating pain attacks The aim of the present pilot investigation was to compare the effectiveness of six treatment protocol s providing temporom and ibular joint ( TMJ ) arthrocentesis with or without additional drugs to manage symptoms in patients with inflammatory-degenerative TMJ disease . A consecutive series of 72 patients with TMJ osteoarthritis ( axis group IIIb ) with pain lasting from more than 6 months were r and omly assigned to one of the groups receiving the following treatment protocol s : single-session two-needle arthrocentesis ( A ) , single-session two-needle arthrocentesis plus corticosteroid ( B ) , single-session two-needle arthrocentesis plus low molecular weight hyaluronic acid ( HA ) ( C ) , single-session two-needle arthrocentesis plus high molecular weight HA ( D ) , 5 weekly two-needle arthrocenteses plus low molecular weight HA ( E ) and 5 weekly single-needle arthrocenteses plus low molecular weight HA ( F ) . At the 3-month follow-up , improvement with respect to mean baseline values was recorded in all the five treatment groups completing the protocol . No significant differences emerged between groups in any outcome variable . The protocol providing five sessions of two-needle arthrocenteses plus low molecular weight HA allowed achieving the highest improvement in almost all the outcome variables . Findings suggested that no statistically significant differences existed between the treatment groups . The clinical significance of these findings needs to be tested with future studies on larger sample s with longer follow-up periods BACKGROUND Burning mouth syndrome ( BMS ) is a major diagnostic and therapeutic problem . Systemic and topical treatments ( capsaicin , lidocaine , anti-histamines , sucralfate and benzydiamine ) have been tried , but they appear to be inadequate . Topical capsaicin is bitter , may cause burning and has low therapeutic efficacy . We hypothesized that systemic administration of capsaicin could reduce the limitations of topical administration and have better therapeutic efficacy ; this hypothesis was tested in a controlled trial . METHODS Systemic oral capsaicin 0.25 % was used for patients with BMS , recruited in our single centre . After the diagnosis of BMS , patients were dentally and medically examined . They were alternatively assigned to treatment with capsaicin or to a shape/smell/taste/color matched placebo . The severity of symptoms was scored at trial entry and 30 days thereafter by investigators who were unaware of the assigned intervention . The visual analogical scale ( VAS ) measure was used to score the severity of pain , and results for the treated and untreated groups were compared by Fisher 's exact test . Analysis was performed by intention-to-treat . Statistical significance was considered for values of P < 0.05 . Data are expressed as mean + /- SD . RESULTS Fifty patients were enrolled ( 25 assigned to systemic capsaicin and 25 to placebo ) . The VAS score was significantly lower in treated patients ( 5.84 + /- 1.17 ) as compared to the placebo-control group ( 6.24 + /- 0.96 ) . The use of systemic capsaicin implied significant gastric toxicity ( referred gastric pain ) with eight cases ( 32 % ) documented in the treatment group as compared to zero cases ( 0 % ) in the placebo control group . CONCLUSION Systemic capsaicin is therapeutically effective for the short-term treatment of BMS but major gastrointestinal side-effects may threaten its large-scale , long-term use . This preliminary study suggests that more , adequately powered , r and omized controlled trials are necessary and worthy to come to a definitive assessment of this matter The aim of the study was to compare the effectiveness of two single-session protocol s , either adopting high- ( protocol A ) or medium-molecular weight hyaluronic acid ( protocol B ) , with the reference five-session protocol of temporom and ibular joint ( TMJ ) lavage plus viscosupplementation ( protocol C ) in the management of chronic TMJ degenerative disorders . A r and omized clinical trial ( RCT ) with ten participants per treatment group was design ed , with multiple observation points , ending at 6 months after treatment . Pain levels on a 10-point VAS scale were selected as the primary outcome variable to rate treatment effectiveness , along with a number of secondary outcome parameters . Findings showed that Group C patients had the highest decrease in pain levels . Nonparametric permutation analyses revealed that the global effect of treatment was significantly different between the three protocol s ( P = 0·024 ) . Pairwise comparisons showed that the differences of treatment effect between the two single-session interventions were negligible ( global P-value = 0·93 ) . On the contrary , the five-session protocol was significantly superior to both single-session protocol s ( global P-values ranging from 0·003 to 0·012 ) . In conclusion , in a population of age- , sex- , and psychosocial aspects-matched study groups , the st and ard of reference five-session protocol proved to be superior at 6 months as far as the decrease in pain levels was concerned , whilst there were no differences between the two single-session interventions . The absence of differences in treatment effect as for some other secondary clinical outcome variables may suggest that there is further space for future investigations attempting to reduce the number of multiple interventions for TMJ viscosupplementation 66 female in patients with dysfunction pain syndrome , chronic cephalgia and facial pain participated in a r and omized , placebo-controlled double-blind study , half the patients receiving a multivitamin preparation for 12 days and the other half a placebo . The biochemically determined vitamin status at the start of the study revealed gaps in the coverage of the vitamin supply , particularly with regard to the vitamins thiamin , riboflavin and folic acid . 65 % of the patients showed a sub clinical vitamin deficiency of two or more vitamins . With regard to the development of pain during the study no statistically significant differences could be determined , however , between the active-treatment and placebo groups . Nevertheless , a clear reduction in pain was more frequently observed in the active-treatment group , and a deterioration of pain more frequently in the placebo group . A reduction in pain was reported more often by patients in whom the values of alpha-ETK , alpha-EGOT , folic acid and cyanocobalamin improved in the course of the study . Vitamin administration in physiological doses evidently have only weak effects on the behavior of pain ; analgesic vitamin effects may be presumed in the case of correspondingly high therapeutic doses for a prolonged period UNLABELLED Lafutidine is a unique histamine H(2)-receptor antagonist ( H2RA ) that has a sensitizing effect on capsaicin-sensitive afferent neurons ( CSAN ) . This effect may make lafutidine useful for the treatment of burning mouth syndrome ( BMS ) . METHODS To evaluate the efficacy and safety of lafutidine in patients with oral burning sensation , a r and omized controlled trial was performed . Patients who had been receiving other H2RAs with no sensitizing effect on CSAN were r and omly assigned to receive lafutidine 10 mg twice daily for 12 weeks , instead of the previous H2RAs , plus gargling with azulene sulfonate sodium ( ASS ) ( lafutidine group , n = 36 ) or to continue to receive the previous H2RAs plus ASS gargling ( control group , n = 35 ) . The intensity of burning sensation was scored by means of a visual analog scale ( VAS ) . RESULTS Thirty-four patients in the lafutidine group and 30 in the control group completed the study . In the lafutidine group , the rate of improvement in the VAS score as compared with the baseline value was significant after 4 , 8 , and 12 weeks of treatment ( P < 0.05 ) . The improvement rate was consistently higher in the lafutidine group than in the control group ; the differences between the groups were significant ( P < 0.05 ) after 4 , 8 , and 12 weeks of treatment . Only two mild abdominal adverse events occurred in the lafutidine group , but neither required the termination of treatment . CONCLUSION Oral lafutidine is very safe and effective for reducing the intensity of oral burning sensation and may therefore be a viable option for the treatment of BMS Myofascial pain syndrome of the head and neck is a frequent cause of facial pain and is characterized by tender trigger points . In a double-blind study of 107 patients , local injection therapy using one of three solutions was applied at the trigger points by intracutaneous injection of 0.3 ml solution followed by deep infiltration of the site . Results using bupivacaine 0.25 % , lignocaine 1 % and saline 0.9 % were compared . There was no significant difference among groups with respect to reduction of pain and overall rating by patients of the therapeutic benefits . Fifty-three patients ( 49 % ) were free of symptoms after treatment , 40 patients ( 38 % ) reported substantial relief and in 14 patients ( 13 % ) symptoms remained unchanged . The findings suggest that relief of pain is mainly due to reflex mechanisms rather than to the pharmacological effects of the injected solutions . Physiological saline solution is recommended for use in local injection therapy OBJECTIVE The effectiveness of nonsteroidal anti-inflammatory drugs ( NSAIDs ) and physical therapy for disk displacement without reduction is unknown . This study compared this treatment method with nontreatment controls . METHODS Sixty patients with painful disk displacement without reduction and without osseous changes were r and omly divided in 2 groups , consisting of NSAID and physical therapy and a nontreated control group . Both groups were observed at 2 weeks and , for those patients who did not show any improvement , again at 4 weeks . RESULTS There was 60 % improvement in the treatment group compared with 33 % in the control group during the entire 4 weeks of the study . The number needed to treat for benefit was 3.75 , with a 95 % CI 2.103 to 65.935 . CONCLUSIONS A combination of NSAID and physical therapy for 4 weeks is effective as a primary treatment of patients with disk displacement without reduction and without osseous changes Our aim was to find out whether pain was better controlled if morphine or tramadol was injected intra-articularly after arthrocentesis with Ringer 's lactate in patients with painful temporom and ibular joints ( TMJ ) . This placebo-controlled , double-blind study involved 30 patients who had not responded to conservative treatment and who were divided r and omly into 3 groups of 10 patients each . All patients had arthrocentesis , and the drugs were given as intra-articular injections immediately after the procedure . One group was give 5 % Ringer 's lactate 1ml , the second morphine 1 mg , and the third tramadol 50 mg . Visual analogue scales ( VAS ) for pain were recorded at maximum mouth opening and at rest before intra-articular injection and after 15 and 30min ; at 1 , 2 , 3 , 8 , 12 , 24 , 36 and 48h ; and at 1 , 3 , and 6 monthly follow-up . The mean ( SD ) VAS decreased from 6.90 ( 1.45 ) to 2.6 ( 2.5 ) in the control group , from 7.30 ( 1.64 ) to 1.20 ( 0.79 ) in the morphine group ( p=0.005 ) , and from 7.10 ( 1.73 ) to 1.50 ( 1.78 ) in the tramadol group ( p=0.005 ) . We conclude that morphine given by intra-articular injection after arthrocentesis gives a significant , sustained ( 6 months ) improvement in pain relief compared with simple arthrocentesis alone . The effect was similar with tramadol except that it was shorter lived BACKGROUND Patients often present to otolaryngologists with chronic facial pain , presumed to be of sinus origin despite normal nasal endoscopy and sinus CT . This pain has increasingly been recognized as being of neurological origin with one of the commonest underlying causes being mid-facial segmental tension-type pain ( MFP ) which is a version of tension-type headache affecting the midface . OBJECTIVES PRIMARY OUTCOME MEASURES 1 . To determine whether low-dose amitriptyline reduces pain scores compared to surrogate placebo in patients with chronic MFP . 2 . To determine whether the addition of pindolol , a beta blocker with serotonin receptor blocking properties hastens onset of action or improves efficacy of amitriptyline . SECONDARY OUTCOME MEASURE to determine whether amitriptyline or amitriptyline with pindolol significantly reduces analgesic consumption . METHODOLOGY Sixty two patients were r and omized to three treatment groups ( a ) amitriptyline 10 mg daily ( b ) amitriptyline 10 mg daily with pindolol 5 mg twice daily and ( c ) loratadine 10 mg daily . Daily pain scores using a facial pain diary were recorded over eight weeks . RESULTS At 8 weeks , pain frequency and intensity were significantly reduced in patients treated with amitriptyline and in those receiving amitriptyline with pindolol compared to surrogate placebo . Patients on the combination therapy showed significantly improved clinical outcome and significantly reduced analgesic intake compared to those on amitriptyline alone . CONCLUSION Low dose amitriptyline is effective in the management of MFP and is enhanced by the addition of pindolol OBJECTIVE The aim of this study was to evaluate the clinical effects of oral glucosamine sulfate , compared with placebo , on osteoarthritis in the temporom and ibular joints ( TMJs ) . STUDY DESIGN Fifty-nine patients , consecutive referrals fulfilling the research diagnostic criteria for temporom and ibular disorder for TMJ osteoarthritis , confirmed roentgenographically , were r and omized to the daily intake of 1,200 mg glucosamine sulfate or identical placebo capsules in this double-blind trial . Pain on visual and verbal rating scales and opening capacity were registered before and after 6 weeks of medication . RESULTS The signs and symptoms were similar in the groups initially and they were ameliorated over time . No differences in improvement between groups after treatment were indicated . Eight patients in the glucosamine group and 2 in the placebo group stopped the medication prematurely . Gastrointestinal side effects were reported by a total of 10 and 3 patients , respectively . CONCLUSIONS Oral glucosamine sulfate was not superior to placebo in reducing signs and symptoms of osteoarthritis in the TMJs in this short-term trial The pain-relieving effect of indomethacin phonophoresis on temporom and ibular ( TMJ ) joint pain was evaluated in a double-blind , placebo-controlled clinical trial . Twenty subjects , who have TMJ pain , were included for this study and r and omly assigned to either the experimental group ( n = 10 ) or the control group ( n = 10 ) . Each treatment consisted of the application of ultrasound massage ( 1.0 MHz , 0.8 to 1.5 W/cm2 continuous output ) for 15 minutes to the painful temporom and ibular joint . As a conducting medium , 1 % indomethacin cream was used for the experimental group and placebo cream for the control group respectively . Pre- and post-treatment pain levels and pain sensitivity were assessed with visual analogue scales ( VAS ) and pressure pain threshold ( PPT ) . Mean data indicated that post-treatment VAS was significantly decreased and post-treatment PPT was significantly increased in the experimental group , not in the control group . The results of this study suggest that indomethacin phonophoresis provides significant pain relieving effect over the TMJ pain OBJECTIVE Patients with burning mouth syndrome ( BMS ) often represent a clinical challenge as available agents for symptomatic treatment are few and often ineffective . The aim was to evaluate the effect of a bupivacaine lozenge on oral mucosal pain , xerostomia , and taste alterations in patients with BMS . METHODS Eighteen patients ( 4 men and 14 women ) aged 39 - 71 years with BMS were included in this r and omized , double-blinded , placebo-controlled , crossover trial . Lozenges ( containing bupivacaine or placebo ) were administrated three times a day for 2 weeks for two separate treatment periods . Assessment of oral mucosal pain , xerostomia , and taste alterations was performed in a patient diary on a visual analog scale ( ranging from 0 to 100 mm ) before and after the lozenge was dissolved . RESULTS The bupivacaine lozenge significantly reduced the burning oral pain ( P < 0.001 ) , increased the sense of taste disturbances ( P < 0.001 ) , and had no impact on xerostomia , when adjusted for the treatment period . CONCLUSIONS Our results indicate that the bupivacaine lozenge offers a novel therapeutic modality to patients with BMS , although without alleviating effect on the associated symptoms , taste alterations , and xerostomia The long-term effect ( 2 years ) of occlusal treatment and intra-articular injections of a mixture of corticosteroid and local anaesthetic was investigated in two groups of patients with pain and dysfunction in the temporom and ibular joint ( TMJ ) . Fifteen patients were treated with injections and eighteen patients with occlusal adjustment . The TMJ was tender to palpation in all patients . The intra-articular injections were given once a week for three weeks . The occlusal treatment included splints , grinding on natural teeth and occlusal correction of complete dentures . The severity of the subjective symptoms and clinical signs was estimated before and after treatment . Both sorts of treatment reduced the subjective symptoms and the clinical signs significantly , but the reduction was significantly greater after the intra-articular injections . The effect of the injections was less efficient in patients with radiographic signs of remodelling of the TMJ and general joint symptoms . It was concluded that both intra-articular injections of corticosteroid combined with local anaesthetic and occlusal treatment have a long palliative effect on TMJ pain and dysfunction . The intraarticular treatment , however , had a greater effect on the clinical signs The clinical efficacy , side effect liability , and hormonal effects of two prototypic pharmacologic agents were evaluated for the management of chronic myogenous facial pain in a double-blind , r and omized , controlled clinical trial . Thirty-nine subjects ( 35 women , . 4 men ) with daily or near-daily orofacial pain of at least 3 months ' duration and tenderness to palpation of masticatory muscles participated . Patients were r and omly allocated to one of four treatments : placebo , diazepam , ibuprofen , or the combination of diazepam and ibuprofen . Pain , mood , muscle tenderness , maximal interincisal opening , and plasma levels of beta-endorphin were measured following 2-week baseline and 4-week treatment periods . Pain , as measured by a visual analog scale , was significantly decreased in the diazepam and diazepam plus ibuprofen groups but not for the ibuprofen or placebo groups . Analysis of variance showed a significant drug effect for diazepam but not for ibuprofen , indicating that pain relief was attributable to diazepam . No significant changes were noted in muscle tenderness , interincisal opening , or plasma beta-endorphin level . This study supports the efficacy of diazepam in the short-term management of chronic orofacial muscle pain . The lack of effect following administration of an anti-inflammatory analgesic suggests that inflammation is not the basis for chronic muscle pain in the orofacial region , and that the analgesic effect of such medications is not sufficient for pain relief in this condition R and omized clinical trials of amitriptyline will require data from pilot studies to be used for sample size estimates , but such data are lacking . This study investigated the 6-week and 1-year effectiveness of low dose amitriptyline ( 10 - 30 mg ) for the treatment of patients with chronic temporom and ibular disorder ( TMD ) pain . Based on clinical examination , patients were divided into two groups : myofascial and mixed ( myofascial and temporom and ibular joint disorders ) . Baseline pain was assessed by a Visual Analogue Scale ( VAS ) for pain intensity and by the McGill Pain Question naire ( MPQ ) . Depression was assessed by the Beck Depression Inventory ( BDI ) short form . Patient assessment of global treatment effectiveness was obtained after 6 weeks and 1 year of treatment by using a five-point ordinal scale : ( 1 ) worse , ( 2 ) unchanged , ( 3 ) minimally improved , ( 4 ) moderately improved , ( 5 ) markedly improved . The results showed a significant reduction for all pain scores after 6 weeks and 1 year post-treatment . The depression scores changed in depressed but not in non-depressed patients . Global treatment effectiveness showed significant improvement 6 weeks and 1 year post-treatment . However , pain and global treatment effectiveness were less improved at 1 year than at 6 weeks Our aim was to evaluate the efficacy of autologous blood injection in the treatment of chronic recurrent dislocation of the temporom and ibular joint ( TMJ ) in a prospect i ve r and omised controlled clinical study . Forty-eight patients ( 11 men and 37 women ) with chronic recurrent dislocation of the TMJ were r and omly assigned to 1 of 3 equally sized groups . Patients in the first group were treated with injection of autologous blood ( ABI ) alone into the superior joint space and the pericapsular tissues . Those in the second group were treated with intramaxillary fixation ( IMF ) alone for 4 weeks , and those in the third group were treated with ABI and IMF for 4 weeks . Interincisal distance , digital panoramic radiograph , incidence of recurrent dislocation , and pain in the TMJ were assessed postoperatively at 2 weeks and at 1 , 3 , 6 , and 12 months . The mean ( SD ) reduction in interincisal distance in the group treated with both techniques was 11.0 ( 1.9 ) , which was significantly higher than in either the group treated with ABI , which was 8.5 ( 2.4 ) or IMF , which was 9.1 ( 2.1 ) . The results in the ABI group and the IMF group did not differ significantly . The combined group showed the biggest decrease . The ABI alone group had the most recurrences ( n=8 , which were treated by repeated injections with no recurrence after the third ) . The IMF alone group had only 3 and there were none in the combined group . We conclude that ABI is a simple and safe technique for the treatment of dislocation of the TMJ in the outpatient clinic . Recurrence can be overcome by multiple injections . However , the best clinical results are given by a combination of ABI and IMF PURPOSE Many different surgical and nonsurgical techniques have been used to treat patients with chronic recurrent temporom and ibular joint ( TMJ ) dislocation . The nonsurgical techniques consist of injecting different substances into the TMJ area . This study was carried out to assess autologous blood injection to the TMJ for treatment of chronic recurrent TMJ dislocation . PATIENTS AND METHODS Thirty patients having chronic recurrent TMJ dislocation were r and omly divided into 2 equal groups ( 15 patients in each ) . Group A was treated only by autologous blood injection into the superior joint space ( SJS ) , whereas group B received autologous blood injections to the SJS and the pericapsular tissues ( PT ) . RESULTS At the end of the follow-up period of 1 year , the results of the current study have showed that injection of autologous blood to the SJS and PT gave a higher success rate ( 80 % ) than its injection only into the SJS ( 60 % ) . Moreover , the patients of group B had an average decrease in their maximal mouth opening ( 5.3 + /- 2.1 ) higher than that of group A ( 3.6 + /- 1.5 ) . Also , the digital radiographic imaging of the joints in group B only showed the condylar head posterior to the articular eminence , in open position , instead of being anterior to it before the injection . In both groups , no destructive changes to the bony components of the joint have been observed . CONCLUSIONS We could conclude from this study that the injection of autologous blood into the TMJ in patients with chronic recurrent dislocation is a simple , safe and cost-effective technique . So , we encourage injection of autologous blood to the SJS and PT for treatment of patients with chronic recurrent TMJ dislocation , as it has shown better clinical and radiographic results than its injection only to the SJS OBJECTIVE To assess the effect of sodium hyaluronate ( HA ) for degenerative disorders of the temporom and ibular joint ( TMJ ) . METHODS A prospect i ve r and omized controlled clinical trial was conducted . The experimental group received injections in the upper compartments of the involved TMJs with 1 % HA 6 mg , whereas the control group received prednisolone ( PS ) 12.5 mg once a week . Three to four injections were as one course . Before and one week after the treatment courses , clinical symptoms , amount of interleukin-6 ( IL-6 ) and total protein of synovial fluid were measured and compared . RESULTS Sixty-seven patients were included and 4 out of them were dropped out . There were 12 males and 51 females , among them , 14 cases with synovitis , 21 with anterior disc displacement without reduction and 28 with osteoarthritis of the TMJ . Thirty-five patients allocated in HA group and 28 in PS group . Both drugs could relieve the clinical symptoms of TMJ degenerative disorders . In HA group , marked improvement rate was 51.43 % and failure rate was 2.86 % , whereas marked improvement rate 39.29 % and failure rate 17.86 % in PS group . The declined levels of IL-6 in synovial fluid was notably greater in HA group than those in PS group . CONCLUSION Intra-articular injection of HA is effective and safe to treat TMJ degenerative disorders with mild adverse reactions , better in terms of effective rate and declined level of IL-6 than PS Objectives A r and omized double-blind study was conducted to compare the efficacy of superpulsed low-level laser therapy ( SLLLT ) with nonsteroidal anti-inflammatory drugs in the treatment of pain caused by temporom and ibular joint disorders . Methods A total of 99 patients with temporom and ibular joint disorders , secondary to disc displacement without reduction or osteoarthritis were r and omly divided into 3 groups . Thirty-nine patients received SLLLT in 10 sessions over 2 weeks , 30 patients received ibuprofen 800 mg twice a day for 10 days , and 30 patients received sham laser as placebo in 10 sessions over 2 weeks . Pain intensity was measured by visual analog scale at baseline , 2 , 5 , 10 , and 15 days of treatment . M and ibular function was evaluated by monitoring active and passive mouth openings and right and left lateral motions at baseline , 15 days , and 1 month of treatment . Magnetic resonance imaging was performed at baseline and the end of therapy . Results Mean visual analog scale pain scores in SLLLT group was significantly lower than in nonsteroidal anti-inflammatory drug group and control group ( P=0.0001 ) from fifth day up to the end of the observation period . As for active and passive mouth openings and right and left lateral motions , superiority of SLLLT was evident 1 month after treatment ( interaction time treatment , P=0.0001 ) . Discussion M and ibular function improved in all SLLLT patients proving the effectiveness in the treatment of pain , as demonstrated by a significant improvement in clinical signs and symptoms of temporom and ibular joint disc displacement without reduction and osteoarthritis at the end of treatment and stability over a period of 1 month — The results of a double blind crossover trial evaluating a proprietary analgesic/antihistamine preparation showed that the preparation was capable of significantly relieving the pain associated with temporom and ibular joint pain dysfunction syndrome The most frequent symptom of craniom and ibular dysfunction is pain in the preauricular area or in the temporo-m and ibular joint , usually localized at the level of the masticatory musculature . Patients sometimes also complain of reflect otalgia , headaches and facial pain . Osteoarthrosis is a frequent degenerative debilitating chronic disorder that can affect the temporom and ibular joint . It causes pain and articular rigidity , a reduction in mobility , and radiological alterations are visible in stratigraphy . The aim of this study was to compare the efficacy of a topically applied non-steroid anti-inflammatory drug that has recently become commercially available ( diclofenac sodium in a patented carrier containing dimethyl sulfoxide , that favours transcutaneous absorption ) which is commonly used to alleviate pain in knee or elbow joints , versus oral diclofenac , in the treatment of symptoms of temporom and ibular joint dysfunction . Dysfunction of the temporom and ibular joint was diagnosed in 36 adult patients . The patients were r and omized in two age- and gender -matched groups . Group A ( 18 patients ) received oral diclofenac sodium administered after a meal in 50-mg tablets twice a day for 14 days . Group B ( 18 patients ) received 16 mg/ml topical diclofenac ( diclofenac topical solution , 10 drops 4 times a day for 14 days ) . All patients completed a question naire at the start and end of therapy . Patients were asked to quantify on a grade d visual analogue scale and to reply to questions about the pain and tenderness of the temporom and ibular joint and the functional limitation of mouth opening . Patients were also requested to report side-effects of the treatment . All patients showed relief from pain after treatment : the difference between the two groups was not significant ( p > 0.05 ) . Post-treatment , 16 patients of group A had epigastralgic symptoms . Three patients treated with topical diclofenac showed a modest irritation of the temporom and ibular joint region , and disappeared spontaneously . Our results demonstrate that topically applied diclofenac and oral diclofenac are equally effective in the treatment of temporom and ibular joint dysfunction symptoms . Topical diclofenac has the advantage that it does not have adverse systemic effects , whereas oral diclofenac had untoward effects on the gastric apparatus . The efficacy of diclofenac topically applied on the temporom and ibular joint region observed in group B is explained by the association of diclofenac with dimethyl-sulfoxide , which enables a rapid effective penetration into the joint tissues . It is noteworthy that dimethyl-sulfoxide favours transuctaneous absorption when used in a multi-dose regime as in our study with 4 doses a day . Thus , single , " as required " , applications should be avoided because this practice results in scarce absorption of diclofenac Objective : To investigate the analgesic efficacy of lamotrigine in the treatment of painful HIV-associated distal sensory polyneuropathy ( DSP ) . Background : The pathogenesis of HIV-associated DSP is unknown and there is no effective treatment . A novel anticonvulsant , lamotrigine , blocks voltage-sensitive sodium channels and inhibits the release of glutamate and aspartate . There have been anecdotal reports of efficacy of lamotrigine in the treatment of painful neuropathy and trigeminal neuralgia . Methods : In a multicenter , r and omized , double-blind , placebo-controlled study , lamotrigine was initiated at 25 mg per day and slowly titrated over 7 weeks to 300 mg per day . Study duration was 14 weeks . The primary outcome measure was change in pain on the modified Gracely scale with secondary outcome measures including change in neurologic examination , use of concomitant analgesic medications , and global pain relief . Results : Of 42 enrolled subjects , 13 did not complete the 14-week study endpoint . In five of these , rash was the cause for dropout . In the remaining 29 evaluable subjects , 20 patients received placebo and 9 received lamotrigine . The pain scores at baseline were not significantly different . The reduction in average pain from baseline to week 14 was greater ( p = 0.03 ) in the lamotrigine group ( −0.55 ) than in the placebo group ( −0.18 ) , adjusting for baseline levels of pain . There was no difference between the groups on the change in peak worst pain . Conclusions : In this small trial , lamotrigine showed promise in the treatment of pain associated with HIV-related DSP . The frequency of rash was greater than in lamotrigine studies in epilepsy . A larger controlled study of lamotrigine is warranted OBJECTIVE Temporom and ibular disorders ( TMD ) is a term reflecting chronic , painful , craniofacial conditions usually of unclear etiology with impaired jaw function . The effect of osteopathic manual therapy ( OMT ) in patients with TMD is largely unknown , and its use in such patients is controversial . Nevertheless , empiric evidence suggests that OMT might be effective in alleviating symptoms . A r and omized controlled clinical trial of efficacy was performed to test this hypothesis . METHODS We performed a r and omized , controlled trial that involved adult patients who had TMD . Patients were r and omly divided into two groups : an OMT group ( 25 patients , 12 males and 13 females , age 40.6+/-11.03 ) and a conventional conservative therapy ( CCT ) group ( 25 patients , 10 males and 15 females , age 38.4+/-15.33 ) . At the first visit ( T0 ) , at the end of treatment ( after six months , T1 ) and two months after the end of treatment ( T2 ) , all patients were subjected to clinical evaluation . Assessment s were performed by subjective pain intensity ( visual analogue pain scale , VAS ) , clinical evaluation ( Temporom and ibular index ) and measurements of the range of maximal mouth opening and lateral movement of the head around its axis . RESULTS Patients in both groups improved during the six months . The OMT group required significantly less medication ( non-steroidal medication and muscle relaxants ) ( P<0.001 ) . CONCLUSIONS The two therapeutic modalities had similar clinical results in patients with TMD , even if the use of medication was greater in CCT group . Our findings suggest that OMT is a valid option for the treatment of TMD Burning mouth syndrome ( BMS ) is an intensive chronic oral mucosal pain condition of unknown aetiology . The aim of this study was to evaluate the clinical performance of lycopene-enriched virgin olive oil used to treat the condition , comparing this with a placebo . This study took the form of a double-bind , r and omised clinical trial . A total of 60 patients with BMS were r and omly divided into two groups : Group I ( n = 30 ) treated with lycopene-enriched virgin olive oil ( 300 ppm ) ( 1.5 mL three times a day ) and Group II ( n = treated with a placebo ( 1.5 mL three times a day ) . Evaluations were made before and after 12 weeks of product/placebo application . Symptoms were evaluated by VAS , whilst patient psychological profiles were assessed using the HAD scale and patient quality of life using the Oral Health Impact Profile-14 ( OHIP-14 ) and the Medical Outcome Short Form Health Survey question naire ( SF36 ) . Fifty patients completed the 12-week treatment ( 26 in Group I and 24 in Group II ) . Visual analogue scale pain values improved in both groups but without statistically significant differences between the groups ( P = 0.57 ) . Oral quality of life also improved . Four patients in Group I ( treatment ) left the study and six left Group II ( placebo ) . No patients experienced any adverse effects result ing from treatment at any of the evaluation times . Patients were lost from the sample due to lack of compliance . It was found that the lipid profile did not change during the 3-month study period as a result of the application of lycopene-enriched olive oil ( Group I ) ; nor did any change occur in the placebo group ( Group II ) . In this way , the placebo effect was seen to be strong . The topical lycopene-enriched virgin olive oil is a very safe and an effective similar way that the placebo for treating patients with BMS . However , future studies are required to establish the treatment for patients with chronic and painful syndrome OBJECTIVE To investigate the effect of intra-articular irrigation-injection therapy in treating osteoarthrosis of the temporom and ibular joint . MATERIAL S AND METHODS Thirty-seven patients ( the test group ) received intra-articular irrigation injection ; 26 patients ( the control group ) received intra-articular injection of steroid . The synovial fluid , aspirated from five subjects of the test group before and after the therapy , was assayed to determine the tumor necrosis factor . RESULTS Clinical evaluations were performed 3 months after the therapy . Thirteen subjects in the test group fell into the " excellent " category , 19 into the " good " category , and five into the " no effect " category ; in the control group , eight subjects fell into the " excellent " category ; nine into the " good " category , and nine into the " no effect " category . The category difference in total effectiveness between the test group and the control group is statistically significant ( X2 = 3.9340 P < 0.05 ) . TNF in synovial fluid also showed statistically significant differences before and after treatment ( T = 2.8825 , P < 0.05 ) . CONCLUSIONS Intra-articular irrigation injection is an effective therapy method for treating osteoarthrosis and is superior to intra-articular injection of steroid This study examined the clinical and radiological effects of intra-articular tenoxicam injection following arthrocentesis and compared them with arthrocentesis alone in patients with disc displacement without reduction ( DDwoR ) . 24 temporom and ibular joints ( TMJs ) in 21 patients with DDwoR were studied . Patients were divided r and omly into Group A in which only arthrocentesis was performed ( 14 TMJs in 14 patients ) and Group AT which received arthrocentesis plus intra-articular injection of tenoxicam ( 10 TMJs in 7 patients ) . Patients were evaluated before the procedure , on postoperative day 7 , then 2 , 3 , 4 weeks , and 2 , 3 , 4 , 5 , 6 months postoperatively . Intensity of joint pain was assessed using a visual analog scale . Maximum mouth opening was recorded at each follow-up . TMJ sounds and palpation scores were noted as positive or negative . Magnetic resonance imaging ( MRI ) was performed before and 6 months after treatment in both groups . Disc form , disc location during neutral position , reduction with movement , joint effusion , structures of the articular surfaces , and bone marrow anomalies were evaluated all in MRIs . Both treatments succesfully increased maximum mouth opening and reduced TMJ pain ; there were no complications . Difference between the groups was not statistically significant and a larger controlled study is necessary to clarify this use of tenoxicam & NA ; To compare the efficacy and adverse effects of celecoxib , a cyclooxygenase‐2 ( COX‐2 ) inhibitor , with naproxen , a non‐steroidal anti‐inflammatory drug , and placebo in the treatment of painful temporom and ibular joints ( TMJs ) . In this r and omized , double‐blind , placebo‐controlled trial , 68 subjects with painful TMJs secondary to disc‐displacement with reduction , received celecoxib 100 mg twice a day ; naproxen , 500 mg twice a day ; or placebo for 6 weeks . Subjects were evaluated with st and ard measures of efficacy : pain intensity measured by visual analogue scale , maximal comfortable m and ibular opening , and quality of life ( SF‐36 ) , at baseline ( 1 week after discontinuing previous analgesic therapy ) and again after 6 weeks of drug treatment . Naproxen significantly reduced the symptoms of painful temporom and ibular joint disc‐displacement ( TMJ DD ) with reduction as determined by most efficacy measures . Significant improvement in pain intensity occurred within 3 weeks of treatment , and was sustained throughout the 6‐week study . Clinical ly significant improvement in m and ibular range of motion was observed for naproxen compared to celecoxib and placebo . Celecoxib showed slightly better pain reduction than placebo , but was not significantly effective for temporom and ibular disorder pain . Celecoxib and naproxen were well tolerated , with similar number of reported adverse effects . Dual COX‐1 and COX‐2 inhibition with naproxen was demonstrated to be effective for the treatment of painful TMJs , as seen by significant improvement in clinical signs and symptoms of TMJ DD with reduction compared to celecoxib and placebo . Inhibition of both COX isozymes is needed to achieve effective analgesia for this type of musculoskeletal pain PURPOSE A number of reports have shown a direct analgesic effect of opioids by way of the peripheral receptors . Nevertheless , only a very few studies have reported using opioids in the temporom and ibular joint ( TMJ ) , and nearly all of them were connected to surgical patient groups . The present study was design ed to evaluate the analgesic efficacy and safety of repeated intra-articular morphine applications compared with a local anesthetic and saline solution in the management of TMJ pain . PATIENTS AND METHODS A total of 48 patients with articular pain related to the TMJ were entered in a clinical , prospect i ve , r and omized , double-blind , single-center study . The analgesic effect of repeated intra-articular infiltration with morphine ( 5 or 10 mg morphine sulfite ) , bupivacaine 0.5 % ( Carbostesin ; AstraZeneca , London , UK ) , and isotonic saline solution as a placebo in the TMJ was examined . The efficiency after 3 injections of the same substance with an interval of 48 hours between each application was measured using a pain relief scale , visual analog scale , pain intensity scale , and the potential need for accessory peripheral analgesics ( paracetamol ) . RESULTS All patients showed , independent of the treatment group , pain relief within 60 minutes after the first injection . Patients with saline and Carbostesin reported almost complete pain recurrence before the second injection . At 1 week after the last and third injection , the 10-mg morphine group still showed a distinct effect , with 16.7 % reporting complete ( no pain ) and 41.7 % distinct pain relief . In addition , 33.3 % had a poor response and 8.3 % had no improvement . None of the other groups reported complete improvement ; however , 25 % of the patients who received 5 mg morphine had distinct pain relief , and 50 % had at least poor pain relief . In the Carbostesin group , distinct improvement was reported by 8.3 % , with a poor response in 41.7 % , and no effect in the remaining 50 % . Patients treated with saline had a poor response in 16.7 % , but most ( 83.3 % ) reported no improvement 1 week after treatment . CONCLUSIONS Independent of the applied substances , initial pain relief can be registered in the TMJ : either from the arthrocentesis effect or at least the placebo effect . Morphine at a dosage of 10 mg showed the best and most long-lasting analgesic efficiency . Morphine , in general ( 5 and 10 mg ) , and , with limitations , Carbostesin were more or less efficient for postoperative pain control but without distinct effects in the long term . With regard to our results , we can recommend intra-articular morphine application at a dose of 10 mg for pain management . Carbostesin showed no promising long-term effects Comparison between low-level laser therapy ( LLLT ) and clonazepam for treating burning mouth syndrome ( BMS ) patients has never been documented ; the aim of this study was to assess the effects of LLLT photobiomodulation versus medical therapy with clonazepam on BMS . Thirty-three patients ( 25 female , 8 male , mean age = 67.12 ) were r and omly allocated to two different groups : the first one ( group A , 18 patients ) underwent two laser irradiation sessions weekly for 5 weeks , whereas the second one ( group B , 15 patients ) received topical clonazepam therapy [ half a tablet ( 2 mg ) in the mouth without swallowing for 3 min , three times a day for 21 days ] . LLLT was delivered with a continuous wave 980-nm aluminum gallium arsenide ( AlGaAs ) diode laser and the output of 300 mW , delivering a Fluence of 10 J/cm2 , using a “ spot technique , ” with an average power density of about 1 W/cm2 . The laser probe was held perpendicularly at a distance of about 2 mm from the mucosa . Visual analogue scale ( VAS ) , McGill Pain Question naire , present pain intensity ( PPI ) , and Oral Health Impact Profile ( OHIP-49 ) assessed sensation of pain . Hospital Anxiety and Depression Scale and Geriatric Depression Scale assessed levels of anxiety and depression . Twelve weeks after the end of treatment , patients treated with LLLT experienced a decrease in pain sensation reported for all the parameters analyzed : VAS ( P = 0.004 ) , McGill Pain Question naire ( P = 0.002 ) , PPI ( P = 0.002 ) , and OHIP-49 ( P = 0.010 ) . The group treated with clonazepam had less favorable results for VAS ( P = 0.33 ) , McGill Pain Question naire ( P = 0.005 ) , PPI ( P = 0.013 ) , and OHIP-49 ( P = 0.25 ) . Levels of anxiety and depression did not change statistically in any groups ( P > 0.05 ) . Comparing the two groups , LLLT appeared to be superior in improving pain perception , but statistically only at 8 weeks after the end of the protocol proposed ( P = 0.026 ) . Based on this preliminary trial , LLLT is capable of reducing the symptoms of patients with BMS with a constant and long-lasting effect , experienced since the end of the first applications Methods One hundred sixty-eight TMD patients received TCM or enhanced self-care using a stepped-care design where those who failed on self-care were offered TCM . This report includes 121 patients during their first 16 TCM visits . The initial 8 occurred more often than weekly ; patients and practitioners determined subsequent schedules . Outcome data were collected via study -administered question naires at st and ard times , and self-report at every treatment visit . Here we report on average pain ( VAS 0 - 10 ) and pain medications over the previous week , collected at treatment visits . We converted pain medication intake to equivalent weekly doses of aspirin ( for NSAIDs and acetaminophen ) or morphine ( 7.5 mg for narcotics ) . Pain was analyzed by linear regression with r and om effects for within-individual correlations . Medication use was log-transformed and analyzed using quadratic splines The long-term effect of intra-articular injections of sodium hyaluronate and corticosteroid ( betamethasone ) was compared in a sample of 24 patients who had pain and tenderness to palpation in the temporom and ibular joint ( TMJ arthritis ) of at least six months duration , and who had not responded to conservative treatment . The two drugs were r and omly allocated to the patients . The drugs , 0.5 ml , were injected twice into the superior joint compartment of the TMJ with a two-week interval between injections . The effect on subjective symptoms , clinical signs , and bite force was assessed . At the one and two-year follow-ups both the hyaluronate- and the corticosteroid-group had significantly reduced subjective symptoms as well as clinical signs , and the maximum voluntary bite force was significantly increased . The differences in effect between treatments were not statistically significant . It was concluded that both drugs have a significant long-term effect on chronic arthritis of the TMJ and that either of the drugs can be helpful ; however , sodium hyaluronate might be the best alternative due to the least risk for side effects BACKGROUND To compare different therapeutic supportive approaches in patients with burning mouth syndrome . A prospect i ve study was carried out for this purpose . MATERIAL S AND METHODS The study involved 56 patients with burning mouth syndrome . They were r and omly assigned to treatment with capsaicin , alpha-lipoic acid or lysozyme-lactoperoxidase ( test drugs ) or boric acid ( control group ) . Symptoms were scored after 60 days treatment and 60 days after drug discontinuation . RESULTS At the end of the treatment period , there was a significant reduction in the symptom scores of all of the patients who received the test drugs ( P<0.01 ) , and at the end of the follow-up period in the test groups as a whole ( P<0.01 ) ; the reduction was not significant when considering each test group separately after the treatment period . All of the treatments were more effective than boric acid and there was no significant difference in the symptom scores of the control group at either of the study time-points . CONCLUSIONS Our results demonstrate the similar effectiveness of capsaicin and alpha-lipoic acid in controlling the symptoms of burning mouth syndrome . Lysozyme-lactoperoxidase may be effective in the supportive care of BMS patients with xerostomia . The transitory effect observed after discontinuing drug administration justifies the use of prolonged therapy in chronically affected patients This study aim ed to evaluate the efficacy of piroxicam associated with low-level laser therapy compared with single therapies in 32 patients presenting temporom and ibular joint arthralgia in a r and om and double-blind research design . The sample , divided into laser + piroxicam , laser + placebo piroxicam and placebo laser + piroxicam groups , was su bmi tted to the treatment with infrared laser ( 830 nm , 100 mW , 28 s , 100 J cm(-2 ) ) at 10 temporom and ibular joint and muscle points on each side during four sessions concomitant to take one capsule a day of piroxicam 20 mg during 10 days . The treatment was evaluated throughout four sessions and 30 days follow-up through visual analogue scale ( VAS ) , maximum mouth opening and joint and muscle ( temporal and masseter ) pain on palpation . The results showed that all the study groups had a significant improvement in the VAS scores ( P < 0·05 ) , and there were no significant group differences . Piroxicam was effective in the reduction of joint and muscle pain on palpation ( P < 0·05 ) and showed the lowest temporal pain ( P = 0·02 ) at the 30-day follow-up . The combination of low-level laser therapy and piroxicam was not more effective than single therapies in the treatment of temporom and ibular joint arthralgia . The use of piroxicam was more effective in the following 30 days OBJECTIVES To assess the feasibility and acceptability of study ing whole systems of Traditional Chinese Medicine ( TCM ) and Naturopathic medicine ( NM ) in the treatment of temporom and ibular disorders ( TMD ) , and to determine whether there is indication to support further research . DESIGN A pilot study using a r and omized controlled clinical trial design of whole system TCM and NM versus state-of-the-art specialty care ( SC ) . SETTING /LOCATION Kaiser Permanente Northwest ( KPNW ) , and practitioner offices in Portl and , Oregon . SUBJECTS One hundred and sixty ( 160 ) women 25 - 55 years of age attending a KPNW TMD specialty clinic . INTERVENTIONS Whole system TCM and NM , and KPNW TMD clinic SC ; the intervention protocol s were design ed to model the individually tailored type of community care offered in alternative medicine practice s in Portl and and in the KPNW TMD clinic , using protocol s that enhanced similarities among practitioners within each system and permitted full descriptions of the treatments provided . OUTCOME MEASURES TMD was ascertained using the Research Diagnostic Criteria /TMD ; outcomes were self-reported worst and average facial pain and interference with activities ( scaled 0 - 10 where 10 is worst ) . RESULTS Of 948 consecutive eligible patients , 160 were r and omized to one of three arms ; 128 provided endpoint data . TCM and NM demonstrated significantly greater in-treatment reductions for worst facial pain compared to SC ( adjusted regression analysis ; higher negative values indicate greater improvement , = -1.11 + /- 0.43 , p = 0.010 and -1.02 + /- 0.45 , p = 0.025 for TCM and NM , respectively , compared to SC ) and at 3 months post-treatment ( -1.07 + /- 0.51 , p = 0.037 and -1.27 + /- 0.54 , p = 0.019 for TCM and NM versus SC , respectively ) . Additionally , TCM provided significantly greater decreases in average pain than SC ; NM provided significantly greater decreases than SC or TCM in TMD-related psychosocial interference . CONCLUSIONS These alternative medicine approaches each result ed in significantly greater reduction of pain and psychosocial interference than SC . Further research on the potential benefits of traditional whole systems of medicine for TMD appears warranted AIMS To investigate the effects of local intramuscular injection of the N-methyl-D-aspartate ( NMDA ) receptor antagonist ketamine on chronic myofascial pain and m and ibular function in temporom and ibular disorder patients . METHODS Fourteen myofascial temporom and ibular disorder pain patients ( 10 women and 4 men ) were recruited . The subjects completed 2 sessions in a double-blinded r and omized and placebo-controlled trial . They received a single injection of 0.2 mL ketamine or placebo ( buffered isotonic saline [ NaCl ] , 155 mmol/L ) into the most painful part of the masseter muscle . The primary outcome parameters were spontaneous pain assessed on an electronic visual analog scale and numeric rating scale . In addition , numeric rating scale of unpleasantness , numeric rating scale of pain relief , pressure pain threshold , pressure pain tolerance , completion of a McGill Pain Question naire and pain drawing areas , maximum voluntary bite force and maximum voluntary jaw opening were obtained . Paired t tests and analysis of variance were performed to compare the data . RESULTS There were no main effects of the treatment on the outcome parameters except for a significant effect of time for maximum voluntary bite force ( analysis of variance ; P = .030 ) and effects of treatment , time , and interactions between treatment and time for maximum voluntary jaw opening ( analysis of variance ; P < .047 ) . CONCLUSION These results suggest that peripheral NMDA receptors do not play a major role in the pathophysiology of chronic myofascial temporom and ibular disorder pain . Although there was a minor effect of ketamine on maximum voluntary jaw opening , local administration may not be promising treatment for these patients AIMS To study in a r and omized placebo-controlled design the efficacy of the antidepressant venlafaxine , a serotonin and a weak noradrenaline reuptake inhibitor , in the treatment of atypical facial pain ( AFP ) . METHODS The study was a r and omized , double-blind , crossover comparison of venlafaxine and a placebo . It consisted of 2 treatment periods , each of 4 weeks ' duration , separated by a 2-week washout period . Thirty patients suffering from chronic pain who had been diagnosed with AFP after a thorough clinical examination were recruited . Pain intensity and pain relief were registered at 6 visits . Anxiety , depression , and adverse effects were recorded . Venous blood sample s were collected at the end of each treatment period for the determination of serum levels of venlafaxine and its metabolites . RESULTS Twenty patients completed the trial . Eight patients discontinued because of adverse effects and 2 patients were excluded because of noncompliance . Two patients completed the trial but were excluded from the analysis because they experienced no pain at the baseline visit . There was no significant difference in pain intensity reduction between the maximum tolerated dose of venlafaxine ( 75 mg in most cases ) and the placebo . Pain relief was significantly greater with venlafaxine than with the placebo treatment . Significantly more escape medication was consumed during the placebo period compared with the venlafaxine period . No significant correlation was found between the serum concentration of the drug and the response to treatment . Anxiety and depression scores did not differ between venlafaxine and placebo treatment . Adverse effects were equally common during both treatments . CONCLUSION Venlafaxine was only modestly effective in the treatment of AFP AIMS Chronic neurogenic facial pain is commonly resistant to treatment and is often the source of significant patient morbidity . Adrenergic mechanisms are postulated to play a role in producing this type of pain , and adrenergic blocking agents are frequently used in clinical practice for pain control therapy . The analgesic effectiveness of an adrenergic blocking agent , intravenous phentolamine , was compared to saline and intravenous lidocaine in the present study using a single-blind protocol in patients with chronic neurogenic facial pain . METHODS Thirty patients were studied whose common clinical features included pain for more than 6 months , unilateral trigeminal distribution , constant dysesthesia , and no evidence of pathology or known etiology . Phentolamine ( 30 mg ) , lidocaine ( 100 mg ) , and saline were each infused over periods of 5 to 10 minutes . Pain ratings were assessed every 4 minutes throughout each study period using a 10-point pain intensity scale . RESULTS No patient reported subjective improvement of pain during or immediately following phentolamine or saline infusions alone . Sixteen of the 30 patients reported decreased pain following lidocaine infusion . In the majority of the patients , the duration of lidocaine analgesia was less than 30 minutes ; however , some patients reported decreased pain for a longer time . CONCLUSION The results do not support an adrenergic mechanism for chronic neurogenic facial pain . The response to lidocaine , a nonadrenergic , membrane-stabilizing agent , suggests that it may have clinical effectiveness in certain neurogenic facial pain patients This double-blind study evaluated the short-term effect of iontophoretic delivery of dexamethasone on the signs and symptoms of temporom and ibular disorders in patients who had concurrent temporom and ibular joint disc displacement without reduction and capsulitis . Twenty-seven patients with this clinical diagnosis were r and omized to one of three groups : treatment group ( dexamethasone sodium phosphate and lidocaine hydrochloride ) ; control group ( lidocaine hydrochloride ) ; and placebo group ( pH-buffered saline ) . Pretreatment and posttreatment data included items to calculate Helkimo 's Anamnestic Dysfunction index , Helkimo 's Clinical Dysfunction index , the Symptom Severity Index , and the Craniom and ibular Index ( CMI ) . The CMI is composed of the Dysfunction index ( DI ) and Muscle index . Analysis of variance showed no baseline differences on these measures between the three groups . Pretreatment and posttreatment values were compared with the paired t tests . Posttreatment , the treatment group had an increased mean maximal active m and ibular opening of 6 mm ( P = .02 ) , increased mean lateral excursion of 1.2 mm to the noninvolved side ( P = .05 ) , and reduced mean DI scores of 0.51 to 0.39 ( P = .01 ) ; no statistically significant decrease in pain symptoms was reported . Analysis of variance showed a significant difference in the DI scores ( P = .04 ) between groups from pretreatment to posttreatment , with the treatment group showing the greatest improvement in the DI scores relative to the other two groups . No other question naire items , exam items , or result ant indexes showed changes in any of the groups at P < or = .05 . These results suggest that iontophoretic delivery of dexamethasone and lidocaine was effective in improving m and ibular function , but not in reducing pain , in temporom and ibular disorders patients who had concurrent temporom and ibular joint capsulitis and disc displacement without reduction For individuals with temporom and ibular joint ( TMJ ) disc displacement without reduction with limited mouth opening ( closed lock ) , interventions vary from minimal treatment to surgery . In a single-blind trial , 106 individuals with TMJ closed lock were r and omized among medical management , rehabilitation , arthroscopic surgery with post-operative rehabilitation , or arthroplasty with post-operative rehabilitation . Evaluations at baseline , 3 , 6 , 12 , 18 , 24 , and 60 months used the Craniom and ibular Index ( CMI ) and Symptom Severity Index ( SSI ) for jaw function and TMJ pain respectively . Using an intention-to-treat analysis , we observed no between-group difference at any follow-up for CMI ( p ≥ 0.33 ) or SSI ( p ≥ 0.08 ) . Both outcomes showed within-group improvement ( p < 0.0001 ) for all groups . The findings of this study suggest that primary treatment for individuals with TMJ closed lock should consist of medical management or rehabilitation . The use of this approach will avoid unnecessary surgical procedures The common methods for treating anterior disk displacement without reduction ( ADDwor ) are not based on r and omized controlled clinical trials . Our study evaluated non-surgical treatments in 69 MRI-confirmed ADDwor subjects ( m/f = 6/63 ) . Subjects were r and omly assigned to a control group and one of two treatment groups . Outcomes included maximum mouth opening , visual analogue scale of pain , and daily activity limitation . Calibrated examiners collected data at the initial interview and at 0 , 2 , 4 , and 8 weeks of treatment . At the eight-week point , within-group improvements were present for all variables , for all groups . Between-group differences were not highly evident , with only mean daily activity limitation for the self-care/NSAID group being significantly lower than that of the occlusal appliance/jaw mobilization + self-care/NSAID group at the two- and four-week time-points . These results suggest that ADDwor subjects will improve with only minimal treatment intervention , and no significant difference was evident for the treatments tested and the control condition BACKGROUND Alpha-lipoic acid ( ALA ) is a potent antioxidant mitochondrial coenzyme , trometamol salt of thioctic acid , shown in clinical studies to be neuroprotective and in a preliminary study to have an effect on the symptomatology of Burning Mouth Syndrome ( BMS ) . METHODS We were interested in extending our studies as to whether alpha-lipoic acid might improve the symptomatology in BMS and therefore carried out a larger open controlled clinical study on the effects of alpha-lipoic acid on BMS symptomatology . RESULTS We have examined the effects on 4 groups of 20 patients with BMS of ALA , compared with bethanecol , Biotene and placebo , and found ALA of remarkable benefit with minimal adverse effects . CONCLUSIONS These results suggest that double-blind r and omized controlled multicenter studies of ALA are indicated AIMS To carry out a r and omized clinical trial to compare the effect of palmitoylethanolamide ( PEA ) versus ibuprofen , a nonsteroidal anti-inflammatory drug ( NSAID ) , for pain relief in temporom and ibular joint ( TMJ ) osteoarthritis or arthralgia . PEA acts as an endogenous agent with an autacoid local inflammation antagonism and modulates mast cell behavior controlling both acute and chronic inflammation . METHODS A triple-blind r and omized clinical trial was conducted on 24 patients ( 16 women and 8 men ) aged 24 to 54 years and suffering from TMJ osteoarthritis or arthralgia . The patients were enrolled from a group of 120 consecutive patients referred to the University of Bologna 's Department of Orthodontics . Patients were r and omly divided into two groups : group A ( 12 subjects ) received PEA 300 mg in the morning and 600 mg in the evening for 7 days and then 300 mg twice a day for 7 more days . Group B ( 12 subjects ) received ibuprofen 600 mg three times a day for 2 weeks . Every patient recorded the intensity of spontaneous pain on a visual analog scale twice a day . Maximum mouth opening was recorded by a blind operator during the first visit and again after the 14th day of drug treatment . A t test was used for data comparisons . RESULTS Pain decrease after 2 weeks of treatment was significantly higher in group A than in group B ( P = .0001 ) ; maximum mouth opening improved more in group A than in group B ( P = .022 ) . CONCLUSION These data suggest that PEA is effective in treating TMJ inflammatory pain Abstract Pain , mood and hemodynamic effects of intranasal ( IN ) cocaine were studied in patients suffering from chronic facial pain of myofascial or deafferentation neuralgia origin . Fifteen and 25 % aqueous solutions of cocaine were compared with a placebo of normal saline solution and 4 % lidocaine , which served as an " active " control . Trials were evaluated on separate days in a r and omized , double-blind cross-over comparison . Subjective reports of pain and mood and objective physiological measures were obtained before and at regular intervals during administration of each solution . Reductions in pain occurred at both cocaine concentrations but were statistically significant only after the 15 % solution . On completion of the experimental phase , 11 patients participated in a single trial of a 40 % cocaine solution under similar study conditions with the exception of the cross-over procedure . The 40 % solution produced significantly greater improvement in analgesic effects than the 15 % or 25 % concentrations . No significant mood effects were observed for any of the treatments as compared to placebo . Pulse rate was increased after all cocaine doses . IN lidocaine produced a significant reduction of systolic blood pressure , but no significant changes in pain or mood AIM Burning mouth syndrome could be considered an expression of atypical facial pain . The recent neuropathological findings in BMS may suggest the need for alternative therapies . This paper aims to evaluate if systemic capsaicin could be used for BMS the- rapy . METHODS Eighty-four BMS patients ( 19 males and 63 females , aged 36 to 74 years , mean 54.6 ) were referred to the Oral Medicine and Oral Pathology Department , Dental University Institute , Milan-Bicocca University . They were divided in 2 groups : 1(st ) Group : the first group ( 42 patients ) received 3 capsules of capsaicin ( 50 mg of powder of red pepper with 0,25 % of capsaicin ) a day for one month . 2(nd ) Group : the control group ( 42 patients ) received 3 capsules of placebo ( empty capsules ) a day for one month . The intensity of pain was measured on the visuo-analogical scale VAS . T test of Student was applied to analyse results of VAS . P values of less than 0.05 were interpreted as significant , and the level in confidence intervals was 95 % . RESULTS Significant differences were noted between the two groups at the end of our study ( p<0.05 ) . No important side effects were reported . CONCLUSION Systemic capsaicin could be considered a successful therapeutical approach for BMS patients AIM The aim of the study was to evaluate and compare the analgesic efficacy of placebo and diazepam in patients with temporom and ibular disorder . MATERIAL S AND METHODS Thirty-five patients were recruited with a diagnosis of temporom and ibular disorder based on st and ard clinical diagnostic criteria for temporom and ibular disorder . The patients were put in to one of the two groups : placebo or diazepam at r and om . The average pain intensity was recorded with visual analog scale ( VAS ) at pretreatment , at weekly interval till the completion of a three-week trial and at post-treatment visit on the eighth week from baseline . The secondary outcome measures were changes in masticatory muscle tenderness , viz . massater muscle , lateral pterygoid muscle , medial pterygoid muscle and temporalis muscle and changes in mouth opening . STATISTICAL ANALYSIS Intra-group comparison for analgesic efficacy and mouth opening was carried out by Wilcoxon 's signed ranked test . Inter-group comparison for analgesic efficacy was also carried out using Mann-Whitney 's test . RESULTS A statistically significant ( P<0.01 ) decrease in temporom and ibular disorder pain in the placebo group ( 65 % ) and statistically highly significant ( P<0.001 ) decrease in the diazepam group ( 72 % ) were observed on VAS after three weeks of treatment . The inter-group comparison demonstrated no statistically significant difference between the groups . CONCLUSION This study suggests that the placebo can give near similar results as diazepam can . So the role of placebo should also be considered as one of the important management strategies . In the short term , reduction in the masticatory muscle tenderness and significant improvement in the mouth opening in both the groups were observed This study analysed the prognostic factors for successful arthrocentesis with and without sodium hyaluronate ( SH ) injection for the treatment of temporom and ibular joint ( TMJ ) disc displacement without reduction ( DDwoR ) using clinical and radiological results . 29 TMJs in 25 patients with DDwoR were included . Patients were treated with arthrocentesis or arthrocentesis followed by intra-articular ( i.a . ) injection of SH . Treatment was evaluated for postoperative range of maximum mouth opening and the degree of postoperative pain on a VAS . Prognostic factors analysed were age , sex , duration of locking , trauma history , previous TMJ treatment , depression , bruxism , malocclusion and missing teeth . Degenerative changes were evaluated as probable prognostic factors . After treatment , 24 joints ( 83 % ) fulfilled the criteria for success . Duration of locking and present preoperative degenerative changes were the most significant factors for treatment outcome . The results suggest it is sufficient to use only arthrocentesis in patients without preoperative degenerative changes and arthrocentesis with SH in patients with degenerative changes on their preoperative MRIs , but because there were some significant differences between the two groups preventing the authors from comparing them statistically , they can not come to that conclusion . To clarify the use of SH in such cases , st and ardized study groups are necessary for future studies The aim of the study was to compare the effectiveness of five weekly two-needle arthrocentesis plus hyaluronic injections vs. the same protocol performed with a single-needle technique in patients with inflammatory-degenerative disorders of the temporom and ibular joint ( TMJ ) . 80 patients with TMJ osteoarthritis were r and omly assigned to the two-needle or single-needle protocol and followed up for 6 months after treatment . Several outcome parameters , such as maximum pain at rest and maximum pain on chewing , subjective chewing efficiency , limitation in jaw function , jaw range of motion in mm , were recorded at baseline and multiple follow up assessment s. Both treatment groups recorded significant improvement with respect to baseline levels in almost all outcome variables . The rate of improvement was not significantly different between the treatment protocol s in any of the outcome variables ( p-values between 0.143 and 0.970 ) . No between-group differences emerged for the perceived subjective efficacy ( p=0.321 ) and the treatment tolerability ( p=0.783 ) . The present investigation did not support the existence of significant differences in the treatment effectiveness for inflammatory-degenerative TMJ disorders of a cycle of five weekly injections of arthrocentesis plus hyaluronic acid injections performed according to the classical two-needle or the single-needle technique Summary In order to evaluate the efficacy , time-course of action and predictors of response to topical capsaicin , 39 patients with chronic post-herpetic neuralgia ( PHN ) , median duration 24 months , were treated with 0.025 % capsaicin cream for 8 weeks . During therapy the patients rated their pain on a visual analogue scale ( VAS ) and a verbal outcome scale . A follow-up investigation was performed 10–12 months after study onset on the patients who had improved . Nineteen patients ( 48.7 % ) substantially improved after the 8-week trial ; 5 ( 12.8 % ) discontinued therapy due to side-effects such as intolerable capsaicin-induced burning sensations ( 4 ) or mastitis ( 1 ) ; 15 ( 38.5 % ) reported no benefit . The decrease in VAS ratings was significant after 2 weeks of continuous application . Of the responders 72.2 % were still improved at the follow-up ; only one-third of them had continued application irregularly . Treatment effect was not dependent on patient 's age , duration or localization of PHN ( trigeminal involvement was excluded ) , sensory disturbance or pain character . Treatment response was not correlated with the incidence , time-course or severity of capsaicin-induced burning . If confirmed in controlled trials , the long-term results of this open , non-r and omized study might indicate that the analgesic effect of capsaicin in PHN is mediated by both interference with neuropeptide metabolism and morphological changes ( perhaps degeneration ) of nociceptive afferents BACKGROUND Many patients and physicians interpret episodic headache in the presence or absence of nasal symptoms as " sinus ' headache , while ignoring the possible diagnosis of migraine . OBJECTIVE The purpose of this study was to assess the efficacy and tolerability of sumatriptan succinate 50-mg tablets in patients with migraine presenting with " sinus " headache . METHODS A r and omized , double-blind , placebo-controlled , multicenter study was conducted in adult ( aged 18 - 65 years ) migraine patients presenting with self-described or physician-diagnosed " sinus " headache . From November 2001 to March 2002 , patients meeting International Headache Society criteria for migraine ( with > or = 2 of the following : unilateral location , pulsating quality , moderate or severe intensity , aggravation by moderate physical activity ; and > or = 1 of : phonophobia and phonophobia , nausea and /or vomiting ) and with no evidence of bacterial rhinosinusitis were enrolled and r and omized in a 1:1 ratio via computer-generated r and omization schedule to receive either 1 sumatriptan 50-mg tablet or matching placebo tablet . The primary efficacy end point was headache response ( moderate or severe headache pain reduced to mild or no headache pain ) at 2 hours after administration . The presence or absence of migraine-associated symptoms and sinus and nasal symptoms was also measured . Tolerability was assessed through patient-reported adverse events ( AEs ) . RESULTS Two hundred sixteen patients with self-described or physician-diagnosed " sinus " headache received a migraine diagnosis and treated 1 migraine attack with sumatriptan 50 mg . The efficacy ( intent-to-treat ) analysis included 215 patients treated with sumatriptan 50 mg ( n = 108 ; mean [ SD ] age , 39.6 [ 12.3 ] years ; mean [ SD ] weight , 77.7 [ 17.7 ] kg ; sex , 71 % female ; race , 69 % white ) or placebo ( n = 107 ; mean [ SD ] age , 41.0 [ 11.3 ] years ; mean [ SD ] weight 80.7 [ 20.9 ] kg ; sex , 69 % female ; race , 64 % white ) . Significantly more patients treated with sumatriptan 50 mg achieved a positive headache response at 2 and 4 hours after administration compared with those treated with placebo ( 69 % vs 43 % at 2 hours and 76 % vs 49 % at 4 hours , respectively ; both , P < 0.001 ) . Significantly more sumatriptan-treated patients were free from sinus pain compared with placebo recipients at 2 hours ( 63 % vs 49 % placebo , P = 0.049 ) and 4 hours ( 77 % vs 55 % , P = 0.001 ) . All treatments were generally well tolerated . The most common drug-related AEs reported in the sumatriptan and placebo groups , respectively , were dizziness ( 5 % vs < 1 % ) , nausea ( 3 % vs 2 % ) , other pressure/tightness ( defined as sense of heaviness ; heaviness of upper body , upper extremities ; jaw tension ; neck tension ) ( 4 % vs 0 % ) , and temperature sensations ( defined as warm feeling of back of neck , or flushing ) ( 2 % vs 0 % ) . No patients experienced any serious AEs . CONCLUSIONS Sumatriptan 50-mg tablets were effective and generally well tolerated in the treatment of these patients presenting with migraine headaches that were self-described or physician-diagnosed as sinus headaches Twenty patients were enrolled in a double-blind , placebo-controlled crossover study of meclofenamate sodium in headache and craniofacial pain . There were four observation periods of 15 days each : Period 1 was a wash-out period . In period 2 , subjects were r and omly assigned to a 15-day regimen of taking two capsules a day of 100 mg meclofenamate sodium ( group 1 ) or placebo ( group 2 ) . In period 3 , group 1 was switched to placebo and group 2 to meclofenamate sodium for the next 15 days . Lastly , the patients took no medication for a further 15 days ( period 4 ) . A thermographic record of the craniofacial and neck areas was taken at the end of periods 1 and 4 . A record of the pressure threshold and tissue compliance at different sites of the craniofacial , neck and shoulder areas was taken at the end of each period . During the trial , number and duration of painful events were recorded daily by the patients , and the level of pain evaluated on a visual analog scale . Mean data were analyzed for significant difference by ANOVA and paired t-test . During the meclofenamate sodium period , there was a significant decrease of days with painful events compared to the wash-out period in group 1 and compared to the placebo period in group 2 . In the majority of patients , the meclofenamate sodium period scored lowest or second-lowest after the follow-up period in mean pain intensity . Data for pressure threshold , although not significant , were indicative of a possible increase during and after intake of meclofenamate sodium . ( ABSTRACT TRUNCATED AT 250 WORDS We examined the role of N-methyl-D-aspartate ( NMDA ) receptors in chronic ( pathological ) pain in humans by using the NMDA receptor antagonist ketamine as a probe . Thirty patients with neuropathic pain in the trigeminal area were given an i.m . injection of ketamine 0.4 mg/kg combined with midazolam 0.05 mg/kg . Pethidine 1.0 mg/kg served as a control . Three different response patterns were observed . Ketamine caused a long-term ( 6 - 24 h ) analgesic effect partly dissociated from the mental side effects in 8 of the 26 patients who completed the study ; these patients also had a slight analgesic effect of pethidine . In nine patients , ketamine caused a short-lasting ( < 2 h ) analgesic effect closely associated with the mental side effects , whereas pethidine caused little or no analgesia . The remaining nine patients did not experience any reduction of pain after either drug in spite of characteristic side effects . One week after the i.m . challenge the patients received either 4.0 mg/kg ketamine hydrochloride or placebo capsules to be taken orally as a nightly dose for three consecutive nights . Five of the eight patients who had a long-term analgesic effect of the i.m . challenge reported decreased pain on days after ketamine . None of the others reported an analgesic effect . The phenomenon of long-term depression of pain in a subgroup of patients was thus confirmed when ketamine was given p.o . These findings indicate that NMDA receptors are involved in the perception and maintenance of pathological pain in some patients . In others , pain appears to be mediated by NMDA receptor-independent mechanisms . We suggest that NMDA receptor-independent transmission in central pain pathways may contribute to the reduced efficiency of analgesic drugs often seen in chronic pain states This study assessed the efficacy of high-molecular-weight sodium hyaluronate as a treatment for certain intracapsular temporom and ibular joint ( TMJ ) disorders . One hundred twenty-one patients were studied at three test sites using a r and omized , double-blind , placebo-controlled experimental design . Patients were selected on the basis of 1 ) confirmed diagnosis of either degenerative joint disease ( DJD ) , reducing displaced disc ( DDR ) , or nonreducing displaced disc ( DDN ) ; 2 ) nonresponsiveness to nonsurgical therapies ; and 3 ) severe dysfunction as established by the Helkimo indices ( HI ) , visual analog scales ( VASs ) , and physical measurements of joint movement and joint noise ( arthrophonometry [ APM ] ) . Subjects received a unilateral upper joint space injection of either 1 ) 1 % sodium hyaluronate in physiologic saline ( MedChem Products , Woburn , MA ) or 2 ) USP physiologic saline . Clinical evaluations were performed using HI , VAS , and APM at weekly intervals for the first month and then at monthly intervals up to 6 months postinjection . Statistical analyses for both categorical and continuous variables were performed for each diagnostic category at each examination interval . For DJD , no difference in outcome was seen between treatment groups . For DDN , significant between-group differences were seen through 1 month ; however , beyond this time point , the number of DDN patients was insufficient to draw meaningful conclusions concerning efficacy . For DDR , statistically significant within-group and between-group improvement in all three measures ( HI , VAS , APM ) was seen for the hyaluronate group compared to the saline group throughout the 6-month test period . At the month-2 and month-3 examination intervals , twice as many patients treated with hyaluronate ( 90 % ) showed improvement compared to patients given placebo . Further , only 3 % of patients with DDR who were treated with hyaluronate relapsed compared with 31 % of patients with DDR given placebo Burning mouth syndrome ( BMS ) or stomatodynia is characterized by a spontaneous burning pain in the oral mucosa without known cause or recognized treatment . This double-blind , r and omized , placebo-controlled , single-center study evaluated the effects of systemic Hypericum perforatum extract in patients with BMS . Forty-three patients participated , of whom 39 ( 35 women , four men , aged 64.9 + /- 4.7 years ) completed the study . The patients took indistinguishable 300-mg capsules containing either H. perforatum extract ( hypericin 0.31 % and hyperforin 3.0 % ) or placebo three times a day for 12 weeks . The intensity of burning pain was evaluated using a 10-cm visual analog scale ( VAS ) before the first dose and at visits after 4 , 8 , and 12 weeks . Furthermore , we also recorded the number of oral mucosa sites with reported burning symptoms and the self-reported descriptions of the patient 's condition before and after the treatment . Pain , measured using the VAS , was similar at the beginning of the study and even though a slightly better performance in the test group , the difference was not statistically significant ( P = 0.2216 ) . The results failed to demonstrate that 300 mg of H. perforatum extract taken three times a day for 12 weeks improved the pain of BMS patients , although the general reduction in the number of sites with reported burning sensation , a less accurate and objective score , was significant In this clinical trial , we examined the efficacy of intra-articular hyaluronic acid ( HA ) treatment in 38 patients with reducing displaced disc of the temporom and ibular joint ( TMJ ) . Subjects received two unilateral upper space injections of HA or physiological saline solution with 1 week apart . Efficacy was based on the following measurements : pain and sound intensity of the joint measured by visual analogue scale ( VAS ) , modified Helkimo 's clinical dysfunction index and the intensity of joint vibration during opening and closing the mouth measured by accelerometers . These measurements were performed before the first injection and 1 and 6 months after the last injection . In the treatment group ( n=19 ) , all measurements improved significantly at month 1 and at month 6 compared with the baseline ( P < 0.01 ) . The same measurements , in the placebo group ( n=19 ) , did not show any change , except for the pain intensity which improved at month 1 and month 6 ( P < 0.05 ) . The change in baseline measurements of all of the efficacy criteria at month 1 and at month 6 in the treatment group was significantly better compared with the change obtained with placebo at the same time intervals . This study demonstrates that intra-articular sodium hyaluronate ( Orthovisc ) injection into the TMJ is an effective treatment for a reducing displaced disc The effect of cognitive therapy ( CT ) on resistant burning mouth syndrome ( BMS ) was studied . Thirty patients with resistant BMS after odontological and medical treatment were r and omly divided into two equal groups ; a therapy group ( TG ) was treated with CT and an attention/placebo group ( APG ) served as a control group . The intensity of BMS , which was estimated by the use of a visual analogue scale , was significantly reduced in the TG directly after CT was completed and was further reduced in a 6-month follow-up . The APG did not show any decrease in intensity of BMS . The results of this study indicate that , in some cases , resistant BMS probably is of psychological origin OBJECTIVES Myofascial pain is the most common temporom and ibular disorder . The objective of this study was to compare the effectiveness of combined treatment modalities in the management of myofascial temporom and ibular pain . METHODS Fifty patients ( 44 female , 6 male ) clinical ly and radiologically diagnosed with myofascial temporom and ibular disorder ( TMD ) were selected for the study and r and omly assigned to two groups of 25 patients . Group 1 patients were treated with stabilization splint ( SS ) and Group 2 patients were treated with trigger point injection combined with SS therapy . RESULTS Positive improvement in overall signs and symptoms with statistically significant differences was observed in both groups . Group 2 showed significant reduction in visual analogue scale ( VAS ) scores , and statistical analysis revealed a significant difference between the VAS scores of Group 1 and Group 2 at the 4th and 12th weeks of treatment follow-up ( p<0.001 ) . CONCLUSION Our results indicate that trigger point injection therapy combined with splint therapy is effective in the management of myofascial TMD pain . Further research , especially r and omized controlled trials , should be carried out to ascertain its effectiveness over other treatment modalities OBJECTIVES /HYPOTHESIS In the treatment of burning mouth syndrome ( BMS ) , various approaches have been tried with equivocal results . The aim of the present r and omized clinical trial was to determine the efficacy of clonazepam , a GABA agonist design ed as an antiepileptic drug that exerts the typical effects of benzodiazepines . STUDY DESIGN R and omized clinical trial . METHODS Twenty patients with idiopathic BMS were carefully selected . Clonazepam ( 0.5 mg/day , n = 10 ) or placebo ( lactose , n = 10 ) were r and omly assigned to the patients . RESULTS Patients on clonazepam significantly improved in pain ratings ( P < .001 ) . These changes were less pronounced in the placebo group ( P < .11 ) . No significant changes were observed in a mood scale ( P = .56 ) or for depression scores ( P = .56 ) . Taste test and salivary flow increased over sessions , but were not different between groups ( P = .83 and P = .06 , respectively ) . CONCLUSIONS Clonazepam appears to have a positive effect on pain in BMS patients A double-blind , placebo-controlled crossover study was undertaken to assess the efficacy and tolerability of sumatriptan in patients with atypical facial pain . Patients were aged 18 - 65 years and had at least a 6 months history of atypical facial pain . A total of 19 patients were recruited and assessed for pain scores ( total , sensory and affective ) by using a short form McGill pain question naire preinjection and and at 60 and 120 minutes after subcutaneous injection of sumatriptan ( 6 mg ) or placebo . Safety and tolerability was assessed by recording adverse events during and after the injection . One patient received only one treatment since her pain symptoms resolved after the first treatment . Rest of the patients returned to the clinic 3 - 6 weeks later and received alternate treatment for atypical facial pain in the same fashion as on the first occasion . Treatment of patients with sumatriptan produced significant relief in sensory , affective and total pain at 120 minutes postinjection ( P < .05 ) . Sumatriptan failed to produce a significant reduction in sensory and total pain scores at 60 minutes following treatment , however the result was statistically significant for the affective pain score ( P < .05 ) . No death or other serious adverse events were reported . No patient was withdrawn from the study due to an adverse event . However , all the patients treated with sumatriptan experienced one or more adverse events . The most common reported adverse symptoms during the sumatriptan treatment period were injection site reactions , headache , feeling of heaviness , warm or hot sensation and disorders of mouth or tongue . However , most of these side effects were mild and transient . In conclusion , this study points towards some beneficial effect of a single subcutaneous injection of sumatriptan in the treatment of atypical facial pain . However , this data is not sufficient to suggest the clinical utility of subcutaneous sumatriptan ( 6 mg ) for the management of atypical facial pain . Further studies are necessary to test the effects of prolonged subcutaneous and oral multiple dose administration of sumatriptan for the treatment of atypical facial pain ABSTRACT Loss of function , muscle inflammation , and pain are some of the signs and symptoms of temporom and ibular dysfunction ( TMD ) . Pharmacological strategies to minimize the clinical manifestation of these disorders often focus on blocking or inhibiting the pain-causing symptom . Re sources such as muscle-relaxants , anxiety-relief drugs , and splint therapy are often used to reduce muscular hyper-activity related to TMD muscle pain . This study compares the effect of a r and omly ordered association of occlusal splint therapy ( S ) , nonsteroid anti-inflammatory with a muscle-relaxant drug ( orphenadrine citrate ) ( O ) , and an anxiety-relief drug ( benzodiazepine ) ( B ) , to ease painful TMD muscle symptoms . Clinical and anamnestic analyses were recorded in accordance with the Helkimo TMD index and applied before and after treatments . Twenty-one group two Helkimo TMD adult female patients were treated , all of whom were subjected to the three r and om therapeutic associations proposed : SBO , BOS , and OSB . The same operator applied the three specific associations over a period of 21 days in the proposed sequence , seven days for each therapy . The results show that all the groups presented the best results in terms of relief from pain after the therapeutic association ( 28.5 % showed a decrease and 47.6 % showed an absence of symptoms ) . No significant difference was observed among association therapeutic protocol CONTEXT The association between myofascial temporom and ibular disorder ( TMD ) and nonrestorative sleep supports the investigation of therapies that can modulate the sleep/wake cycle . In this context , melatonin becomes an attractive treatment option for myofascial TMD pain . OBJECTIVES To investigate the effects of melatonin on pain ( primary aim ) and sleep ( secondary aim ) as compared with placebo in a double-blind , r and omized , parallel-group trial . METHODS Thirty-two females , aged 20 - 40 years , with myofascial TMD pain were r and omized into placebo or melatonin ( 5 mg ) treatment groups for a period of four weeks . RESULTS There was a significant interaction ( time vs. group ) for the main outcomes of pain scores as indexed by the visual analogue scale and pressure pain threshold ( analysis of variance ; P<0.05 for these analyses ) . Post hoc analysis showed that the treatment reduced pain scores by -44 % ( 95 % CI -57 % , -26 % ) compared with placebo , and it also increased the pressure pain threshold by 39 % ( 95 % CI 14 % , 54 % ) . The use of analgesic doses significantly decreased with time ( P<0.01 ) . The daily analgesic doses decreased by -66 % ( 95 % CI -94 % , -41 % ) when comparing the two groups . Additionally , melatonin improved sleep quality , but its effect on pain was independent of the effect on sleep quality . CONCLUSION This study provides additional evidence supporting the analgesic effects of melatonin on pain scores and analgesic consumption in patients with mild-to-moderate chronic myofascial TMD pain . Furthermore , melatonin improves sleep quality but its effect on pain appears to be independent of changes in sleep quality Myalgias and arthralgias are prominent toxicities associated with paclitaxel . Pursuant to pilot information suggesting that glutamine could markedly alleviate this toxicity , we developed a placebo-controlled , double-blind , r and omized crossover trial to test this hypothesis . This trial studied 36 patients who had experienced myalgias/arthralgias related to a prior paclitaxel-containing regimen and who were then r and omized to receive oral glutamine ( 10 grams three times a day , starting on the day of chemotherapy ) x 5 days or an identical-appearing placebo . For the subsequent cycle of chemotherapy , patients were crossed over , again in a double-blind manner , to receive the alternative treatment . Patients recorded daily myalgia/arthralgia scores on numerical scales . Physicians recorded patient-reported myalgias/arthralgias using National Cancer Institute common toxicity criteria at baseline and after each course of therapy . The results of this study revealed that glutamine had no effect on the development or severity of paclitaxel-induced myalgias/arthralgias , as recorded either by the patients ' daily logs or by physician-reported information . Glutamine was well tolerated , with no suggestion of more toxicity compared to placebo . Upon completion of the two cycles , patients were asked to indicate which of the two blinded courses they preferred . Of those patients indicating a preference , 29 % preferred the glutamine cycle , compared with 33 % who preferred the placebo cycle ( P = 0.96 ) . Thus this trial did not suggest any role for oral glutamine , compared with placebo , for preventing the development , or alleviating the severity , of paclitaxel-induced myalgias/arthralgias A previous r and omized controlled trial ( RCT ) by Schiffman et al. (2007)(15 ) compared four treatments strategies for temporom and ibular joint ( TMJ ) disc displacement without reduction with limited mouth opening ( closed lock ) . In this parallel group RCT , 106 patients with magnetic resonance imaging (MRI)-confirmed TMJ closed lock were r and omized between medical management , non-surgical rehabilitation , arthroscopic surgery , and arthroplasty . Surgical groups also received rehabilitation post-surgically . The current paper reassesses the effectiveness of these four treatment strategies using outcome measures recommended by the International Association of Oral and Maxillofacial Surgeons ( IAOMS ) . Clinical assessment s at baseline and at follow-up ( 3 , 6 , 12 , 18 , 24 , and 60 months ) included intensity and frequency of TMJ pain , m and ibular range of motion , TMJ sounds , and impairment of chewing . TMJ MRIs were performed at baseline and 24 months , and TMJ tomograms at baseline , 24 and 60 months . Most IAOMS recommended outcome measures improved significantly over time ( P≤0.0003 ) . There was no difference between treatment strategies relative to any treatment outcome at any follow-up ( P≥0.16 ) . Patient self- assessment of treatment success correlated with their ability to eat , with pain-free opening ≥35 mm , and with reduced pain intensity . Given no difference between treatment strategies , non-surgical treatment should be employed for TMJ closed lock before considering surgery The effects of carisoprodol and a placebo were compared in a sample of 60 patients with the clinical diagnosis of myofascial pain-dysfunction syndrome using double-blind design . Carisoprodol failed to show a significantly greater effect than the placebo . The side effects were about the same with both agents BACKGROUND Alpha-lipoic acid ( ALA ) , is a potent antioxidant mitochondrial coenzyme , the trometamol salt of thioctic acid that has been shown in clinical studies to be neuroprotective . This study examined the effect of ALA on the symptomatology of Burning mouth syndrome ( BMS ) . SUBJECTS AND METHODS Forty-two patients with BMS and no clinical or laboratory evidence of organic oral disease were divided into two groups ( Test and Control ) each of 21 subjects , matched for age and sex . The Test group were given ALA ( thioctic acid ; Tiobec ) for 30 days , as 600 mg per day orally for 20 days followed by 200 mg per day for 10 days . The Control group were given cellulose starch 100 mg per day as placebo for 30 days . All BMS patients were review ed at 10-day intervals and scored for changes in symptomatology . RESULTS Significant improvements were shown in the symptomatology of BMS in up to two-thirds of patients with BMS receiving alpha-lipoic acid , in about 15 % of those using placebo and also in up to two-thirds of those who , having tried placebo , were switched to ALA & NA ; The efficacy of topical aspirin/diethyl ether ( ADE ) mixture in the treatment of acute herpetic neuralgia and postherpetic neuralgia , suggested in a previous open‐label study ( De Benedittis et al. 1992 ) , has been evaluated in a double‐blind crossover placebo‐controlled study as compared with two other NSAID ( indomethacin and diclofenac ) drug/ether mixtures . The study included 37 patients ( 15 with acute herpetic neuralgia ( AHN ) and 22 with postherpetic neuralgia ( PHN ) ) . Comparative treatment results showed that only aspirin ( but not indomethacin and diclofenac ) was significantly superior to placebo , as compared with baseline and duration of pain relief ( P < 0.05 and P < 0.01 , respectively ) , in both AHN and PHN groups . Good‐to‐excellent results were achieved by 87 % of AHN patients and by 82 % of PHN patients treated with the ADE mixture , with no significant differences between the two groups . On the whole , patients with trigeminal involvement , less severe pain and with dysaesthetic quality of pain yielded best results The short-term effect of intra-articular injections of sodium hyaluronate and a corticosteroid ( betamethasone ) was compared in a sample of 33 patients who had pain and tenderness to palpation in the temporom and ibular joint of at least six months duration that had not responded to previous conservative treatment . The two drugs were r and omly allocated to the patients . A volume of 0.5 ml of the drug was injected twice into the superior joint compartment of the TMJ with a two-week interval between injections . The effect on subjective symptoms , clinical signs , and bite force was assessed . Both drugs reduced the symptoms and signs significantly , and no statistically significant difference in effect could be found between drugs in this regard . The results indicate that the difference between the drugs in terms of short-term therapeutic effects is small , and that sodium hyaluronate could be used as an alternative to corticosteroid for patients who have signs of TMJ inflammation , especially for those who have symptomatic osteoarthrosis Patients experiencing the symptoms of pain , tenderness , clicking , and limitation of function , which characterize the myofascial pain-dysfunction ( MPD ) syndrome have been subjected over the years to a variety of therapeutic measures . An investigation was made of the effectiveness of meprobamate in treatment of the MPD syndrome . Of the 90 patients studied , 58 % reported some improvement after taking the drug , and 31 % after taking a placebo . The subjective symptoms were reported as improved most frequently , whereas the more objective symptoms seemed less affected by either the meprobamate or the placebo OBJECTIVE To compare the efficacy and radiographic changes after arthrocentesis followed or not followed by intra-articular corticosteroid injection in patients with temporom and ibular disc displacement without reduction . METHODS Ninty patients were enrolled in the r and omized clinical trial . After receiving arthrocentesis , either 0.5 mL triamcinolone acetonide plus 0.5 mL saline ( experimental group , n = 46 ) or 1 mL saline solution as control ( control group , n = 44 ) was injected . Patients were assessed by visual analogue scale ( VAS ) pain scores and Fricton temporom and ihular joint ( TMJ ) index at first visit before treatment , 3 - 4 weeks and 6 months after treatment respectively . Transpharyngeal and lateral transcranial projections for temporom and ibular joints were taken for imaging evaluation . The pain score of patients with pain complaint were recorded everyday for 1 week after treatment . RESULTS Glucocorticoid injection showed more effective pain control over the first week ( P < 0.05 ) , and both groups reported symptom and clinical sign relief significantly after treatment ( P < 0.001 ) . However , quantitative evaluation for pain reduction , maximal mouth opening improvement and Friction TMJ index showed no significant difference between two groups at 3 - 4 weeks and 6 months after the treatment . Also there was no significant difference for condylar bone changes radiographically between the two groups . CONCLUSION Arthrocentesis is an effective treatment for temporom and ibular joint disc displacement without reduction , but it is not necessary to inject corticosteroid after arthrocentesis . Intra-articular corticosteroid injection after arthrocentesis is indicated for only those patients with severe pain AIMS To determine the effectiveness of topical capsaicin cream application on localized pain in the temporom and ibular joint ( TMJ ) area . METHODS A r and omized , double-blind , placebo-controlled study was conducted on 30 patients suffering from unilateral pain in the TMJ area . Patients were r and omly divided into experimental and placebo groups ; they were instructed to apply 0.025 % capsaicin cream or its vehicle to the painful TMJ area 4 times daily for 4 weeks . Subjective parameters of present pain , most severe pain , effect of pain on daily activities , and pain relief were assessed each week on a visual analog scale . Muscle and joint sensitivity to palpation on the painful and contralateral joints and maximal mouth opening ( assisted/passive and non-assisted/active ) were examined weekly by the same experienced examiner . RESULTS Capsaicin cream produced no statistically significant influence on measured variables when compared to placebo . Both experimental and placebo groups showed statistically significant improvement in most variables during the experiment . CONCLUSION The factor of time had a major effect in the non-specific improvement of the parameters assessed . The placebo effect played an important role in the treatment of patients with pain in the TMJ area OBJECTIVE The goal of the present study is to verify the efficacy of stellate ganglion block ( SGB ) in the treatment of facial pain that can be found in different pathological syndromes , and also to examine whether the efficacy is dependent upon when this therapy is administered . PATIENTS Fifty patients ( divided into two r and omized groups ) with facial pain caused by traumas , iatrogenic issues , herpes zoster , or neurological pathologies participated in this study . DESIGN AND INTERVENTIONS The first group ( N = 25 ) was treated with SGB produced by 10 administrations of 10 mg of levobupivacaine given every other day , followed by one administration per month for 6 months thereafter . The second group was treated with the drugs tramadol 100 mg/day and gabapentin 1800 mg/day orally for 6 months ; during the 7th month they were given SGB therapy using the same methodology as that described for the first group . RESULTS Before treatment , the mean visual analog scale ( VAS ) pain score for the first group was 8.89 ; after the 10th block treatment it was just 0.2 , and it remained at that reduced level for the 6th and 12th months . Before treatment , the mean VAS pain score for the second group was 8.83 ; after the 20th day on medication it was reduced to 4.1 , after 6 months it was 5.7 and after 12 months it was 4.9 . CONCLUSIONS Our results indicate that patients must be treated with SGB therapy precociously to receive its full benefits BACKGROUND Burning mouth syndrome ( BMS ) has features of a neuropathy and could be related to the production of the toxic free radicals that are released in stress situations . Alpha-lipoic acid is an antioxidant able to increase the levels of intracellular glutathione and eliminate free radicals . This study aim ed to examine the effectiveness of alpha-lipoic acid in the therapy of BMS . METHOD This was a double blind , controlled study conducted for two months on 60 patients with constant BMS . Comparing alpha-lipoic acid ( test ) with cellulose starch ( placebo ) , there was no laboratory evidence of deficiencies in iron , vitamins or thyroid function and no hyperglycaemia . RESULTS AND CONCLUSION Following treatment with alpha-lipoic acid , there was a significant symptomatic improvement , compared with placebo , with the majority showing at least some improvement after 2 months , thus supporting the hypothesis that burning mouth syndrome is a neuropathy . This improvement was maintained in over 70 % of patients at the 1 year follow-up The aim of the study was to compare treatment with diclofenac sodium ( Voltaren 3 x 50 mg ) to occlusal splint therapy in a r and omized , single-blind controlled trial of patients with a diagnosis of temporom and ibular joint ( TMJ ) osteoarthritis ( OA ) in accordance with Research Diagnostic Criteria for temporom and ibular disorders . Patients with general joint disorders or restrictions against medication with non-steroidal anti-inflammatory drug were not included . Twenty-seven females and two males ( aged 36 - 76 years ) included , answered a st and ardized question naire and were clinical ly examined and they underwent TMJ tomography . The treatment was r and omized to either splint ( n = 15 ) or diclofenac ( n = 14 ) . The temperatures over the TMJs were determined . The patients were re-examined 1 week , 1 month and 3 months after the start of treatment . A 1-year follow-up was carried out using question naires . After 1 week of treatment with diclofenac , significant reductions of pain and discomfort , TMJ tenderness and joint pain on jaw movements were noted . The splint therapy gave a significant reduction of reported symptoms after 1 month of treatment . Both treatments gave few adverse effects and were on an equal level . Estimation of the degree of inflammation by measuring the surface temperature over the TMJ was not reliable . Structural changes of the symptomatic TMJs were radiographically found in 82 % , the contralateral , symptom-free TMJ had changes in 36 % . There was a discrepancy between the clinical and the radiographical findings . Diclofenac gave a more rapid improvement , but both treatments gave a significant reduction of symptoms of TMJ OA within 3 months which remained at the one-year follow-up Abstract Objective : To investigate the effectiveness of repeated topical application of oral capsaicin gel in two different concentrations for relief of burning/stinging sensations in patients with burning mouth syndrome ( BMS ) . Material and methods : This r and omized double-blind cross-over study included 22 female patients with BMS . The patients were r and omized for topical application of either 0.01 % or 0.025 % oral capsaicin gel on the dorsal part of tongue three times daily for 14 days , followed by 14 days wash-out period , and finally treatment with the other concentration of oral gel three times daily for 14 days . A visual analogue scale ( VAS ) was used to assess the severity of pain five times during the intervention period . Results : 18 patients completed the intervention . Their VAS score at baseline was 5.5 ± 0.6 cm ( mean ± SD ) . Treatment with the two concentrations of capsaicin gels significantly improved the burning/stinging symptoms assessed on VAS compared with baseline ( p = 0.002 ) . There was no statistically significant difference between the two concentrations of the gels on relieving symptoms . Four patients dropped out during the intervention period due to gastrointestinal side-effects . Conclusions : Topical capsaicin might be an alternative for the short-term treatment of BMS . However , further studies are needed to investigate especially the gastro-intestinal side-effects which may limit its long-term use PURPOSE To compare the outcome of inferior and superior joint space injection of sodium hyaluronate in patients with disc displacement without reduction of the temporom and ibular joint ( TMJ ) . MATERIAL S AND METHODS One hundred twenty patients with disc displacement without reduction of TMJ were r and omized into 2 experimental groups . One group of patients received superior joint space injections of sodium hyaluronate and the other group was treated with inferior joint space injections . Patient 's TMJ status and clinical symptoms were evaluated at the 3 and 6 month follow-up appointments . The clinical parameters recorded were maximal mouth opening ( MMO ) , pain intensity on a visual analog scale ( VAS ) , and modified Helkimo 's clinical dysfunction index and analyzed with ANCOVA . RESULTS Fifty of the superior and 54 of the inferior joint space injection therapy group returned for the 3 and 6 month evaluations ; 86.67 % of the patients were retained in the follow-up . MMO , VAS , and Helkimo 's index of both groups improved at the 3 and 6 month follow-ups . The results of MMO changes and TMJ function were almost the same in both groups at 3 month follow-up . However , there was a significant reduction in TMJ pain in the inferior joint injection group at 3 month follow-up compared with the superior joint injection group ( P < .001 ) . There were also significant differences between the inferior joint injection group and superior joint injection group in MMO ( P < .005 ) , VAS ( P < .001 ) , and Helkimo 's index ( P < .001 ) at 6 month follow-up . CONCLUSION This study showed that inferior joint space injection with sodium hyaluronate is a valid method of treating disc displacement without reduction of TMJ and a long-term study will be needed to assess the effect of inferior joint injection on the morphologic changes of the TMJ PURPOSE To compare the long-term clinical and radiologic outcomes of temporom and ibular joint osteoarthritis ( TMJ-OA ) treated with arthrocentesis plus platelet-rich plasma ( PRP ) versus arthrocentesis alone . MATERIAL S AND METHODS A r and omized clinical trial in adult patients with TMJ-OA referred to the authors ' clinic from May 2012 through July 2013 was implemented . The sample was composed of 30 consecutive patients with TMJ-OA treated r and omly with arthrocentesis alone ( control group ) or initial arthrocentesis plus PRP injection and then 4 consecutive PRP injections ( study group ) . The predictor variable was treatment technique . The outcome variables were visual analog scale evaluations ( masticatory efficiency , joint sounds , and pain complaints ) , maximal interincisal opening , and cone-beam computed tomographic ( CBCT ) findings . Outcome variables were recorded preoperatively and 12 months postoperatively . Descriptive and bivariate statistics were computed , and significance was set at a P value less than .05 . The paired t and Student t tests were used for intragroup and intergroup comparisons , respectively . RESULTS The sample was composed of 47 joints of 30 patients with OA ( control group : 15 joints of 12 patients ; mean age , 35.08 ± 14.84 yr ; study group : 32 joints of 18 patients ; mean age , 32.22 ± 14.32 yr ) . Joint sounds and general pain complaints decreased statistically in the 2 groups , whereas masticatory efficiency , painless interincisal opening , and lateral motion increased statistically only in the study group . However , only masticatory efficiency showed statistically greater improvement in the study group compared with the control group . CBCT evaluations showed that reparative remodeling of the osseous abnormalities occurred at rates of 87.5 and 46.6 % in the study and control groups , respectively . CONCLUSIONS These findings suggested that arthrocentesis and PRP injections constitute a safe and promising method for the treatment of TMJ-OA that is superior to arthrocentesis alone Objective Burning mouth syndrome ( BMS ) is a chronic oral condition , characterised by burning symptoms , which mainly affects perimenopausal and postmenopausal women . Neuropathy might be the underlying cause of the condition . There are still insufficient data regarding successful therapy . The aim of this study was to compare the effectiveness of acupuncture and clonazepam . Methods Forty-two patients with BMS ( 38 women , 4 men ) aged 66.7±12.0 years were r and omly divided into two groups . Acupuncture was performed on 20 participants over 4 weeks , 3 times per week , on points ST8 , GB2 , TE21 , SI19 , SI18 and LI4 bilaterally as well as GV20 in the midline , each session lasting half an hour . Twenty-two patients took clonazepam once a day ( 0.5 mg in the morning ) for 2 weeks and , after 2 weeks , two tablets ( 0.5 mg in the morning and in the evening ) were taken for the next 2 weeks . Prior to and 1 month after either therapy , participants completed question naires : visual analogue scale , Beck Depression Inventory , Leeds Assessment of Neuropathic Symptoms and Signs ( LANSS ) pain scale , 36-item Short Form Health Survey ( SF-36 ) and Montreal Cognitive Assessment ( MoCA ) . Results There were significant improvements in the scores of all outcome measures after treatment with both acupuncture and clonazepam , except for MoCA . There were no significant differences between the two therapeutic regimens regarding the scores of the performed tests . Conclusions Acupuncture and clonazepam are similarly effective for patients with BMS |
13,375 | 23,021,324 | In all patients after correction for tetralogy of Fallot , BNP levels were elevated and correlated significantly with right ventricular end-diastolic dimensions and severity of pulmonary valve regurgitation .
Patients with a systemic right ventricle had elevated BNP levels , and positive correlations between BNP and right ventricular function were seen .
In conclusion , this review shows an overall increase in BNP values in complex CHD , although differences between types of congenital heart anomaly are present . | Brain natriuretic peptide ( BNP ) and N-terminal pro-brain natriuretic peptide ( NT-proBNP ) are well-established markers for heart failure in the general population .
However , the value of BNP as a diagnostic and prognostic marker for patients with structural congenital heart disease ( CHD ) is still unclear .
Therefore , the purpose of this study was to evaluate the clinical utility of BNP in patients with CHD . | The measurement of plasma B-type natriuretic peptide ( BNP ) has emerged as a useful biomarker of heart failure in patients with cardiomyopathy . The pathophysiology of heart failure in single ventricle ( SV ) circulation may be distinct from that of cardiomyopathies . A distinct pattern of BNP elevation in heart failure in the SV population was hypothesized : it is elevated in heart failure secondary to ventricular dysfunction but not in isolated cavopulmonary failure . BNP was measured prospect ively in SV patients at catheterization ( n = 22 ) and when assessing for heart failure ( n = 11 ) ( 7 normal controls ) . Of 33 SV subjects ( median age 62 months ) , 13 had aortopulmonary connections and 20 had cavopulmonary connections . Median and mean + /- SD BNP levels by shunt type were 184 and 754 + /- 1,086 pg/ml in the patients with aortopulmonary connections , 38 and 169 + /- 251 pg/ml in the patients with cavopulmonary connections , and 10 and 11 + /- 5 pg/ml in normal controls , respectively ( p = 0.004 ) . Median systemic ventricular end-diastolic pressure ( 8 mm Hg , R = 0.45 ) , mean pulmonary artery pressure ( 14.5 mm Hg , R = 0.62 ) , and mean right atrial pressure ( 6.5 mm Hg , R = 0.54 ) were correlated with plasma BNP . SV subjects with symptomatic heart failure from dysfunctional systemic ventricles had median and mean + /- SD BNP levels of 378 and 714 + /- 912 pg/ml ( n = 18 ) compared with patients with isolated failed Glenn or Fontan connections ( 19 and 23 + /- 16 pg/ml [ n = 7 , p = 0.001 ] ) and those with no heart failure ( 22 and 22 + /- 12 pg/ml [ n = 8 , p = 0.001 ] ) . Excluding the group with cavopulmonary failure , the severity of heart failure from systemic ventricular dysfunction was associated with plasma BNP . In conclusion , plasma BNP is elevated in SV patients with systemic ventricular or left-sided cardiac failure . BNP is not elevated in patients missing a pulmonary ventricle with isolated cavopulmonary failure Background —Impaired cardiac autonomic nervous activities and increased neurohumoral activities ( CANA , NHA ) characterize Fontan patients . However , the clinical significance of these changes is not clearly understood . Our purpose was to clarify the clinical significance of the CANA and NHA in stable Fontan patients . Methods and Results —We divided 22 atriopulmonary connection ( APC ) and 75 total cavopulmonary connection ( TCPC ) patients into 4 subgroups according to New York Heart Association ( NYHA ) class ( 1.8±0.6 ) and measured various CANA and NHA indices . All NHA indices were elevated in the symptomatic patients ( P<0.001 ) . Natriuretic peptides were higher in the APC than in the TCPC patients , and the hemodynamics showed no correlation with brain natriuretic peptide in the APC patients . Low arterial oxygen saturation and impaired hemodynamics greatly influenced all elevated NHA indices ( P<0.01 ) , except for plasma renin activity , in the TCPC patients . Impaired CANA indices did not relate to NYHA class , although surgeries were associated with lower heart rate variability . In addition to poor correlation between NHA and CANA , age and ventricular morphology had no impact on all CANA and NHA indices , except for high norepinephrine in right ventricular Fontan patients . Conclusions —Although symptomatic Fontan patients exhibit higher NHA , CANA is not related to either NYHA class or NHA . APC itself is responsible for higher natriuretic peptides , and arterial oxygen desaturation has a great impact on elevated NHA in the TCPC patients . These characteristics of the NHA and CANA differ from those of heart failure patients with biventricular physiology Background — Children and young adults with single-ventricle physiology have abnormal exercise capacity after the Fontan operation . A medication capable of decreasing pulmonary vascular resistance should allow improved cardiac filling and improved exercise capacity . Methods and Results — This study was a double-blind , placebo-controlled , crossover trial conducted in children and young adults after Fontan . Subjects were r and omized to receive placebo or sildenafil ( 20 mg three times daily ) for 6 weeks . After a 6-week washout , subjects crossed over for an additional 6 weeks . Each subject underwent an exercise stress test at the start and finish of each phase . After taking sildenafil , subjects had a significantly decreased respiratory rate and decreased minute ventilation at peak exercise . At the anaerobic threshold , subjects had significantly decreased ventilatory equivalents of carbon dioxide . There was no change in oxygen consumption during peak exercise , although there was a suggestion of improved oxygen consumption at the anaerobic threshold . Improvement at the anaerobic threshold was limited to the subgroup with single left or mixed ventricular morphology and to the subgroup with baseline serum brain natriuretic peptide levels ≥100 pg/mL. Conclusions — In this cohort , sildenafil significantly improved ventilatory efficiency during peak and submaximal exercise . There was also a suggestion of improved oxygen consumption at the anaerobic threshold in 2 subgroups . These findings suggest that sildenafil may be an important agent for improving exercise performance in children and young adults with single-ventricle physiology after the Fontan operation . Clinical Trial Registration — URL : http:// clinical trials.gov . Unique identifier : NCT00507819 To evaluate the relationship between plasma concentration of amino-terminal fragment of pro-brain natriuretic peptide ( NT-proBNP ) , functional capacity , and right ventricular overload in survivors of tetralogy of Fallot ( TOF ) repair , we prospect ively studied 70 operated TOF patients ( 44 males , 21 ± 1 years old ; mean ± SEM ) who underwent , during the same day , echocardiography , cardiac magnetic resonance imaging , neurohormonal characterization ( plasma NT-proBNP , catecholamines , plasma renin activity , and aldosterone assay ) , and cardiopulmonary exercise testing . Forty-eight age- and sex-matched healthy volunteers served as the control group . Compared to controls , maximal workload and peak oxygen consumption ( VO2/kg ) were lower in operated TOF patients ( p < 0.001 ) , whereas NT-proBNP concentration was elevated ( p < 0.001 ) . No difference was found among the other neurohormones . In operated TOF patients , NT-proBNP showed a significant positive correlation with right ventricular ( RV ) end systolic and end diastolic volumes and RV systolic pressure , and it showed a negative correlation with peak VO2/kg and RV ejection fraction . From multivariable analysis , NT-proBNP concentration was found to be an independent predictor of peak VO2/kg , RV end systolic volume , and RV systolic pressure . These results show an association among RV overload , decrease in functional capacity , and cardiac natriuretic peptide expression in operated TOF patients . NT-proBNP plasma assay may be a useful tool for diagnostic purpose s and for decision making in this setting BACKGROUND The aim of this study was to assess the relation between plasma B-type natriuretic peptide ( BNP ) levels and right ventricular function evaluated by tissue Doppler imaging ( TDI ) in patients after repair of tetralogy of Fallot ( ToF ) . METHODS Twenty-five patients with a mean age of 14.1 + /- 4.4 years who underwent repair of ToF at a mean age of 4.9 + /- 5.1 years enrolled in this study . The control group consisted of 29 healthy children at a mean age of 13.1 + /- 2.8 years . The right ventricle and pulmonary regurgitation ( PR ) were assessed by two-dimensional echocardiography and color Doppler . Blood sample s for BNP levels were taken and TDI was performed at rest . RESULTS Plasma BNP levels were significantly higher in patients than in controls ( 28.3 + /- 24.1 vs. 7.4 + /- 2.3 pg/mL , P = 0.0001 ) . The myocardial performance index ( MPI ) ( 1.08 + /- 0.35 vs. 0.58 + /- 0.11 , P = 0.0001 ) was higher and isovolumic acceleration ( IVA ) ( 3.1 + /- 0.7 vs. 5.4 + /- 1.0 m/s(2 ) , P = 0.0001 ) was lower in patients . The correlations were also significant between the degree of PR and MPI ( r = 0.7 , P = 0.0001 ) and also IVA ( r = -0.7 , P = 0.0001 ) . The correlations were also significant between the BNP level and MPI ( r = 0.6 , P = 0.0001 ) , IVA ( r = -0.4 , P = 0.002 ) and the degree of PR ( r = 0.6 , P = 0.0001 ) . CONCLUSION As a result , plasma BNP level increases in patients with ToF and both MPI and IVA from the right ventricular basal segments might be used to assess the right ventricular function Background — Pharmacological blockade of the renin-angiotensin system improves exercise tolerance in patients with left ventricular dysfunction , yet its impact on patients with systemic right ventricles ( RVs ) remains unknown . Methods and Results — A multicenter , r and omized , double-blind , placebo-controlled , crossover clinical trial was performed to assess the effects of losartan on exercise capacity and neurohormonal levels in patients with systemic RVs . Of 29 patients studied ( age , 30.3±10.9 years ) , 21 had transposition of the great arteries with a Mustard baffle , and 8 had congenitally corrected transposition of the great arteries . Baseline values were as follows : & OV0312;o2max , 29.8±5.6 mL · kg−1 · min−1 ( 73.5±12.9 % predicted value ) ; RV ejection fraction , 41.6±9.3 % ; N-terminal pro brain natriuretic peptide ( NT-proBNP ) , 257.7±243.4 pg/mL ( normal < 125 pg/mL ) ; and angiotensin II , 5.7±4.9 pg/mL ( normal < 5.0 pg/mL ) . Comparing losartan to placebo showed no differences in & OV0312;o2max ( 29.9±5.4 versus 29.4±6.2 mL · kg−1 · min−1 ; P=0.43 ) , exercise duration ( 632.3±123.0 versus 629.9±140.7 seconds ; P=0.76 ) , and NT-proBNP levels ( 201.2±267.8 versus 229.7±291.5 pg/mL ; P=0.10 ) , despite a trend toward increased angiotensin II levels ( 15.2±13.8 versus 8.8±12.5 pg/mL ; P=0.08 ) . Conclusions — In adults with systemic RVs , losartan did not improve exercise capacity or reduce NT-proBNP levels . Minimal baseline activation of the renin-angiotensin system may explain this lack of benefit and imply an alternative pathophysiological mechanism for the progressive ventricular dysfunction and impaired exercise capacity observed in such patients AIMS Our purpose was to evaluate the effect of a treatment over six months with bisoprolol on the surrogate parameters of N-Terminal-pro brain natriuretic peptide , subsequently to be described as brain natriuretic peptide , peak uptake of oxygen , and ventricular function assessed by magnetic resonance imaging in grown ups and adults who had undergone surgical correction of tetralogy of Fallot . METHODS AND RESULTS We design ed a prospect i ve , r and omized , double-blind , placebo controlled trial . We enrolled 33 patients , aged 30.9 plus or minus 9.5 years in either class 1 or 2 of the grading of the New York Heart Association class with both levels of brain natriuretic peptide greater than 100 pg/ml and a reduced peak uptake of oxygen less than 25 ml/kg/min . During treatment with Bisoprolol , the levels of brain natriuretic peptide increased significantly from 206 plus or minus 95 to 341 plus or minus 250 pg/ml ( p < 0.05 ) , and those of atrial natriuretic peptide from 4117 plus or minus 1837 to 5340 plus or minus 2102 fmol/ml ( p = 0.0005 ) . These measures remained unchanged in the group of patients receiving the placebo . Peak uptake of oxygen did not differ significantly in either group , nor did treatment have any significant effect on right and left ventricular volumes and ejection fractions as determined by magnetic resonance imaging . The clinical state as judged within the grading system of the New York Heart Association was also unchanged by beta-blockade . CONCLUSION Beta blockade with Bisoprolol seems to have no beneficial effect on asymptomatic or mildly symptomatic patients with right ventricular dysfunction secondary to repaired tetralogy of Fallot with residual pulmonary regurgitation and /or stenosis BACKGROUND In acquired heart disease , brain natriuretic peptide ( BNP ) and N-Terminal pro-brain natriuretic peptide ( NT-proBNP ) are increasingly used as diagnostic and prognostic markers . In adult congenital heart disease , the abnormal anatomy and physiology complicate assessment of cardiac function . We studied the clinical correlates of measurement of natriuretic peptides ( NP ) in adults with a right ventricle in the systemic position or with Fontan-type physiology . METHODS A prospect i ve longitudinal study ( follow up time 23+/-13 months , mean+/-S.D. ) was conducted in a specialised centre on 61 patients ( age 26+/-8 years ; NYHA class 1.5+/-0.6 ) including Senning/Mustard corrected transposition , congenitally corrected transposition and Fontan/total cavopulmonary connection . Plasma NP concentration was compared with NYHA class , exercise capacity and echocardiographically determined systemic systolic ventricular function . RESULTS Neurohormone concentrations were generally elevated ( mean=290 % of upper reference limit ) and related to NYHA class ( P<0.001 , NYHA I vs. II-IV ) . No clinical ly significant relationship to ventricular function or exercise capacity was found however . An NP measurement could not predict the future course of the disease in terms of functional status or ventricular function . CONCLUSION In contrast to patients with acquired heart disease , measurement of NP seems to have low clinical value in adults with a right ventricle in the systemic position or with Fontan-type physiology The right ventricle , which faces systemic pressure due to congenital heart disease , often develops premature systolic dysfunction . Cardiac hormones might be useful to identify patients with such systolic dysfunction . This prospect i ve study investigated the relationship of atrial natriuretic peptide ( ANP ) and brain natriuretic peptide ( BNP ) levels with right ventricular ejection fraction ( RVEF ) and exercise performance in patients with a systemic right ventricle . ANP levels were obtained in 24 patients and BNP levels were obtained in 22 patients with systemic right ventricle . Patients underwent exercise study ( n = 22 ) and cardiovascular magnetic resonance imaging ( n = 11 ) or equilibrium radionuclide angiography ( n = 13 ) to determine RVEF . There were 17 patients with complete transposition and 7 patients with corrected transposition . ANP showed an inverse correlation with RVEF ( r2 = 0.63 , p < 0.001 ) , a weak but statistically significant inverse correlation with exercise duration ( r2 = 0.18 , p = 0.047 ) and no relationship with maximal oxygen consumption ( peak V′O2 ) ( r2 = 0.10 , p = NS ) . BNP did not show a relationship with any of the parameters measured . ANP shows a strong inverse correlation with RVEF and a weak correlation with exercise duration in patients with a systemic right ventricle . BNP does not show a significant relationship when compared with either parameter . ANP might be a useful tool for identification of systolic right ventricular dysfunction BACKGROUND Accurate estimation of right ventricular ( RV ) function in patients with repaired tetralogy of Fallot ( RTOF ) is difficult , partly due to the presence of tricuspid regurgitation and pulmonary regurgitation and /or stenosis . The aim of the present study was to evaluate RV systolic and diastolic function of adult asymptomatic patients with RTOF by means of tissue Doppler imaging ( TDI ) and brain natriuretic peptide ( BNP ) values . METHODS 25 adult patients with RTOF and 25 healthy controls were studied . The following echocardiographic measurements were obtained : RV diameter/left ventricular ( LV ) diameter ( RVD/LVD ) and systolic ( Sa ) and diastolic ( Ea , Aa ) velocities at the RV free wall tricuspid annulus site . Serum BNP levels were measured as well . RESULTS Patients with RTOF demonstrated reduced TDI velocities : Sa , 8.16 + /- 1.15 versus 16.43 + /- 1.15 cm/sec ( P < .001 ) ; Ea , 10.00 + /- 2.18 versus 18.99 + /- 1.00 cm/sec ( P < .001 ) ; Aa , 5.64 + /- 1.77 vs. 13.69 + /- 0.86 cm/sec ( P < .001 ) . Patients with RTOF also had higher BNP levels than controls ( 85.0 + /- 87.0 vs 5.36 + /- 1.0 pg/mL ; P < .001 ) . The increased BNP levels in RTOF patients correlated with the RVD/LVD ratio ( r = .521 ; P < .01 ) . CONCLUSIONS Our results indicate that although our cohort of patients was asymptomatic , using TDI and BNP allowed us to easily discriminate them from the healthy controls . The ability of TDI to assess ventricular function even in the presence of valvular lesions , as in RTOF patients , makes it a valuable tool in the investigation and follow-up of these patients BACKGROUND Although surgical treatment for tetralogy of Fallot ( TOF ) has been used with considerable success , right ventricular function may remain altered after repair . The NT-proBNP assessment has been shown to be a reliable parameter for the heart failure assessment . AIM To determine NT-proBNP values in assessment of right ventricular function in children after TOF correction . METHODS In 20 patients after TOF correction aged from 10 to 17 years ( follow-up period ranged from 7 to 16 years ) NT-proBNP level at rest and after exertion , treadmill test and echocardiography were performed . In the control healthy children NT-proBNP level at rest was assessed . RESULTS The mean values of NT-proBNP level in the TOF patients were significantly higher than in controls ( 11.0 + /- 12.0 fmol/l and 5.4 + /- 7.5 fmol/l , p < 0.05 ) . In patients repaired with a transannular patch the mean value of NT-proBNP level was higher than in children operated on without a transannular patch ( 18.3 + /- 16.5 vs. 6.8 + /- 7.9 fmol/l , p < 0.05 ) . In children in whom physiological shortening of QRS complex during treadmill test was observed , NT-proBNP level was lower ( mean values at rest 5.0 + /- 4.8 fmol/l and after exertion 7.3 + /- 6.3 fmol/l ) compared to patients with prolongation of QRS duration ( mean values at rest 17.7 + /- 15.6 fmol/l and after exertion 20.3 + /- 17.8 fmol/l ) ( p < 0.05 ) . Significant differences in NT-proBNP levels between children with severe pulmonary regurgitation and mild/moderate pulmonary regurgitation were detected ( mean values at rest 18.6 + /- 15.0 vs. 4.2 + /- 3.9 fmol/l and after exertion 20.0 + /- 18.6 vs. 5.7 + /- 4.6 fmol/l ) ( p < 0.05 ) . The NT-proBNP levels were also higher in children with severe tricuspid valve insufficiency compared to children with mild/moderate tricuspid valve regurgitation ( mean values at rest 19.5 + /- 15.0 vs. 4.9 + /- 3.7 fmol/l and after exertion 22.5 + /- 17.1 vs. 7.0 + /- 4.6 fmol/l ) . CONCLUSIONS The NT-proBNP level in patients after TOF correction is higher than in healthy children . The NT-proBNP level is higher and exertion tolerance is lower in children repaired with rather than without transannular patch . In patients with severe pulmonary regurgitation and /or severe tricuspid valve insufficiency NT-proBNP level is higher than in patients without right ventricular volume overload . The measurement of NT-proBNP level might be helpful in order to separate those patients after TOF correction who are at increased risk of heart failure and arrhythmia OBJECTIVE The objective of the study was to determine perioperative B-type natriuretic peptide levels in infants and children undergoing bidirectional cavopulmonary anastomosis or total cavopulmonary connection , and the predictive value of B-type natriuretic peptide levels for outcome . METHODS Plasma B-type natriuretic peptide levels were measured before and 2 , 12 , and 24 hours after surgery in 36 consecutive patients undergoing bidirectional cavopulmonary anastomosis ( n = 25 ) or total cavopulmonary connection ( n = 11 ) . B-type natriuretic peptide levels were evaluated as predictors of outcome . RESULTS B-type natriuretic peptide levels increased after surgery , peaking at 12 hours in most patients . In the bidirectional cavopulmonary anastomosis group , patients with 12-hour B-type natriuretic peptide > or = 500 pg/mL had a longer duration of mechanical ventilation ( 165 + /- 149 hours vs 20 + /- 9 hours , P = .004 ) , longer intensive care unit stay ( 11 + /- 7 days vs 4 + /- 2 days , P = .001 ) , and longer hospital stay ( 20 days + /- 12 vs 9 days + /- 5 , P = .003 ) . A 12-hour B-type natriuretic peptide > or = 500 pg/mL had a sensitivity of 80 % and a specificity of 80 % for predicting an unplanned surgical or transcatheter cardiac intervention , including transplantation ( P = .03 ) . In the total cavopulmonary connection group , preoperative B-type natriuretic peptide levels were highest in patients with total cavopulmonary connection failure compared with patients with a good outcome ( 88 + /- 46 pg/mL vs 15 + /- 6 pg/mL , P = .03 ) . CONCLUSION Postoperative B-type natriuretic peptide levels predict outcome after bidirectional cavopulmonary anastomosis , and preoperative levels are greater in patients with both early and late total cavopulmonary connection failure compared with patients with a good outcome Objective The mechanisms underlying adverse electro-mechanical interaction after tetralogy of Fallot ( TOF ) repair remain unclear . This study investigated biventricular dyssynchrony in children with TOF and its relationship to exercise , QRS duration ( QRSd ) and ventricular mechanics . Methods 29 asymptomatic children ( 5–18 years ) with repaired TOF were prospect ively evaluated by MRI , cardiopulmonary exercise testing and echocardiography at rest and during bicycle exertion . Their dyssynchrony results were compared with those of 44 resting and 27 exercising , age- and sex-matched controls . An intraventricular dyssynchrony index was calculated from the SD of regional time intervals in 12 left ventricular ( LV ) ‘ Ts LV-12SD ’ and eight right ventricular ( RV ) ‘ Ts RV-8SD ’ segments . Ventricular size , volumes , ejection fractions , pulmonary regurgitant volumes and peak oxygen consumption and N-terminal BNP levels were quantified in the patients . Results Despite moderate RV dilatation ( median indexed RV end-diastolic volume 145.2 ml/m2 ) and right bundle branch block ( median QRSd 130 ms ) compared with controls , children with TOF demonstrated neither RV nor LV dyssynchrony at rest ( Ts RV-8SD , 37.9±10.2 vs 44.3±10.3 , 95 % CI −11.8 to −0.99 , p=0.02 ; Ts LV-12SD , 38.6±16.8 vs 34.0±10.8 , 95 % CI −1.8 to 11.0 , p=0.16 ) . Exercise stress induced biventricular dyssynchrony in patients with TOF but not in controls ( Ts RV-8SD , 59.9±34.4 vs 28.2±10.4 , p<0.0001 , 95 % CI 17.2 to 46.3 ; Ts LV-12SD , 48.0±18.6 vs 31.9±10.7 , 95 % CI 7.9 to 24.4 , p=0.002 ) . This was unrelated to QRSd , ventricular volumes and function , or peak oxygen consumption . Conclusion Exercise induces biventricular mechanical dyssynchrony in children with TOF |
13,376 | 27,355,911 | However , supplementation may have little or no effect on weight gain during treatment ( data not pooled ; five trials , 2940 participants , low quality evidence ) , and no studies have assessed the effect on quality of life .
Plasma levels of vitamin A appear to increase following initiation of tuberculosis treatment regardless of supplementation .
In contrast , supplementation probably does improve plasma levels of zinc , vitamin D , vitamin E , and selenium , but this has not been shown to have clinical ly important benefits .
Of note , despite multiple studies of vitamin D supplementation in different doses , statistically significant benefits on sputum conversion have not been demonstrated .
Authors ' conclusions There is currently insufficient research to know whether routinely providing free food , or energy supplements improves tuberculosis treatment outcomes , but it probably improves weight gain in some setting s. Although blood levels of some vitamins may be low in people starting treatment for active tuberculosis , there is currently no reliable evidence that routinely supplementing above recommended daily amounts has clinical benefits . | Abstract Background Tuberculosis and malnutrition are linked in a complex relationship .
Tuberculosis may cause undernutrition through increased metabolic dem and s and decreased intake , and nutritional deficiencies may worsen the disease , or delay recovery by depressing important immune functions .
At present , there is no evidence ‐based nutritional guidance for adults and children being treated for tuberculosis .
Objectives To assess the effects of oral nutritional supplements in people being treated with antituberculous drug therapy for active tuberculosis . | OBJECTIVE To assess the effect of micronutrient supplementation on tuberculosis ( TB ) patient outcomes . MATERIAL AND METHODS The r and omized , double-blinded , placebo-controlled study was conducted in pulmonary TB patients undergoing directly observed treatment short course/ tratamiento acortado estrictamente supervisado ( TAES/ DOTS ) at IMSS in Ciudad Juarez , Chihuahua , Mexico , who were recruited during August 2005-July 2006 . Consecutive patients received zinc and vitamin A supplements or matched placebo for four months . Dietary intake , blood zinc and vitamin A , immune response ( IFN-gamma , TNF-alpha , and IL-10 mRNA ) , and sputum smear conversion were measured . RESULTS The proportion of micronutrient compared to placebo group subjects with a negative sputum smear by month 3 was significantly increased ( p= 0.03 ) . This occurred subsequent to increased TNF-alpha and IFN-gamma and decreased IL-10 observed at month 2 . Micronutrient supplementation appeared to accelerate the beneficial therapeutic effect of chemotherapy . CONCLUSIONS The earlier elimination of bacilli from sputum was associated with improved zinc status and Th1 immune response . The therapeutic effect of vitamin A was less evident RATIONALE Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis . OBJECTIVES To test whether vitamin D supplementation of patients with tuberculosis ( TB ) improved clinical outcome and reduced mortality . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau . We included 365 adult patients with TB starting antituberculosis treatment ; 281 completed the 12-month follow-up . The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment . MEASUREMENTS AND MAIN RESULTS The primary outcome was reduction in a clinical severity score ( TBscore ) for all patients with pulmonary TB . The secondary outcome was 12-month mortality . No serious adverse effects were reported ; mild hypercalcemia was rare and present in both arms . Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo . Overall mortality was 15 % ( 54 of 365 ) at 1 year of follow-up and similar in both arms ( 30 of 187 for vitamin D treated and 24 of 178 for placebo ; relative risk , 1.19 [ 0.58 - 1.95 ] ) . HIV infection was seen in 36 % ( 131 of 359 ) : 21 % ( 76 of 359 ) HIV-1 , 10 % ( 36 of 359 ) HIV-2 , and 5 % ( 19 of 357 ) HIV-1 + 2 . CONCLUSIONS Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB ; it is possible that the dose used was insufficient . Clinical trial registered with www.controlled-trials.com/is rct n ( IS RCT N35212132 ) Background The association between pulmonary tuberculosis ( PTB ) and diabetes mellitus ( DM ) has been previously attracted much attention . Diabetes alters immunity to tuberculosis , leading to more frequent treatment failure in TB patients with DM . Moreover , TB and DM often coincide with micronutrients deficiencies , such as retinol and vitamin D , which are especially important to immunity of the body and may influence pancreas β-cell function . However , the effects of retinol and vitamin D supplementation in active TB patients with diabetes on treatment outcomes , immune and nutrition state are still uncertain . We are conducting a r and omized controlled trial of vitamin A and /or D in active PTB patients with DM in a network of 4 TB treatment clinics to determine whether the supplementation could improve the outcome in the patients . Methods / design This is a 2 × 2 factorial trial . We plan to enroll 400 active PTB patients with DM , and r and omize them to VA ( 2000 IU daily retinol ) ; VD ( 400 IU daily cholecalciferol ) ; VAD ( 2000 IU daily retinol plus 400 IU cholecalciferol ) or control ( placebo ) group . Our primary outcome measure is the efficacy of anti-tuberculosis treatment and ameliorating of glucose metabolism , and the secondary outcome measure being immune and nutrition status of the subjects . Of the first 37 subjects enrolled : 8 have been r and omized to VA , 10 to VD , 9 to VAD and 10 to control . To date , the sample is 97.3 % Han Chinese and 91.9 % female . The average fasting plasma glucose level is 12.19 mmol/L. Discussion This paper describes the design and rationale of a r and omized clinical trial comparing VA and /or VD supplementation to active pulmonary TB patients with DM . Our trial will allow rigorous evaluation of the efficacy of the supplementation to active TB and DM therapy for improving clinical outcomes and immunological condition . This detailed description of trial methodology can serve as a template for the development of future treatment scheme for active TB patient with DM.Trial registration In tuberculosis ( TB ) , the production of nitric oxide ( NO ) is confirmed but its importance in host defense is debated . Our aim was to investigate whether a food supplement rich in arginine could enhance clinical improvement in TB patients by increased NO production . Smear positive TB patients from Gondar , Ethiopia ( n = 180 ) were r and omized to a food supplementation rich in arginine ( peanuts , equivalent to 1 g of arginine/day ) or with a low arginine content ( wheat crackers , locally called daboqolo ) during four weeks . The primary outcome was cure rate according to the WHO classification and secondary outcomes were sputum smear conversion , weight gain , sedimentation rate , reduction of cough and chest X-ray improvement as well as levels of NO in urine ( uNO ) or exhaled air ( eNO ) at two months . There was no effect of the intervention on the primary outcome ( OR 1.44 , 95 % CI : 0.69 - 3.0 , p = 0.39 ) or secondary outcomes . In the subgroup analysis according to HIV status , peanut supplemented HIV+/TB patients showed increased cure rate ( 83.8 % ( 31/37 ) vs 53.1 % ( 17/32 ) , p < 0.01 ) . A low baseline eNO ( < 10 ppb ) in HIV+/TB patients was associated with a decreased cure rate . We conclude that nutritional supplementation with a food supplement rich in arginine did not have any overall clinical effect . In the subgroup of HIV positive TB patients , it significantly increased the cure rate and as an additional finding in this subgroup , low initial levels of NO in exhaled air were associated with a poor clinical outcome but this needs to be confirmed in further studies Background . Dietary supplementation has been used as a mechanism to augment the immune system . Adjunctive therapy with L-arginine has the potential to improve outcomes in active tuberculosis . Methods . In a r and omized clinical trial 63 participants with smear-positive pulmonary tuberculosis in Markazi Province of Iran were given arginine or placebo for 4 weeks in addition to conventional chemotherapy . The final treatment success , sputum conversion , weight gain , and clinical symptoms after one and two months were considered as primary outcomes and secondary outcomes were ESR , CRP , and Hg . Data were collected and analyzed with SPSS software ( ver . 18 ) . Results . Arginine supplementation reduced constitutional symptoms ( P = 0.032 ) in patients with smear-positive TB at the end of the first month of treatment . Arginine treated patients had significantly increased BMI at the end of the first and second months of treatment ( P = 0.032 and P = 0.04 ) and a reduced CRP at the end of the first month of treatment ( P = 0.03 ) versus placebo group . Conclusion . Arginine is useful as an adjunctive therapy in patients with active tuberculosis , in which the effects are more likely mediated by the increased production of nitric oxide and improved constitutional symptoms and weight gain . This trial is registered with Clinical Trials Registry of Iran : I RCT 201211179855N2 Background Vitamin D ( vitD ) and L-arginine have important antimycobacterial effects in humans . Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis ( TB ) . Methods In a 4-arm r and omised , double-blind , placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis ( PTB ) in Timika , Indonesia , we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo , and L-arginine 6.0 g daily or matching placebo , for 8 weeks , on proportions of participants with negative 4-week sputum culture , and on an 8-week clinical score ( weight , FEV1 , cough , sputum , haemoptysis ) . All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned . Adults with new smear-positive PTB were eligible . The trial was registered at Clinical Trials.gov NCT00677339 . Results 200 participants were enrolled , less than the intended sample size : 50 received L-arginine + active vitD , 49 received L-arginine + placebo vit D , 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model , 99 people received arginine , 101 placebo arginine , 101 vitamin D , 99 placebo vitamin D. Results for the primary endpoints were available in 155 ( 4-week culture ) and 167 ( clinical score ) participants . Sputum culture conversion was achieved by week 4 in 48/76 ( 63 % ) participants in the active L-arginine versus 48/79 ( 61 % ) in placebo L-arginine arms ( risk difference −3 % , 95 % CI −19 to 13 % ) , and in 44/75 ( 59 % ) in the active vitD versus 52/80 ( 65 % ) in the placebo vitD arms ( risk difference 7 % , 95 % CI −9 to 22 % ) . The mean clinical outcome score also did not differ between study arms . There were no effects of the interventions on adverse event rates including hypercalcaemia , or other secondary outcomes . Conclusion Neither vitD nor L-arginine supplementation , at the doses administered and with the power attained , affected TB outcomes . Registry Clinical Trials.gov . Registry number : BACKGROUND The results of cross-sectional studies indicate that micronutrient deficiencies are common in patients with tuberculosis . No published data exist on the effect of vitamin A and zinc supplementation on antituberculosis treatment . OBJECTIVE Our goal was to investigate whether vitamin A and zinc supplementation increases the efficacy of antituberculosis treatment with respect to clinical response and nutritional status . DESIGN In this double-blind , placebo-controlled trial , patients with newly diagnosed tuberculosis were divided into 2 groups . One group ( n = 40 ) received 1500 retinol equivalents ( 5000 IU ) vitamin A ( as retinyl acetate ) and 15 mg Zn ( as zinc sulfate ) daily for 6 mo ( micronutrient group ) . The second group ( n = 40 ) received a placebo . Both groups received the same antituberculosis treatment recommended by the World Health Organization . Clinical examinations , assessment s of micronutrient status , and anthropometric measurements were carried out before and after 2 and 6 mo of antituberculosis treatment . RESULTS At baseline , 64 % of patients had a body mass index ( in kg/m(2 ) ) < 18.5 , 32 % had plasma retinol concentrations < 0.70 micromol/L , and 30 % had plasma zinc concentrations < 10.7 micromol/L. After antituberculosis treatment , plasma zinc concentrations were not significantly different between groups . Plasma retinol concentrations were significantly higher in the micronutrient group than in the placebo group after 6 mo ( P < 0.05 ) . Sputum conversion ( P < 0.05 ) and resolution of X-ray lesion area ( P < 0.01 ) occurred earlier in the micronutrient group . CONCLUSION Vitamin A and zinc supplementation improves the effect of tuberculosis medication after 2 mo of antituberculosis treatment and results in earlier sputum smear conversion BACKGROUND Nutritional support is often recommended as part of the treatment of tuberculosis , but it has never been properly tested . OBJECTIVE We assessed the effects of early nutritional intervention on lean mass and physical function in patients with tuberculosis and wasting . DESIGN Patients who started antituberculous therapy within the previous 2 wk were r and omly assigned to receive st and ard nutritional counseling ( control group ) or nutritional counseling to increase their intake through diet and high-energy supplements ( nutritional supplement group ) for 6 wk . Body composition was measured by dual-energy X-ray absorptiometry , and physical function was assessed by maximum grip strength . RESULTS Patients in the nutritional supplement group ( n = 19 ) had a significantly greater increase in body weight ( 2.57 + /- 1.78 compared with 0.84 + /- 0.89 kg , P = 0.001 ) , total lean mass ( 1.17 + /- 0.93 compared with 0.04 + /- 1.26 kg , P = 0.006 ) , and grip strength ( 2.79 + /- 3.11 compared with -0.65 + /- 4.48 kg , P = 0.016 ) than did the control subjects ( n = 17 ) at week 6 . During subsequent follow-up , the increase in body weight remained greater in the nutritional supplement group , but this increase was due mainly to a greater gain in fat mass in the nutritional supplement group than in the control group . CONCLUSIONS Early intervention to increase nutritional intake increases lean mass and physical function . This adjunct to tuberculosis therapy could confer socioeconomic and survival benefits that deserve investigation in large-scale trials . Nutritional intervention after the initial phase of treatment could be less beneficial because it mainly increases fat OBJECTIVE To investigate the effects of nutritional supplementation on the outcome and nutritional status of south Indian patients with tuberculosis ( TB ) with and without human immunodeficiency virus ( HIV ) coinfection on anti-tuberculous therapy . METHOD R and omized controlled trial on the effect of a locally prepared cereal-lentil mixture providing 930 kcal and a multivitamin micronutrient supplement during anti-tuberculous therapy in 81 newly diagnosed TB alone and 22 TB-HIV-coinfected patients , among whom 51 received and 52 did not receive the supplement . The primary outcome evaluated at completion of TB therapy was outcome of TB treatment , as classified by the national programme . Secondary outcomes were body composition , compliance and condition on follow-up 1 year after cessation of TB therapy and supplementation . RESULTS There was no significant difference in TB outcomes at the end of treatment , but HIV-TB coinfected individuals had four times greater odds of poor outcome than those with TB alone . Among patients with TB , 1/35 ( 2.9 % ) supplemented and 5/42(12 % ) of those not supplemented had poor outcomes , while among TB-HIV-coinfected individuals , 4/13 ( 31 % ) supplemented and 3/7 ( 42.8 % ) non-supplemented patients had poor outcomes at the end of treatment , and the differences were more marked after 1 year of follow-up . Although there was some trend of benefit for both TB alone and TB-HIV coinfection , the results were not statistically significant at the end of TB treatment , possibly because of limited sample size . CONCLUSION Nutritional supplements in patients are a potentially feasible , low-cost intervention , which could impact patients with TB and TB-HIV . The public health importance of these diseases in re source -limited setting s suggests the need for large , multi-centre r and omized control trials on nutritional supplementation BACKGROUND Low serum concentrations of vitamin A and zinc are common in tuberculosis and may have an adverse effect on host cell-mediated responses . The role of adjunctive micronutrient supplementation on treatment outcomes is uncertain . OBJECTIVE The objective was to assess the efficacy of vitamin A and zinc supplementation on sputum smear and culture conversion and time to culture detection in adults with sputum smear-positive pulmonary tuberculosis . DESIGN Participants attending a primary care tuberculosis clinic in Cape Town , South Africa , were r and omly assigned to receive micronutrients ( single dose of 200,000 IU retinyl palmitate plus 15 mg Zn/d for 8 wk ) or matching placebo . Sputum was collected weekly for 8 wk for auramine staining and culture on liquid media ( BACTEC MGIT 960 ; Becton Dickinson , Sparks , MD ) . Performance status , chest radiographs , and anthropometric measures were assessed at baseline and again at 8 wk . RESULTS The participants ( n = 154 ) were r and omly assigned to the micronutrient ( n = 77 ) or placebo ( n = 77 ) group . Twenty participants were HIV infected ( 13 % ) , and 12 participants had an unknown HIV status ( 8 % ) . No differences in time to smear or culture conversion were observed between the treatment groups by Kaplan-Meier analysis ( P = 0.15 and P = 0.38 , respectively ; log-rank test ) . Log-logistic regression analysis found no significant group interaction effect in time to culture detection over the 8-wk period ( P = 0.32 ) . No significant differences in weight gain ( 2.3 ± 3.5 compared with 2.2 ± 2.4 kg , P = 0.68 ) or radiologic resolution were observed between the treatment groups . CONCLUSION Supplementation with vitamin A and zinc did not affect treatment outcomes in participants with pulmonary tuberculosis at 8 wk . This trial was registered at controlled-trials.com as IS RCT N80852505 Background Poverty undermines adherence to tuberculosis treatment . Economic support may both encourage and enable patients to complete treatment . In South Africa , which carries a high burden of tuberculosis , such support may improve the currently poor outcomes of patients on tuberculosis treatment . The aim of this study was to test the feasibility and effectiveness of delivering economic support to patients with pulmonary tuberculosis in a high-burden province of South Africa . Methods This was a pragmatic , unblinded , two-arm cluster-r and omized controlled trial , where 20 public sector clinics acted as clusters . Patients with pulmonary tuberculosis in intervention clinics ( n = 2,107 ) were offered a monthly voucher of ZAR120.00 ( approximately US$ 15 ) until the completion of their treatment . Vouchers were redeemed at local shops for foodstuffs . Patients in control clinics ( n = 1,984 ) received usual tuberculosis care . Results Intention to treat analysis showed a small but non-significant improvement in treatment success rates in intervention clinics ( intervention 76.2 % ; control 70.7 % ; risk difference 5.6 % ( 95 % confidence interval : -1.2 % , 12.3 % ) , P = 0.107 ) . Low fidelity to the intervention meant that 36.2 % of eligible patients did not receive a voucher at all , 32.3 % received a voucher for between one and three months and 31.5 % received a voucher for four to eight months of treatment . There was a strong dose – response relationship between frequency of receipt of the voucher and treatment success ( P < 0.001 ) . Conclusions Our pragmatic trial has shown that , in the real world setting of public sector clinics in South Africa , economic support to patients with tuberculosis does not significantly improve outcomes on treatment . However , the low fidelity to the delivery of our voucher meant that a third of eligible patients did not receive it . Among patients in intervention clinics who received the voucher at least once , treatment success rates were significantly improved . Further operational research is needed to explore how best to ensure the consistent and appropriate delivery of such support to those eligible to receive it . Trial registration Current Controlled TrialsIS RCT Background Children with tuberculosis often have underlying nutritional deficiencies . Multivitamin supplementation has been proposed as a means to enhance the health of these children ; however , the efficacy of such an intervention has not been examined adequately . Methods 255 children , aged six weeks to five years , with tuberculosis were r and omized to receive either a daily multivitamin supplement or a placebo in the first eight weeks of anti-tuberculous therapy in Tanzania . This was only 64 % of the proposed sample size as the trial had to be terminated prematurely due to funding constraints . They were followed up for the duration of supplementation through clinic and home visits to assess anthropometric indices and laboratory parameters , including hemoglobin and albumin . Results There was no significant effect of multivitamin supplementation on the primary endpoint of the trial : weight gain after eight weeks . However , significant differences in weight gain were observed among children aged six weeks to six months in subgroup analyses ( n = 22 ; 1.08 kg , compared to 0.46 kg in the placebo group ; 95 % CI = 0.12 , 1.10 ; p = 0.01 ) . Supplementation result ed in significant improvement in hemoglobin levels at the end of follow-up in children of all age groups ; the median increase in children receiving multivitamins was 1.0 g/dL , compared to 0.4 g/dL in children receiving placebo ( p < 0.01 ) . HIV-infected children between six months and three years of age had a significantly higher gain in height if they received multivitamins ( n = 48 ; 2 cm , compared to 1 cm in the placebo group ; 95 % CI = 0.20 , 1.70 ; p = 0.01 ; p for interaction by age group = 0.01 ) . Conclusions Multivitamin supplementation for a short duration of eight weeks improved the hematological profile of children with tuberculosis , though it did n't have any effect on weight gain , the primary outcome of the trial . Larger studies with a longer period of supplementation are needed to confirm these findings and assess the effect of multivitamins on clinical outcomes including treatment success and growth failure . Clinical trials.gov OBJECTIVE Previous economic analyses of tuberculosis control interventions have focused on the provider perspective . To assess the overall economic impact of the disease and the adequacy of current control strategies from a societal viewpoint , the determination of direct and indirect patient costs is required . SETTING AND DESIGN In a cross-sectional survey , all adult tuberculosis patients who completed treatment between August 1996 and February 1997 at 16 r and omly selected government health care facilities in Thail and ( n = 673 ) were interviewed using a structured question naire . Information were obtained on direct and indirect patient costs before and after diagnosis , and on financing methods and changes in household consumption patterns . All results were stratified for three levels of patient household income : above national average , below national average but above the poverty line , and below the poverty line . RESULTS Illness-related costs particularly affected patients with incomes below the poverty line ( n = 153 ) . In this group , average out-of-pocket expenditures for the disease amounted to more than 15 % of annual household income , while incomes were reduced by 5 % due to illness-related effects . Expenditures were most frequently financed from household savings or transfer payments from community members and relatives . However , 11.8 % of patient households took out bank loans , and 15.9 % sold part of their property . CONCLUSION The current low case detection and treatment completion rates for tuberculosis patients in Thail and may partly be due to the inability of poor patients to cope with the economic consequences of diagnosis and treatment . Suggested improvements include the strict enforcement of an existing government policy of free care , the further de central ization of services to reduce travel costs and work absences , and social security payments for patients undergoing treatment Twenty-one cases of pulmonary tuberculosis seen in the last two years in the chest clinic of the University College Hospital , Ibadan were studied for their haematological patterns at diagnosis and three months after . One group was put on anti-tuberculosis drugs only while the other group was put on anti-tuberculosis drugs and oral iron . The haematological results after 3 months show a significant rise in packed cell volume ( PCV ) less than 0.01 in the group given oral suppliments . Megaloblastic bone marrow changes occurred in 20 per cent of the patients after 3 months . Seventy-five per cent of the patients had myeloid hyperplasia of the bone marrow at diagnosis and only one of the patients had hypoplastic marrow . It is suggested that oral iron and folate be added to anti-tuberculosis therapy in these patients as part of their management OBJECTIVE To assess the efficacy of weekly zinc or zinc plus retinol as adjuncts for the treatment of pulmonary tuberculosis . METHODS Double-blind , r and omized , placebo-controlled trial in 350 patients > 15 years old with smear-positive tuberculosis in Nigeria ( IS RCT N36636609 ) . In addition to antituberculous treatment , patients were r and omly allocated to weekly supplements of zinc ( 90 mg ) , zinc plus retinol ( 5000 IU ) or placebos for 6 months . Primary outcomes were time to sputum smear conversion and resolution of radiographic abnormalities . RESULTS After 8 weeks of treatment , 68 % had achieved sputum smear conversion , and the median conversion time was 6.5 weeks . Hazard ratios ( HR , 95%CI ) for sputum conversion relative to the placebo group were not significant for zinc ( 1.07 , 0.92 - 1.29 ) or zinc plus retinol ( 0.89 , 0.76 - 1.07 ) . Significant predictors of time to sputum conversion were lung abnormality score , sputum smear grade , age and serum C-reactive protein . HIV co-infection and gender were not independent predictors of time to sputum conversion . There were no significant differences between supplement groups in clinical , radiological or laboratory outcomes at 2 months or 6 months . There were 9 , 9 and 2 deaths in patients receiving zinc , zinc plus retinol or placebos , respectively . Mortality in those who received zinc ( HR 1.71 , 0.88 - 3.58 ) or zinc plus retinol ( HR 1.54 , 0.78 - 3.26 ) did not differ significantly from those who received placebos . Most deaths occurred in patients co-infected with HIV . CONCLUSIONS Supplementation with zinc or zinc plus retinol did not lead to better outcomes than placebos , and caution is warranted regarding routine micronutrient supplementation , particularly in patients co-infected with HIV BACKGROUND Micronutrients play an important role in immune function . To our knowledge , there have been no comprehensive studies on the role of micronutrient supplementation in children with tuberculosis . OBJECTIVE We assessed the effect of micronutrient supplementation in children treated with antituberculosis therapy ( ATT ) . DESIGN A r and omized , double-blind , placebo-controlled trial that used a 2 × 2 factorial design was undertaken at 2 teaching hospitals in Delhi . Children with newly diagnosed intrathoracic tuberculosis were enrolled , and they received ATT together with daily supplementation for 6 mo with either zinc alone , micronutrients without zinc , micronutrients in combination with zinc , or a placebo . Main outcomes were weight gain and an improvement in a chest X-ray ( CXR ) lesion assessed at 6 mo of treatment . RESULTS A total of 403 children were enrolled and r and omly assigned . A microbiological diagnosis of tuberculosis was confirmed in 179 children ( 44.4 % ) . The median ( 95 % CI ) increase in weight-for-age z score at 6 mo was not significantly different between subjects who received micronutrients [ 0.75 ( 0.66 , 0.84 ) ] and those who did not receive micronutrients [ 0.76 ( 0.67 , 0.85 ) ] and between subjects who received zinc [ 0.76 ( 0.68 , 0.85 ) ] and those who did not receive zinc [ 0.75 ( 0.66 , 0.83 ) ] . An improvement in CXR was observed in 285 children , but there was no difference between those receiving zinc and no zinc or between those receiving micronutrients and no micronutrients after 6 mo of ATT . However , children who received micronutrients had a faster gain in height over 6 mo than did those who did not receive micronutrients ( height-for-age z score Δ = 0.08 ; P = 0.014 ) . CONCLUSIONS Micronutrient supplementation did not modify the weight gain or clearance of lesions on CXR in children with intrathoracic tuberculosis . However , micronutrient supplementation during treatment may improve height gain in children with intrathoracic tuberculosis . This trial was registered at clinical trials.gov as NCT00801606 Objective To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis . Design Parallel group r and omised controlled trial . Setting Three primary care clinics in Dili , Timor-Leste . Participants 270 adults aged ≥18 with previously untreated newly diagnosed pulmonary tuberculosis . Main outcome measures Completion of treatment ( including cure ) . Secondary outcomes included adherence to treatment , weight gain , and clearance of sputum smears . Outcomes were assessed remotely , blinded to allocation status . Interventions Participants started st and ard tuberculosis treatment and were r and omly assigned to intervention ( nutritious , culturally appropriate daily meal ( weeks 1 - 8 ) and food package ( weeks 9 - 32 ) ( n=137 ) or control ( nutritional advice , n=133 ) groups . R and omisation sequence was computer generated with allocation concealment by sequentially numbered , opaque , sealed envelopes . Results Most patients with tuberculosis were poor , malnourished men living close to the clinics ; 265/270 ( 98 % ) contributed to the analysis . The intervention had no significant beneficial or harmful impact on the outcome of treatment ( 76 % v 78 % completion , P=0.7 ) or adherence ( 93 % for both groups , P=0.7 ) but did lead to improved weight gain at the end of treatment ( 10.1 % v 7.5 % improvement , P=0.04 ) . Itch was more common in the intervention group ( 21 % v 9 % , P<0.01 ) . In a subgroup analysis of patients with positive results on sputum smears , there were clinical ly important improvements in one month sputum clearance ( 85 % v 67 % , P=0.13 ) and completion of treatment ( 78 % v 68 % , P=0.3 ) . Conclusion Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste . Further studies in different setting s and measuring different outcomes are required . Trial registration Clinical Trials NCT0019256 Background & objectives : Deficiency of vitamin D , an immunomodulator agent , is associated with increased susceptibility to tuberculosis in adults , but only limited studies are available in the paediatric age group , especially regarding association of vitamin D with type and outcome of tuberculosis . We conducted this study to determine the baseline 25-hydroxy vitamin D levels in children suffering from intrathoracic tuberculosis and its association with type and outcome of tuberculosis . Methods : Children with intrathoracic tuberculosis , diagnosed on the basis of clinico-radiological criteria , were enrolled as part of a r and omized controlled trial on micronutrient supplementation in paediatric tuberculosis patients . Levels of 25-hydroxy vitamin D were measured in serum sample s collected prior to starting antitubercular therapy by chemiluminescent immunoassay technology . Results : Two hundred sixty six children ( mean age of 106.9 ± 43.7 months ; 57.1 % girls ) were enrolled . Chest X-ray was suggestive of primary pulmonary complex , progressive disease and pleural effusion in 81 ( 30.5 % ) , 149 ( 56 % ) and 36 ( 13.5 % ) subjects , respectively . Median serum 25-hydroxy vitamin D level was 8 ng/ml ( IQR 5 , 12 ) . One hundred and eighty six ( 69.9 % ) children were vitamin D deficient ( serum 25-hydroxy vitamin D < 12 ng/ml ) , 55 ( 20.7 % ) were insufficient ( 12 to < 20 ng/ml ) and 25 ( 9.4 % ) were vitamin D sufficient ( ≥ 20 ng/ml ) . Levels of 25-hydroxy vitamin D were similar in all three types of intrathoracic tuberculosis , and in microbiologically confirmed and probable cases . Levels of 25-hydroxy vitamin D did not significantly affect outcome of the disease . Children who were deficient or insufficient were less likely to convert ( become smear/culture negative ) at two months as compared to those who were 25-hydroxy vitamin D sufficient ( P<0.05 ) . Interpretation & conclusions : Majority of Indian children with newly diagnosed intrathoracic tuberculosis were deficient in vitamin D. Type of disease or outcome was not affected by 25-hydroxy vitamin D levels in these children . However , children who did not demonstrate sputum conversion after intensive phase of antitubercular therapy had lower baseline 25-hydroxy vitamin D levels as compared to those who did Undernutrition is common among smear-positive pulmonary tuberculosis ( PTB+ ) patients . Micronutrient supplementation may improve treatment outcomes , but it is unclear whether additional energy-protein would be beneficial . The present study aim ed to assess the effect of energy-protein supplementation on weight , body composition and h and grip strength against a background of high micronutrient intake during tuberculosis ( TB ) treatment . A total of 377 PTB+ patients co-infected with HIV were r and omly allocated one or six biscuits daily for 60 d during TB treatment . Weight , arm fat area , arm muscle area and h and grip strength were assessed at baseline and 2 and 5 months . There were no effects on any outcome at 2 months , but energy-protein supplementation was associated with a 1·3 ( 95 % CI - 0·1 , 2·8 ) kg marginally significant gain in h and grip strength at 5 months . However , after 2 months , energy-protein supplementation led to a weight gain of 1·9 ( 95 % CI 0·1 , 3·7 ) kg among patients with cluster of differentiation 4 ( CD4 ) counts ≥ 350 cells/μl , but not among patients with low CD4 counts ( - 0·2 kg ; 95 % CI - 1·3 , 0·8 , Pinteraction = 0·03 ) . Similarly , at 5 months , energy-protein supplementation led to a 2·3 ( 95 % CI 0·6 , 4·1 ) kg higher h and grip strength gain among patients with CD4 counts < 350 cells/μl , but not in those with high CD4 counts ( Pinteraction = 0·04 ) . In conclusion , energy-protein supplementation to PTB+ HIV-co-infected patients had no overall effects on weight and body composition , but was associated with marginally significant gain in h and grip strength . More research is needed to develop an effective supplement , before it is recommended to TB programmes BACKGROUND Vitamin D was used to treat tuberculosis in the pre-antibiotic era , and its metabolites induce antimycobacterial immunity in vitro . Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent . METHODS We undertook a multicentre r and omised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London , UK . 146 patients were allocated to receive 2·5 mg vitamin D(3 ) or placebo at baseline and 14 , 28 , and 42 days after starting st and ard tuberculosis treatment . The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion . Patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor , and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D(3 ) . This trial is registered with Clinical Trials.gov number NCT00419068 . FINDINGS 126 patients were included in the primary efficacy analysis ( 62 assigned to intervention , 64 assigned to placebo ) . Median time to sputum culture conversion was 36·0 days in the intervention group and 43·5 days in the placebo group ( adjusted hazard ratio 1·39 , 95 % CI 0·90 - 2·16 ; p=0.14 ) . TaqI genotype modified the effect of vitamin D supplementation on time to sputum culture conversion ( p(interaction)=0·03 ) , with enhanced response seen only in patients with the tt genotype ( 8·09 , 95 % CI 1·36 - 48·01 ; p=0·02 ) . FokI genotype did not modify the effect of vitamin D supplementation ( p(interaction)=0·85 ) . Mean serum 25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/L in the intervention group and 22·8 nmol/L in the placebo group ( 95 % CI for difference 68·6 - 88·2 ; p<0·0001 ) . INTERPRETATION Administration of four doses of 2·5 mg vitamin D(3 ) increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis . Vitamin D did not significantly affect time to sputum culture conversion in the whole study population , but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism . FUNDING British Lung Foundation AIM to compare the vitamin D group of pulmonary tuberculosis patients with a placebo group in terms of clinical improvement , nutritional status , sputum conversion , and radiological improvement . METHODS sixty seven tuberculosis patient visiting the Pulmonary Clinic , of Cipto Mangunkusumo Hospital , Jakarta , from January 1st to August 31st , 2001 were included in this study . The subjects were r and omised to receive vitamin D ( 0.25 mg/day ) or placebo in a double blind method , during the 6th initial week of Tb treatment . The rate of sputum conversion , complete blood counts , blood chemistry as well as radiologic examination were evaluated . RESULTS there were more male patients than females ( 39:28 ) , 78.7 % were in the productive age group , 71.6 % had low nutritional status , 62.4 % with low education level , and 67.2 % with low income . One hundred percent of the vitamin D group and only 76.7 % of the placebo group had sputum conversion . This difference is statistically significant ( p=0.002 ) . CONCLUSION the sputum conversion had no correlation with the hemoglobin level , blood clotting time , calcium level , lymphocyte count , age , sex , and nutritional status . There were more subjects with radiological improvement in the vitamin D group Background Development of new tuberculosis ( TB ) drugs and alternative treatment strategies are urgently required to control the global spread of TB . Previous results have shown that vitamin D3 ( vitD3 ) and 4-phenyl butyrate ( PBA ) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects . Objective To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to st and ard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients . Methods Adult TB patients ( n = 288 ) were enrolled in a r and omized , double-blind , placebo-controlled trial conducted in Bangladesh . Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8 . Clinical assessment s and sputum smear microscopy were performed weekly up to week 4 , fortnightly up to week 12 and at week 24 ; TB culture was performed at week 0 , 4 and 8 ; concentrations of LL-37 in cells , 25-hydroxyvitamin D3 ( 25(OH)D3 ) in plasma and ex vivo bactericidal function of monocyte-derived macrophages ( MDM ) were determined at week 0 , 4 , 8 , 12 and additionally at week 24 for plasma 25(OH)D3 . Results At week 4 , 71 % ( 46/65 ) of the patients in the PBA+vitD3-group ( p = 0.001 ) and 61.3 % ( 38/62 ) in the vitD3-group ( p = 0.032 ) were culture negative compared to 42.2 % ( 27/64 ) in the placebo-group . The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group ( p = 0.001 ) and 2.2 times higher in vitD3-group ( p = 0.032 ) compared to placebo . The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 ( p = 0.034 ) . Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo ( log rank 11.38 , p = 0.01 ) . Conclusion Adjunct therapy with PBA+vitD3 or vitD3 or PBA to st and ard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB . Trial Registration clinical trials.gov Nitric oxide ( NO ) is involved in the host defence against tuberculosis ( TB ) . Patients with TB exhibit increased catabolism and reduced energy intake . Thus the hypothesis for this study was that restoring a relative deficiency in the amino acid arginine , the substrate for mycobactericidal NO production , would improve the clinical outcome of TB by increasing NO production . In a r and omised double-blind study , patients with smear-positive TB ( n=120 ) were given arginine or placebo for 4 weeks in addition to conventional chemotherapy . Primary outcomes were sputum conversion , weight gain , and clinical symptoms after week 8 . Secondary outcomes were sedimentation rate and levels of NO metabolites , arginine , citrulline , and tumour necrosis factor‐α . Compared with the human immunodeficiency virus (HIV)−/TB+ placebo group , the HIV−/TB+ patients in the arginine group showed significant improvement , defined as increased weight gain , higher sputum conversion rate and faster reduction of symptoms , such as cough . The arginine level increased after week 2 in the HIV−/TB+ arginine group ( 100.2 µM ( range 90.5–109.9 ) versus 142.1 µM ( range 114.1–170.1 ) ) compared with the HIV−/TB+ placebo group ( 105.5 µM ( range 93.7–117.3 ) versus 95.7 µM ( range 82.4–108.9 ) ) . HIV seroprevalence was 52.5 % . No clinical improvement or increase in serum arginine was detected in arginine supplemented HIV+/TB+ patients compared with placebo . Arginine is beneficial as an adjuvant treatment in human immunodeficiency virus-negative patients with active tuberculosis , most likely mediated by increased production of nitric oxide Malnutrition is common in pulmonary tuberculosis ( TB ) , and may impair survival . The objective of this study was to assess effects of multi-vitamin/mineral ( MVM ) and zinc ( Zn ) supplementation during TB treatment on mortality . Patients diagnosed with sputum-positive pulmonary TB in Mwanza , Tanzania , were r and omised , using a two-by-two factorial design , to Zn ( 45 mg ) or placebo , and MVM ( vitamins A , B , C , D , E , and selenium and copper ) or placebo . Survival status was ascertained at the end of the 8-month TB treatment and supplementation period . Of 499 TB patients , 213 ( 43 % ) had HIV . The mean weight gain at 7 months was 6.88 kg ( 95 % CI 6.36 , 7.41 ) . Zn and MVM combined , but neither alone ( interaction , P=0.03 ) , increased weight gain by 2.37 kg ( 95 % CI 0.91 , 3.83 ) , irrespective of HIV status . Survival status at 8 months was determined for 422 patients ( 84.6 % ) , of which fifty-two ( 12.3 % ) had died . Among fifty-two deaths , there were no effects of MVM ( relative risk ( RR ) 0.73 ; 95 % CI 0.43 , 1.23 ) and Zn ( RR 0.76 ; 95 % CI 0.46 , 1.28 ) . However , among HIV co-infected patients , marginally significant effects of both MVM ( RR 0.60 ; 95 % CI 0.34 , 1.05 ) and Zn ( RR 0.63 , 95 % CI 0.37 , 1.08 ) were seen , and MVM and Zn combined reduced mortality ( RR 0.29 ; 95 % CI 0.10 , 0.80 ; interaction ratio 0.52 ) . In conclusion , supplementation with MVM , including Zn , during treatment of pulmonary TB may reduce mortality in those co-infected with HIV . A r and omised trial of the effect of the combined intervention used in this study should be conducted in a different setting to confirm the finding OBJECTIVE To develop a method for determining the acceptability and safety of ready-to-use therapeutic foods ( RUTF ) before clinical trialing . Acceptability was defined using a combination of three consumption , nine safety , and six preference criteria . These were used to compare a soy/maize/sorghum RUTF ( SMS-RUTFh ) , design ed for the rehabilitation of human immunodeficiency virus/tuberculosis ( HIV/TB ) wasted adults , with a peanut-butter/milk-powder paste ( P-RUTF ; br and : Plumpy'nut ) design ed for pediatric treatment . METHODS A cross-over , r and omized , controlled trial was conducted in Kenya . Ten days of repeated measures of product intake by 41 HIV/TB patients , > 18 y old , body mass index ( BMI ) 18 - 24 kg · m(-2 ) , 250 g were offered daily under direct observation as a replacement lunch meal . Consumption , comorbidity , and preferences were recorded . RESULTS The study arms had similar age , sex , marital status , initial BMI , and middle upper-arm circumference . No carryover effect or serious adverse events were found . SMS-RUTFh energy intake was not statistically different from the control , when adjusted for BMI on day 1 , and the presence of throat sores . General preference , taste , and sweetness scores were higher for SMS-RUTFh compared to the control ( P < 0.05 ) . Most consumption , safety , and preference criteria for SMS-RUTFh were satisfied except for the average number of days of nausea ( 0.16 versus 0.09 d ) and vomiting ( 0.04 versus 0.02 d ) , which occurred with a higher frequency ( P < 0.05 ) . CONCLUSION SMS-RUTFh appears to be acceptable and can be safely clinical ly trialed , if close monitoring of vomiting and nausea is included . The method reported here is a useful and feasible approach for testing the acceptability of ready-to-use foods in low income countries BACKGROUND Tuberculosis ( TB ) often coincides with nutritional deficiencies . The effects of micronutrient supplementation on TB treatment outcomes , clinical complications , and mortality are uncertain . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of micronutrients ( vitamins A , B complex , C , and E , as well as selenium ) in Dar es Salaam , Tanzania . We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months . RESULTS Micronutrients decreased the risk ofTB recurrence by 45 % overall ( 95 % confidence interval [ CI ] , 7 % to 67 % ; P = .02 ) and by 63 % in HIV-infected patients ( 95 % CI , 8 % to 85 % ; P = .02 ) . There were no significant effects on mortality overall ; however , we noted a marginally significant 64 % reduction of deaths in HIV-negative subjects ( 95 % CI , -14 % to 88 % ; P = .08 ) . Supplementation increased CD3 + and CD4 + cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients . Micronutrients reduced the incidence of peripheral neuropathy by 57 % ( 95 % CI , 41 % to 69 % ; P < .001 ) , irrespective of HIV status . There were no significant effects on weight gain , body composition , anemia , or HIV load . CONCLUSIONS Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania Undernutrition is common among tuberculosis ( TB ) patients . The objective of this study was to assess the effect of multi-micronutrient supplementation during TB treatment on weight , body composition , and h and grip strength . A total of 865 patients with smear-positive ( PTB+ ) or -negative ( PTB- ) pulmonary TB were r and omly allocated to receive a daily biscuit with or without multi-micronutrients for 60 d during the intensive phase of TB treatment . Weight , arm fat area , arm muscle area , and h and grip strength were assessed at baseline and after 2 and 5 mo . At 2 mo , the multi-micronutrient supplementation led to a higher h and grip gain ( 1.22 kg ; 95 % CI = 0.50 , 1.94 ; P = 0.001 ) but had no effects on other outcomes . The effects of multi-micronutrient supplementation were modified by HIV infection ( P-interaction = 0.002 ) . Among HIV- patients , multi-micronutrient supplementation increased weight gain by 590 g ( 95 % CI = -40 , 1210 ; P = 0.07 ) and h and grip strength by 1.6 kg ( 95 % CI = 0.78 , 2.47 ; P < 0.001 ) , whereas among HIV+ patients , it reduced weight gain by 1440 g ( 95 % CI = 290 , 2590 ; P = 0.002 ) and had no effect on h and grip strength ( 0.07 kg ; 95 % CI = -1.30 , 1.46 ; P = 0.91 ) . The reduced weight gain among HIV+ patients receiving multi-micronutrient supplementation seemed to be explained by a higher proportion of patients reporting fever . At 5 mo , the effects on weight were sustained , whereas there was no effect on h and grip strength . In conclusion , multi-micronutrient supplementation given as a biscuit is beneficial among HIV- PTB patients and may be recommended to TB programs . More research is needed to develop an effective supplement for HIV+ PTB patients SETTING Newham Chest Clinic , London , UK . OBJECTIVE To determine the safety and efficacy of the administration of bolus-dose vitamin D(2 ) in elevating serum 25-hydroxyvitamin D ( 25[OH]D ) concentrations in tuberculosis ( TB ) patients . DESIGN A multi-ethnic cohort of TB patients was r and omised to receive a single oral dose of 2.5 mg vitamin D(2 ) ( n = 11 ) or placebo ( n = 14 ) . Serum 25(OH)D and corrected calcium concentrations were determined at baseline and 1 week and 8 weeks post-dose , and compared to those of a multi-ethnic cohort of 56 healthy adults receiving an identical dose of vitamin D(2 ) . RESULTS Hypovitaminosis D ( serum 25[OH]D < 75 nmol/l ) was present in all patients at baseline . A single oral dose of 2.5 mg vitamin D2 corrected hypovitaminosis D in all patients in the intervention arm of the study at 1 week post-dose , and induced a 109.5 nmol/l mean increase in their serum 25(OH)D concentration . Hypovitaminosis D recurred in 10/11 patients at 8 weeks post-dose . No patient receiving vitamin D(2 ) experienced hypercalcaemia . Patients receiving 2.5 mg vitamin D(2 ) experienced a greater mean increase in serum 25(OH)D at 1 week post-dose than healthy adults receiving 2.5 mg vitamin D(2 ) . CONCLUSION A single oral dose of 2.5 mg vitamin D(2 ) corrects hypovitaminosis D at 1 week but not at 8 weeks post-dose in TB patients BACKGROUND Hypocholesterolemia is common among tuberculous patients and is associated with mortality in miliary cases . Some in vitro studies have shown that cholesterol is necessary for the good functioning of macrophages and lymphocytes . STUDY OBJECTIVES To determine whether a cholesterol-rich diet could accelerate sputum sterilization in patients with pulmonary tuberculosis . DESIGN An 8-week follow-up , r and omized , controlled trial carried out from March 2001 to January 2002 . SETTING A third-level hospital for respiratory diseases in Mexico City . PATIENTS AND INTERVENTIONS Adult patients with newly diagnosed pulmonary tuberculosis were hospitalized for 8 weeks and r and omly assigned to receive a cholesterol-rich diet ( 800 mg/d cholesterol [ experimental group ] ) or a normal diet ( 250 mg/d cholesterol [ control group ] ) . All patients received the same four-drug antitubercular regimen ( ie , isoniazid , rifampin , pyrazinamide , and ethambutol ) . MEASUREMENTS AND RESULTS Every week , a quantitative sputum culture and laboratory tests were done and respiratory symptoms were recorded . Patients in the experimental group ( 10 patients ) and the control group ( 11 subjects ) were HIV-negative and harbored Mycobacterium tuberculosis that was fully sensitive to antitubercular drugs . Sterilization of the sputum culture was achieved faster in the experimental group , as demonstrated either by the percentage of negative culture findings in week 2 ( 80 % ; control group , 9 % ; p = 0.0019 ) or by the Gehan-Breslow test for Kaplan-Meier curves ( p = 0.0037 ) . Likewise , the bacillary population decreased faster ( p = 0.0002 ) in the experimental group . Respiratory symptoms improved in both groups , but sputum production decreased faster in the experimental group ( p < 0.05 ) . Laboratory test results did not differ between the groups . CONCLUSIONS A cholesterol-rich diet accelerated the sterilization rate of sputum cultures in pulmonary tuberculosis patients , suggesting that cholesterol should be used as a complementary measure in antitubercular treatment BACKGROUND / PURPOSE Under the directly observed treatment , short course ( DOTS ) program , antituberculosis ( anti-TB ) medications were possibly taken at r and om time , regardless of whether it was prior to or after meals . This study was to evaluate the impact of food intake on pharmacokinetic profiles of first-line TB drugs in Taiwanese TB patients , as well as the relationship between drug levels and pharmacogenetics . METHODS This open-label , r and omized , cross-over study included newly diagnosed Taiwanese TB patients treated between January 2010 and February 2011 at Taipei Medical University-Wan Fang Hospital . Rifater [ a fixed-dose combination formulation of isoniazid ( INH ) , rifampicin ( RIF ) , and pyrazinamide ( PZA ) ] and ethambutol ( EMB ) were given according to national TB guidelines . Blood sample s were collected prior to and 1 hour , 2 hours , 4 hours , 6 hours , and 10 hours after dosing under fasting or postpr and ial conditions . Pharmacokinetic parameters of the maximum serum concentration ( Cmax ) , time to Cmax , and area under the serum concentration-time curve from the beginning to the 10(th ) hour ( AUC0 - 10 ) were calculated . RESULTS Sixteen TB patients were included and received anti-TB treatment under the DOTS program after discharge . The overall effects showed that food intake reduced the mean Cmax ( INH : 40.6 % , RIF : 40.2 % , EMB 34.4 % , PZA : 24.4 % ) and AUC0 - 10 ( INH : 21.3 % , RIF : 26.4 % , EMB : 12.2 % , PZA : 12.0 % ) . Meanwhile , food increased the time to Cmax ( INH : 78.1 % , RIF : 151.3 % , EMB : 41.4 % , PZA : 148.9 % ) . CONCLUSION Significantly lower serum drug concentrations were observed under postpr and ial conditions than fasting conditions for INH , RIF , and PZA . The impact of taking r and om anti-TB drugs under the DOTS program instead of taking drugs regularly prior to meals requires further study SETTING Zomba and Blantyre , Malawi , Africa . OBJECTIVES To determine whether daily micronutrient supplementation reduces the mortality of human immunodeficiency virus ( HIV ) infected adults with pulmonary tuberculosis ( TB ) . DESIGN A r and omised , controlled clinical trial of micronutrient supplementation for HIV-positive and HIV-negative adults with pulmonary TB . Participants were enrolled at the commencement of chemotherapy for sputum smear-positive pulmonary TB and followed up for 24 months . RESULTS A total of 829 HIV-positive and 573 HIV-negative adults were enrolled . During follow-up , 328 HIV-positive and 17 HIV-negative participants died . The proportion of HIV-positive participants who died in the micronutrient and placebo groups was 38.7 % and 40.4 % , respectively ( P = 0.49 ) . Micronutrient supplementation did not reduce mortality ( hazard ratio [ HR ] 0.93 , 95%CI 0.75 - 1.15 ) among HIV-positive adults . CONCLUSIONS Micronutrient supplementation at the doses used in this study does not reduce mortality in HIV-positive adults with pulmonary TB in Malawi BACKGROUND Vitamin D has immunomodulatory effects that might aid clearance of mycobacterial infection . We aim ed to assess whether vitamin D supplementation would reduce time to sputum culture conversion in patients with active tuberculosis . METHODS We did this r and omised , double-blind , placebo-controlled , superiority trial at 13 sites in India . Treatment-naive patients who were sputum-smear positive , HIV negative , and had pulmonary tuberculosis were r and omly assigned ( 1:1 ) , with central ly labelled , serially numbered bottles , to receive st and ard active tuberculosis treatment with either supplemental high-dose oral vitamin D3 ( four doses of 2·5 mg at weeks 0 , 2 , 4 , and 6 ) or placebo . Neither the patients nor the clinical and laboratory investigators and personnel were aware of treatment assignment . The primary efficacy outcome was time to sputum culture conversion . Analysis was by modified intention to treat . This trial is registered with Clinical Trials.gov , number NCT00366470 . FINDINGS Between Jan 20 , 2010 , and Aug 23 , 2011 , we r and omly assigned 247 participants to the vitamin D group ( n=121 ) or the placebo group ( n=126 ) , of whom 211 participants ( n=101 and n=110 , respectively ) were included in the primary efficacy analysis . Median time to culture conversion in the vitamin D group was 43·0 days ( 95 % CI 33·3 - 52·8 ) versus 42·0 days ( 33·9 - 50·1 ) in the placebo group ( log-rank p=0·95 ) . Three ( 2 % ) patients died in the vitamin D group and one ( 1 % ) patient died in the placebo group ; no death was considered attributable to the study intervention . No patients had hypercalcaemia . INTERPRETATION Our findings show that vitamin D supplementation did not reduce time to sputum culture conversion . Further studies should investigate the role of vitamin D in prevention or reactivation of tuberculosis infection . FUNDING Dalhousie University and Infectious Diseases Training and Research Centre Limited studies exist regarding whether incorporating micronutrient supplements during tuberculosis ( TB ) treatment may improve cell-mediated immune response . We examined the effect of micronutrient supplementation on lymphocyte proliferation response to mycobacteria or T-cell mitogens in a r and omized trial conducted on 423 patients with pulmonary TB . Eligible participants were r and omly assigned to receive a daily dose of micronutrients ( vitamins A , B-complex , C , E , and selenium ) or placebo at the time of initiation of TB treatment . We found no overall effect of micronutrient supplements on lymphocyte proliferative responses to phytohaemagglutinin or purified protein derivatives in HIV-negative and HIV-positive TB patients . Of HIV-negative TB patients , the micronutrient group tended to show higher proliferative responses to concanavalin A than the placebo group , although the clinical relevance of this finding is not readily notable . The role of nutritional intervention in this vulnerable population remains an important area of future research The study examined the effect of supplementation with multivitamins and trace elements on microbiological and radiological recovery in patients with pulmonary tuberculosis . Forty-four patients aged 28 - 50 years were diagnosed with active pulmonary tuberculosis based on X-ray of the chest and smear examination of the sputum for the presence of acid-fast bacilli . They were all treated for six months with a st and ard anti-tuberculosis regimen that has been found to be effective worldwide for disease control . The subjects were r and omized to receive either a multivitamin-trace element supplement or a placebo containing calcium . The two groups were matched on all relevant confounding variables . At two months into the treatment , the group that was supplemented with a multivitamin-trace element preparation showed a significant reduction in the number of individuals with sputum smear positive for acid-fast bacillus : two out of 22 individuals , compared with seven out of 22 among placebo-treated controls ( p = 0.028 , Fisher 's test ) . It is concluded that patients with tuberculosis should be supplemented with a suitable micronutrient preparation that contains optimum amounts of all vitamins and trace elements that have been documented to enhance the immune response Our study was done to assess the value of administration of vitamin D to tuberculous children . The study included twenty four newly diagnosed tuberculous children ; eleven males and thirteen females . Their age ranged from one and half to thirteen years . Thirteen patients were extra thoracic type of T.B. , while only seven were intrathoracic and the rest were mixed . They were r and omly divided into two Groups according to the treatment administered : Group A patients were given Rifampicin , Isoniazid and Streptomycin . Group B received in addition vitamin D. After eight weeks therapy , the patients of each group were evaluated regarding clinical , laboratory , and radiological improvement . Vitamin D level is raised after treatment in both Groups A and B , but this rise is not significant . It also showed insignificant difference between the two groups . Vitamin D level showed very high significant decrease in tuberculous children than matched healthy controls ( non tuberculous children ) . Calcium was significantly elevated after treatment in Group A whereas no significant change was detected in Group B. Phosphorous was highly significantly elevated after treatment in Group A , whereas in Group B it is just significantly elevated . Alkaline phosphatase level in both groups A and B were slightly decreased after treatment . However , this decrease was not significant . Clinical improvement was more evident in Group B patients ( those taking vitamin D ) as compared to Group A patients . The same was noted with X-ray and Sonographic findings . We concluded that vitamin D therapy may be of great value in addition to antituberculous drugs in the treatment of tuberculous children , and its use is highly recommended INTRODUCTION Wasting is the cardinal feature of tuberculosis , but not much documentary evidence supporting food supplements exists . This study was done to assess the effects of food supplements on body weight , physical function , quality of life and treatment outcomes in patients with tuberculosis and wasting . METHODS The study was conducted in 30 Anganwadi centres of 16 villages in the catchment area of Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation and the Gannavaram Directly Observed Treatment Short Course chemotherapy centre from August 2005 to December 2005 . A total of 100 patients participated in the study . Patients who were started on anti-tubercular therapy within the previous two weeks were r and omly assigned to either the control or the food supplement group . At the end of three months , their body weight was measured and physical function and quality of life were assessed . Treatment outcomes were assessed at the one-year follow-up for both groups . RESULTS Patients who received supplements had a significant increase in body weight ( 8.6 percent versus 2.6 percent , p-value less than 0.001 ) and maximum grip strength ( p-value less than 0.001 ) , a higher sputum conversion rate ( p-value is 0.039 ) , a higher treatment completion rate ( p-value is 0.031 ) and improvements in the quality of life scores . CONCLUSION Intake of food supplements result ed in a definitive increase in body weight and physical function in our study sample . Improvements can be observed in all areas , including psychologically , physiologically , socially and in the treatment outcomes OBJECTIVE The aim of the study was to assess the effects of micronutrient supplementation on culture conversion in tuberculosis ( TB ) patients . DESIGN The study was a r and omized , double-blind placebo-controlled 2 x 2 trial of zinc and multi-micronutrient ( MMN ) supplementation in pulmonary TB patients in Tanzania . RESULTS A total of 499 pulmonary TB patients were included in the trial after being confirmed sputum-positive by microscopy or culture . At 8 weeks , 25 % were sputum-smear positive but only 11 % were culture-positive ( P<0.0001 ) . No significant differences were observed in culture conversion rate among those allocated to MMN or placebo ( 89.5 vs. 86.2 % , P=0.29 ) at 8 weeks , although at week 4 those allocated to MMN had a slightly reduced culture conversion rate ( 42.8 vs. 52.8 % , P=0.058 ) . Zinc had no effects on culture conversion . MMN increased weight gain by 0.78 kg [ 95 % confidence interval ( CI ) : 0.12 - -1.43 ] at week 8 , while zinc supplementation had no effect . The effects of MMN and zinc did not interact and neither MMN nor zinc interacted with human immunodeficiency virus status , sex and culture-intensity at baseline . CONCLUSION Neither zinc nor MMN supplementation had significant effects on culture conversion , but MMN supplementation increased weight gain in TB patients We present the results of a prospect i ve single blind placebo controlled study performed to establish whether vitamin B6 supplementation of isoniazid therapy is useful in childhood tuberculosis . Eighty-five children suffering from tuberculosis ( TB ) and admitted between 1 October 1993 and 31 March 1995 to the Hospital of IME-Kimpese ( Lower Zaire ) were included . All were treated with isoniazid and other antitubercular drugs and were r and omized to receive either vitamin B6 supplementation or placebo . No case of neurological or neuropsychiatric disorder was observed in the two groups during the 6 months of the treatment and 3 months after the treatment . These results suggest that the vitamin B6 supplementation of isoniazid therapy is unnecessary in childhood TB AIM Diabetes and vitamin D deficiency are widely prevalent in India . Studies have proven correlation between low vitamin D levels and pulmonary tuberculosis ( PTB ) and low vitamin D levels and insulin resistance . We evaluated the effects of vitamin D supplementation on type 2 diabetes mellitus patients with pulmonary tuberculosis ( PTB ) . METHODS Forty-five subjects ( M : F=34:11 ) were screened . Inclusion criteria were age > 15 years , newly diagnosed PTB cases with uncontrolled diabetes , serum vitamin D<20 ng/ml . The patients with vitamin D level<20 ng/ml were r and omly assigned to 2 groups . Group 1 subjects received oral cholecalceferol ( 60,000 units/week ) and calcium carbonate ( 1g/day ) along with anti tubercular treatment ( ATT ) , while group 2 subjects did not . Sputum was checked at interval of 2 weeks for 12 weeks . Primary end point was time to achieve sputum smear conversion . RESULTS Fifteen patients having vitamin D>20 ng/ml were excluded . Age of the patients was 42.9±13.2 years and serum vitamin D levels were 18.4±15.3 ng/ml . Sputum smear conversion was 6 weeks in group 1 versus 8 weeks in group 2 ( p=0.067 ) . Glycated hemoglobin levels reduced from 11.1±1.3 to 7.7±0.9 in group 1 versus 10.3±1.2 to 7.8±1.1 ( p>0.1 ) . CONCLUSION Vitamin D can serve as adjuvant treatment of tuberculosis in diabetics with vitamin D deficiency . Further studies are required to vali date this observation and define a cut off for vitamin D level to prevent immunological alterations BACKGROUND Tuberculosis , including multidrug-resistant tuberculosis ( MDR-TB ) , is a major global health problem . Individuals with tuberculosis disease commonly exhibit vitamin D deficiency , which may adversely affect immunity and the response to therapy . OBJECTIVE We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease . DESIGN The study was a double-blind , r and omized , placebo-controlled , intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi , Georgia . Subjects were r and omly assigned to receive oral vitamin D3 [ 50,000 IUs ( 1.25 mg ) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk ] or a placebo concomitant with st and ard first-line antituberculosis drugs . The primary outcome was the time for the conversion of a Mycobacterium tuberculosis ( Mtb ) sputum culture to negative . RESULTS Baseline characteristics between groups were similar . Most subjects ( 74 % ) were vitamin D deficient ( plasma 25-hydroxyvitamin D [ 25(OH)D ] concentration < 50 nmol/L ) . With vitamin D3 , plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16 . Adverse events and plasma calcium concentrations were similar between groups . In 192 subjects with culture-confirmed tuberculosis , an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [ 29 and 27 d , respectively ; HR : 0.86 ; 95 % CI : 0.63 , 1.18 ; P = 0.33 ) . Eight-week culture-conversion rates were also similar ( 84.0 % and 82.1 % for vitamin D3 and placebo , respectively ; P = 0.99 ) . CONCLUSION A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort . This trial was registered at clinical trials.gov at NCT00918086 Low plasma vitamin A levels ( mean , 18.1 + /- 10.3 micrograms/dl , 62 % below normal ) were demonstrated in South African children with pulmonary tuberculosis . More extensive or severe disease ( e.g. , additional extrapulmonary tuberculosis ) and low levels of retinol binding protein , prealbumin , and albumin were associated with low vitamin A levels . High-dose vitamin A therapy had no effect on disease outcome ABSTRACT Nutritional supplementation to tuberculosis ( TB ) patients has been associated with increased weight and reduced mortality , but its effect on the pharmacokinetics of first-line anti-TB drugs is unknown . A cohort of 100 TB patients ( 58 men ; median age , 35 [ interquartile range { IQR } , 29 to 40 ] years , and median body mass index [ BMI ] , 18.8 [ 17.3 to 19.9 ] kg/m2 ) were r and omized to receive nutritional supplementation during the intensive phase of TB treatment . Rifampin plasma concentrations were determined after 1 week and 2 months of treatment . The effects of nutritional supplementation , HIV , time on treatment , body weight , and SLCO1B1 rs4149032 genotype were examined using a population pharmacokinetic model . The model adjusted for body size via allometric scaling , accounted for clearance autoinduction , and detected an increase in bioavailability ( + 14 % ) for the patients in the continuation phase . HIV coinfection in patients not receiving the supplementation was found to decrease bioavailability by 21.8 % , with a median maximum concentration of drug in serum ( Cmax ) and area under the concentration-time curve from 0 to 24 h ( AUC0–24 ) of 5.6 μg/ml and 28.6 μg · h/ml , respectively . HIV-coinfected patients on nutritional supplementation achieved higher Cmax and AUC0–24 values of 6.4 μg/ml and 31.6 μg · h/ml , respectively , and only 13.3 % bioavailability reduction . No effect of the SLCO1B1 rs4149032 genotype was observed . In conclusion , nutritional supplementation during the first 2 months of TB treatment reduces the decrease in rifampin exposure observed in HIV-coinfected patients but does not affect exposure in HIV-uninfected patients . If confirmed in other studies , the use of defined nutritional supplementation in HIV-coinfected TB patients should be considered in TB control programs . ( This study has the controlled trial registration number IS RCT N 16552219 . We report the first prospect i ve controlled study design ed to determine the effect of vitamin D ingestion on serum calcium concentration in patients with tuberculosis . Every patient admitted to the tuberculosis ward over a 6 month period , who was free of any condition which might influence serum calcium concentration , was r and omly assigned to one of two groups . The diet of the first group was substituted with ergocalciferol 5000 units daily . The diet of the second group was not supplemented . In addition , the second group was r and omly subdivided into two subgroups . The first subgroup received a diet unrestricted in vitamin D. The second subgroup received a diet containing less than 50 units of vitamin D. Serum calcium was determined at weekly intervals . In contradistinction to the results of a previously reported retrospective study , there was no significant difference between the group receiving supplemental vitamin D and the control group at any time during the entire period of study . Furthermore , there was no significant difference between the subgroup of patients receiving normal dietary vitamin D and the subgroup maintained on the diet restricted in vitamin Background A previous study showed that combination of zinc and vitamin A reduced sputum conversion time in pulmonary tuberculosis ( TB ) patients . Objective We studied the efficacy of which single micronutrient contributed more to the sputum conversion time . Methods In a double-blind r and omized community trial , newly sputum smear positive pulmonary TB patients were assigned r and omly to receive zinc , vitamin A , zinc + vitamin A or placebo on top of TB treatment . Patients were asked to deliver their sputum on weekly basis to measure positivity of the bacteria . Nutritional status , chest x-ray , hemoglobin , C-reactive protein ( CRP ) , retinol and zinc level were examined prior to , after 2 and 6 months of treatment . Results Initially , 300 patients were enrolled , and 255 finished the treatment . Most patients were severely malnourished ( mean BMI 16.5 ± 2.2 Kg/m2 ) . Patients in the zinc + vitamin A group showed earlier sputum conversion time ( mean 1.9 weeks ) compared with that in the other groups ; however the difference was not significant . Also , no benefit could be demonstrated of any of the used supplementations on clinical , nutritional , chest x-ray , or laboratory findings . Conclusions This study among severely malnourished TB patients , did not confirm that single or combined supplementation of zinc and vitamin A significantly reduced sputum conversion time or had other significant benefit |
13,377 | 25,188,673 | Lipid-based amphotericin B was not more effective than conventional amphotericin B on mortality ( relative risk ( RR ) 0.5 ; 95 % confidence interval ( CI ) 0.64 to 1.14 ) but decreased invasive fungal infection ( RR 0.65 ; 95 % CI 0.44 to 0.97 ) , nephrotoxicity defined as a 100 % increase in serum creatinine ( RR 0.45 ; 95 % CI 0.37 to 0.54 ) , and number of dropouts ( RR 0.78 ; 95 % CI 0.62 to 0.97).For the drug used in most patients , AmBisome ( 4 trials , 1214 patients ) , there was no significant difference in mortality ( RR 0.77 ; 95 % CI 0.54 to 1.10 ) whereas it tended to be more effective than conventional amphotericin B on invasive fungal infection ( RR 0.63 ; 95 % CI 0.39 to 1.01 , P value 0.053).AmBisome , amphotericin B in Intralipid ( 6 trials , 379 patients ) , amphotericin B colloidal dispersion ( ABCD ) ( 2 trials , 262 patients ) , and amphotericin B lipid complex ( ABLC ) ( 1 trial , 105 patients ) all decreased the occurrence of nephrotoxicity , but conventional amphotericin B was rarely administered under optimal circumstances . | BACKGROUND Patients with cancer who are treated with chemotherapy or receive a bone marrow transplant have an increased risk of acquiring fungal infections .
Such infections can be life-threatening .
Antifungal drugs are therefore often given prophylactically to such patients , or when they have a fever .
OBJECTIVES To compare the benefits and harms of lipid soluble formulations of amphotericin B with conventional amphotericin B in cancer patients with neutropenia . | PURPOSE In a r and omized , double-blind , comparative , multicenter trial , liposomal amphotericin B was equivalent to conventional amphotericin B for empirical antifungal therapy in febrile neutropenic patients , using a composite end point , but was more effective in reducing proven emergent fungal infections , infusion-related toxicities , and nephrotoxicity . The purpose of this study was to compare the pharmacoeconomics of liposomal versus conventional therapy . PATIENTS AND METHODS Itemized hospital billing data were collected on 414 patients from 19 of the 32 centers that participated in the trial . Hospital length of stay and costs from the first dose of study medication to the time of hospital discharge were assessed . RESULTS Hospital costs from the time of first dose to discharge were significantly higher for all patients who received liposomal amphotericin B ( $ 48,962 v $ 43,183 ; P = .022 ) . However , hospital costs were highly sensitive to the cost of study medication ( $ 39,648 v $ 43,048 when drug costs were not included ; P = .416 ) . Using decision analysis models and sensitivity analyses to vary the cost of study medications and the risk of nephrotoxicity , the break-even points for the cost of liposomal therapy were calculated to range from $ 72 to $ 87 per 50 mg for all patients and $ 83 to $ 112 per 50 mg in allogeneic bone marrow transplant patients . CONCLUSION The cost of liposomal amphotericin B and patient risk for developing nephrotoxicity play large roles in determining whether liposomal amphotericin B is cost-effective as first-line empirical therapy in persistently febrile neutropenic patients Abstract Objective : To test the hypothesis that amphotericin B deoxycholate is less toxic when given by continuous infusion than by conventional rapid infusion . Design : R and omised , controlled , non-blinded , single centre study . Setting : University hospital providing tertiary clinical care . Patients : 80 mostly neutropenic patients with refractory fever and suspected or proved invasive fungal infections . Intervention : Patients were r and omised to receive 0.97 mg/kg amphotericin B by continuous infusion over 24 hours or 0.95 mg/kg by rapid infusion over four hours . Main outcome measures : Patients were evaluated for side effects related to infusion , nephrotoxicity , and mortality up to three months after treatment . Analysis was on an intention to treat basis . Results : Patients in the continuous infusion group had fewer side effects and significantly reduced nephrotoxicity than those in the rapid infusion group . Overall mortality was higher during treatment and after three months ' follow up in the rapid infusion than in the continuous infusion group . Conclusion : Continuous infusions of amphotericin B reduce nephrotoxicity and side effects related to infusion without increasing ABSTRACT A multicentric r and omized trial was undertaken to compare the toxicity of amphotericin B in 5 % dextrose with that of amphotericin B in a fat emulsion ( Intralipid ) in cancer patients . Group 1 ( n = 33 ) received amphotericin B diluted in 5 % dextrose with premedication consisting of promethazine plus an antipyretic . Group 2 ( n = 28 ) received amphotericin B diluted in 20 % Intralipid without premedication . Amphotericin B was infused daily at a dose of 1 mg/kg of body weight over a 1-h period to members of both groups for empirical antifungal therapy ( in neutropenic patients ) or for the treatment of documented fungal infections . The majority of patients ( 80 % ) received empirical amphotericin B treatment . The two groups were comparable with regard to age , gender , underlying disease , and the following baseline characteristics : use of other nephrotoxic drugs and serum levels of potassium and creatinine . The median cumulative doses of amphotericin B were 240 mg in group 1 and 245 mg in group 2 ( P = 0.73 ) . Acute adverse events occurred in 88 % of patients in group 1 and in 71 % of those in group 2 ( P = 0.11 ) . Forty percent of the infusions in group 1 were associated with fever , compared to 23 % in group 2 ( P < 0.0001 ) . In addition , patients in group 2 required less meperidine for the control of acute adverse events ( P = 0.008 ) , and fewer members of this group presented with hypokalemia ( P = 0.004 ) or rigors ( P < 0.0001 ) . There was no difference in the proportions of patients with nephrotoxicity ( P = 0.44 ) . The success rates of empirical antifungal treatment were similar in the two groups ( P = 0.9 ) . Amphotericin B diluted in a lipid emulsion seems to be associated with a smaller number of acute adverse events and fewer cases of hypokalemia than amphotericin B diluted in 5 % dextrose ABSTRACT In a prospect i ve , r and omized clinical trial , the toxicity of 1 mg of amphotericin B ( AmB ) per kg of body weight per day infused in 5 % dextrose was compared with that of AmB infused in lipid emulsion in children with malignant disease . In an analysis of 82 children who received a full course of 6 days or more of AmB ( 117 courses ) , it was shown that there were significant increases in plasma urea and creatinine concentrations and in potassium requirement after 6 days of therapy with both AmB infused in dextrose and AmB infused in lipid emulsion , with there being no difference between the two methods of AmB administration . An intent-to-treat comparison of the numbers of courses affected by acute toxicity ( fever , rigors ) and chronic toxicity ( nephrotoxicity ) also indicated that there was no significant difference between AmB infused in dextrose ( 78 courses ) and AmB infused in lipid emulsion ( 84 courses ) . The pharmacokinetics of AmB were investigated in 20 children who received AmB in dextrose and 15 children who received AmB in lipid emulsion . Blood sample s were collected up to 24 h after administration of the first dose , and the concentration of AmB in plasma was analyzed by a high-performance liquid chromatography assay . The clearance ( CL ) of AmB in dextrose ( 0.039 ± 0.016 liter · h−1 · kg−1 ) was significantly lower ( P < 0.005 ) than the CL of AmB in lipid emulsion ( 0.062 ± 0.024 liter · h−1 · kg−1 ) . The steady-state volume of distribution for AmB in dextrose ( 0.83 ± 0.33 liter · kg−1 ) was also significantly lower ( P < 0.005 ) than that for AmB in lipid emulsion ( 1.47 ± 0.77 liter · kg−1 ) . Although AmB in lipid emulsion is apparently cleared faster and distributes more widely than AmB in dextrose , this study did not reveal any significant advantage with respect to safety and tolerance in the administration of AmB in lipid emulsion compared to its administration in dextrose in children with malignant disease We report a r and omized , double-blind , multicenter trial in which amphotericin B colloidal dispersion ( ABCD [ Amphotec ] ; 6 mg/kg/day ) was compared with amphotericin B ( AmB ; 1.0 - 1.5 mg/kg/day ) for the treatment of invasive aspergillosis in 174 patients . For evaluable patients in the ABCD and AmB treatment groups , respective rates of therapeutic response ( 52 % vs. 51 % ; P=1.0 ) , mortality ( 36 % vs. 45 % ; P=.4 ) , and death due to fungal infection ( 32 % vs. 26 % ; P=.7 ) were similar . Renal toxicity was lower ( 25 % vs. 49 % ; P=.002 ) and the median time to onset of nephrotoxicity was longer ( 301 vs. 22 days ; P<.001 ) in patients treated with ABCD . Rates of drug-related toxicity in patients receiving ABCD and AmB , respectively , were 53 % versus 30 % ( chills ) , 27 % versus 16 % ( fever ) , 1 % versus 4 % ( hypoxia ) and 22 % versus 24 % ( toxicity requiring study drug discontinuation ) . ABCD appears to have equivalent efficacy and superior renal safety , compared with AmB , in the treatment of invasive aspergillosis . However , infusion-related chills and fever occurred more frequently in patients receiving ABCD than in those receiving Abstract Objective : To compare the feasibility of treatment , safety , and toxicity of intravenous amphotericin B deoxycholate prepared in either glucose or intralipid for empirical antimycotic treatment of neutropenic cancer patients . Design : Single centre stratified , r and omised non-blinded phase II study . Setting : University hospital providing tertiary clinical care . Subjects : 51 neutropenic patients ( leukaemia ( 35 ) , lymphoma ( 11 ) , solid tumours ( 5 ) ) with refractory fever of unknown origin ( 24 ) or pneumonia ( 27 ) . Interventions : Amphotericin B 0.75 mg/kg/day in 250 ml glucose 5 % solution or mixed with 250 ml intralipid 20 % , given on eight consecutive days then alternate days , as a 1 - 4 hour infusion . Main outcome measures : Feasibility of treatment , subjective tolerance ( question naire ) , and objective toxicity ( common toxicity criteria of the National Cancer Institute ) . Results : Study arms were balanced for age , sex , underlying malignancy , renal and liver function , and pre- and concomitant treatment with antibiotics and nephrotoxic agents . No statistically significant or clinical ly relevant differences were found between the treatment groups for : daily or cumulative dose and duration of treatment with amphotericin B ; incidence and time of dose modifications or infusion duration changes related to toxicity ; dose or duration of symptomatic support with opiates , antipyretics , or antihistamines ; renal function ; subjective tolerance ; most common toxicity scores ; course of infection ; and incidence of treatment failures . Patients treated with amphotericin B in intralipid were given fewer diuretics ( P<0.05 ) and therefore had more peripheral oedema ( P<0.01 ) and needed less potassium supplementation ( P<0.05 ) than patients given amphotericin in glucose . Acute respiratory events were more common in the intralipid arm ( P<0.05 ) . Conclusions : Amphotericin B 0.75 mg/kg/day in intralipid given on eight consecutive days then alternate days provides no benefit and is associated with potential pulmonary side effects possibly because of fat overload or an incompatibility of the two drugs We conducted a prospect i ve , r and omized , double-blind study comparing amphotericin B colloidal dispersion ( ABCD ) with amphotericin B in the empirical treatment of fever and neutropenia . Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus . Patients were then r and omized to receive therapy with ABCD ( 4 mg/[kg.d ] ) or amphotericin B ( 0.8 mg/[kg.d ] ) for < or = 14 days . A total of 213 patients were enrolled , of whom 196 were evaluable for efficacy . Fifty percent of ABCD-treated patients and 43.2 % of amphotericin B-treated patients had a therapeutic response ( P = .31 ) . Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients ( P < .001 for both parameters ) . Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients ( P = .013 and P = .018 , respectively ) . ABCD appeared comparable in efficacy with amphotericin B , and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However , infusion-related events were more common with ABCD treatment than with amphotericin B treatment The clinical use of amphotericin B is sometimes limited by nephrotoxicity . In a r and omized prospect i ve study , 32 patients treated for haematological malignancies received either amphotericin B in 5 % dextrose ( group A , 16 patients , 0.7 - 1 mg/kg/day ) , or amphotericin B mixed with Intralipid ( group B , 16 patients , 0.7 - 1 mg/kg/day ) during prolonged neutropenia . Renal dysfunction occurred in 9/16 patients in group A and 2/16 patients in group B ( P < 0.05 ) . Clinical tolerance was improved with a reduction of fever with chills in 12/16 patients in group A compared with 5/16 in group B ( P < 0.05 ) . Preparation of amphotericin B with Intralipid reduces nephrotoxicity , improves clinical tolerance , may allow an increase in the daily dose of amphotericin B , and be an alternative to liposomal-amphotericin B infusion Invasive fungal infections ( IFI ) are a major cause of morbidity and mortality in patients with cancer . A retrospective analysis of children with cancer at high risk for IFI treated at Münster University Hospital showed that the incidence ( 7.4 % vs. 1.8 % ) and lethality ( 28.1 % vs. 0 ) of documented IFI were lower in patients receiving systemic antifungal prophylaxis with liposomal amphotericin B ( l-AmB ) in comparison to a historical control group . To determine whether this decline in incidence and lethality was due to antifungal prophylaxis or was produced by advances in diagnostic procedures and early empirical antifungal therapy , a prospect i ve study was initiated . Patients in the prophylaxis arm received thrice-weekly 1 mg kg(-1 ) body weight l-AmB , whilst patients in the early intervention arm received no prophylaxis . Diagnostic procedures and antifungal therapy for suspected or proven IFI were initiated as clinical ly indicated for all patients . The primary endpoint of the study was the incidence of IFI . Secondary endpoints were the use of therapeutic doses of l-AmB , the safety of prophylactic l-AmB , and the total consumption of l-AmB for antifungal therapy . The interim analysis after 1 year showed no differences between the two approaches with respect to the incidence of IFI and to safety issues PURPOSE To describe the experience with a new lipid-based amphotericin product ( amphotericin B colloidal dispersion or ABCD ) in children with fever and neutropenia who are at high risk for fungal infection . PATIENTS AND METHODS Forty-nine children with febrile neutropenia were treated in a prospect i ve , r and omized trial comparing ABCD with amphotericin B. An additional 70 children with presumed or proven fungal infection were treated with 5 different open-label studies of ABCD . Patients were registered into these studies for reasons of : 1 ) failure to respond to amphotericin B ; 2 ) development of nephrotoxicity or preexisting renal impairment ; or 3 ) willingness to participate in a dose-escalation study . Extensive data detailing response and toxicity were collected from each patient . RESULTS In the r and omized trial , there was significantly less renal toxicity in the children receiving ABCD than in those receiving amphotericin B ( 12.0 % vs. 52.4 % [ P = 0.003 ] ) . Other adverse symptoms were not significantly different . In the additional open-label studies , although 80 % of patients receiving ABCD reported some adverse symptom , the majority of these were infusion related , and nephrotoxicity was reported in only 12 % of these patients . CONCLUSIONS ABCD was well-tolerated at doses up to 5 times greater then those usually tolerated with amphotericin B. Renal toxicity was markedly less than expected , and there were no other unexpected severe toxicities . Further r and omized studies are needed to further define the role of this and other liposomal products in children It has been suggested that a better outcome of neutropenia‐associated invasive fungal infections can be achieved when high doses of lipid formulations of amphotericin B are used . We now report a r and omized multicentre study comparing liposomal amphotericin B ( AmBisome , 5 mg/kg/d ) to amphotericin B deoxycholate ( AmB , 1 mg/kg/d ) in the treatment of these infections . Of 106 possible patients , 66 were enrolled and analysed for efficacy : nine had documented fungaemia , 17 had other invasive mould infections and 40 had suspected pulmonary aspergillosis . After completion of the course medication , in the AmBisome group ( n = 32 ) 14 patients had achieved complete response , seven a partial response and 11 were failures as compared to 6 , 13 and 15 patients ( n = 34 ) treated with AmB ( P = 0.09 ) ; P = 0.03 for complete responders . A favourable trend for AmBisome was found at day 14 , in patients with documented infections and in patients with pulmonary aspergillosis ( P = 0.05 and P = 0.096 respectively ) . Mortality rates were lower in patients treated with AmBisome ( adjusted for malignancy status , P = 0.03 ) . More patients on AmB had a > 100 % increase of their baseline serum creatinine ( P < 0.001 ) Patients with haematological malignancies requiring an antifungal therapy were r and omly assigned to receive amphotericin B diluted in either 5 % dextrose or in fat emulsion ( Intralipid ) . Twenty-one patients were included in each group . Mean duration of amphotericin B therapy was 8.4 days in the dextrose group and 12.8 days in the Intralipid group . Amphotericin B infusion induced chills in 16 of 21 patients in the dextrose group and in 5 of 21 in the Intralipid group ( P = 0.0008 ) . Serum creatinine increased > 75 % from baseline in ten patients in the dextrose group compared with only two in the Intralipid group ( P = 0.007 ) . A > or = 50 % decrease of creatinine clearance was observed in 14 of 21 patients in the dextrose group compared with seven of 21 patients in the Intralipid group ( P = 0.025 ) . No difference was found between the two groups with regard to potassium and sodium requirement . Among patients who did not receive magnesium before antifungal therapy , magnesium supplementation was required more frequently in the dextrose group ( 8/12 vs 2/11 ; P = 0.02 ) . Concomitant amikacin dosage reduction was more frequent in the dextrose group due to nephrotoxicity ( 7/19 vs 2/20 ; P = 0.045 ) . A similar difference in vancomycin dosage reduction was observed between the two groups ( 12/20 vs 5/19 ; P = 0.03 ) Results of a double-blind r and omized non-crossover study of rapid ( 45 min ) versus slow ( 4 h ) infusion of amphotericin B administered to 20 patients with proven or suspected fungal infection are reported . Toxicity was higher in the rapid infusion group than it was in the slow infusion group ( mean total 7-day chill score , 173 + /- 276 versus 20 + /- 30 [ P less than 0.01 ] ; mean total 7-day dosage of meperidine required to abate rigors , 180 + /- 133 versus 58 + /- 78 mg [ P less than 0.05 ] ; and mean maximum total 7-day pulse rise , 225 + /- 64 versus 135 + /- 56 beats per min [ P less than 0.02 ] , respectively ) . When analyzed on a daily basis , the mean chill score , meperidine dosage , and pulse rise were also higher ; and in addition , nausea and vomiting ( 5 of 11 patients who received a rapid infusion versus 0 of 9 patients who received a slow infusion [ P less than 0.01 ] ) appeared to be more common in those who received amphotericin B rapidly . The daily analysis approach proved that tolerance to these side effects developed with each subsequent infusion day , and by day 7 the incidence and severity were the same . This development of tolerance was significant for the mean chill score in the rapid infusion group ( P less than 0.05 ) and for the proportion of patients with chills ( P less than 0.005 for the slow infusion group ; P less than 0.05 for the rapid infusion group ) . A decrease in creatinine clearance to greater than 51 % of the baseline value was seen in two patients in each group . There were five deaths ( four in the rapid infusion group , 1 in the slow infusion group ) within 1 month , but none was clearly related to the amphotericin B infusion . The mean time to defervescence was similar for each group ( 10.8 + /- 4.1 days in the slow infusion group versus 9.9 + /- 5 days in the rapid infusion group ) . A rapid infusion regimen for amphotericin B can not be recommended , at least during the first 5 to 7 days of treatment Systemic fungal infections are recognized at increasing frequency during the course of intensive therapy for acute leukemias and require parenteral antifungal treatment mostly by amphotericin B ( ampho B ) alone or in combination with 5‐Fluorocytosine ( 5‐FC ) . Because of the potential myelosuppressive side effects of 5‐FC it was the aim of the current study to evaluate the recovery of hematopoietic cells after intensive antileukemic therapy in patients receiving ampho B and 5‐FC treatment for proven or suspected systemic fungal infections . The study population comprised 87 patients who were treated by st and ard chemotherapy for acute myeloid leukemia ( AML ) at first diagnosis or relapse . Twenty‐two patients underwent systemic antifungal therapy consisting of ampho B ( 3 to 10 mg/kg/d ) and 5‐FC ( 150 mg/kg/d ) for 3 to 33 days ( median , 12 days ) . The remaining 65 patients served as controls to assess the hematologic recovery time ( TR ) as defined by the interval between the onset of chemotherapy and the post‐treatment rise of granulocyte levels to greater than 500 cmm and thrombocyte levels to greater than 20,000 cmm . In patients receiving antifungal therapy , a significant prolongation of TR was observed with a median TR of 29 days compared with a median TR of 24 days ( P = 0.0016 ) for the control group . No correlation was found between TR and the total dose of either ampho B or 5‐FC or the type of antileukemic regimen . A possibly direct myelosuppressive effect of a fungal infection was unlikely to explain the findings because the ampho B/5‐FC treatment was started in patients with proven or only suspected fungal infections , causing a similar delay of TR in both groups . The present data strongly suggest a myelosuppressive effect of ampho B/5‐FC antifungal treatment in patients after intensive chemotherapy for acute leukemias Objective : To evaluate the usefulness of a 20 % lipid emulsion as a delivery system for amphotericin B ( 1 mg/mL ) administered over 1 hour to patients with neutropenia with hematologic malignancies compared with amphotericin B ( 0.1 mg/mL ) administered in dextrose 5 % solution over the same time . Design : A prospect i ve , comparative , r and omized , labeled study . Setting : Hematology unit , pharmacy service , university general hospital . Participants : Twenty patients with neutropenia with hematologic malignancies and proven or suspected fungal infections , 10 in the fat emulsion group ( group 1 ) and 10 in the dextrose 5 % group ( group 2 ) . Main Outcome Measures : Clinical tolerance ( i.e. , fever , shaking chills , nausea , blood pressure , pulse rate ) and biologic tolerance ( i.e. , urea , creatinine , sodium , potassium ) . Results : Clinical tolerance was comparable in both groups although amphotericin B in fat emulsion was better tolerated . Medication for symptoms related to the administration of amphotericin B was given in 6 cases in group 1 and in 8 cases in group 2 . There was a statistically significant difference in the urea concentrations between the 2 groups ( p = 0.023 ) ; there was an observed increase between the initial and the final serum urea ( 56.8 mg/d in group 1 , 79.8 mg/dL in group 2 ) . Statistically significant differences in creatinine serum concentrations ( 84.9 μmol/L in group 1 , 123.8 μmol/L in group 2 ) ( p = 0.047 ) were found . No differences were found in the antifungal efficacy of the treatment . However , as amphotericin B was started in the majority of cases ( 75 % ) as empiric treatment for fever unresponsive to antibiotic therapy , it is difficult to compare the efficacy of both preparations . Conclusions : The clinical tolerance of lipid-emulsion infusions is similar to that of conventionally administered amphotericin B therapy . Renal toxicity appears to be decreased when the drug is administered in a fat emulsion . This type of preparation permits the reduction of the volume and the time of administration for amphotericin B therapy Background : Conventional amphotericin B ( c‐AmB ) remains the empirical antifungal treatment of choice for neutropenic patients with persistent fever of unknown origin ( FUO ) . Unfortunately , empirical treatment with c‐AmB is hampered by its safety profile , with frequent infusion‐related adverse events ( IRAEs ) and renal toxicity . Amphotericin B lipid complex ( ABLC ) has been investigated for this indication due to its low toxicity profile . The recommended dose of ABLC is 5 mg/kg/d , which is five to seven times higher than the recommended dose of BACKGROUND Treatment of invasive mold infection in immunocompromised patients remains challenging . Voriconazole has been shown to have efficacy and survival benefits over amphotericin B deoxycholate , but its utility is limited by drug interactions . Liposomal amphotericin B achieves maximum plasma levels at a dosage of 10 mg/kg per day , but clinical efficacy data for higher doses are lacking . METHODS In a double-blind trial , patients with proven or probable invasive mold infection were r and omized to receive liposomal amphotericin B at either 3 or 10 mg/kg per day for 14 days , followed by 3 mg/kg per day . The primary end point was favorable ( i.e. , complete or partial ) response at the end of study drug treatment . Survival and safety outcomes were also evaluated . RESULTS Of 201 patients with confirmed invasive mold infection , 107 received the 3-mg/kg daily dose , and 94 received the 10-mg/kg daily dose . Invasive aspergillosis accounted for 97 % of cases . Hematological malignancies were present in 93 % of patients , and 73 % of patients were neutropenic at baseline . A favorable response was achieved in 50 % and 46 % of patients in the 3- and 10-mg/kg groups , respectively ( difference , 4 % ; 95 % confidence interval , -10 % to 18 % ; P>.05 ) ; the respective survival rates at 12 weeks were 72 % and 59 % ( difference , 13 % ; 95 % confidence interval , -0.2 % to 26 % ; P>.05 ) . Significantly higher rates of nephrotoxicity and hypokalemia were seen in the high-dose group . CONCLUSIONS In highly immunocompromised patients , the effectiveness of 3 mg/kg of liposomal amphotericin B per day as first-line therapy for invasive aspergillosis is demonstrated , with a response rate of 50 % and a 12-week survival rate of 72 % . The regimen of 10 mg/kg per day demonstrated no additional benefit and higher rates of nephrotoxicity One hundred and thirty‐four adults and 204 children were r and omized in two prospect i ve , parallel comparative multicentre trials to receive either conventional amphotericin B 1 mg/kg/d ( c‐AMB ) , liposomal amphotericin B 1 mg/kg/d ( L‐AMB1 ) or liposomal amphotericin B 3 mg/kg/d ( L‐AMB3 ) . Patients were entered if they had a pyrexia of unknown origin ( PUO ) defined as temperature of 38 ° C or more , not responding to 96 h of systemic broad‐spectrum antibiotic treatment , and neutropenia ( < 0.5 × 109/l ) . The safety and toxicity of liposomal amphotericin B was compared with that of conventional amphotericin B. Efficacy of treatment was assessed , with success defined as resolution of fever for 3 consecutive days ( < 38 ° C ) without the development of any new fungal infection . Clinical and laboratory parameters were collected for safety analysis . In both the paediatric and adult population s , L‐AMB treated patients had a 2–6‐fold decrease in the incidence ( P 0.01 ) of test‐drug‐related side‐effects , compared to c‐AMB . Severe trial‐drug‐related side‐effects were seen in 1 % of L‐AMB treated patients , in contrast to 12 % of patients on c‐AMB ( P < 0.01 ) . Nephrotoxicity , in the patient subset not receiving concomitant nephrotoxic agents , defined as a doubling from the patients baseline serum creatinine level , was not observed in the L‐AMB1 arm whereas the incidence was 3 % in patients on L‐AMB3 and 23 % in those on c‐AMB ( P < 0.01 ) . Moreover , time to develop nephrotoxicity was longer in both L‐AMB arms than c‐AMB ( P < 0.01 ) . Severe hypokalaemia was observed less frequently in both L‐AMB arms ( P < 0.01 ) BACKGROUND In patients with persistent fever and netropenia , amphotericin B is administered empirically for early treatment and prevention of systemic fungal infections . Despite this treatment , there are chances of breakthrough fungal infections and drug is also toxic . MATERIAL S AND METHODS A multicentric , r and omized , controlled clinical trial was conducted to compare liposomal amphotericin B two doses with conventional amphotericin B as empirical antifungal therapy . RESULTS The average body weight of patients was 26.4 ± 14.8 ( n=22 ) , 32.9 ± 19.4 ( n=23 ) and 37.9 ± 20.0 ( n=20 ) kg in 1 mg , 3 mg Fungisome ( liposomal amphotericin B ) and 1 mg/kg/day conventional amphotericin B group , respectively . The mean age was 16.2 ± 13.4 , 16.0 ± 10.9 and 22.7 ± 16.2 yrs in 1 and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional AMP B group , respectively . The average duration of treatment with 1 mg and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional amphotericin B was 17 ± 9.8 , 16.2 ± 8.3 , and 14.7 ± 10.7 days , respectively . The time to resolve fever was 13.3 ± 10.2 , 10.9 ± 7.1 , 10.1 ± 6.7 days , and for absolute neutrophil count ( ANC ) to be above 500 cells per microliter , it took 13.4 ± 9.6 , 10.6 ± 7.6 and 7.3 ± 3.4 days , respectively . Liposomal formulations were well-tolerated compared to conventional amphotericin B. CONCLUSIONS This small r and omized study showed that the indigenous liposomal formulation Fungisome appears to be equally efficacious and safer than conventional amphotericin B. Also , the lower dose Fungisome ( 1 mg/kg/day ) appears to be equally efficacious and was well-tolerated as compared to higher dose Fungisome ( 3 mg/kg/day ) . Treatment cost would be a major factor for limiting use of higher dose of Fungisome This is the first completed prospect i ve r and omized clinical efficacy trial of antifungals in the treatment of invasive aspergillosis ( IA ) and the first to compare the clinical efficacy of two dosages of liposomal amphotericin B ( L-AmB ) for IA in neutropenic patients with cancer or those undergoing bone marrow transplantation . Eighty-seven of 120 patients were eligible and evaluable . Clinical responses were documented for 26 ( 64 % ) of 41 patients receiving 1 mg/(kg.d ) ( L-AmB-1 ) and 22 ( 48 % ) of 46 receiving 4 mg/(kg.d ) ( L-AmB-4 ) . Radiologic response rates were similar : 24 ( 58 % ) of the L-AmB-1 recipients and 24(52 % ) of the L-AmB-4 recipients . The six-month survival rates were 43 % ( L-AmB-1 ) and 37 % ( L-AmB-4 ) . These differences were not significant . The numbers of deaths directly due to IA at 6 months were similar : 9 ( 22 % ) of 41 L-AmB-1 recipients and 9 ( 20 % ) of 46 L-AmB-4 recipients . No other variable independently influenced survival , apart from central nervous system IA . L-AmB is effective in treating approximately 50%-60 % of patients who have IA . A 1-mg/(kg.d ) dosage is as effective as a 4-mg/(kg.d ) dosage , and no advantages to use of the higher , more expensive , dosage has been observed |
13,378 | 24,151,035 | Adverse events were generally of mild or moderate intensity and consistent with events normally associated with anaesthesia and surgery .
The information from these two studies in acute postoperative pain suggested that dexibuprofen may be a useful analgesic , but at doses not very different from racemic ibuprofen , for which considerably more evidence exists | BACKGROUND This review is an up date of a previously published review in The Cochrane Data base of Systematic Review s Issue 3 , 2009 on single dose oral dexibuprofen ( S(+)-ibuprofen ) for acute postoperative pain in adults .
Dexibuprofen is a non-steroidal anti-inflammatory drug ( NSAID ) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK , and widely available in other countries worldwide .
It is an active isomer of ibuprofen .
This review sought to evaluate the efficacy and safety of oral dexibuprofen in acute postoperative pain , using clinical studies in patients with established pain , and with outcomes measured primarily over four to six hours , using st and ard methods .
This type of study has been used for many decades to establish that drugs have analgesic properties .
OBJECTIVES To assess the efficacy and adverse effects of single dose oral dexibuprofen for acute postoperative pain using methods that permit comparison with other analgesics evaluated in st and ardised studies using almost identical methods and outcomes . | 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 Two bioavailability studies of S(+)-ibuprofen ( dexibuprofen ) were conducted in healthy volunteers to define the relationship between the bioavailability of the drug after administration of dexibuprofen alone or as part of ibuprofen racemate . Enantioselective plasma drug analysis was used throughout . In the first study , the bioavailability of dexibuprofen from a 400 mg tablet formulation was compared with that from 400 mg in aqueous solution . The tablet formulation did not influence the bioavailability of the drug and dexibuprofen was well absorbed from the gastro-intestinal tract . The second study was divided into three identical parts . Bioavailability of dexibuprofen 200 , 400 and 600 mg was compared with its bioavailability from ibuprofen racemate 400 , 800 and 1200 mg . The second study showed that the mean relative bioavailability of dexibuprofen to ibuprofen racemate was 0.66 , thus enabling the estimation of clinical ly useful dexibuprofen doses from the usual doses of the racemate . The 95 % confidence interval limits did not include 0.5 , leading to the conclusion that administering half of the racemate dose would not provide patients with an adequate amount of therapeutically active drug OBJECTIVE Treatment with non-steroidal anti-inflammatory drugs is the most common pharmacological therapy of rheumatic diseases . For the symptomatic treatment of painful disorders a dose-response relationship of the NSAID should be a basic requirement , which is difficult to be proven in studies because rheumatic diseases are heterogenous in terms of clinical involvement . The aim of this double-blind r and omized trial was to compare the isolated active enantiomer dexibuprofen ( S(+)-ibuprofen ) with the double dose of racemic ibuprofen and to show a dose-response relationship of dexibuprofen in painful osteoarthritis of the hip . METHODS 178 patients were r and omly assigned to dexibuprofen 600/1,200 mg or racemic ibuprofen 2,400 mg daily . The primary endpoint was the improvement of the WOMAC osteoarthritis index after 15 days of therapy . The analysis was by intention to treat . RESULTS The evaluation of the WOMAC OA index showed statistically significant equivalence of dexibuprofen 400 mg t.i.d . compared with racemic ibuprofen 800 mg t.i.d . by a Mann-Whitney statistic of 0.578 and the corresponding lower bound of the 95 % confidence interval of 0.498 . The test for superiority of dexibuprofen was borderline significant with p = 0.055 . Dexibuprofen 400 mg t.i.d . and dexibuprofen 200 mg t.i.d . showed a statistically significant dose-response relationship in improving the WOMAC OA index ( p = 0.023 ) . Patients suffered from adverse drug reactions , mainly gastrointestinal disorders , 13.34 % on dexibuprofen 200 mg , 15.25 % on dexibuprofen 400 mg and 16.94 % on racemic ibuprofen 800 mg . CONCLUSIONS The active enantiomer dexibuprofen ( S(+)-ibuprofen ) proved to be an effective non-steroidal anti-inflammatory drug with a significant dose-response relationship in patients with painful osteoarthritis of the hip . Compared with racemic ibuprofen half of the daily dose of dexibuprofen shows at least equivalent efficacy . In contrast to pharmacokinetic data , the additional administration of R(-)-ibuprofen in form of racemate does not contribute to the clinical efficacy of racemic ibuprofen 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 & 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 Summary A rapid , sensitive and stereoselective HPLC method based on chiral column analysis was developed and fully vali date d for the simultaneous determination of the two enantiomers of ibuprofen in human plasma . Using this method , a chiral pharmacokinetic study of two different ibuprofen tablets , i.e. dexibuprofen tablets and racemic ibuprofen tablets , was carried out on 20 healthy Chinese male volunteers according to a single-dose ( 400 mg ) , two-way , cross-over r and omized design . When a ‘ non-chiral calculation method ’ was used , the statistical analysis showed no significant difference for the pharmacokinetic parameters ( AUC0–∞ , AUC0-t , Cmax , and tmax ) between the two oral formulations , suggesting that they were pharmaceutically bioequivalent . Considering that the pharmacological activity of ibuprofen resides exclusively in the S(+)-enantiomer , and that the unidirectional inversion of the R(− ) to the S(+)-enantiomer is incomplete and might be race-dependent , the pharmacokinetic parameters for only the S(+)-enantiomer were further compared and the inversion ratio calculated . It was found that only 25 % of R(−)-ibuprofen in the racemic ibuprofen tablets was inverted into S(+)-ibuprofen in the Chinese population , which suggested that dexibuprofen might possess a much stronger pharmacological activity than that of racemic ibuprofen when administered at the same dose CONTEXT Osteoarthritis ( OA ) is often treated with nonsteroidal anti-inflammatory drugs ( NSAIDs ) or selective inhibitors of cyclooxygenase-2 ( COX-2 ) . OBJECTIVE This clinical trial aim ed to assess directly the relative therapeutic efficacy of the isolated active enantiomer of ibuprofen , named dexibuprofen ( S(+)-ibuprofen ) in a special crystal form , and the selective COX-2 inhibitor celecoxib in adults with OA of the hip . Moreover , the hypothesis that the tolerability/safety profile of dexibuprofen is comparable to celecoxib is to be tested . METHODS The investigation was a r and omized , parallel-group , double-blind , active controlled clinical trial , conducted from January 2001 to February 2002 in 4 rehabilitation centers in Austria . 148 in patients were r and omly assigned to dexibuprofen 800 mg or celecoxib 200 mg daily . The primary criterion was the improvement in the Western Ontario and ' McMasters osteoarthritis index ( WOMAC OA index ) after 15 days of therapy . RESULTS Evaluation of the WOMAC OA index proved that dexibuprofen 400 mg b.i.d . is not inferior to celecoxib 100 mg b.i.d . with the Mann-Whitney estimator equal to 0.5129 and the corresponding lower boundary of the 95 % confidence interval equal to 0.4409 . The overall incidence of adverse drug reactions was 12.16 % in the dexibuprofen group and 13.51 % in the celecoxib group . 8.1 % of patients on dexibuprofen and 9.5 % on celecoxib suffered from gastrointestinal disorders . CONCLUSION In the presented clinical trial dexibuprofen has at least equal efficacy and a comparable safety/tolerability profile as celecoxib in adult patients suffering from osteoarthritis of the hip Background : Primary dysmenorrhea is estimated to affect 40–50 % of menstruating young women . Methods : R and omized , double-blind , 3-cycle crossover , active-controlled clinical trial conducted in 102 out patients . Results : 102 patients entered the study and 77 were eligible for analyses . The mean ( SD ) age was 31.1 ( 7.0 ) years , and the mean cycle duration was 28.1 days ( 1.89 ) with a mean menstrual phase of 5.3 days ( 1.28 ) . 40.26 % of patients reported moderate pain from dysmenorrhea , and the remaining 59.74 % reported severe pain . Compared to ibuprofen 400 mg , both dexibuprofen doses ( 200 and 300 mg ) showed a trend towards superiority for sum of pain intensity difference ( sum of PID ) , PID and total pain relief . Furthermore , dexibuprofen 200 mg had a faster onset of action compared to the double dose of ibuprofen ( p = 0.035 ) . A dose-effect relationship could be demonstrated for dexibuprofen in this visceral pain model . Tolerability was similar across all treatments . Conclusions : In patients experiencing acute visceral pain as a result of primary dysmenorrhea , dexibuprofen was associated with a dose-dependent effective analgesia ; this effect was at least equivalent to that of the double dose of ibuprofen . With its lower body-loading dose , dexibuprofen exp and s the alternatives available to treat this condition & 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 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 Peripheral nociceptive barrage after tissue injury results in acute pain and a variety of physiologic responses , including pituitary secretion of β‐endorphin . This study evaluated whether administration of the pharmacologically active S(+)‐isomer of ibuprofen suppresses acute pain and plasma β‐endorphin levels in the oral surgery model of acute pain |
13,379 | 21,332,763 | Evidence for any benefit of insoluble fibre was conflicting .
Soluble fibre may be of benefit in chronic idiopathic constipation , but data for insoluble fibre are conflicting . | BACKGROUND Patients with chronic idiopathic constipation are often told to increase dietary fibre intake .
Whether this is of any benefit remains unclear .
AIM To conduct a systematic review of the efficacy of soluble and insoluble fibre supplementation in the management of chronic idiopathic constipation . | After a two-week basal period , 24 patients were r and omly allocated to receive , with a crossover double-blind design , for two consecutive four-week periods , bran ( 20 g/24 hr ) or placebo . The daily intake of water and dietary fibers was st and ardized . Symptomatology , oroanal transit time , bowel frequency , and stool weight were assessed in basal conditions and at week 4 and 8 of the treatment . Oroanal transit time decreased and bowel frequency and stool weight increased significantly during both bran and placebo administration in comparison with basal period . Bran treatment was more effective than placebo in improving bowel frequency and oroanal transit . During bran treatment oroanal transit time became normal only in patients with slow colonic transit and not in those with slow rectal transit . Neither the occurrence nor the severity of the most frequent accompanying symptoms of chronic constipation differed significantly between placebo and bran treatments The aim of this study was to evaluate the effect of a novel laxative preparation , composed of cel and in , aloevera and psyllium in patients with chronic constipation . Thirty-five men and women were r and omized to receive capsules containing cel and in-aloevera-psyllium , or placebo , in a double-blind trial lasting 28 days . Symptoms in the last 2 weeks of the treatment period were compared to those in the 14-day pre-trial basal period . In the cel and in , aloevera and psyllium group , bowel movements became more frequent , the stools were softer and laxative dependence was reduced . In the placebo group , all these parameters were unchanged . Abdominal pain was not reduced in either group . The results of this study show that the preparation is an effective laxative in the treatment of constipation Objective To determine the effectiveness of increasing the dietary content of soluble fibre ( psyllium ) or insoluble fibre ( bran ) in patients with irritable bowel syndrome . Design R and omised controlled trial . Setting General practice . Participants 275 patients aged 18 - 65 years with irritable bowel syndrome . Interventions 12 weeks of treatment with 10 g psyllium ( n=85 ) , 10 g bran ( n=97 ) , or 10 g placebo ( rice flour ) ( n=93 ) . Main outcome measures The primary end point was adequate symptom relief during at least two weeks in the previous month , analysed after one , two , and three months of treatment to assess both short term and sustained effectiveness . Secondary end points included irritable bowel syndrome symptom severity score , severity of abdominal pain , and irritable bowel syndrome quality of life scale . Results The proportion of responders was significantly greater in the psyllium group than in the placebo group during the first month ( 57 % v 35 % ; relative risk 1.60 , 95 % confidence interval 1.13 to 2.26 ) and the second month of treatment ( 59 % v 41 % ; 1.44 , 1.02 to 2.06 ) . Bran was more effective than placebo during the third month of treatment only ( 57 % v 32 % ; 1.70 , 1.12 to 2.57 ) , but this was not statistically significant in the worst case analysis ( 1.45 , 0.97 to 2.16 ) . After three months of treatment , symptom severity in the psyllium group was reduced by 90 points , compared with 49 points in the placebo group ( P=0.03 ) and 58 points in the bran group ( P=0.61 versus placebo ) . No differences were found with respect to quality of life . Fifty four ( 64 % ) of the patients allocated to psyllium , 54 ( 56 % ) in the bran group , and 56 ( 60 % ) in the placebo group completed the three month treatment period . Early dropout was most common in the bran group ; the main reason was that the symptoms of irritable bowel syndrome worsened . Conclusions Psyllium offers benefits in patients with irritable bowel syndrome in primary care . Trial registration Clinical trials NCT00189033 Background : Psyllium is widely used in the symptomatic therapy of constipation . Its effects on colonic function and their correlation with symptomatic response have not been defined The digestibility of ispaghula , a mucilage from Plantago ovata composed mainly of arabinoxylans , and its faecal bulking effect were studied in seven healthy volunteers who ingested a low fibre controlled diet plus either placebo or 18 g/day of ispaghula for two 15 day periods . Whole gut transit time and gas excretion in breath and flatus were not different during the periods of ispaghula and placebo ingestion . Faecal wet and dry weights rose significantly , however , during ispaghula ingestion . Faecal short chain fatty acid concentrations and the molar proportions of propionic and acetic acids also increased . Most of the ispaghula had reached the caecum four hours after ingestion in an intact highly polymerised form . During ispaghula ingestion , the increase in the faecal output of neutral sugars was accounted for by the faecal excretion of arabinose and xylose in an intact highly polymerised form ; the apparent digestibilities of these sugars were 24 ( 11 ) and 53 % ( 6 ) respectively ( mean ( SEM ) ) . In conclusion , ispaghula is more resistant to fermentation than previously reported in humans , and its bulking effect largely results from intact material In 18 students and two members of staff at a boys ' boarding school , the time taken to pass 20 out of 25 radiopaque pellets varied from one to seven days while the subjects were eating a normal English diet . After the additon of bran , about 20 g daily , to this diet transit time fell from 2 - 75 plus or minus 1 - 6 to 2 - 0 plus or minus 0 - 9 days ( P smaller than 0 - 025 ) . Transit became faster in all nine subjects who had an initial time of three days or more , and in three of seven with an initial time of two days , but became slower in all four boys with an initial one-day transit . Frequency of defaecation correlated poorly with transit time ( a once daily bowel action being found with transit times ranging from one to four days ) , and did not increase significantly with bran . In 10 additional adults with slow initial transit ( three or four days ) the effect of bran was compared with that of an equal volume of ground oatflakes in a double-blind crossover trial . Bran caused a significant acceleration of transit , wherease oatmeal had no effect . These studies confirm that bran accelerates slow intestinal transit and show that this is not simply a psychological effect . Bran may also slow down fast transit BACKGROUND Chronic constipation may result from many mechanisms including colonic inertia or rectosigmoid outlet delay , but risk factors for constipation in the community are poorly defined . The prevalence of and predictors for symptoms consistent with functional constipation and outlet delay were estimated . METHODS An age- and gender-stratified r and om sample of 1,021 residents of Olmsted County , MN , aged 30 - 64 years , was mailed a valid self-report question naire ; 835 responded ( 82 % ) . These respondents were mailed a second question naire 12 - 20 months later that gathered data on symptoms compatible with functional constipation and outlet delay ; 690 responded ( 83 % ) . RESULTS Self-reported constipation did not reliably identify functional constipation or outlet delay . The overall age- and gender-adjusted prevalences ( per 100 ) of functional constipation and outlet delay were 19.2 ( 95 % confidence interval [ CI ] , 16.1 - 22.3 ) and 11.0 ( 95 % CI , 8.7 - 13.3 ) , respectively . Outlet delay but not functional constipation was more frequent in women . After adjusting for age , gender , and other symptoms , an increased usage of aspirin was associated with functional constipation but not outlet delay . CONCLUSIONS In apparently healthy middle-aged persons , approximately 1 in 5 have symptoms compatible with functional constipation , and 1 in 10 may experience outlet delay , but these groups correspond poorly with self-reported constipation Objective : The aim of the study was to investigate the effects of fibre-rich rye bread and yoghurt containing Lactobacillus GG ( LGG ) on intestinal transit time and bowel function , and to test whether they have an interaction in cases of self-reported constipation . Design : The study was carried out as a two-by-two factorial design . Setting : Free-living subjects . Subjects : A total of 59 healthy women with self-reported constipation , recruited by advertisement . Interventions : After a baseline period , the subjects were r and omized into four diet groups : ( 1 ) rye bread+LGG yoghurt , ( 2 ) rye bread , ( 3 ) LGG yoghurt , and ( 4 ) control . The 3-week dietary intervention was followed by a 3-week follow-up period . During each period , total intestinal transit time was measured and the subjects recorded faecal frequency and consistency , difficulty in defecation and gastrointestinal symptoms . Results : The rye bread shortened total intestinal transit time ( mean difference , −0.7 ; CI95 , −1.1 to −0.2 ; P=0.007 ) , increased faecal frequency ( 0.3 ; CI95 , 0.1 to 0.5 ; P=0.001 ) , softened faeces ( −0.3 ; CI95 , −0.4 to −0.2 ; P<0.001 ) and made defecation easier ( −0.4 ; CI95 , −0.5 to −0.2 ; P<0.001 ) , but also increased gastrointestinal symptoms ( 1.6 ; CI95 , 0.7 to 2.4 ; P<0.001 ) compared to the low-fibre toast consumed in the LGG and control groups . There were fewer symptoms in the rye bread+LGG group compared to the rye bread group ( −1.3 ; CI95 , −2.4 to −0.2 ; P=0.027 ) . Conclusions : Fibre-rich rye bread can be recommended in the treatment of constipation , and the simultaneous consumption of LGG yoghurt relieves the adverse gastrointestinal effects associated with increased intake of fibre . Sponsorship : Valio Ltd , R&D , and Fazer Bakeries OBJECTIVES : Although it has been used as a laxative for many years , high- quality trials assessing the efficacy of the laxative sodium picosulfate ( SPS ) are lacking . The purpose of this study was to assess the efficacy and safety of 4-week treatment with SPS in patients with functional constipation as defined by the Rome III diagnostic criteria . METHODS : This study was a r and omized , double-blind , placebo-controlled , parallel-group study in 45 general practice s in Germany . A total of 468 patients with chronic constipation presenting to their general practitioner and fulfilling the Rome III diagnostic criteria were screened . After a 2-week baseline period , 367 patients were r and omized to either SPS drops or matching placebo in a 2:1 ratio for 4 weeks . Dose titration was permitted throughout treatment . Patients without a bowel movement for more than 72 h were allowed to use a “ rescue ” bisacodyl suppository . The primary end point was the mean number of complete spontaneous bowel movements ( CSBMs ) per week . A spontaneous bowel movement ( SBM ) was defined as a stool not induced by rescue medication , whereas a CSBM was defined as an SBM associated with a sensation of complete evacuation . RESULTS : The mean number ( ±s.e . ) of CSBMs per week increased from 0.9±0.1 to 3.4±0.2 in the SPS group and from 1.1±0.1 to 1.7±0.1 in the placebo group ( P<0.0001 ) . The percentage of patients reaching an increase of ≥1 in the mean number of CSBMs per week compared to baseline was 65.5 % vs. 32.3 % , respectively ( P<0.0001 ) . The percentage of patients reaching a mean number of at least three CSBMs per week was 51.1 % in the SPS group and 18.0 % in the placebo group ( P<0.0001 ) . After 24 h , approximately 69 % of patients in the SPS group and 53 % in the placebo group had their first SBM . The SPS dose was titrated down during the study by nearly 50 % of patients . Assessment of quality of life ( QoL ) by the constipation-related Patient Assessment of Constipation (PAC)-QoL question naire showed significant improvement in SPS-treated patients compared to the placebo group . CONCLUSIONS : Treatment of chronic constipation with SPS improves bowel function , symptoms , and QoL and is well tolerated . The dose can be adjusted individually while maintaining benefit Until recently many clinical trials of functional gastrointestinal disorders ( FGIDs ) suffered from important weaknesses in trial design , study execution , and data analysis . This makes it difficult to determine whether truly efficacious therapies exist for these disorders . One of the important method ologic problems is the absence of vali date d outcome measures and lack of consensus among stakeholders on how to measure outcome . Currently much of the effort is being put into the development of vali date d outcome measures for several of the FGIDs . The r and omized , controlled trial with parallel groups is the design of choice . In this report , guidelines are given for the basic architecture of intervention studies of FGIDs . Further studies on design issues are required to ensure the recommendations will become evidence based in the future Our objective was to obtain national data of the estimated prevalence , sociodemographic relationships , and health impact of persons with functional gastrointestinal disorders . We surveyed a stratified probability r and om sample of U.S householders selected from a data base of a national market firm ( National Family Opinion , Inc. ) . Questions were asked about bowel symptoms , sociodemographic associations , work absenteeism , and physician visits . The sampling frame was constructed to be demographically similar to the U.S. householder population based on geographic region , age of householder , population density , household income and household size . Of 8250 mailings , 5430 were returned suitable for analysis ( 66 % response ) . The survey assessed the prevalence of 20 functional gastrointestinal syndromes based on fulfillment of multinational diagnostic ( Rome ) criteria . Additional variables studied included : demographic status , work absenteeism , health care use , employment status , family income , geographic area of residence , population density , and number of persons in household . For this sample , 69 % reported having at least one of 20 functional gastrointestinal syndromes in the previous three months . The symptoms were attributed to four major anatomic regions : esophageal ( 42 % ) , gastroduodenal ( 26 % ) , bowel ( 44 % ) , and anorectal ( 26 % ) , with considerable overlap . Females reported greater frequencies of globus , functional dysphagia , irritable bowel syndrome , functional constipation , functional abdominal pain , functional biliary pain and dyschezia ; males reported greater frequencies of aerophagia and functional bloating . Symptom reporting , except for incontinence , declines with age , and low income is associated with greater symptom reporting . The rate of work/school absenteeism and physician visits is increased for those having a functional gastrointestinal disorder . Furthermore , the greatest rates are associated with those having gross fecal incontinence and certain more painful functional gastrointestinal disorders such as chronic abdominal pain , biliary pain , functional dyspepsia and IBS . Preliminary information on the prevalence , socio-demographic features and health impact is provided for persons who fulfill diagnostic criteria for functional gastrointestinal disorders |
13,380 | 32,425,867 | Overall , the current evidence shows that exposure to green space may potentially increase prosocial behaviour among children and adolescents , with some contingencies ( e.g. , child 's sex and ethnic background ) . | The plausible role of nearby green space in influencing prosocial behaviour among children and adolescents has been studied recently .
However , no review has been conducted of the evidence testing the association between green space and prosocial behaviour .
This systematic review addresses this gap among children and adolescents . | BACKGROUND We examined the effectiveness of Peaceful Playgrounds ™ ( P2 ) to decrease antisocial behaviors ( ASB ) while increasing physical activity ( PA ) and prosocial behaviors ( PSB ) in elementary school children . METHODS A longitudinal , cluster-r and omized design was employed in 4 elementary school playgrounds where students ( third to fifth ) from 2 intervention and 2 control schools were observed during recess periods . The intervention included environmental changes ( eg , marked surfaces ) and student education . Data were collected using systematic observations of youth behavior and semistructured interviews conducted with key informants . Mixed-effects regression models controlling for scans nested within days nested within schools estimated the interaction of measurement period and treatment condition on children 's PA , PSB , and ASB . It was hypothesized that children in intervention , but not control schools , would demonstrate increased PA/PSB and decreased ASB . RESULTS Contrary to the hypotheses , intervention and control schools showed favorable changes for all dependent variables except for PSB , but 1 intervention and 1 control school drove these effects . Follow-up interviews indicated variability in implementation and lack of adherence to the control condition . CONCLUSIONS P2 may promote increased PA during recess , but these results demonstrate the complexity of intervention implementation and the need for rigor when measuring intervention fidelity in real-world setting Humans are extraordinarily prosocial , and research conducted primarily in North America indicates that giving to others is emotionally rewarding . To examine whether the hedonic benefits of giving represent a universal feature of human behavior , we extended upon previous cross-cultural examinations by investigating whether inhabitants of a small-scale , rural , and isolated village in Vanuatu , where villagers have little influence from urban , Western culture , survive on subsistence farming without electricity , and have minimal formal education , report or display emotional rewards from engaging in prosocial ( vs. personally beneficial ) behavior . In Study 1 , adults were r and omly assigned to purchase c and y for either themselves or others and then reported their positive affect . Consistent with previous research , adults purchasing goods for others reported greater positive emotion than adults receiving re sources for themselves . In Study 2 , 2- to 5-year-old children received c and y and were subsequently asked to engage in costly giving ( sharing their own c and y with a puppet ) and non-costly giving ( sharing the experimenter 's c and y with a puppet ) . Emotional expressions were video-recorded during the experiment and later coded for happiness . Consistent with previous research conducted in Canada , children displayed more happiness when giving treats away than when receiving treats themselves . Moreover , the emotional rewards of giving were largest when children engaged in costly ( vs. non-costly ) giving . Taken together , these findings indicate that the emotional rewards of giving are detectable in people living in diverse societies and support the possibility that the hedonic benefits of generosity are universal Background : Green spaces have been associated with improved physical and mental health ; however , the available evidence on the impact of green spaces on pregnancy is scarce . Objectives : We investigated the association between surrounding greenness and birth weight , head circumference , and gestational age at delivery . Methods : This study was based on 2,393 singleton live births from four Spanish birth cohorts ( Asturias , Gipuzkoa , Sabadell , and Valencia ) located in two regions of the Iberian Peninsula with distinct climates and vegetation patterns ( 2003–2008 ) . We defined surrounding greenness as average of satellite-based Normalized Difference Vegetation Index ( NDVI ) ( L and sat 4–5 TM data at 30 m × 30 m resolution ) during 2007 in buffers of 100 m , 250 m , and 500 m around each maternal place of residence . Separate linear mixed models with adjustment for potential confounders and a r and om cohort effect were used to estimate the change in birth weight , head circumference , and gestational age for 1-interquartile range increase in surrounding greenness . Results : Higher surrounding greenness was associated with increases in birth weight and head circumference [ adjusted regression coefficients ( 95 % confidence interval ) of 44.2 g ( 20.2 g , 68.2 g ) and 1.7 mm ( 0.5 mm , 2.9 mm ) for an interquartile range increase in average NDVI within a 500-m buffer ] but not gestational age . These findings were robust against the choice of the buffer size and the season of data acquisition for surrounding greenness , and when the analysis was limited to term births . Stratified analyses indicated stronger associations among children of mothers with lower education , suggesting greater benefits from surrounding greenness . Conclusions : Our findings suggest a beneficial impact of surrounding greenness on measures of fetal growth but not pregnancy length Background : Green spaces have been associated with improved mental health in children ; however , available epidemiological evidence on their impact on child behavioral development is scarce . Objectives : We investigated the impact of contact with green spaces and blue spaces ( beaches ) on indicators of behavioral development and symptoms of attention deficit/hyperactivity disorder ( ADHD ) in schoolchildren . Methods : This study was based on a sample of 2,111 schoolchildren ( 7–10 years of age ) from 36 schools in Barcelona in 2012 . We obtained data on time spent in green spaces and beaches and Strengths and Difficulties Question naires ( SDQ ) from parents , and ADHD/DSM-IV question naires from teachers . Surrounding greenness was abstract ed as the average Normalized Difference Vegetation Index ( NDVI ) in buffers of 100 m , 250 m , and 500 m around each home address . Proximity to green spaces was defined as living within 300 m of a major green space ( ≥ 0.05 km2 ) . We applied quasi-Poisson mixed-effects models ( with school r and om effect ) to separately estimate associations between indicators of contact with green spaces and SDQ and ADHD total and subscale scores . Results : We generally estimated beneficial associations between behavioral indicators and longer time spent in green spaces and beaches , and with residential surrounding greenness . Specifically , we found statistically significant inverse associations between green space playing time and SDQ total difficulties , emotional symptoms , and peer relationship problems ; between residential surrounding greenness and SDQ total difficulties and hyperactivity/inattention and ADHD/DSM-IV total and inattention scores ; and between annual beach attendance and SDQ total difficulties , peer relationship problems , and prosocial behavior . For proximity to major green spaces , the results were not conclusive . Conclusion : Our findings support beneficial impacts of contact with green and blue spaces on behavioral development in schoolchildren . Citation : Amoly E , Dadv and P , Forns J , López-Vicente M , Basagaña X , Julvez J , Alvarez-Pedrerol M , Nieuwenhuijsen MJ , Sunyer J. 2014 . Green and blue spaces and behavioral development in Barcelona schoolchildren : the BREATHE Project . Environ Health Perspect 122:1351–1358 ; This research explored the influence of empathic distress on prosocial behavior in a re source allocation task with children . Children were r and omly assigned to one of two conditions before engaging in a sticker sharing task ; watching either a video of a girl upset that her dog had gone missing ( emotion induction condition ) , or a video of the same girl preparing for a yard sale ( control condition ) . In study one , 5–6 year old children in the emotion induction condition rated the emotional state of both the protagonist and the self more negatively , and also exhibited more prosocial behavior ; sharing more in advantageous inequity ( AI ) trials , and less often withholding a benefit in disadvantageous inequity trials , than the control group . Prosocial behavior was significantly correlated with ratings of the emotional state of the protagonist but not with own emotional state , suggesting that empathic concern rather than personal distress was the primary influence on prosocial behavior . In study two , 3-year-olds were tested on AI trials alone , and like the 5 and 6-year-olds , showed more prosocial behavior in the emotion induction condition than the control We conducted a r and omized controlled trial of a 5-month resilience-based program ( Girls First Resilience Curriculum or RC ) among 2308 rural adolescent girls at 57 government schools in Bihar , India . Local women with at least a 10th grade education served as group facilitators . Girls receiving RC improved more ( vs. controls ) on emotional resilience , self-efficacy , social-emotional assets , psychological wellbeing , and social wellbeing . Effects were not detected on depression . There was a small , statistically significant negative effect on anxiety ( though not likely clinical ly significant ) . Results suggest psychosocial assets and wellbeing can be improved for girls in high-poverty , rural schools through a brief school-day program . To our knowledge , this is one of the largest developing country trials of a resilience-based school-day curriculum for adolescents Autism spectrum disorder ( ASD ) and reduced prosocial behaviour are strongly intertwined . However , social interactions with peers may be increasingly practice d over the course of development and may instigate a reduction in ASD symptoms and vice versa . We , therefore , sought to determine if , during adolescence , possible improvements in prosocial behaviours and ASD symptoms may benefit one another over time . Participants were 2773 adolescents from the Tracking Adolescents ’ Individual Lives Survey ( TRAILS ) cohorts . Measurements took place over three waves ( mean ages : 11.1 , 13.4 , and 16.2 years ) . Longitudinal associations between teacher-rated classroom prosocial skills and parent-rated ASD symptoms were examined using the r and om intercept cross-lagged panel model ( RI-CLPM ) . In addition to estimating the stable , between-person associations , the dynamical effects between prosocial skills and ASD symptoms over time were estimated at the within-person level . At the between-person level , prosocial skills and ASD symptoms were substantially negatively correlated . At the within-person level , a small and unexpected positive cross-lagged effect from wave 1 ASD symptoms on wave 2 prosocial skills was observed . We added to the existing literature by showing that , in addition to replicating the already firmly established between-person association between low prosocial skills and ASD , within-person gains in prosocial skills do not lead to subsequent reduction of ASD symptoms , and reductions in ASD symptoms do not lead to subsequent enhancement of prosocial skills . We , therefore , conclude from our findings that the inverse association between autistic symptoms and prosocial skills in adolescence is highly stable |
13,381 | 21,731,062 | Salt restriction increased the risk of all-cause mortality in those with heart failure ( end of trial RR 2.59 , 1.04 - 6.44 , 21 deaths).We found no information on participant 's health-related quality of life .
Despite collating more event data than previous systematic review s of RCTs ( 665 deaths in some 6,250 participants ) there is still insufficient power to exclude clinical ly important effects of reduced dietary salt on mortality or CVD morbidity .
Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small BP reduction achieved | BACKGROUND Although meta-analyses of r and omized controlled trials ( RCTs ) of salt reduction report a reduction in the level of blood pressure ( BP ) , the effect of reduced dietary salt on cardiovascular disease ( CVD ) events remains unclear . | The Hypertension Prevention Trial ( HPT ) was a r and omized , controlled , multicenter ( four clinics , four re source centers ) trial design ed to test the feasibility of achieving and sustaining dietary changes in the intake of calories , sodium , and potassium and to assess the effect of those changes on blood pressure in a normotensive population . The trial involved 841 men and women ( plus a test cohort of 78 ) who , at the first baseline ( BL ) examination were in the age range of 25 - 49 years and had diastolic blood pressure ( DBP ) greater than or equal to 76 but less than 100 mm Hg ( average of two readings ) , and at the examination prior to r and omization ( BL 2 ) , had DBP greater than or equal to 78 but less than 90 mm Hg ( also averaged ) . Participants were r and omly assigned to a control treatment group ( no dietary counseling ) or to one of four dietary treatment groups involving counseling design ed to reduce calorie intake , reduce sodium intake , reduce sodium and calorie intake , and reduce sodium and increase potassium intake . This chapter describes the process of recruiting participants for the trial . Methods used to identify and contact study participants are presented . Details of the steps involved in the recruitment process and strategies for reducing costs are discussed Phase I of the Trials of Hypertension Prevention ( TOHP ) was a r and omized , multicenter investigation that included double-blind , placebo-controlled testing of calcium and magnesium supplementation among 698 healthy adults ( 10.5 % blacks and 31 % women ) aged 30 to 54 years with high-normal diastolic blood pressure ( DBP ) ( 80 to 89 mm Hg ) . Very high compliance ( 94 to 96 % by pill counts ) with daily doses of 1 g of calcium ( carbonate ) , 360 mg of magnesium ( diglycine ) , or placebos was corroborated for the active supplements by significant net increases in all urine and serum compliance measures in white men and for urine compliance measures in white women . Overall , neither calcium nor magnesium produced significant changes in blood pressure at 3 and 6 months . Analyses stratified by baseline intakes of calcium , magnesium , sodium , or initial blood pressures also showed no effect of supplementation . These analyses suggested that calcium supplementation may have result ed in a DBP decrease in white women and that response modifiers in this subgroup might have included lower initial urinary calcium levels , urinary sodium levels , or lower body mass index . However , overall analyses indicated that calcium and magnesium supplements are unlikely to lower blood pressure in adults with high-normal DBP . The subgroup analyses , useful to formulate hypotheses , raise the possibility of a benefit to white women , which requires testing in future trials The aim of the present study was to evaluate the effects of a normal-sodium ( 120 mmol sodium ) diet compared with a low-sodium diet ( 80 mmol sodium ) on readmissions for CHF ( congestive heart failure ) during 180 days of follow-up in compensated patients with CHF . A total of 232 compensated CHF patients ( 88 female and 144 male ; New York Heart Association class II-IV ; 55 - 83 years of age , ejection fraction < 35 % and serum creatinine < 2 mg/dl ) were r and omized into two groups : group 1 contained 118 patients ( 45 females and 73 males ) receiving a normal-sodium diet plus oral furosemide [ 250 - 500 mg , b.i.d . ( twice a day ) ] ; and group 2 contained 114 patients ( 43 females and 71 males ) receiving a low-sodium diet plus oral furosemide ( 250 - 500 mg , b.i.d . ) . The treatment was given at 30 days after discharge and for 180 days , in association with a fluid intake of 1000 ml per day . Signs of CHF , body weight , blood pressure , heart rate , laboratory parameters , ECG , echocardiogram , levels of BNP ( brain natriuretic peptide ) and aldosterone levels , and PRA ( plasma renin activity ) were examined at baseline ( 30 days after discharge ) and after 180 days . The normal-sodium group had a significant reduction ( P<0.05 ) in readmissions . BNP values were lower in the normal-sodium group compared with the low sodium group ( 685+/-255 compared with 425+/-125 pg/ml respectively ; P<0.0001 ) . Significant ( P<0.0001 ) increases in aldosterone and PRA were observed in the low-sodium group during follow-up , whereas the normal-sodium group had a small significant reduction ( P=0.039 ) in aldosterone levels and no significant difference in PRA . After 180 days of follow-up , aldosterone levels and PRA were significantly ( P<0.0001 ) higher in the low-sodium group . The normal-sodium group had a lower incidence of rehospitalization during follow-up and a significant decrease in plasma BNP and aldosterone levels , and PRA . The results of the present study show that a normal-sodium diet improves outcome , and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated CHF patients . Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet The Hypertension Prevention Trial ( HPT ) , was a r and omized , controlled , multicenter ( four clinics , four re source centers ) trial design ed to test the feasibility of achieving and sustaining dietary changes in the intake of calories , sodium , and potassium and to assess the effect of those changes on blood pressure in a normotensive population . The trial involved 841 men and women ( plus a test cohort of 78 ) who , at the first baseline ( BL ) examination were in the age range of 25 - 49 years and had diastolic blood pressure ( DBP ) greater than or equal to 76 but less than 100 mm Hg ( average of two readings ) , and at the examination prior to r and omization ( BL 2 ) had DBP greater than or equal to 78 but less than 90 mm Hg ( also averaged ) . Participants were r and omly assigned to a control treatment group ( no dietary counseling ) or to one of four dietary treatment groups involving counseling design ed to reduce calorie intake , reduce sodium intake , reduce sodium and calorie intake , and reduce sodium and increase potassium intake . This chapter describes HPT procedures for training and certifying clinic staff , for data entry checks and data audits of its distributed data entry system , and for inspecting clinical equipment . Replicate analyses were performed regularly by the two arms of the Data Coordinating Center . The Food Coding Center and the Central Laboratory were evaluated by both internal and external monitoring techniques . The performance monitoring report , prepared semiannually for the governing committees of the HPT , reported on the effectiveness of quality assurance procedures and served to alert staff to developing problems The Hypertension Prevention Trial ( HPT ) was a r and omized , controlled , multicenter ( four clinics , four re source centers ) trial design ed to test the feasibility of achieving and sustaining dietary changes in the intake of calories , sodium , and potassium and to assess the effect of those changes on blood pressure in a normotensive population . The trial involved 841 men and women ( plus a test cohort of 78 ) who , at the first baseline ( BL ) examination were in the age range of 25 - 49 years and had diastolic pressure ( DBP ) greater than or equal to 76 but less than 100 mm Hg ( average of two readings ) , and at the examination prior to r and omization ( BL 2 ) , had DBP greater than or equal to 78 but less than 90 mm Hg ( also averaged ) . Participants were r and omly assigned to a control treatment group ( no dietary counseling ) or to one of four dietary treatment groups involving counseling design ed to reduce calorie intake ; reduce sodium intake , reduce sodium and calorie intake , and reduce sodium and increase potassium intake . This chapter presents HPT baseline characteristics by weight stratum , clinic , and treatment group for various demographic , medical history , and nutritional characteristics , for several physiologic variables used in monitoring treatment compliance , and for blood pressure . The degree of comparability observed among treatment groups was within the range expected for the r and omization procedure used The Hypertension Prevention Trial ( HPT ) was a r and omized , controlled , multicenter ( four clinics , four re source centers ) trial design ed to test the feasibility of achieving and sustaining dietary changes in the intake of calories , sodium , and potassium and to assess the effect of those changes on blood pressure in a normotensive population . The trial involved 841 men and women ( plus a test cohort of 78 ) who , at the first baseline ( BL ) examination , were in the age range of 25 - 49 years and had diastolic blood pressure ( DBP ) greater than or equal to 76 but less than 100 mm Hg ( average of two readings ) , and at the examination prior to r and omization ( BL 2 ) had DBP greater than or equal to 78 but less than 90 mm Hg ( also averaged ) . Participants were r and omly assigned to a control treatment group ( no dietary counseling ) or to one of four dietary treatment groups involving counseling design ed to reduce calorie intake , reduce sodium intake , reduce sodium and calorie intake , and reduce sodium and increase potassium intake . Dietary counseling was provided primarily in group setting s and was aim ed at changing participants ' shopping , cooking , and eating habits related to a design ated treatment assignment . The effect of dietary counseling was measured through changes in urinary excretion of sodium and potassium , changes in body weight , and changes in reported food intake based on 24-hour food records . Blood pressure changes during the 3-year course of followup were based on measurements taken at 6-month intervals from enrollment using a r and om-zero sphygmomanometer . This chapter provides a general description of the design and methods of the HPT and the underlying rationale for decisions affecting the design BACKGROUND The beneficial effects of potassium-enriched salt on blood pressure have been reported in a few short-term trials . The long-term effects of potassium-enriched salt on cardiovascular mortality have not been carefully studied . OBJECTIVE The objective was to examine the effects of potassium-enriched salt on cardiovascular disease ( CVD ) mortality and medical expenditures in elderly veterans . DESIGN Five kitchens of a veteran retirement home were r and omized into 2 groups ( experimental or control ) and veterans assigned to those kitchens were given either potassium-enriched salt ( experimental group ) or regular salt ( control group ) for approximately 31 mo . Information on death , health insurance cl aims , and date s that veterans moved in or out of the home was gathered . RESULTS Altogether , 1981 veterans , 768 in the experimental [ x ( + /-SD ) age : 74.8 + /- 7.1 y ] and 1213 in the control ( age : 74.9 + /- 6.7 y ) groups , were included in the analysis . The experimental group had better CVD survivorship than did the control group . The incidence of CVD-related deaths was 13.1 per 1000 persons ( 27 deaths in 2057 person-years ) and 20.5 per 1000 ( 66 deaths in 3218 person-years ) for the experimental and control groups , respectively . A significant reduction in CVD mortality ( age-adjusted hazard ratio : 0.59 ; 95 % CI : 0.37 , 0.95 ) was observed in the experimental group . Persons in the experimental group lived 0.3 - 0.90 y longer and spent significantly less ( approximately US Dollars 426/y ) in inpatient care for CVD than did the control group , after control for age and previous hospitalization expenditures . CONCLUSIONS This study showed a long-term beneficial effect on CVD mortality and medical expenditure associated with a switch from regular salt to potassium-enriched salt in a group of elderly veterans . The effect was likely due to a major increase in potassium and a moderate reduction in sodium intakes The Hypertension Prevention Trial ( HPT ) was a r and omized unmasked multicenter trial design ed to address questions concerning the feasibility and efficacy of dietary intervention in the primary prevention of hypertension . Participants in the diet treatments were given counseling to achieve and sustain changes in calorie , sodium , and /or potassium intake . Diet composition , sodium and potassium excretion , and body weight were assessed for all participants at 6-mo intervals over 3 y. This paper provides information about extent and possible sources of bias in the dietary assessment methodology used in the HPT . Estimates of nutrient intake were derived from food records , urinalysis , and measurement of body weight . Reported potassium intake increased and sodium intake declined to a greater degree during the study than did potassium and sodium excretion . Our results indicate that repeated assessment s of diet , which depend upon participant recording , may not accurately represent usual diet in a dietary trial To examine the long-term effects of weight loss and dietary sodium reduction on the incidence of hypertension , we studied 181 men and women who participated in the Trials of Hypertension Prevention , phase 1 , in Baltimore , Md. At baseline ( 1987 to 1988 ) , subjects were 30 to 54 years old and had a diastolic blood pressure ( BP ) of 80 to 89 mm Hg and systolic BP < 160 mm Hg . They were r and omly assigned to one of two 18-month lifestyle modification interventions aim ed at either weight loss or dietary sodium reduction or to a usual care control group . At the posttrial follow-up ( 1994 to 1995 ) , BP was measured by blinded observers who used a r and om-zero sphygmomanometer . Incident hypertension was defined as systolic BP > or = 160 mm Hg and /or diastolic BP > or = 90 mm Hg and /or treatment with antihypertensive medication during follow-up . Body weight and urinary sodium were not significantly different among the groups at the posttrial follow-up . After 7 years of follow-up , the incidence of hypertension was 18.9 % in the weight loss group and 40.5 % in its control group and 22.4 % in the sodium reduction group and 32.9 % in its control group . In logistic regression analysis adjusted for baseline age , gender , race , physical activity , alcohol consumption , education , body weight , systolic BP , and urinary sodium excretion , the odds of hypertension was reduced by 77 % ( odds ratio 0.23 ; 95 % confidence interval 0.07 to 0.76 ; P=0.02 ) in the weight loss group and by 35 % ( odds ratio 0.65 ; 95 % confidence interval 0.25 to 1.69 ; P=0.37 ) in the sodium reduction group compared with their control groups . These results indicate that lifestyle modification such as weight loss may be effective in long-term primary prevention of hypertension BACKGROUND Few trials have evaluated the effects of reduced sodium intake in older individuals , and no trial has examined the effects in relevant subgroups such as African Americans . PATIENTS AND METHODS The effects of sodium reduction on blood pressure ( BP ) and hypertension control were evaluated in 681 patients with hypertension , aged 60 to 80 years , r and omly assigned to a reduced sodium intervention or control group . Participants ( 47 % women , 23 % African Americans ) had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while taking 1 antihypertensive medication . Three months after the start of intervention , medication was withdrawn . The primary end point was occurrence of an average systolic BP of 150 mm Hg or more , an average diastolic BP of 90 mm Hg or more , the resumption of medication , or a cardiovascular event during follow-up ( mean , 27.8 months ) . RESULTS Compared with control , mean urinary sodium excretion was 40 mmol/d less in the reduced sodium intervention group ( P<.001 ) ; significant reductions in sodium excretion occurred in subgroups defined by sex , race , age , and obesity . Prior to medication withdrawal , mean reductions in systolic and diastolic BPs from the reduced sodium intervention , net of control , were 4.3 mm Hg ( P<.001 ) and 2.0 mm Hg ( P = .001 ) . During follow-up , an end point occurred in 59 % of reduced sodium and 73 % of control group participants ( relative hazard ratio = 0.68 , P<.001 ) . In African Americans , the corresponding relative hazard ratio was 0.56 ( P = .005 ) ; results were similar in other subgroups . In dose-response analyses , end points were progressively less frequent with greater sodium reduction ( P for trend = .002 ) . CONCLUSION A reduced sodium intake is a broadly effective , nonpharmacologic therapy that can lower BP and control hypertension in older individuals We conducted a r and omized , double-blind , placebo-controlled trial of oral potassium chloride supplementation ( 60 mmol/d ) in 353 men and women with an initial average diastolic blood pressure between 80 and 89 mm Hg . In the active ( n = 178 ) compared to the placebo ( n = 175 ) treatment group , the urinary potassium level was significantly ( p < 0.001 ) increased by an average of 44.0 and 42.3 mmol/24 h following 3 and 6 months of therapy , respectively . Compared to placebo , active treatment was associated with a small ( mean = 1.8 mm Hg ) but significant ( p = 0.04 ) reduction in diastolic blood pressure following 3 months of therapy . Following 6 months , however , this apparent treatment effect had virtually disappeared ( mean reduction in diastolic blood pressure = 0.3 mm Hg ) . There was no significant effect of potassium supplementation on systolic blood pressure at either follow-up visit . There was a significant , independent , dose-response relationship between change in both 24-hour urinary potassium excretion and urinary sodium-potassium ratio and the corresponding change in diastolic blood pressure ( -1.49 mm Hg for the highest versus the lowest quartile of change in urinary potassium excretion Phase II of the Trials of Hypertension Prevention is a multicenter , r and omized , controlled trial design ed to determine the efficacy of weight loss and reduction of sodium intake for lowering blood pressure and incidence of hypertension among persons with high-normal levels of blood pressure . The 2 x 2 factorial study design includes weight loss alone , restricted sodium intake alone , the combination of weight loss and sodium restriction , and a control group . Nine clinical centers used a variety of recruitment strategies to enroll 2382 participants over 17 months , which exceeded the sample size goal of 2250 . Among r and omized participants , 21 % were minorities and 34 % were women . Overall , direct mail generated the most r and omized participants ( 73 % ) , followed by community screening ( 12 % ) and media advertisement ( 11 % ) . Referrals from community health care providers yielded few participants . Prescreening improved overall efficiency and reduced costs . Participants who were more likely to drop out voluntarily during the three-visit screening regimen tended to be younger , single , male , smokers , and less educated Phase 1 of the Trials of Hypertension Prevention was conducted in 2182 adults , aged 35 - 54 y , with diastolic blood pressure of 80 - 89 mm Hg to test the feasibility and blood pressure-lowering effects of seven nonpharmacologic interventions ( weight loss , sodium reduction , stress management , and supplementation with calcium , magnesium , potassium , and fish oil ) . At 6 and 18 mo , weight loss and sodium reduction were well-tolerated and produced significant declines in systolic and diastolic blood pressures ( -2.9/-2.4 and -2.1/-1.2 mm Hg for weight loss and sodium reduction , respectively , at 18 mo ) . None of the other interventions lowered blood pressure significantly at either the 6- or 18-mo follow-up visits . These results suggest that both weight loss and sodium reduction provide an effective means to prevent hypertension . The long-term effects of both of these interventions are being tested in phase 2 of the trial The angiotensinogen gene has been linked to essential hypertension and increased blood pressure . A functional variant believed to be responsible for hypertension susceptibility occurs at position -6 in the promoter region of the gene in which an A for G base pair substitution is associated with higher angiotensinogen levels . To test whether an allele within the angiotensinogen gene is related to subsequent incidence of hypertension and blood pressure response to sustained sodium reduction , 1509 white male and female subjects participating in phase II of the Trials of Hypertension Prevention were genotyped at the angiotensinogen locus . Participants had diastolic blood pressures between 83 and 89 mm Hg and were r and omized in a 2x2 factorial design to sodium reduction , weight loss , combined intervention , or usual care groups . Persons in the usual care group with the AA genotype at nucleotide position -6 had a higher 3-year incidence rate of hypertension ( 44.6 % ) compared with those with the GG genotype ( 31.5 % ) , with a relative risk of 1.4 ( 95 % confidence interval [ 0.87 , 2.34 ] , test for trend across all 3 genotypes , P=0.10 ) . In contrast , the incidence of hypertension was significantly lower after sodium reduction for persons with the AA genotype ( relative risk=0.57 [ 0.34 , 0.98 ] versus usual care ) but not for persons with the GG genotype ( relative risk=1.2 [ 0.79 , 1.81 ] , test for trend P=0.02 ) . Decreases of diastolic blood pressure at 36 months in the sodium reduction group versus usual care showed a significant trend across all 3 genotypes ( P=0.01 ) , with greater net blood pressure reduction in those with the AA genotype ( -2.2 mm Hg ) than those with the GG genotype ( + 1.1 mm Hg ) . A similar trend across the 3 genotypes for net systolic blood pressure reduction ( -2.7 for AA versus -0.2 mm Hg for GG ) was not significant ( P=0.17 ) . Trends across genotypes for the effects of weight loss on hypertension incidence and decreases in blood pressure were similar to those for sodium reduction . We conclude that the angiotensinogen genotype may affect blood pressure response to sodium or weight reduction and the development of hypertension 31 patients with a diastolic blood-pressure between 95 and 109 mm Hg have been treated for two years with a regimen involving a moderate restriction of salt in the diet . The results are compared with those in a control group and in a drug-treated group . Salt restriction has reduced the diastolic blood-pressure by 7.3+/-1.6 mm Hg , a result similar to that in patients treated with antihypertensive drugs . In the untreated group the diastolic blood-pressure rose by 1.8+/-1.1 mm Hg . Most patients did not achieve the desired amount of salt restriction and a stricter adherence to the diet might have caused further falls in blood-pressure . Excessive salt intake is probably a major cause of the epidemic of hypertension in " civilised " countries and a reduction in salt intake may help to control the epidemic . In persons with a diastolic blood-pressure between 90 and 105 mm Hg salt restriction should be tried before drugs Sodium reduction is efficacious for primary prevention of hypertension , but the feasibility of achieving this effect is unclear . The objective of the paper is detailed analyses of adherence to and effects of the sodium reduction intervention among overweight adults in the Trials of Hypertension Prevention , Phase II . Sodium reduction ( comprehensive education and counselling about how to reduce sodium intake ) was tested vs no dietary intervention ( usual care ) for 36–48 months . A total of 956 white and 203 black adults , ages 30–54 years , with diastolic blood pressure 83–89 mmHg , systolic blood pressure ( SBP ) < 140 mmHg , and body weight 110–165 % of gender-specific st and ard weight were included in the study . At 36 months , urinary sodium excretion was 40.4 mmol/24 h ( 24.4 % ) lower in sodium reduction compared to usual care participants ( P<0.0001 ) , but only 21 % of sodium reduction participants achieved the targeted level of sodium excretion below 80 mmol/24 h. Adherence was positively related to attendance at face-to-face contacts . Net decreases in SBP at 6 , 18 , and 36 months of 2.9 ( P<0.001 ) , 2.0 ( P<0.001 ) , and 1.3 ( P=0.02 ) mmHg in sodium reduction vs usual care were associated with an overall 18 % lower incidence of hypertension ( P=0.048 ) ; were relatively unchanged by adjustment for ethnicity , gender , age , and baseline blood pressure , BMI , and sodium excretion ; and were observed in both black and white men and women . From these beneficial but modest results with highly motivated and extensively counselled individuals , sodium reduction sufficient to favourably influence the population blood pressure distribution will be difficult to achieve without food supply changes OBJECTIVE To compare the effectiveness of different approaches to participant enrollment in a behavior modification trial . DESIGN Concurrent , prospect i ve evaluation performed in context of recruitment for a r and omized , controlled trial . SETTING Four study centers located in Baltimore , Maryl and , Memphis , Tennessee New Brunswick , New Jersey , and Winston-Salem , North Carolina . PARTICIPANTS Men and women aged 60 to 80 years who were being treated with a prescription medication for control of hypertension . MAIN OUTCOME MEASURES Visit counts and percent yields were assessed at each stage of the screening and r and omization process . Logistic regression was used to contrast the r and omization yields for different recruitment strategies and to explore the impact of sociodemographic characteristics and geographic location on recruitment yields . RESULTS The overall r and omization yields from a prescreen contact and a first screening visit to enrollment in the trial were 11 % and 31 % , respectively . R and omization yields varied significantly by participant age , education , and marital status . CONCLUSIONS Our results demonstrate the feasibility of recruitment for trials of nonpharmacologic interventions in older people and suggest that mass mailing and mass media advertising campaigns provide an effective means of enrolling in such studies participants with a broad range of personal characteristics Phase II of the Trials of Hypertension Prevention ( TOHP ) is a multicenter , r and omized trial sponsored by the National Heart , Lung , and Blood Institute design ed to test whether weight loss alone , sodium reduction alone , or the combination of weight loss and sodium reduction will decrease diastolic ( DBP ) and systolic blood pressure ( SBP ) as well as the incidence of hypertension ( DBP > or = 90 mm Hg , SBP > or = 140 mm Hg , and /or use of antihypertensive medications ) in subjects with high-normal DBP ( 83 to 89 mm Hg ) and SBP less than 140 mm Hg at entry . These interventions were chosen for longer-term testing with end points including hypertension prevention as well as blood pressure ( BP ) change based on their demonstrated short-term efficacy in reducing BP in phase I of TOHP . The phase II study population is comprised of 2382 participants ( 1566 men and 816 women ) who are 110 to 165 % of desirable body weight , allocated at r and om to the four treatment arms using a 2 x 2 factorial design . The trial has 80 % power to detect an overall treatment effect on DBP of 1.2 mm Hg for weight loss or sodium reduction and a difference of 1.6 mm Hg between the combined intervention and placebo groups . BP observers are blinded to participant treatment assignments . Participants will be followed for 3 to 4 years . This trial may have important public policy implication s concerning the ability of life-style modifications to reduce BP and prevent the development of hypertension over the long term , thereby avoiding the need for drug therapy which while effective is costly and may have side effects The Fifth Report of the Joint National Committee on Detection , Evaluation , and Treatment of High Blood Pressure recommends that attempts to discontinue antihypertensive drug therapy be considered after blood pressure ( BP ) has been controlled for 1 year . However , discontinuation of drug therapy could unmask underlying conditions and precipitate clinical cardiovascular events . The Trial of Nonpharmacologic Interventions in the Elderly ( TONE ) was a clinical trial of the efficacy of weight loss and /or sodium reduction in controlling BP after withdrawal of drug therapy in patients with a BP < 145/85 mm Hg on 1 antihypertensive medication . Of 975 participants , 886 entered the drug withdrawal phase of the trial and 774 were successfully withdrawn from their medications . Thirty-three events ( stroke , transient ischemic attack , myocardial infa rct ion , arrhythmia , congestive heart failure , angina , other ) occurred between r and omization and the onset of drug withdrawal ( median time 3.6 months ) , 57 events occurred either during or after drug withdrawal ( 14.0 months ) , and 36 events occurred after resumption of antihypertensive therapy ( 15.9 months ) . Event rates per 100 person-years were 5.5 , 5.5 , and 6.8 for the 3 time periods ( p=0.84 ) in the nonoverweight group and 7.2 , 5.2 , and 5.6 ( p=0.08 ) in the overweight group . The study shows that antihypertensive medication can be safely withdrawn in older persons without clinical evidence of cardiovascular disease who do not have diastolic pressure > or = 150/90 mm Hg at withdrawal , providing that good BP control can be maintained with nonpharmacologic therapy Phase I of the Trials of Hypertension Prevention was design ed to test the effectiveness and safety of three life-style ( weight loss , sodium restriction , and stress management ) and four nutrition supplement ( calcium , magnesium , potassium , and fish oil ) interventions in reducing diastolic blood pressure ( DBP ) in persons with a high-normal blood pressure . A total of 2182 persons with a DBP between 80 and 89 mm Hg met the eligibility criteria for participation in phase I and were r and omized to one of the active intervention or control treatment groups . Most were white ( 82 % ) , male ( 70 % ) , married ( 76 % ) , nonsmoking ( 88 % ) , college graduate ( 53 % ) , full-time employees ( 91 % ) . The average blood pressure prior to entry into the trial was 124.9 mm Hg systolic and 83.8 mm Hg diastolic . A variety of baseline observations , including sociodemographic characteristics , personal and family medical history , health habits , diet , and biologic measurements , were documented before r and omization and compared among the seven active intervention and control groups . As might be expected in a r and omized trial of this sample size , the distribution of measured baseline characteristics was virtually identical in the treated and control groups . Based on this finding and the knowledge that r and omization procedures were implemented without deviation from the phase I protocol , it is probable that unknown potential confounders were also equally distributed at entry into the study . Given the achievement of high rates of follow-up , subsequent differences in blood pressure are unlikely to have been due to baseline differences between the active treatment and control groups , and can probably be attributed to effects of the active interventions Intraperson variability in both blood pressure ( BP ) and sodium excretion dilutes associations and leads to underestimates of the dose-response relation . The authors applied statistical correction techniques to data from the Trials of Hypertension Prevention ( TOHP ) , Phase I , carried out 1987 - 1990 . Men and women with high normal diastolic BP ( 80 - 89 mmHg ) were r and omized to sodium reduction ( n = 327 ) or a usual care comparison group ( n = 417 ) . Regression estimates of the effects of change in sodium and sodium/potassium ratio ( Na/K ratio ) on blood pressure change in the pooled sample were corrected for both the within-person variance of the excretion measures and the within-person covariance with blood pressure using a multivariate error correction . The estimated cross-sectional reliability was 0.36 for square root(Na ) and 0.42 for square root(Na/K ratio ) and that for change was 0.31 and 0.28 , respectively . Corrected coefficients suggested a decrease of 4.4 mmHg in systolic BP ( 95 % confidence interval ( CI ) 0.1 - 8.8 ) and 2.8 mmHg in diastolic BP ( 95 % CI -0.2 to 5.8 ) per 100 mmol/24 hour reduction in sodium , and of 3.4 mmHg in systolic BP ( 95 % CI 0.8 - 6.1 ) and 1.7 mmHg in diastolic BP ( 95 % CI 0.0 - 3.5 ) per unit decrease in Na/K. These results are comparable with those from the Intersalt Study , and suggest that the true effect of sodium change on blood pressure change in normotensives over 18 months is underestimated by more than half in uncorrected data The associations of diastolic blood pressure ( DBP ) with stroke and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any " threshold " below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at " baseline " with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this " regression dilution " bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrected analyses . ( This regression dilution bias is quite general , so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths . ) The DBP results suggest that for the large majority of individuals , whether conventionally " hypertensive " or " normotensive " , a lower blood pressure should eventually confer a lower risk of vascular disease National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure ( BP ) . However , data to support such recommendations in older persons are virtually nonexistent . The Trials of Nonpharmacologic Intervention in the Elderly ( TONE ) is a r and omized , controlled trial that will test whether weight loss or a reduced sodium ( Na ) intake or both can maintain satisfactory BP control , without unacceptable side effects , after withdrawal of antihypertensive drug therapy . Medication-treated hypertensives ( aged 60 to 80 years ) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are r and omly assigned to one of four groups : ( 1 ) weight loss alone , ( 2 ) reduced Na intake alone , ( 3 ) combined weight loss and reduced Na intake , or ( 4 ) usual life-style ( control group ) . Overweight participants are r and omized to one of these four groups , while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group . The interventions , tailored to the needs of older persons , use behavioral approaches to accomplish intervention-specific goals ( weight loss > or = 10 lb , daily Na intake < or = 80 mEqa ) . Three months after the start of intervention , antihypertensive drug therapy is withdrawn . The primary trial end point is a BP of 150/90 mm Hg or higher , resumption of antihypertensive drug therapy , or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up . It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy Objective To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol . Methods The participants were 350 normotensive men and women aged 30–54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention . They were r and omly assigned to receive placebo or 6 g purified fish oil once a day , which supplied 3 g n-3 polyunsaturated fatty acids for 6 months . Results Baseline blood pressure was ( mean ± SD ) 123±9/81 ±5mmHg . The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant . There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressures in the upper versus the lower quartile ( 132/87 versus 114/75 mmHg ) , low habitual fish consumption ( 0.4 versus 2.9 times a week ) or low baseline plasma levels of n-3 fatty acids . Fish oil increased HDL2-cholesterol significantly compared with the placebo group . Subgroup analysis showed this effect to be significant in the women but not in the men . Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL2-cholesterol and decreases in systolic blood pressure . Conclusion Moderate amounts of fish oil ( 6g/day ) are unlikely to lower blood pressure in normotensive persons , but may increase HDL2-cholesterol , particularly in women CONTEXT Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly , but there is a paucity of evidence from r and omized controlled trials in support of this recommendation . OBJECTIVE To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension . DESIGN R and omized controlled trial . PARTICIPANTS A total of 975 [ corrected ] men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication . SETTING Four academic health centers . INTERVENTION The 585 obese participants were r and omized to reduced sodium intake , weight loss , both , or usual care , and the 390 nonobese participants were r and omized to reduced sodium intake or usual care . Withdrawal of antihypertensive medication was attempted after 3 months of intervention . MAIN OUTCOME MEASURE Diagnosis of high blood pressure at 1 or more follow-up visits , or treatment with antihypertensive medication , or a cardiovascular event during follow-up ( range , 15 - 36 months ; median , 29 months ) . RESULTS The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake ( relative hazard ratio , 0.69 ; 95 % confidence interval [ CI ] , 0.59 - 0.81 ; P<.001 ) and , in obese participants , among those assigned vs not assigned to weight loss ( relative hazard ratio , 0.70 ; 95 % CI , 0.57 - 0.87 ; P<.001 ) . Relative to usual care , hazard ratios among the obese participants were 0.60 ( 95 % CI , 0.45 - 0.80 ; P<.001 ) for reduced sodium intake alone , 0.64 ( 95 % CI , 0.49 - 0.85 ; P=.002 ) for weight loss alone , and 0.47 ( 95 % CI , 0.35 - 0.64 ; P<.001 ) for reduced sodium intake and weight loss combined . The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups . CONCLUSION Reduced sodium intake and weight loss constitute a feasible , effective , and safe nonpharmacologic therapy of hypertension in older persons Identifying effective , nonpharmacologic means of preventing or significantly delaying the onset of hypertension would be a major advance in the primary prevention of cardiovascular disease . In the first phase of the Trials of Hypertension Prevention ( TOHP I ) , adults with high-normal diastolic blood pressure were r and omly assigned to one of seven nonpharmacologic interventions . Only weight loss and reduction of dietary sodium proved to be effective strategies for reducing blood pressure . The second phase of TOHP ( TOHP II ) will test the effectiveness of weight loss , reduction of dietary sodium , and their combination of lowering blood pressure and preventing the onset of hypertension over a 3- to 4-year follow-up period . This article describes the three interventions used in TOHP II , methods used to maintain continued participation in this long-term trial , and protocol enhancements design ed to maximize intervention effectiveness BACKGROUND Phase 1 of the Trials of Hypertension Prevention was a collaborative , r and omized controlled clinical trial design ed to determine the feasibility and efficacy of selected nonpharmacologic interventions in reducing or preventing an increase in diastolic blood pressure . METHODS Participants aged 30 to 54 years who had a high-normal diastolic blood pressure ( 80 to 89 mm Hg ) , and were between 115 % and 165 % of their desirable body weight , were r and omly assigned to either an 18-month weight loss intervention ( n = 308 ) or a usual-care control condition ( N = 256 ) . Intervention consisted of 14 weekly group meetings followed by monthly maintenance sessions . Intervention participants received training in behavioral self-management technique and were asked to make life-style changes aim ed at achieving a moderate reduction in energy intake and an increase in physical activity . RESULTS The average weight losses in the intervention group at 6 , 12 , and 18 months of follow-up were 6.5 , 5.6 , and 4.7 kg for men and 3.7 , 2.7 , and 1.6 kg for women . The mean ( + /- SE ) change in diastolic blood pressure for intervention participants compared with controls at termination was -2.8 + /- 0.6 mm Hg for men and -1.1 + /- 0.9 mm Hg for women . For systolic blood pressure , the corresponding change was -3.1 + /- 0.7 mm Hg for men and -2.0 + /- 1.3 mm Hg for women . Blood pressure reductions were greater for those who lost larger amounts of weight . Sex-related differences in blood pressure response were largely due to the smaller amount of weight lost by women , and sex differences in weight loss could be accounted for by differences in baseline body weight . CONCLUSIONS During an 18-month follow-up period , this weight reduction program was shown to be an effective nonpharmacologic intervention for reducing blood pressure in overweight adults with high-normal blood pressure The Hypertension Prevention Trial ( HPT ) was a multicenter r and omized trial design ed to assess the effects of long-term dietary changes on blood pressure in a normotensive population ( diastolic blood pressure greater than or equal to 78 but less than 90 mm Hg ) for a period of 3 years . The dietary treatments were reduction of sodium intake , increase of potassium intake , and decrease of energy intake . Estimates of changes in food intake were made by comparing 24-hour food records of the treatment and control participants . The participants in the treatment groups reported sodium intakes that were 30 % to 40 % lower than those of the controls . The restriction was achieved mainly by reducing intake of salt , meats , and grain products . Meats and grain products were still a major source of total sodium intake after treatment ( 41 % to 47 % ) , perhaps because of continued use of processed foods . Potassium intake was reported to be 16 % to 25 % higher in the treatment groups than in the controls , the increase achieved largely through increased consumption of fruits , with a lesser contribution from vegetables . Participants with higher initial body weights reported smaller increases in fruit and vegetable consumption than participants of normal weight , perhaps because of concerns about weight gain . Energy intake in the weight loss groups was 8 % to 11 % less than that of the controls . Men reported success in restricting calories from meats , dairy products , fats , beverages , and sugars . Women were less successful in restricting calories from most food groups . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol . METHODS The participants were 350 normotensive men and women aged 30 - 54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention . They were r and omly assigned to receive placebo or 6 g purified fish oil once a day , which supplied 3 g n-3 polyunsaturated fatty acids for 6 months . RESULTS Baseline blood pressure was ( mean + /- SD ) 123 + /- 9/81 + /- 5 mmHg . The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant . There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressures in the upper versus the lower quartile ( 132/87 versus 114/75 mmHg ) , low habitual fish consumption ( 0.4 versus 2.9 times a week ) or low baseline plasma levels of n-3 fatty acids . Fish oil increased HDL2-cholesterol significantly compared with the placebo group . Subgroup analysis showed this effect to be significant in the women but not in the men . Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL2-cholesterol and decreases in systolic blood pressure . CONCLUSION Moderate amounts of fish oil ( 6 g/day ) are unlikely to lower blood pressure in normotensive persons , but may increase HDL2-cholesterol , particularly in women The Hypertension Prevention Trial ( HPT ) was a multicenter , r and omized trial testing calorie control , sodium restriction , and potassium increases in the prevention of hypertension in 841 men and women . Thirty four variables that were potentially related to changes in urine sodium , urine potassium , and weight were examined individually and together across 3 years of treatment and maintenance sessions . Univariate and multivariate analysis did not reveal a consistent pattern of variables associated with successful attainment of treatment goals or failure to do so . Baseline levels of urine sodium , urine potassium , and weight were the variables most consistently associated with compliance . Household composition , such as number of people living in the house or marital status and control over selection and preparation of foods , was associated with compliance in sodium reduction treatments . Number of complaints about the diets were positively associated with noncompliance . Attendance at treatment sessions was generally associated with compliance especially for weight loss . Practical implication s of these results are discussed Phase II of the Trials of Hypertension Prevention ( TOHP II ) is a multicenter , controlled clinical trial design ed to test whether weight loss , a reduced sodium intake , or a combination of weight loss and a reduced sodium intake will lower blood pressure ( BP ) and prevent the occurrence of hypertension . The study population consists of middle-aged , moderately overweight individuals with a diastolic BP between 83 and 89 mm Hg . Of the 2382 r and omized participants , 816 ( 34 % ) are female and 494 ( 21 % ) are from a racial or ethnic minority background . At baseline , mean dietary intakes of sodium , based on measurements of 24-hour urinary excretion , were 199 mmol/d in men and 154 mmol/d in women . The average body mass index was 30.9 kg/m2 . Across the four r and omized groups , there was no substantial imbalance in the distribution of baseline variables ; however , the mean age in the four groups was slightly but significantly different ( range : 43.2 to 44.2 years , P = 0.02 ) . A comparison of baseline characteristics of TOHP II participants with those of participants in three other primary prevention trials reveals a high level of mean dietary sodium intake in each study . Data reported in this article indicate that any subsequent differences in BP among the r and omized groups are unlikely to result from maldistribution of known confounding variables at baseline . Finally , because of the high prevalence of overweight and excessive sodium intake in the United States , results from TOHP II should be broadly applicable to the general population Phase I of the Trials of Hypertension Prevention ( TOHP ) was a National Heart , Lung , and Blood Institute-sponsored , 3-year , national , multicenter , r and omized , controlled trial design ed to test the feasibility and efficacy of three life-style ( weight loss , sodium restriction , and stress management ) and four nutrition supplement ( calcium , magnesium , fish oil , and potassium ) interventions aim ed at lowering diastolic blood pressure in those whose blood pressure was initially in the high normal range ( 80 to 89 mm Hg ) . A total of 2182 volunteers were recruited and allocated to the various treatment arms , such that each hypothesis was tested with a power of 85 % or higher to detect a diastolic blood pressure treatment effect of 2 mm Hg . The four nutrition supplement interventions were delivered in a double-blinded fashion and the three life-style interventions , single ( observed ) -blinded . Phase I was design ed to provide a rigorous test of short-term lowering of blood pressure for each of the seven treatments chosen and provides the basis for planning of a subsequent long-term trial of hypertension prevention OBJECTIVE To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure . DESIGN R and omized control multicenter trials . SETTING Volunteers recruited from the community , treated and followed up at special clinics . PARTICIPANTS Of 16,821 screenees , 2182 men and women , aged 30 through 54 years , with diastolic blood pressure from 80 through 89 mm Hg were selected . Of these , 50 did not return for follow-up blood pressure measurements . INTERVENTIONS Three life-style change groups ( weight reduction , sodium reduction , and stress management ) were each compared with unmasked nonintervention controls over 18 months . Four nutritional supplement groups ( calcium , magnesium , potassium , and fish oil ) were each compared singly , in double-blind fashion , with placebo controls over 6 months . MAIN OUTCOME MEASURES Primary : change in diastolic blood pressure from baseline to final follow-up , measured by blinded observers . Secondary : changes in systolic blood pressure and intervention compliance measures . RESULTS Weight reduction intervention produced weight loss of 3.9 kg ( P less than .01 ) , diastolic blood pressure change of -2.3 mm Hg ( P less than .01 ) , and systolic blood pressure change of -2.9 mm Hg ( P less than .01 ) . Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h ( P less than .01 ) , diastolic blood pressure by 0.9 mm Hg ( P less than .05 ) , and systolic blood pressure by 1.7 mm Hg ( P less than .01 ) . Despite good compliance , neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly ( P greater than .05 ) . CONCLUSIONS Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons . Sodium reduction is also effective . The long-term effects of weight reduction and sodium reduction , alone and in combination , require further evaluation Assigned participants in the Hypertension Prevention Trial to one of four diets for a period of 3 years : ( a ) weight loss , ( b ) reduced sodium , ( c ) weight loss plus reduced sodium , and ( d ) reduced sodium plus increased potassium . At 6-month intervals , they reported problems they were having adhering to their diets . Problem attributions were coded along the dimensions of internality , stability , and controllability and were categorized as intrapersonal or extrapersonal . Attributions were found to differ by type of diet and sex of participant . Participants assigned to weight-loss groups were significantly more likely than those assigned to non-weight-loss groups to blame themselves for their problems with adherence , making characterological as opposed to external or situational attributions . Men perceived problems to be more controllable than women . Attributions did not predict weight loss , change in urinary sodium , or change in potassium excretion |
13,382 | 21,992,675 | The identified studies indicate that regimens containing rituximab may be highly efficacious in the fludarabine-refractory CLL setting . | The increase of fludarabine-resistant chronic lymphocytic leukemia ( CLL ) presents a new treatment challenge .
The aim of this review is to evaluate the efficacy and safety of rituximab for patients with fludarabine-refractory CLL . | Cladribine has been reported to have little activity in fludarabine- refractory chronic lymphocytic leukemia ( CLL ) . We sought to determine whether resistance to therapy with cladribine in fludarabine-refractory CLL patients represented primary drug resistance or the inability to tolerate the myelosuppression associated with this therapy . Patients with fludarabine refractory CLL patients without severe thrombocytopenia ( platelets ≥50 × 109/l ) or granulocytopenia ( neutrophils > 1.5 × 109/l ) were enrolled . All patients received cladribine ( 0.14 mg/kg ) as a 2-h intravenous infusion daily for 5 days , repeated every 4 weeks . Patients received up to six cycles of therapy . Twenty-eight patients enrolled ; 13 had intermediate ( Rai stage I or II ) and 15 high ( Rai stage III and IV ) risk stages . No patient had a complete remission , but nine ( 32 % ; 95 % confidence interval , 15–49 % ) attained a partial remission when assessed using the modified NCI criteria ( 1996 ) . The median time to relapse for responders was 12 months , while median progression-free survival for the entire group was 9 months ( 95 % confidence interval , 4–14 months ) . The median overall survival was 2.2 years ( 95 % confidence interval , 0.8–3.1 years ) . Response was predicted by pre-treatment Rai status with seven of 13 ( 54 % ) intermediate risk vs two of 15 ( 13 % ) high-risk patients responding ( P = 0.04 ) . Toxicity was myelosuppression and infections ( grade 3–5 : neutropenia 75 % , thrombocytopenia 68 % , and infections 43 % ) . Cladribine has modest clinical activity and considerable toxicity in a very selected group of patients with fludarabine-refractory CLL lacking pre-treatment neutropenia and thrombocytopenia Rituximab ( IDEC-C2B8 ) is a chimeric antibody that binds to the B-cell surface antigen CD20 . Rituximab has significant activity in follicular non-Hodgkin lymphomas . Much less is known about the effects in chronic lymphocytic leukemia ( CLL ) . We have initiated a phase II trial to evaluate the efficacy and safety of rituximab in patients with CD20 + pretreated CLL . To avoid the rituximab-associated toxicity , we restricted the tumor cell load , as measured by the number of circulating lymphocytes and the spleen size , in the first 2 cohorts of patients included in the study . Patients received 4 intravenous infusions of 375 mg/m2 once a week over a period of 1 month . Of the 28 patients evaluable for response , 7 patients showed a partial remission ( National Cancer Institute criteria ) lasting for a median of 20 weeks , with 1 patient still in remission after 71 weeks . Based on lymphocyte counts only , we found at least a 50 % reduction of lymphocyte counts lasting for at least 4 weeks in 13 ( 45 % ) of 29 patients . Fifteen patients from 3 institutions were monitored for the immunophenotype profile of lymphocyte subsets . The number of CD5+CD20 + cells decreased significantly and remained low until day 28 after therapy . T-cell counts were not affected . With the exception of one rituximab-related death , adverse events in the remaining patients were mild . The results suggest that rituximab has clinical activity in pretreated patients with B-CLL . Toxicity is tolerable . Response duration after withdrawal of rituximab is rather short . Therefore , other modes of application and the combination with other agents need to be tested OBJECTIVES This prospect i ve multicentre study was conducted to assess the efficacy of the monoclonal anti-CD20 antibody rituximab in patients with chronic lymphocytic leukaemia ( CLL ) . Secondary objectives were defined as the tolerability and feasibility of rituximab in patients with CLL . METHODS Twenty-four heavily pretreated patients with CLL were treated with a st and ard dose of 375 mg m-2 of rituximab given once weekly for four doses . RESULTS The overall response rate was 35 % and all the responses were partial as defined by the revised NCI criteria . In 17 ( 85 % ) of 20 patients with initially measurable peripheral lymph nodes the size of lymph nodes decreased by at least 50 % , while an improvement of the bone marrow infiltration was observed only in two ( 11 % ) of 18 evaluable patients . The median duration of the overall response was 12.5 wk . Rituximab was relatively well tolerated . Although side-effects were common ( 75 % ) they were usually mild or moderate . There was only one grade 3 adverse event and no grade 4 events . CONCLUSIONS St and ard-dose rituximab has activity in heavily pretreated patients with CLL , although the response is mainly limited to the lymph nodes and of short duration . Since rituximab has in vitro synergism with chemotherapeutic agents and is well tolerated by CLL patients , it is reasonable to investigate rituximab in combination with other treatments We have developed a new chemoimmunotherapy for patients with relapsed or refractory CD20-positive indolent lymphomas and CLL by combining the chemotherapeutic agents Bendamustine ( B ) and Mitoxantrone ( M ) with the monoclonal antibody Rituximab . Treatment consisted of ( B ) : 90 mg/m2 ( 80 mg/m2 in CLL ) day 1 + 2 , ( M ) : 10 mg/m2 day 1 and ( R ) : 375 mg/m2 day 8,15,22 and 29 . BM was repeated 3 times starting on day 36 , thereafter every 4 weeks . The maximal therapy consisted of 1 × BMR followed by 5 × BM . We have treated 54 patients with BMR . Median age was 68 years ( 36 - 82 ) . Disease distribution was as follows : 21 B-CLL , 1 B-PLL , 8 lymphoplasmacytic , 14 follicular , 2 mantle cell , 2 marginal zone , 6 secondary high grade . Median number of previous treatments was 2 ( 1 - 7 ) . ORR was 96 % with 41 % CR and 55 % PR . Median time to progression is 17 months in CLL and has not been reached in indolent lymphomas with a median observation time of 27 months ( 3 - 60 + ) . The time to next antilymphoma treatment is prolonged significantly by BMR . No therapy associated death or hospitalization occurred within the study period . BMR is a well tolerated very effective outpatient treatment for relapsed and refractory CD20-positive indolent lymphomas and CLL PURPOSE Richter 's syndrome ( RS ) and fludarabine-refractory chronic lymphocytic leukemia ( CLL ) are associated with poor clinical outcomes . We conducted a phase I-II trial of oxaliplatin , fludarabine , cytarabine , and rituximab ( OFAR ) in these diseases . PATIENTS AND METHODS The OFAR regimen consisted of increasing doses of oxaliplatin ( 17.5 , 20 , or 25 mg/m(2)/d ) on days 1 to 4 ( phase I ) , fludarabine 30 mg/m(2 ) on days 2 to 3 , cytarabine 1 g/m(2 ) on days 2 to 3 , rituximab 375 mg/m(2 ) on day 3 of cycle 1 and day 1 of subsequent cycles , and pegfilgrastim 6 mg on day 6 , every 4 weeks for a maximum of six courses . Dose-limiting toxicity ( DLT ) was defined as any nonhematologic , treatment-related toxicity > /= grade 3 . RESULTS Fifty patients were treated ( 20 patients had RS , and 30 had CLL ) . The highest tolerated oxaliplatin dose was 25 mg/m(2 ) , which was the highest dose tested . DLT was not observed . Pharmacodynamic analyses demonstrated enhanced leukemia cell killing by oxaliplatin in the presence of fludarabine and cytarabine . The overall response rates were 50 % in RS and 33 % in fludarabine-refractory CLL . The overall response rate in 14 patients with age > /= 70 years was 50 % . Responses were achieved in seven ( 35 % ) of 20 patients with 17p deletion , two ( 29 % ) of seven patients with 11q deletion , all four patients with trisomy 12 , and two ( 40 % ) of five patients with 13q deletion . The median response duration was 10 months . Toxicities were mainly hematologic ; prolonged myelosuppression was not observed . CONCLUSION The OFAR regimen is highly active in RS and has activity in fludarabine-refractory patients with CLL . This regimen warrants further investigation in the treatment of these disorders PURPOSE Rituximab has been reported to have little activity in small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia ( CLL ) and to be associated with significant infusion-related toxicity . This study sought to decrease the initial toxicity and optimize the pharmacokinetics with an alternative treatment schedule . PATIENTS AND METHODS Thirty three patients with SLL/CLL received dose 1 of rituximab ( 100 mg ) over 4 hours . In cohort I ( n = 3 ; 250 mg/m(2 ) ) and cohort II ( n = 7 ; 375 mg/m(2 ) ) rituximab was administered on day 3 and thereafter three times weekly for 4 weeks using a st and ard administration schedule . Cohort III ( n = 23 ; 375 mg/m(2 ) ) administered rituximab similar to cohort II for the first two treatments and then over 1 hour thereafter . RESULTS A total of 33 CLL/SLL patients were enrolled ; only one patient discontinued therapy because of infusion-related toxicity . Thirteen patients developed transient hypoxemia , hypotension , or dyspnea that were associated with significant changes in baseline interleukin-6 , interleukin-8 , tumor necrosis factor alpha , and interferon gamma compared with those not experiencing such reactions . Infusion-related toxicity occurred more commonly in older ( median age 73 v 62 years ; P = .02 ) patients with no other pretreatment clinical or laboratory features predicting occurrence of these events . The overall response rate was 45 % ( 3 % CR , 42 % PR ; 95 % CI 28 % to 64 % ) . Median response duration for these 15 patients was 10 months ( 95 % CI , 6.8 - 13.2 ; range , 3 to 17 + ) . CONCLUSION Rituximab administered thrice weekly for 4 weeks demonstrates clinical efficacy and acceptable toxicity . Initial infusion-related events seem to be cytokine mediated and resolve by the third infusion making rapid administration possible . Future combination studies of rituximab with other therapies in CLL seem warranted Safety and efficacy of the fully human anti-CD20 monoclonal antibody , ofatumumab , was analyzed in a multicenter dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia . Three cohorts of 3 ( A ) , 3 ( B ) , and 27 ( C ) patients received 4 , once weekly , infusions of ofatumumab at the following doses : ( A ) one 100 mg and three 500 mg ; ( B ) one 300 mg and three 1000 mg ; ( C ) one 500 mg and three 2000 mg . Sixty-seven percent of the patients were Binet stage B , and the median number of previous treatments was 3 . The maximum tolerated dose was not reached . The majority of related adverse events occurred at first infusion , and the number of adverse events decreased at each subsequent infusion . Seventeen ( 51 % ) of 33 patients experienced infections , 88 % of them of grade 1 - 2 . One event of interstitial pneumonia was fatal ; all other cases resolved within one month . The response rate of cohort C was 50 % ( 13/26 ) , one patient having a nodular partial remission and 12 patients partial remission . In conclusion , ofatumumab was found to be well tolerated in patients with chronic lymphocytic leukemia ( CLL ) in doses up to 2000 mg . Preliminary data on safety and objective response are encouraging and support further studies on the role of ofatumumab in CLL patients . This trial was registered at www . clinical trials.gov as no. NCT00093314 We conducted a multicenter , community-based phase II trial of PCR biochemotherapy ( pentostatin 4 mg/m2 , cyclophosphamide 600 mg/m2 , and rituximab 375 mg/m2 ) every 3 weeks for up to 6 cycles in patients with chronic lymphocytic leukemia ( CLL ) or small lymphocytic lymphoma ( SLL ) . The study was stopped after enrolling 24 patients because of diminished investigator interest after 8 patients discontinued treatment because of adverse events , and 5 others died during treatment . The median age of patients was 69 years ; 11 patients were over age 70 , and 71 % had Rai stage III or IV disease . The response rate among the 17 evaluable patients who completed 3 cycles of therapy was 58 % ( 35%-81 % , 95 % confidence interval ) , with 2 complete responders ( both greater than 70 years of age ) and 7 partial responders . No patients developed progressive disease while receiving PCR . This is the first report of a trial in CLL utilizing a combination of purine analog , alkylator , and rituximab , in which most patients were older than 65 years and had high-risk disease . PCR is active in CLL/SLL , but appears to be less active and associated with more complications in the community setting , compared to trials with younger , lower risk patients who travel to academic referral centers for treatment PURPOSE To conduct a dose-escalation trial of rituximab in patients with chronic lymphocytic leukemia ( CLL ) to define the maximum-tolerated dose ( MTD ) , to evaluate first-dose reactions in patients with high circulating lymphocyte counts , and to assess the efficacy at higher versus lower doses . PATIENTS AND METHODS Fifty patients with CLL ( n = 40 ) or other mature B-cell lymphoid leukemias ( n = 10 ) were treated with four weekly infusions of rituximab . The first dose was 375 mg/m(2 ) for all patients ; dose- escalation began with dose 2 but was held constant for each patient . Escalated doses were from 500 to 2,250 mg/m(2 ) . RESULTS Toxicity with the first dose ( 375 mg/m(2 ) ) was noted in 94 % of patients but was grade 1 or 2 in most , predominantly fever and chills . Six patients ( 12 % ) experienced severe toxicity with the first dose , including fever , chills , dyspnea , and hypoxia in all six patients , hypotension in five , and hypertension in one . Toxicity on subsequent doses was minimal until a dose of 2,250 mg/m(2 ) was achieved . Eight ( 67 % ) of 12 patients had grade 2 toxicity , including fever , chills , nausea , and malaise , although no patient had grade 3 or 4 toxicity . Severe toxicity with the first dose was significantly more common in patients with other B-cell leukemias , occurring in five ( 50 % ) of 10 patients versus one ( 2 % ) of 40 patients with CLL ( P < .001 ) . The overall response rate was 40 % ; all responses in patients with CLL were partial remissions . Response rates were 36 % in CLL and 60 % in other B-cell lymphoid leukemias . Response was correlated with dose : 22 % for patients treated at 500 to 825 mg/m(2 ) , 43 % for those treated at 1,000 to 1,500 mg/m(2 ) , and 75 % for those treated at the highest dose of 2,250 mg/m(2 ) ( P = .007 ) . The median time to disease progression was 8 months . Myelosuppression and infections were uncommon . CONCLUSION Rituximab has significant activity in patients with CLL at the higher dose levels . Severe first-dose reactions were uncommon in patients with CLL , even with high circulating lymphocyte counts , but were frequent in patients with other mature B-cell leukemias in which CD20 surface expression is increased . Efficacy of rituximab was also significant in this group of patients Purpose : Therapeutic antibodies have improved the outcome for patients with chronic lymphocytic leukemia ( CLL ) . We conducted a phase 1 , dose escalation and schedule optimization study of the primatized anti-CD23 antibody , lumiliximab , in patients with previously treated and refractory CLL . Experimental Design : Forty-six patients were assigned sequentially to cohorts 1 through 6 and received lumiliximab at 125 , 250 , or 375 mg/m2 weekly for 4 weeks ; 500 mg/m2 weekly for 4 weeks [ 500(A ) ] ; 500 mg/m2 thrice during week 1 then 500 mg/m2 weekly for the next 3 weeks [ 500(B ) ] ; or 500 mg/m2 thrice a week for 4 weeks [ 500(C ) ] , respectively . Results : The median age was 62 years ( range , 47 - 80 ) , and the median number of prior regimens was four ( range , 1 - 13 ) . No partial or complete responses were observed . Toxicity was limited and unrelated to dose . The pharmacokinetics of lumiliximab was similar to other IgG1 monoclonal antibodies with accumulation at doses ≥250 mg/m2 and a median terminal half-life of 7 days . Pharmacodynamic studies showed dose-dependent increases in soluble CD23 , but no down-regulation of CD23 antigen . Saturation of CD23 receptors occurred at 250 mg/m2 and was maintained for ≥1 week following completion of therapy at ≥375 mg/m2 . Conclusions : Treatment with lumiliximab seemed to be well tolerated and to have clinical activity in patients with relapsed or refractory CLL PURPOSE New treatments are needed for patients with fludarabine- and alemtuzumab-refractory ( FA-ref ) chronic lymphocytic leukemia ( CLL ) or patients with fludarabine-refractory CLL with bulky ( > 5 cm ) lymphadenopathy ( BF-ref ) who are less suitable for alemtuzumab treatment ; these groups have poor outcomes with available salvage regimens . Ofatumumab ( HuMax-CD20 ) is a human monoclonal antibody targeting a distinct small-loop epitope on the CD20 molecule . We conducted an international clinical study to evaluate the efficacy and safety of ofatumumab in patients with FA-ref and BF-ref CLL . PATIENTS AND METHODS Patients received eight weekly infusions of ofatumumab followed by four monthly infusions during a 24-week period ( dose 1 = 300 mg ; doses 2 to 12 = 2,000 mg ) ; response by an independent review committee ( 1996 National Cancer Institute Working Group criteria ) was assessed every 4 weeks until week 24 and then every 3 months until month 24 . RESULTS This planned interim analysis included 138 treated patients with FA-ref ( n = 59 ) and BF-ref ( n = 79 ) CLL . The overall response rates ( primary end point ) were 58 % [ corrected ] and 47 % in the FA-ref and BF-ref groups , respectively . Complete resolution of constitutional symptoms and improved performance status occurred in 57 % and 48 % of patients , respectively . Median progression-free survival and overall survival times were 5.7 and 13.7 months in the FA-ref group , respectively , and 5.9 and 15.4 months in the BF-ref group , respectively . The most common adverse events during treatment were infusion reactions and infections , which were primarily grade 1 or 2 events . Hematologic events during treatment included anemia and neutropenia . CONCLUSION Ofatumumab is an active , well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL Pre clinical data demonstrate enhanced antitumor effect when lumiliximab , an anti-CD23 monoclonal antibody , is combined with fludarabine or rituximab . Clinical data from a phase 1 trial with lumiliximab demonstrated an acceptable toxicity profile in patients with relapsed or refractory chronic lymphocytic leukemia ( CLL ) . We therefore pursued a phase 1/2 dose-escalation study of lumiliximab added to fludarabine , cyclophosphamide , and rituximab ( FCR ) in previously treated CLL patients . Thirty-one patients received either 375 mg/m(2 ) ( n = 3 ) or 500 mg/m(2 ) ( n = 28 ) of lumiliximab in combination with FCR for 6 cycles . The toxicity profile was similar to that previously reported for FCR in treatment of relapsed CLL . The overall response rate was 65 % , with 52 % of patients achieving a complete response ( CR ) , which compares favorably with the CR rate previously reported for the FCR regimen alone in relapsed CLL . The estimated median progression-free survival for all responders was 28.7 months . The addition of lumiliximab to FCR therapy is feasible , achieves a high CR rate , and does not appear to enhance toxicity in previously treated patients with CLL . A r and omized trial comparing lumiliximab plus FCR with FCR alone is underway to define the benefit of this combination in relapsed CLL . This trial was registered at clinical trials.gov as NCT00103558 PURPOSE To test whether eradication of minimal residual disease ( MRD ) in B-cell chronic lymphocytic leukemia ( CLL ) by alemtuzumab is associated with a prolongation of treatment-free and overall survival . PATIENTS AND METHODS Ninety-one previously treated patients with CLL ( 74 men and 17 women ; median age , 58 years [ range , 32 to 75 years ] ; 44 were refractory to purine analogs ) received a median of 9 weeks of alemtuzumab treatment between 1996 and 2003 . Regular bone marrow assessment s by MRD flow cytometry were performed with the aim of eradicating detectable MRD ( < 1 CLL cell in 10(5 ) normal cells ) . RESULTS Responses according to National Cancer Institute-sponsored working group response criteria were complete remission ( CR ) in 32 patients ( 36 % ) , partial remission ( PR ) in 17 patients ( 19 % ) , and no response ( NR ) in 42 patients ( 46 % ) . Twenty-two ( 50 % ) of 44 purine analog-refractory patients responded to alemtuzumab . Detectable CLL was eradicated from the blood and marrow in 18 patients ( 20 % ) . Median survival was significantly longer in MRD-negative patients compared with those achieving an MRD-positive CR , PR , or NR . Patients achieving an MRD-negative CR had a longer treatment-free survival than patients with MRD-positive CRs , PR , or NR : MRD-negative CRs , not reached ; MRD-positive CRs , 20 months ; PRs , 13 months ; NR , 6 months ( P < .0001 ) . Overall survival for the 18 patients with MRD-negative remissions was 84 % at 60 months . Eight ( 47 % ) of the MRD-negative patients converted to MRD positivity at a median of 28 months . CONCLUSION MRD-negative remission in CLL is achievable with alemtuzumab , leading to an improved overall and treatment-free survival We explored the safety and efficacy of rituximab plus alemtuzumab in patients with relapsed or refractory lymphoid malignancies . Forty-eight patients were treated and were assessable for response ( 32 with chronic lymphocytic leukemia [ CLL ] , 9 with CLL/prolymphocytic leukemia [ PLL ] , 1 with PLL , 4 with mantle cell leukemia/lymphoma , 2 with Richter transformation ) . The overall response rate was 52 % ( complete remission , 8 % ; nodular partial response , 4 % ; partial response , 40 % ) . With a median follow-up of 6.5 months ( range , 1 - 20 months ) , the median time to progression was 6 months ( range , 1 - 20 months ) ; median survival , 11 months ( 11 + months for responders vs 6 months for nonresponders ) . Most toxicities were grade 2 or lower and infusion-related . Infections occurred in 52 % of the patients . Cytomegalovirus ( CMV ) antigenemia assays were positive in 27 % of the patients , but only 15 % were symptomatic and required therapy . The combination of rituximab and alemtuzumab is feasible , has an acceptable safety profile , and has clinical activity with a short course in a group of patients with poor prognoses Monoclonal antibodies may be used more effectively in combination . A previous study of intravenous ( iv ) bolus alemtuzumab plus rituximab in patients with chronic lymphocytic leukemia ( CLL ) recurrence produced a response rate of 54 % after a 4‐week treatment period The treatment of patients with chronic lymphocytic leukemia ( CLL ) who fail purine analogues is sub optimal . CLL lymphocytes express two antigens , namely CD 20 and CD 52 , for which monoclonal antibodies are readily available . Rituximab is a chimeric monoclonal antibody targeted against CD 20 , which has some activity in refractory CLL , with primary effect on nodal disease . Alemtuzumab is a humanized anti-CD 52 antibody that is approved for the treatment of CLL in patients who fail alkylating agents and purine analogues . Alemtuzumab has better activity in the peripheral blood and the bone marrow compared to nodal disease . We investigated whether combining both antibodies is safe in refractory CLL . Both antibodies were given to a total of 12 patients divided into 3 cohorts with escalating alemtuzumab doses ( 3 mg , 10 mg , and 30 mg ) . The combination was proven to be safe , not toxic , feasible , and active . One patient attained PR by NCI criteria while all other patients had stable disease lasting a median of 101.5 days . All patients normalized their peripheral lymphocytosis within a median of 23.5 days . No treatment-related mortality was identified . No CMV reactivation occurred . Additional studies are needed to investigate the clinical significance of such a combination in this patient population , and whether this combination can be administered safely with systemic chemotherapy . These studies are currently underway Background : Patients with chronic lymphocytic leukemia ( CLL ) are sometimes resistant to treatment or relapse soon after the administration of the currently available frontline therapy including chlorambucil-prednisolone CHOP and fludarabine . We report the beneficial effect of an alternative chemotherapeutic regimen containing 2’-deoxycoformycin ( pentostatin ) and the monoclonal antibody anti-CD20 ( rituximab ) in 5 patients with resistant/relapsing CLL . Patients : Five patients ( 4 men and 1 woman ) with CLL at stage C , according to Binet ’s classification , were included in the therapeutic protocol . The median age of the patients was 76 years ( range 57–84 years ) . Previous treatment consisted of chlorambucil-prednisolone , fludarabine , and CHOP . The current regimen comprised six 2-week cycles of pentostatin , 4 mg/m2 i.v . , combined with four cycles of rituximab , in a dose of 375 mg/m2 , every other week . Results : Three patients responded to therapy , 2 achieved complete remission and 1 a partial response . Two patients did not respond to treatment . Toxicity was mild and well tolerated . The median survival duration of the responders was 19 months . These promising results suggest that salvage therapy with a combination regimen including pentostatin and rituximab may have a beneficial effect in patients with resistant/relapsing CLL PURPOSE The objective of this trial was to evaluate safety and efficacy of bendamustine combined with rituximab ( BR ) in patients with relapsed and /or refractory chronic lymphocytic leukemia ( CLL ) . PATIENTS AND METHODS Seventy-eight patients , including 22 patients with fludarabine-refractory disease ( 28.2 % ) and 14 patients ( 17.9 % ) with deletion of 17p , received BR chemoimmunotherapy . Bendamustine was administered at a dose of 70 mg/m(2 ) on days 1 and 2 combined with rituximab 375 mg/m(2 ) on day 0 of the first course and 500 mg/m(2 ) on day 1 during subsequent courses for up to six courses . RESULTS On the basis of intent-to-treat analysis , the overall response rate was 59.0 % ( 95 % CI , 47.3 % to 70.0 % ) . Complete response , partial response , and nodular partial response were achieved in 9.0 % , 47.4 % , and 2.6 % of patients , respectively . Overall response rate was 45.5 % in fludarabine-refractory patients and 60.5 % in fludarabine-sensitive patients . Among genetic subgroups , 92.3 % of patients with del(11q ) , 100 % with trisomy 12 , 7.1 % with del(17p ) , and 58.7 % with unmutated IGHV status responded to treatment . After a median follow-up time of 24 months , the median event-free survival was 14.7 months . Severe infections occurred in 12.8 % of patients . Grade 3 or 4 neutropenia , thrombocytopenia , and anemia were documented in 23.1 % , 28.2 % , and 16.6 % of patients , respectively . CONCLUSION Chemoimmunotherapy with BR is effective and safe in patients with relapsed CLL and has notable activity in fludarabine-refractory disease . Major but tolerable toxicities were myelosuppression and infections . These promising results encouraged us to initiate a further phase II trial evaluating the BR regimen in patients with previously untreated CLL |
13,383 | 22,542,974 | On the other h and , our results support the hypothesis that administrations of Ca/Mg do not impair the efficacy of oxaliplatin-based chemotherapy . | BACKGROUND It is hypothesised that infusion of calcium and magnesium ( Ca/Mg ) can reduce the occurrence of oxaliplatin-related sensory neurotoxicity .
However , more recent data have drawn a controversial picture concerning this topic . | BACKGROUND Peripheral sensory neurotoxicity is a frequent and potentially debilitating side effect of oxaliplatin treatment . Calcium and magnesium ( Ca/Mg ) infusions are frequently used to prevent this toxicity . However , concerns about a negative impact of Ca/Mg infusions on outcome have been raised . We retrospectively assessed the effect of Ca/Mg infusions on the incidence of neurotoxicity and on clinical outcome in advanced colorectal cancer ( ACC ) patients treated in the phase III CAIRO2 study . MATERIAL S AND METHODS Seven hundred and fifty five previously untreated ACC patients were r and omised between treatment with capecitabine , oxaliplatin and bevacizumab or the same combination with the addition of cetuximab . Patients were retrospectively divided into two groups : patients in the Ca/Mg(+ ) group received Ca/Mg at least during their first treatment cycle , and patients in the Ca/Mg(- ) group did not . RESULTS Seven hundred and thirty two patients were evaluable for this analysis . The Ca/Mg(+ ) group consisted of 551 patients , the Ca/Mg(- ) group consisted of 181 patients . The incidence of all grade neurotoxicity in the Ca/Mg(+ ) group and the Ca/Mg(- ) group was 85 % and 92 % , respectively ( p = 0.02 ) , and the incidence of grade ≥ 2 neurotoxicity was 40 % and 45 % , respectively ( p = 0.22 ) . The median PFS in the Ca/Mg(+ ) versus Ca/Mg(- ) group was 10.1 versus 10.7 months ( p = 0.92 ) , the median OS was 19.8 versus 20.7 months ( p = 0.10 ) , and the response rate was 43.1 % versus 50 % ( p = 0.11 ) , respectively . CONCLUSIONS In this largest retrospective analysis to date we observed that Ca/Mg infusions significantly reduced all grade oxaliplatin-related neurotoxicity . Ca/Mg infusions did not affect the clinical efficacy of treatment Meta-analytic investigations sometimes use assessment s of research quality according to a formal protocol as a tool for improving research synthesis . We asked whether a particular quality scoring system could have a direct use in adjusting the summary estimates of a treatment difference . In an empirical study of the relation of quality scores to treatment differences in published meta-analyses of 7 groups of controlled r and omized clinical trials comprising 107 primary studies , we found no relation between treatment difference and overall quality score . We also found no relation between quality score and variation in treatment difference . The level of quality scores has increased at a rate of 9 % per decade for three decades , averaging 0.51 on a scale of 0 to 1 for the 1980s , and leaving much room for improvement . Nevertheless , attention to quality of studies by editors , review ers , and authors may be raising both the level of research done and quality of the reports BACKGROUND Oxaliplatin , a platinum compound , has been commonly used around the world for treating advanced colorectal cancer . The generally recommended dose and schedule of oxaliplatin monotherapy is 130 mg/m(2 ) every 3 weeks . This trial was conducted to evaluate the safety and pharmacokinetics of oxaliplatin monotherapy in Japanese patients with solid tumors . METHODS Oxaliplatin was administered as a 2-h intravenous infusion every 3 weeks at a dose of 90 and 130 mg/m(2 ) . Blood was collected to determine the total platinum and the ultrafiltrate platinum concentrations in plasma in all cycles . RESULTS Nine patients were enrolled ; three were given oxaliplatin monotherapy at 90 mg/m(2 ) and six received 130 mg/m(2 ) . All tumors were colorectal cancer . The major adverse reactions included myelosuppressive , neurological and gastrointestinal toxicities , although most were grade s 1 and 2 at both dose levels . Peripheral sensory neuropathy of without movement disturbance ( grade 1 or 2 ) was observed in all patients at both dose levels . The 130 mg/m(2 ) dose level was not found to be the maximum tolerated dose , but was judged to be the recommended dose . No objective responses were seen and five cases of no change were observed . A bi-exponential open model best described the disappearance of platinum in the plasma , and a tri-exponential open model best described the disappearance of ultrafilterable platinum in the plasma at both dose levels . No racial difference was suggested in the pharmacokinetics of oxaliplatin . CONCLUSIONS The oxaliplatin monotherapy dose schedule of 130 mg/m(2 ) every 3 weeks , recommended worldwide , is acceptable for Japanese patients Aim : Oxaliplatin‐related neurotoxicity is frequently dose‐limiting . Following retrospective studies suggesting neuroprotective effects of calcium and magnesium ( Ca and Mg ) , we conducted a prospect i ve study using nerve conduction studies ( NCS ) to evaluate the effectiveness of such infusions in oxaliplatin‐related neuropathy Background Whether the administration of calcium ( Ca ) and magnesium ( Mg ) can reduce oxaliplatin-related neurotoxicity remains controversial . In addition , little is known about the effects of Ca/Mg on the blood level of platinum or objective tumor progression . Patients and methods Patients receiving modified FOLFOX6 for metastatic colorectal cancer were double-blinded and r and omized to receive additional treatment with Ca/Mg or placebo before and after the administration of oxaliplatin . The plasma and ultrafiltrable concentrations of platinum during the first and fifth cycles of treatment were determined using inductively coupled plasma spectrometry . Results Patients were r and omized to receive Ca/Mg ( Ca/Mg group , n = 17 ) or placebo ( placebo group , n = 16 ) before and after the administration of oxaliplatin ( 85 mg/m2 ) . The incidence of neurotoxicity after six cycles was not significantly different between the two groups . Blood concentrations of platinum at each time and the area under the curve were also not significantly different between the two groups . Furthermore , the response rate ( RR ) and disease control rate ( DCR ) did not differ significantly between the two groups ( Ca/Mg group : RR 36 % , DCR 73 % . Placebo group : RR 40 % , DCR 70 % , P > 0.99 ) . The median progression-free survival time was 9.2 months in the Ca/Mg group and 8.1 months in the control group ; these survival times were not significantly different ( P = 0.56 ) . Conclusion These data are insufficient to conclude with any certainty that the administration of Ca/Mg is not neuroprotective ; however , the administration of Ca/Mg may not have any influence on antitumor activity and the blood concentration profile of platinum in patients receiving oxaliplatin-based chemotherapy BACKGROUND The st and ard adjuvant treatment of colon cancer is fluorouracil plus leucovorin ( FL ) . Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer . We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting . METHODS We r and omly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months . The primary end point was disease-free survival . RESULTS A total of 1123 patients were r and omly assigned to each group . After a median follow-up of 37.9 months , 237 patients in the group given FL plus oxaliplatin had had a cancer-related event , as compared with 293 patients in the FL group ( 21.1 percent vs. 26.1 percent ; hazard ratio for recurrence , 0.77 ; P=0.002 ) . The rate of disease-free survival at three years was 78.2 percent ( 95 percent confidence interval , 75.6 to 80.7 ) in the group given FL plus oxaliplatin and 72.9 percent ( 95 percent confidence interval , 70.2 to 75.7 ) in the FL group ( P=0.002 by the stratified log-rank test ) . In the group given FL plus oxaliplatin , the incidence of febrile neutropenia was 1.8 percent , the incidence of gastrointestinal adverse effects was low , and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment , decreasing to 1.1 percent at one year of follow-up . Six patients in each group died during treatment ( death rate , 0.5 percent ) . CONCLUSIONS Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer OBJECTIVE To assess the efficacy of calcium-magnesium ( Ca/Mg ) infusion and glutathione ( GSH ) for preventing the neurotoxicity induced by oxaliplatin . METHODS This is a r and omized , double blind , placebo controlled clinical trail . The patients receiving FOLFOX4 chemotherapy for their solid tumor were r and omized to receive Ca/Mg , GSH or normal saline with chemotherapy simultaneously . The incidence and severity of oxaliplatin-induced neurotoxicity were observed . The ECOG performance status was recorded and compared among the 3 groups . RESULTS Ninety-three patients admitted in our department from Mar 2006 to Dec 2007 were entered into this study , including 29 patients in the Ca/Mg group , 33 in the GSH group and 31 in the chemotherapy alone group . The incidences of acute neurotoxicity were 82.8 % , 90.9 % and 93.5 % , respectively . At the third cycle , the incidences of grade 1 - 2 chronic neurotoxicity were 37.9 % , 48.5 % and 42.0 % , respectively . No grade 3 neuropathy was observed . After 6 cycles , the incidence of grade 1 - 2 neuropathy was increased to 68.2 % , 88.9 % and 85.2 % , respectively . A lower percentage was observed in Ca/Mg arm without a statistically significant difference , and grade 3 neuropathy occurred in 5 patients . After 9 cycles , the incidence of grade 1 - 2 neuropathy was increased to 81.3 % , 90.0 % and 92.9 % , respectively . Grade 3 neuropathy occurred in another 2 patients . No statistically significant difference was observed among the 3 arms . Changes of patient 's ECOG score after chemotherapy were similar . CONCLUSION This study did n't provide evidence that Ca/Mg infusion and GSH can prevent the oxaliplatin-induced neurotoxicity Oxaliplatin , a platinum-based chemotherapeutic agent , is effective in the treatment of solid tumors , particularly colorectal cancer . During and immediately following oxaliplatin infusion , patients may experience cold-induced paresthesias , throat and jaw tightness , and occasionally focal weakness . We assessed nerve conduction studies and findings on needle electromyography of patients with metastatic colorectal cancer before and during treatment with oxaliplatin . Twenty-two patients had follow-up studies within 48 h following oxaliplatin infusions , and 14 patients had follow-up studies after 3 - 9 treatment cycles . Repetitive compound muscle action potentials and neuromyotonic discharges were observed in the first 24 - 48 h following oxaliplatin infusion , but resolved by 3 weeks . After 8 - 9 treatment cycles , sensory nerve action potential amplitudes declined , without conduction velocity changes or neuromyotonic discharges . The acute neurological symptoms reflect a state of peripheral nerve hyperexcitability that likely represents a transient oxaliplatin-induced channelopathy . Chronic treatment causes an axonal neuropathy similar to other platinum-based chemotherapeutic agents PURPOSE Cumulative sensory neurotoxicity ( sNT ) is the dose-limiting toxicity of oxaliplatin , which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant setting s. In a nonr and omized , retrospective study , intravenous ( IV ) calcium/magnesium ( Ca/Mg ) was associated with reduced oxaliplatin-induced sNT . METHODS Patients with colon cancer undergoing adjuvant therapy with infusional fluorouracil , leucovorin , and oxaliplatin ( FOLFOX ) were r and omly assigned to Ca/Mg ( 1 g calcium gluconate plus 1 g magnesium sulfate pre- and post-oxaliplatin ) or placebo , in a double-blinded manner . The primary end point was the percentage of patients with grade 2 or greater sNT at any time during or after oxaliplatin-based therapy by National Cancer Institute Common Terminology Criteria for Adverse Events ( NCI CTCAE ; version 3 ) criteria . An oxaliplatin-specific sNT scale and patient question naires were also used to assess sNT . After 104 of 300 planned patients were enrolled , the study was closed . This was due to preliminary reports from another trial that suggested that Ca/Mg decreased treatment efficacy ; these data were subsequently found to be incorrect . RESULTS Overall , 102 patients were available for analysis . Ca/Mg decreased the incidence of chronic , cumulative , grade 2 or greater sNT , as measured by NCI CTCAE ( P = .038 ) and also by the oxaliplatin-specific sNT scale ( P = .018 ) . In addition , acute muscle spasms associated with oxaliplatin were significantly reduced ( P = .01 ) No effect on acute , cold-induced sNT was found . No substantial differences in adverse effects were noted between Ca/Mg and placebo . CONCLUSION Despite early termination and decreased statistical power , this study supports IV Ca/Mg as an effective neuroprotectant against oxaliplatin-induced cumulative sNT in adjuvant colon cancer PURPOSE In a previous study of treatment for advanced colorectal cancer , the LV5FU2 regimen , comprising leucovorin ( LV ) plus bolus and infusional fluorouracil ( 5FU ) every 2 weeks , was superior to the st and ard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen . This phase III study investigated the effect of combining oxaliplatin with LV5FU2 , with progression-free survival as the primary end point . PATIENTS AND METHODS Four hundred twenty previously untreated patients with measurable disease were r and omized to receive a 2-hour infusion of LV ( 200 mg/m(2)/d ) followed by a 5FU bolus ( 400 mg/m(2)/d ) and 22-hour infusion ( 600 mg/m(2)/d ) for 2 consecutive days every 2 weeks , either alone or together with oxaliplatin 85 mg/m(2 ) as a 2-hour infusion on day 1 . RESULTS Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival ( median , 9.0 v 6.2 months ; P = .0003 ) and better response rate ( 50.7 % v 22.3 % ; P = .0001 ) when compared with the control arm . The improvement in overall survival did not reach significance ( median , 16.2 v 14.7 months ; P = . 12 ) . LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia ( 41 . 7 % v 5.3 % of patients ) , grade 3/4 diarrhea ( 11.9 % v 5.3 % ) , and grade 3 neurosensory toxicity ( 18.2 % v 0 % ) , but this did not result in impairment of quality of life ( QoL ) . Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment ( P = .004 ) . CONCLUSION The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer , demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of |
13,384 | 22,767,204 | The 5-antibody immunohistochemistry panel and 70-gene signature satisfied Level II evidence for estimating DRR and OS .
Adjuvant !
Online satisfied Level II evidence for estimating DRR , OS , and chemotherapy response .
The 5-gene expression index satisfied Level III evidence for predicting DRR . | BACKGROUND At least 14 stratifiers exist to assess recurrence risk , chemotherapy response , and overall survival ( OS ) in women with early-stage breast cancer ( ESBC ) .
These stratifiers have not been compared using a recently developed rigorous framework .
We performed a systematic review of the literature on clinical validity/utility , change in clinical practice , and economic implication s of ESBC stratifiers . | Introduction The HOXB13:IL17BR index has been identified to predict clinical outcome in the setting of adjuvant tamoxifen monotherapy of breast cancer . Further studies have shown that HOXB13 in particular can indicate benefit of prolonged tamoxifen treatment . Patients with high-expressing tumors did not benefit from prolonged treatment , suggesting that HOXB13 might be involved in tamoxifen resistance . No studies have been made regarding the HOXB13 protein levels in breast cancer . The aim of our study was to investigate whether tamoxifen benefit can be correlated to different levels of HOXB13 protein expression . Methods We used immunohistochemistry to analyze protein levels of HOXB13 in tumor sample s from 912 postmenopausal node-negative breast cancer patients r and omized to adjuvant tamoxifen therapy or no endocrine treatment . Results Tamoxifen-treated patients with estrogen receptor-positive tumors expressing none or low levels of HOXB13 had a clear benefit from tamoxifen in terms of longer distant recurrence-free survival ( DRFS ) ( hazard ratio = 0.38 , 95 % confidence interval = 0.23 to 0.60 , P = 0.000048 ) . However , for patients with a high or intermediate HOXB13 tumor expression , tamoxifen did not prolong the DRFS compared with the untreated patients ( hazard ratio = 0.88 , 95 % confidence interval = 0.47 to 1.65 , P = 0.69 ) . Interaction between HOXB13 expression and benefit from tamoxifen was statistically significant for DRFS ( P = 0.035 ) . No prognostic value could be ascribed to HOXB13 among systemically untreated patients . Conclusions A high HOXB13 expression was associated with decreased benefit from tamoxifen , which indicates that HOXB13 protein level may be used as a predictive marker for tamoxifen treatment BACKGROUND The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures . METHODS We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction ( RT-PCR ) assay of 21 prospect ively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative , tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14 . The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospect ively defined algorithm to calculate a recurrence score and to determine a risk group ( low , intermediate , or high ) for each patient . RESULTS Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks . The proportions of patients categorized as having a low , intermediate , or high risk by the RT-PCR assay were 51 , 22 , and 27 percent , respectively . The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk , intermediate-risk , and high-risk groups were 6.8 percent ( 95 percent confidence interval , 4.0 to 9.6 ) , 14.3 percent ( 95 percent confidence interval , 8.3 to 20.3 ) , and 30.5 percent ( 95 percent confidence interval , 23.6 to 37.4 ) . The rate in the low-risk group was significantly lower than that in the high-risk group ( P<0.001 ) . In a multivariate Cox model , the recurrence score provided significant predictive power that was independent of age and tumor size ( P<0.001 ) . The recurrence score was also predictive of overall survival ( P<0.001 ) and could be used as a continuous function to predict distant recurrence in individual patients . CONCLUSIONS The recurrence score has been vali date d as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative , estrogen-receptor-positive breast cancer PURPOSE The 70-gene prognosis-signature is a prognostic tool for early breast cancer analysis . In addition to scientific evidence , implementation of the signature in clinical trials and daily practice requires logistical feasibility . The aim of our study was to test logistics for gene expression profiling on fresh frozen tumour tissue in the preparation for the prospect i ve , multinational Microarray In Node-negative Disease may Avoid ChemoTherapy ( MINDACT ) trial . METHODS Sixty-four patients were included in six European hospitals . Fresh frozen tumour sample s were shipped on dry ice to Agendia B.V. , where RNA was isolated and subsequently hybridised on the 70-gene prognosis-signature ( MammaPrint ) . RESULTS Tumour sample s were obtained in 60 of 64 patients . Among the 60 sample s , 11 contained insufficient tumour cells ( < 50 % ) and three contained insufficient RNA quality . All 46 sample s eligible for genomic profiling were successfully hybridised , and the results were reported on average within 4 - 5d . CONCLUSION Gene expression profiling on fresh frozen tissue is feasible in daily clinical practice Purpose Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment . We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy . Patients and Methods Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks × 3 and docetaxel 40 mg/M2 weekly × 6 ; treatment order was r and omly assigned . Pretreatment core biopsy sample s were interrogated for genes that might correlate with pathologic complete response ( pCR ) . In addition to the individual genes , the correlation of the Oncotype DX Recurrence Score with pCR was examined . Results Of 70 patients enrolled in the parent trial , core biopsies sample s with sufficient RNA for gene analyses were available from 45 patients ; 9 ( 20 % ) had inflammatory breast cancer ( IBC ) . Six ( 14 % ) patients achieved a pCR . Twenty-two of the 274 c and i date genes assessed correlated with pCR ( p < 0.05 ) . Genes correlating with pCR could be grouped into three large clusters : angiogenesis-related genes , proliferation related genes , and invasion-related genes . Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR . In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer ; twenty-four ( 9 % ) of the genes were differentially expressed ( p < 0.05 ) , 5 were upregulated and 19 were downregulated in IBC . Conclusion Gene expression analysis on core biopsy sample s is feasible and identifies c and i date genes that correlate with pCR to primary chemotherapy . Gene expression in IBC differs significantly from noninflammatory breast cancer Introduction Patients with early-stage breast cancer , treated with endocrine therapy , have approximately 90 % 5-year disease-free survival . However , for patients at higher risk of relapse despite endocrine therapy , additional adjuvant therapy , such as chemotherapy , may be indicated . The challenge is to prospect ively identify such patients . The Mammostrat ® test uses five immunohistochemical markers to stratify patients on tamoxifen therapy into risk groups to inform treatment decisions . We tested the efficacy of this panel in a mixed population of cases treated in a single center with breast-conserving surgery and long-term follow-up . Methods Tissue microarrays from a consecutive series ( 1981 to 1998 ) of 1,812 women managed by wide local excision and postoperative radiotherapy were collected following appropriate ethical review . Of 1,390 cases stained , 197 received no adjuvant hormonal or chemotherapy , 1,044 received tamoxifen only , and 149 received a combination of hormonal therapy and chemotherapy . Median age at diagnosis was 57 , 71 % were postmenopausal , 23.9 % were node-positive and median tumor size was 1.5 cm . Sample s were stained using triplicate 0.6 mm2 tissue microarray cores , and positivity for p53 , HTF9C , CEACAM5 , NDRG1 and SLC7A5 was assessed . Each case was assigned a Mammostrat ® risk score , and distant recurrence-free survival ( DRFS ) , relapse-free survival ( RFS ) and overall survival ( OS ) were analyzed by marker positivity and risk score . Results Increased Mammostrat ® scores were significantly associated with reduced DRFS , RFS and OS in estrogen receptor (ER)-positive breast cancer ( P < 0.00001 ) . In multivariate analyses the risk score was independent of conventional risk factors for DRFS , RFS and OS ( P < 0.05 ) . In node-negative , tamoxifen-treated patients , 10-year recurrence rates were 7.6 ± 1.5 % in the low-risk group versus 20.0 ± 4.4 % in the high-risk group . Further , exploratory analyses revealed associations with outcome in both ER-negative and untreated patients . Conclusions This is the fifth independent study providing evidence that Mammostrat ® can act as an independent prognostic tool for ER-positive , tamoxifen-treated breast cancer . In addition , this study revealed for the first time a possible association with outcome regardless of node status and ER-negative tumors . When viewed in the context of previous results , these data provide further support for this antibody panel as an aid to patient management in early-stage breast cancer Background The two-gene expression ratio HOXB13:IL17BR has been proposed to predict the outcome of tamoxifen-treated breast cancer patients . We intended to examine whether this ratio can predict the benefit of 5 years vs. 2 years of tamoxifen treatment of postmenopausal patients . A further objective was to investigate any prognostic effects of the ratio in systematic ally untreated premenopausal patients . Based on the current knowledge of HOXB13 and IL17BR , we hypothesized that these genes may have individual prognostic or predictive power . Patients and methods Expression of HOXB13 and IL17BR were quantified by real-time PCR in tumors from 264 r and omized postmenopausal patients and 93 systemically untreated premenopausal patients . Results A high HOXB13:IL17BR ratio was associated with aggressive tumor characteristics , as were low levels of IL17BR alone . The ratio and HOXB13 alone predicted recurrence-free survival after endocrine treatment , with a benefit of prolonged treatment in estrogen receptor-positive patients correlated to a low ratio ( recurrence rate ratio : RR = 0.39 ; P = 0.030 ) , or low expression of HOXB13 ( RR = 0.37 ; P = 0.015 ) . No difference in recurrence-free survival was seen for the high ratio or high HOXB13 subgroups . The predictive value of HOXB13 and HOXB13:IL17BR was significant in multivariate analysis . In the systemically untreated cohort , only IL17BR showed independent prognostic significance . Conclusion We conclude that the ratio or HOXB13 alone can predict the benefit of endocrine therapy , with a high ratio or a high expression rendering patients less likely to respond . We have also shown that IL17BR might be an independent prognostic factor in breast cancer PURPOSE The 21-gene Recurrence Score ( RS ) assay has been vali date d to quantify the risk of distant recurrence in tamoxifen-treated patients with lymph node-negative , estrogen receptor-positive breast cancer and predict magnitude of chemotherapy benefit . This multicenter study was design ed to prospect ively examine whether RS affects physician and patient adjuvant treatment selection and satisfaction . PATIENTS AND METHODS Before and after obtaining the 21-gene RS assay , medical oncologists stated their adjuvant treatment recommendation and confidence in it . Patients also indicated their treatment choice pre- and post-RS assay . Patients completed measures for decisional conflict , anxiety , and quality of life . RESULTS Seventeen medical oncologists at one community and three academic practice s consecutively enrolled 89 assessable patients . The medical oncologist treatment recommendation changed for 28 patients ( 31.% ) . Twenty-four patients ( 27 % ) changed their treatment decision . The largest change after the RS results was conversion from the medical oncologist 's pretest recommendation for chemotherapy plus hormonal therapy ( CHT ) to post-test recommendation for hormone therapy ( HT ) in 20 cases ( 22.5 % ) . Nine patients ( 10.1 % ) changed their treatment decision from CHT to HT . RS results increased medical oncologist confidence in their treatment recommendation in 68 cases ( 76 % ) . Patient anxiety and decisional conflict were significantly lower after RS results . CONCLUSION The results of this study indicate that the RS assay impacts medical oncologist adjuvant treatment recommendations , patient treatment choice , and patient anxiety Novel genetic profiling tests of breast cancer tissue have been shown to be prognostic for overall survival and predictive of local and distant rates of recurrence in breast cancer patients . One of these tests , Oncotype DXtrade mark , is a diagnostic test comprised of a 21-gene assay applied to paraffin-embedded breast cancer tissue , which allows physicians to predict subgroups of hormone-receptor-positive , node-negative patients who may benefit from hormonal therapy alone or require adjuvant chemotherapy to attain the best survival outcome . The results of the assay are converted to a recurrence score ( 0 - 100 ) that has been found to be predictive of 10- and 15-year local and distant recurrence in node-negative , estrogen-receptor-positive breast cancer patients . Previous studies have shown that patients with high recurrence scores benefit from adjuvant chemotherapy , whereas patients with low recurrence scores do not . To evaluate the ability to guide treatment decisions in the group with a mid-range recurrence score , the North American Cooperative Groups developed the Trial Assessing IndiviuaLized Options for Treatment for breast cancer , a r and omized trial of chemotherapy followed by hormonal therapy versus hormonal therapy alone on invasive disease-free survival-ductal carcinoma in situ ( IDFS-DCIS ) survival in women with node-negative , estrogen-receptor-positive breast cancer with a recurrence score of 11 - 25 . The study was initiated in May 2006 and approximately 4500 patients will be r and omized . This article describes the rationale , methodology , statistical ana-lysis and implication s of the results on clinical practice The development of tumor biomarkers ready for clinical use is complex . We propose a refined system for biomarker study design , conduct , analysis , and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies , including those using archived specimens . Although fully prospect i ve r and omized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold st and ard , such trials are costly , so we discuss more efficient indirect " prospect ive-retrospective " design s using archived specimens . In particular , we propose new guidelines that stipulate that 1 ) adequate amounts of archived tissue must be available from enough patients from a prospect i ve trial ( which for predictive factors should generally be a r and omized design ) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial ; 2 ) the test should be analytically and preanalytically vali date d for use with archived tissue ; 3 ) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier ; and 4 ) the results from archived specimens should be vali date d using specimens from one or more similar , but separate , studies Purpose : To test the association between risk stratification and outcome in a prospect ively design ed , blinded retrospective study using tissue arrays of available paraffin blocks from the estrogen receptor – expressing , node-negative sample s from the National Surgical Adjuvant Breast and Bowel Project B14 and B20 tamoxifen and chemotherapy trials . Experimental Design : Tissue arrays were stained by immunohistochemistry targeting p53 , NDRG1 , SLC7A5 , CEACAM5 , and HTF9C . Risk stratification was done using predefined scoring rules , algorithm for combining scores , and cutoff points for low-risk , moderate-risk , and high-risk patient strata . Results : In a univariate Cox model , this test was significantly associated with recurrence-free interval [ HR , 1.3 ( 95 % confidence interval , 1.1 - 1.6 ) ; P = 0.006 ] . In a multivariate model it contributed information independent of age , tumor size , and menopausal status ( P = 0.007 ) . The Kaplan-Meier estimates of the proportion of recurrence-free after 10 years were 73 % , 86 % , and 85 % for the high-risk , moderate-risk , and low-risk groups ( P = 0.001 ) . The Kaplan-Meier estimates of the breast-cancer-specific-death rate were 23 % , 10 % , and 9 % ( P < 0.0001 ) . Exploratory analysis in patients ≥60 years old showed Kaplan-Meier estimates of the proportion of recurrence-free of 78 % , 89 % , and 92 % . Both high-risk and low-risk groups showed significant improvement on treatment with cytotoxic chemotherapy . Conclusions : Immunohistochemistry using five monoclonal antibodies assigns breast cancer patients to a risk index that was significantly associated with clinical outcome among the estrogen receptor – expressing , node-negative tamoxifen-treated patients . It seems that the test may be able to identify patients who have greater absolute benefit from adjuvant chemotherapy compared with unstratified patient population s. Exploratory analysis suggests that this test will be most useful in clinical decision making for postmenopausal patients Previously , we had identified gene expression patterns that predicted response to neoadjuvant docetaxel . Other studies have vali date d that a high Recurrence Score ( RS ) by the 21-gene RT-PCR assay is predictive of worse prognosis but better response to chemotherapy . We investigated whether tumor expression of these 21 genes and other c and i date genes can predict response to docetaxel . Core biopsies from 97 patients were obtained before treatment with neoadjuvant docetaxel ( 4 cycles , 100 mg/m2 q3 weeks ) . Three 10-μm FFPE sections were su bmi tted for quantitative RT-PCR assays of 192 genes that were selected from our previous work and the literature . Of the 97 patients , 81 ( 84 % ) had sufficient invasive cancer , 80 ( 82 % ) had sufficient RNA for QRTPCR assay , and 72 ( 74 % ) had clinical response data . Mean age was 48.5 years , and the median tumor size was 6 cm . Clinical complete responses ( CR ) were observed in 12 ( 17 % ) , partial responses in 41 ( 57 % ) , stable disease in 17 ( 24 % ) , and progressive disease in 2 patients ( 3 % ) . A significant relationship ( P < 0.05 ) between gene expression and CR was observed for 14 genes , including CYBA . CR was associated with lower expression of the ER gene group and higher expression of the proliferation gene group from the 21 gene assay . Of note , CR was more likely with a high RS ( P = 0.008 ) . We have established molecular profiles of sensitivity to docetaxel . RT-PCR technology provides a potential platform for a predictive test of docetaxel chemosensitivity using small amounts of routinely processed material PURPOSE Patients with breast cancer experience progression and respond to treatment in diverse ways , but prognostic and predictive tools for the oncologist are limited . We have used gene expression data to guide the production of hundreds of novel antibody reagents to discover novel diagnostic tools for stratifying carcinoma patients . PATIENTS AND METHODS One hundred forty novel and 23 commercial antisera , selected on their ability to differentially stain tumor sample s , were used to stain paraffin blocks from a retrospective breast cancer cohort . Cox proportional hazards and regression tree analysis identified minimal panels of reagents able to predict risk of recurrence . We tested the prognostic association of these prospect ively defined algorithms in two independent cohorts . RESULTS In both validation cohorts , the Kaplan-Meier estimates of recurrence confirmed that both the Cox model using five reagents ( p53 , NDRG1 , CEACAM5 , SLC7A5 , and HTF9C ) and the regression tree model using six reagents ( p53 , PR , Ki67 , NAT1 , SLC7A5 , and HTF9C ) distinguished estrogen receptor (ER)-positive patients with poor outcomes . The Cox model was superior and distinguished patients with poor outcomes from patients with good or moderate outcomes with a hazard ratio of 2.21 ( P = .0008 ) in validation cohort 1 and 1.88 ( P = .004 ) in cohort 2 . In multivariable analysis , the calculated risk of recurrence was independent of stage , grade , and lymph node status . A model proposed for ER-negative patients failed validation in the independent cohorts . CONCLUSION A panel of five antibodies can significantly improve on traditional prognosticators in predicting outcome for ER-positive breast cancer patients BACKGROUND A microarray-based 70-gene prognosis signature might improve the selection of patients with node-negative breast cancer for adjuvant systemic treatment . The main aims of this MicroarRAy PrognoSTics in Breast CancER ( RASTER ) study were to assess prospect ively the feasibility of implementation of the 70-gene prognosis signature in community-based setting s and its effect on adjuvant systemic treatment decisions when considered with treatment advice formulated from the Dutch Institute for Healthcare Improvement ( CBO ) and other guidelines . METHODS Between January , 2004 and December , 2006 , 812 women aged under 61 years with primary breast carcinoma ( clinical T1 - 4N0M0 ) were enrolled . Fresh tumour sample s were collected in 16 hospitals in the Netherl and s within 1 h after surgery . Clinicopathological factors were collected and microarray analysis was done with a custom- design ed array chip that assessed the mRNA expression index of the 70 genes previously identified for the prognostic signature . Patients with a " good " signature were deemed to have a good prognosis and , therefore , could be spared adjuvant systemic treatment with its associated adverse effects , whereas patients with a " poor " signature were judged to have a poor prognosis and should be considered for adjuvant systemic treatment . Concordance between risk predicted by the prognosis signature and risk predicted by commonly used clinicopathological guidelines ( ie , St Gallen guidelines , Nottingham Prognostic Index , and Adjuvant ! Online ) was assessed . FINDINGS Of 585 eligible patients , 158 patients were excluded because of sampling failure ( n=128 ) and incorrect procedure ( n=30 ) . Prognosis signatures were assessed in 427 patients . The 70-gene prognosis signature identified 219 ( 51 % ) patients with good prognosis and 208 ( 49 % ) patients with poor prognosis . The Dutch CBO guidelines identified 184 patients ( 43 % ) with poor prognosis , which was discordant with those findings obtained with the prognosis signature in 128 ( 30 % ) patients . Oncologists recommended adjuvant treatment in 203 ( 48 % ) patients based on Dutch CBO guidelines , in 265 ( 62 % ) patients if the guidelines were used with the prognosis signature , and in 259 ( 61 % ) patients if Dutch CBO guidelines , prognosis signature , and patients ' preferences for treatment were all taken into account . Adjuvant ! Online guidelines identified more patients with poor prognosis than did the signature alone ( 294 [ 69 % ] ) , and discordance with the signature occurred in 160 ( 37 % ) patients . St Gallen guidelines identified 353 ( 83 % ) patients with poor prognosis with the signature and discordance in 168 ( 39 % ) patients . Nottingham Prognostic Index recorded 179 ( 42 % ) patients with poor prognosis with the signature and discordance in 117 ( 27 % ) patients . INTERPRETATION Use of the prognosis signature is feasible in Dutch community hospitals . Adjuvant systemic treatment was advised less often when the more restrictive Dutch CBO guidelines were used compared with that finally given after use of the prognosis signature . For the other guidelines assessed , less adjuvant chemotherapy would be given when the data based on prognosis signature alone are used , which might spare patients from adverse effects and confirms previous findings . Future studies should assess whether use of the prognosis signature could improve survival or equal survival while avoiding unnecessary adjuvant systemic treatment without affecting patients ' survival , and further assess the factors that physicians use to recommend adjuvant systemic treatment The prognostic accuracy for distant recurrence‐free survival using a 21‐gene reverse‐transcriptase polymerase chain reaction ( RT‐PCR ) assay underwent validation in 668 lymph node‐negative , estrogen receptor‐positive women with early‐stage breast cancer receiving tamoxifen on National Surgical Adjuvant Breast Program ( NSABP ) B‐14 . The predictive accuracy for treatment efficacy also underwent validation in 651 patients r and omized on NSABP B‐20 and 645 patients on NSABP B‐14 PURPOSE The 21-gene recurrence score ( RS ) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive , lymph node-negative breast cancer treated with adjuvant tamoxifen . The relationship between the RS and chemotherapy benefit is not known . METHODS The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B20 trial . Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS . RESULTS A total of 651 patients were assessable ( 227 r and omly assigned to tamoxifen and 424 r and omly assigned to tamoxifen plus chemotherapy ) . The test for interaction between chemotherapy treatment and RS was statistically significant ( P = .038 ) . Patients with high-RS ( > or = 31 ) tumors ( ie , high risk of recurrence ) had a large benefit from chemotherapy ( relative risk , 0.26 ; 95 % CI , 0.13 to 0.53 ; absolute decrease in 10-year distant recurrence rate : mean , 27.6 % ; SE , 8.0 % ) . Patients with low-RS ( < 18 ) tumors derived minimal , if any , benefit from chemotherapy treatment ( relative risk , 1.31 ; 95 % CI , 0.46 to 3.78 ; absolute decrease in distant recurrence rate at 10 years : mean , -1.1 % ; SE , 2.2 % ) . Patients with intermediate-RS tumors did not appear to have a large benefit , but the uncertainty in the estimate can not exclude a clinical ly important benefit . CONCLUSION The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative , estrogen receptor-positive breast cancer , but also predicts the magnitude of chemotherapy benefit PURPOSE Adjuvant ! is a st and ardized vali date d decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy . Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features . PATIENTS AND METHODS A sample of 465 patients with hormone receptor ( HR ) -positive breast cancer with zero to three positive axillary nodes who did ( n = 99 ) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay . Histologic grade and HR expression were evaluated locally and in a central laboratory . RESULTS Recurrence Score ( RS ) was a highly significant predictor of recurrence , including node-negative and node-positive disease ( P < .001 for both ) and when adjusted for other clinical variables . RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant ! that was adjusted to 5-year outcomes . The 5-year recurrence rate was only 5 % or less for the estimated 46 % of patients who have a low RS ( < 18 ) . CONCLUSION The 21-gene assay was a more accurate predictor of relapse than st and ard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging , such as tumor size and lymph node involvement . The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments Adjuvant ! © Online ( Adjuvant ! ) is a user-friendly , web-based tool that provides estimates of adjuvant therapy outcomes for individual patients . While reliable evidence underpins estimates for most patient cohorts , there is a paucity of data on the effect of adding chemotherapy to complete estrogen blockade for premenopausal women with estrogen-receptor positive breast cancer . International Breast Cancer Study Group ( IBCSG ) Trial 11 - 93 enrolled 174 premenopausal women with estrogen-receptor positive , node-positive breast cancer . Among these patients , 55 % had one positive axillary lymph node and 97 % had three or fewer positive nodes . Patients were r and omized to receive ovarian function suppression plus 5 years of tamoxifen with or without anthracycline-based chemotherapy . Estimated hazard rates and corresponding 10-year relapse-free survival percentages obtained from Trial 11 - 93 data were compared with those predicted using Adjuvant!. The 10-year relapse-free survival percentages predicted from Adjuvant ! were 64.4 % ( 95 % CI , 61.9–67.2 % ) for endocrine therapy alone and 74.9 % ( 95 % CI , 73.1–76.8 % ) for chemoendocrine therapy . By contrast , these estimates in Trial 11 - 93 were 76.4 % ( 95 % CI , 65.8–84.0 % ) for endocrine therapy alone and 74.9 % ( 95 % CI , 64.5–82.7 % ) for chemoendocrine therapy . The Adjuvant ! estimate for the endocrine-alone control group is lower than that observed in Trial 11 - 93 ( P = 0.03 ) , while the estimates for the two chemoendocrine therapy groups are similar . Adjuvant ! appears to underestimate the effectiveness of adjuvant endocrine therapy alone for premenopausal women with endocrine responsive breast cancer , thus overestimating the added benefit , if any , from chemotherapy for this patient population PURPOSE The goal of the computer program Adjuvant ! is to allow health professionals and their patients with early breast cancer to make more informed decisions about adjuvant therapy . METHODS Actuarial analysis was used to project outcomes of patients with and without adjuvant therapy based on estimates of prognosis largely derived from Surveillance , Epidemiology , and End- Results data and estimates of the efficacy of adjuvant therapy based on the 1998 overviews of r and omized trials of adjuvant therapy . These estimates can be refined using the Prognostic Factor Impact Calculator , which uses a Bayesian method to make adjustments based on relative risks conferred and prevalence of positive test results . RESULTS From the entries of patient information ( age , menopausal status , comorbidity estimate ) and tumor staging and characteristics ( tumor size , number of positive axillary nodes , estrogen receptor status ) , baseline prognostic estimates are made . Estimates for the efficacy of endocrine therapy ( 5 years of tamoxifen ) and of polychemotherapy ( cyclophosphamide/methotrexate/fluorouracil-like regimens , or anthracycline-based therapy , or therapy based on both an anthracycline and a taxane ) can then be used to project outcomes presented in both numerical and graphical formats . Outcomes for overall survival and disease-free survival and the improvement seen in clinical trials , are reasonably modeled by Adjuvant ! , although an ideal validation for all patient subsets with all treatment options is not possible . Additional speculative estimates of years of remaining life expectancy and long-term survival curves can also be produced . Help files supply general information about breast cancer . The program 's Internet links supply national treatment guidelines , cooperative group trial options , and other related information . CONCLUSION The computer program Adjuvant ! can play practical and educational roles in clinical setting PURPOSE The Oncotype Dx Recurrence Score ( RS ) , is often employed in patients with estrogen receptor-positive , node negative ( ER+LN- ) breast cancer . We investigated the impact of the RS on actual chemotherapy administration and the effect of the assay on a panel of breast oncology experts . PATIENTS AND METHODS The prospect i ve adjuvant chemotherapy recommendations ( prior to RS ) and actual adjuvant therapy ( after RS ) for consecutive patients with ER+LN- breast cancer were recorded . After 6 months and with the same information , a panel of five experts made adjuvant therapy recommendations with and without RS and rated the strength of their recommendations . Rates of panel consensus , recommendation changes , and changes in recommendation strength were compared . RESULTS There were 29 patients ( 28 women ) . RS results altered the plan for chemotherapy in 9 patients ( 31 % ) ; 7 of 13 patients ( 54 % ) initially recommended for chemotherapy did not receive it , and 2 of 16 ( 13 % ) received chemotherapy following initial recommendations against it . RS results changed the panel 's chemotherapy recommendation in 7 patients ( 24 % ) : 5 of 12 ( 42 % ) recommendations for changed to against , and 2 of 17 ( 12 % ) recommendations against changed to for chemotherapy . RS increased consensus by the panel 10 % , but did not increase the reported strength in chemotherapy recommendations . CONCLUSIONS RS results were associated with real-world decision changes in 31 % of patients and 24 % of panel recommendations and increased panel consensus by 10 % . However RS did not increase the strength of panelist 's recommendations BACKGROUND Decision aids are tools that help patients make specific and deliberative choices among options . This study was a group r and omized controlled trial of a novel decision aid to help patients with breast cancer make adjuvant therapy ( AT ) decisions . METHODS Fourteen oncology practice s ( n=58 physicians ) were r and omized to receive the decision aid or a control pamphlet . Complete data were obtained from 405 patient-oncologist pairs . Eligible patients had stage I-III disease and had completed their primary treatment . The decision aid is a simple to use computer program , titled Adjuvant ! , that provides estimates of outcome with and without AT . Graphical representations of outcome are shared with patients . Consultations were audiotaped , patients interviewed , and physicians completed a self-administered survey . RESULTS In a multivariable model , the 54 patients ( 13.3 % ) who took no AT were more likely to have received the decision aid ( p=0.02 ) . A differential effect of the Adjuvant ! Decision Guide was noted between node negative and positive patients . It was stated by 86.2 % of patients that the decision aid was influential when making their treatment decision . Over 95 % of patients reported that the Adjuvant Decision Guide was easy to underst and and 75 % of physicians believed that it helped them underst and their patient 's treatment preferences and 81.4 % reported the information as useful for themselves . CONCLUSIONS This study showed that a decision aid made a difference in the choice of whether or not to take AT . The decision aid allowed patients and physicians to consider the benefits of AT in an easy to underst and format . Treatment decisions were more individualized for patients in the intervention than in the control group . The use of the decision aid was acceptable to both patients and physicians Both the 70-gene signature and the 21-gene assay are novel prognostic tests used to guide adjuvant chemotherapy decisions in patients with early breast cancer . Although the results of ongoing prospect i ve trials will only become available in some years , the tests have already been included in clinical guidelines such as St. Gallen ’s . In literature , the cost-effectiveness ( CE ) of both tests as compared to conventional prognostic tests has been described . We report on a direct comparison of CE ; as different compliance rates were reported , we also taken these into account . A Markov decision model with a time horizon of 20 years was developed to assess the effects , costs and CE of three alternatives ; 21-gene , 70-gene , and St. Gallen ( SG ) or Adjuvant Online ( AO ) , dependent on the data set used in patients with early , node-negative , breast cancer . Sensitivity and specificity were based on two data sets , incorporating compliances rates based on literature . For both data sets , whereas the 70-gene signature yielded more quality adjusted life years ( QALYs ) and was less costly ; the 21-gene amounted more life years ( LYs ) but was more costly . The decision uncertainty surrounding the probability of CE of the Thomassen-series amounted 55 % for both cost/LY and cost/QALY , for the Fan-series 80 % for LY and 65 % for QALYs . Taking reported compliance with discordant test results into account , in general , the effect of all strategies decreased , while the costs increased , without relatively influencing the CEA performance . This comparison indicates that the performances of the 70-gene and the 21-gene based on reported studies are close . The 21-gene has the highest probability of being cost-effective when focusing on cost/LY , while focusing on cost/QALY , the 70-gene signature was most cost-effective . The level of compliance can have serious impact on the CE . With additional data , preferably from head-to-head outcome studies and especially on compliance concerning discordant test results , calculations can be made with higher degrees of certainty |
13,385 | 24,950,727 | Since QCA is predicated on the assumption that multiple pathways might lead to the same outcome and does not assume a linear additive model in terms of changes to a particular condition ( that is , it can cope with ‘ tipping points ’ in complex interventions ) , it appears not to suffer from some of the limitations of the statistical methods often used in meta- analysis .
Results The worked example shows how the QCA reveals that our initial theories of change were unable to distinguish between ‘ effective ’ and ‘ highly effective ’ interventions .
Through the iterative QCA process , other intervention characteristics are identified that better explain the observed results . | Background Systematic review s that address policy and practice questions in relation to complex interventions frequently need not only to assess the efficacy of a given intervention but to identify which intervention - and which intervention components - might be most effective in particular situations .
Here , intervention replication is rare , and commonly used synthesis methods are less useful when the focus of analysis is the identification of those components of an intervention that are critical to its success .
Methods Having identified initial theories of change in a previous analysis , we explore the potential of qualitative comparative analysis ( QCA ) to assist with complex syntheses through a worked example .
Developed originally in the area of political science and historical sociology , a QCA aims to identify those configurations of participant , intervention and context ual characteristics that may be associated with a given outcome .
Analysing studies in these terms facilitates the identification of necessary and sufficient conditions for the outcome to be obtained . | Breastfeeding rates among low-income women in the east-south- central United States are among the lowest in the country . This study examined the effect of a peer counseling program on breastfeeding initiation and duration in a low-income rural population in West Tennessee . A postpartum survey and chart review were conducted with WIC clients at nine health departments . Response rate was 99 % ( 291/293 ) . Breastfeeding initiation and duration at 6 weeks were increased in the peer counselor group ( n= 156 ) compared with women in the no-peer counselor group ( n= 135 ) ( 53 % vs. 33%,p<0.001 , and 26 % vs. 13%,p=0.006 , respectively ) . Multivariate analysis revealed that women in the peer counselor group were significantly more likely to initiate breastfeeding ( OR=2.43 , 95 % CI=1.23 - 4.67 ) and to be breastfeeding at 6 weeks ( OR=2.78 , 95 % CI=2.08 - 9.5 1 ) , than those in the no-peer counselor group We evaluated the single and combined effects of introducing a motivational video and peer counseling into four matched WIC clinics on breastfeeding initiation and continuation at 7 - 10 days among African-American WIC participants . Of the 242 women with complete data , 48 % initiated breastfeeding , but only 31 % were still breastfeeding at 7 - 10 days . Initiation was associated with cesarean delivery , infant feeding instruction , no artificial milk discharge pack , attending the peer counselor only-intervention site , and intention to breastfeed . Continuation was influenced by infant feeding instruction , no artificial milk discharge pack , and intention to breastfeed . Overall , trends toward a positive impact of the breastfeeding promotion activities were evident but weak , and largely gone by 7 - 10 days postpartum BACKGROUND The purpose of this demonstration project was to test the effectiveness of a volunteer peer counseling program for promoting breastfeeding in a community . METHODS The two-year project was conducted in Iowa from September 1994 to September 1996 . Both intervention and control groups were rural low-income pregnant and postpartum women who qualified for the Women , Infants and Children 's ( WIC ) nutritional program . The intervention was initiated in two counties with 143 clients , of whom 72 completed the project . The control group was drawn from six counties that had received no significant breastfeeding promotion programs during the previous three years . The intervention was the assignment of trained volunteers with previous successful personal experience with breastfeeding as peer counselors to low-income pregnant women . Both before and after the baby was born , the volunteers taught a series of in-home , one-to-one lessons about healthy diet and breastfeeding , and maintained informal contact to answer questions or help with concerns . RESULTS Women in the intervention group improved dietary intake when compared with the control group . Knowledge of breastfeeding and good nutrition improved slightly . Eighty-two percent of intervention compared with 31 percent of control group women initiated breastfeeding . Mean duration of breastfeeding for intervention and control group women was 5.7 and 2.5 weeks , respectively . At 4 weeks , 56 percent of intervention and 10 percent of control group women were still breastfeeding . CONCLUSION A volunteer peer counseling program that provides low-income women with role models , accurate information , support , and encouragement can increase the duration of breastfeeding , and thus contribute to healthier infants BACKGROUND Breastfeeding can ameliorate some of the complex health issues faced by low-income families . Women who breastfeed and their infants have lower health care costs compared with those who formula feed . Increasing the duration of breastfeeding is recognized as a national priority , particularly for low-income women . This community-based r and omized clinical trial involving low-income mothers compared usual care with an intervention comprising hospital and home visits , and telephone support by a community health nurse/peer counselor team for 6 months after delivery . METHODS Forty-one women were recruited after delivery of a full-term singleton infant and r and omly assigned to intervention or usual care groups . RESULTS Women receiving the community health intervention breastfed longer than the women receiving usual care . The infants in the intervention group had fewer sick visits and reported use of fewer medications than infants in the usual care group . The intervention cost ( $ 301/mother ) was partially offset by cost savings on formula and health care . CONCLUSIONS Community health nurse and peer counselor support can increase breastfeeding duration in low-income women , and has the potential to reduce total costs including the cost of support OBJECTIVE To assess the efficacy of peer counseling to promote exclusive breastfeeding ( EBF ) among low-income inner-city women in Hartford , Conn. DESIGN Participants recruited prenatally were r and omly assigned to either receive support for EBF from a peer counselor plus conventional breastfeeding support ( peer counseling group [ PC ] ) or only conventional breastfeeding support ( control group [ CG ] ) and followed through 3 months post partum . SETTING Low-income predominantly Latina community . PARTICIPANTS Expectant mothers , less than 32 weeks gestation and considering breastfeeding ( N = 162 ) . Intervention Exclusive breastfeeding peer counseling support offering 3 prenatal home visits , daily perinatal visits , 9 postpartum home visits , and telephone counseling as needed . MAIN OUTCOME MEASURES Exclusive breastfeeding rates at hospital discharge , 1 , 2 , and 3 months post partum ( n = 135 ) . RESULTS At hospital discharge , 24 % in the CG compared with 9 % in the PC had not initiated breastfeeding , with 56 % and 41 % , respectively , nonexclusively breastfeeding . At 3 months , 97 % in the CG and 73 % in the PC had not exclusively breastfed ( relative risk [ RR ] = 1.33 ; 95 % CI , 1.14 - 1.56 ) during the previous 24 hours . The likelihood of nonexclusive breastfeeding throughout the first 3 months was significantly higher for the CG than the PC ( 99 % vs 79 % ; RR = 1.24 ; 95 % CI , 1.09 - 1.41 ) . Mothers in the CG were less likely than their PC counterparts to remain amenorrheic at 3 months ( 33 % vs 52 % ; RR = 0.64 ; 95 % CI , 0.43 - 0.95 ) . The likelihood of having 1 or more diarrheal episode in infants was cut in half in the PC ( 18 % vs 38 % ; RR = 2.15 ; 95 % CI , 1.16 - 3.97 ) . CONCLUSION Well-structured , intensive breastfeeding support provided by hospital and community-based peer counselors is effective in improving exclusive breastfeeding rates among low-income , inner-city women in the United States BACKGROUND Breastfeeding peer counseling has improved breastfeeding rates in developing countries ; however , its impact in this country has not been adequately evaluated . OBJECTIVE To evaluate the effectiveness of an existing , breastfeeding peer counseling program within the United States . DESIGN R and omized , prospect i ve , controlled trial in which participants were recruited prenatally and r and omly assigned to receive either routine breastfeeding education or routine breastfeeding education plus peer counseling . SETTING An urban hospital serving a large population of low-income Latinas . PARTICIPANTS Pregnant women ( < or = 26 weeks ' gestation ) were recruited from the hospital 's prenatal clinic . Inclusion criteria specified that participants be low income , be considering breastfeeding , have delivered a healthy , full-term singleton , and have access to a telephone . Intervention Breastfeeding peer counseling services included 1 prenatal home visit , daily perinatal visits , 3 postpartum home visits , and telephone contact as needed . MAIN OUTCOME MEASURES Breastfeeding rates at birth and 1 , 3 , and 6 months postpartum . RESULTS The proportion not initiating breastfeeding was significantly lower in the intervention group than among controls ( 8/90 [ 9 % ] vs 17/75 [ 23 % ] ; relative risk , 0.39 ; 95 % confidence interval , 0.18 - 0.86 ) . The probability of stopping breastfeeding also tended to be lower in the intervention group at both 1 month ( 36 % vs 49 % ; relative risk , 0.72 ; 95 % confidence interval , 0.50 - 1.05 ) and 3 months ( 56 % vs 71 % ; relative risk , 0.78 ; 95 % confidence interval , 0.61 - 1.00 ) . CONCLUSION These findings demonstrate that , in the United States , peer counselors can significantly improve breastfeeding initiation rates and have an impact on breastfeeding rates at 1 and 3 months post partum Excess weight gain in American Indian/Alaskan native ( AI/AN ) children is a public health concern . This study tested ( 1 ) the feasibility of delivering community-wide interventions , alone or in combination with family-based interventions , to promote breastfeeding and reduce the consumption of sugar-sweetened beverages ; and ( 2 ) whether these interventions decrease Body Mass Index ( BMI ) -Z scores in children 18–24 months of age . Three AI/AN tribes were r and omly assigned to two active interventions ; a community-wide intervention alone ( tribe A ; n = 63 families ) or community-wide intervention containing a family component ( tribes B and C ; n = 142 families ) . Tribal staff and the research team design ed community-tailored interventions and trained community health workers to deliver the family intervention through home visits . Feasibility and acceptability of the intervention and BMI -Z scores at 18–24 months were compared between tribe A and tribes B & C combined using a separate sample pretest , posttest design . Eighty-six percent of enrolled families completed the study . Breastfeeding initiation and 6-month duration increased 14 and 15 % , respectively , in all tribes compared to national rates for American Indians . Breastfeeding at 12 months was comparable to national data . Parents expressed confidence in their ability to curtail family consumption of sugar-sweetened beverages . Compared to a pretest sample of children of a similar age 2 years before the study begun , BMI -Z scores increased in all tribes . However , the increase was less in tribes B & C compared to tribe A ( −0.75 , P = 0.016 ) . Family , plus community-wide interventions to increase breastfeeding and curtail sugar-sweetened beverages attenuate BMI rise in AI/AN toddlers more than community-wide interventions alone This study examined the effect of support from trained peer counselors on breastfeeding initiation , duration , and exclusivity among low-income urban women . Training of counselors , under the supervision of a registered nurse certified in lactation , adapted education techniques from Paulo Freire to provide information about lactation management and other health care issues . The study compared infant feeding practice s of women who planned to breastfeed and received support from counselors ( counselor group , N=59 ) to women who requested counselors but , owing to inadequate numbers of trained counselors , did not have a counselor ( No-counselor group , N=43 ) . Women in the counselor group had significantly greater ( p<.05 ) breastfeeding initiation ( 93 percent vs. 70 percent ) , exclusivity ( 77 percent vs. 40 percent ) , and duration ( mean of 15 weeks vs. mean of 8 weeks ) than women in the no-counselor group . The findings suggest that peer counselors , well-trained , and with on-going supervision , can have a positive effect on breastfeeding practice s among low-income urban women who intend to breastfeed |
13,386 | 25,222,701 | Globally , low ( early follicular and the entire follicular phase for estrogen and progesterone , respectively ) and high ( COC , CSHT , late follicular and luteal phase for estrogen ; COC , mid- and late-luteal phase for progesterone ) hormonal milieu diversely affected the response of several brain regions including the amygdala , anterior cingulate cortex , and inferior frontal gyrus , but their functional recruitment across groups and domains was scattered .
The constellation of findings provides initial evidence of the influence of sex steroid hormones on cortical and subcortical regions implicated in emotional and cognitive processing . | Ovarian hormones are pivotal for the physiological maintenance of the brain function as well as its response to environmental stimuli .
There is mounting evidence attesting the relevance of endogenous ovarian hormones as well as exogenous estradiol and progesterone for emotional and cognitive processing .
The present review systematic ally summarized current knowledge on sex steroid hormonal modulation of neural substrates of emotion and cognition revealed by functional magnetic resonance imaging ( fMRI ) . | Although it 's been reported that women with premenstrual dysphoric disorder ( PMDD ) have increased negative mood , appetite ( food cravings and food intake ) , alcohol intake and cognitive deficits premenstrually , few studies have examined these changes concurrently within the same group of women or compared to women without PMDD . Thus , to date , there is not a clear underst and ing of the full range of PMDD symptoms . The present study concurrently assessed mood and performance tasks in 29 normally cycling women ( 14 women who met DSM-IV criteria for PMDD and 15 women without PMDD ) . Women had a total of ten sessions : two practice sessions , 4 sessions during the follicular phase and 4 sessions during the late luteal phase of the menstrual cycle . Each session , participants completed mood and food-related question naires , a motor coordination task , performed various cognitive tasks and ate lunch . There was a significant increase in dysphoric mood during the luteal phase in women with PMDD compared to their follicular phase and compared to Control women . Further , during the luteal phase , women with PMDD showed impaired performance on the Immediate and Delayed Word Recall Task , the Immediate and Delayed Digit Recall Task and the Digit Symbol Substitution Test compared to Control women . Women with PMDD , but not Control women , also showed increased desire for food items high in fat during the luteal phase compared to the follicular phase and correspondingly , women with PMDD consumed more calories during the luteal phase ( mostly derived from fat ) compared to the follicular phase . In summary , women with PMDD experience dysphoric mood , a greater desire and actual intake of certain foods and show impaired cognitive performance during the luteal phase . An altered serotonergic system in women with PMDD may be the underlying mechanism for the observed symptoms ; correspondingly , treatment with specific serotonin reuptake inhibitors ( SSRIs ) remains the preferred treatment at this time Estrogen has been shown to influence several brain functions as well as the expression of neuropsychiatric diseases . To date , two estrogen receptor ( ER ) subtypes have been identified , ERalpha and ERbeta . ERalpha messenger ribonucleic acid ( mRNA ) distribution in the human forebrain was recently characterized , and the highest expression was found in restricted areas of the amygdala and hypothalamus . However , no information exists with regard to ERbeta mRNA distribution in the human brain . To this end , the anatomical distribution pattern of ERbeta mRNA expression in the human forebrain was investigated in the present study . Overall , the ERbeta mRNA hybridization signal was relatively low , but the most abundant ERbeta mRNA areas were the hippocampal formation ( primarily the subiculum ) , claustrum , and cerebral cortex ; expression was also present in the subthalamic nucleus and thalamus ( ventral lateral nucleus ) . In contrast to ERalpha ( studied on adjacent brain sections ) , ERbeta mRNA expression was low in the hypothalamus and amygdala . Based on the revealed anatomical distribution of the human ERbeta gene expression , a putative role for ERbeta in the modulation of cognition , memory , and motor functions is suggested Underst and ing genetic factors that affect monoamine neurotransmitters flux in prefrontal cortex may help to further specify the complex neurobiological processes that underlie cognitive function and dysfunction in health and illness . The current study examined the associations between the polymorphisms of dopaminergic ( COMT Met158Val ) and serotoninergic ( 5-HTTLPR ) genes and the sequential pattern of responses in a motor r and om generation task providing well-established indexes for executive functioning in a large sample of 255 healthy women . Participants homozygous for the Met allele of the COMT polymorphism showed impaired inhibition of prepotent responses , whereas individuals homozygous for the s-allele of the 5-HTTLPR showed a restricted ability to up date information in working memory . Taken together the results indicate differentiated influences of dopaminergic and serotonergic genes on important and definite executive sub-processes related to cognitive flexibility BACKGROUND Despite overwhelming evidence that major depression is highly heritable , recent studies have localized only a single depression-related locus reaching genome-wide significance and have yet to identify a causal gene . Focusing on family-based studies of quantitative intermediate phenotypes or endophenotypes , in t and em with studies of unrelated individuals using categorical diagnoses , should improve the likelihood of identifying major depression genes . However , there is currently no empirically derived statistically rigorous method for selecting optimal endophentypes for mental illnesses . Here , we describe the endophenotype ranking value , a new objective index of the genetic utility of endophenotypes for any heritable illness . METHODS Applying endophenotype ranking value analysis to a high-dimensional set of over 11,000 traits drawn from behavioral/neurocognitive , neuroanatomic , and transcriptomic phenotypic domains , we identified a set of objective endophenotypes for recurrent major depression in a sample of Mexican American individuals ( n = 1122 ) from large r and omly selected extended pedigrees . RESULTS Top-ranked endophenotypes included the Beck Depression Inventory , bilateral ventral diencephalon volume , and expression levels of the RNF123 transcript . To illustrate the utility of endophentypes in this context , each of these traits were utlized along with disease status in bivariate linkage analysis . A genome-wide significant quantitative trait locus was localized on chromsome 4p15 ( logarithm of odds = 3.5 ) exhibiting pleiotropic effects on both the endophenotype ( lymphocyte-derived expression levels of the RNF123 gene ) and disease risk . CONCLUSIONS The wider use of quantitative endophenotypes , combined with unbiased methods for selecting among these measures , should spur new insights into the biological mechanisms that influence mental illnesses like major depression There is strong evidence of sex differences in mental rotation tasks . Transsexualism is an extreme gender identity disorder in which individuals seek cross-gender treatment to change their sex . The aim of our study was to investigate if male-to-female ( MF ) and female-to-male ( FM ) transsexuals receiving cross-sex hormonal treatment have different patterns of cortical activation during a three-dimensional ( 3D ) mental rotation task . An fMRI study was performed using a 3-T scan in a sample of 18 MF and 19 FM under chronic cross-sex hormonal treatment . Twenty-three males and 19 females served as controls . The general pattern of cerebral activation seen while visualizing the rotated and non-rotated figures was similar for all four groups showing strong occipito-parieto-frontal brain activation . However , compared to control males , the activation of MF transsexuals during the task was lower in the superior parietal lobe . Compared to control females , MF transsexuals showed higher activation in orbital and right dorsolateral prefrontal regions and lower activation in the left prefrontal gyrus . FM transsexuals did not differ from either the MF transsexual or control groups . Regression analyses between cerebral activation and the number of months of hormonal treatment showed a significant negative correlation in parietal , occipital and temporal regions in the MF transsexuals . No significant correlations with time were seen in the FM transsexuals . In conclusion , although we did not find a specific pattern of cerebral activation in the FM transsexuals , we have identified a specific pattern of cerebral activation during a mental 3D rotation task in MF transsexuals under cross-sex hormonal treatment that differed from control males in the parietal region and from control females in the orbital prefrontal region . The hypoactivation in MF transsexuals in the parietal region could be due to the hormonal treatment or could reflect a priori cerebral differences between MF transsexual and control subjects OBJECTIVE Most women on combined oral contraceptives ( COC ) report high levels of satisfaction , but 4 - 10 % complain of adverse mood effects . The aim of this r and omized , double-blinded , placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood . A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing . METHODS Thirty-four women with previous experience of mood deterioration during COC use were r and omized to one treatment cycle with a levonorgestrel-containing COC or placebo . An emotional face matching task ( vs. geometrical shapes ) was administered during functional magnetic resonance imaging ( fMRI ) prior to and during the COC treatment cycle . Throughout the trial , women recorded daily symptom ratings on the Cyclicity Diagnoser ( CD ) scale . RESULTS During the last week of the treatment cycle COC users had higher scores of depressed mood , mood swings , and fatigue than placebo users . COC users also had lower emotion-induced reactivity in the left insula , left middle frontal gyrus , and bilateral inferior frontal gyri as compared to placebo users . In comparison with their pretreatment cycle , the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri , whereas placebo users had decreased reactivity in the right amygdala . CONCLUSION COC use in women who previously had experienced emotional side effects result ed in mood deterioration , and COC use was also accompanied by changes in emotional brain reactivity . These findings are of relevance for the underst and ing of how combined oral contraceptives may influence mood . Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives OBJECTIVE To evaluate cognitive functioning throughout the menstrual cycle in women who suffer from premenstrual dysphoric disorder ( PDD ) and controls . RESEARCH HYPOTHESIS : Measures of cognitive function will discriminate between women with prospect ively documented PDD and women without PDD during the late-luteal phase of the menstrual cycle . PARTICIPANTS The participants consisted of 37 women who met operationalized , prospect ively documented criteria of premenstrual dysphoric disorder and 32 women without PDD who served as controls . DESIGN A series of neurocognitive tasks were used to assess selective , sustained attention , reaction time , and cognitive flexibility in women with PDD and controls . Tests were administered on two occasions : once during the follicular phase of the menstrual cycle , and once during the late-luteal phase . RESULTS Repeated measures and discriminant analyses failed to demonstrate significant group differences between women with PDD and controls in neurocognitive functioning . CONCLUSIONS The findings indicated that cognitive functioning in the late-luteal phase was not compromised in either group , in spite of subjective reports from the PDD group . The findings suggest that complaints of cognitive dysfunction may be mediated by altered perceptions and sociocultural expectations rather than by identifiable cognitive deficits The association between administered estrogen and performance on verbal memory and other cognitive tasks was examined . Male-to-female transsexuals undergoing estrogen treatment for sex reassignment ( n = 29 ) scored higher on Paired Associate Learning ( PAL ) compared to a similar transsexual control group , awaiting estrogen treatment ( n = 30 ) ( P < 0.05 ) . No differences between groups receiving and not receiving estrogen were detected on a control memory task ( Digit Span ) or on other cognitive tasks including Mental Rotations and Controlled Associations . There were no group differences in age . Group differences in mood or in general intellectual ability also did not explain the findings . Results suggest a specific influence of estrogen in men on verbal memory tasks , similar to that seen in prior studies of women . They are discussed in terms of differential processing dem and s of the two memory tasks and possible differences between estrogenic influences on Mental Rotations and Controlled Associations in men versus women Surgical or pharmacological suppression of ovarian hormones leads to declines in verbal memory , and estrogen treatment reverses these deficits . In the current study , we investigated the effects of menstrual cycle phase and oral contraceptives on verbal memory , as measured by the California Verbal Learning Test , in two groups of premenopausal women - 16 naturally cycling women and 20 current users of estrogen-based oral contraceptives ( OCs ) . Naturally cycling women were assessed twice - once during the early follicular phase ( Days 2 - 4 ) and once during the midluteal phase ( Days 20 - 22 ) of the menstrual cycle . OC users were tested on the same cycle days , corresponding to inactive and active pill phases , respectively . We predicted that naturally cycling women would show improved verbal memory during the midluteal phase , when estradiol levels are high , compared with the follicular phase , when estradiol levels are low . We also predicted that OC users , who show no change in endogenous estradiol across the cycle , would show no change in verbal memory . Contrary to predictions , naturally cycling women showed no changes in verbal memory across the cycle , whereas OC users showed enhanced memory during the active pill phase ( p<.05 ) . None of the secondary cognitive outcome measures varied with cycle phase or OC use including measures of visuospatial memory , verbal fluency , visuospatial abilities , and attention . Overall , these results suggest that verbal memory performance in premenopausal women varies across the cycle with OC use , but does not vary systematic ally with changes in endogenous estradiol Humans share with animals a primitive neural system for processing emotions such as fear and anger . Unlike other animals , humans have the unique ability to control and modulate instinctive emotional reactions through intellectual processes such as reasoning , rationalizing , and labeling our experiences . This study used functional MRI to identify the neural networks underlying this ability . Subjects either matched the affect of one of two faces to that of a simultaneously presented target face ( a perceptual task ) or identified the affect of a target face by choosing one of two simultaneously presented linguistic labels ( an intellectual task ) . Matching angry or frightened expressions was associated with increased regional cerebral blood flow ( rCBF ) in the left and right amygdala , the brain 's primary fear centers . Labeling these same expressions was associated with a diminished rCBF response in the amygdalae . This decrease correlated with a simultaneous increase in rCBF in the right prefrontal cortex , a neocortical region implicated in regulating emotional responses . These results provide evidence for a network in which higher regions attenuate emotional responses at the most fundamental levels in the brain and suggest a neural basis for modulating emotional experience through interpretation and labeling BACKGROUND Premenstrual dysphoric disorder ( PMDD ) has generally not been associated with impulsive behavior . However , some studies suggest that women with PMDD have higher impulsivity scores than healthy controls and that brain activity during response inhibition may vary across the menstrual cycle . Therefore , our aim was to unravel potentially important cognitive aspects of PMDD by investigating brain activity during response inhibition in women with PMDD and healthy controls in relation to menstrual cycle phase . METHODS Fourteen PMDD patients and 13 healthy controls performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging . RESULTS Women with PMDD displayed decreased activity during both menstrual cycle phases compared to healthy controls in several task-related parietal areas . A significant group by phase interactions was found in the left insula , driven by enhanced activity among healthy controls in the follicular phase and by enhanced insula activity during the luteal phase among PMDD patients . LIMITATIONS The limitations of the present study are the relatively limited sample size , the relatively small number of NoGo trials and the lack of a baseline contrast for the NoGo trials . CONCLUSIONS During response inhibition women with PMDD have reduced activity in areas associated with attention and motor function which is unrelated to menstrual cycle phase . Insular cortex activity , involved in both affective and cognitive processing , was significantly activated during the luteal phase among PMDD women . These findings are relevant for the underst and ing of how ovarian steroids influence mood symptoms in women |
13,387 | 22,434,689 | In conclusion , individuals who considered themselves more masculine and less sensitive to pain than the typical man showed higher pain thresholds and tolerances .
Gender stereotypes specific to pain scales showed stronger associations with sex differences in pain sensitivity response than masculine and feminine personality trait scales | Gender role refers to the culturally and socially constructed meanings that describe how women and men should behave in certain situations according to feminine and masculine roles learned throughout life .
The aim of this meta- analysis was to evaluate the relationship between gender role and experimental pain responses in healthy human participants . | & NA ; The aim of this study was to examine how men and women observe experimentally induced pain in male and female participants and to specifically determine the accuracy of observed pain ratings , the possible interactions between the sex of the viewer and the sex of the individual being observed , and the influence of gender role expectations on observed pain ratings . The sample comprised 29 participants ( 15 females ) . They each completed a battery of psychological question naires and viewed a presentation of 10 r and omly ordered video clips . Each presentation consisted of 10 video clips , lasting 30 s , of a participant ( five males and five females ) in the cold pressor task . The participants viewing the videos were asked to provide several ratings , including observed pain intensity and gender role related characteristics of the individual in the video . In terms of sex of the video participant , results indicated that viewers rated male videos as having less pain than female videos although the effect was small . Regarding sex of the viewer , results indicated that for both male and female videos , female viewers rated observed pain intensity significantly higher than did male viewers . In terms of accuracy , results indicated that on average , female video participants ' pain was underestimated by 14 points , while male videos participants ' pain was underestimated by 22 points ( on a 0–100‐point scale ) . Pain intensity ratings and pain tolerance from the participants in the videos did not differ significantly with respect to sex , though women had shorter tolerance times and higher pain ratings than men . Hierarchical regression analyses indicated that expectations of gender related ‘ endurance of pain ’ significantly predicted ratings of both male and female videos . When endurance expectations were controlled , sex of the viewer no longer significantly predicted observed pain ratings . The ‘ willingness to report pain ’ variable was not a significant predictor of observed pain ratings . Our results show that women are perceived to have more pain than men , that there was a tendency by both sexes to underestimate pain in others , but men showed even greater underestimation , and that gender role expectations of pain endurance given by the video observers accounted for substantial variance in their ratings of pain in the videos & NA ; Aims of investigation : To quantify the magnitude of putative gender differences in experimental pressure pain threshold ( PPT ) , and to establish the relevance of repeated measurements to any such differences . Methods : Two separate studies were undertaken . A pressure algometer was used in both studies to assess PPT in the first dorsal interosseous muscle . Force was increased at a rate of 5 N /s . In study 1 , two measurements were taken from 240 healthy volunteers ( 120 males , 120 females ; mean age 25 years ) giving a power for statistical analysis of & bgr;=0.80 at & agr;=0.01 . In study two , 30 subjects ( 15 males , 15 females mean age 28 years ) were r and omly selected from study one . Fourteen repeated PPT measurements were recorded at seven , 10 min intervals . Mean PPT data for gender groups , from both studies , were analysed using analysis of covariance with repeated measures , and age as the covariate . Results : The mean PPT for each of the two measurements in study one showed a difference between gender of 12.2 N ( f=30.5 N , m=42.7 N ) and 12.8 N ( f=29.5 N , m=42.3 N ) , respectively , representing a difference of 28 % with females exhibiting a lower threshold . In study two , the mean difference calculated from 14 PPT repeated measurements over a 1 h period was comparable to that in study one at 12.3 N ( range 10.4–14.4 N ) again females exhibited the lower threshold . The differences in mean PPT values between gender were found to be significant in both study one , at ( P<0.0005 , F=37.8 , df=1 ) and study two ( P=0.01 , F=7.6 , df=1 ) . No significant differences were found in either study with repeated measurement ( P=0.892 and P=0.280 ) , or on the interaction of gender and repeated measurement after controlling for age ( P=0.36 and P=0.62 ) . Conclusion : Healthy females exhibited significantly lower mean PPTs in the first dorsal interosseous muscle than males , which was maintained for fourteen repeated measures within a 1 h period . This difference is likely to be above clinical ly relevant levels of change , and it has clear implication s for the use of different gender subjects in laboratory based experimental design s utilising PPT as an outcome measure UNLABELLED Two experiments assessed how interpersonal transactions influence responses to cold pressor pain in women versus men . In Experiment 1 , 91 young adults ( 57 women , 34 men ) were r and omly assigned to either a no transaction ( NT ) condition in which they coped alone with the cold pressor test or a transaction opportunity ( TO ) condition in which they also had the option of interacting with an empathetic , reflecting experimenter . Compared to men , women had lower pain tolerance and reported more pain and catastrophizing , although there were no gender differences in support seeking or other ways of coping . Within the TO condition , women were no more likely than men to initiate a transaction , but female speakers were more pain-focused than male speakers , and speaking with the empathetic interaction partner had generally negative effects on pain perception and coping . In Experiment 2 , 126 young adults ( 76 women , 50 men ) were r and omly assigned to NT , TO , or experimenter-directed ( 1 ) Distraction ( DT ) , ( 2 ) Reinterpretation ( RT ) , or ( 3 ) Encouragement ( ET ) conditions . Although men had similar levels of pain tolerance across the 5 transaction conditions , women in NT and TO conditions exhibited reduced tolerance compared with those in the DT , RT , and ET conditions . Pain tolerance times among women in DT , RT , and ET conditions were equal to or exceeded those of men in these conditions . Together , findings suggest the nature of interpersonal transactions exerts a greater influence on women 's responses to noxious stimulation than those of men . PERSPECTIVE This study adds to literature indicating that women exhibit reduced tolerance for experimentally induced pain compared with men . These results suggest that the nature of interpersonal transactions also affects women 's responses to noxious stimulation , more than those of men The aim of the present study was to examine the possible role of personality traits , in accordance with Cloninger 's theory , and gender , in the variability of responsiveness to opioids . Specifically , it was intended to test whether or not the three personality dimensions - harm avoidance ( HA ) , reward dependence ( RD ) and novelty seeking ( NS ) - as suggested by Cloninger , can predict inter-personal differences in responsiveness to morphine after exposure to experimental cold pain . Thirty-four healthy volunteers ( 15 females , 19 males ) were given the cold pressor test ( CPT ) . Pain threshold , tolerance , and magnitude ( VAS ) were measured before and after ( six measures , 30 min apart ) the administration of either 0.5 mg/kg oral morphine sulphate ( n=21 ) or 0.33 mg/kg oral active placebo ( diphenhydramine ) ( n=13 ) in a r and omized , double blind design . Assessment of the three personality traits , according to Cloninger 's Tridimensional Personality Question naire , was performed before the CPT . A high HA score ( but not RD , NS , or baseline values of the three pain parameters ) predicted a significantly larger pain relief following the administration of morphine sulphate ( but not of the placebo ) . Women exhibited a larger response in response to both treatments , as indicated by a significantly increased threshold and tolerance following morphine sulphate as well as significantly increased tolerance and decreased magnitude following placebo administration . The present study confirms the existence of individual differences in response to analgesic treatment . It suggests that high HA personality trait is associated with better responsiveness to morphine treatment , and that females respond better than men to both morphine and placebo UNLABELLED Pain catastrophizing is among the most robust predictors of pain outcomes , and a disruption in endogenous pain-inhibitory systems is 1 potential mechanism that may account for increased pain among individuals who report higher pain catastrophizing . Pain catastrophizing may negatively influence diffuse noxious inhibitory controls ( DNIC ) , a measure of endogenous pain inhibition , through complex anatomical circuitry linking cortical responses to pain with processes that modulate pain . The current study examined whether DNIC mediated the relationship between catastrophizing and pain among 35 healthy young adults and examined the moderating effects of sex to determine whether the magnitude or direction of associations differed among men and women . DNIC was assessed using pressure pain thresholds on the forearm before and during a cold pressor task . Using bias-corrected bootstrapped confidence intervals , results showed that diminished DNIC was a significant partial mediator of the relation between greater pain-related catastrophizing and more severe pain ratings . Participant sex moderated these associations ; higher catastrophizing predicted lower DNIC for men and women , however , the effect of catastrophizing on pain ratings was partially mediated by DNIC for women only . These findings further support the primary role of pain catastrophizing in modulation of pain outcomes . PERSPECTIVE These findings support the hypothesis that the heightened pain reported by individuals higher in pain catastrophizing may be related to a disruption in the endogenous modulation of pain , operationalized by assessing DNIC . Whether interventions that reduce pain catastrophizing affect pain outcomes via effects on DNIC is in need of investigation Anxiety sensitivity ( AS ) has been shown previously to be an important factor in the perception and experience of experimentally induced pain within healthy adults . The aim of the current study was to extend this research by : ( i ) using the Anxiety Sensitivity Profile ( ASP ) as an alternative measure of AS ; ( ii ) examining whether different coping instructions affect pain reports ; and ( iii ) investigating potential differences between men and women . Participants were 50 healthy adults ( 23 males , 27 females ) who were required to complete 2 versions of the cold pressor pain task ; one version required the use of control instructions , whereas the other made use of acceptance‐based instructions . Although the coping instructions were found to affect pain thresholds ( acceptance result ed in lower thresholds ) , a similar pattern of correlations were found between the pain indexes and AS under both conditions . Of the ASP subscales , the gastrointestinal and cognitive concerns components were found to be the most strongly related to pain experiences . When the analysis was conducted separately for each sex , the ASP scales were related to the self‐report measures of pain in women , whereas they were related to the behavioural measures of pain in men . These results not only confirm that AS is associated with experimental pain , but that there may be sex differences in this relationship The literature demonstrating sex differences in pain is sizable . Most explanations for these differences have focused on biologic mechanisms , and only a few studies have examined social learning . The purpose of this study was to examine the contribution of gender-role stereotypes to sex differences in pain . This study used experimental manipulation of gender-role expectations for men and women . One hundred twenty students participated in the cold pressor task . Before the pain task , participants were given 1 of 3 instructional sets : no expectation , 30-second performance expectation , or a 90-second performance expectation . Pain ratings , threshold , and tolerance were recorded . Significant sex differences in the " no expectation " condition for pain tolerance ( t = 2.32 , df = 38 , P < .05 ) and post-cold pressor pain ratings ( t = 2.6 , df = 37 , P < .05 ) were found . Women had briefer tolerance times and higher post-cold pressor ratings than men . When given gender-specific tolerance expectations , men and women did not differ in their pain tolerance , pain threshold , or pain ratings . This is the first empirical study to show that manipulation of expectations alters sex differences in laboratory pain 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 Objective Sex differences in pain perception have been widely reported , with women typically displaying greater pain sensitivity than men , but the mechanisms underlying these differences remain unclear . One possible explanation suggests that men are more motivated to tolerate and suppress expressions of pain because of the masculine sex role , whereas the feminine sex role encourages pain expression and produces lower motivation to tolerate pain among women . Methods To examine the influence of motivation on perceptual and cardiovascular responses to pain among women and men , different levels of monetary incentive ( high vs. low incentive ) were provided to a group of 81 healthy young adults undergoing the cold pressor pain procedure . It was anticipated that men would have greater endogenous motivation and would therefore be less affected by the external incentive . Results Men had higher pain thresholds and tolerances and lower pain ratings than women , but the incentive condition produced no significant effect on pain responses . Resting blood pressure was positively correlated with pain tolerance among the low incentive group , whereas blood pressure reactivity to the cold pressor predicted pain tolerance in the high incentive group . Conclusions Thus , monetary incentive did not influence pain responses , but the relationship between cardiovascular measures and pain responses was influenced by the incentive manipulation . Potential explanations for the observed results are presented , and the implication s for applying the biopsychosocial model to pain research are discussed Objective : To take a different perspective in assessing young men with chronic prostatitis-like symptoms , this study was design ed since few prospect i ve studies are available to survey a population of young men . Material and Methods : One hundred and fifty men aged 20 years dwelling in the community were r and omly selected . Chronic prostatitis-like symptoms were measured by the National Institutes of Health-Chronic Prostatitis Symptom Index and the selfreported scores for pain and urinary symptoms were used to identify chronic prostatitis-like symptoms . The psychological methods used were the Beck Depression Inventory , the State-Trait Anxiety Inventory , and the Bem Sex Role Inventory . A total of 87 men ( a response rate 58 % ) completed self-administered question naires . Results : As the scores for pain and urinary symptoms increased , those for depression increased ( p < 0.001 and p = 0.01 , respectively ) . However , the mean scores for state and trait anxiety were not different according to the scores for pain and urinary symptoms . The mean masculinity scores were not different according to the scores for pain but those were significantly different according to the scores of urinary symptoms ( p = 0.042 ) . The mean femininity scores were not different according to the scores of pain and urinary symptoms . Conclusions : Our findings suggest that psychological factors , especially depression and weak masculine identity may be associated with an early stage of chronic prostatitis-like symptoms . Young men with chronic prostatitis-like symptoms also have psychological problems & NA ; The objective of this research was to identify the psychological and physiological variables that differentiate persons reporting masticatory muscle pain ( MMP ) from normal controls ( NC ) . This study examined the characteristics of 35 MMP patients in comparison to 35 age‐ , sex‐ , and weight‐matched NCs . All subjects completed a series of st and ardized question naires prior to undergoing a laboratory evaluation consisting of a psychosocial stressor and pressure pain stimulation at multiple body sites . During the evaluation , subjects ’ emotional and physiological responses ( heart rate , blood pressure , respiration , skin temperature , and muscle activity ) were monitored . Results indicated that persons with MMP reported greater fatigue , disturbed sleep , depression , anxiety , menstrual symptoms , and less self‐deception ( P’s<0.05 ) than matched controls . At rest , MMPs had lower end tidal carbon dioxide levels ( P<0.04 ) and lower diastolic blood pressures than the NCs ( P<0.02 ) . During laboratory challenge , both groups responded to the st and ard stressor with significant physiological activity and emotional responding consistent with an acute stress response ( P<0.01 ) , but there were no differences between the MMPs and NCs . Muscle pain patients reported lower pressure pain thresholds than did NCs at the right/left masseter and right temporalis sites ( P’s<0.05 ) ; there were no differences in pressure pain thresholds between MMPs and NCs for the left temporalis ( P<0.07 ) and right/left middle finger sites ( P’s>0.93 ) . These results are discussed in terms of the psychological and physiological processes that may account for the development of muscle pain in the masticatory system UNLABELLED Research examining perceptions of subjects participating in an experimental pain task has not been widely studied . The primary purpose of this study was to examine the influence of prior experience with the cold pressor on subsequent perceptions of others experiencing this same pain task . Furthermore , to replicate our previous work , we examined how individuals observe experimentally induced pain in male and female participants . Possible interactions between order of cold pressor experience , sex of the viewer , sex of the individual being observed , and characteristics attributed to the individuals in the videos were also analyzed . The sample was composed of 57 participants . They were each r and omized to 1 of 2 conditions : ( 1 ) participate in cold pressor task before viewing a presentation of 10 video clips ( of subjects in cold pressor task ) , rate videos , and complete battery of question naires or ( 2 ) cold pressor participation after completion of the same question naires , and viewing/rating videos . Participants viewing the videos provided ratings including observed pain and emotional characteristics they attributed to the individuals . These results replicated and extended our previous work by demonstrating a gender bias ( ie , a stereotypical belief about an individual on the basis of their sex ) in the observation of pain , such that participants rated female subjects as experiencing greater pain intensity when undergoing a cold pressor task compared to male subjects . Furthermore , experiencing the cold pressor before watching the videos increased a participant 's pain ratings of observed pain . There were also several significant interactions between cold pressor condition , sex of video participant , sex of viewer , and emotional/behavioral characteristics attributed to the video participant . PERSPECTIVE Results of this study demonstrate that prior experience with pain increases accuracy of estimating others ' pain . Gender role expectations also influence observer 's ratings of pain , and prior experience of pain influences men and women differently Using a crossover , r and omized , double-blind , cumulative-dosing procedure , we examined whether a painful stimulus modulated subjective and psychomotor effects of butorphanol in eight male and eight female volunteers . During each session , volunteers received four intravenous injections of either butorphanol ( 0 , 0.5 , 1 , and 2 mg/70 kg ) or saline ( placebo ) at hourly intervals . Saline and butorphanol were tested in two conditions , forearm immersion 30 min after each injection into either 2 or 37 degrees C water . During the 180-s immersion , volunteers completed a visual analog scale ( VAS ) , psychomotor test , and pain ratings . VAS ratings of " Coasting ( ' spaced out ' ) " , " heavy or sluggish feeling , " and " sleepy " were lower in the 2 degrees C than in the 37 degrees C condition during butorphanol administration , but only in females . Modulation by a painful stimulus of sleepy ratings was confined to the third immersion ( i.e. , a dose effect ) . The cold-water stimulus significantly decreased butorphanol-induced impairment during the third immersion for males , and females showed a similar trend . Overall , pain ratings were higher in females , and although not significant , males reported a greater degree of analgesia . The differences in pain ratings and degree of analgesia between the sexes are discussed as a possible mechanism for the sex differences in modulatory effects Sex differences in responses to experimental pain have been widely reported , with women typically showing lower pain threshold and tolerance than men . One possible explanation for these differences is that traditional gender roles may lead to sex differences in perceived ability to tolerate pain . To address this possibility , the present study evaluated the influence of a sex-related perceived ability manipulation on pain tolerance and cardiovascular responses to ischemic pain assessed via the submaximal effort tourniquet procedure . A sample of 68 young adults ( 35 women , 33 men ) were r and omly assigned to 1 of 2 perceived ability conditions , which depicted either women ( FEM condition ) or men ( MASC condition ) as more able to tolerate the painful task . The results indicated that men had higher pain tolerance than women . Although there was no overall effect of the experimental condition , only men in the FEM condition had higher tolerance than women . Also , men had greater blood pressure reactivity than women , and further analysis showed that women in the MASC condition had the lowest systolic blood pressure reactivity . Cardiovascular reactivity and motivation to tolerate the pain were positively correlated with pain tolerance only among men in the FEM condition . These findings indicate that the perceived ability manipulation produced only modest effects on pain tolerance and cardiovascular reactivity , but the relationship of cardiovascular and subjective responses to pain tolerance differed across conditions . These findings suggest that perceived ability may contribute to perceptual and cardiovascular responses to pain in a complex fashion , and further research to explicate these relationships is needed Sex differences in pain perception and analgesic responses have garnered increasing attention in recent years . We examined the association of psychological factors to baseline pain perception and pentazocine analgesia among 49 healthy women and 39 men . Subjects completed psychological question naires measuring positive and negative affect as well as catastrophizing . Subsequently , responses to experimental pain were assessed before and after double-blind administration of intravenous pentazocine ( 0.5mg/kg ) . In correlational analyses , positive affect predicted lower pain sensitivity among men but not women . Negative affect predicted lower baseline pain tolerances among both sexes but predicted poorer analgesia only among men . Catastrophizing was associated with greater pain sensitivity and less analgesia more consistently in men than women . Regression models revealed that positive affect predicted lower overall pain sensitivity and catastrophizing predicted poorer overall analgesic responses among men , while no significant predictors of overall pain or analgesia emerged for women . Moreover , positive affect and catastrophizing were negatively and positively correlated , respectively , with side effects from the medication , but only among men . These findings indicate sex-dependent associations of psychological factors with baseline pain perception , analgesic responses , and medication side effects |
13,388 | 27,841,439 | The radiological assessment of colonic transit outcomes means that these results might not translate to important improvement in clinical symptoms or increased bowel movements . | BACKGROUND Childhood constipation is a common problem with substantial health , economic and emotional burdens .
Existing therapeutic options , mainly pharmacological , are not consistently effective , and some are associated with adverse effects after prolonged use .
Transcutaneous electrical stimulation ( TES ) , a non-pharmacological approach , is postulated to facilitate bowel movement by modulating the nerves of the large bowel via the application of electrical current transmitted through the abdominal wall .
OBJECTIVES Our main objective was to evaluate the effectiveness and safety of TES when employed to improve bowel function and constipation-related symptoms in children with constipation . | Purpose Transcutaneous electrical stimulation ( TES ) speeds up colonic transit in children with slow-transit constipation ( STC ) . This study examined if concurrent upper gastrointestinal dysmotility ( UGD ) affected response to TES . Methods Radio-nuclear transit studies ( NTS ) were performed before and after TES treatment of STC as part of a larger r and omised controlled trial . UGD was defined as delayed gastric emptying and /or slow small bowel transit . Improvement was defined as increase of ≥1 Geometric Centre ( median radiotracer position at each time [ small bowel = 1 , toilet = 6 ] ) . Results Forty-six subjects completed the trial , 34 had NTS after stimulation ( 21 M , 8–17 years , mean 11.3 years ; symptoms > 9 years ) . Active stimulation increased transit in > 50 % versus only 25 % with sham ( p = 0.04 ) . Seventeen children also had UGD . In children with STC and either normal upper GI motility ( NUGM ) and UGD , NTS improved slightly after 1 month ( 57 vs. 60 % ; p = 0.9 ) and more after 2 months ( 88 vs. 40 % ; p = 0.07 ) . However , mean transit rate significantly increased with NUGM , but not UGD ( 5.0 ± 0.2 : 3.6 ± 0.6 , p < 0.01 ) . Conclusion Transcutaneous electrical stimulation was beneficial for STC , with response weakly associated with UGD . As measured by NTS , STC children with NUGM responded slightly more , but with significantly greater increased transit compared to those with UGD . Higher numbers are needed to determine if the difference is important OBJECTIVE To evaluate our initial experience using sacral neuromodulation via implanted pulse generator as a treatment for children with dysfunctional elimination syndrome and symptoms refractory to maximum medical therapy . MATERIAL S AND METHODS There were 105 consecutive patients who underwent a 2-stage procedure with a trial period ( n = 89 ) or a single procedure ( n = 16 ) for device implantation . They were followed up prospect ively for a median of 2.72 years ( average , 3.18 years ; range , 0.01 - 9.63 years ) for symptom improvement and resolution . RESULTS Nearly all children ( 99 of 105 [ 94 % ] ) experienced improvement of at least 1 symptom ; 12 of 105 patients ( 11 % ) had at least 1 symptom worsen . Urinary incontinence , constipation , frequency and /or urgency , and nocturnal enuresis improved in 89 of 101 ( 88 % ) , 73 of 92 ( 79 % ) , 54 of 81 ( 67 % ) , and 59 of 89 ( 66 % ) children , respectively , and resolved in 41 of 101 ( 41 % ) , 37 of 92 ( 40 % ) , 23 of 81 ( 28 % ) , and 25 of 89 ( 28 % ) children , respectively . Outcomes among patients who did and did not undergo the trial were not significantly different ( P = .19 - 1.00 ) , and only 2 of 88 patients did not undergo permanent implantation . Reoperations ( n = 85 ) occurred in 59 of 105 children ( 56 % ) , mainly for device malfunction ( n = 42 ) , whereas explantation was performed in 36 of 104 children ( 35 % ) at an average of 2.68 years since implantation ( median , 2.36 years ; range , 0.03 - 9.04 years ) , mainly for complete symptom resolution ( n = 12 ) . Explantation for any reason was less common after single-stage procedures ( 1 of 16 [ 6 % ] vs 35 of 88 [ 40 % ] patients ; P = .01 ) . CONCLUSION Sacral neuromodulation should be considered for children with dysfunctional elimination syndrome whose symptoms are refractory to maximum medical therapy underst and ing that the risk of reoperation is > 50 % . Elimination of the trial period reduces the number of general anesthetics without sacrificing outcomes PURPOSE Idiopathic slow transit constipation ( STC ) describes a clinical syndrome characterised by intractable constipation . It is diagnosed by demonstrating delayed colonic transit on nuclear transit studies ( NTS ) . A possible new treatment is interferential therapy ( IFT ) , which is a form of electrical stimulation that involves the transcutaneous application of electrical current . This study aim ed to ascertain the effect of IFT on colonic transit time . METHODS Children with STC diagnosed by NTS were r and omised to receive either 12 real or placebo IFT sessions for a 4-week period . After a 2-month break , they all received 12 real IFT sessions-again for a 4-week period . A NTS was repeated 6 to 8 weeks after cessation of each treatment period where able . Geometric centres ( GCs ) of activity were calculated for all studies at 6 , 24 , 30 , and 48 hours . Pretreatment and posttreatment GCs were compared by statistical parametric analysis ( paired t test ) . RESULTS Thirty-one pretreatment , 22 postreal IFT , and 8 postplacebo IFT studies were identified in 26 children ( mean age , 12.7 years ; 16 male ) . Colonic transit was significantly faster in children given real treatment when compared to their pretreatment NTS at 24 ( mean CG , 2.39 vs 3.04 ; P < or = .0001 ) , 30 ( mean GC , 2.79 vs 3.47 ; P = .0039 ) , and 48 ( mean GC , 3.34 vs 4.32 ; P = .0001 ) hours . By contrast , those children who received placebo IFT had no significant change in colonic transit . CONCLUSIONS Transcutaneous electrical stimulation with interferential therapy can significantly speed up colonic transit in children with slow transit constipation AIMS Transcutaneous electrical stimulation ( TES ) was used to treat children with slow-transit constipation ( STC ) for 1 to 2 months in a r and omized controlled trial during 2006 to 2008 . We aim ed to determine long-term outcomes , hypothesizing that TES produced sustained improvement . METHODS Physiotherapists administered 1 to 2 months of TES to 39 children ( 20 minutes , 3 times a week ) . Fifteen continued to self-administer TES ( 30 minutes daily for more than 2 months ) . Mean long-term follow-up of 30 of 39 patients was conducted using question naire review 3.5 years ( range 1.9 - 4.7 years ) later . Outcomes were evaluated by confidence intervals or paired t test . RESULTS Seventy-three percent of patients perceived improvement , lasting more than 2 years in 33 % and less than 6 months in 25 % to 33 % . Defecation frequency improved in 30 % . Stools got wetter in 62 % after stimulation and then drier again . Soiling improved in 75 % and abdominal pain in 59 % . Laxative use stopped in 52 % , and 43 % with appendicostomies stopped washouts . Soiling/Holschneider continence score improved in 81 % ( P = .0002 ) . Timed sits switched to urge-initiated defecations in 80 % patients . Eighty percent of relapsed patients elected to have home stimulation . CONCLUSION TES holds promise for STC children . Improvement occurred in two thirds of children , lasting more than 2 years in one third , whereas symptoms recurred after 6 months in one third of children Aim Transcutaneous electrical nerve stimulation ( TENS ) is a possible alternative to sacral nerve stimulation because the neurophysiologic targets might be similar but the former method is non-invasive and cheaper . The aim of the study was to assess both symptom and quality of life ( QoL ) improvements in patients suffering from severe FI . Methods Thirty two patients ( M/F , 30/2 ; age , 61 ± 13 years ) were enrolled in a pilot trial because they suffered from a severe and stable FI ( Clevel and Score14.5 ± 2.8 [ 11–20 ] ) for a long duration ( 95 ± 91 months ) . TENS was delivered 20 min bis in die at home ( Schwa Medico , P3 ) . Assessment was realized at 1 , 3 , and 6 months with both semi-directive and self-administered question naires . Main endpoint was the quantified success rate after 1 month of follow-up . Results Mean subjective improvement was 26 ± 30 % : 20 ( 63 % ) patients reported some degree of improvement and 10 ( 32 % ) at least a 25 % improvement in fecal incontinence . The Clevel and score significantly decreased at 1 ( 11 ± 4 ; p < 0.001 ) , 3 ( 11 ± 5 ; p < 0.001 ) , and 6 ( 10 ± 5 ; p < 0.001 ) months . All subscales of QoL were significantly improved after a 3-month period of stimulation . However , constipation score and number of pads did not change . There was no adverse event . Conclusion TENS provides slight improvement in FI . This justifies both neurophysiology assessment and r and omized controlled studies before further diffusion of the technique PURPOSE Transcutaneous electrical stimulation ( TES ) ( 3 sessions/wk ) over the abdomen stimulated bowel functions in a r and omized controlled trial . This pilot study assessed whether daily TES at home with a safe , portable machine would be possible and more efficacious than trial results . METHODS Eleven patients ( 6 male/5 female ; mean age , 14 years ; range , 12 - 18 years ) with slow-transit constipation who relapsed or responded poorly in the trial were recruited ( 11 + /- 5 months later ) . An EPM-IF-4160 ( Fuji Dynamics , Hong Kong ) portable machine ( sine waveform , 4 kHz carrier frequency , 80 - 160 Hz beat frequency , intensity <33 mA ) delivering interferential current ( 2 electrodes over epigastrium + 2 over kidneys ) was applied 1 hour daily at home . Continence diaries were kept for 1 month before and 2 months during treatment . RESULTS All children completed more than 1 month of treatment after baseline recording . Defecation increased in 9 of 11 children , and soiling decreased in 4 of 11 children . There was a significant increase in total episodes of defecation per week ( mean + /- SD , 2.5 + /- 2.1 vs 6.7 + /- 4.4 ; P = .008 ) and a nonsignificant decrease in soiling ( 3.8 + /- 1.6 vs 1.1 + /- 0.5 episodes/wk , P = .1 ) . Daily stimulation does not affect abdominal pain . No adverse events occurred . CONCLUSIONS Daily TES at home is safe and significantly improved bowel function in children who did not respond to 3 times per week of TES . Home TES may be a novel treatment of intractable slow transit constipation , avoiding hospital visits OBJECTIVES : Although it has been used as a laxative for many years , high- quality trials assessing the efficacy of the laxative sodium picosulfate ( SPS ) are lacking . The purpose of this study was to assess the efficacy and safety of 4-week treatment with SPS in patients with functional constipation as defined by the Rome III diagnostic criteria . METHODS : This study was a r and omized , double-blind , placebo-controlled , parallel-group study in 45 general practice s in Germany . A total of 468 patients with chronic constipation presenting to their general practitioner and fulfilling the Rome III diagnostic criteria were screened . After a 2-week baseline period , 367 patients were r and omized to either SPS drops or matching placebo in a 2:1 ratio for 4 weeks . Dose titration was permitted throughout treatment . Patients without a bowel movement for more than 72 h were allowed to use a “ rescue ” bisacodyl suppository . The primary end point was the mean number of complete spontaneous bowel movements ( CSBMs ) per week . A spontaneous bowel movement ( SBM ) was defined as a stool not induced by rescue medication , whereas a CSBM was defined as an SBM associated with a sensation of complete evacuation . RESULTS : The mean number ( ±s.e . ) of CSBMs per week increased from 0.9±0.1 to 3.4±0.2 in the SPS group and from 1.1±0.1 to 1.7±0.1 in the placebo group ( P<0.0001 ) . The percentage of patients reaching an increase of ≥1 in the mean number of CSBMs per week compared to baseline was 65.5 % vs. 32.3 % , respectively ( P<0.0001 ) . The percentage of patients reaching a mean number of at least three CSBMs per week was 51.1 % in the SPS group and 18.0 % in the placebo group ( P<0.0001 ) . After 24 h , approximately 69 % of patients in the SPS group and 53 % in the placebo group had their first SBM . The SPS dose was titrated down during the study by nearly 50 % of patients . Assessment of quality of life ( QoL ) by the constipation-related Patient Assessment of Constipation (PAC)-QoL question naire showed significant improvement in SPS-treated patients compared to the placebo group . CONCLUSIONS : Treatment of chronic constipation with SPS improves bowel function , symptoms , and QoL and is well tolerated . The dose can be adjusted individually while maintaining benefit BACKGROUND Slow transit constipation ( STC ) causes intractable symptoms not responsive to medical treatment . Children have irregular bowel motions , colicky abdominal pain , and frequent soiling . Transcutaneous electrical stimulation using interferential current ( interferential therapy [ IFT ] ) is a novel treatment of STC . This study assessed quality of life ( QOL ) in STC children before and after IFT treatment . METHODS Eligible STC children were r and omized to receive either real or placebo IFT ( 12 sessions for 4 weeks ) . Question naires ( Pediatric Quality of Life Inventory ) were administered before and 6 weeks after treatment , with parallel parent and child self-report scales . Higher scores indicate better QOL . Holschneider and Templeton scores were also obtained . The QOL scores were compared using paired t tests . RESULTS Thirty-three children ( 21 male ) , with a mean age of 11.8 years ( range , 7.4 - 16.5 years ) , were recruited ; 16 received real IFT . Child-perceived QOL was improved after real IFT compared with baseline ( 81.1 vs 72.9 , P = .005 ) but not after placebo IFT ( 78.1 vs 74.9 , P = .120 ) . The Holschneider score improved after real IFT ( 10 vs 8 , P = .015 ) but not after placebo IFT ( 9 vs 8 , P = .112 ) . Parentally perceived QOL was similar after real IFT ( 70.1 vs 70.3 , P = .927 ) and placebo IFT ( 70.2 vs 69.8 , P = .899 ) . There were no differences in Templeton scores . CONCLUSION Interferential therapy is a novel therapy for children with STC that improves their self-perceived QOL Objectives : Neurostimulation is increasingly used in treating bladder and bowel dysfunction , but its effect on rectal motility is obscure . The aim of the study was to evaluate the acute effect of transcutaneous electrical nerve stimulation ( TENS ) on rectal motility in children with overactive bladder ( OAB ) . Methods : In this double-blind placebo-controlled study in 20 children with OAB ( mean age 8.6 ± 1.8 years ; 7 girls ) , 48-hour urodynamic monitoring including rectal manometry was performed . After 24-hours of baseline investigation without stimulation the children were r and omised to either active TENS ( n = 10 ) or placebo ( n = 10 ) . Surface electrodes were placed over the sacral bone . The exterior of active and placebo stimulators was identical . Starting in the morning , the children received either continuous TENS stimulation or placebo until bedtime . Rectal contractions were defined as pressure runs exceeding 5 cm H2O and lasting ≥3 minutes . Results : At baseline there was no significant difference in proportion of time with rectal contractions in the 2 groups ( TENS group median 31 % [ range 12%–66 % ] vs placebo group median 31 % [ range 10%–66 % ] ; P = 0.75 ) ; however , on the day of stimulation there was more time with rectal contractions in the group receiving TENS ( median 51 % [ range 25%–78 % ] ) compared with placebo ( median 32 % [ range 4%–68 % ] ; P = 0.02 ) . Also , there was an increase in time with rectal contractions in the TENS group ( P = 0.007 ) but not in the placebo group ( P = 0.39 ) . The night after the TENS was disabled , rectal activity in both groups returned to baseline level . Conclusions : TENS acutely increases time with rectal contractions in children undergoing urodynamic investigation . The effect disappears when the stimulator is turned off BACKGROUND : Sacral neuromodulation therapy has been successfully applied in adult patients with urinary and fecal incontinence and in adults with constipation not responding to intensive conservative treatment . No data , however , are available on sacral neuromodulation therapy as a treatment option in adolescents with refractory functional constipation . OBJECTIVES : This study aim ed to describe the short-term results of sacral neuromodulation in adolescents with chronic functional constipation refractory to intensive conservative treatment . DESIGN : This is a retrospective review . SETTING : This study took place at the Department of Surgery , Maastricht University Medical Centre , The Netherl and s. PATIENTS : Thirteen patients ( all girls , age 10–18 years ) with functional constipation according to the ROME III criteria not responding to intensive oral and rectal laxative treatment were assigned for sacral neuromodulation . MAIN OUTCOME MEASURES : When improvement of symptoms was observed during the testing phase , a permanent stimulator was implanted . Patients were prospect ively followed up to at least 6 months after implantation of the permanent stimulator by interviews , bowel diaries , and Clevel and Clinic constipation score . Improvement was defined as spontaneous defecation ≥2 times a week . RESULTS : At presentation , none of the patients had spontaneous defecation or felt the urge to defecate . All patients had severe abdominal pain . Regular school absenteeism was present in 10 patients . After the testing phase , all but 2 patients had spontaneous defecation ≥2 times a week with a reduction in abdominal pain . After implantation , 11 ( of 12 ) had a normal spontaneous defecation pattern of ≥2 times a week without medication , felt the urge to defecate , and perceived less abdominal pain without relapse of symptoms until 6 months after implantation . The average Clevel and Clinic constipation score decreased from 20.9 to 8.4 . One lead revision and 2 pacemaker relocations were necessary . LIMITATIONS : This study is limited by its small sample size , single-institution bias , and retrospective nature . CONCLUSION : Sacral neuromodulation appears to be a promising new treatment option in adolescents with refractory functional constipation not responding to intensive conservative therapy . Larger r and omized studies with long-term follow-up are required PURPOSE This study aim ed to test the effectiveness of home transcutaneous electrical stimulation ( TES ) when patients with slow-transit constipation ( STC ) were trained by a naive clinician . METHODS A surgeon was trained to teach the TES method to STC children who then self-administered at home ( 1 hour a day , 3 - 6 months ) using a battery-powered interferential stimulator . Bowel diaries , PedsQL4.0 question naires , and radio-nuclear colonic transit studies were completed before and after treatment . RESULTS Thirty-two children ( 16 female ; mean age , 8.3 years ; range , 3 - 17 years ) self-administered 3 to 6 months of TES . Three did not return diaries . Group 1 ( n = 13 ) started with less than 3 bowel actions per week , and group 2 ( n = 16 ) , with more than 3 bowel actions per week . Defecation frequency increased in 69 % of group 1 ( mean , 1.4 - 3.0 per week ; P = .02 ) . Soiling frequency decreased in 50 % of group 2 ( 5.4 - 1.9 per week , P = .04 ) . Of 13 patients , 7 improved with development of urge-initiated defecation . Abdominal pain decreased in 48 % ( 1.6 episodes per week to 0.9 per week , P = .06 ) . Stool consistency improved in 56 % . There was significant improvement in child-reported and parent-reported PedsQL Scores . Colonic transit improved in 13 of 25 patients . CONCLUSION Home TES provides a new treatment for STC children , with 50 % of treatment-resistant patients benefited . Success requires clinician training and close patient contact . Transcutaneous electrical stimulation increased defecation and reduced soiling |
13,389 | 28,333,286 | SUMMARY ANSWER Women with PCOS have significantly increased odds of moderate and severe depressive and anxiety symptoms , independent of obesity , and the symptoms are weakly associated with age , BMI , elevated testosterone , hirsutism and IR .
WHAT IS KNOWN ALREADY Previous studies have reported that women with PCOS have an increased prevalence of mild depressive and anxiety symptoms or an increase in mean depression and anxiety scores , although these scores are usually within the normal range .
Thus , it is therefore not clear whether these findings are clinical ly significant .
WIDER IMPLICATION S OF THE FINDINGS This evidence - synthesis analysis shows that PCOS diagnosis is associated with an increased risk of moderate and severe depressive and anxiety symptoms and suggests that providers should consider screening women with PCOS for both depression and anxiety . | STUDY QUESTION Do women with polycystic ovary syndrome ( PCOS ) have an increased prevalence of moderate and severe depressive and anxiety symptoms compared with control women , and do these symptoms correlate with age , BMI , testosterone , hirsutism or insulin resistance ( IR ) ?
The prevalence of moderate and severe depressive and anxiety symptoms , which require follow-up and would benefit from treatment , is not known in this population . | STUDY QUESTION We aim ed to determine the impact of an oral contraceptive ( OC ) treatment on health-related quality of life ( HRQOL ) , depressive and anxiety symptoms in polycystic ovary syndrome ( PCOS ) . SUMMARY ANSWER OC therapy in PCOS improves hirsutism and menstrual disturbances , along with HRQOL . This improvement is not associated with any change in the prevalence of depressive and anxiety symptoms . WHAT IS KNOWN AND WHAT THIS ARTICLE ADDS : Limited data are available regarding the effects of an OC on HRQOL , and depressive and anxiety symptoms in PCOS . This study reports the effects of the ethinyl estradiol/drospirenone ( EE/DRSP ) OC on an HRQOL question naire for women with PCOS ( PCOSQ ) , depressive and anxiety symptoms after 6 months of treatment . DESIGN Prospect i ve observational study . All participants completed PCOSQ , Beck Depression Inventory , Hospital Anxiety and Depression Scale and General Health Question naire . Serum and rogens , fasting insulin , fasting and postload glucose values during an oral glucose tolerance test were measured . Changes in these variables and the scores of question naires were evaluated after 6 months of treatment with EE/DRSP ( 3 mg/30 μg ) . PARTICIPANTS AND SETTING Thirty-six patients with PCOS without a previous psychiatric diagnosis were included in the study . MAIN RESULTS AND THE ROLE OF CHANCE The main complaints of the patients were hirsutism and irregular menses . Accordingly , menstrual and hirsutism problems were the most serious concerns followed by emotional problems on the PCOSQ . Eight patients ( 22.2 % ) had clinical depression scores . After treatment , regular menstrual cycles were attained and hirsutism was significantly improved in all patients . Hirsutism and emotion domains of the PCOSQ improved at 6 months ( P < 0.05 for both ) . Depression was improved in five of eight depressive patients and four new patients showed increased depression scores . Overall , depression , anxiety mean scores and depression rates did not show a significant change . BIAS , CONFOUNDING AND OTHER REASONS FOR CAUTION The study is subject to the strengths and limitations of observational study design . A limitation of our study is the small sample size and lack of data related to possible confounding factors . GENERALIZABILITY TO OTHER POPULATION S Generalizable to Caucasian PCOS OBJECTIVE To evaluate the ability of women affected by functional hypothalamic secondary amenorrhea ( FHSA ) or polycystic ovary syndrome ( PCOS ) to adapt to stress . DESIGN Controlled clinical study . SETTING University hospital . PATIENT(S ) Thirty-one patients affected by FHSA , 29 patients with PCOS , and 30 eumenorrheic women . INTERVENTION(S ) The subjects took the Stroop Color Word ( Stroop CW ) test and underwent blood sampling . MAIN OUTCOME MEASURE(S ) Heart rate ( HR ) , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and serum cortisol levels . RESULT ( S ) The healthy controls had better Stroop CW scores than patients with FHSA . Serum cortisol levels significantly increased during Stroop CW with respect to the baseline in patients with FHSA or PCOS but not in the healthy controls . The SBP , DBP , and HR of the controls as well as SBP and DBP of patients with PCOS were significantly higher than those measured in patients with FHSA both at the baseline and during Stroop CW . CONCLUSION ( S ) Patients with FHSA do not cope as well as healthy patients , and their autonomic response to stress is worse than both controls and patients with PCOS CONTEXT The contribution of reproductive hormones to mood has been the focus of considerable research . Results from clinical and epidemiological studies have been inconsistent . It remains unclear whether alterations in serum hormone levels across the menopausal transition are linked to depressive symptoms . OBJECTIVES To evaluate the relationship between serum hormone levels and high depressive symptoms and whether hormone levels or their change might explain the association of menopausal status with depressive symptoms previously reported in a national sample of midlife women . DESIGN A longitudinal , community-based , multisite study of menopause . Data were collected at baseline and annually from December 1995 to January 2008 on a range of factors . Early follicular phase serum sample s were assayed for levels of estradiol , follicle-stimulating hormone , testosterone , and dehydroepi and rosterone sulfate . SETTING Seven communities nationwide . PARTICIPANTS A community-based sample of 3302 multiethnic women , aged 42 to 52 years , still menstruating and not using exogenous reproductive hormones . Main Outcome Measure Depressive symptoms assessed with the Center for Epidemiological Studies Depression Scale ( CES-D ) . The primary outcome was a CES-D score of 16 or higher . RESULTS In multivariable r and om-effects logistic regression models , log-transformed testosterone level was significantly positively associated with higher odds of a CES-D score of 16 or higher ( odds ratio = 1.15 ; 95 % confidence interval , 1.01 - 1.31 ) across 8 years , and a larger increase in log-transformed testosterone from baseline to each annual visit was significantly associated with increased odds of a CES-D score of 16 or higher ( odds ratio = 1.23 ; 95 % confidence interval , 1.04 - 1.45 ) . Less education , being Hispanic , and vasomotor symptoms , stressful life events , and low social support at each visit were each independently associated with a CES-D score of 16 or higher . No other hormones were associated with a CES-D score of 16 or higher . Being perimenopausal or postmenopausal compared with being premenopausal remained significantly associated with a CES-D score of 16 or higher in all analyses . CONCLUSIONS Higher testosterone levels may contribute to higher depressive symptoms during the menopausal transition . This association is independent of menopausal status , which remains an independent predictor of higher depressive symptoms BACKGROUND We analyzed the neuroendocrine and immune cell responses to psychosocial stress in PCOS patients compared to BMI -matched healthy controls . METHODS Responses to public speaking stress were analyzed in 32 PCOS patients and 32 BMI -matched healthy controls . At baseline , during , and 10- and 45-min after stress , state anxiety , cardiovascular responses , cortisol , ACTH , as well as circulating leukocyte sub population s were analyzed , together with hsCRP and serum IL-6 concentrations . RESULTS In response to public speaking stress , both groups showed significant but comparable increases in state anxiety , and blood pressure ( all p<0.001 ; time effects ) . The ACTH and cortisol stress responses were significantly enhanced in PCOS ( both p<0.05 ; interaction effect ) . In addition , heart rate was significantly higher in PCOS ( p<0.05 ; group effect ) . PCOS patients displayed a reduced upregulation of IL-6 levels in response to stress ( p<0.05 ; interaction effect ) . Baseline levels of circulating leukocyte sub population s , IL-6 and hsCRP concentrations did not differ between BMI -matched controls and PCOS patients . PCOS patients were characterized by markedly increased psychological distress . CONCLUSIONS PCOS patients showed enhanced HPA-axis and heart rate reactivity as well as a reduced upregulation of IL-6 in response to stress . The altered stress reactivity in PCOS patients may constitute a link between depression , overweight , and the cardiovascular and diabetes risks associated with the diagnosis CONTEXT Polycystic ovary syndrome ( PCOS ) is associated with reduced health-related quality of life ( HRQOL ) and increased prevalence of depressive and anxiety disorders . The impact of PCOS-specific treatments on these co-morbidities is unclear . OBJECTIVE To assess the impact of weight loss and decreasing hyper and rogenism on HRQOL and mood and anxiety disorders in women with PCOS . DESIGN / SETTING / PARTICIPANTS A secondary analysis of a r and omized controlled trial ( OWL-PCOS ) of preconception treatment conducted at two academic centers in women ( age , 18 - 40 years ; body mass index , 27 - 42 kg/m(2 ) ) with PCOS defined by Rotterdam criteria . INTERVENTION Continuous oral contraceptive pill ( OCP ) or intensive lifestyle intervention or the combination ( Combined ) for 16 weeks . MAIN OUTCOME MEASURE(S ) Changes in HRQOL assessed by PCOSQ and SF-36 and prevalence of depression and anxiety disorder assessed by PRIME-MD PHQ . RESULTS The lowest scores were noted on the general health domain of the SF-36 and the weight and infertility domains on the PCOSQ . All three interventions result ed in significant improvement in the general health score on the SF-36 . Both the OCP and Combined groups showed improvements in all domains of the PCOSQ ( P < .01 ) compared to baseline scores . The Combined group had significant improvements in the weight , body hair , and infertility domains compared to a single treatment group ( P < .05 ) . In a linear regression model , change in weight correlated with improvements in the weight domain ( P < .001 ) and physical well-being ( P < .02 ) , change in T correlated with improvements in the hair domain ( P < .001 ) , and change in both weight and T correlated with the infertility ( P < .001 ) and menstrual domains ( P < .05 ) . CONCLUSIONS Both weight loss and OCP use result in significant improvements in several physical and mental domains related to quality of life , depressive symptoms , and anxiety disorders , and combined therapies offer further benefits in overweight/obese women with PCOS INTRODUCTION In the current study we aim ed to determine body image , self-esteem and depressive symptomatology in women with Polycystic ovary syndrome ( PCOS ) and compare with healthy controls . METHOD This study was conducted among the patients with untreated PCOS who admitted to the Outpatient Clinic of Gynecology and Obstetrics of Faculty of Medicine of Selçuk University . A total 83 consecutive women with PCOS met the criteria of present study were included in the study . Age matched healthy controls ( n=64 ) were recruited from employees at Selçuk University Hospital . PCOS was defined according to Rotterdam criteria . After socio-demographic characteristics of the participants were recorded , Body Image Scale , Rosenberg Self-Esteem Scale and Beck Depression Inventory were completed by the participants . RESULTS Patients with PCOS and healthy controls did not differ in some sociodemographic variables , including age , education and economic status ( p>.05 ) . Previous psychiatric history was more prevalent among the PCOS group ( p<. 05 ) . Body mass index ( BMI ) was ≤25 kg/m2 in both groups . BMI values in the PCOS group were significantly higher than in the controls ( p<.05 ) . BDI scores were significantly higher in the PCOS group compared to that in the healthy controls ( p<.05 ) . There was no significant difference between the PCOS group and healthy controls in BIS and RSES scores ( p>.05 ) . CONCLUSION The present study suggests that PCOS seems to be associated with depressive symptomatology . Furthermore , rising BMI values of these women may be an indicator for the onset of PCOS . However , these results should be confirmed by prospect i ve studies CONTEXT The polycystic ovary syndrome ( PCOS ) is the commonest endocrine abnormality in women of reproductive age . OBJECTIVE To determine the rate of hospital admissions for women with PCOS in Western Australian population in comparison to women without PCOS . DESIGN A population -based retrospective cohort study using data linkage in a statewide hospital morbidity data base system . SETTING All hospitals within Western Australia . PARTICIPANTS A total of 2566 women with PCOS hospitalized from 1997 - 2011 and 25 660 r and omly selected age-matched women without a PCOS diagnosis derived from the electoral roll . MAIN OUTCOME MEASURES Hospitalizations by ICD-10-M diagnoses from 15 years were compared . RESULTS Hospitalizations were followed until a median age of 35.8 years ( interquartile range , 31.0 - 39.9 ) . PCOS was associated with more nonobstetric and non-injury-related hospital admissions ( median , 5 vs 2 ; P < .001 ) , a diagnosis of adult-onset diabetes ( 12.5 vs 3.8 % ) , obesity ( 16.0 vs 3.7 % ) , hypertensive disorder ( 3.8 vs 0.7 % ) , ischemic heart disease ( 0.8 vs 0.2 % ) , cerebrovascular disease ( 0.6 vs 0.2 % ) , arterial and venous disease ( 0.5 vs 0.2 % and 10.4 vs 5.6 % , respectively ) , asthma ( 10.6 vs 4.5 % ) , stress/anxiety ( 14.0 vs 5.9 % ) , depression ( 9.8 vs 4.3 % ) , licit/illicit drug-related admissions ( 8.8 vs 4.5 % ) , self-harm ( 7.2 vs 2.9 % ) , l and transport accidents ( 5.2 vs 3.8 % ) , and mortality ( 0.7 vs 0.4 % ) ( all P < .001 ) . Women with PCOS had a higher rate of admissions for menorrhagia ( 14.1 vs 3.6 % ) , treatment of infertility ( 40.9 vs 4.6 % ) , and miscarriage ( 11.1 vs 6.1 % ) and were more likely to require in vitro fertilization ( 17.2 vs 2.0 % ) . CONCLUSION PCOS has profound medical implication s for the health of women , and health care re sources should be directed accordingly OBJECTIVE To determine the conversion risk and predictors for depression in women with polycystic ovary syndrome . DESIGN Prospect i ve longitudinal study . SETTING University practice . PATIENT(S ) Subjects with polycystic ovary syndrome who had participated in a previous study . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) The Primary Care Evaluation of Mental Disorders Patient Health Question naire was used to diagnose major depressive disorder and other depressive syndromes , anxiety syndromes , and binge eating disorder . Subjects completed a question naire on knowledge about polycystic ovary syndrome and treatment satisfaction . RESULT ( S ) A total of 60 of 103 subjects responded to the second survey . Mean time between the two surveys was 22 months ( range 12 - 26 months ) . The overall prevalence of depression was 40 % ( 24/60 ) . Of these , 10 women screened positive for major depressive disorder or other depressive syndromes and 14 were receiving antidepressant medications . There were 11 new cases identified in the second survey ( 19 % conversion ) . Total subjects with mood disorders in this study were 34/60 ( 56.6 % ) , including 11.6 % with anxiety syndromes and 23.3 % with binge eating disorder . Difficulties with menstrual function , fertility , and body image ( weight , hirsutism , acne ) were not significantly different in women with and without depression . CONCLUSION ( S ) There is a significant risk for mood disorders ( defined by the Diagnostic and Statistical Manual of Mental Disorders-IV ) in women with polycystic ovary syndrome . This finding together with a high conversion risk for depression over a 1- to 2-year period underscores the importance of routine screening and aggressive treatment of mental health disorders in this population |
13,390 | 26,700,137 | Results : College students and younger , more educated , adults prefer shared decision making .
Shared decision making shows promise for decreasing antibiotic use for respiratory tract infections . | ABSTRACT Objective : This systematic review examines shared decision making to promote the appropriate use of antibiotics for college students with respiratory tract infections . | Background : Few interventions have proven effective in reducing the overuse of antibiotics for acute respiratory infections . We evaluated the effect of DECISION+2 , a shared decision-making training program , on the percentage of patients who decided to take antibiotics after consultation with a physician or resident . Methods : We performed a r and omized trial , clustered at the level of family practice teaching unit , with 2 study arms : DECISION+2 and control . The DECISION+2 training program included a 2-hour online tutorial followed by a 2-hour interactive seminar about shared decision-making . The primary outcome was the proportion of patients who decided to use antibiotics immediately after consultation . We also recorded patients ’ perception that shared decision-making had occurred . Two weeks after the initial consultation , we assessed patients ’ adherence to the decision , repeat consultation , decisional regret and quality of life . Results : We compared outcomes among 181 patients who consulted 77 physicians in 5 family practice teaching units in the DECISION+2 group , and 178 patients who consulted 72 physicians in 4 family practice teaching units in the control group . The percentage of patients who decided to use antibiotics after consultation was 52.2 % in the control group and 27.2 % in the DECISION+2 group ( absolute difference 25.0 % , adjusted relative risk 0.48 , 95 % confidence interval 0.34–0.68 ) . DECISION+2 was associated with patients taking a more active role in decision-making ( Z = 3.9 , p < 0.001 ) . Patient outcomes 2 weeks after consultation were similar in both groups . Interpretation : The shared decision-making program DECISION+2 enhanced patient participation in decision-making and led to fewer patients deciding to use antibiotics for acute respiratory infections . This reduction did not have a negative effect on patient outcomes 2 weeks after consultation . Clinical Trials.gov trial register no. NCT01116076 OBJECTIVES Assessing the efficacy of an educational intervention that aim ed to reduce unnecessary antibiotic prescriptions in primary care by motivating GPs to change their attitudes to communication and by empowering patients . METHODS One hundred and four GPs in North-Rhine/Westphalia-Lippe , Germany were cluster-r and omized into intervention and control . GPs r and omized to receive the intervention were visited by peers . The intervention strategy was focused on the communication within the encounter , not on sharing knowledge about antibiotic prescribing . Leaflets and posters were provided that aim ed at patient empowerment , thus enabling patients to raise the topic of antibiotic prescriptions themselves . RESULTS Eighty-six GPs ( 83 % ) remained in the study at 6 weeks and 61 GPs ( 59 % ) at 12 months . Antibiotic prescription rates within the control group were 54.7 % at baseline and 36.4 % within the intervention group at baseline . Generalized estimating equation models were applied . Baseline imbalances and confounding variables were controlled by adjustment . After the intervention , the ORs for the prescription of an antibiotic dropped to 0.58 [ 95 % CI : ( 0.43;0.78 ) , P < 0.001 ] after 6 weeks and were 0.72 [ 95 % CI : ( 0.54;0.97 ) , P = 0.028 ] after 12 months in the intervention group . In the control group , the ORs rose to 1.52 [ 95 % CI : ( 1.19;1.95 ) , P = 0.001 ] after 6 weeks and were 1.31 [ 95 % CI : ( 1.01;1.71 ) , P = 0.044 ] after 12 months ; these ORs correspond to an approximately 60 % relative reduction in antibiotic prescription rates at 6 weeks and a persistent 40 % relative reduction at 12 months . CONCLUSIONS An interventional strategy that focused on doctor-patient communication and patient empowerment is an effective concept to reduce antibiotic prescriptions in primary care UNLABELLED A cluster-r and omised controlled trial in general practice BACKGROUND Physician-patient communication plays a key role in treatment decisions in primary care . We aim ed to reduce the antibiotic prescription rate for acute respiratory tract infections using a short training programme in patient-centred communication . METHODS We conducted a cluster-r and omised controlled trial in 45 general practice s in Switzerl and . Thirty physicians received evidence -based guidelines for the management of acute respiratory tract infections ; 15 physicians r and omised to the full intervention additionally received training in patient-centred communication . A further 15 physicians , not r and omised , served as a control to blind the physicians in the other two groups to the true comparison . The primary outcome was the antibiotic prescription rate reported by pharmacists . Secondary outcomes were patient satisfaction and enablement , re-consultation rates , days with restrictions , and days off work . 1108 adults with acute respiratory infections were screened between January and May 2004 . Outcomes were measured in 837 consultations ; 624 patients had follow-up interviews at 7 and 14 days . RESULTS The antibiotic prescription rate reported by pharmacists was low in both full and limited intervention groups ( 13.5 % and 15.7 % respectively ) but only half of the antibiotics were prescribed according to guidelines ( 53.8 % and 53.1 % ) . No significant differences were seen between the two r and omised groups in primary and secondary outcomes . In both groups patient satisfaction was high ( median score for both 68 out of 70 ) . CONCLUSIONS In this trial , patient-centred communication training did not reduce the rate of antibiotic prescriptions below an already unusually low level . Even with this low prescription rate , patient satisfaction with received care was high |
13,391 | 28,986,982 | We found no RCTs as evidence to support or refute the use of EEG and its timing after complex febrile seizures among children . | BACKGROUND Febrile seizures can be classified as simple or complex .
Complex febrile seizures are associated with fever that lasts longer than 15 minutes , occur more than once within 24 hours , and are confined to one side of the child 's body .
It is common in some countries for doctors to recommend an electroencephalograph ( EEG ) for children with complex febrile seizures .
A limited evidence base is available to support the use of EEG and its timing after complex febrile seizures among children .
OBJECTIVES To assess the use of EEG and its timing after complex febrile seizures in children younger than five years of age . | The results of the initial North American trial of the nonionic , water-soluble contrast medium iopamidol for lumbosacral myelography are reported . The iopamidol was easily visualized by fluoroscopy during introduction , and the radiographic quality of all 12 conventional myelographic examinations was excellent . The diagnoses were herniated nucleus pulposus ( seven ) , traumatic dislocation ( one ) , metastasis ( one ) , and normal ( three ) . One patient had a repeat myelogram with a different hydrosoluble contrast medium 2 months after his iopamidol examination and surgery and showed no radiographic evidence of arachnoiditis . The adverse reactions were all mild and transient : headache ( four cases ) , nausea ( two ) , and leg pain ( one ) . There were no diaphoresis , fever , seizures , hallucinations , agitation , or vital sign changes . Electrocardiography , hematology , and blood chemistries were all normal . In two patients , electroencephalogram changes , three to four bursts of diffuse intermittent rhythmic delta activity with no spiking , were present at 6 hr with return to normal at 24 hr OBJECTIVE To evaluate the efficacy of different antipyretic agents and their highest recommended doses for preventing febrile seizures . DESIGN R and omized , placebo-controlled , double-blind trial . SETTING Five hospitals , each working as the only pediatric hospital in its region . PARTICIPANTS A total of 231 children who experienced their first febrile seizure between January 1 , 1997 , and December 31 , 2003 . The children were observed for 2 years . INTERVENTIONS All febrile episodes during follow-up were treated first with either rectal diclofenac or placebo . After 8 hours , treatment was continued with oral ibuprofen , acetaminophen , or placebo . MAIN OUTCOME MEASURE Recurrence of febrile seizures . RESULTS The children experienced 851 febrile episodes , and 89 of these included a febrile seizure . Febrile seizure recurrences occurred in 54 of the 231 children ( 23.4 % ) . There were no significant differences between the groups in the main measure of effect , and the effect estimates were similar , as the rate was 23.4 % ( 46 of 197 ) in those receiving antipyretic agents and 23.5 % ( 8 of 34 ) in those receiving placebo ( difference , 0.2 ; 95 % confidence interval , -12.8 to 17.6 ; P = .99 ) . Fever was significantly higher during the episodes with seizure than in those without seizure ( 39.7 degrees C vs 38.9 degrees C ; difference , 0.7 degrees C ; 95 % confidence interval , -0.9 degrees C to -0.6 degrees C ; P < .001 ) , and this phenomenon was independent of the medication given . CONCLUSIONS Antipyretic agents are ineffective for the prevention of recurrences of febrile seizures and for the lowering of body temperature in patients with a febrile episode that leads to a recurrent febrile seizure OBJECTIVE To analyze clinical , electrophysiologic , and neuroradiologic characteristics and prognostic factors in a group of patients with temporal lobe epilepsy ( TLE ) and complex partial seizures ( CPS ) occurring exclusively or predominantly after they fall asleep or before they awaken . BACKGROUND CPS arising during sleep are classically identified with frontal lobe epilepsy . TLE associated with seizures occurring only or predominantly during sleep ( nocturnal TLE ) is less common . METHODS From a series of patients with refractory TLE studied between 1980 and 1996 , the authors identified 26 patients ( 15 men ) with nonlesional nocturnal TLE ( mean age , 40 years ) . Clinical and laboratory characteristics of these individuals were studied and compared with a group of 72 age-matched , r and omly selected patients with nonlesional TLE and predominantly diurnal seizures ( diurnal TLE ) . RESULTS Mean age at seizure onset was similar for both groups ( 16.3 versus 18.7 years ) . In the nocturnal TLE group , 2 of 26 patients had a positive family history of epilepsy , 18 reported an aura , 4 presented with CPS in clusters , 11 had unilateral and 15 bilateral temporal EEG abnormalities , and 14 of 21 studied had unilateral mesial temporal atrophy . None of these factors differed significantly in the two groups except for higher frequency of the following in the diurnal TLE group compared with the nocturnal TLE group : positive family history for epilepsy ( 33 % versus 8 % , p=0.01 ) , estimated frequency of seizures ( median , 14 versus 2 per month ; p < 0.01 ) , and presence of antecedent febrile convulsions ( 33 % versus 11 % , p=0.04 ) . In the nocturnal TLE group , eight patients underwent surgical therapy and became seizure free ( follow-up , > 12 months ) . Only two were seizure free on medication . CONCLUSIONS Infrequent and nonclustered seizures , rare family history of epilepsy , and low prevalence of childhood febrile convulsions characterize nocturnal TLE . Within the TLEs , the nocturnal TLE form seems to have a better surgical prognosis This study aim ed to determine the reliability of clinical history and seizure semiology for distinguishing between frontal lobe seizures ( FLS ) and temporal lobe seizures ( TLS ) . FLS patients ( n=23 ) were consecutively identified through an epilepsy surgery data base . TLS patients ( n=27 ) were selected r and omly from 238 patients who had undergone temporal lobe surgery for epilepsy . The criterion st and ard for seizure localization was the location of resective epilepsy surgery that controlled seizures for a minimum of 2 years . Blinded comparisons of 13 historical information items ( HII ) and 19 video-recorded semiologic features ( VSF ) were made . We identified 3 HII ( sex , history of febrile convulsions , and history of generalized tonic-clonic seizures ) and 2 VSF ( fencing posturing and postictal confusion ) that significantly distinguished between FLS and TLS . The multivariate analysis model correctly identified 87 % of FLS patients and 74 % of TLS patients . No single HII or VSF is sufficient for distinguishing between FLS and TLS . A model integrating multiple HII and VSF may assist in this differentiation , but some patients still may be misclassified The efficacy of short-term diazepam prophylaxis in febrile convulsions was evaluated in a prospect i ve , controlled study . A total of 289 consecutive children admitted with their first febrile seizure were r and omized into two groups . One group received short-term prophylaxis for 18 months with rectally administered diazepam in solution whenever the temperature was greater than or equal to 38.5 degrees C. The control group received no prophylaxis , but diazepam rectally in the event of new seizures . The short-term prophylaxis , a mean of five doses of diazepam per child per year , afforded effective seizure control ; the 18-month recurrence rate was reduced from 39 % to 12 % ( P less than 0.001 ) , the total number of recurrences from 77 to 23 ( P less than 0.001 ) , the long-lasting recurrences from 5.0 % to 0.7 % ( P less than 0.05 ) . The risk of subsequent epilepsy within the first 2 years was the same , regardless of receiving prophylaxis ( 3 % ) or not ( 3 % ) ; it was low after simple febrile convulsions ( no cases of epilepsy in 230 children ) but considerable after complex febrile seizures ( 20 % ) or seizures associated with severe interictal EEG abnormalities ( 50 % ) PURPOSE Febrile seizures are the commonest convulsive event in children younger than 5 years of age ( incidence of 2 - 5 % ) . Electroencephalography ( EEG ) is not indicated in the work up of simple febrile seizures . Information about its role in the assessment of complex febrile seizures ( CFSs ) is unclear and EEGs are frequently ordered . This study was design ed to assess utility of clinical variables at presentation in predicting the likelihood of an abnormal EEG . METHODS EEG requisitions , EEG reports , clinic charts and medical records over an 11-year period ( 1990 - -2001 ) were retrospectively review ed . The relationship between clinical variables like age , timing of the EEG since CFS , family history of seizures , neurological assessment and EEG abnormalities was statistically analyzed . RESULTS One hundred and seventy-five children were included in the study . Of these 39.43 % had EEG abnormalities . Children with a normal EEG were younger than those with an abnormal EEG ( mean age 15.72 months versus 19.75 months , p<0.05 ) . Using multivariate analysis , factors predictive of abnormal EEGs in children with CFS were ; age > 3 years ( p=0.010 ; 95 % CI : 1.5 - -18.8 ) , EEGs performed within 7 days ( p=0.00 ; 95 % CI : 1.78 - -7.12 ) and an abnormal neurological exam ( p=0.053 ; 95 % CI : 0.98 - -16.9 ) . A family history of febrile seizures was more likely to be associated with a normal EEG ( p=0.01 ; 95 % CI : 0.04 - -0.60 ) . CONCLUSIONS Clinical variables at presentation can be used to screen children with CFS for whom an EEG is considered . This may lead to better use of re sources . Whether abnormal EEG translates to future recurrences or epilepsy needs a prospect i ve study PURPOSE To distinguish various types of childhood severe cryptogenic/idiopathic generalised epilepsy on the basis of reproducible diagnostic criteria , using multiple correspondence analysis ( MCA ) . METHODS We applied MCA to a series of 72 children with no evidence of brain damage , starting epilepsy between 1 and 10 years , with two or more types of generalised seizures . We excluded patients with infantile spasms or typical absences . MCA was performed on all clinical and EEG parameters , first throughout follow-up , then restricted to the first year of the disease . RESULTS When including all follow-up variables , there were three groups : ( 1 ) Thirty-seven children with male predominance , familial history of epilepsy , simple febrile convulsions , massive myoclonus , tonic-clonic fits . Outcome was favourable , with no seizures and mildly affected cognitive functions . Interictal EEG showed short sequences of irregular 3-Hz spike-waves . ( 2 ) In 18 children , clinical characteristics were similar to those of the first group at the early stage , but 95 % exhibited myoclonic status and vibratory tonic seizures , with persisting seizures on follow-up . EEG showed long sequences of generalised irregular spike and slow waves . Those two groups meet the characteristics of childhood onset myoclonic-astatic epilepsy ( MAE ) with respectively , favourable and unfavourable outcome . ( 3 ) Eleven children had later onset , atypical absences , tonic and partial seizures , and no myoclonus , or vibratory tonic seizures . All had mental retardation and persisting seizures . EEG showed long sequences of slow spike-wave activity and half the patients had spike and slow wave foci . These patients met the major characteristics of Lennox-Gastaut syndrome . Initial parameters failed to distinguish the first two groups , but Lennox-Gastaut syndrome ( the third group ) was distinct from both groups of myoclonic astatic epilepsy from the onset . Within MAE groups combined , clinical and EEG risk factors for mental retardation could be identified . CONCLUSION It is possible to vali date statistically the distinction between discrete epileptic syndromes . Myoclonic astatic epilepsy is therefore distinct from Lennox-Gastaut syndrome , and the distinction appears from the first year of the disorder Objective : To evaluate the efficacy and safety of adjunctive topiramate ( sprinkle capsules or oral liquid ) in reducing daily rates of partial-onset seizures ( POS ) in infants with refractory POS . Methods : In this double-blind , placebo-controlled , parallel-group , international study , infants ( n = 149 ) with clinical or EEG evidence of refractory POS were r and omly allocated ( 1:1:1:1 ) to receive adjunctive topiramate 5 , 15 , or 25 mg/kg/d or placebo for 20 days . The primary variable was the median percentage reductions in daily POS rate from baseline to final assessment as recorded on a 48-hour video-EEG . Results : Of the 149 infants ( mean age 12 months ) included in the intent-to-treat analysis set , 130 completed the study . Median percentage reduction from baseline in daily POS rate was not significantly different ( p = 0.97 ) between topiramate 25 mg/kg ( 20.4 % ) and placebo ( 13.1 % ) . Lower doses were not formally tested , but nominal p values for comparisons with placebo were not significant ( 15-mg/kg/d dose : p = 0.97 ; 5-mg/kg/d dose : p = 0.91 ) . Treatment-emergent fever , diarrhea , vomiting , anorexia , weight decrease , somnolence , and viral infection occurred more frequently ( ≥10 % difference ) with topiramate than with placebo . Conclusion : In infants aged 1–24 months , topiramate 5 , 15 , or 25 mg/kg/d was not effective as adjunctive treatment for refractory partial-onset seizures . No new safety concerns associated with topiramate use were noted . Classification of evidence : This interventional study provides Class I evidence that topiramate 5 , 15 , or 25 mg/kg/d compared with placebo does not significantly reduce seizure rates in infants aged 1 month to 2 years with refractory partial-onset seizures A prospect i ve epidemiological study of the incidence of simple febrile convulsions ( FC ) was performed in a northern Swedish county . The yearly incidence was 700/100 000 . The children with FC were re-examined three years later . The pre- and perinatal complications were significantly more common in the group of children with FC than in a r and omly collected group of controls . The value of an extensive investigation program is discussed . Between six months and five years of age the children with FC can be separated from those with other cerebral diseases causing epileptic seizures by recording a thorough history followed by a somatic and neurological physical examination and a determination of acute blood glucose . In children less than six months of age and in children in which meningitis or encephalitis can not be ruled out , a lumbar puncture and a blood culture should be performed . If the onset of the convulsion has been after five years of age , if the seizures are partial or have a duration of more than 30 minutes , or if signs of cerebral disease are found , the examination should be supplemented with EEG and relevant investigations . There is no need for an extensive routine program of investigations in the care of children with FC Midazolam , a water-soluble benzodiazepine , is usually given intravenously in status epilepticus . The aim of this study was to determine whether intranasal midazolam is as safe and effective as intravenous diazepam in the treatment of acute childhood seizures . Seventy children aged 2 months to 15 years with acute seizures ( febrile or afebrile ) admitted to the pediatric emergency department of a general hospital during a 14-month period were eligible for inclusion . Intranasal midazolam 0.2 mg/kg and intravenous diazepam 0.2 mg/kg were administered after intravenous lines were established . Intranasal midazolam and intravenous diazepam were equally effective . The mean time to control of seizures was 3.58 ( SD 1.68 ) minutes in the midazolam group and 2.94 ( SD 2.62 ) in the diazepam group , not counting the time required to insert the intravenous line . No significant side effects were observed in either group . Although intranasal midazolam was as safe and effective as diazepam , seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam . Intranasal midazolam can possibly be used not only in medical centers , but also in general practice and at home after appropriate instructions are given to families of children with recurrent seizures The aim of this study was to compare the efficacy and safety of different oral chloral hydrate and dexmedetomidine doses used for sedation during electroencephalography ( EEG ) in children . One hundred sixty children aged 1 to 9 years with American Society of Anesthesiologists physical status I-II who were uncooperative during EEG recording or who were referred to our electrodiagnostic unit for sleep EEG were included to the study . The patients were r and omly assigned into 4 groups . In groups D1 and D2 , patients received oral dexmedetomidine doses of 2 and 3 µg/kg , respectively . In group C1 and C2 , patients received oral chloral hydrate doses of 50 and 100 mg/kg , respectively . The induction time was significantly shorter in group C2 compared with other groups ( P = .000 ) . The rate of adverse effects was significantly higher in group C2 compared with the dexmedetomidine groups ( D1 and D2 ; P = .004 ) . In conclusion , dexmedetomidine can be used safely for sedation during EEG in children The aim of our study was to estimate the role of Mexidol in ceasing of epileptic fits and improving electroencephalographic ( EEG ) pathological patterns in children . 120 patients with generalized epilepsy ( from 4 to 16 years old ) were investigated . All patients were treated by Depakin chrono 30 mg/kg . Children were divided into 2 groups : 1st-- study group consisted of 60 children with combined treatment with Depakin and Mexidol ( 5 mg/kg ) . In the control group ( 60 children ) treatment was performed only by Depakin . 100 children with the first episode of febrile seizures ( from 6 months to 4 years old ) were investigated . 50 children composed the study group with monotheraphy by Mexidol and 50 patients --the control group , without any treatment . The EEG examination was done by computer EEG Topography " Brain Surveyor Saico " . Using Depakin in combination with Mexidol in the study group of patients with generalized epilepsy , improvement of clinical picture of disease and normalization of EEG patterns in 93 % of cases has been observed . In the study group of patients with febrile seizures , normalization of EEG pathological patterns was observed in 82 % cases and in 18 % its improvement was seen . The relapse of seizures at high temperature was observed in 3 patients . In control group EEG patterns were improved only in 20 % , in 48 % no positive effect was observed and in 41 % the worsening of EEG findings was seen . The relapse of febrile seizures was observed in 26 cases . Mexidol titrated to the target doze of 5mg/kg may be effective in combination with Depakin for treatment of patients with generalized epilepsy and as monotherapy in patients with first episode of febrile seizures Varicella-zoster virus ( VZV ) is one of our most common viruses causing central nervous system ( CNS ) infection with sometimes severe neurological complications . Glial fibrillary acidic protein ( GFAp ) , light subunit of neurofilament protein ( NFL ) and S-100β protein are cerebrospinal fluid ( CSF ) biomarkers that have been used to estimate the severity of brain damage and outcome in various CNS diseases . So far , these biomarkers have not been utilised to investigate glial pathology and neuronal damage in patients with VZV CNS infections . In this prospect i ve study , we measured CSF GFAp , NFL and S-100β as markers of brain damage in 24 patients with acute neurological manifestations and VZV DNA detected in CSF by PCR and compared with a control group ( n = 14 ) . Concentrations of CSF NFL and GFAp were increased in patients with VZV CNS infection compared with controls ( p = 0.002 and p = 0.03 ) while levels of S-100β were reduced . In patients with VZV encephalitis the elevations of CSF NFL and GFAp were more pronounced compared with patients with other VZV CNS syndromes . No correlations between the levels of biomarkers and viral load , neurological sequels or clinical outcome were found in this limited number of patients . These results indicate that VZV induces neuronal damage and astrogliosis with more severe brain damage in patients with VZV encephalitis than in patients with other neurological complications caused by this virus The purpose of this study was to compare three different modes of treatment in the prevention of relapses of febrile convulsions ( Phenobarbital = PH , Sodium Valproate = SV , Placebo = PO ) in a r and omized therapeutic trial . The patients included in the study had shown their first generalized convulsive seizure during a bout of fever ( greater than or equal to 38.5 degrees C ) and were aged between 6 months and 4 years . They were subsequently followed up as out patients , and Phenobarbital and sodium valproate levels were measured regularly to ascertain compliance with the treatment and to adjust the dosage accordingly . The patients ' families were question ed with respect to the occurrence of feverish bouts and convulsive seizures during the interval between visits , as well as possible adverse reactions . An EEG was carried out yearly . Results were as follows : - 69 patients - 35 boys and 34 girls - with an average age of 24 months were divided into 3 groups according to treatment : 21 cases on PH , 22 cases on SV , and 26 cases on PO . - they were followed up for an average duration of 21 months . - the average number of feverish bouts per child and per year was evaluated at 2.5 , no statistically significant difference being noticeable between the various modes of prophylaxis . - 15 relapses of febrile seizures were noted in 14 children , over an average duration of 23 months ; on average , relapses occurred after 9 months ; among the 14 children who had relapsed , one had been treated with SV , 4 with PH and 9 with PO , leading to estimated relapse rates of 4 % , 19 % , and 35 % respectively . There is a statistically significant difference in the relapse rates between the treated groups ( SV and PH ) and the Placebo group , and a particularly significant difference between Sodium Valproate and Placebo . ( ABSTRACT TRUNCATED AT 250 WORDS The efficacy of intermittent rectal diazepam prophylaxis is assessed in the prevention of febrile seizures . In a prospect i ve r and omized cohort trial , 139 children ( 77 girls , 62 boys ) who experienced a first febrile seizure were allocated to two groups : group A , which received intermittent diazepam ( n = 68 ) , and group B , which received no prophylaxis ( n = 71 ) . All children had a 3-year follow-up . The inclusion criteria were no personal history of afebrile seizures , normal neurodevelopment , no previous anticonvulsant therapy , and age between 6 months and 3 years . Each group was stratified to low , intermediate , and high risk according to the available clinical data . The 36-month recurrence rates in the no-prophylaxis group were 83 % in high-risk patients , 55 % in intermediate-risk patients , and 46 % in low-risk patients . In the prophylaxis group , the recurrence rates were reduced in all risk groups : 38 % , 35 % , and 33 % , respectively . Intermittent diazepam prophylaxis reduces the recurrence rate mainly in high-risk children provided that sufficient doses are given on time and adequately PURPOSE Anterior temporal lobectomy ( ATL ) is an important option for treatment of medically refractory seizures . Patient selection is not always clear-cut , and there is inherent morbidity and mortality associated with the invasive and expensive surgical protocol s. To determine whether patient selection might be facilitated by application of artificial intelligence , we developed a model that predicted seizure outcome after ATL , using a simulated neural network ( SNN ) . METHODS Predictions of the model were compared with predictions derived from conventional discriminant function analysis . Neural networks and discriminant functions were devised that would predict the occurrence of both Class 1 outcomes ( totally seizure-free ) , and Class 1 or Class 2 outcomes ( nearly or totally seizure-free ) , using data from 87 patients from three surgical centers . The SNNs and discriminant functions were developed using data from a r and omly selected sub sample of 65 patients , and both models were cross-vali date d , using the remaining 22 patients . RESULTS The discriminant functions showed overall predictive accuracy of 78.5 % and 72.7 % , while the neural networks demonstrated overall accuracy of 81.8 % and 95.4 % . CONCLUSIONS Simulated neural networks show promise as adjuncts to decision-making in the selection of epilepsy surgery patients Objective : To evaluate the efficacy , safety , and pharmacokinetics of oxcarbazepine as adjunctive therapy in infants and young children ( 1 month to < 4 years ) . Methods : Children 1 month to < 4 years of age with inadequately controlled partial seizures taking up to two concomitant antiepileptic drugs ( AEDs ) were enrolled in this rater-blind , r and omized , parallel-group study . Patients received either high-dose ( 60 mg/kg/day ) or low-dose ( 10 mg/kg/day ) oxcarbazepine as oral suspension . The primary efficacy variable was the absolute change in electrographic partial seizures with a behavioral correlate ( type 1 seizure ) frequency per 24 hours during the last 72 hours of continuous video-EEG monitoring in the treatment phase compared with baseline seizure frequency . Results : Of 191 patients screened , 128 were r and omized : 64 to both oxcarbazepine dose groups . The median absolute change in type 1 seizure frequency per 24 hours was more effective for the high-dose group ( −2.00 ) compared with the low-dose group ( −1.37 ; p = 0.043 ) . The median percentage reduction in type 1 seizure frequency per 24 hours was also greater in the high-dose group ( 83.33 % ) than in the low-dose group ( 46.18 % ; p = 0.047 ) . The most frequent adverse events ( ≥10 % ) were somnolence and pyrexia , and most were mild in severity . Conclusions : In this study , high-dose oxcarbazepine was significantly more effective than low-dose oxcarbazepine in controlling partial seizures in infants and very young children PURPOSE The success of epilepsy surgery in temporal lobe epilepsy reaches a 64 % rate of seizure freedom , based on a r and omized control trial . Observational studies from epilepsy centers worldwide indicate seizure freedom rates up to 93 % when the etiology is unilateral hippocampal sclerosis . Several risk factors are attributed to the recurrence of seizures following the surgical procedure . Nonetheless , whether race influences the outcome of temporal lobe surgery is unknown . The purpose of this study was to evaluate if race plays a role in outcome following surgery . METHODS Data were obtained from the discharge data base of the University of Alabama at Birmingham video/EEG monitoring unit , between 1998 and 2003 , as well as the clinical charts . Seizure recurrence was evaluated 1 year following surgery . The sample consisted of all patients with a primary diagnosis of mesial temporal sclerosis ( MTS ) who underwent anterior temporal lobectomy . Multiple logistic regression analysis was used to model the presence of seizure recurrence after anterior temporal lobectomy for MTS . Two sets of logistic regression models were estimated to generate odds ratios ( ORs ) for seizure recurrence after an anterior temporal lobectomy for African-Americans or other possible ethnic/racial group present relative to non-Hispanic Caucasians . The first model incorporated only ethnicity as the independent variable and generated unadjusted ORs for seizure recurrence following the surgical procedure . The second set included the independent variables : duration of epilepsy , history of febrile seizures , lateralization of epileptogenic focus , h and edness , and age . RESULTS Seventy patients underwent surgical treatment and all of them had pathologic confirmation of MTS . Follow-up information for six was not available . Analysis of the remaining 64 patients revealed that African-Americans were more likely than non-Hispanic Caucasians to have seizure recurrence after surgery ( OR=2.1 , 95 % CI=0.6 - 8.0 ) . After potential confounders ( duration of epilepsy , history of febrile seizures , lateralization of epileptogenic focus , h and edness , and age ) were controlled , this finding did not change ( OR=1.7 , 95 % CI=0.3 - 10.7 ) . CONCLUSION Our data suggest that race may be an important factor related to seizure outcome following temporal lobectomy OBJECTIVES Up to one-third of the children with epilepsy are diagnosed with cryptogenic localization related epilepsy ( CLRE ) . As yet , there is a lack of studies that specify the short- and long-term prognosis for this group . In this study , we systematic ally established neurological outcome ( represented by seizure frequency ) as well as neuropsychological outcome in a cohort of 68 children with CLRE who had been referred to our tertiary outpatient clinic . Also , we analysed correlations with risk and prognostic factors . PATIENTS AND METHODS A systematic cross-sectional open clinical and non-r and omized design was used including 68 children admitted to our epilepsy centre in a child neurological programme between January 1999 and December 2004 . A model was defined , distinguishing risk factors with a potential effect on epileptogenesis ( history of febrile seizures , family history of epilepsy , history of early mild development delay and serious diagnostic delay ) and prognostic factors , with a potential effect on the course of the epilepsy ( neurological symptoms or soft signs , age at onset , duration of epilepsy , seizure type , percentage of time with epileptiform activity , localization of epileptiform activity , treatment history and treatment duration ) . Seizure frequency was used as the primary outcome variable , whereas three neuropsychological outcomes ( IQ , psychomotor delay and educational delay ) were used as secondary outcome variables . RESULTS The children experienced a broad range of seizure types with the ' absence-like ' complex partial seizure as the most commonly occurring seizure type . Almost half of the children of the study sample had a high seizure frequency . They experienced several seizures per month , week or even daily seizures . Also a substantial impact on neuropsychological outcome was observed . Mean full scale IQ was 87.7 , mean academic delay was almost 1 school year and 27 children showed psychomotor delay on the Movement ABC . Only ' having more than one seizure type ' showed a prognostic value for seizure frequency , and no factors were found to be correlated with the secondary outcome measures . None of the risk factors show a differential impact on seizure outcome . CONCLUSION CLRE has a non-predictable course ; clinical variability is high and prognosis in many children with CLRE is obscure . Having more than one seizure type was the only factor correlated to seizure frequency . Further longitudinal studies are needed OBJECTIVE To describe the clinical , neuropsychological , and psychopathologic features of a cohort of children with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy at time of recruitment and through the first month . The selected population will be followed for 2 - 5 years after enrollment to investigate the epilepsy course and identify early predictors of drug resistance . METHODS In this observational , multicenter , nationwide study , children ( age 1 month-12.9 years ) with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy were consecutively enrolled in 15 Italian tertiary childhood epilepsy centers . Inclusion criteria were as follows : ( 1 ) diagnosis of symptomatic focal epilepsy due to acquired and developmental etiologies , and presumed symptomatic focal epilepsy ; ( 2 ) age at diagnosis older than 1 month and < 13 years ; and ( 3 ) written informed consent . Children were subdivided into three groups : ≤3 years , > 3 to 6 years , and > 6 years . Clinical , electroencephalography ( EEG ) , neuroimaging , and neuropsychological variables were identified for statistical analyses . RESULTS Two hundred fifty-nine children were enrolled ( 116 female and 143 male ) . Median age : 4.4 years ( range 1 month-12.9 years ) ; 46.0 % ( n = 119 ) of children were younger than 3 years , 24 % ( 61 ) from 3 to 6 years of age , and 30 % ( 79 ) older than 6 years . Neurologic examination findings were normal in 71.8 % . Brain magnetic resonance imaging ( MRI ) was abnormal in 59.9 % . Children age ≤3 years experienced the highest seizure frequency in the first month after recruitment ( p < 0.0001 ) . Monotherapy in the first month was used in 67.2 % . Cognitive tests at baseline revealed abnormal scores in 30 % ; behavioral problems were present in 21 % . At multivariate analysis , higher chances to exhibit more than five seizures in the first month after epilepsy onset was confirmed for younger children and those with temporal lobe epilepsy . SIGNIFICANCE In this prospect i ve cohort study , an extensive characterization of epilepsy onset in children with symptomatic or presumed symptomatic focal epilepsies is reported in relation to the age group and the localization of the epileptogenic zone All children 3 years of age on January 1 , 1975 in the Fuchu area of Tokyo were neurologically examined for 6 years ( number examined : 17,044 ) . The cumulative incidence of epilepsy ( i.e. , recurrent nonfebrile seizures ) was 4.3/1,000 and that of occurrence of a single nonfebrile seizure ( NS ) was 4.7/1,000 . Febrile convulsions ( FCs ) were observed in 82/1,000 in this population . The population was followed for 6 - 11 years after the first examination . During the follow-up ( a ) 4 of 80 children who had a single NS before age 3 years developed recurrence after age 3 years ; ( b ) development of epilepsy was found in three of 1,323 r and omly ( 10 % ) selected healthy children for comparison ( 2.3/1,000 ) ; ( c ) among 1,406 children with FCs , epilepsy developed in 24 ( 17/1,000 ) and a single NS occurred in 28 ( 20/1,000 ) ; and ( d ) the total cumulative incidence of epilepsy was 8.2/1,000 in the population aged 9 - 14 years . Age-specific annual incidence of epilepsy was highest in the age range 0 - 1 year ( 1.9/1,000 ) , gradually falling with advancing age . The point prevalence for active epilepsy ( having had a seizure within the past 5 years ) was 2.8/1,000 ; that for inactive epilepsy was 5.4/1,000 ( total 8.2/1,000 ) . Epilepsy developed by age 14 years in ( a ) one-half of children with NS , ( b ) approximately 2 % children with FCs , ( c ) 0.2 % of healthy children with no seizure before age 3 years , and ( d ) an estimated 2 % of potential epileptic carriers ( having spike EEG abnormality by age 3 ; 15 % of the population ) who had not had a seizure by age 3 years Febrile seizure is the most common neurologic disorder in infants and children . This study aim ed to elaborate safe and effective therapy for preventing FS recurrence by levetiracetam ( LEV ) . A prospect i ve study was performed in two groups of children , the no treatment group ( n=51 , 24.1±9.0 months ) and the LEV treatment group ( n=45 , 23.3±8.9 months ) . The findings demonstrated that a significant difference ( P<0.01 ) was observed between the no treatment group 51.0 % ( 26/51 ) and LEV treatment group 15.5 % ( 7/45 ) in terms of FS recurrence after 50 weeks . FS recurrence/fever episode was 12.4 % ( 12/97 ) in the LEV treatment group and 51.8 % ( 57/110 ) in the no treatment group . Furthermore , LEV administration significantly improved ( P<0.001 ) epileptiform + nonspecific EEG abnormalities ( 17.8 % ; 8/45 ) , as compared with the no treatment group ( 68.6 % ; 35/51 ) . In conclusion , LEV could function as an effective therapeutic agent for the prevention of FS recurrence and reducing the frequency of fever episodes . Furthermore , LEV administration significantly improved nonspecific EEG abnormalities , which may be used as a clinical monitoring index for LEV treatment in patients with FS Objective : To analyze clinical , electrophysiologic , and neuroradiologic characteristics of a group of patients with nonlesional intractable temporal lobe epilepsy ( TLE ) and rare or absent interictal epileptiform abnormalities ( IEA ) . Methods : Between 1990 and 2000 , 31 patients ( 11 men ; mean ± SD age 34.3 ± 11.7 years ) with nonlesional intractable TLE were consecutively selected on the basis of the absence or paucity of IEA ( < 1/h ) on serial scalp EEG recording ; these were defined as “ oligospikers . ” The clinical and laboratory characteristics of oligospikers were compared with those of a group of 27 age-matched control subjects ( 10 men ; mean ± SD age 38.5 ± 11 years ) , r and omly selected from a pool of patients with nonlesional TLE with frequent IEA . Results : Oligospikers showed a later age at seizure onset ( mean ± SD 19.1 ± 14.4 versus 10.2 ± 7.4 years ; p = 0.004 ) , lower monthly frequency of complex partial seizures ( median 6 versus 12 ; p = 0.035 ) , lower incidence of secondarily generalized tonic-clonic seizures ( 10 versus 81 % ; p < 0.001 ) , and no status epilepticus ( 0 versus 22 % ) than control subjects . Also , hippocampal atrophy ( HA ) was less commonly found in oligospikers ( 55 versus 96 % ; p = 0.001 ) . However , there were no differences between the two groups in the frequency of family history of epilepsy , risk factors , febrile convulsions , and type of medication . Twenty-three ( 74 % ) oligospikers and 25 ( 93 % ) control patients underwent either a selective amygdalohippocampectomy or corticoamygdalohippocampectomy . Excellent surgical outcome ( Engel ’s Class Ia ) was found in 14 of 23 ( 61 % ) oligospikers and 17 of 25 ( 67 % ) control patients . Conclusions : This study identified a subgroup of patients with nonlesional intractable TLE with no or few IEA . Oligospikers have a later age at seizure onset , less frequent and less severe seizures , besides a lower incidence of HA . The similarity of etiologic factors compared with patients with frequent IEA suggests that the rarity of spikes could reflect a disease not really distinct but less severe , even though still intractable and incapacitating enough to consider surgery . In spite of the absence or paucity of IEA , oligospikers have excellent surgical outcome Objective : To evaluate the efficacy of intermittent clobazam therapy in preventing the recurrence of febrile seizures and to assess its safety . Methods : The study was a prospect i ve , r and omized , double-blind placebo-controlled trial conducted in the Department of Child Health , Christian Medical College Hospital , Vellore between July 2001 and September 2002 . Neurologically normal children between 6 months and 3 years of age with a history of febrile seizures and no evidence of acute CNS infection or EEG abnormality were included into the study . 19 children in a clobazam group and 20 in the placebo group were r and omly allocated . Temperature reduction measures with paractamol and tepid sponging were advised to all children . In addition the dispensed medication was to be administered at the onset of fever and continued for 48 hours irrespective of the duration of fever . The children were then monitored for seizures and adverse effects of clobazam . The children were followed up for a mean period of 9.9 months . The analysis was done on the number of febrile episodes in both the groups . Results : There were a total of 110 episodes of fever during the study period . Mean number of febrile episodes in the clobazam group was 3.1 and in placebo group 2.56 . Six ( 12.5 % ) of the 48 episodes in placebo group and one ( 1.7 % ) of 60 episodes in clobazam group had seizure recurrence . This was statistically significant ( p=0.01 ) . Drowsiness and weakness were present equally in both clobazam and placebo group whereas ataxia was present only in the clobazam group , the difference being statistically significant ( p=0.04 ) . Conclusion : Intermittent clobazam therapy is an effective measure in the prevention of recurrence of febrile seizures . The ataxia due to clobazam was much lower than that reported with diazepam puncture was performed . Specimens of CSF were sent to the laboratory for estimation of the cell count , sugar , protein and amino acids , and for the isolation of bacteria and viruses . Feces was su bmi tted for virus isolation and paired specimens of serum for virology subsequently were taken . Treatment of the initial convulsion was not usually necessary but antibiotics often were needed for associated infections . An EEG was performed at least Background In previous study , we have found intermittent oral levetiracetam ( LEV ) can effectively prevent recurrence of febrile seizure ( FS ) . This study aim ed to analyze the effects of the preventive on the patients with frequent FS accompanied with epileptiform discharge . Methods Patients with frequent FS were assigned to undergo Electroencephalogram ( EEG ) . At the onset of fever , the patients who presented epileptiform discharge were orally administered with LEV with a dose of 15–30 mg/kg per day twice daily for 1 week , thereafter , the dosage was gradually reduced until totally discontinued in the second week . The seizure frequency associated with febrile events and FS recurrence rate during a 48-week follow-up were analyzed . Results among the 19 patients presented epileptiform discharge on EEG , 31.58 % ( 6 of 19 ) had complex FS , 68.42 % ( 13 of 19 ) had simple FS . Up to 57.89 % ( 11 of 19 ) had a family history of seizure disorder and 36.84 % ( 7 of 19 ) had a family history of FS in first-degree relatives . 42.11 % ( 8 of 19 ) happened the first FS episode at the age < 18 months . 36.84 % ( 7/19 ) presented generalized spikes , 63.16 % ( 12/19 ) showed focal spikes . During the 48-week follow-up period , the patients experienced 26 febrile episodes , none of them presented seizure recurrence . Conclusion Intermittent oral LEV can prevent the seizure recurrence of FS accompanied with epileptiform discharge in 48-week . However , further r and omized controlled trials should be conducted . Trial registration ChiCTR-IPR-15007241 ; Registered 1 January 2014 - Retrospectively registered PURPOSE OF THE STUDY To reassess the predictive role of clinical parameters and epileptiform paroxysmal EEG abnormalities for subsequent epilepsy in patients with febrile seizures . PATIENTS AND METHODS 179 patients with febrile seizures were included in a prospect i ve study investigating the impact of some clinical parameters and EEG abnormalities that could be important for future epilepsy . EEGs were performed in afebrile patients after hospital discharge . The follow-up period from the first presentation ranged from 2.1 to 9.2 years ( mean , 6.6 years ) . The correlation between the development of epileptic seizures and the presence of epileptiform EEG abnormalities in the two groups was evaluated with the Mann-Whitney and chi-square test . Statistical significance was set at p<0.05 . RESULTS Febrile seizures occurred more than once in 58 ( 32.5 % ) patients , with one recurrence in 32 ( 17.9 % ) patients and multiple recurrences in 26 ( 14.5 % ) patients . The incidence of paroxysmal abnormalities was 16.8 % . Of these , 15 patients ( 50 % ) showed generalized paroxysms only , while in 15 patients ( 50 % ) , focal abnormalities were found . Epilepsy developed in 12 patients ( 6.7 % ) . There were 27 patients with clinical ly focal features of the first febrile seizure , five ( 18.5 % ) of whom developed epilepsy . With focal EEG abnormalities included , the incidence of epilepsy increased to 50 % . CONCLUSION Generalized EEG discharges in patients with febrile seizures are not predictive of later epilepsy , but focal discharges are |
13,392 | 21,237,544 | The average weighted pre-to-follow-up effect size for the CBT group suggested that these effects were maintained over time .
Smaller but yet statistically significant effects of CBT were found for mood outcome measures .
The results suggest that CBT is an effective treatment of tinnitus distress . | Tinnitus is defined as a sound in the ear(s ) and /or head without external origin and is a serious health concern for millions worldwide .
The aim of the present study was to determine whether Cognitive Behavior Therapy ( CBT ) is effective in reducing distress associated with tinnitus . | OBJECTIVE Using a r and omized group design , the efficacy of an outpatient cognitive-behavioral Tinnitus Coping Training ( TCT ) was compared to two minimal-contact ( MC ) interventions . METHODS TCT was conducted in a group format with 11 sessions ( total n=43 ) . One MC [ MC-E ( education ) , n=16 ] consisted of two group sessions in which education on tinnitus was presented and self-help strategies were introduced . The second MC [ MC-R ( relaxation ) , n=16 ] comprised four sessions . Besides education , music-supported relaxation was suggested as self-help strategy and audiotapes with relaxing music were provided . Furthermore , a waiting-list control group was installed ( WC , n=20 ) . Data were assessed at baseline ( pretherapy ) and at posttherapy period . Only TCT was additionally evaluated at a 6-month and a 12-month follow-up . Several outcome variables ( e.g. , awareness of tinnitus ) were recorded in a tinnitus diary . Tinnitus coping and disability due to tinnitus were assessed by question naires . Subjective ratings of improvement were also requested from the patients . Furthermore , inventories of psychopathology were given to the patients . RESULTS Findings reveal highly significant improvements in TCT in comparison to the control group ( WC ) . MC interventions do not differ significantly from each other , but are superior to WC in a few domains of outcome . Outcome in TCT is somewhat superior to combined MC interventions in two domains of data , but not regarding disability reduction . Effect sizes , nevertheless , indicate distinct differences in degree of improvement , with TCT achieving the best results . CONCLUSIONS A sequential scheme for the treatment of chronic tinnitus is discussed on the basis of cost-effectiveness considerations Many tinnitus sufferers believe that their tinnitus has an organic basis and thus seek medical rather than psychological treatments . Tinnitus has been found to be associated with negative appraisal , dysfunctional attention shift , and heightened psychophysiological arousal , so cognitive-behavioral interventions and biofeedback are commonly suggested as treatments . This study developed and investigated the efficacy of a biofeedback-based cognitive-behavioral treatment for tinnitus . In total , 130 tinnitus patients were r and omly assigned to an intervention or a wait-list control group . Treatment consisted of 12 sessions of a biofeedback-based behavioral intervention over a 3-month period . Patients in the wait-list group participated in the treatment after the intervention group had completed the treatment . Results showed clear improvements regarding tinnitus annoyance , diary ratings of loudness , and feelings of controllability . Furthermore , changes in coping cognitions as well as changes in depressive symptoms were found . Improvements were maintained over a 6-month follow-up period in which medium-to-large effect sizes were observed . The treatment developed and investigated in this study is well accepted and leads to clear and stable improvements . Through demonstration of psychophysiological interrelationships , the treatment enables patients to change their somatic illness perceptions to a more psychosomatic point of view Twenty-four patients with moderately severe ( grade 2 ) to severe ( grade 3 ) subjective tinnitus participated in an experimental group study . The patients were r and omly assigned to a treatment group and a waiting-list control group . Treatment was given with a coping technique and comprised 10 one-hour sessions . Following a corresponding period without treatment , the control group was treated similarly . Daily self-recording of the subjective tinnitus loudness , the discomfort from the tinnitus , depression and irritation was performed before and after treatment . In addition , psychoacoustic measurement was undertaken on three occasions . The treatment group improved significantly more than the waiting-list control group . After treatment of the latter group , combined data of both groups showed statistically significant improvements in all variables . The results show that tinnitus annoyance can be treated by psychological methods This study is a r and omized , waitlist-controlled trial testing the effect of a brief , " manualized " cognitive-behavioral group therapy on distress associated with tinnitus , quality of well-being , psychological distress including depression , and internal focus . Cognitive-behavioral therapy ( CBT ) included training in activity planning , relaxation training and , primarily , cognitive restructuring . Sixty-five participants were recruited , and 41 completed treatment . Participants were r and omly assigned to receive 8 weeks of manualized group CBT either immediately or after an 8-week waiting period . Participants completed outcome measures at the time of their r and om assignment and at 8 , 16 , and 52 weeks later . Repeated-measure analysis of covariance revealed significant group-by-time interactions on measures of tinnitus distress and depression , indicating that CBT led to greater improvement in those symptoms . The current results suggest that CBT , applied in a group format using a manual , can reduce the negative emotional distress , including depression , associated with tinnitus Objective The aim of this study was to investigate if cognitive behavior therapy ( CBT ) provided via the Internet results in significant decreases of distress in individuals with tinnitus . Methods Participants were recruited through Web pages and newspaper articles and thereafter r and omly allocated to a CBT self-help manual in six modules or to a waiting-list control group ( WLC ) . All treatment and contact with participants were conducted via the Internet with Web pages and E-mail correspondence . Participants were 117 individuals with tinnitus of duration of more than 6 months . In the first r and omized controlled phase of the study , 26 completed all stages of treatment ( 51 % dropout ) , and 64 of the WLC group completed measures . At 1-year follow-up , all participants had been offered the program and 96 provided outcome measures ( 18 % dropout rate from baseline ) . Tinnitus-related problems were assessed before and after treatment and at the 1-year follow-up . Daily diary ratings were included for 1 week before and 1 week following the treatment period . Results Tinnitus-related distress , depression , and diary ratings of annoyance decreased significantly . Immediately following the r and omized controlled phase ( with a WLC ) , significantly more participants in the treatment group showed an improvement of at least 50 % on the Tinnitus Reaction Question naire . At the uncontrolled follow-up , 27 ( 31 % ) of all participants had achieved a clinical ly significant improvement . Conclusions CBT via the Internet can help individuals decrease annoyance associated with tinnitus . High dropout rates or delay in completing treatment can be a characteristic of treatment studies using the Internet but should be contrasted with the cost effectiveness and accessibility of the Internet Disabling tinnitus in 27 patients was treated in an experimental setting with two different type of therapy aim ing at the development of coping behaviour . One was focused on behavioural control procedures , while the other aim ed at more cognitive control methods such as distraction . The results of the two forms of therapy were compared with each other and with observations of the untreated control subjects . Assessment s of subjective loudness , discomfort from tinnitus and controllability were made on analogue scales and at a question naire follow-up . Psychoacoustic measures such as personal loudness units ( PLU ) were used in connection with these self-recordings and for evaluation of treatment effects . The results confirmed favourable reports on behavioural methods in tinnitus . However , no differences were found between therapies . The results are discussed in the light of the coping and adaptation theory Sixty subjects with chronic tinnitus were r and omly allocated to one of three experimental conditions : ( 1 ) cognitive coping skills training ( attention diversion , imagery training and thought management skills ) combined with education . ( 2 ) education-only , or ( 3 ) waiting-list control . The two treatment groups improved significantly more than the waiting-list control on measures of frequency of use of coping strategies , benefits derived from the use of coping strategies , irrational beliefs and knowledge about tinnitus . Subjects who received the combined cognitive/education intervention demonstrated significantly greater reductions in distress and h and icaps associated with tinnitus , and engagement in dysfunctional cognitions , than the subjects who received education alone . No significant effects were obtained on measures of depression , locus of control , or on daily ratings of subjective loudness , noticeability or bothersomeness of the tinnitus . At the 12-month follow-up , the differential treatment effects had dissipated . Although the treatment result ed in statistically significant effects , the size of the clinical effects is rather modest . Implication s for the further development of treatment techniques are discussed OBJECTIVE Tinnitus distress can be reduced by means of cognitive-behavior therapy ( CBT ) . To compensate for the shortage of CBT therapists , we aim ed , in this study , to investigate the effects of a CBT-based self-help book guided by brief telephone support . METHODS Seventy-two patients were r and omized either to a self-help book and seven weekly phone calls or to a wait-list control condition , later on receiving the self-help book with less therapist support . The dropout rate was 7 % . Follow-up data 1 year after completion of treatment were also collected ( 12 % dropout ) . The Tinnitus Reaction Question naire ( TRQ ) was the main outcome measure , complemented with daily ratings of tinnitus and measures of insomnia , anxiety , and depression . RESULTS On the TRQ , significant reductions were found in the treatment group both immediately following treatment and at 1-year follow-up . In the treatment group , 32 % reached the criteria for clinical significance ( at least 50 % reduction of the TRQ ) compared to 5 % in the wait-list group . Directly after treatment , two out of five measures showed significant differences in favor of the treatment with more therapist support compared with the group who , after their waiting period , received little therapist support . The self-help treatment was estimated to be 2.6 ( seven phone calls ) and 4.8 ( one phone call ) times as cost-effective as regular CBT group treatment . CONCLUSIONS Guided self-help can serve as an alternative way to administer CBT for tinnitus . Preliminary results cast some doubts on the importance of weekly therapist contact . The effect size was somewhat smaller than for regular CBT , but on the other h and , the self-help seems far more cost-effective . Future studies should compare treatment modalities directly and explore cost-effectiveness more thoroughly Three thous and six hundred r and omly selected adults in the city of Gothenburg ( 425,000 inhabitants ) stratified by age and gender , were question ed by mail concerning tinnitus . We received 66 % useful answers , 14.2 % suffered from tinnitus ' often ' or ' always ' . Tinnitus was more common in males than in females . Tinnitus was much more common in the left than in the right ear . 2.4 % of the whole population suffered from the worst severity degree , ' tinnitus plagues me all day ' . Tinnitus was clearly more common with hearing loss than with subjectively normal hearing . Sleep disturbances were common and increased with tinnitus severity . A majority of the question ed subjects wanted further examination and treatment Using a r and omized control group trial the long-term efficacy of a habituation-based treatment as conceived by Jastreboff , and a cognitive-behavioural tinnitus coping training were compared . An educational intervention was administered as a control condition . Both treatments were conducted in a group format ( habituation-based treatment , 5 sessions ; tinnitus coping training , 11 sessions ) . Educational intervention was delivered in a single group session . Patients were categorized according to their level of disability due to tinnitus ( low , high ) , age and gender and then r and omly allocated to the treatment conditions ( habituation-based treatment , n = 30 ; tinnitus coping training , n = 27 ; educational intervention , n = 20 ) . Data assessment included follow-ups of up to 21 months . Several outcome variables including disability due to tinnitus were assessed either by question naire or diary . Findings reveal highly significant improvements in both tinnitus coping training and habituation-based treatment in comparison with the control group . While tinnitus coping training and habituation-based treatment do not differ significantly in reduction of tinnitus disability , improvement in general well-being and adaptive behaviour is greater in tinnitus coping training than habituation-based treatment . The decrease in disability remains stable throughout the last follow-up in both treatment conditions Two non-medical treatment strategies for chronic idiopathic tinnitus were evaluated in a r and omized control group design . A cognitive-behavioural tinnitus coping training ( TCT ) was developed and compared to yoga and a self-monitoring control condition . Forty-three chronic tinnitus patients , were assessed at baseline , directly after therapy , and at 3 months follow-up . For evaluation , differential psychoacoustic variables were registered , a tinnitus diary as well as the Tinnitus Question naire and different measures of general well-being were used . Statistical analyses showed effects favouring the TCT treatment in comparison to the control and yoga treatment . The TCT-treated patients reported more satisfaction with the training than the yoga group . Participants in the self-monitoring control group were treated either by TCT or yoga after a waiting period . The outcome in this group was even better than in the experimental groups while yoga again showed rather poor effects The aim of the study was to investigate the effects of cognitive behavioral therapy ( CBT ) in elderly people with tinnitus ( < 65 years ) . Thirty-seven patients were called in for a structured interview . Following exclusion , twenty-three participated in the trial . All participants underwent medical ear , nose , and throat ( ENT ) examination , audiometry , and tinnitus matchings . A r and omized controlled design with a waiting list control group was used . A CBT treatment package was delivered in six weekly two hour group sessions . Outcome was measured using vali date d self-report inventories and daily diary ratings of annoyance , loudness and sleep quality for one week pre-treatment , post-treatment . A three month follow-up was included at which time all participants had received treatment , but in a shorter format for the control group . Results showed statistically significant reductions of tinnitus-related distress . Thus , CBT was better than no treatment , but the particular aspects of CBT that contributed to the effects can not be established . In conclusion , the findings give some support for the use of group CBT for elderly people with tinnitus . Sumario El objetivo de este estudio fue investigar los efectos de la terapia conductual cognitiva ( CBT ) en ancianos con acúfeno ( < 65 años ) Se llamaron 37 pacientes para una entrevista estructurada y de ellos 23 participaron en la prueba después de un proceso de exclusión . Todos los participantes fueron objeto de un examen médico ORL , audiometría y acufenometría . Se uso un diseño controlado al azar con un grupo de control de una lista de espera . Se dio un paquete de tratamiento en sesiones grupales de 2 horas seis veces por semana . Los result ados se midieron us and o cuestionarios de autoreporte y las anotaciones diarias del índice de molestia , intensidad subjetiva y calidad del sueño durante una semana previa y una posterior al tratamiento , pero en un formato corto para el grupo control . Los result ados muestran reducciones estadísticamente significativas del malestar relacionado con el acúfeno . Así , la CBT se considera mejor que la ausencia de tratamiento . Pero los aspectos particulares de la CBT que contribuyeron a obtener esos efectos no pueden ser establecidos . En conclusión , los hallazgos apoyan en alguna forma el uso de CBT grupal para ancianos con acúfeno Background : Tinnitus seems to be associated with psychophysiological over-activation ( e.g. , of head and shoulder muscles ) . Therefore we aim ed to develop and evaluate a new intervention program including a psychophysiological approach . Methods : Forty-three tinnitus sufferers were r and omized to 2 groups , one receiving a psychophysiologically oriented intervention lasting 7 intervention sessions ( plus 2 assessment sessions ) , whereas the other group waited for a comparable time period . Afterward , patients on the waiting list also received the intervention . Physiological variables were muscle activity of head and shoulders and electrodermal activity . Psychological assessment s took place at pretreatment , post-treatment , and 6 months later . Follow-up data were available from 95 % of participants . Major outcome variables were self-rating scales ( e.g. , tinnitus annoyance assessed by the Tinnitus Question naire ) , and diary data ( self-control , daily time of perceiving the tinnitus ) . Results : On most tinnitus specific variables , patients in the treatment group improved significantly more than patients on the waiting list . Main effect sizes for tinnitus-specific variables were up to 0.89 . Muscle reactivity of head muscles at the beginning predicted significant treatment effects . Conclusion : Compared with meta-analytical review s of psychological interventions for tinnitus sufferers , the presented treatment is brief and in the upper range of effectiveness . ES = effect size ; GSI = General Symptomatic Index ( mean score of Brief Symptom Inventory ) ; IG = intervention group ; MG = merged group ; SCL-90R = symptom check list ; TQ = Tinnitus Question naire ; WLG = waiting list group |
13,393 | 26,896,044 | In both intervention and active control groups , suicidality decreased over time ; however , most structured psychological depression treatment interventions did not outperform pharmaceutical or treatment as usual control groups .
Depression prevention studies demonstrated small but statistically significant reductions in suicidality .
Conclusions : It is unclear whether psychological treatments are more effective than no treatment since no study has used a no-treatment control group .
There is evidence to suggest that Cognitive Behavioural Therapy interventions produce pre – post reductions in suicidality with moderate effect sizes and are at least as efficacious as pharmacotherapy in reducing suicidality ; however , it is unclear whether these effects are sustained .
Depression prevention interventions show promising short-term effects | Objective : Given depression is a significant risk factor for suicidal behaviour , it is possible that interventions for depression may also reduce the risk of suicide in adolescents .
The purpose of this literature review is to determine whether psychological interventions aim ed to prevent and /or treat depression in adolescents can also reduce suicidality . | BACKGROUND There is great heterogeneity of clinical presentation and outcome in paediatric depression . AIMS To identify which clinical and environmental risk factors at baseline and during treatment predicted major depression at 28-week follow-up in a sample of adolescents with depression . METHOD One hundred and ninety-two British adolescents with unipolar major depression were enrolled in a r and omised controlled trial ( the Adolescent Depression Antidepressants and Psychotherapy Trial , ADAPT ) . Participants were treated for 28 weeks with routine psychosocial care and selective serotonin reuptake inhibitors ( SSRIs ) , with half also receiving cognitive-behavioural therapy ( CBT ) . Full clinical and demographic assessment was carried out at baseline and 28 weeks . RESULTS Depression at 28 weeks was predicted by the additive effects of severity , obsessive-compulsive disorder and suicidal ideation at entry together with presence of at least one disappointing life event over the follow-up period . CONCLUSIONS Clinicians should assess for severity , suicidality and comorbid obsessive-compulsive disorder at presentation and should monitor closely for subsequent life events during treatment OBJECTIVE The authors sought to identify predictors of self-harm adverse events in treatment-resistant , depressed adolescents during the first 12 weeks of treatment . METHOD Depressed adolescents ( N=334 ) who had not responded to a previous trial with an SSRI antidepressant were r and omized to a switch to either another SSRI or venlafaxine , with or without cognitive behavior therapy . Self-harm events , i.e. , suicidal and non-suicidal self-injury adverse events were assessed by spontaneous report for the first 181 participants , and by systematic weekly assessment for the last 153 participants . RESULTS Higher rates of suicidal ( 20.8 % vs. 8.8 % ) and nonsuicidal self-injury ( 17.6 % vs. 2.2 % ) , but not serious adverse events ( 8.4 % vs. 7.3 % ) were detected with systematic monitoring . Median time to a suicidal event was 3 weeks , predicted by high baseline suicidal ideation , family conflict , and drug and alcohol use . Median time to nonsuicidal self-injury was 2 weeks , predicted by previous history of nonsuicidal self-injury . While there were no main effects of treatment , venlafaxine treatment was associated with a higher rate of self-harm adverse events in those with higher suicidal ideation . Adjunctive use of benzodiazepines , while in a small number of participants ( N=10 ) was associated with higher rate of both suicidal and nonsuicidal self-injury adverse events . CONCLUSIONS Since predictors of suicidal adverse events also predict poor response to treatment , and many of these events occurred early in treatment , improving the speed of response to depression , by targeting of family conflict , suicidal ideation , and drug use may help to reduce their incidence . The relationship of venlafaxine and of benzodiazepines to self-harm events requires further study and clinical caution AIM The aim of the present study was to examine the intervention effects of intensive interpersonal psychotherapy for depressed adolescents with suicidal risk ( IPT-A-IN ) by comparison with treatment as usual ( TAU ) at schools . METHODS A total of 347 students from one-fifth of the classes of a high school in southern Taiwan completed the Beck Depression Inventory-II , the Beck Scale for Suicide Ideation , the Beck Anxiety Inventory and the Beck Hopelessness Scale for screening for suicidal risk . Of them , 73 depressed students who had suicidal risk on screening were r and omly assigned to the IPT-A-IN or TAU group . Analysis of covariance ( ANCOVA ) was performed to examine the effect of IPT-A-IN on reducing the severity of depression , suicidal ideation , anxiety and hopelessness . RESULTS Using the pre-intervention scores as covariates , the IPT-A-IN group had lower post-intervention severity of depression , suicidal ideation , anxiety and hopelessness than the TAU group . CONCLUSION Intensive school-based IPT-A-IN is effective in reducing the severity of depression , suicidal ideation , anxiety and hopelessness in depressed adolescents with suicidal risk The objective of this paper is to adapt attachment-based family therapy ( ABFT ) for use with suicidal lesbian , gay , and bisexual ( LGB ) adolescents and to obtain preliminary data on the feasibility and efficacy of the treatment with this population . In Phase I , a treatment development team modified ABFT to meet the unique needs of LGB suicidal youth . In Phase II , 10 suicidal LGB youth were offered 12 weeks of LGB sensitive ABFT . Adolescents ' report of suicidal ideation , depressive symptoms , and maternal attachment-related anxiety and avoidance were gathered at pretreatment , 6 weeks , and 12 weeks ( posttreatment ) . In Phase I , the treatment was adapted to : ( a ) include more individual time working with parents in order to process their disappointments , pain , anger , and fears related to their adolescent 's minority sexual orientation ; ( b ) address the meaning , implication s , and process of acceptance ; and ( c ) heighten parents ' awareness of subtle yet potent invalidating responses to their adolescents ' sexual orientation . Results of Phase II suggest this population can be recruited and successfully treated with a family based therapy , evidence d by high levels of treatment retention and significant decreases in suicidal ideation , depressive symptoms , and maternal attachment-related anxiety and avoidance . This is the first family-based treatment adapted and tested specifically for suicidal LGB adolescents . Though promising , the results are preliminary and more research on larger sample s is warranted BACKGROUND Efficacy trials suggest that structured psychological therapies may significantly reduce recurrence rates of major mood episodes in individuals with bipolar disorders . AIMS To compare the effectiveness of treatment as usual with an additional 22 sessions of cognitive-behavioural therapy ( CBT ) . METHOD We undertook a multicentre , pragmatic , r and omised controlled treatment trial ( n=253 ) . Patients were assessed every 8 weeks for 18 months . RESULTS More than half of the patients had a recurrence by 18 months , with no significant differences between groups ( hazard ratio=1.05 ; 95 % CI 0.74 - 1.50 ) . Post hoc analysis demonstrated a significant interaction ( P=0.04 ) such that adjunctive CBT was significantly more effective than treatment as usual in those with fewer than 12 previous episodes , but less effective in those with more episodes . CONCLUSIONS People with bipolar disorder and comparatively fewer previous mood episodes may benefit from CBT . However , such cases form the minority of those receiving mental healthcare In this report , we conducted a secondary analysis of the Treatment of SSRI-Resistant Depression in Adolescents ( TORDIA ) study to explore the impact of specific cognitive-behavioral therapy ( CBT ) treatment components on outcome . In TORDIA , 334 youths ( ages 12 to 18 years ) with major depressive disorder who had failed to respond to an adequate course of selective serotonin reuptake inhibitor ( SSRI ) medication were r and omized to a medication switch ( either to an alternative SSRI or venlafaxine ) with or without 12 weeks of adjunctive CBT . Participants who had more than 9 CBT sessions were 2.5 times more likely to have adequate treatment response than those who had 9 or fewer sessions . CBT participants who received problem-solving and social skills treatment components , controlling for number of sessions and other confounding variables , were 2.3 and 2.6 times , respectively , more likely to have a positive response . These preliminary findings underscore the importance of receiving an adequate number of sessions to attain an adequate clinical response . Finally , social skills and problem solving may be active elements in CBT for adolescent depression and should be considered in treatment by those working with seriously depressed youths BACKGROUND Previous studies in non clinical sample s have shown psychosocial treatments to be efficacious in the treatment of adolescent depression , but few psychotherapy treatment studies have been conducted in clinical ly referred , depressed adolescents . METHODS One hundred seven adolescent patients with DSM-III-R major depressive disorder ( MDD ) were r and omly assigned to 1 of 3 treatments : individual cognitive behavior therapy , systemic behavior family therapy ( SBFT ) , or individual nondirective supportive therapy ( NST ) . Treatments were 12 to 16 sessions provided in as many weeks . Intent-to-treat analyses were conducted using all follow-up data . RESULTS Of the 107 patients enrolled in the study , 78 ( 72.9 % ) completed the study , 4 ( 3.7 % ) never initiated treatment , 10 ( 9.3 % ) had exclusionary criteria that were undetected at entry , 8 ( 7.5 % ) dropped out , and 7 ( 6.5 % ) were removed for clinical reasons . Cognitive behavior therapy showed a lower rate of MDD at the end of treatment compared with NST ( 17.1 % vs 42.4 % ; P = .02 ) , and result ed in a higher rate of remission ( 64.7 % , defined as absence of MDD and at least 3 consecutive Beck Depression Inventory scores < 9 ) than SBFT ( 37.9 % ; P = .03 ) or NST ( 39.4 % ; p = .04 ) . Cognitive behavior therapy result ed in more rapid relief in interviewer-rated ( vs both treatments , P = .03 ) and self-reported depression ( vs SBFT , P = .02 ) . All 3 treatments showed significant and similar reductions in suicidality and functional impairment . Parents ' views of the credibility of cognitive behavior therapy improved compared with parents ' views of both SBFT ( P = .01 ) and NST ( P = .05 ) . CONCLUSIONS Cognitive behavior therapy is more efficacious than SBFT or NST for adolescent MDD in clinical setting s , result ing in more rapid and complete treatment response OBJECTIVE To examine the course of depression during the treatment of adolescents with depression who had recently attempted suicide . METHOD Adolescents ( N = 124 ) , ages 12 to 18 years , with a 90-day history of suicide attempt , a current diagnosis of depressive disorder ( 96.0 % had major depressive disorder ) , and a Children 's Depression Rating Scale-Revised ( CDRS-R ) score of 36 or higher , entered a 6-month treatment with antidepressant medication , cognitive-behavioral therapy focused on suicide prevention , or their combination ( Comb ) , at five academic sites . Treatment assignment could be either r and om or chosen by study participants . Intent-to-treat , mixed effects regression models of depression and other relevant ratings were estimated . Improvement and remission rates were computed with the last observation carried forward . RESULTS Most patients ( n = 104 or 84 % ) chose treatment assignment , and overall , three fourths ( n = 93 ) received Comb . In Comb , CDRS-R declined from a baseline adjusted mean of 49.6 ( SD 12.3 ) to 38.3 ( 8.0 ) at week 12 and to 27.0 ( 10.1 ) at week 24 ( p < .0001 ) , with a Clinical Global Impression -defined improvement rate of 58.0 % at week 12 and 72.2 % at week 24 and a remission ( CDRS-R ≤ 28 ) rate of 32.5 % at week 12 and 50.0 % at week 24 . The CDRS-R and the Scale for Suicidal Ideation scores were correlated at baseline ( r = 0.43 , p < .0001 ) and declined in parallel . CONCLUSIONS When vigorously treated with a combination of medication and psychotherapy , adolescents with depression who have recently attempted suicide show rates of improvement and remission of depression that seem comparable to those observed in nonsuicidal adolescents with depression Background : Informant discrepancies have been reported between parent and adolescent measures of depressive disorders and suicidality . We aim ed to examine the concordance between adolescent and parent ratings of depressive disorder using both clinical interview and question naire measures and assess multi-informant and multi- method approaches to classification . Method : Within the context of assessment of eligibility for a r and omized clinical trial , 50 parent – adolescent pairs ( mean age of adolescents = 15.0 years ) were interviewed separately with a structured diagnostic interview for depression , the KID-SCID . Adolescent self-report and parent-report versions of the Strengths and Difficulties Question naire , the Short Mood and Feelings Question naire and the Depressive Experiences Question naire were also administered . We examined the diagnostic concordance rates of the parent vs. adolescent structured interview methods and the prediction of adolescent diagnosis via question naire methods . Results : Parent proxy reporting of adolescent depression and suicidal thoughts and behavior is not strongly concordant with adolescent report . Adolescent self-reported symptoms on depression scales provide a more accurate report of diagnosable adolescent depression than parent proxy reports of adolescent depressive symptoms . Adolescent self-report measures can be combined to improve the accuracy of classification . Parents tend to over report their adolescent ’s depressive symptoms while under reporting their suicidal thoughts and behavior . Conclusion : Parent proxy report is clearly less reliable than the adolescent ’s own report of their symptoms and subjective experiences , and could be considered inaccurate for research purpose s. While parent report would still be sought clinical ly where an adolescent refuses to provide information , our findings suggest that parent reporting of adolescent suicidality should be interpreted with caution OBJECTIVE The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents ( TORDIA ) trial after 24 weeks of treatment , including remission and relapse rates and predictors of treatment outcome . METHOD Adolescents ( ages 12 - 18 years ) with selective serotonin reuptake inhibitor (SSRI)-resistant depression were r and omly assigned to either a medication switch alone ( alternate SSRI or venlafaxine ) or a medication switch plus cognitive-behavioral therapy ( CBT ) . At week 12 , responders could continue in their assigned treatment arm and nonresponders received open treatment ( medication and /or CBT ) for 12 more weeks ( 24 weeks total ) . The primary outcomes were remission and relapse , defined by the Adolescent Longitudinal Interval Follow-Up Evaluation as rated by an independent evaluator . RESULTS Of 334 adolescents enrolled in the study , 38.9 % achieved remission by 24 weeks , and initial treatment assignment did not affect rates of remission . Likelihood of remission was much higher ( 61.6 % versus 18.3 % ) and time to remission was much faster among those who had already demonstrated clinical response by week 12 . Remission was also higher among those with lower baseline depression , hopelessness , and self-reported anxiety . At week 12 , lower depression , hopelessness , anxiety , suicidal ideation , family conflict , and absence of comorbid dysthymia , anxiety , and drug/alcohol use and impairment also predicted remission . Of those who responded by week 12 , 19.6 % had a relapse of depression by week 24 . CONCLUSIONS Continued treatment for depression among treatment-resistant adolescents results in remission in approximately one-third of patients , similar to adults . Eventual remission is evident within the first 6 weeks in many , suggesting that earlier intervention among nonresponders could be important OBJECTIVE The Treatment for Adolescents With Depression Study ( TADS ) evaluates the effectiveness of fluoxetine , cognitive-behavioral therapy ( CBT ) , and their combination in adolescents with major depressive disorder . The authors report effectiveness outcomes across a 1-year naturalistic follow-up period . METHOD The r and omized , controlled trial was conducted in 13 academic and community sites in the United States . Stages I , II , and III consisted of 12 , 6 , and 18 weeks of acute , consolidation , and continuation treatment , respectively . Following discontinuation of TADS treatments at the end of stage III , stage IV consisted of 1 year of naturalistic follow-up . The participants were 327 subjects between the ages of 12 and 17 with a primary DSM-IV diagnosis of major depressive disorder . No TADS treatment was provided during the follow-up period ; treatment was available in the community . The primary dependent measures , rated by an independent evaluator blind to treatment status , were the total score on the Children 's Depression Rating Scale-Revised and the rate of response , defined as a rating of much or very much improved on the Clinical Global Impressions improvement measure . RESULTS Sixty-six percent of the eligible subjects participated in at least one stage IV assessment . The benefits seen at the end of active treatment ( week 36 ) persisted during follow-up on all measures of depression and suicidality . CONCLUSIONS In contrast to earlier reports on short-term treatments , in which worsening after treatment is the rule , the longer treatment in the TADS was associated with persistent benefits over 1 year of naturalistic follow-up OBJECTIVES Borderline personality disorder ( BPD ) is frequently encountered in both adult and youth population s. There is a robust literature supporting psychotherapy for adults with BPD , but the literature supporting its use for BPD in youth is more limited . METHODS A literature review was conducted using the keywords " borderline personality disorders " and " adolescence . " Relevant articles were review ed for inclusion . RESULTS Several specialized treatments have been studied with mixed results . Dialectical behaviour therapy has no r and omized controlled trials in adolescents , emotion regulation training has not demonstrated superiority of treatment as usual , and cognitive analytic therapy has demonstrated more rapid recovery but little difference at follow-up . Mentalization-based treatment has one study supporting its use in self-harming adolescents . Pharmacotherapy has no evidence supporting its use in this population . CONCLUSIONS Structured therapy may be the most important therapeutic component in this population BACKGROUND We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents ( TORDIA ) study , a r and omized trial of 334 adolescents ( aged 12 - 18 years ) with DSM-IV-defined major depressive disorder initially resistant to selective serotonin reuptake inhibitor ( SSRI ) treatment who were subsequently treated for 12 weeks with another SSRI , venlafaxine , another SSRI + cognitive-behavioral therapy ( CBT ) , or venlafaxine + CBT . Responders then continued with the same treatment through week 24 , while nonresponders were given open treatment . METHOD For the current study , patients were reassessed 48 ( n = 116 ) and 72 ( n = 130 ) weeks from intake . Data were gathered from February 2001 to February 2007 . St and ardized diagnostic interviews and measures of depression , suicidal ideation , related psychopathology , and level of functioning were periodically administered . Remission was defined as ≥ 3 weeks with ≤ 1 clinical ly significant symptom and no associated functional impairment ( score of 1 on the adolescent version of the Longitudinal Interval Follow-Up Evaluation [ A-LIFE ] ) , and relapse , as ≥ 2 weeks with probable or definite depressive disorder ( score of 3 or 4 on the A-LIFE ) . Mixed-effects regression models were applied to estimate remission , relapse , and functional recovery . RESULTS By 72 weeks , an estimated 61.1 % of the r and omized youths had reached remission . R and omly assigned treatment ( first 12 weeks ) did not influence remission rate or time to remission , but the group assigned to SSRIs had a more rapid decline in self-reported depressive symptoms and suicidal ideation than those assigned to venlafaxine ( P < .03 ) . Participants with more severe depression , greater dysfunction , and alcohol or drug use at baseline were less likely to remit . The depressive symptom trajectory of the remitters diverged from that of nonremitters by the first 6 weeks of treatment ( P < .001 ) . Of the 130 participants in remission at week 24 , 25.4 % relapsed in the subsequent year . CONCLUSIONS While most adolescents achieved remission , more than one-third did not , and one-fourth of remitted patients experienced a relapse . More effective interventions are needed for patients who do not show robust improvement early in treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00018902 OBJECTIVE The Treatment for Adolescents with Depression Study ( TADS ) data base was analyzed to determine whether suicidal events ( attempts and ideation ) occurred early in treatment , could be predicted by severity of depression or other clinical characteristics , and were preceded by clinical deterioration or symptoms of increased irritability , akathisia , sleep disruption , or mania . METHOD TADS was a 36-week r and omized , controlled clinical trial of pharmacologic and psychotherapeutic treatments involving 439 youths with major depressive disorder ( DSM-IV criteria ) . Suicidal events were defined according to the Columbia Classification Algorithm of Suicidal Assessment . Patients were r and omly assigned into the study between spring 2000 and summer 2003 . RESULTS Forty-four patients ( 10.0 % ) had at least 1 suicidal event ( no suicide occurred ) . Events occurred 0.4 to 31.1 weeks ( mean + /- SD = 11.9 + /- 8.2 ) after starting TADS treatment , with no difference in event timing for patients receiving medication versus those not receiving medication . Severity of self-rated pretreatment suicidal ideation ( Suicidal Ideation Question naire adapted for adolescents score > or = 31 ) and depressive symptoms ( Reynolds Adolescent Depression Scale score > or = 91 ) predicted occurrence of suicidal events during treatment ( P < .05 ) . Patients with suicidal events were on average still moderately ill prior to the event ( mean + /- SD Clinical Global Impressions-Severity of Illness scale score = 4.0 + /- 1.3 ) and only minimally improved ( mean + /- SD Clinical Global Impressions-Improvement scale score = 3.2 + /- 1.1 ) . Events were not preceded by increased irritability , akathisia , sleep disturbance , or manic signs . Specific interpersonal stressors were identified in 73 % of cases ( N = 44 ) . Of the events , 55 % ( N = 24 ) result ed in overnight hospitalization . CONCLUSIONS Most suicidal events occurred in the context of persistent depression and insufficient improvement without evidence of medication-induced behavioral activation as a precursor . Severity of self-rated suicidal ideation and depressive symptoms predicted emergence of suicidality during treatment . Risk for suicidal events did not decrease after the first month of treatment , suggesting the need for careful clinical monitoring for several months after starting treatment The purpose of this article is to describe feasibility , safety , and outcome results from a treatment development trial of the SAFETY Program , a brief intervention design ed for integration with emergency services for suicide-attempting youths . Suicide-attempting youths , ages 11 to 18 , were enrolled in a 12-week trial of the SAFETY Program , a cognitive-behavioral family intervention design ed to increase safety and reduce suicide attempt ( SA ) risk ( N = 35 ) . Rooted in a social-ecological cognitive-behavioral model , treatment sessions included individual youth and parent session-components , with different therapists assigned to youths and parents , and family session-components to practice skills identified as critical in the pathway for preventing repeat SAs in individual youths . Outcomes were evaluated at baseline , 3-month , and 6-month follow-ups . At the 3-month posttreatment assessment , there were statistically significant improvements on measures of suicidal behavior , hopelessness , youth and parent depression , and youth social adjustment . There was one reported SA by 3 months and another by 6 months , yielding cumulative attempt rates of 3 % and 6 % at 3 and 6 months , respectively . Treatment satisfaction was high . Suicide-attempting youths are at high risk for repeat attempts and continuing mental health problems . Results support the value of a r and omized controlled trial to further evaluate the SAFETY intervention . Extension of treatment effects to parent depression and youth social adjustment are consistent with our strong family focus and social-ecological model of behavior change Background The goal of this pilot study was to examine the feasibility and clinical outcomes of a brief ( 6-session ) group therapy programme in adolescent out patients with depression . The programme had previously been assessed in in- patients , with positive results . Methods A total of 15 out patients aged 13 to 18 years took part in the programme between October 2010 and May 2011 , in 3 separate groups of 4–6 participants each . The outcomes measured were feasibility of the programme , as assessed by attendance rate , user feedback , fidelity of implementation , and response to treatment , as assessed by pre- and post-intervention measurement of depressive symptoms , quality of life , and suicidal ideation . Results The programme demonstrated good feasibility , with a mean attendance rate of 5.33 out of 6 sessions , a mean rating by participants on overall satisfaction with the programme of 7.21 out of 10 ( SD = 1.89 ) , and a 93 % concurrence between the contents of the sessions and the contents of the treatment manual . Compared to baseline scores , depressive symptoms at follow-up test were significantly reduced , as assessed by the Children ’s Depression Rating Scale Revised ( F(1 , 12 ) = 11.76 , p < .01 ) and the Beck Depression Inventory Revision ( F(1 , 32 ) = 11.19 , p < .01 ) ; quality of life improved , as assessed by the Inventory of Quality of Life ( F(1 , 31 ) = 5.27 , p < .05 ) ; and suicidal ideation was reduced . No significant changes were seen on the measures of the Parent Rating Scale for Depression and the Clinical Global Impression scale . Conclusions Based on the results of this pilot study , it is feasible to further assess this brief outpatient treatment programme in a r and omized controlled trial without further modifications CONTEXT The Treatment for Adolescents With Depression Study evaluates the effectiveness of fluoxetine hydrochloride therapy , cognitive behavior therapy ( CBT ) , and their combination in adolescents with major depressive disorder . OBJECTIVE To report effectiveness outcomes across 36 weeks of r and omized treatment . DESIGN AND SETTING R and omized , controlled trial conducted in 13 academic and community sites in the United States . Cognitive behavior and combination therapies were not masked , whereas administration of placebo and fluoxetine was double-blind through 12 weeks , after which treatments were unblinded . Patients assigned to placebo were treated openly after week 12 , and the placebo group is not included in these analyses by design . PARTICIPANTS Three hundred twenty-seven patients aged 12 to 17 years with a primary DSM-IV diagnosis of major depressive disorder . INTERVENTIONS All treatments were administered per protocol . MAIN OUTCOME MEASURES The primary dependent measures rated blind to treatment status by an independent evaluator were the Children 's Depression Rating Scale-Revised total score and the response rate , defined as a Clinical Global Impressions-Improvement score of much or very much improved . RESULTS Intention-to-treat analyses on the Children 's Depression Rating Scale-Revised identified a significant time x treatment interaction ( P < .001 ) . Rates of response were 73 % for combination therapy , 62 % for fluoxetine therapy , and 48 % for CBT at week 12 ; 85 % for combination therapy , 69 % for fluoxetine therapy , and 65 % for CBT at week 18 ; and 86 % for combination therapy , 81 % for fluoxetine therapy , and 81 % for CBT at week 36 . Suicidal ideation decreased with treatment , but less so with fluoxetine therapy than with combination therapy or CBT . Suicidal events were more common in patients receiving fluoxetine therapy ( 14.7 % ) than combination therapy ( 8.4 % ) or CBT ( 6.3 % ) . CONCLUSIONS In adolescents with moderate to severe depression , treatment with fluoxetine alone or in combination with CBT accelerates the response . Adding CBT to medication enhances the safety of medication . Taking benefits and harms into account , combined treatment appears superior to either monotherapy as a treatment for major depression in adolescents This study explored the intervention processes of an indicated prevention program for high-risk youth . It was hypothesized that intervention effects would be influenced by the direct and mediating effects of teacher social support on both peer group support and perceived personal control . In turn , personal control was hypothesized to mediate between teacher and peer group support , contributing to reductions in depression and suicide risk behaviors . The hypotheses were tested using a three-wave , longitudinal design incorporating data from preintervention , 5-month follow-up , and 10-month follow-up assessment s of 106 high-risk youth divided into three comparison groups : two experimental , one control . For the two intervention groups , there were direct and /or indirect effects of teacher and peer group support on personal control , depression , and suicide risk behaviors . The general hypothesis that personal control mediates between support re sources and reductions in depression and suicide risk behaviors received partial support across the study groups Background The US Food and Drug Administration ’s meta-analyses of placebo-controlled antidepressant trials found approximately twice the rate of suicidal behaviors among children and adults aged 24 years and younger who were r and omized to receive antidepressant medication than among those who were r and omized to placebo . Rates of suicidal behavior were similar for subjects aged 25–64 years whether they received antidepressants or placebo , and subjects aged 65 years or older r and omized to antidepressants were found to have lower rates of suicidal behavior . The age-stratified FDA meta-analyses did not have adequate power to investigate rates of suicidal behaviors by antidepressant drug class . Objective Our objective was to assess the risk of deliberate self-harm associated with the two most commonly prescribed classes of antidepressant agents . Design Propensity score matched cohort study of incident users of antidepressant agents . Setting Population -based healthcare utilization data of US residents . Patients US residents aged 10–64 years with a recorded diagnosis of depression who initiated use of selective serotonin reuptake inhibitors ( SSRIs ) or serotonin norepinephrine reuptake inhibitors ( SNRIs ) between 1 January 1998 and 31 December 2010.Main Outcome Measures ICD-9 external cause of injury codes E950.x – E958.x ( deliberate self-harm ) . Results A total of 102,647 patients aged between 10 and 24 years , and 338,021 aged between 25 and 64 years , initiated therapy with antidepressants . Among 10–24 year olds , prior to propensity score matching , 75,675 initiated therapy with SSRIs and 5,344 initiated SNRIs . After matching , there were 5,344 SNRI users and 10,688 SSRI users . Among the older cohort , 36,037 SNRI users were matched to 72,028 SSRI users ( from an unmatched cohort of 225,952 SSRI initiators ) . Regardless of age cohort , patients initiating SSRIs and patients initiating SNRIs had similar rates of deliberate self-harm . Restriction to patients with no antidepressant use in the past 3 years did not alter our findings . Conclusions Our findings of similar rates of deliberate self-harm for depressed patients who initiate treatment with either an SSRI or an SNRI suggests that physicians who have decided that their patients would benefit from initiating antidepressant therapy need not weigh differential suicide risk when deciding which class of antidepressant to prescribe OBJECTIVE To describe a manual-based intervention to address clinical crises and retain participants in the Treatment for Adolescents With Depression Study ( TADS ) . METHOD The use of adjunct services for attrition prevention ( ASAP ) is described for adolescents ( ages 12 - 17 years ) during the 12-week acute treatment in TADS , from 2000 to 2003 . Logistic regression , controlling for site , was used to predict use . RESULTS Of 439 enrolled participants , 17.8 % ( n = 78 ) used ASAP primarily for suicidality or worsening of depression . Of these , 46.2 % continued in their assigned treatment through week 12 , 47.4 % received out-of- protocol treatment but continued participating in assessment s , and 10.3 % withdrew consent , including 3 who terminated treatment and withdrew consent on the same date . ASAP use did not differ between treatments ( p = .97 ) and typically occurred early in treatment . At the end of the 12 weeks , 37.2 % of participants using ASAP remained in their assigned treatment , although 80.8 % continued participating in assessment s. ASAP was associated with , at baseline , a higher severity of depression ( p < .01 ) , substance use ( p < .01 ) , and precontemplation level of change ( p < .02 ) . CONCLUSIONS ASAP may be useful to retain adolescent participants and as a safety intervention in placebo-controlled trials . In clinical practice ASAP-like procedures may be useful to encourage adherence in patients engaging in long-term treatment . Clinical trial registration information-URL : http://www . clinical trials.gov . Unique identifier : NCT00006286 OBJECTIVE To evaluate cognitive-behavioral therapy , antidepressant medication alone , and combined CBT and antidepressant medication in the treatment of depressive disorders in adolescents . METHOD Seventy-three adolescents ( ages 12 - 18 years ) with a primary diagnosis of DSM-IV major depressive disorder , dysthymic disorder , or depressive disorder not otherwise specified were r and omly allocated to one of three treatments . Treatment outcome measures were administered before and after acute treatment , and at a 6-month follow-up . Depression diagnosis was the primary outcome measure ; secondary measures were self- and other report and clinician rating of global functioning . The trial was conducted at three community-based clinics between July 2000 and December 2002 . Data analyses used an intent-to-treat strategy . RESULTS Following acute treatment , all treatment groups demonstrated statistically significant improvement on outcome measures ( depressive diagnosis , Reynolds Adolescent Depression Scale , Revised Children 's Manifest Anxiety Scale , Suicidal Ideation Question naire ) , and improvement was maintained at follow-up . Combined cognitive-behavioral therapy and antidepressant medication was not found to be superior to either treatment alone . Compared with antidepressant medication alone , participants receiving cognitive-behavioral therapy alone demonstrated a superior acute treatment response ( odds ratio = 6.86 ; 95 % confidence interval 1.12 - 41.82 ) . Although cognitive-behavioral therapy was found to be superior to antidepressant medication alone for the acute treatment of mild to moderate depression among youth , this may have stemmed from the relatively low dose of sertraline used . CONCLUSIONS All treatments led to a reduction in depression , but the advantages of a combined approach were not evident OBJECTIVE The purpose of this study was to conduct a treatment development study to examine the feasibility , acceptability , and preliminary efficacy of treating depressed , suicidal adolescents and their depressed parent concurrently in a cognitive behavioral therapy ( CBT ) protocol ( Parent-Adolescent-CBT [ PA-CBT ] ) . METHODS A r and omized , controlled , repeated measures design was used to test the hypothesis that PA-CBT would lead to greater reductions in suicidality and depression compared with Adolescent Only CBT ( AO-CBT ) . Participants included 24 adolescent and parent dyads in which the adolescent met American Psychiatric Association , Diagnostic and Statistical Manual of Mental Disorders , 4th ed . ( DSM-IV ) criteria for current major depressive episode ( MDE ) and the parent met DSM-IV criteria for current or past MDE . RESULTS The concurrent protocol was found to be feasible to implement with most depressed adolescents and parents . Adolescent ratings of program satisfaction were somewhat lower in PA-CBT , suggesting that some teens view treatment negatively when they are required to participate with a parent . The concurrent treatment protocol was more effective in reducing depressed mood in the parent-adolescent dyad at the end of maintenance treatment ( 24 weeks ) than treating an adolescent alone for depression ; the largest effect was on parental depressed mood . This difference between dyads was no longer significant , however , at the 48 week follow-up . Adolescent and parent suicidal ideation improved equally in both groups during active and maintenance treatment , and remained low at follow-up in both groups . CONCLUSIONS The PA-CBT protocol is feasible to conduct and acceptable to most but not all adolescents . The strongest effect was on parental depressed mood . A larger study that has sufficient power to test efficacy and moderators of treatment outcome is necessary to better underst and which adolescents would benefit most from concurrent treatment with a parent OBJECTIVE Family processes are a risk factor for suicide but few studies target this domain . We evaluated the effectiveness of a family intervention , the Re source ful Adolescent Parent Program ( RAP-P ) in reducing adolescent suicidal behavior and associated psychiatric symptoms . METHOD A preliminary r and omized controlled trial compared RAP-P plus Routine Care ( RC ) to RC only , in an outpatient psychiatric clinic for N = 48 suicidal adolescents and their parents . Key outcome measures of adolescent suicidality , psychiatric disability , and family functioning were completed at pre-treatment , 3-month , and 6-month follow-up . RESULTS RAP-P was associated with high recruitment and retention , greater improvement in family functioning , and greater reductions in adolescents ' suicidal behavior and psychiatric disability , compared to RC alone . Benefits were maintained at follow-up with a strong overall effect size . Changes in adolescent 's suicidality were largely mediated by changes in family functioning . CONCLUSION The study provides preliminary evidence for the use of family-focused treatments for adolescent suicidal behavior in outpatient setting s. Clinical trial registration information-Family intervention for adolescents with suicidal behaviour : A r and omized controlled trial and mediation analysis ; http://anzctr.org/ ; ACTRN12613000668707 This study investigates the impact of suicidality on treatment outcome in 107 depressed adolescents who participated in a clinical trial , and received either cognitive-behavioral ( CBT ) , systemic-behavioral-family ( SBFT ) , or non-directive-supportive therapy ( NST ) . Suicidal depressed adolescents had a higher dropout rate and were more likely to be depressed at the end of treatment , in large part due to the particularly poor response of suicidal patients to NST . The relationship between suicidality and treatment response was mediated by severity of depression and hopelessness at intake . Hopelessness should be specifically targeted early in treatment . Suicidal depressed adolescents should not receive NST but a specific treatment like CBT This study tested the efficacy of a school-based prevention program for reducing suicide potential among high-risk youth . A sample of 105 youth at suicide risk participated in a three-group , repeated- measures , intervention study . Participants in ( 1 ) an assessment plus 1-semester experimental program , ( 2 ) an assessment plus 2-semester experimental program , and ( 3 ) an assessment -only group were compared , using data from preintervention , 5-month , and 10-month follow-up assessment s. All groups showed decreased suicide risk behaviors , depression , hopelessness , stress , and anger ; all groups also reported increased self-esteem and network social support . Increased personal control was observed only in the experimental groups , and not in the assessment -only control group . The potential efficacy of the experimental school-based prevention program was demonstrated . The necessary and sufficient strategies for suicide prevention , however , need further study as the assessment -only group , who received limited prevention elements , showed improvements similar to those of the experimental groups CONTEXT Only about 60 % of adolescents with depression will show an adequate clinical response to an initial treatment trial with a selective serotonin reuptake inhibitor ( SSRI ) . There are no data to guide clinicians on subsequent treatment strategy . OBJECTIVE To evaluate the relative efficacy of 4 treatment strategies in adolescents who continued to have depression despite adequate initial treatment with an SSRI . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of a clinical sample of 334 patients aged 12 to 18 years with a primary diagnosis of major depressive disorder that had not responded to a 2-month initial treatment with an SSRI , conducted at 6 US academic and community clinics from 2000 - 2006 . INTERVENTIONS Twelve weeks of : ( 1 ) switch to a second , different SSRI ( paroxetine , citalopram , or fluoxetine , 20 - 40 mg ) ; ( 2 ) switch to a different SSRI plus cognitive behavioral therapy ; ( 3 ) switch to venlafaxine ( 150 - 225 mg ) ; or ( 4 ) switch to venlafaxine plus cognitive behavioral therapy . MAIN OUTCOME MEASURES Clinical Global Impressions-Improvement score of 2 or less ( much or very much improved ) and a decrease of at least 50 % in the Children 's Depression Rating Scale-Revised ( CDRS-R ) ; and change in CDRS-R over time . RESULTS Cognitive behavioral therapy plus a switch to either medication regimen showed a higher response rate ( 54.8 % ; 95 % confidence interval [ CI ] , 47%-62 % ) than a medication switch alone ( 40.5 % ; 95 % CI , 33%-48 % ; P = .009 ) , but there was no difference in response rate between venlafaxine and a second SSRI ( 48.2 % ; 95 % CI , 41%-56 % vs 47.0 % ; 95 % CI , 40%-55 % ; P = .83 ) . There were no differential treatment effects on change in the CDRS-R , self-rated depressive symptoms , suicidal ideation , or on the rate of harm-related or any other adverse events . There was a greater increase in diastolic blood pressure and pulse and more frequent occurrence of skin problems during venlafaxine than SSRI treatment . CONCLUSIONS For adolescents with depression not responding to an adequate initial treatment with an SSRI , the combination of cognitive behavioral therapy and a switch to another antidepressant result ed in a higher rate of clinical response than did a medication switch alone . However , a switch to another SSRI was just as efficacious as a switch to venlafaxine and result ed in fewer adverse effects . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00018902 OBJECTIVE To identify the predictors of suicidal events and attempts in adolescent suicide attempters with depression treated in an open treatment trial . METHOD Adolescents who had made a recent suicide attempt and had unipolar depression ( n = 124 ) were either r and omized ( n = 22 ) or given a choice ( n = 102 ) among three conditions . Two participants withdrew before treatment assignment . The remaining 124 youths received a specialized psychotherapy for suicide attempting adolescents ( n = 17 ) , a medication algorithm ( n = 14 ) , or the combination ( n = 93 ) . The participants were followed up 6 months after intake with respect to rate , timing , and predictors of a suicidal event ( attempt or acute suicidal ideation necessitating emergency referral ) . RESULTS The morbid risks of suicidal events and attempts on 6-month follow-up were 0.19 and 0.12 , respectively , with a median time to event of 44 days . Higher self-rated depression , suicidal ideation , family income , greater number of previous suicide attempts , lower maximum lethality of previous attempt , history of sexual abuse , and lower family cohesion predicted the occurrence , and earlier time to event , with similar findings for the outcome of attempts . A slower decline in suicidal ideation was associated with the occurrence of a suicidal event . CONCLUSIONS In this open trial , the 6-month morbid risks for suicidal events and for reattempts were lower than those in other comparable sample s , suggesting that this intervention should be studied further . Important treatment targets include suicidal ideation , family cohesion , and sequelae of previous abuse . Because 40 % of events occurred with 4 weeks of intake , an emphasis on safety planning and increased therapeutic contact early in treatment may be warranted PROBLEM Few empirically tested , school-based , suicide-prevention programs exist . The purpose of this study was to evaluate the postintervention efficacy of Counselors-CARE ( C-CAST ) and Coping and Support Training ( CAST ) vs. " usual care " controls for reducing suicide risk . METHODS A r and omized prevention trial ; 341 potential dropouts , 14 to 19 years old , from seven high schools ( 52 % female , 56 % minorities ) participated . Trend analyses using data from three time points assessed over time changes . FINDINGS Significant decreases occurred for all youth in suicide-risk behaviors , depression , and drug involvement . Intervention-specific effects occurred for decreases in depression . CONCLUSIONS School-based prevention approaches are feasible and show promise for reducing suicidal behaviors and related depression The Treatment of SSRI-Resistant Depression in Adolescents study ( TORDIA ) was design ed to inform clinicians as to the best next step in the treatment after a depressed adolescent has not responded to an adequate trial with a selective serotonin re-uptake inhibitor (SSRI).[1 ] In this six-site study , conducted from 2000 to 2006 , 334 treatment-resistant adolescents with major depressive disorder ( MDD ) were r and omized to one of the four treatment strategies in a two-by-two balanced factorial design : ( a ) switch to another SSRI ; ( b ) switch to venlafaxine ; ( c ) switch to another SSRI and add cognitive behavioral therapy ( CBT ) ; or ( d ) switch to venlafaxine and add CBT . The SSRI switch options were fluoxetine , and for the first half of the trial ( n = 181 ) , paroxetine . Because of the concerns about the safety and efficacy of paroxetine , citalopram was used instead during the second half of the trial ( n = 153 ) . All enrolled youth had not responded to an “ adequate trial ” with an SSRI , defined as treatment for at least 8 weeks , with the last 4 weeks at a dosage that was the equivalent of 40 mg of fluoxetine . This communication focuses on acute treatment , which was 12 weeks in duration OBJECTIVES To determine if , in the short term , depressed adolescents attending routine NHS Child and Adolescent Mental Health Services ( CAMHS ) , and receiving ongoing active clinical care , treatment with selective serotonin reuptake inhibitors ( SSRIs ) plus cognitive behaviour therapy ( CBT ) compared with SSRI alone , results in better healthcare outcomes . DESIGN A pragmatic r and omised controlled trial ( RCT ) was conducted on depressed adolescents attending CAMHS who had not responded to a psychosocial brief initial intervention ( BII ) prior to r and omisation . SETTING Six English CAMHS participated in the study . PARTICIPANTS A total of 208 patients aged between 11 and 17 years were recruited and r and omised . INTERVENTIONS All participants received active routine clinical care in a CAMHS outpatient setting and an SSRI and half were offered CBT . MAIN OUTCOME MEASURES The duration of the trial was a 12-week treatment phase , followed by a 16-week maintenance phase . Follow-up assessment s were at 6 , 12 and 28 weeks . The primary outcome measure was the Health of the Nation Outcome Scales for Children and Adolescents ( HoNOSCA ) . Secondary outcome measures were self-report depressive symptoms , interviewer-rated depressive signs and symptoms , interviewer-rated psychosocial impairment and clinical global impression of response to treatment . Information on re source use was collected in interview at baseline and at the 12- and 28-week follow-up assessment s using the Child and Adolescent Service Use Schedule ( CA-SUS ) . RESULTS Of the 208 patients r and omised , 200 ( 96 % ) completed the trial to the primary end-point at 12 weeks . By the 28-week follow-up , 174 ( 84 % ) participants were re-evaluated . Overall , 193 ( 93 % ) participants had been assessed at one or more time points . Clinical characteristics indicated that the trial was conducted on a severely depressed group . There was significant recovery at all time points in both arms . The findings demonstrated no difference in treatment effectiveness for SSRI + CBT over SSRI only for the primary or secondary outcome measures at any time point . This lack of difference held when baseline and treatment characteristics where taken into account ( age , sex , severity , co-morbid characteristics , quality and quantity of CBT treatment , number of clinic attendances ) . The SSRI + CBT group was somewhat more expensive over the 28 weeks than the SSRI-only group ( p=0.057 ) and no more cost-effective . Over the trial period there was on average a decrease in suicidal thoughts and self-harm compared with levels recorded at baseline . There was no significant increase in disinhibition , irritability and violence compared with levels at baseline . Around 20 % ( n=40 ) of patients in the trial were non-responders . Of these , 17 ( 43 % ) showed no improvement by 28 weeks and 23 ( 57 % ) were considered minimally ( n=10 ) or moderately to severely worse ( n=13 ) . CONCLUSIONS For moderately to severely depressed adolescents who are non-responsive to a BII , the addition of CBT to fluoxetine plus routine clinical care does not improve outcome or confer protective effects against adverse events and is not cost-effective . SSRIs ( mostly fluoxetine ) are not likely to result in harmful adverse effects . The findings are broadly consistent with existing guidelines on the treatment of moderate to severe depression . Modification is advised for those presenting with moderate ( 6 - 8 symptoms ) to severe depressions ( > 8 symptoms ) and in those with either overt suicidal risk and /or high levels of personal impairment . In such cases , the time allowed for response to psychosocial interventions should be no more than 2 - 4 weeks , after which fluoxetine should be prescribed . Further research should focus on evaluating the efficacy of specific psychological treatments against brief psychological intervention , determining the characteristics of patients with severe depression who are non-responsive to fluoxetine , relapse prevention in severe depression and improving tools for determining treatment responders and non-responders Evidence suggests that poor mental health literacy is a key barrier to help-seeking for mental health difficulties in adolescence . Educational programs have shown positive effects on literacy , however , the evidence base remains limited and available studies have many method ological limitations . Using cluster R and omised Control Trial ( RCT ) methodology , the current study examines the impact of ' HeadStrong ' , a school-based educational intervention , on mental health literacy , stigma , help-seeking , psychological distress and suicidal ideation . A total of 380 students in 22 classes ( clusters ) from 10 non-government secondary schools was r and omised to receive either HeadStrong or Personal Development , Health and Physical Education ( PDHPE ) classes . Participants were assessed pre- and post-intervention , and at 6-month follow-up . Literacy improved and stigma reduced in both groups at post-intervention and follow-up , relative to baseline . However , these effects were significantly greater in the HeadStrong condition . The study demonstrates the potential of HeadStrong to improve mental health literacy and reduce stigma BACKGROUND To identify distinct depressive symptom trajectories in the TORDIA study and determine their correlates . METHODS Latent Class Growth Analysis ( LCGA ) using the Children 's Depression Rating Scale-Revised ( CDRS-R ) through 72 weeks from intake . RESULTS 3 classes were identified : ( 1 ) little change in symptomatic status ( " NO " ) , comprising 24.9 % of participants , with a 72-week remission rate of 25.3 % ; ( 2 ) slow , steady improvement ( " SLOW " ) , comprising 47.9 % of participants , with a remission rate of 60.0 % , and ( 3 ) rapid symptom response ( " GO " ) , comprising 27.2 % of participants , with a remission rate of 85.7 % . Higher baseline CDRS-R ( p<0.001 ) and poorer functioning ( p=0.03 ) were the strongest discriminators between NO and GO . Higher baseline CDRS ( p<0.001 ) and scores on the Mania Rating Scale ( MRS ) ( p=0.01 ) were the strongest discriminators between SLOW and GO . Other variables differentiating GO from both NO and from SLOW , were better baseline functioning , lower hopelessness , and lower family conflict . Both NO and SLOW showed increases on the MRS over time compared to GO ( ps ≤ 0.04 ) , and increasing MRS was strongly associated with lack of remission by 72 weeks ( p=0.02 ) . LIMITATIONS High rate of open treatment by the end of the follow-up period creates difficulty in drawing clear inferences about the long-term impact of initial r and omization . CONCLUSION Along with depressive severity , sub-syndromal manic symptoms , at baseline , and over time emerged as important predictors and correlates of poor outcome in this sample . Further research is needed on the treatment of severe depression , and on the assessment and management of sub-syndromal manic symptoms in treatment resistant depression |
13,394 | 16,244,186 | A synthesis of several small , low quality trials indicates that exercise may have short term beneficial effects on self esteem in children and adolescents . | A systematic review to determine if exercise alone or as part of a comprehensive intervention can improve self esteem in children and young people is described . | This study compared the physical and psychological effects of running to those of the normal physical education program of activities among 154 fourth , fifth , and sixth grade rs who were r and omly assigned to conditions within a true experimental design . The running program consisted of three 30-min sessions per week for 12 weeks in lieu of attendance in regular physical education classes . Findings showed that although boys tended to run faster than girls overall and that older children run faster than younger children , running-program participants performed better on an 800-m run , had lower pulse rates , and performed better on a test of creativity than did regular physical education participants . Running boys had less body fat , and running girls had more creative involvement in class . No differences were found on 50-m dash performance or perceptual skill . On total behavior , girls were more self-controlled than boys , and self-concept tended to become less positive with increased grade level . Running performance for 800 m persisted for 5 months among boys in the treatment , but not among girls . Running was judged effective for enhancing the cardiorespiratory health and creativity of school children 36 boys and 36 girls in 4 fourth grade s were exposed to basketball movement conditions which included the skills of dribble , chest pass , lay-up , pivot , guarding , and two-h and set shot . Eight 1/2-hr . treatment periods were spread evenly over 4 wk . and took place within the regularly assigned school physical education period . Two class groups , which included 9 boys and 9 girls each , were r and omly assigned by class to an experimental group which received treatment while two class groups were assigned by class to the control group . No differences between changes in self-concept as estimated by the Piers-Harris scale for treatment and control conditions were significant Aerobic exercise has been associated with improvements in psychological status and physical fitness in adults , but its effects on children are less clear . The purpose of this study was to evaluate the effects of an aerobic exercise program on the self-concept , academic achievement , motor proficiency , and cardiovascular fitness of boys with learning disabilities . Fifty-four boys were r and omly assigned to one of two exercise programs lasting 20 weeks . One program emphasized aerobic exercise and the other consisted of similar but less vigorous activities . The self-concept , academic achievement , motor proficiency , and physical fitness of each subject was assessed before and after the exercise programs . The results from group comparisons demonstrated an association between the aerobic exercise program and improvement of self-concept and physical fitness . No effect on academic achievement or motor proficiency could be attributed to the aerobic exercise program . J Dev Behav Pediatr 8:274–277 , 1987 . Index terms : aerobic exercise , learning disabilities , sports , self-concept Preschool teachers from four different day care centers assessed four- and five-year-old children for deficits in gross-motor skill and self-concept . Forty subjects were r and omly assigned to experimental and control groups . The experimental group participated in a 30 minute per day , 5 day per week perceptual-motor training program for 10 weeks , while the control group received no specialized intervention other than their regular classroom activities . Two posttests were administered : Cratty 's Six-Category Gross-Motor Test and Goodenough 's House , Tree , Person Projective Test . The experimental group performed better on the gross-motor test , but the results were not statistically significant . Analysis of the projective test supported the hypothesis that a perceptual-motor program may improve the self-concept of young children . Specialized intervention with perceptual-motor activities improved self-concept and these results were discussed in relation to recognizing the need for early screening and remediation of perceptual-motor dificits exhibited by preschool children The article examines whether participation in an aerobic exercise program ( AE ) , as compared with a traditional physical education class ( PE ) , significantly increased children 's perceived athletic competence , physical appearance , social acceptance , behavioral conduct , and global self-worth ; increased their figural creativity ; and improved aerobic power as measured by an 800-meter run around a track . Further research on the effects of different types of AE is discussed , as well as the need for aerobic conditioning in the elementary school This study investigated the relationship between improvement in Total Positive Self-concept scores and increase in sports skills before and after training of 10 weeks for 45 minutes daily by 12- to 14-yr.-old junior high school and 16- to 18-yr.-old senior high school boys and girls . The 288 subjects were selected using a stratified ( intact class ) r and om technique . Subjects were r and omly assigned to different sports , 96 to field-hockey and 96 to athletics ( 32 to discuss , 32 to long jump , and 32 to sprints ) . 96 control subjects were r and omly selected from one class of each age bracket . Analysis of covariance showed that the trained subjects scored significantly higher in total positive self . A positive correlation between gain in sports skill and increase in self-concept scores was noted for both boys and girls within each age group . Age and sex had no effect on this pattern . The result supports inclusion of success-oriented sports in the high school curriculum Aerobic exercise has been associated with improved psychological status and physical fitness in adults , but its effects in adolescents have been less clear . This study evaluated the effects of aerobic exercise on the self-concept , depression level , and physical fitness of juvenile delinquents . Ninety-eight incarcerated youths who volunteered to participate were assigned in a blind fashion to one of two exercise programs lasting three months . Sixty-nine completed all phases of the study and are the subjects of this report . One exercise program ( 32 subjects ) emphasized aerobic exercise ; the other ( 37 subjects ) , limited exertion . Before and after participating , each subject underwent measurement of self-concept , mood , and physical fitness . While the aerobic and comparison groups were initially similar , the data demonstrated an association between participation in the aerobic exercise program and improved self-concept , mood , and fitness . Improvement in psychological variables was not dependent on improved physical fitness and was not related to preintervention measures |
13,395 | 25,357,011 | Sensitivity analyses excluding heavily weighted studies result ed in non-statistically significant effects for acute kidney injury and mechanical ventilation time .
Conclusion A weak but significant association between higher chloride content fluids and unfavourable outcomes was found , but mortality was unaffected by chloride content | Background The objective of this systematic review and meta- analysis was to assess the relationship between the chloride content of intravenous resuscitation fluids and patient outcomes in the perioperative or intensive care setting . | BACKGROUND Normal saline ( NS ) and lactated Ringer 's solution ( LR ) continue to be used interchangeably for the resuscitation of hemorrhagic shock in some institutions . We hypothesized that , aside from hyperchloremic acidosis , NS resuscitation would be similar to that of LR in a swine model of uncontrolled hemorrhage . METHODS Twenty swine weighing a mean of 37 kg underwent invasive line placement , midline celiotomy , and splenectomy . After a 15-minute stabilization period , we recorded a baseline mean arterial pressure ( MAP ) and created a grade V liver injury . The animals bled freely for 30 minutes after which we measured blood loss . We blindly r and omized the swine to receive NS ( 10 animals ) versus LR ( 10 animals ) to achieve and maintain the baseline MAP for 90 minutes postinjury . Laboratory values were obtained at baseline and upon completion of the 2-hour study period . RESULTS Initial blood loss was 25 mL/kg in the NS group and 22 mL/kg in the LR group ( p = 0.54 ) . Animals required 256.3 + /- 145.4 mL/kg of fluid in the NS group as compared with 125.7 + /- 67.3 mL/kg in the LR group ( p = 0.04 ) . The urine output was higher in the NS group ( 46.6 + /- 39.5 mL/kg versus 18.9 + /- 12.9 mL/kg , p = 0.04 ) . Upon study completion , the NS group had a significant hyperchloremia ( 119 + /- 1.9 mEq/L versus 105 + /- 2.9 mEq/L , p < 0.01 ) with acidosis ( 7.28 + /- 0.12 versus 7.45 + /- 0.06 , p < 0.01 ) in comparison to the LR group . In addition , resuscitation with NS result ed in significantly lower fibrinogen levels ( 99 + /- 21 mg/dL versus 123 + /- 20 mg/dL , p = 0.02 ) . The serum lactate was 4.7 + /- 2.2 in the LR group and 1.7 + /- 1.7 in the NS swine ( p < 0.01 ) at the end of the study . CONCLUSIONS Resuscitation of uncontrolled hemorrhagic shock with NS requires significantly greater volume and is associated with greater urine output , hyperchloremic acidosis , and dilutional coagulopathy as compared with LR . Resuscitation with LR results in an elevation of the lactate level that is not associated with acidosis . Lactated Ringer 's solution is superior to NS for the resuscitation of uncontrolled hemorrhagic shock in swine Objective : Isotonic saline is the most commonly used crystalloid in the ICU , but recent evidence suggests that balanced fluids like Lactated Ringer ’s solution may be preferable . We examined the association between choice of crystalloids and in-hospital mortality during the resuscitation of critically ill adults with sepsis . Design : A retrospective cohort study of patients admitted with sepsis , not undergoing any surgical procedures , and treated in an ICU by hospital day 2 . We used propensity score matching to control for confounding and compared the following outcomes after resuscitation with balanced versus with no-balanced fluids : in-hospital mortality , acute renal failure with and without dialysis , and hospital and ICU lengths of stay . We also estimated the dose-response relationship between receipt of increasing proportions of balanced fluids and in-hospital mortality . Setting : Three hundred sixty U.S. hospitals that were members of the Premier Healthcare alliance between November 2005 and December 2010 . Patients : A total of 53,448 patients with sepsis , treated with vasopressors and crystalloids in an ICU by hospital day 2 including 3,396 ( 6.4 % ) that received balanced fluids . Interventions : None . Measurements and Main Results : Patients treated with balanced fluids were younger and less likely to have heart or chronic renal failure , but they were more likely to receive mechanical ventilation , invasive monitoring , colloids , steroids , and larger crystalloid volumes ( median 7 vs 5 L ) . Among 6,730 patients in a propensity-matched cohort , receipt of balanced fluids was associated with lower in-hospital mortality ( 19.6 % vs 22.8 % ; relative risk , 0.86 ; 95 % CI , 0.78 , 0.94 ) . Mortality was progressively lower among patients receiving larger proportions of balanced fluids . There were no significant differences in the prevalence of acute renal failure ( with and without dialysis ) or in-hospital and ICU lengths of stay . Conclusions : Among critically ill adults with sepsis , resuscitation with balanced fluids was associated with a lower risk of in-hospital mortality . If confirmed in r and omized trials , this finding could have significant public health implication s , as crystalloid resuscitation is nearly universal in sepsis BACKGROUND The safety and efficacy of hydroxyethyl starch ( HES ) for fluid resuscitation have not been fully evaluated , and adverse effects of HES on survival and renal function have been reported . METHODS We r and omly assigned 7000 patients who had been admitted to an intensive care unit ( ICU ) in a 1:1 ratio to receive either 6 % HES with a molecular weight of 130 kD and a molar substitution ratio of 0.4 ( 130/0.4 , Voluven ) in 0.9 % sodium chloride or 0.9 % sodium chloride ( saline ) for all fluid resuscitation until ICU discharge , death , or 90 days after r and omization . The primary outcome was death within 90 days . Secondary outcomes included acute kidney injury and failure and treatment with renal-replacement therapy . RESULTS A total of 597 of 3315 patients ( 18.0 % ) in the HES group and 566 of 3336 ( 17.0 % ) in the saline group died ( relative risk in the HES group , 1.06 ; 95 % confidence interval [ CI ] , 0.96 to 1.18 ; P=0.26 ) . There was no significant difference in mortality in six predefined subgroups . Renal-replacement therapy was used in 235 of 3352 patients ( 7.0 % ) in the HES group and 196 of 3375 ( 5.8 % ) in the saline group ( relative risk , 1.21 ; 95 % CI , 1.00 to 1.45 ; P=0.04 ) . In the HES and saline groups , renal injury occurred in 34.6 % and 38.0 % of patients , respectively ( P=0.005 ) , and renal failure occurred in 10.4 % and 9.2 % of patients , respectively ( P=0.12 ) . HES was associated with significantly more adverse events ( 5.3 % vs. 2.8 % , P<0.001 ) . CONCLUSIONS In patients in the ICU , there was no significant difference in 90-day mortality between patients resuscitated with 6 % HES ( 130/0.4 ) or saline . However , more patients who received resuscitation with HES were treated with renal-replacement therapy . ( Funded by the National Health and Medical Research Council of Australia and others ; CHEST Clinical Trials.gov number , NCT00935168 . ) BACKGROUND It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units ( ICUs ) affects survival . We conducted a multicenter , r and omized , double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU . METHODS We r and omly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days . The primary outcome measure was death from any cause during the 28-day period after r and omization . RESULTS Of the 6997 patients who underwent r and omization , 3497 were assigned to receive albumin and 3500 to receive saline ; the two groups had similar baseline characteristics . There were 726 deaths in the albumin group , as compared with 729 deaths in the saline group ( relative risk of death , 0.99 ; 95 percent confidence interval , 0.91 to 1.09 ; P=0.87 ) . The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups ( P=0.85 ) . There were no significant differences between the groups in the mean ( + /-SD ) numbers of days spent in the ICU ( 6.5+/-6.6 in the albumin group and 6.2+/-6.2 in the saline group , P=0.44 ) , days spent in the hospital ( 15.3+/-9.6 and 15.6+/-9.6 , respectively ; P=0.30 ) , days of mechanical ventilation ( 4.5+/-6.1 and 4.3+/-5.7 , respectively ; P=0.74 ) , or days of renal-replacement therapy ( 0.5+/-2.3 and 0.4+/-2.0 , respectively ; P=0.41 ) . CONCLUSIONS In patients in the ICU , use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days The high chloride content of 0.9 % saline leads to adverse pathophysiological effects in both animals and healthy human volunteers , changes not seen after balanced crystalloids . Small r and omized trials confirm that the hyperchloremic acidosis induced by saline also occurs in patients , but no clinical outcome benefit was demonstrable when compared with balanced crystalloids , perhaps due to a type II error . A strong signal is emerging from recent large propensity-matched and cohort studies for the adverse effects that 0.9 % saline has on the clinical outcome in surgical and critically ill patients when compared with balanced crystalloids . Major complications are the increased incidence of acute kidney injury and the need for renal replacement therapy , and that pathological hyperchloremia may increase postoperative mortality . However , there are no large-scale r and omized trials comparing 0.9 % saline with balanced crystalloids . Some balanced crystalloids are hypo-osmolar and may not be suitable for neurosurgical patients because of their propensity to cause brain edema . Saline may be the solution of choice used for the resuscitation of patients with alkalosis and hypochloremia . Nevertheless , there is evidence to suggest that balanced crystalloids cause less detriment to renal function than 0.9 % saline , with perhaps better clinical outcome . Hence , we argue that chloride-rich crystalloids such as 0.9 % saline should be replaced with balanced crystalloids as the mainstay of fluid resuscitation to prevent ‘ pre-renal ' acute kidney injury Metabolic acidosis and changes in serum osmolarity are consequences of 0.9 % normal saline ( NS ) solution administration . We sought to determine if these physiologic changes influence patient outcome . Patients undergoing aortic reconstructive surgery were enrolled and were r and omly assigned to receive lactated Ringer ’s ( LR ) solution ( n = 33 ) or NS ( n = 33 ) in a double-blinded fashion . Anesthetic and fluid management were st and ardized . Multiple measures of outcome were monitored . The NS patients developed a hyperchloremic acidosis and received more bicarbonate therapy ( 30 ± 62 mL in the NS group versus 4 ± 16 mL in the LR group ; mean ± sd ) , which was given if the base deficit was greater than −5 mEq/L. The NS patients also received a larger volume of platelet transfusion ( 478 ± 302 mL in the NS group versus 223 ± 24 mL in the LR group ; mean ± sd ) . When all blood products were summed , the NS group received significantly more blood products ( P = 0.02 ) . There were no differences in duration of mechanical ventilation , intensive care unit stay , hospital stay , and incidence of complications . When NS was used as the primary intraoperative solution , significantly more acidosis was seen on completion of surgery . This acidosis result ed in no apparent change in outcome but required larger amounts of bicarbonate to achieve predetermined measurements of base deficit and was associated with the use of larger amounts of blood products . These changes should be considered when choosing fluids for surgical procedures involving extensive blood loss and requiring extensive fluid administration Study objective : To compare the effect of normal saline ( NS ) , lactated Ringer 's , and Plasmalyte on the acid-base status of dehydrated patients in the emergency department ( ED ) . Method : We conducted a prospect i ve , double-blind , r and omized trial of consecutive adult patients who presented to the emergency department with moderate-severe dehydration . Patients were r and omly allocated to blindly receive normal saline ( NS ) , lactated Ringer 's or Plasmalyte at 20 ml/kg/h for 2 hours . Outcome measures of the study were pH and changes in electrolytes , including serum potassium , sodium , chloride and bicarbonate levels at 0 , 60 , and 120 minutes in venous blood gas sample s. Results : Ninety patients participated in the study and were r and omized to NS ( 30 patients ) , lactated Ringer 's ( 30 patients ) and Plasmalyte ( 30 patients ) groups . Mean age was 48±20 years and 50 % ( n=45 ) of the patients were female . All pH values were in the physiological range ( 7.35 - 7.45 ) throughout the study period . In the NS group there was a significant tendency to lower pH values , with pH values of 7.40 , 7.37 , and 7.36 at 0 , 1 , and 2 hours respectively . Average bicarbonate levels fell in the NS group ( 23.1 , 22.2 , and 21.5 mM/L ) and increased in the Plasmalyte group ( 23.4 , 23.9 , and 24.4 mM/L ) at 0 , 1 , and 2 hours , respectively . There were no significant changes in potassium , sodium , or chloride levels . Conclusions : NS , lactated Ringer 's , and Plasmalyte have no significant effect on acid-base status and all can be used safely to treat dehydrated patients in the emergency department . However , NS can effect acidosis which might be significant in patients who have underlying metabolic disturbances ; thus , its use should be weighed before fluid administration in the ED CONTEXT Administration of traditional chloride-liberal intravenous fluids may precipitate acute kidney injury ( AKI ) . OBJECTIVE To assess the association of a chloride-restrictive ( vs chloride-liberal ) intravenous fluid strategy with AKI in critically ill patients . DESIGN , SETTING , AND PATIENTS Prospect i ve , open-label , sequential period pilot study of 760 patients admitted consecutively to the intensive care unit ( ICU ) during the control period ( February 18 to August 17 , 2008 ) compared with 773 patients admitted consecutively during the intervention period ( February 18 to August 17 , 2009 ) at a university-affiliated hospital in Melbourne , Australia . INTERVENTIONS During the control period , patients received st and ard intravenous fluids . After a 6-month phase-out period ( August 18 , 2008 , to February 17 , 2009 ) , any use of chloride-rich intravenous fluids ( 0.9 % saline , 4 % succinylated gelatin solution , or 4 % albumin solution ) was restricted to attending specialist approval only during the intervention period ; patients instead received a lactated solution ( Hartmann solution ) , a balanced solution ( Plasma-Lyte 148 ) , and chloride-poor 20 % albumin . MAIN OUTCOME MEASURES The primary outcomes included increase from baseline to peak creatinine level in the ICU and incidence of AKI according to the risk , injury , failure , loss , end-stage ( RIFLE ) classification . Secondary post hoc analysis outcomes included the need for renal replacement therapy ( RRT ) , length of stay in ICU and hospital , and survival . RESULTS Chloride administration decreased by 144 504 mmol ( from 694 to 496 mmol/patient ) from the control period to the intervention period . Comparing the control period with the intervention period , the mean serum creatinine level increase while in the ICU was 22.6 μmol/L ( 95 % CI , 17.5 - 27.7 μmol/L ) vs 14.8 μmol/L ( 95 % CI , 9.8 - 19.9 μmol/L ) ( P = .03 ) , the incidence of injury and failure class of RIFLE-defined AKI was 14 % ( 95 % CI , 11%-16 % ; n = 105 ) vs 8.4 % ( 95 % CI , 6.4%-10 % ; n = 65 ) ( P < .001 ) , and the use of RRT was 10 % ( 95 % CI , 8.1%-12 % ; n = 78 ) vs 6.3 % ( 95 % CI , 4.6%-8.1 % ; n = 49 ) ( P = .005 ) . After adjustment for covariates , this association remained for incidence of injury and failure class of RIFLE-defined AKI ( odds ratio , 0.52 [ 95 % CI , 0.37 - 0.75 ] ; P < .001 ) and use of RRT ( odds ratio , 0.52 [ 95 % CI , 0.33 - 0.81 ] ; P = .004 ) . There were no differences in hospital mortality , hospital or ICU length of stay , or need for RRT after hospital discharge . CONCLUSION The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00885404 UNLABELLED Animal studies have shown that large volumes of IV lactated Ringer 's solution ( LR ) decrease serum osmolality , thereby increasing cerebral water . These studies have led to recommendations to limit LR to avoid cerebral edema in neurosurgical patients . Eighteen healthy human volunteers aged 20 - 48 yr received 50 mL/kg LR over 1 h on one occasion and 0.9 % sodium chloride ( NS ) on another . Venous sample s were taken at baseline ( T1 ) , at infusion end ( T2 ) , and 1 h after T2 ( T3 ) . Time until first urination was noted . With LR , serum osmolality decreased by 4+/-3 mOsm/kg from T1 to T2 and increased insignificantly with NS . At T3 , osmolality returned almost to baseline in the LR group . Blood pH increased from T1 to T2 with LR by 0.04+/-0.04 and decreased with NS by 0.04+/-0.04 . These pH changes persisted at T3 . Subjective mental changes occurred only with NS . Abdominal discomfort was more common with NS . Time until first urination was longer with NS ( 106+/-11 min ) than with LR ( 75+/-10 min ) ( P < 0.001 ) . In healthy humans , an infusion of large volumes of LR , but not NS , transiently decreased serum osmolality , whereas acidosis associated with NS persisted and urinary output was slower with NS . IMPLICATION S Large volumes of lactated Ringer 's solution administered to healthy humans produced small transient changes in serum osmolality . Large volumes of sodium chloride did not change osmolality but result ed in lower Normal saline ( NS ; 0.9 % NaCl ) is administered during kidney transplantation to avoid the risk of hyperkalemia associated with potassium-containing fluids . Recent evidence suggests that NS may be associated with adverse effects that are not seen with balanced-salt fluids , e.g. , lactated Ringer ’s solution ( LR ) . We hypothesized that NS is detrimental to renal function in kidney transplant recipients . Adults undergoing kidney transplantation were enrolled in a prospect i ve , r and omized , double-blind clinical trial of NS versus LR for intraoperative IV fluid therapy . The primary outcome measure was creatinine concentration on postoperative Day 3 . The study was terminated for safety reasons after interim analysis of data from 51 patients . Forty-eight patients underwent living donor kidney transplants , and three patients underwent cadaveric donor transplants . Twenty-six patients received NS , and 25 patients received LR . There was no difference between groups in the primary outcome measure . Five ( 19 % ) patients in the NS group versus zero ( 0 % ) patients in the LR group had potassium concentrations > 6 mEq/L and were treated for hyperkalemia ( P = 0.05 ) . Eight ( 31 % ) patients in the NS group versus zero ( 0 % ) patients in the LR group were treated for metabolic acidosis ( P = 0.004 ) . NS did not adversely affect renal function . LR was associated with less hyperkalemia and acidosis compared with NS . LR may be a safe choice for IV fluid therapy in patients undergoing kidney transplantation INTRODUCTION Although experience within Peru suggests clinical and physiological benefits of treating dehydration caused by diarrhoea with Lactated Ringer 's solution ( LR ) over sodium chloride 0.9 % , ( NaCl ) there is little documented scientific evidence supporting this view . It is important to clarify this issue and determine the best solution for use during epidemics . METHODOLOGY Forty patients suffering from dehydration due to choleriform diarrhoea were enrolled in the study . Twenty patients were treated using NaCl ( Group A ) and the other twenty with LR ( Group B ) . After diuresis recovery was achieved , the patients were continued on a course of oral rehydration salts . Serum electrolytes , arterial pH , HCO3- , and pCO2 were measured at three stages : at admission , after diuresis recovery , and after 12 hours . RESULTS Acidosis was corrected more quickly with LR that NaCl . The hyperosmolality and hypernatremic states were corrected with both solutions . CONCLUSION LR use result ed in a better clinical response than NaCl , illustrated by more rapid physiological correction , showing that mixed metabolic acidosis was corrected more quickly and more appropriately with this treatment STUDY OBJECTIVE To determine the effects of hyperchloremic acidosis , induced by dilute HCl infusion , on BP and circulating inflammatory mediators in an experimental model of severe sepsis in the rat . DESIGN R and omized , open-label , controlled experiment . SETTING University research laboratory . PARTICIPANTS Twenty-four adult , male , Sprague-Dawley rats . INTERVENTION Eighteen hours after inducing lethal sepsis by cecal ligation and puncture , animals were r and omized and classified into three groups . In groups 2 and 3 , we began an IV infusion of 0.1 N HCl to reduce the st and ard base excess ( SBE ) by 5 to 10 mEq/L and 10 to 15 mEq/L , respectively . In group 1 , we infused a similar volume of lactated Ringer solution . In all groups , infusions were continued for 8 h or until the animals died . MEASUREMENTS We measured mean arterial pressure ( MAP ) , arterial blood gases , electrolytes , plasma nitrate/nitrite , tumor necrosis factor (TNF)-alpha , interleukin (IL)-6 , and IL-10 levels at 0 h , 3 h , 6 h , and 8 h. RESULTS MAP remained stable in group 1 but decreased in groups 2 and 3 ( p < 0.001 ) , such that at 8 h MAP was much higher in group 1 ( 94 + /- 9.2 mm Hg ) [ + /- SD ] compared to either group 2 ( 71.6 + /- 20.1 mm Hg ) or group 3 ( 49.4 + /- 33.2 mm Hg ) [ p = 0.01 ] . This change in MAP correlated with the increase in plasma Cl(- ) ( R(2 ) = 0.50 , p < 0.0001 ) and less well with the decrease in pH ( R(2 ) = 0.24 , p < 0.001 ) . After 6 h of acidosis , plasma nitrite levels were significantly higher in group 2 animals compared to either group 1 or group 3 animals ( p < 0.05 ) . Plasma TNF-alpha , IL-6 , or IL-10 levels were not significantly different from control animals . CONCLUSION Moderate acidosis ( SBE of 5 to 10 mEq/L ) , induced by HCl infusion , worsened BP and increased plasma nitrate/nitrite levels but had no effect on circulating cytokines in septic rats . However , severe acidosis ( SBE of 10 to 15 mEq/L ) , while still causing hypotension , did not affect plasma nitrate/nitrite levels Thirty patients undergoing major hepatobiliary or pancreatic surgery were r and omly allocated to receive either 0.9 % saline or Plasmalyte 148 ( a balanced salt solution ) , at 15 ml.kg‐1.h‐1 . Arterial blood gas analysis was performed before and after surgery . Plasma biochemistry ( Na+ , K+ , Cl‐ , lactate ) measurements were made before and after surgery and at 24 h after surgery . The patients receiving 0.9 % saline had significantly increased chloride concentrations ( p < 0.01 ) , decreased st and ard bicarbonate concentrations ( p < 0.01 ) and increased base deficit ( p < 0.01 ) compared to those receiving Plasmalyte 148 . There were no significant changes in plasma sodium or potassium or blood lactate concentrations in either group . The exclusive use of 0.9 % saline intra‐operatively can produce a temporary hyperchloraemic acidosis which could be given false pathological significance . In addition it may exacerbate an acidosis result ing from an actual pathological stale . The use of a balanced salt solution such as Plasmalyte 148 may avoid these complications OBJECTIVE To determine if Ringer 's lactate is superior to 0.9 % sodium chloride solution for resolution of acidosis in the management of diabetic ketoacidosis ( DKA ) . DESIGN Parallel double blind r and omized controlled trial . METHODS Patients presenting with DKA at Kalafong and Steve Biko Academic hospitals were recruited for inclusion in this study if they were > 18 years of age , had a venous pH > 6.9 and ≤7.2 , a blood glucose of > 13 mmol/l and had urine ketones of ≥2 + . All patients had to be alert enough to give informed consent and should have received < 1 l of resuscitation fluid prior to enrolment . RESULTS Fifty-seven patients were r and omly allocated , 29 were allocated to receive 0.9 % sodium chloride solution and 28 to receive Ringer 's lactate ( of which 27 were included in the analysis in each group ) . An adjusted Cox proportional hazards analysis was done to compare the time to normalization of pH between the 0.9 % sodium chloride solution and Ringer 's lactate groups . The hazard ratio ( Ringer 's compared with 0.9 % sodium chloride solution ) for time to venous pH normalization ( pH = 7.32 ) was 1.863 ( 95 % CI 0.937 - 3.705 , P = 0.076 ) . The median time to reach a pH of 7.32 for the 0.9 % sodium chloride solution group was 683 min ( 95 % CI 378 - 988 ) ( IQR : 435 - 1095 min ) and for Ringer 's lactate solution 540 min ( 95 % CI 184 - 896 , P = 0.251 ) . The unadjusted time to lower blood glucose to 14 mmol/l was significantly longer in the Ringer 's lactate solution group ( 410 min , IQR : 240 - 540 ) than the 0.9 % sodium chloride solution group ( 300 min , IQR : 235 - 420 , P = 0.044 ) . No difference could be demonstrated between the Ringer 's lactate and 0.9 % sodium chloride solution groups in the time to resolution of DKA ( based on the ADA criteria ) ( unadjusted : P = 0.934 , adjusted : P = 0.758 ) CONCLUSION This study failed to indicate benefit from using Ringer 's lactate solution compared to 0.9 % sodium chloride solution regarding time to normalization of pH in patients with DKA . The time to reach a blood glucose level of 14 mmol/l took significantly longer with the Ringer 's lactate solution OBJECTIVE WHO recommends Ringers lactate ( RL ) and Normal Saline ( NS ) for rapid intravenous rehydration in childhood diarrhea and severe dehydration . We compared these two fluids for improvement in pH over baseline during rapid intravenous rehydration in children with acute diarrhea . DESIGN Double-blind r and omized controlled trial SETTING Pediatric emergency facilities at a tertiary-care referral hospital . INTERVENTION Children with acute diarrhea and severe dehydration received either RL ( RL-group ) or NS ( NS-group ) , 100 mL/kg over three or six hours . Children were reassessed after three or six hours . Rapid rehydration was repeated if severe dehydration persisted . Blood gas was done at baseline and repeated after signs of severe dehydration disappeared . OUTCOME MEASURES Primary outcome was change in pH from baseline . Secondary outcomes included changes in serum electrolytes , bicarbonate levels , and base-deficit from baseline ; mortality , duration of hospital stay , and fluids requirement . RESULTS Twenty two children , 11 each were r and omized to the two study groups . At primary end point ( disappearance of signs of severe dehydration ) , the improvement in pH from baseline was not significant in RL-group [ from 7.17 ( 0.11 ) to 7.28 ( 0.09 ) ] as compared to NS-group [ 7.09 ( 0.11 ) to 7.21 ( 0.09 ) ] , P=0.17 ( after adjusting for baseline serum Na/ Cl ) . Among this limited sample size , children in RL group required less fluids [ median 310 vs 530 mL/kg , P=0.01 ] and had shorter median hospital stay [ 38 vs 51 hours , P=0.03 ] . CONCLUSIONS There was no difference in improvement in pH over baseline between RL and NS among children with acute diarrhea and severe dehydration Aim . We hypothesized that normal saline ( NS ) may have more deleterious effects compared with lactated ringer ( LR ) in kidney transplant recipients because of the higher risk of acidosis and higher levels of serum potassium . Thus , the aim of this study was to determine the safety of LR if used during a renal transplant . Methods . Adults undergoing kidney transplantations were enrolled in a double-blinded r and omized prospect i ve clinical trial . They were divided into two groups in order to receive NS and LR infusion as intraoperative IV fluid replacement therapy . Results . There was a significant difference in the serum potassium level ( p = .000 ) and the PH ( p = .007 ) between the two groups at the end of transplantations . Two patients in the LR group lost their kidneys due to vascular graft thrombosis . In other words , hyperkalemia and acidosis occurred more frequently in the NS group while thrombotic events may be of concern in the LR group . Conclusion . Compared with NS , LR infusion may lead to a lower serum potassium level and a lower risk of acidosis , while there is major concern of the hypercoagulable state in these patients Objective : We compared the effects of intravenous infusions of 0.9 % saline ( [ Cl− ] 154 mmol/L ) and Plasma-Lyte 148 ( [ Cl− ] 98 mmol/L , Baxter Healthcare ) on renal blood flow velocity and perfusion in humans using magnetic resonance imaging ( MRI ) . Background : Animal experiments suggest that hyperchloremia result ing from 0.9 % saline infusion may affect renal hemodynamics adversely , a phenomenon not studied in humans . Methods : Twelve healthy adult male subjects received 2-L intravenous infusions over 1 hour of 0.9 % saline or Plasma-Lyte 148 in a r and omized , double-blind manner . Crossover studies were performed 7 to 10 days apart . MRI scanning proceeded for 90 minutes after commencement of infusion to measure renal artery blood flow velocity and renal cortical perfusion . Blood was sample d and weight recorded hourly for 4 hours . Results : Sustained hyperchloremia was seen with saline but not with Plasma-Lyte 148 ( P < 0.0001 ) , and fall in strong ion difference was greater with the former ( P = 0.025 ) . Blood volume changes were identical ( P = 0.867 ) , but there was greater expansion of the extravascular fluid volume after saline ( P = 0.029 ) . There was a significant reduction in mean renal artery flow velocity ( P = 0.045 ) and renal cortical tissue perfusion ( P = 0.008 ) from baseline after saline , but not after Plasma-Lyte 148 . There was no difference in concentrations of urinary neutrophil gelatinase – associated lipocalin after the 2 infusions ( P = 0.917 ) . Conclusions : This is the first human study to demonstrate that intravenous infusion of 0.9 % saline results in reductions in renal blood flow velocity and renal cortical tissue perfusion . This has implication s for intravenous fluid therapy in perioperative and critically ill patients . BACKGROUND : This study aim ed to quantify changes in acid-base balance , potassium and lactate levels as a function of administration of different crystalloid solutions during kidney transplantation , and to determine the ideal fluid for such patients . METHODS : In this double-blind study , patients were r and omized to three groups ( n = 30 each ) to receive either normal saline , lactated Ringer 's , or Plasmalyte , all at 20–30 mL · kg−1 · h−1 . Arterial blood analyses were performed before induction of anesthesia , and at 30-min intervals during surgery , and total IV fluids recorded . Urine volume , serum creatinine and BUN , and creatinine clearance were recorded on postoperative days 1 , 2 , 3 , and 7 . RESULTS : There was a statistically significant decrease in pH ( 7.44 ± 0.50 vs 7.36 ± 0.05 ) , base excess ( 0.4 ± 3.1 vs –4.3 ± 2.1 ) , and a significant increase in serum chloride ( 104 ± 2 vs 125 ± 3 mM/L ) in patients receiving saline during surgery . Lactate levels increased significantly in patients who received Ringer 's lactate ( 0.48 ± 0.29 vs 1.95 ± 0.48 ) . No significant changes in acid-base measures or lactate levels occurred in patients who received Plasmalyte . Potassium levels were not significantly changed in any group . CONCLUSIONS : All three crystalloid solutions can be safely used during uncomplicated , short- duration renal transplants ; however , the best metabolic profile is maintained in patients who receive Plasmalyte BACKGROUND Changes in acid-base balance caused by infusion of a 0.9 % saline solution during anesthesia and surgery are poorly characterized . Therefore , the authors evaluated these phenomena in a dose-response study . METHODS Two groups of 12 patients each who were undergoing major intraabdominal gynecologic surgery were assigned r and omly to receive 0.9 % saline or lactated Ringer 's solution in a dosage of 30 ml x kg(-1 ) x h(-1 ) . The pH , arterial carbon dioxide tension , and serum concentrations of sodium , potassium , chloride , lactate , and total protein were measured in 30-min intervals . The serum bicarbonate concentration was calculated using the Henderson-Hasselbalch equation and also using the Stewart approach from the strong ion difference and the amount of weak plasma acid . The strong ion difference was calculated as serum sodium + serum potassium - serum chloride - serum lactate . The amount of weak plasma acid was calculated as the serum total protein concentration in g/dl x 2.43 . RESULTS Infusion of 0.9 % saline , but not lactated Ringer 's solution , caused a metabolic acidosis with hyperchloremia and a concomitant decrease in the strong ion difference . Calculating the serum bicarbonate concentration using the Henderson-Hasselbalch equation or the Stewart approach produced equivalent results . CONCLUSIONS Infusion of approximately 30 ml x kg(-1 ) x h(-1 ) saline during anesthesia and surgery inevitably leads to metabolic acidosis , which is not observed after administration of lactated Ringer 's solution . The acidosis is associated with hyperchloremia Objective : To compare the effectiveness and side effects of lactated Ringer ’s solution ( LR ) and 0.9 % saline ( NS ) in the treatment of rhabdomyolysis induced by doxylamine intoxication . Methods : In this 15-month-long prospect i ve r and omised single-blind study , after excluding 8 patients among 97 doxylamine-intoxicated patients , 28 ( 31 % ) patients were found to have developed rhabdomyolysis and were r and omly allocated to NS group ( n = 15 ) or LR group ( n = 13 ) . Results : After 12 h of aggressive hydration ( 400 ml/h ) , urine/serum pH was found to be significantly higher in the LR group , and serum Na+/Cl− levels to be significantly higher in the NS group . There were no significant differences in serum K+ level and in the time taken for creatine kinase normalisation . The amount of sodium bicarbonate administered and the frequency administration of diuretics was significantly higher in the NS group . Unlike the NS group , the LR group needed little supplemental sodium bicarbonate and did not develop metabolic acidosis . Conclusion : LR is more useful than NS in the treatment of rhabdomyolysis induced by doxylamine intoxication In this study , we compared the effects of large intravascular volume infusion of 0.9 % saline ( NS ) or lactated Ringer ’s ( LR ) solution on electrolytes and acid base balance during major spine surgery and evaluated the postoperative effects . Thirty patients aged 18–70 yr were included in the study . General anesthesia was induced with 5 mg/kg thiopental and 0.1 mg/kg vecuronium IV . Anesthesia was maintained with oxygen in 70 % nitrous oxide and 1.5%–2 % sevoflurane . In Group I , the NS solution , and in Group II , the LR solution were infused 20 mL · kg−1 · h−1 during the operation and 2.5 mL · kg−1 · h−1 , postoperatively . Electrolytes ( Na+ , K+ , Cl− ) and arterial blood gases were measured preoperatively , every hour intraoperatively and at the 1st , 2nd , 4th , 6th , and 12th hours postoperatively . In the NS group , pHa , HCO3 and base excess decreased , and Cl− values increased significantly at the 2nd hour and Na+ values increased at the 4th hour intraoperatively ( P < 0.001 ) . The values returned to normal ranges at the 12th hour postoperatively . In the LR group , blood gas analysis and electrolyte values did not show any significant difference intraoperatively , but the increase in Paco2 and the decrease in pHa and serum Na+ was significant at the 1st hour postoperatively . Although intraoperative 20 mL · kg−1 · h−1 LR infusion does not cause hyperchloremic metabolic acidosis as does NS infusion , it leads to postoperative respiratory acidosis and mild hyponatremia RATIONALE Hyperchloremic acidosis is common in the critically ill and is often iatrogenic . We have previously shown that hyperchloremic acidosis increases nuclear factor-kappaB DNA binding in lipopolysaccharide-stimulated RAW 264.7 cells . However , evidence that hyperchloremic acidosis leads to increased inflammation in vivo has been limited to nitric oxide . OBJECTIVES To determine if acidosis , induced by dilute hydrochloric acid ( HCl ) infusion , will increase circulating inflammatory mediator levels in an experimental model of severe sepsis in rats . METHODS Eighteen hours after inducing lethal sepsis by cecal ligation and puncture in 20 adult , male , Sprague-Dawley rats , we r and omized animals into three groups . In groups 2 and 3 , we began an IV infusion of 0.1 N HCl to reduce the st and ard base excess ( SBE ) by 5 to 10 mEq/L and 10 to 15 mEq/L , respectively . In group 1 , we infused a similar volume of lactated Ringer solution . In all groups infusion continued 8 h or until the animal died . MEASUREMENTS AND MAIN RESULTS We measured arterial blood gases , whole-blood lactate , and chloride , tumor necrosis factor ( TNF ) , interleukin (IL)-6 , and IL-10 levels at 0 h , 4 h , and 8 h. All measured cytokines increased over time . Compared to group 1 , animals in groups 2 and 3 exhibited greater increase in all three cytokines , with the greatest increases seen with severe acidosis . CONCLUSION Moderate ( SBE , - 5 to - 10 ) and severe ( SBE , - 10 to - 15 ) acidosis , induced by HCl infusion , increases circulating levels of IL-6 , IL-10 , and TNF in normotensive septic rats BACKGROUND Ischemia-reperfusion injury is an inevitable consequence of kidney transplantation , leading to metabolic acidosis . This study compared the effects of normal saline ( NS ) and Plasmalyte on acid-base balance and electrolytes during living donor kidney transplantation using the Stewart and base excess ( BE ) methods . METHODS Patients were r and omized to an NS group ( n = 30 ) or a Plasmalyte group ( n = 30 ) . Arterial blood sample s were collected for acid-base analysis after induction of anesthesia ( T0 ) , prior to clamping the iliac vein ( T1 ) , 10 minutes after reperfusion of the donated kidney ( T2 ) , and at the end of surgery ( T3 ) . In addition serum creatinine and 24-hour urine output were recorded on postoperative days 1,2 , and 7 . Over the first postoperative 7 days we recorded episodes of graft failure requiring dialysis . RESULTS Compared with the Plasmalyte group , the NS group showed significantly lower values of pH , BE , and effective strong ion differences during the postreperfusion period ( T2 and T3 ) . Chloride-related values ( chloride [ Cl(- ) ] , free-water corrected Cl(- ) , BEcl ) were significantly higher at T1 , T2 , and T3 , indicating hyperchloremic rather than dilutional metabolic acidosis . Early postoperative graft functions in terms of serum creatinine , urine output , and graft failure requiring dialysis were not significantly different between the groups . CONCLUSIONS Both NS and Plamalyte can be used safely during uncomplicated living donor kidney transplantation . However , Plasmalyte more stably maintains acid-base and electrolyte balance compared with NS especially during the postreperfusion period Objective : We sought to compare resuscitation with 0.9 % NaCl versus Plasma-Lyte A , a calcium-free balanced crystalloid solution , hypothesizing that Plasma-Lyte A would better correct the base deficit 24 hours after injury . Background : Sodium chloride ( 0.9 % ) ( 0.9 % NaCl ) , though often used for resuscitation of trauma patients , may exacerbate the metabolic acidosis that occurs with injury , and this acidosis may have detrimental clinical effects . Methods : We conducted a r and omized , double-blind , parallel-group trial ( NCT01270854 ) of adult trauma patients requiring blood transfusion , intubation , or operation within 60 minutes of arrival at the University of California Davis Medical Center . Based on a computer-generated , blocked sequence , subjects received either 0.9 % NaCl or Plasma-Lyte A for resuscitation during the first 24 hours after injury . The primary outcome was mean change in base excess from 0 to 24 hours . Secondary outcomes included 24-hour arterial pH , serum electrolytes , fluid balance , re source utilization , and in-hospital mortality . Results : Of 46 evaluable subjects ( among 65 r and omized ) , 43 % had penetrating injuries , injury severity score was 23 ± 16 , 20 % had admission systolic blood pressure less than 90 mm Hg , and 78 % required an operation within 60 minutes of arrival . The baseline pH was 7.27 ± 0.11 and base excess −5.9 ± 5.0 mmol/L. The mean improvement in base excess from 0 to 24 hours was significantly greater with Plasma-Lyte A than with 0.9 % NaCl { 7.5 ± 4.7 vs 4.4 ± 3.9 mmol/L ; difference : 3.1 [ 95 % confidence interval ( CI ) : 0.5–5.6]}. At 24 hours , arterial pH was greater [ 7.41 ± 0.06 vs 7.37 ± 0.07 ; difference : 0.05 ( 95 % CI : 0.01–0.09 ) ] and serum chloride was lower [ 104 ± 4 vs 111 ± 8 mEq/L ; difference : −7 ( 95 % CI : −10 to −3 ) ] with Plasma-Lyte A than with 0.9 % NaCl . Volumes of study fluid administered , 24-hour urine output , measures of re source utilization , and mortality did not significantly differ between the 2 arms . Conclusions : Compared with 0.9 % NaCl , resuscitation of trauma patients with Plasma-Lyte A result ed in improved acid-base status and less hyperchloremia at 24 hours postinjury . Further studies are warranted to evaluate whether resuscitation with Plasma-Lyte A improves clinical outcomes . R and omized controlled trial , level I. ( Clinical Trials.gov Record UCDIRB-200917793 . BACKGROUND & AIMS Aggressive fluid resuscitation is recommended for initial management of acute pancreatitis . We performed a r and omized controlled trial to evaluate the impact of a goal -directed fluid resuscitation protocol on systemic inflammation in patients with acute pancreatitis . We then determined the impact of resuscitation with lactated Ringer 's solution , compared with normal saline . METHODS We performed a r and omized controlled trial of 40 patients with acute pancreatitis at 3 New Engl and hospitals from May 2009-February 2010 . Patients received goal -directed fluid resuscitation with lactated Ringer 's solution , goal -directed fluid resuscitation with normal saline , st and ard fluid resuscitation with lactated Ringer 's solution , or st and ard fluid resuscitation with normal saline . Systemic inflammation was measured on the basis of levels of systemic inflammatory response syndrome ( SIRS ) and C-reactive protein ( CRP ) level after 24 hours . RESULTS The volumes of fluid administered during a 24-hour period were similar among patients given goal -directed or st and ard fluid resuscitation ( mean , 4300 vs 4600 mL , respectively ; P = .87 ) . Goal -directed resuscitation did not significantly reduce incidence of SIRS , compared with st and ard resuscitation ( 11.8 % vs 13.0 % , respectively ; P = .85 ) or levels of CRP after 24 hours ( 87.1 vs 69.2 mg/dL , respectively ; P = .75 ) . By contrast , there was a significant reduction in SIRS after 24 hours among subjects resuscitated with lactated Ringer 's solution , compared with normal saline ( 84 % reduction vs 0 % , respectively ; P = .035 ) ; administration of lactated Ringer 's solution also reduced levels of CRP , compared with normal saline ( 51.5 vs 104 mg/dL , respectively ; P = .02 ) . CONCLUSIONS Patients with acute pancreatitis who were resuscitated with lactated Ringer 's solution had reduced systemic inflammation compared with those who received saline |
13,396 | 27,115,326 | From the limited results it is unclear whether the wearing of surgical face masks by members of the surgical team has any impact on surgical wound infection rates for patients undergoing clean surgery | BACKGROUND Surgical face masks were originally developed to contain and filter droplets containing microorganisms expelled from the mouth and nasopharynx of healthcare workers during surgery , thereby providing protection for the patient .
However , there are several ways in which surgical face masks could potentially contribute to contamination of the surgical wound , e.g. by incorrect wear or by leaking air from the side of the mask due to poor string tension .
OBJECTIVES To determine whether the wearing of disposable surgical face masks by the surgical team during clean surgery reduces postoperative surgical wound infection . | Background Arthroplasty surgeons are increasingly using personal protection systems with helmets . It is theoretically possible for the fans in these helmets to blow squames , sweat droplets and orobronchial fomites onto the surgical site . A controlled experiment was set up to investigate the effect of different surgical gowns on counts of airborne particles measuring ≥0.3 μm , using a h and -held particle counter . Methods The clothing that was sequentially tested included the following:1.Barrier ® surgical gown ( single use ) made from nonwoven polypropylene ( Mölnlycke Health Care Ltd , Dunstable , UK)2.Stryker ® T5 Helmet ( reusable ) covered with a disposable Stryker ® T4/T5 urethane hood worn separate to and enclosed by the Barrier ® surgical gown both at the front and back3.Stryker ® T5 Helmet ( reusable ) worn within a disposable Stryker ® T4/T5 urethane zippered toga ( Stryker Corporation , Kalamazoo , MI , USA)Six readings were taken for each of the following three setups in a r and omised order:1.Gown : surgeon with surgical gown and face mask2.Hood : surgeon with surgical gown and hood , maximum fan speed3.Toga : surgeon with toga , maximum fan speedWilcoxon rank sum tests were applied to assess e quality of means between the three occlusive measures ( gown , hood , toga ) . P values were computed based upon one-sided tests and adjusted for multiple comparisons using the Bonferroni correction . Results The mean particle counts ( over more than 5 L of air ) for the three set-ups were : gown : 1178 ( least protective ) , hood : 328 , toga : 42 ( most protective ) . There was a significant reduction in particle counts for the toga versus gown ( p = 0.007 ) and toga versus hood ( p = 0.037 ) ; differences in particle counts were not significant between the hood and gown ( p = 0.140 ) . Conclusions The fans in the helmets do not increase contaminants by blowing particles from the head area . A significant reduction in surgeon-originated contaminants was seen with the toga compared to both the hood/gown separate ensemble and gowns alone Bacterial shedding , wound contamination and clinical -infection rates in clean wounds are influenced by operating-theatre dress . The aim of this study was to clarify the relative contribution of hats , masks and clothing to the control of wound contamination in both ultraclean ( enclosed vertical laminar-flow ) and conventional ( plenum ventilated ) airflow theatres . Personnel wore varying combinations of dress in both types of theatre . Colony forming units ( cfus ) were measured on settle plates at head and waist height , and in the air by a centrifugal air sample r. Bacterial counts in conventional theatres were consistently high and were not significantly influenced by theatre dress . There was a 22-fold increase in cfus on settle plates at waist height when neither hat nor mask were worn , a 15-fold increase when a hat but no mask was worn and a fourfold increase with a mask but no hat in vertical laminar airflow enclosures , although air sample counts remained low . When balloon-cotton clothing was worn , rather than cuffed polyester with microfilament barrier-fabric gowns , cfu counts rose by a factor of six . The bacterial inoculum in conventionally ventilated theatres , or in ultraclean theatres if hat or mask are omitted or balloon-cotton clothing worn , is theoretically sufficient to infect a prosthetic arthroplasty . Theatre-air sampling alone does not reflect local contamination when a surgeon st and s over a wound in a vertical laminar-flow enclosure , and both hats and masks are an important part of dress in such environments The influence of surgical mask usage on bacterial contamination of the operative field was studied during 30 cardiac catheterization procedures . Mask position was varied during each procedure according to a pre design ed r and om table . The number of bacterial colonies recoverable when no mask was worn was significantly higher than that detected when a full mask was worn ( P < 0.002 ) . Shedding of Staphylococcus epidermidis was greater when no mask was worn ( mean 5.2 colonies 10 min-1 ) than shedding with full mask ( mean 2.7 colonies 10 min-1 ; P < 0.004 ) . Although mask placement below the nose was associated with higher mean colony counts than that above the nose , these differences were not statistically significant It has never been shown that wearing surgical face masks decreases postoperative wound infections . On the contrary , a 50 % decrease has been reported after omitting face masks . The present study was design ed to reveal any 30 % or greater difference in general surgery wound infection rates by using face masks or not . During 115 weeks , a total of 3,088 patients were included in the study . Weeks were denoted as “ masked ” or “ unmasked ” according to a r and om list . After 1,537 operations performed with face masks , 73 ( 4.7 % ) wound infections were recorded and , after 1,551 operations performed without face masks , 55 ( 3.5 % ) infections occurred . This difference was not statistically significant ( p > 0.05 ) and the bacterial species cultured from the wound infections did not differ in any way , which would have supported the fact that the numerical difference was a statistically “ missed ” difference . These results indicate that the use of face masks might be reconsidered . Masks may be used to protect the operating team from drops of infected blood and from airborne infections , but have not been proven to protect the patient operated by a healthy operating team . RésuméIl n'a jamais été démontré que le port d'une bavette chirurgicale diminue le nombre des infections pariétales . Au contraire , on a même rapporté une diminution de 50 % lorsqu'on ne les utilisait pas . Cette étude a été élaborée pour déceler l'influence du port de la bavette dans la réduction des taux d'infections pariétales chez l'opéré en chirurgie générale de 30 % au moins . Pendant 115 semaines , 3,088 patients ont été inclus dans cette étude . Pendant une semaine donnée , tirée au sort , les chirurgiens mettaient ou ne mettaient pas de bavette . Aprés 1,537 opérations effectuées avec bavette , on a trouvé 73 ( 4.7 % ) abcès de paroi alors qu'après 1,551 interventions sans bavette , il y a eu 55 ( 3.5 % ) infections . Cette différence n'est pas statistiquement significative ( p>0.05 ) et les cultures bactériennes à partir de la plaie opératoire ne différaient en aucune manière ce qui renforçait la conclusion que cette absence de différence statistiquement significative était réele . Ces résultats indiquent que l'utilisation de la bavette chirurgicale pourrait être remise en question . La bavette joue un rôle de protection de l'équipe chirurgicale contre les infections portées par le sang éclaboussé en salle ou contre les infections aériennes , mais son effet sur la protection du patient n'a pas été prouvé lorsque l'équipe chirurgicale elle-même est en bonne santé . ResumenNo ha sido demostrado que el uso de la máscara facial quirúrgica disminuya la tasa de infecfión postoperatoria ; por el contrario , algunos autores han informado una reducción de 50 % al omitir su uso . El présente estudio fue diseñado con el propósito de revelar una diferencia de 30 % o más en las tasas de infección de la herida en procedimientos de cirugía general con el uso y sin el uso de la máscara quirúrigica . En el curso de 115 semanas , 3,088 pacientes fueron incluídos en el estudio . Las semanas fueron design adas como “ con máscara ” o “ sin mascara , ” según la lista de r and omización . En 1,537 operaciones realizadas con máscara se registraron , 73 ( 4.7 % ) infecciones de herida y en 1,551 operaciones realizadas sin máscara se informaron 55 ( 3.5 % ) infecciones . Esta diferencia no es estadísticamente significativa ( p>0.05 ) ; las especies de bacterias aisladas de las heridas no exhibieron diferencias que puedieran hacer pensar que la diferencia númerica en favor de las operaciones sin máscara tenga importancia . Tales result ados indican que el uso de máscaras faciales puede ser reconsiderado . Las mascaras pueden ser utilizadas para proteger al personal quirúrgico de gotas de sangre infectada y de infecciones en el ambiente , pero no han demostrado que protejan al paciente que es operado por un equipo quirúrgico sano Aim : To assess whether facemask utilisation by the surgeon during cataract surgery has any effect on the bacterial load falling onto the operative site . Method : Prospect i ve r and omised masked study . Consent was obtained from 221 patients . Cases were r and omised to wearing a new mask or not wearing any mask throughout the procedure . Blood agar settle plates were placed adjacent to the patient 's head in the operative field . Duration of procedure was noted . Plates were incubated and read at 48 hours . Colony forming bacteria were counted and identified . Results : There were significantly fewer organisms cultured when the surgeon used a facemask ( p=0.0006 ) . The majority of organisms were Staphylococcus epidermidis , Bacillus spp , and Diphtheroid spp ; however Staphylococcus aureus and Pseudomonas aeruginosa were cultured on several occasions . There were no cases of infective complication . Conclusions : The main purpose of an operating mask is to prevent bacteria falling on to the operative site from the surgeon 's oropharynx or nasopharynx with the concomitant theoretical risk of infective complication . Operating masks were shown to have a significant effect on the volume of bacterial organisms falling to the operative site ; however , whether this is clinical ly significant is unknown INTRODUCTION Despite the lack of scientific evidence , surgical caps and masks are worn routinely by many physicians and nurses in the catheterisation laboratories to avoid local and generalised infections . When we changed our practice , we performed a r and omised study to assure the quality of our routine . MATERIAL AND METHODS All patients undergoing left- or right-sided cardiac catheterisation were r and omly allocated to our five laboratories . About two months after the procedure , the patients were sent a question naire concerning signs and symptoms of possible inflammation or infection after the procedure . RESULTS Of 1,034 patients , 855 ( 82.7 % ) responded to the question naire . Although 25 patients in the caps and mask group vs 19 patients in the other group ( 6.1 % vs 4.3 % , ns ) had complaints from the procedural access site in the groin , none of these could be ascribed to definite infection . DISCUSSION The use of caps and masks during percutaneous cardiac catheterisation procedures is based on the concept that the infection rate of patients is reduced . The size of the catheter used , procedure time , and the use of caps and masks by both the surgeon and the assisting staff are discussed . CONCLUSION The routine use of caps and masks does not seem to have that much beneficial impact on the occurrence of procedure-related inflammations or infections in the cardiac catheterisation laboratory To find out if the wearing of masks influenced the number of colony forming units ( CFU ) of bacteria in the vicinity of the wound , 14 operations on the thyroid gl and were divided in 30 min periods during which personnel were r and omly allocated to wear or not to wear masks . There was at least one period with , and one without masks during each operation . Air was sample d 20 cm from the wound using a Sartorius membrane filter sample r. There were no significant differences between the groups in either numbers of CFU or species of pathogenic bacteria found The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating A r and omly controlled trial was performed on 41 women having gynaecological surgery in which the team of surgeons and nurses wore or did not wear masks . After major abdominal surgery , 3 of 5 patients in the unmasked group developed wound infections whereas no infection was observed in the 4 patients of the masked group . A greater number of Streptococci were also found by settle-plates on the operating table in the unmasked group . No infection was recorded after minor or vaginal surgery |
13,397 | 23,737,396 | We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening , mainly because of differential misclassification of cause of death .
Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out , it is likely that the absolute effect of screening today is smaller than in the trials .
Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening | BACKGROUND A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary .
OBJECTIVES To assess the effect of screening for breast cancer with mammography on mortality and morbidity . | Summary In March 1981 , 40,318 women in Stockholm , aged 40–64 , entered a r and omized trial of breast cancer screening by single-view mammography alone versus no intervention in a control group of 20,000 women . The attendance rate during the first screening round was 81 per cent and the cancer detection rate was 4.0 per 1000 women . The detection the rate fell to 3.1 per 1000 in the second round , which was completed in October 1985 . During 1986 the controlled design of the study was broken and the contro women were invited once to screening which was completed the same year . A total of 428 cases of breast cancer were thus diagnosed in the study group and 439 in the adjusted control group . After a mean follow-up of 7.4 years the number of breast cancer deaths in the study and control groups was 39 and 30 respectively . The relative risk of breast cancer death ( screening versus control ) was 0.71 ( 95 per cent confidence interval : 0.4–1.2 ) . Among women older than 50 years at entry the relative risk was 0.57 ( 95 per cent confidence interval : 0.3–1.1 ) . Cancer deaths among women under 50 were few and perhaps because of this no mortality reduction was seen in this age group . The estimate of mortality reduction lies between the results from two earlier Swedish r and omized controlled trials A cross-sectional , r and omized screening with mammary radiography of 15 748 women aged 45 to 69 and living in Malmö for the detection of breast carcinoma is described . The detection rate of breast carcinoma was 7.5 per 1 000 , 16 per cent of the carcinoma being non-invasive and 43 invasive with a diameter of at most 10 mm . The overall rate of axillary metastases was 18 per cent . The sensitivity of the radiography was 91.5 per cent , the specificity 99.2 per cent and the predictive value 47 per cent . It is concluded that mammary radiography is an effective screening method for detecting early carcinoma The Canadian National Breast Screening Study ( NBSS ) is a r and omized controlled trial to assess the effect of screening on breast cancer mortality . The NBSS design ated a single reference radiologist who blindly review ed over the course of the study 5200 r and omly selected two-view mammographic examinations of women not known to have breast cancer . He also review ed 575 screening-detected breast cancer ( SBC ) cases and 102 interval breast cancer ( IBC ) cases . All cancers were histologically proven . As a result of the review s , comments on inter-observer agreement , interpretation , and technical quality were conveyed on an ongoing basis to radiologists appointed to 15 NBSS screening centers . Agreement of the reference radiologist with center radiologists was better for breast cancer cases ( kappa = 0.511 , P less than .002 ) than for those not known to have breast cancer ( kappa = 0.307 , P less than .002 ) . Observer error and technical problems led to delayed detection in 22 % of SBCs and 35 % of IBCs . Another 11 % of SBCs and 58 % of IBCs were probably mammographically occult . No similarly comprehensive review of mammography during a screening program has been published . Suggestions arising from the NBSS review were sometimes resisted by center radiologists . Measures are suggested which might facilitate acceptance of recommendations arising from audit mechanisms in mammography screening programs , thereby enhancing opportunities for mammographic excellence Characteristics of women aged 40 - 59 , recorded at an initial breast screen , were compared with the outcome of incident , invasive breast cancer occurring up to 3 years after the initial screen . The study design was case-control , nested within the study population of the Canadian National Breast Screening Study . Screening consisted of a two-view mammographic examination and physical examination of the breasts ; additional risk factor information was obtained from self-administered question naires . Of the etiological risk factors considered only age at entry or years menstruating were significant risk factors for breast cancer ( P < 0.0025 ) . Years menstruating accounted for much of the age effect and all of the menopausal status effect . Risk factors obtainable from mammography and physical examination were more significant than self-reported risk factors , other than age or years menstruating . In spite of possible misclassification of the variable parenchymal pattern , women with a mammographic film classified as either P2 or DY had a 2-fold risk of breast cancer ( odds ratio = 2.1 ; 95 % confidence interval = 1.5 - 2.9 , P = 2.9E-05 ) . An abnormality reported by either the radiologist [ odds ratio = 1.7 ( 1.3 - 2.3 ) ] or nurse examiner [ odds ratio = 1.9 ( 1.4 - 2.6 ) ] was also associated with an independent significant risk OBJECTIVES : To estimate women 's expectations of the accuracy of screening mammography and to explore attitudes towards compensation for missed cancers . DESIGN : Cross sectional survey ( by telephone ) . SETTING : Australia ; population -based survey conducted in April 1996 . PARTICIPANTS : R and om sample of women aged 30 - 69 years . A total of 2935 women completed the Breast Health Survey ( adjusted response rate 65 % ) . A r and om sample of 115 completed this sub-survey on perceived sensitivity of mammographic screening and compensation for missed cancers . RESULTS : About one third of women ( 32.2 % , 95 % CI 23.7 , 40.7 ) had an unrealistically high expectation of the sensitivity of screening mammography , reporting it to be 95 % or higher . Approximately 40 % of the women ( 43.5 % , 95 % CI 34.4 , 52.6 ) thought that screening mammography should pick up all cancers ( should have a sensitivity of 100 % ) . Just under half the women ( 45.2 % , 95 % CI 36.1 , 54.3 ) said financial compensation should be awarded for a cancer missed by screening mammography even if the cancer was missed as a consequence of the small failure rate of the test . Younger women living in metropolitan areas and women who had realistic expectations of the accuracy of the tests were more likely to favour financial compensation . CONCLUSION : Unrealistically high expectations of the sensitivity of screening mammography were common in this group of women . Many women favoured financial compensation for missed cancers even if the cancer was missed solely because of the failure rate of the test . Public education is required to inform women of the limited sensitivity of breast cancer tests but this may not reduce cl aims for financial compensation when cancers are missed Results from the r and omized trial conducted by the Health Insurance Plan ( HIP ) to determine the efficacy of breast cancer screening with mammography and palpation are reported for longer periods than previously available . By the end of 10 years after entry , the study group 's mortality due to breast cancer was about 30 % below the control group 's . Arithmetic gains due to screening were maintained through year 14 ; relative gains declined . With increases in the period of follow-up , cumulative survival rates among cases detected by mammography alone ( palpation negative during screening ) , decreased more rapidly than rates among other subgroups , but survival rates for mammography cases remained relatively high . Study women aged 40 - 49 years at entry began to show lower breast cancer mortality than those in the control group as duration of follow-up increased . Reservations are advanced about the acceptance of this finding as evidence of the efficacy of screening under age 50 under the conditions of the HIP study . The reservations are based on the observation that the decrease of mortality among the study group aged 45 - 49 at entry is concentrated entirely among cases diagnosed after they reached 50 years of age A trial in the UK to study the effect on mortality from breast cancer of invitation for annual mammography from the age of 40–41 , has r and omised a total of 160 921 women in the ratio 1 : 2 to the intervention and control arms . All breast cancers diagnosed in the two arms have been identified , and the histology review ed . This paper presents the results of an interim analysis using surrogate outcome measures to compare predicted breast cancer mortality in the two arms based on 1287 cases diagnosed to 31.12.1999 . Due to earlier diagnosis , there is currently an 8 % excess of invasive breast cancers in the intervention arm . The ratio of predicted deaths at 10 years in the intervention arm relative to the control arm , adjusted for this excess diagnosis , ranges from 0.89 ( 95 % confidence interval ( CI ) 0.78–1.01 ) to 0.90 ( 95 % CI 0.80–1.01 ) . Screening from age 40 may result in a lower reduction in breast cancer mortality than that observed in other trials including women below age 50 . This analysis based on surrogate outcome measures suggests that a reduction in breast cancer mortality may be observed in this trial . However , a number of assumptions have been necessary and firm conclusions must await the analysis of observed mortality from breast cancer The Canadian National Breast Screening Study ( CNBSS ) , conducted on women age 40 - 49 , was design ed to evaluate the efficacy of combined annual mammography and physical examination of the breasts in reducing breast cancer mortality in comparison to usual care ( UC ) controls . From January 1980 through March 1985 , 25,214 women were individually r and omized to the mammography/physical exam ( MP ) arm and 25,216 to the UC . The integrity of the r and omization has been review ed and confirmed to be unbiased . During an average , follow-up of 10.5 years from entry ( range : 8.75 - 13 years ) , 82 women died from breast cancer in the MP arm and 72 in the UC , for a rate ratio of 1.14 ( 95 % confidence interval : 0.83 - 1.56 ) . All-cause mortality was almost identical comparing the two groups ; the nonsignificant excess of breast cancer deaths in the MP arm was balanced by an excess of other cancer deaths in the UC arm Large-scale public health trials are often r and omized by geographic or administrative clusters , for reasons of financial or organizational exigency . In this paper , we deal with the situation where the dependent variable is a count of events , such as mortality from , or incidence of a given disease . Simulation results show that this design may decrease power by more than 50 per cent . The lost power can largely be replaced by incorporating information on the dependent variable , within clusters , before the start of the trial . The pretrial and trial data can be analysed by negative trinomial models Eighteen months after the 1980 initiation of the Canadian National Breast Screening Study ( NBSS ) ( a multicenter r and omized controlled trial that will involve 90,000 women ) , the Toronto center experience such severe problems with recruitment that the study as a whole was jeopardized . Impediments to recruitment arose in five areas . The design of the protocol was criticized by some physicians and participants , a problem that could only be met by justifying the design . A second problem was a lack of underst and ing of the concept of screening and mistaken assumptions about what participation in the NBSS entailed . Thirdly , recruitment problems occurred at a time when the media were focusing much attention on the hazards of low-level ionizing radiation . Fourthly , women were found to have a variety of personal reasons for delaying or avoiding entry into the study . Finally , factors characteristic of the Canadian milieu such as universal health coverage may have acted as a disincentive to entry . To improve physician underst and ing , NBSS personnel made presentations at medical rounds and scientific meetings ; articles were written for medical journals . To win support from the lay public , talks were given to recreation or work-based groups . Appearances on radio and television talk shows were sought out . Mass mailings to university staff and professional associations did not produce large responses , nor did advertisements on television , radio , or in newspapers . The distribution of a check insert in a government mailing gave rise to hundreds of appointments across Canada . However , for generating an ongoing adequate level of recruitment , the best measure has been the mailing of personally addressed letters to eligible women followed by a telephone call . Data on response rates , cost and women 's attitudes toward the study are reported . By early 1983 , Toronto met its recruitment target of 12,000 BACKGROUND The Swedish Two-County Trial has been criticised on the grounds of the cluster r and omisation and alleged bias in classification of cause of death . PATIENTS AND METHODS In the Two-County Trial , 77 080 women were r and omised to regular invitation to screening ( active study population , ASP ) and 55 985 to no invitation ( passive study population , PSP ) , in 45 geographical clusters . After approximately 7 years , the PSP was invited to screening and the trial closed . We analysed data using hierarchical statistical models to take account of cluster r and omisation , and performed a conservative analysis assuming a systematic difference between ASP and PSP in baseline breast cancer mortality in one of the counties . We also analysed deaths from causes other than breast cancer and from all causes among breast cancer cases diagnosed in the ASP and PSP . RESULTS Taking account of the cluster r and omisation there was a significant 30 % reduction in breast cancer mortality in the ASP . Conservatively , assuming a systematic difference between ASP and PSP clusters in baseline breast cancer mortality , there was a significant 27 % reduction in mortality in the ASP . Ignoring classification of cause of death , there was a significant 13 % reduction in all-cause mortality in breast cancer cases in the ASP . CONCLUSIONS Breast cancer mortality is a valid end point and mammographic screening does indeed reduce mortality from breast cancer . The criticisms of the Swedish Two-County Trial are unfounded Edinburgh was selected as one of the centres in the UK Seven-year Trial of Breast Screening of women aged 45 - 65 which began in 1979 . Subsequently , our study was extended to a r and omised trial with its own control population within the city . Half the practice s were r and omly allocated for screening , giving a cluster sampling of women . The total number in the trial is 65,000 . Women with previously diagnosed breast cancer are excluded . Women allocated for screening are invited to the clinic and screened according to the procedures specified in the U.K. protocol , having clinical examination every year and mammography on alternate years . The two modalities of screening are assessed independently and the role of nurses is being evaluated . Breast cancer incidence is monitored by pathology register and the local cancer registry office and deaths from the General Register office . Long-term follow-up will be obtained through flagging at NHS Central Register . To determine the value of screening , st and ard statistical methods will be used to compare breast cancer mortality rates in the whole of the screening population with that of the controls . This trial has a power of 83 % of detecting a reduction in mortality of 35 % after 7 years of follow-up and a power of 95 % of detecting a similar reduction at 10 years ( alpha = 0.05 , one-sided test ) BACKGROUND Following the release of the 2002 report of the Women 's Health Initiative ( WHI ) trial of estrogen plus progestin , the use of menopausal hormone therapy in the United States decreased substantially . Subsequently , the incidence of breast cancer also dropped , suggesting a cause- and -effect relation between hormone treatment and breast cancer . However , the cause of this decrease remains controversial . METHODS We analyzed the results of the WHI r and omized clinical trial -- in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo-- and examined temporal trends in breast-cancer diagnoses in the WHI observational- study cohort . Risk factors for breast cancer , frequency of mammography , and time-specific incidence of breast cancer were assessed in relation to combined hormone use . RESULTS In the clinical trial , there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study , but the number of diagnoses increased over the course of the 5.6-year intervention period . The elevated risk decreased rapidly after both groups stopped taking the study pills , despite a similar frequency of mammography . In the observational study , the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group , but this difference in incidence decreased rapidly in about 2 years , coinciding with year-to-year reductions in combined hormone use . During this period , differences in the frequency of mammography between the two groups were unchanged . CONCLUSIONS The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography Periodic screening for cancer of the breast using mammography as well as clinical examination is being conducted by the Health Insurance Plan in a large r and om sample of women aged 40 to 64 years . A similar group of women has been assigned as controls . The long term objective is to determine whether the screening program results in lowering of mortality from mammary cancer . From the first screening examination among 20,211 women , the following observations can be made : 1 . Screening has result ed in substantial detection of cancer ; mammary cancer is detectable through screening an average of 21 months sooner than usual . 2 . A higher proportion of cancers has been detected in the screened group ( 65 % ) in an early stage ( as shown by the absence of axillary node involvement ) than in the control group ( 41 % ) . 3 . Both mammography and clinical examination contribute to the early detection of cancer in mass screening . 4 . Mammography and clinical examination are complimentary in detection . 5 . Under different conditions of age , breast type and lesion characteristics , the two procedures have different rates of accuracy . 6 . Mammography does comparatively well when the woman is older than 50 , when the breasts are mostly fatty in type and when the lesion is in the lower half of the breast ; clinical examinations do comparatively well when the woman is younger than 50 , when the breasts are small and when the breasts are of the gl and ular type A controlled r and omized trial of breast cancer screening has been initiated in Canada . This paper presents an analysis of the possible benefit from screening relative to the possible radiation risk from mammography for those women who will be screened in the trial . It shows that with modern low-dose mammography , even when a conservative estimate of possible reduction in mortality due to early detection is applied to the data , the estimated benefit substantially exceeds any possible hazard Abstract Objectives : To examine the implication s of false positive results of mammography in terms of the time lag from screening and complete mammography to the point when women with false positive results are declared free of cancer ; the extra examinations , biopsies , and check ups required ; and the cost of these extra procedures . Design : Review of women with false positive results from the Stockholm mammography screening trial . Setting : Department of Oncology , South Hospital , Stockholm . Subjects : 352 and 150 women with false positive results of mammography from the first and second screening rounds of the Stockholm trial . Main outcome measures : Extra examinations and investigations required and the cost of these procedures . Results : The 352 women from the first screening round made 1112 visits to the physician and had 397 fine needle aspiration biopsies , 187 mammograms , and 90 surgical biopsies before being declared free of cancer . After six months 64 % of the women ( 219/342 ) were declared cancer free . The 150 women in the second round made 427 visits to the physician and had 145 fine needle aspiration biopsies , 70 mammograms , and 28 surgical biopsies , and after six months 73 % ( 107/147 ) were declared cancer free . The follow up costs of the false positive screening results were Kr2.54 m ( pounds sterling250000 ) in the first round and Kr0.85 m ( pounds sterling84000 ) in the second round . Women under 50 accounted for about 41 % of these costs . Conclusions : The examinations and investigations carried out after false positive mammography — especially in women under 50— and the cost of these procedures are a neglected but substantial problem . Key messages Key messages These extra costs come from the examinations and investigations required during follow up — for example , repeated biopsy of benign tissue — before the patient is declared cancer free In this series the costs of following up women with false positive mammograms were almost one third of the cost of screening all women in the r and omised Stockholm mammography trial These extra costs and other negative aspects of false positive results of mammography — especially in women under 50—are a neglected but substantial problem The benefits of mammography must be carefully weighed against the potential negative aspects , especially in women under Background : False-positive recall is a recognized disadvantage of mammographic breast screening , and the rate of such recalls may be higher in younger women , potentially limiting the value of screening below age 50 . Methods : Attendance and screening outcome data for 53,884 women in the intervention arm of the U.K. Age trial were analyzed to report observed false-positive recall rates during 13 years of trial fieldwork . The Age trial was a r and omized controlled trial of the effect of mammographic screening from age 40 on breast cancer mortality , conducted in 23 National Health Service screening centers between 1991 and 2004 . Women r and omized to the intervention arm were offered annual invitation to mammography from age 40 or 41 to age 48 . Results : Overall , 7,893 women ( 14.6 % of women the intervention arm and 18.1 % of women attending at least one routine screen ) experienced one or more false-positive screen during the trial . The rates of false-positive mammography at first and subsequent routine screens were 4.9 % and 3.2 % , respectively . The cumulative false-positive rate over seven screens was 20.5 % . Eighty-nine percent of women who had a false-positive recall at their previous screen attended their next invitation to routine screening . Conclusions : The rates of false-positive recall in the Age trial were comparable with the national screening program ; however , the positive predictive value of referral was lower . Experiencing a false-positive screen did not seem to lessen the likelihood of re-attendance in the trial . Impact : The question of greatly increased false-positive rates in this age group and of their compromising re-attendance is refuted by the findings of this study . Cancer Epidemiol Biomarkers Prev ; 19(11 ) ; 2758–64 . © 2010 AACR Debate continues over the effectiveness of screening by mammography in women below age 50 . We report here on results of screening in the first 10 years of a r and omised trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41 compared to first invitation to the 3-yearly UK national programme at age 50–52 . The trial is taking place in 23 NHS breast screening centres . Between 1991 and 1997 , 160 921 women were r and omised in the ratio 1 : 2 to intervention and control arms . Screening is by two views at first screen and single view subsequently ; data on screening up to and including round five are now complete . Uptake of invitation to screening is between 68 and 70 % at all but the latest screening rounds . Rates of referral for assessment are 4.6 % at first screen and 3.4 % at subsequent screens . Invasive cancer detection rates are 0.09 % at first screen , and similar at rescreens until the sixth and later screens . There is little evidence of regular mammography in the trial control arm . The setting of this trial within the NHS breast screening programme should ensure applicability of results to a national programme Objective –To apply an indirect method for estimation of the breast cancer related excess mortality in the Swedish r and omised mammography screening trials . Setting –R and omised trials on mammography screening have , in Sweden , been performed in the counties of Kopparberg ( W ) and Östergötl and ( E ) , the so called WE study , and in the three largest cities in Sweden , Stockholm ( southern part ) , Gothenburg , and Malmö . An overview of the trials was presented in the Lancet in 1993 and included 156 911 women in the invited group and 125 866 in the control group . Methods –The excess mortality in the breast cancer subgroups was estimated by indirect st and ardisation using official national cause of death statistics according to Statistics Sweden as a reference . Results —The estimated reduction of the breast cancer related mortality was 24 % for the whole group ( 40–74 years at r and omisation ) . The corresponding figures for the age groups 40–49 , 50–59 , and 60–69 years were 6 % , 28 % , and 34 % respectively . Conclusion –The results are very similar to those presented earlier based on the traditional comparison of the breast cancer mortality in the invited and in the control group . This analysis further strengthens previous reports on a beneficial effect of mammography screening , which is especially pronounced in the age group 50–69 OBJECTIVE To establish the extent of women 's knowledge of mammographic screening , particularly in relation to the national screening program , BreastScreen Australia , and to estimate the proportion of women who are participating in screening both within and outside BreastScreen Australia . DESIGN AND SETTING Vali date d prospect i ve telephone survey of women aged 30 - 69 years selected at r and om from across Australia . PARTICIPANTS 2935 women with no previous breast cancer diagnosis . RESULTS The adjusted response rate was 64 % . Almost 90 % of women had heard of the national program ; only 1 % correctly stated that screening is for asymptomatic women . 60 % correctly identified the current recommended age of starting screening is about 50 years of age ; 26 % thought screening should begin at about 40 years of age . Approximately 60 % correctly reported that the recommended screening interval is every two years ; 27 % thought screening should be done annually . 55 % reported ever having had a mammogram , and 37 % reported having had at least one screening mammogram . Among women in the target age group ( 50 - 69 years ) about 70 % reported ever having had a screening mammogram , and about 50 % reported having had a screening mammogram within the national program in the last two years . Among women aged 40 - 49 years , 29 % reported ever having had a screening mammogram , and 22 % reported having been screened in the last two years . CONCLUSIONS Awareness of the national screening program is high , but some women do not know the purpose of screening , the target age group and the recommended screening interval . Compliance with screening is good among women in the target age group ; many women in their 40s are also participating in screening Sensitivity and specificity of first screen mammography in a r and omized screening trial at five centers are reported . A total of 23,101 women underwent mammography ; in 139 , breast cancer was detected at first screening ; in 20 , less than 12 months after first screening ; and in 47 , at second screening . All 206 cancer cases were histologically confirmed , and 174 were defined as being detectable at first screening . Average length of follow-up for all women was 3.2 years . Interpretations of first screen mammograms by the center radiologists were matched to known outcomes . Simultaneous blind review was performed by a single reference radiologist with mammograms from all 206 cancer cases and those of a r and om sample of 739 women not known to have breast cancer at 15 months or more after initial screening . Overall , the five screening centers achieved a sensitivity of 69 % ( range , 60%-78 % ) , a specificity of 94 % ( range , 93%-96 % ) , a positive predictive value of 8.6 % ( range , 3%-16 % ) , and a negative predictive value of 99.7 % ( range , 99.6%-99.9 % ) The results of the Swedish two-county trial of mammographic screening for breast cancer are presented , up date d to December 31 , 1990 , which is an average of 10.8 years follow-up per person . The main result of the trial in terms of breast cancer mortality remained the same : compared with the control group , the group invited to screening had a relative breast cancer mortality of 0.70 ( P = 0.0002 ) with 95 % confidence interval ( 0.58 , 0.85 ) . Analysis of survival showed that relative to the control group , the cancers detected at prevalence screen , incidence screens , and in the interval between screens had a good prognosis , whereas cancers detected in those who had refused screening had a very poor prognosis . When adjusted for tumor size , lymph node status , and tumor grade ( differentiation ) , the better survival associated with incidence screen and interval detection was largely accounted for , indicating that the benefit of incidence screening is largely achieved through the effect of screening on the three prognostic variables , notably size of the tumor . Results indicate that to achieve a substantial mortality reduction , 50 % of screen-detected invasive cancers should be less than 15 mm in diameter , at least 30 % of screen-detected grade 3 tumors should be less than 15 mm , and at least 70 % of screen-detected tumors should not have lymph node metastases . The percentage of grade 3 tumors of a given size should be the same in screen-detected cancers as in clinical ly detected , and breast cancer prevalence at first screen should be at least three times the expected incidence rate in the absence of screening . This should be achieved without the recall rate for further examination exceeding 9 % , and procedures including further imaging techniques and fine needle aspiration or core biopsy should be used before resorting to surgical biopsy . These aims can be achieved in specialist screening centers if particular attention is paid to re sources for screening and diagnostic evaluation , specialist training of clinical and technologic screening staff , and ongoing monitoring of mammographic quality , recall rates , and the attributes of the tumors detected BACKGROUND : It has recently been suggested that all-cause mortality is a more appropriate end point than disease specific mortality in cancer screening trials , and that disease specific mortality is biased in favour of screening . This suggestion is based partly on supposed inconsistencies between all-cause mortality results and disease specific results in cancer screening trials , and alleged increases in deaths from causes other than breast cancer among breast cancer cases diagnosed among women invited to screening . METHODS : We used data from the Swedish Two-County Trial of mammographic screening for breast cancer , in which 77 080 women were r and omised to an invitation to screening and 55 985 to no invitation . We estimated relative risks ( RRs ) ( invited v control ) of death from breast cancer , death from other causes within the breast cancer cases , and death from all causes within the breast cancer cases . RRs were adjusted for age and took account of the longer follow up of breast cancer cases in the invited group due to lead time . RESULTS : There was a significant 31 % reduction in breast cancer mortality in the invited group ( RR 0.69 , 95 % confidence interval ( CI ) 0.58–0.80 ; p<0.001 ) . There was no significant increase in deaths from other causes among breast cancer cases in the invited group ( RR 1.12 , 95 % CI 0.96–1.31 ; p=0.14 ) . A significant 19 % reduction in deaths from all causes was observed among breast cancer cases in the group invited to screening ( RR 0.81 , 95 % CI 0.72–0.90 ; p<0.001 ) . A more conservative estimation gave a significant 13 % reduction ( RR 0.87 , 95 % CI 0.78–0.97 ; p=0.01 ) . These findings are consistent with the magnitude of the reduction in breast cancer mortality . CONCLUSIONS : Invitation to screening was associated with a reduction in deaths from all causes among breast cancer cases , consistent with high participation rates in screening . There is no significant evidence of bias in cause of death classification in the Two-County Trial , and as breast cancer mortality is the targeted clinical outcome in breast cancer screening , it is the appropriate end point in a breast cancer screening trial . All-cause mortality is a poor and inefficient surrogate for breast cancer mortality OBJECTIVES To evaluate the efficacy of the combination of annual screening with mammography , physical examination of the breasts and the teaching of breast self-examination in reducing the rate of death from breast cancer among women aged 40 to 49 years on entry . DESIGN Individually r and omized controlled trial . SETTING Fifteen urban centres in Canada with expertise in the diagnosis and treatment of breast cancer . PARTICIPANTS Women with no history of breast cancer and no mammography in the previous 12 months were r and omly assigned to undergo either annual mammography and physical examination ( MP group ) or usual care after an initial physical examination ( UC group ) . The 50,430 women enrolled from January 1980 through March 1985 were followed for a mean of 8.5 years . DATA COLLECTION Derived from the participants by initial and annual self-administered question naires , from the screening examinations , from the patients ' physicians , from the provincial cancer registries and by record linkage to the Canadian National Mortality Data Base . Expert panels evaluated histologic and death data . MAIN OUTCOME MEASURES Rates of referral from screening , rates of detection of breast cancer from screening and from community care , nodal status , tumour size , and rates of death from all causes and from breast cancer . RESULTS Over 90 % of the women in each group attended the screening sessions or returned the annual question naires , or both , over years 2 to 5 . The characteristics of the women in the two groups were similar . Compared with the Canadian population , the participants were more likely to be married , have fewer children , have more education , be in a professional occupation , smoke less and have been born in North America . The rate of screen-detected breast cancer on first examination was 3.89 per 1000 in the MP group and 2.46 per 1000 in the UC group ; more node-positive tumours were found in the MP group than in the UC group . During years 2 through 5 the ratios of observed to expected cases of invasive breast cancer were 1.26 in the MP group and 1.02 in the UC group . Of the women with invasive breast cancer through to 7 years , 191 and 157 women in the MP and UC groups respectively had no node involvement , 55 and 43 had one to three nodes involved , 47 and 23 had four or more nodes involved , and 38 and 49 had an unknown nodal status . There were 38 deaths from breast cancer in the MP group and 28 in the UC group . The ratio of the proportions of death from breast cancer in the MP group compared with those in the UC group was 1.36 ( 95 % confidence interval 0.84 to 2.21 ) . The survival rates were similar in the two groups . The highest survival rate occurred among women whose cancer had been detected by mammography alone . CONCLUSION The study was internally valid , and there was no evidence of r and omization bias . Screening with yearly mammography and physical examination of the breasts detected considerably more node-negative , small tumours than usual care , but it had no impact on the rate of death from breast cancer up to 7 years ' follow-up from entry BACKGROUND The cumulative risk of a false-positive mammogram can be substantial . We studied which variables affect the chance of a false-positive mammogram and estimated cumulative risks over nine sequential mammograms . METHODS We used medical records of 2227 r and omly selected women who were 40 - 69 years of age on July 1 , 1983 , and had at least one screening mammogram . We used a Bayesian discrete hazard regression model developed for this study to test the effect of patient and radiologic variables on a first false-positive screening and to calculate cumulative risks of a false-positive mammogram . RESULTS Of 9747 screening mammograms , 6 . 5 % were false-positive ; 23.8 % of women experienced at least one false-positive result . After nine mammograms , the risk of a false-positive mammogram was 43.1 % ( 95 % confidence interval [ CI ] = 36.6%-53.6 % ) . Risk ratios decreased with increasing age and increased with number of breast biopsies , family history of breast cancer , estrogen use , time between screenings , no comparison with previous mammograms , and the radiologist 's tendency to call mammograms abnormal . For a woman with highest-risk variables , the estimated risk for a false-positive mammogram at the first and by the ninth mammogram was 98.1 % ( 95 % CI = 69.3%-100 % ) and 100 % ( 95 % CI = 99.9%-100 % ) , respectively . A woman with lowest-risk variables had estimated risks of 0.7 % ( 95 % CI = 0.2%-1.9 % ) and 4.6 % ( 95 % CI = 1 . 1%-12.5 % ) , respectively . CONCLUSIONS The cumulative risk of a false-positive mammogram over time varies substantially , depending on a woman 's own risk profile and on several factors related to radiologic screening . By the ninth mammogram , the risk can be as low as 5 % for women with low-risk variables and as high as 100 % for women with multiple high-risk factors First results in a long-term investigation to determine whether periodic breast cancer screening with mammography and clinical examination leads to lowered breast cancer mortality provide grounds for cautious optimism . The study compares the experience in a r and om sample of 31,000 women , aged 40 to 64 years , offered screening examinations with the experience in a similarly constituted " control " group . There were 52 deaths due to breast cancer in the control group , as compared with 31 breast cancer deaths in the study group , in the period available for follow-up . The 3 1/2-year case fatality rates among women with histologically confirmed breast cancers reinforce the impression that screening leads to lowered mortality . More time , possibly ten years of follow-up , is needed to establish whether the effect of the screening program is short-term or long-term The Swedish two county trial of breast cancer screening is now in its tenth year . This paper presents detailed results on mortality from breast cancer and from all other causes , and on the population denominators at risk for each of the first 8 years of follow up , for each county separately . These data represent a two year up date on the last major report . Results show an increasingly significant deficit in deaths from breast cancer among the 77,092 women invited to screening relative to the 56,000 not invited ( RR = 0.68 , p = 0.002 ) , with no significant difference between the effects of screening in the two counties ( p = 0.5 ) . These results remain the same when adjusted for age . Analysis of all cause deaths shows no significant effect of screening ( p = 0.5 ) , nor was there any significant effect of screening on deaths from all causes other than breast cancer ( p = 0.9 ) . The rates of deaths from intercurrent illness in breast cancer cases were almost identical in the group invited to screening and the group not invited ( p = 0.7 ) . This result remained the same when adjusted for age . We calculate that in the age group 50 - 69 at entry , one breast cancer death was prevented per 4000 woman/years , per 1460 mammographic examinations , per 13.5 biopsies , and per 7.4 breast cancers detected One hundred and thirty two women with normal breast screening results were interviewed six months after their attendance at the Edinburgh Breast Screening Clinic . Eight percent of women said screening had made them more anxious about developing breast cancer . Thirty eight percent said they were more aware of the disease since screening but they regarded this as advantageous . Seventy percent of the women were still practising breast self-examination . There was no difference in the psychiatric morbidity of the screened sample when compared with a matched r and om sample community control group . Neither was there any difference in the General Health Question naire case rates before and after screening . Screening does not appear to increase the prevalence of psychiatric morbidity . Twenty nine percent of the interview sample were examining their breasts more than once a month--21 % once a week or more . However , these frequent self-examiners did not have a greater prevalence of psychiatric morbidity than their matched controls BACKGROUND Screening programmes are often actively promoted to achieve high coverage , which may result in unrealistic expectations . We examined women 's underst and ing of the likely benefits of mammography screening . METHODS Telephone survey of r and om sample s of the female population aged > or = 15 years in the US , UK , Italy , and Switzerl and using three closed questions on the expected benefits of mammography screening . RESULTS A total of 5964 women were contacted and 4140 women ( 69 % ) participated . Misconceptions were widespread : a majority of women believed that screening prevents or reduces the risk of contracting breast cancer ( 68 % ) , that screening at least halves breast cancer mortality ( 62 % ) , and that 10 years of regular screening will prevent 10 or more breast cancer deaths per 1000 women ( 75 % ) . In multivariate analysis higher number of correct answers was positively associated with higher educational status ( odds ratio [ OR ] = 1.44 , 95 % CI : 1.25 , 1.66 ) and negatively with having had a mammography in the last 2 years ( OR = 0.86 , 95 % CI : 0.73 , 1.01 ) . Compared with US women ( reference group ) and Swiss women ( OR = 0.98 , 95 % CI : 0.82 , 1.18 ) respondents in Italy ( OR = 0.61 , 95 % CI : 0.50 , 0.74 ) and the UK ( OR = 0.73 , 95 % CI : 0.60 , 0.88 ) gave fewer correct answers . CONCLUSION In the US and three European countries a high proportion of women overestimated the benefits that can be expected from screening mammography . This finding raises doubts on informed consent procedures within breast cancer screening programmes The purpose of this overview is to estimate more precisely the long-term effect of mammography screening by adding four more years of follow-up to women aged 40 - 49 years in the four Swedish trials on mammography screening . Data from the four , trials were merged and linked to the Swedish Cancer and Cause of Death Register for 1958 - 1993 and 1951 - 1993 respectively to identify date of breast cancer diagnosis and cause and date of death . The invited and control groups comprised 48,569 and 40,247 women respectively . At the December 1993 follow-up , 602 and 482 breast cancer cases were identified in the two groups respectively , of which 104 and 111 had breast cancer as the underlying cause of death . This corresponds to a relative risk ( RR ) of 0.77 ( 95 % CI : 0.59 - 1.01 ) for the two groups . In the 40 - 44 age group at r and omization , 94 % of breast cancer patients in the study and 89 % in the control group were diagnosed before the age of 50 ; however , among breast cancer deaths in this age group , only two in the invited and five in the control group died after age 50 . At follow-up of women 40 - 44 years at r and omization 208 women in the invited and 184 in the control group were reported to the Cancer registry with breast cancer . Out of these 195 ( 94 % ) and 163 ( 89 % ) respectively were reported before the age of 50 . Further , the relative risk for the age group 40 - 44 years at r and omization by age at follow-up was 1.11 , 0.51 and 0.46 for the age groups 45 - 49 , 50 - 54 , and 55 - 59 at follow-up . This study shows a 23 % reduction in the breast cancer mortality in women 40 - 49 years at r and omization achieved from a median trial time of 7.0 years , a median follow-up time of 12.8 years , and a screening interval of 18 - 24 months . Almost all of the effect in the 40 - 44 year age group at r and omization was due to screening before the age of 50 Summary Cytometric determination of S-phase fraction and ploidy type was performed on 430 tumors detected within a r and omized trial of mammographic screening . The results were compared to several histopathologic features . A high S-phase fraction was estimated in tumors with a high grade of malignancy and other histopathologic findings related to rapid tumor progression , including lack of tubule formation , a high mitotic index , marked nuclear pleomorphism , multifocal cancer growth , tumor emboli in lymphatic and blood vessels , tumor necrosis , and inflammatory reaction . DNA aneuploidy was correlated with a high malignancy grade , frequent mitoses , a high degree of nuclear pleomorphism , vascular invasion , necrosis , and the presence of noninvasive ductal carcinoma . Both cytometric variables were inversely related to the degree of elastosis . Positive nodes , large tumor size , DNA aneuploidy , a high S-phase fraction , high grade of malignancy , lack of tubule formation , as well as high mitotic index and pleomorphism , presence of multifocal cancer , and vascular invasion , predicted a significantly shorter distant recurrence-free interval after a median follow-up time of 46.6 months . Elastosis and the presence of estrogen and progesterone receptors indicated favorable prognosis . In the multivariate analysis , only lymph node status , tumor size S-phase fraction , and multifocal growth pattern had independent prognostic value Abstract Objective : To compare one view ( oblique ) and two view ( oblique and craniocaudal ) mammography in breast cancer screening . Design : R and omised controlled trial . Setting : Nine breast screening centres in Engl and . Subjects : 40163 women aged 50 - 64 attending their first breast screening examination . Interventions : Women were r and omised to have one view mammography , two view mammography , or two view mammography in which one view was read by one reader and both views were read by another . Main outcome measures : Prevalence of cancer detected , recall rates , cost per cancer detected , and marginal cost per extra cancer detected . Results : Two view mammography detected 24 % more women with breast cancer ( 95 % confidence interval 16 % to 31 % ) than one view mammography . Prevalence of detected cancer was 6.84 with two view mammography and 5.52 per 1000 women with one view . The proportion of women recalled for assessment was 15 % lower ( 95 % confidence interval 6 % to 23 % ) with two view ( 6.97 % ) than with one view ( 8.16 % ) mammography . The cost of two view screening was higher ( pounds sterling26.46 compared with pounds sterling22.00 per examination ) but the average cost per cancer detected was similar ( pounds sterling5330 compared with pounds sterling5310 ) and the marginal cost per extra cancer detected with two views was similar to the average cost ( pounds sterling5400 ) . Conclusion : Two view mammography is medically more effective than one view ; it detects more cancers and reduces recall rates ; it is also similarly cost effective financially BACKGROUND The UK Trial of Early Detection of Breast Cancer ( TEDBC ) is a non-r and omised study , which was set up in 1979 to investigate the effect of screening and education about breast self-examination on breast-cancer mortality . We report mortality results after 16 years of follow-up , including results by age at trial entry . METHODS Eight centres ( two screening , two breast self-examination , and four comparison ) in Engl and and Scotl and recruited women aged 45 - 64 years into the initial cohort , with women reaching age 45 years during the 7-year study period included in later cohorts . The observed number of deaths from breast cancer in each centre was compared with the expected number , which was calculated by Poisson regression model ; expected numbers were adjusted for pretrial breast-cancer mortality . Results were analysed by 5-year age-groups , and for women aged 45 - 46 years and 47 - 49 years at entry . FINDINGS Breast-cancer mortality was 27 % lower ( rate ratio 0.73 [ 95 % CI 0.63 - 0.84 ] ) , adjusted for pretrial rates , in cohort 1 in the two screening centres combined than in the comparison centres . No reduction in mortality in the two breast self-examination centres combined was seen ( rate ratio 0.99 [ 0.87 - 1.12 ] ) . The mortality reduction in the screening centres did not differ significantly across age-groups ; a 35 % reduction was seen in women in all cohorts aged 45 - 46 years at entry ( rate ratio 0.65 [ 0.50 - 0.86 ] ) . Results were similar when deaths were restricted to those in patients diagnosed within 10 years of trial entry . INTERPRETATION The results from TEDBC support those from r and omised trials in Edinburgh and elsewhere , and show that a reduction in breast-cancer mortality result ing from screening can be achieved in the UK . There was no evidence of less benefit in women aged 45 - 46 years at the start of screening ; the effect of screening in this age-group begins to emerge after 3 - 4 years Abstract . The aim of this study was to find out by radiological analysis whether it is possible to prevent interval cancers in screening programmes without a concomitant increase in false positives . Re-scrutiny of all mammograms of 544 interval cancers was implemented . Blinded re-scrutiny of screening mammograms of 390 interval cancers mixed with other cases ( prevalence of detectable cases 37 % ) by two outside radiologists was also carried out . True interval cancers constituted 49 % , missed tumours 25 % , occult tumours 10 % and unclassifiable cases 16 % . There were no significant differences in survival between true interval cancers , overlooked or misinterpreted cancers , and mammographically occult cancers . In the blinded re-scrutiny both examiners reached a positive predictive value for malignancy of 67 % , and a sensitivity of 69 % and 81 % , respectively . In a screening programme such as this , it was estimated that 100–400 additional women would have to be recalled from screening for further workup in order to detect each additional cancer which would otherwise emerge as an interval cancer . The occurrence of interval cancer increased with age and was influenced by the design of screening . The proportion of patients with potential iatrogenic delay in diagnosis ( overlooked and misinterpreted cancers ) was equivalent to figures from other studies . There were no significant differences in survival between the various categories of interval cancer . The study confirmed the association of criteria for referral for further investigation with the number of false positives . Efforts to reduce the number of interval cancers by lowering the threshold for recall are likely to be counterproductive BACKGROUND As mammographic screening becomes more widespread , larger numbers of tumours are diagnosed while small and node negative . METHODS We examined detection mode , tumour size , node status , histological type , therapy and outcome in 1053 breast cancers diagnosed in one county of the Swedish Two-County Trial of mammographic screening for breast cancer . RESULTS Of patients undergoing total mastectomy with axillary dissection , 65 % were found to be node negative . For tumours of size 1 - 9 mm , 95 % were node negative . The major effects on survival were tumour size , node status and histological type . Primary adjuvant therapy had no significant association with survival . CONCLUSIONS The advent of mammography has substantially enhanced the possibilities for less radical treatment . There is an urgent need for therapeutic trials utilizing mammographic-pathological correlations to ascertain in advance which tumours can and which can not benefit from more radical therapy OBJECTIVE Interval carcinoma is the term used to describe malignant breast tumors that are detected in the intervals between mammographic screenings . These tumors are important because they contribute significantly to breast cancer mortality in the screened population . MATERIAL S AND METHODS Two radiologists retrospectively review ed the mammograms of the 96 interval carcinomas ( 17 % of all malignant neoplasms in the screened group ) that were detected during the 10-year Malmö Mammographic Screening Trial in Malmö , Sweden ( average time between screenings , 21 months ) , including one sarcoma , 75 invasive carcinomas , and 20 noninvasive carcinomas . We recorded the interval between screening and detection , and noted the tumor 's appearance on the prior screening mammogram and at the time of diagnosis ; these data were correlated with histologic tumor type and the patients ' mortality . The doubling time for tumor volume of the invasive carcinomas was estimated . RESULTS Excluding the sarcoma , 72 carcinomas ( 75 % ) were detected within 18 months of screening . Retrospective review of the available preceding screening mammograms ( 94 cases ) indicated that 10 tumors were missed ( observer 's error ) , 63 studies showed no tumor ( true interval carcinomas ) , and 21 studies showed subtle signs of malignancy , mostly nonspecific densities or asymmetries ( unrecognized sign ) . Of 66 invasive carcinomas in which doubling times for tumor volume could be calculated , 27 ( 41 % ) had doubling times of less than 100 days . At the end of the study , 20 of the 96 patients had died of breast cancer . CONCLUSION Interval carcinomas in this series were dominated by comedo , medullary , and mucinous carcinomas that often had a nonspecific appearance ( when present ) on prior screening mammograms . The interval carcinomas also contained a subset of rapidly growing tumors with a grave prognosis For r and omised population trials the unit of r and omisation is normally the individual person . In some situations , however , investigators take other groups as basic unit and one such design is cluster r and omisation . Considerable attention has been given to this design recently in statistical and epidemiological literature . The Edinburgh r and omised trial of breast cancer screening is an example which takes general practice s as clusters of patients . The experience of this trial is reported here . Mortality from all causes , cardiovascular disease and lung cancer over the first 5 year period of follow up are examined . We found that spurious mortality differences were present in the analyses , which do not allow for socio-economic status . From examination of methods of adjusting for this , we conclude that allowance can be made at the analysis stage , and it is intended that this approach will be adopted when breast cancer mortality is analysed in the Edinburgh trial . Nevertheless , we recommend that for future studies with outcome related to socio-economic status , r and omisations which use this design be stratified by socio-economic criteria where this is feasible In March 1981 a r and omized single-view mammographic screening for breast cancer was started in the south of Stockholm . The screened population in the first round numbered 40,318 women , and 20,000 women served as a well-defined control group . The age groups represented were 40–64 years , and 80.7 % of the invited women participated in the study . The first round disclosed 128 breast cancers ( 113 invasive and 15 noninvasive ) , or 4.0 per 1,000 women . Mean tumour size was 14.1 mm and axillary lymph node metastases were found in 21.8 % . Fifty-five per cent of the tumours were small ( ⩽10 mm ) or non-invasive , and 71 % were stage I.Participation rates are high in all Swedish trials . The present results differ only slightly from other screening programs ; the percentages of patients with axillary metastases and stage II tumours are similar in the Stockholm , Malmö and Kopparberg/Östergötl and studies . Comparisons of cancer prevalence in the various Swedish screening trials show that , in comparable age groups , there are some differences , even when the differences in the natural cancer incidence are taken into account . A decreased mortality was found recently in a Swedish trial in ages above 50 years but not below . In the Stockholm study more than one-third of the participants were aged 40–49 years Survival differences between clinical ly and screen-detected cancer patients partly result from biases . Well known are lead-time , length bias and overdiagnosis . The survival of the clinical ly detected patients in the study group of the HIP breast cancer screening project is corrected for these biases . The result ing survival curve is only slightly worse than the survival of the screen-detected patients . This suggests a very modest mortality reduction by screening . A much larger reduction is obtained from an analysis of the complete HIP results , including those of the control group . It is concluded that a large unexpected selection bias is present . This bias would not have been detected if the HIP study had not contained a r and omized control group . A misleading and pessimistic conclusion on the effectiveness of breast cancer screening would thus have result ed . This conclusion reinforces the need for r and omized studies OBJECTIVE To measure the effect of breast self-examination ( BSE ) technique and frequency on the risk of death from breast cancer . DESIGN Case-control study nested within the Canadian National Breast Screening Study ( NBSS ) . SETTING The Canadian NBSS , a multicentre r and omized controlled trial of screening for breast cancer in Canadian women . SUBJECTS The case subjects were 163 women who had died from breast cancer and 57 women with distant metastases . Ten control subjects matched by 5-year age group , screening centre , year of enrolment and r and om allocation group were r and omly selected for each case subject . EXPOSURE MEASURES Self-reported BSE frequency before enrolment in the NBSS , annual self-reports of BSE frequency during the program and annual objective assessment s of BSE technique . OUTCOME MEASURES Odds ratios ( ORs ) associated with BSE practice were estimated by conditional multiple logistic regression modelling , which permitted control of covariates . RESULTS Relative to women who , when assessed 2 years before diagnosis , examined their breasts visually , used their finger pads for palpation and examined with their 3 middle fingers , the OR for death from breast cancer or distant metastatic disease for women who omitted 1 , 2 or 3 of these components was 2.20 ( 95 % confidence interval [ CI ] 1.30 to 3.71 , p = 0.003 ) . The OR for women who omitted 1 of the 3 components was 1.82 ( 95 % CI 1.00 to 3.29 , p = 0.05 ) , for those who omitted 2 of the 3 components , 2.84 ( 95 % CI 1.44 to 5.59 , p = 0.003 ) , and for those who omitted all 3 components , 2.95 ( 95 % CI 1.19 to 7.30 , p = 0.02 ) . The results remained unchanged after adjustment for potential confounders . CONCLUSION The results , obtained with the use of prospect ively collected data , suggest that the performance of specific BSE components may reduce the risk of death from breast cancer Abstract Two quite different approaches have been taken to the evaluation of screening programs in the Health Insurance Plan of New York ( HIP ) . In one , a highly specific end result is at issue . The central question in this project is whether periodic screening with mammography and clinical examination of the breast results in a reduction in mortality from breast cancer in the female population . The project is being conducted as a r and omized clinical trial with study and control groups selected from the enrolled population of HIP . Of 31,000 study group women contacted , 20,200 , or 65 % participated in at least one examination . The other study is concerned with whether the impact of a multiple array of services , automated multiphasic health testing , and follow-up paramedical and medical services , on health status and health care behavior is greater among the poor than the rest of the population . The results of the breast cancer study provide clear evidence that over the short run period of 5 years of follow-up , the study women have about one-third lower mortality from breast cancer than the controls . Reduction in breast cancer mortality was found at ages 50 and over but not at ages 40–49 years . In the multiphasic health testing study , preliminary analysis of the data confirms one of the initial assumptions of the study , i.e. that a significant gap exists between the poverty and nonpoverty groups in the occurrence of health problems . A higher proportion of the poverty group reported a health complaint or specific condition . The study indicated that this group was also likely to report these problems with greater frequency and greater severity of the complaints To assess how women regard having had a false positive mammogram screening exam , and the influence that this had on their quality of life , 126 such women were interviewed . Their responses were compared to those of 152 women r and omly selected among screenees with a negative exam . Eighteen months after the screening the reported prevalence of anxiety about breast cancer was 29 % among women with a false positive and 13 % among women with a negative screening mammogram ( P = 0.001 ) . Of 30 women biopsied , 8 ( 27 % ) had pain in the breast and 10 ( 33 % ) had reduced sexual sensitivity . A false positive mammogram was described by 7 ( 5 % ) of the women as the worst thing they ever had experienced . However , most women with a false positive result regarded this experience , in retrospect , as but one of many minor stressful experiences creating a temporary decrease in quality of life . They report the same quality of life today as women with negative screening results and 98 % would attend another screening . Even so , false positive results are a matter of concern , and efforts should be made to minimise this cost whenever a screening programme is conducted The Edinburgh R and omised Trial of Breast Cancer Screening recruited 44,288 women aged 45 - 64 years into the initial cohort of the trial during 1978 - 81 , and 10 years of follow-up is now complete . A total of 22,944 women were r and omised into the study group and were offered screening for 7 years ; the remaining women formed the control group . After 10 years , breast cancer mortality is 14 - 21 % lower in the study group than in the controls depending on the precise definition of the end point . These differences are not statistically significant ; for breast cancer as the underlying cause of death the relative risk is 0.82 ( 95 % confidence interval 0.61 - 1.11 ) . Rates of locally advanced and metastatic cancer were substantially lower in the study group , but screening has failed to achieve marked reductions in rates of small node-positive cancers . Those women who accepted the final invitation to screening have been monitored over the 3 year period prior to their first screen under the UK service screening programme . Interval cases , expressed as a proportion of the control incidence , increased from 12 % in the first year to 67 % in the third year . The reduction in breast cancer mortality for older women ( aged at least 50 years ) is the same as that for the total study group for this duration of follow-up . For analyses of breast cancer mortality in younger women up date s recruited to the trial from 1982 to 1985 ( 10,383 women with 6 - 8 years ' follow-up ) have been included . The reduction in breast cancer mortality for women aged 45 - 49 years at entry was 22 % ( relative risk = 0.78 , 95 % confidence interval = 0.46 - 1.31 ) It is important that the introduction of breast screening is closely monitored . The anticipated effect on breast cancer mortality will take 10 years or more fully to emerge , and will only occur if a succession of more short-term end points are met . Data from the Swedish two-county r and omised trial provide targets that should be achieved , following a logical progression of compliance with the initial invitation , prevalence and stage distribution at the prevalence screen , the rate of interval cancers after the initial screen , the pick-up rate and stage distribution at later screening tests , the rate of interval cancers after later tests , the absolute rate of advanced cancer and finally the breast cancer mortality rate . For evaluation purpose s , historical data on stage at diagnosis is desirable ; it is suggested that tumour size is probably the most relevant variable available in most cases Context Seven- and 10-year results of the Canadian National Breast Screening Study ( CNBSS ) showed no reduction in breast cancer mortality from five annual mammographies and breast examinations for 40- to 49-year-old women . Some authors have argued that longer follow-up would reveal important benefits . Contribution After 11 to 16 years , the cumulative rate ratios for mammography versus usual care were 0.97 ( 95 % CI , 0.74 to 1.27 ) for breast cancer mortality without adjustment for non study mammography and 1.06 ( CI , 0.80 to 1.40 ) with adjustment . Clinical Implication s The CNBSS suggests that screening 40- to 49-year-old women is unlikely to reduce breast cancer by 20 % or more . Controversy will persist because other studies suggest that screening causes small reductions in breast cancer mortality . The Editors The Canadian National Breast Screening Study -1 ( CNBSS-1 ) , an individually r and omized trial in women 40 to 49 years of age at study entry , evaluated the efficacy of annual mammography , breast physical examination , and instruction on breast self-examination in reducing breast cancer mortality ( 1 ) . The 7-year ( 2 ) and preliminary 10-year ( 3 ) mortality results were previously reported . At 7 years , 38 women in the mammography group and 28 women in the usual care group had died of breast cancer , for a rate ratio of 1.36 ( 95 % CI , 0.84 to 2.21 ) ( 2 ) . At 10 years , there were 82 breast cancer deaths in the mammography group and 72 in the usual care group ( rate ratio , 1.14 [ CI , 0.83 to 1.56 ] ) ( 3 ) . This article reports CNBSS-1 results after an average 13-year follow-up from study entry . Methods Patient Selection and Recruitment Participants were recruited through media publicity , personal invitation letters using population lists ( municipal registers and provincial health insurance registers ) , group mailings , and physicians ( 4 ) . Eligibility criteria were age 40 to 49 years , no previous diagnosis of breast cancer , not being pregnant , no mammography in the previous 12 months , and signed informed consent . The Human Experimentation Committee of the University of Toronto ( Toronto , Ontario , Canada ) and Human Experimentation Committees at 15 CNBSS collaborating centers approved the study . A total of 50 430 women age 40 to 49 years were enrolled from January 1980 through March 1985 . R and omization Before r and omization , all participants received an initial breast physical examination and instruction on breast self-examination . They were then immediately r and omly assigned to receive mammography and , thereafter , either annual screening with mammography and breast physical examination ( 25 214 women in the mammography group were available for analysis ) or usual care in the context of the Canadian health care system ( 25 216 women in the usual care group were available for analysis ) . Center coordinators r and omly assigned participants using prepared allocation lists , independent of breast physical examination findings . This sequence ensured that the conduct and interpretation of the breast physical examination would be unbiased by knowledge of whether mammography would follow . Intervention Screening Schedule In the mammography group , 62 % of women received five annual screenings . The remainder , recruited later , received four . Each screening examination comprised mammography , breast physical examination , and instruction and evaluation on breast self-examination . Women in the mammography group completed question naires at each rescreening visit . Women in the usual care group were not recalled for rescreening but were mailed annual question naires . We expected that these participants would continue their normal pattern of medical care as delivered through Canada 's universal health care coverage , including access to mammography for diagnosis . Study Procedures Two-view mammography was done on dedicated mammography units ( 5 ) , and second readers review ed mammograms deemed abnormal . Systematic audit procedures were used ( 6 ) . Nurses provided breast physical examination in 12 centers and physicians in 3 centers in Qubec ( 7 ) . These providers taught and evaluated breast self-examination while conducting their own examination ( 8) . If findings on breast physical examination or mammography were abnormal , participants were referred to a CNBSS review clinic . The study surgeon discussed mammography findings with the study radiologist , examined the participant , and decided whether further diagnostic procedures should be recommended to the woman 's physician . The woman 's physician determined whether and how to implement the study surgeon 's recommendations . Data Collection Protocol During the screening period , the center coordinators collected surgery and pathology reports for breast-related diagnostic and therapeutic procedures . The CNBSS pathologists review ed all slides . If the community and CNBSS pathologist disagreed , a panel of three to five CNBSS pathologists blindedly and independently review ed the slides . Extensive quality control procedures were used during data collection . After the screening centers closed in 1988 , the central CNBSS central office annually followed all women known to have breast cancer until 30 June 1996 , the cut-off for this analysis . Passive follow-up of all participants through linkage with the National Cancer Registry identified new diagnoses of breast cancer in study participants through 31 December 1993 . The central office collected pathology reports for postscreening cases of breast cancer . The community diagnosis was accepted for study purpose s. Family members responding to the annual mailed question naire identified deaths that occurred before completion of a participant 's screening schedule . Thereafter , women not known to have cancer were followed only through registry linkage ; their mammography experience was not traced . However , for women known to have breast cancer , attending physicians received annual requests for up date d clinical information , including death . Attending physicians , who received annual requests for information on women with breast cancer , reported deaths until 30 June 1996 . Linkage with the Canadian Mortality Data base at Statistics Canada ( including deaths in Canadians who resided in the United States at the time of death ) identified causes of death in the entire cohort until 31 December 1993 . The procedures used to verify deaths from breast cancer were described previously ( 2 ) . Investigative procedures were initiated for women dying with breast cancer ; those whose death certificates mentioned breast cancer ; and those whose cause of death was described as unknown , unknown primary , lung cancer , colon cancer , or liver cancer . The review ers were blinded to study group allocation . All other causes of death were accepted as certified . For the most recent record linkage , more stringent confidentiality requirements exercised by many hospitals hindered verification . Thus , of the breast cancer deaths reported in this paper , a panel review ed 67 % in the mammography group and 77 % in the usual care group . The remaining deaths are as reported on death certificates . Study Outcomes Death due to or probably due to breast cancer was the major study outcome . A previous report of the CNBBS-1 noted axillary node status , as assessed by community pathologists , through 7 years of follow-up ( 2 ) . Subsequently ( 1993 to 1997 ) , to achieve consistent reporting of tumor size , all available material for screening-detected cancer and cancer detected between screenings was re-collected from originating institutions and review ed by one of the CNBSS pathologists or a colleague . Slides were obtained for review for nearly 80 % of requested cases . For the current analysis , pathologists measured the size of small tumors as observed on the slide or the size of the invasive component for mixed invasive and in situ tumors . Statistical Analysis Sample Size The CNBSS-1 was planned to evaluate whether breast cancer mortality would decrease by 40 % in the mammography group compared with the usual care group after 5 years of follow-up , with a required sample size of 50 000 women ( = 0.05 ; power , 80 % ) ( 1 ) . At 5 years , however , too few women had died of breast cancer for the study to achieve the planned power . Thus , for the first report on breast cancer mortality , we extended follow-up to 7 years ( 2 ) . CNBSS Data base The data base includes records for 50 430 women , including demographic and risk factor variables and results of screening examinations , diagnostic and therapeutic procedures , pathology results , and causes of death . CNBSS Terminology The terms screen 1 , screen 2 , through screen 5 denote events associated with screening examinations in the mammography group . The initial breast physical examination received by the usual care group is called screen 1 . Screening-detected cancers are those diagnosed after a recommendation made by the study surgeon at the CNBSS review clinic . Interval cancers are cases of cancer that occurred less than 12 months after a screening examination at which no recommendation for diagnostic procedures was made . Incident cancers are cases of cancer that occurred more than 12 months after the previous CNBSS screening examination . Statistical Tests The statistical significance of differences in proportions was determined by using the chi-square test ( two-sided = 0.05 ) . For all observed-to-expected ratios , 95 % CIs were computed . Death rates were computed by using person-years based on stratification by quinquennium of age ; we assumed that all women not known to be dead are alive . Age was defined as age at entry . Because all eligible participants were included in the analysis and follow-up , this is an intention-to-treat analysis . Cox proportional-hazards regression was done to examine variables with the most significant independent influence on survival ( 9 ) , using the PHREG program in SAS software , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . Because the variable allocation to screening was our primary interest , it was A study cohort of 8214 women was formed from all participants in the Canadian National Breast Screening Study who attended their first three screens after the introduction of a structured evaluation protocol involving eight criteria for breast self‐examination ( BSE ) . Self‐reported BSE frequency was collected by question naire at all three screens . Breast self‐examination instruction preceded breast exam at each screen but BSE evaluation occurred only at the second and third screen . Reported monthly BSE frequency increased from 18 % to 51 % to 55 % on first , second , and third screens , respectively . The proportion cl aim ing to do no BSE fell correspondingly : 52 % , 16 % , and 11 % . Compliance with each of the seven other BSE criteria was significantly greater at the third screen than at the second . The mean number of these criteria performed at screen 3 was 5.1 compared with 4.4 at screen 2 ; older women performed as well as younger . The mean number of criteria performed was associated with BSE frequency at screen 3 . The authors conclude that women 's BSE behavior can be altered , and that integration of BSE evaluation and instruction into routine medical exams seems feasible and potentially useful A t least since 1985 , there has been concern in some quarters that the Canadian National Breast Screening Study ( NBSS ) results 1'2 would fail to show a benefit from combined mammographic and clinical screening for breast cancer in women age 40 - 49 years . In the United States , in the spring of 1992 , the controversy about the benefits of screening women age 40 - 49 for the early detection of breast cancer erupted in the media . 3 - 7 The center of attention was the unpublished results of the NBSS . However , the center of controversy is the conflicting guidelines on breast screening for women age 40 - 49 . The very familiar guidelines of the American Cancer Society and the American College of Radiology ( ACR ) exhort women in this age group to " do themselves a favor " and get a mammogram . Although a number of prestigious professional associations have chosen to endorse these guidelines , others have not , including the US Preventive Services Task Force , the American College of Physicians , the Canadian Workshop Group , 8 the National Cancer Institute of Canada , an expert panel in the United Kingdom , 9 and the European Group for Breast Screening . 1 ° To underst and the nature of the controversy , it is helpful to review both the NBSS and published evidence from other screening studies . The Canadian NBSS was design ed to answer two major questions J , 2 First , in women age 40 - 49 , does annual mammography combined with annual physical examination of the breast for 3 or 4 years reduce the mortality rate from breast cancer as compared with a single physical examination alone ? Second , in women age 50 - 59 , how much does mammography contribute to mortality reduction over and above that achieved by physical examination alone when the comparison is annual mammography combined with physical examination versus annual physical examination alone ? The NBSS screened 89,835 women at 15 centers across Canada from 1980 - 1988 , with each woman individually r and omized to the mammography arm or the nonmammography arm of the study . Approximately 50,000 participants were 40 - 49 on entry and the remainder were 50 - 59 years of age . To be eligible , women were required to sign informed consent forms , to never have had a diagnosis of breast cancer , © 1992 by The Jacobs Institute of Women ' s Health 1049 - A population -based , r and omized , controlled breast cancer screening trial with single-view mammography as the only means of primary detection has been under way in Kopparberg county , Sweden , since October 1977 . The 7-year results of the study show ( 1 ) a significant change in the stage distribution of breast cancers in the cohort invited to undergo screening ( ASP ) as compared to the control group . ( 2 ) This change is seen as an initial decrease in the proportion of advanced ( stage II and more advanced ) cancers in the ASP as compared to the control population , followed in the second and third round of screening by a significant decrease in the absolute number of these advanced cancers in the ASP relative to the control group . ( 3 ) A thorough follow-up of both population s will answer whether these preliminary findings will result in decreased breast cancer mortality in the population invited to screening BACKGROUND Although increasing rates of breast carcinoma incidence have been observed in Asian countries , appropriate strategies for detecting early stage breast carcinoma in such communities have been difficult to formulate , particularly because no large population screening trial specifically involving Asian women has been reported . The objective of this study was to evaluate the effectiveness and quality of mammography as a screening technique for Singaporean women , who are predominantly Chinese . METHODS In this prospect i ve study , 166,600 women in Singapore ages 50 - 64 years were r and omized to either 2-view mammography without physical examination ( 67,656 ) or observation ( 97,294 , controls ) over 2 years . RESULTS Of these women , 28,231 ( 41.7 % ) responded and were screened ; they were more likely to be married , have more formal education , be working , be Chinese , and be in a higher socioeconomic group ( P < 0.001 for all variables ) . To assess for response bias that could affect outcome , results were also evaluated for nonrespondents ( n = 39,425 ) . The incidence rate of cancers among nonrespondents ( 1 per 1000 woman-years ) was less than the 1.3 in women not invited to have screening ( P = 0.03 , relative risk [ RR ] , 1.3 ; 95 % confidence interval [ CI ] , 1.0 - 1.7 ) . However , cancers arising from nonrespondents did not differ significantly in stage distribution when compared with cancers within the control group . For every 1000 women screened , 4.8 cancers were detected . The prevalence ratio ( the number of cancers detected per 1000 women at first screening divided by the corresponding incidence rate in controls per year ) was 3.6 for screened women and 2.4 for women invited to have screening . The majority of cancers detected through screening were early stage , with 64 % as either ductal carcinoma in situ ( 26 % ) or Stage I disease ( 38 % ) and was significantly more than the corresponding 26 % in women not invited to have screening ( P < 0.001 ) . When only invasive cancers were considered , screened women still had more early cancers , with 65 % having no lymph node involvement , compared with 47 % in the group not invited to have screening ( P = 0.001 ; RR , 1.4 ; 95 % CI , 1.2 - 1.7 ) . Women who were screened had half the risk of having Stage II or later cancers ( P < 0.0001 ; RR , 0.5 ; 95 % CI , 0.4 - 0.7 ) when compared with women not invited to have screening . This higher detection rate of early cancers through screening was accomplished with acceptable recall rates of 8 % for further mammographic films or physical examination and a biopsy rate of 1.0 % ( 10 per 1000 women screened ) . The interval cancer rate was 2.1 per 10,000 women screened in the first year of follow-up . CONCLUSIONS These positive results of intermediate measures suggest that , in Asian communities , screening mammography could be an important modality for detecting early stage breast carcinoma . However , the low compliance rates suggest that health education efforts must focus on issues related to acceptability if such programs are to succeed We carried out a r and omized trial of invitation to screening mammography in the city of Gothenburg , Sweden , to estimate the effect of screening on breast cancer mortality in women under age 50 years . A total of 11,724 women aged 39 - 49 were r and omized to the study group , which was invited to mammographic screening every 18 months ; 14,217 women in the same age range were r and omized to a control group , which was not invited to screening until the fifth screen of the study group . Breast cancers diagnosed in both groups between r and omization and immediately after the first screen of the control group were followed up for death from breast cancer to the end of December 1994 . There was a significant 44 % reduction in mortality from breast cancer in the study group compared to the control group ( relative risk [ RR ] = 0.56 , P = 0.042 , 95 % confidence interval [ CI ] : 0.32 - 0.98 ) . A conservative estimate based on removal of the cancers detected at the first screen of the control group gave an RR = 0.59 ( P = 0.069 , 95 % CI : 0.33 - 1.05 ) . The true answer is likely to lie between the two estimates . These data suggest that mammographic screening can reduce breast cancer mortality in women under age 50 , particularly if high- quality mammography is used and a short interscreening interval is adhered to A population -based , r and omized breast cancer screening project was undertaken using mammography alone . Of 17,447 invited women aged 50 - 69 , 12,765 ( 73 % ) attended the screening . On the basis of the screening films , malignancy was suspected in 405 women ( 3.2 % ) who were recalled for complete mammography . Additional films showed that the suspicion of malignancy was false in 194 women . The remaining 211 women ( 1.7 % ) were referred for clinical and cytological examination . Of these , 159 had surgery . Breast cancer was proved in 97 women , corresponding to a prevalence rate of 7.6/1000 . Fifty-three ( 55 % ) of the carcinomas were either in situ or invasive with a diameter of less than or equal to 1 cm . Axillary metastases were found in 19 patients ( 19.6 % ) . Cancers detected at screening were significantly less advanced than those in the control group . There was a remarkably high frequency of tubular carcinoma among cancers detected at screening OBJECTIVE : The present study was conducted to examine the relationship between obesity and all-cause mortality in women . STUDY DESIGN AND SETTING S : The subjects were women enrolled from 1980 to 1985 in a Canadian r and omized trial , the National Breast Screening Study ( NBSS ) to evaluate the efficacy of mammographic screening . Mortality was ascertained by record linkage to the Canadian Mortality Data Base . Hazard ratios ( HR ) for the association between body mass index ( BMI ) and all-cause mortality were obtained from Cox proportional hazard regression models . RESULTS : During an average follow-up period of 16.5 years , 2566 deaths were identified among the 49 165 women , age 40–59 y at enrolment . The risk of all-cause death increased linearly above a BMI of 22 kg/m2 and the trend was statistically significant . The HR ( and 95 % confidence intervals ) in the various categories of BMI ( kg/m2 ) were : BMI < 18.5 : 1.12 ( 0.99–1.25 ) ; BMI 18.5–21.9 : 1.00 ( reference ) ; BMI 22–24.9 : 1.15 ( 1.11–1.18 ) ; BMI 25.0–27.9 : 1.28 ( 1.24–1.32 ) ; BMI 28.0 –29.9 : 1.34 ( 1.29–1.39 ) ; BMI 30.0–34.9 : 1.30 ( 1.25,1.35 ) ; and BMI ≥35.0 : 1.40 ( 1.33–1.47 ) . CONCLUSION : This study confirms the association of high BMI with increased all-cause mortality in women Although there is evidence for a reduction in breast carcinoma mortality with mammographic screening , some doubts have been expressed , and there is still uncertainty regarding the age specific effects Background . A major issue in decisions regarding screening women for breast cancer concerns ages of coverage , in particular , whether routine mass screening programs with mammography should cover women aged 40–49 . Interpretation of results of studies on this question is affected by differences in design , adequacy of sample size , quality of mammography , period of follow‐up , and other method ologic and content issues 661 B REAST cancer is the leading cause of death due to cancer in most countries of the Western world , and therapy has to date had little impact on mortality from the disease . The development of mammography offered the prospect of detecting breast cancer at an earlier stage than had previously been possible ; hence , this suggested that the systematic use of mammography might lead to detection of a substantial proportion of breast cancers when they are still curable and to a reduction in mortality . Several clinical trials have been conducted to test this hypothesis , and , while their results vary somewhat , they do in general indicate a reduction in breast cancer mortality as a result of screening with mammography . The magnitude of this reduction in women aged 50 years and older is about 30 % ; we are aware of no r and omized controlled trial performed to date in younger women that showed a statistically signfficant reduction in mortality , except the Health Insurance Plan of New York . However , a recent meta analysis of trials conducted in Sweden shows a 13 % reduction in mortality for younger women ( not statistically significant ) ( 1 ) . A 30 % reduction in mortality for a disease as common as breast cancer is It is the responsibility of the scientist to balance passion with dispassion . John C. Polanyi The Responsibility of the Scientist Department of Physiology Lecture Series : Frontiers in Physiology and Pharmacology , University of Toronto , 22 M Because no previous study evaluating the benefit of screening for breast cancer had specifically addressed efficacy in women aged 40 to 49 years , the results of the Canadian National Breast Screening Study ( NBSS ) were impatiently awaited . When they were finally published in November 1992 [ 1 , 2 ] , the results showed no reduction in breast cancer mortality after 7 years in screened women aged 40 to 49 years . Further , mammography did not achieve an incremental mortality benefit over and above clinical examination in women 50 to 59 years old , although it did achieve higher rates of cancer detection . What one wants to believe is easy to believe . Results from the NBSS , however , were difficult for many to believe . Given the passionately held belief that early detection of breast cancer achieved by mammography screening benefits women aged 40 to 49 years , it was not surprising that the NBSS became the focus of much attention . Some of the criticisms that have been generated are addressed in this article in the hope that a better underst and ing of the issues involved will be reached . Methods Planned in the late 1970s , the NBSS began screening women in January 1980 . Its design [ 3 ] addressed the unanswered questions prevailing at the time . The New York Health Insurance Plan breast screening trial had shown that combined annual screening with mammography and physical examination reduced breast cancer mortality in women 50 years of age and over when compared with no screening [ 4 ] . Although the separate contributions of mammography and physical examination of the breasts to mortality reduction were not known , it was believed that clinical examination of the breasts made a major contribution . Also not known in 1980 was whether combined annual screening reduced breast cancer mortality in women aged 40 to 49 years when compared with no screening intervention . To determine the benefit of combined screening in women aged 40 to 49 years , the NBSS recruited 50 430 women individually r and omly assigned so that 25 214 received annual mammography and physical examination and 25 216 received a single physical examination , thereafter returning to usual community care with annual follow-up by mailed question naire . To determine the separate contribution of mammography to breast cancer mortality reduction , 39 405 women ages 50 to 59 years were recruited , of whom 19 711 were r and omly assigned to receive annual mammography and physical examination of the breasts and 19 694 to receive an annual physical examination alone . Entry criteria included meeting the age criteria , not being pregnant , not having been diagnosed with breast cancer , not having had a mammogram in the 12 months before entry , and signing informed consent forms . Women were instructed in breast self-examination at entry and those eligible for re-screening received repeated instruction and evaluation . All su bmi tted annual question naires that tracked breast procedures generated outside the NBSS . Screening Sites Each of the 15 centers across Canada had an adequate population base from which to draw participants and had recognized expertise in breast cancer . Six centers were in provincial cancer institutions ( all in the forefront of cancer research and treatment ) and eight in university teaching hospitals . Recruitment extended over 6 years , from 1980 to 1985 . R and omization Women who met the entry criteria and completed two question naires ( yielding identifying and demographic data including risk factors for breast cancer ) then signed informed consent forms in the examining room . The screen-examiner asked if the participant had breast symptoms ( lump , pain , discharge ) and recorded the responses . A physical examination of the breasts and instruction in breast self-examination followed , after which the examiner decided if the clinical findings required the participant 's referral to the NBSS surgical review clinic ( usually held within 1 week ) . This decision was documented on the examiner 's form , and the woman was informed . The examiner then left the participant and approached the center coordinator or her deputy , who carried out the r and omization procedure . R and omization lists , contained in four separate books that each included one quinquennium ( 40 to 44 years , 45 to 49 years , and so on ) , were provided to all centers . On learning the participant 's age , the coordinator chose the appropriate book and entered the date and name on the first available line , thus assigning to the participant her identification number and allocation . The coordinator entered the number and allocation on all chart forms , and the examiner told the participant if she was to have mammography . From the examiner 's perspective , it was not important to obtain a mammography allocation if a breast lump had been found because the participant would already be referred for surgical review . From the coordinator 's perspective , skipping a line to achieve a desired allocation was not feasible because she could not predict when the next appropriately aged woman would arrive to fill the skipped slot . The coordinators were well educated , well trained , and responsible , and recognized the importance of the r and omization procedure . At each month 's end , the original r and omization sheets were su bmi tted to the central coordinating office where each sheet was examined for suspicious entries , inappropriate date s , and lack of congruence with participant records . Mammography Mammography was done on site and interpreted by study radiologists . Details of the equipment used , the audit procedures , and sensitivity and specificity estimates have been previously published [ 5 - 7 ] . Clinical Examination of the Breasts Breast examination and breast self-examination instruction and evaluation were done by locally trained nurse-examiners in all centers outside the province of Quebec and by physicians in Quebec . The duration of the clinical examination ranged from 5 to 15 minutes , depending on the size of the breasts and on the amount of verbal interaction required . Descriptions of the role of the nurse-examiner , sensitivity and specificity estimates for breast examination , and breast self-examination behavior have all been previously published [ 8 - 10 ] . Surgical Review Study surgeons appointed at each center to examine women with abnormalities detected by either or both screening interventions decided if diagnostic follow-up was required . If so , they forwarded their recommendations to the woman 's physician , who then determined if and where the procedure would be done . Most recommended procedures were done [ 1 , 2 ] . In women aged 40 to 49 years , diagnostic mammography was done as a consequence of the screening examination in 0.8 % and 1.5 % of the mammography and comparison groups , respectively . Pathology Review Reference pathologists appointed for each center review ed slides from all surgical procedures done on participants from their center , whether or not the procedure result ed from NBSS recommendations . Follow-up Procedures During the 3 or 4 years each participant was in the study ( participants entering in 1984 and 1985 were eligible for only a 3-year and four-screen schedule ) , the centers ' routine follow-up procedures ensured high compliance with screening , and question naire information was obtained for most of the noncompliant participants [ 1 , 2 ] . These procedures also achieved almost complete ascertainment of cases of breast cancer and deaths , shown by subsequent record linkage . After participants ' screening schedules ended , active follow-up continued only for participants with known breast cancer . All such patients have always been and continue to be followed annually through contact with their physicians , whether their breast cancers were detected as a result of screening , during the screening schedule but not as a result of screening , or through record linkage during or after screening . Thus , the vital status of all women identified as having breast cancer is ascertained within , at most , 1 year of death . Passive follow-up to identify new cases of breast cancer through linkage with cancer registries across Canada ascertained breast cancer diagnoses occurring after completion of screening schedules and in the very small proportion of women ( 1 % of women from 40 to 49 years ) who dropped out of the study before completing their schedule . In a few cases , breast cancer was first identified through the National Mortality Data base as a cause of , or contributing to , death . In such cases , surgical , pathology , and other clinical records were review ed retrospectively . Figure 1 shows the follow-up procedures . Figure 1 . Flow chart of follow-up procedures . Results Seven years after entry , breast screening had no effect on breast cancer deaths when women aged 40 to 49 years receiving annual screening with mammography and physical examination ( 38 deaths ) were compared with women receiving only a single physical examination of the breasts at entry into the study followed by usual community care ( 28 deaths ) . The numeric difference is not statistically significant . Further , no effect on breast cancer mortality was observed in women aged 50 to 59 years at entry who received annual mammography and physical examination of the breasts ( 38 deaths ) compared with women who received only annual physical examination of the breasts ( 39 deaths ) . In both age groups , mammography was associated with higher cancer detection rates [ 1 , 2 ] . Controversy When the results were published , controversy arose [ 11 - 13 ] , some of which was defused at a recent International Workshop on Breast Cancer Screening where it was observed that NBSS results were consistent with findings from other screening studies [ 14 ] . Nevertheless , NBSS results were unwelcome in a milieu The issue of whether to screen women aged 40–49 for breast cancer is debated usually in terms of the potential mortality reduction achievable by the application of screening in this age group . Theories regarding why a significant reduction in mortality has not been observed in trials relate to the biologic behavior of tumors in this age group and the screening process itself . Survival curves with respect to node status , size , and grade of the tumor were compared among age groups in the Swedish two‐county trial . In the Kopparberg part of this trial , for the 40–49 age group , predicted survival was calculated from the size , node status , and grade of cancers detected during the trial in comparison with those found in two later series of tumors , one from the 1989–1992 Kopparberg screening program , the other from the British Columbia screening program that began in 1988 . The Kopparberg arm of the Swedish two‐county study used single‐view mammography with extended processing but without grid ; the two more recent programs used two‐view mammography with extended processing and the grid . Both the Kopparberg programs used a 2‐year interval . The effects of grade , node status , and size on survival in the 40–49 age group were very similar to their effects in older age groups . Predicted survival from the later Kopparberg series was essentially the same as that for the earlier . The mortality reduction in this age group in the Kopparberg part of the Swedish two‐county trial was 26 % . The survival results indicate no biologic reason why screening should not be able , theoretically , to reduce mortality . Nonsignificant reductions in mortality have been observed in the Kopparberg part of the two‐county trial and in the overview of Swedish trials . The similar predictive results for the two‐view and one‐view trials suggest that the most likely way to achieve further reductions in mortality is to reduce the interval between screens , possibly to 1 year BACKGROUND Information on breast cancer risk can be obtained both from the histological appearance of the breast epithelium in biopsy specimens and from the pattern of parenchymal densities in the breast revealed by mammography . It is not understood , however , how parenchymal densities influence breast cancer risk or whether these densities are associated with histological risk factors . PURPOSE We have estimated , in a large cohort of women , the relative risk of detecting carcinoma in situ , atypical hyperplasia , hyperplasia without atypia , or nonproliferative disease in biopsy specimens from women with different extents of mammographic density . We also examined the association between these histological classifications and radiological features present specifically at the biopsy site . METHODS The source of study material was a population of women aged 40 - 49 years who were enrolled in the Canadian National Breast Screening Study ( NBSS ) . Mammograms from women who had undergone a biopsy ( n = 441 ) and from a comparison group of women ( n = 501 ) r and omly selected from the mammography arm of the NBSS were classified according to the extent of mammographic density . The corresponding histological slides were independently classified by a review pathologist . RESULTS Compared with women showing no mammographic densities , women with the most extensive densities ( i.e. , occupying greater than 75 % of the breast volume ) had a 9.7 times greater risk of developing carcinoma in situ or atypical hyperplasia ( 95 % confidence interval [ CI ] = 1.75 - 53.97 ) , a 12.2 times greater risk of developing hyperplasia without atypia ( 95 % CI = 2.97 - 50.14 ) , and a 3.1 times greater risk of developing non-proliferative disease ( 95 % CI = 1.20 - 8.11 ) . The gradients in risk were not monotonic across the five classifications of mammographic density . The association could not be explained by the presence of mammographic densities at the biopsy site , but calcification at the biopsy site was strongly associated with high-risk histological changes ( relative risk = 24 ; 95 % CI = 5.0 - 156.0 ) . CONCLUSIONS These results suggest that the radiological patterns referred to as mammographic dysplasia may influence breast cancer risk by virtue of their association with high-risk histological changes in the breast epithelium . IMPLICATION S Identification of the factors responsible for high-risk histological changes may offer new insights into the etiology of breast cancer and potentially lead to the development of methods for its prevention We have examined variation in the interpretation of xeromammograms among radiologists design ated to take part in a Canadian multicenter r and omized controlled trial of screening for breast cancer . Radiologists read 100 xeromammograms comprising 10 histologically proved cancers , 40 benign abnormalities , and 50 normal films . Radiologists ' opinions differed widely on the frequency of suspected or identified cancer . The diagnostic category " suspicion of cancer " or " cancer " was selected by radiologists for 10 - 55 % of the films , and biopsy or aspiration was recommended for 21 to 53 % of patients whose films were examined . Agreement on specific diagnostic categories was greatest for the diagnosis of cancer ; agreement was least for the diagnosis of benign abnormalities and intermediate for the diagnosis of normality . Known cancers were in general correctly identified . These results indicate a need for development of methods to reduce observer variation in a interpretation of xeromammograms while preserving diagnostic sensitivity and validity . Results also emphasize the importance of developing strategies to ensure quality control in multicenter trials Objective — To assess the effect of screening for breast cancer in women aged 40–49 in the Swedish two county trial , in terms of mortality reduction , advanced cancer reduction , mode of detection , and the histology of tumours detected . Setting — The Swedish two county trial of screening for breast cancer , in which 77080 women aged 40–74 ( 19 844 aged 40–49 ) were r and omly allocated to receive regular invitation to mammographic screening for breast cancer , and 55985 women aged 40–74 ( 15 604 aged 40–49 ) were allocated to an unscreened control group . Methods — The screening interval in the younger age group was two years and in the older age group about three years . Statistical analysis of mortality and incidence rates was performed by Poisson regression . Relative survival was estimated using proportional hazards regression . Results — The relative mortality for the group invited to screening compared with the control group was 0·87 ( 95 % confidence interval 0·54 to 1·41 ) in the 40–49 age group , in close agreement with the relative incidence of advanced cancers . For Kopparberg county the relative mortality was 0·73 ( 95 % CI 0·37 to 1·41 ) and for Ostergotl and 1·02 ( 95 % CI 0·52 to 1·99 ) . The lesser effect in the 40–49 group as a whole was largely due to a higher rate of interval cancers in this age group , and the occurrence in Ostergotl and of a higher number of cancers after r and omisation , but before screening started , and in women who refused screening . The higher interval cancer rate was consistent with the higher proportion of ductal grade 3 and medullary cancers in women aged 40–49 at diagnosis . Conclusions — A major difficulty in screening women aged 40–49 is the rapid progression of a subset of tumours arising in this age group . Shortening the screening interval from two years would be necessary to achieve a higher mortality reduction Research ers have noted that mammographic screening has a reduced effect on breast cancer mortality in women in their forties compared to older women . Explanations for this include poorer sensitivity in younger women due to denser breast tissue , as well as more rapid tumor progression , giving a shorter mean sojourn time ( the average duration of the pre clinical screen-detectable period ) . To test these hypotheses , we developed a series of Markov-chain models to estimate tumor progression rates and sensitivity . Parameters were estimated using tumor data from the Swedish two-county trial of mammographic screening for breast cancer . The mean sojourn time was shorter in women aged 40 - 49 compared to women aged 50 - 59 and 60 - 69 ( 2.44 , 3.70 , and 4.17 years , respectively ) . Sensitivity was lower in the 40 - 49 age group compared to the two older groups ( 83 % , 100 % , and 100 % , respectively ) . Thus , both rapid progression and poorer sensitivity are associated with the 40 - 49 age group . We also modeled tumor size , node status , and malignancy grade together with subsequent breast cancer mortality and found that , to achieve a reduction in mortality commensurate with that in women over 50 , the interscreening interval for women in their forties should be less than two years . We conclude that Markov models and the use of tumor size , node status , and malignancy grade as surrogates for mortality can be useful in design and analysis of future studies of breast cancer screening In order to better underst and the effect of breast cancer screening on mortality , we use the theory of competing risks to analyse deaths from the long-term follow-up of the HIP breast cancer screening trial . We conclude that some , but not all , of the breast cancer cases detected early as a result of screening realized a benefit in terms of elimination of the risk of breast cancer mortality . Breast cancer screening appears not to affect the rate of mortality from causes of death other than breast cancer . Method ologically , we demonstrate the importance of analysing mortality separately for the breast cancer cases as well as for the entire population in a trial OBJECTIVE To evaluate women 's psychological responses to abnormal mammograms and the effect on mammography adherence . To identify psychological responses and other factors that predict mammography adherence in women with normal or abnormal mammograms . DESIGN Survey study with prospect i ve analysis of factors associated with mammography adherence . SETTING Health Maintenance Organization of Pennsylvania and New Jersey ( HMO PA/NJ ) . PATIENTS Study patients , members of HMO PA/NJ who were 50 years of age or older , and who had had mammography done 3 months earlier , included women with normal mammograms ( n = 121 ) , women with low-suspicion mammograms ( n = 119 ) , and women with high-suspicion mammograms ( n = 68 ) , but not women with breast cancer . MEASUREMENTS Psychological responses 3 months after mammography and adherence to subsequent annual mammography were assessed . MAIN RESULTS Women with high-suspicion mammograms had substantial mammography-related anxiety ( 47 % ) and worries about breast cancer ( 41 % ) . Such worries affected the moods ( 26 % ) and daily functioning ( 17 % ) of these women , despite diagnostic evaluation excluding malignancy . For each variable , a consistent trend ( P greater than 0.05 ) was seen with degree of mammogram abnormality . Sixty-eight percent of women with normal results , 78 % of women with low-suspicion results , and 74 % of women with high-suspicion results obtained their subsequent annual mammograms ( P greater than 0.05 ) . The number of previous mammograms ( odds ratio , 3.2 ; 95 % CI , 1.6 to 6.2 ) and the effect of the previous results on concerns about breast cancer ( odds ratio , 0.5 ; CI , 0.2 to 1.0 ) were independent predictors of adherence in logistic regression analyses ( P less than 0.05 ) . CONCLUSIONS A substantial proportion of women with suspicious mammograms have psychological difficulties , even after learning that they do not have cancer . Such sequelae do not appear to interfere with subsequent adherence Between 1979 and 1981 , 45,130 women in Edinburgh aged 45 - 64 were entered into a r and omised trial of breast cancer screening by mammography and clinical examination . The initial attendance rate was 61 % but this varied according to age and socioeconomic status and decreased over succeeding years . The cancer detection rate was 6.2 per 1000 women attending at the first visit ; the rate fell to around 3 per 1000 in the years when mammography was routinely repeated and to around 1 per 1000 at the intervening visits with clinical examination alone as the screening method . After 7 years of follow-up the mortality reduction achieved was 17 % ( relative risk = 0.83 , 95 % CI 0.58 - 1.18 ) , which was not statistically significant , even when corrected for socioeconomic status . In women aged 50 years and over a mortality reduction of 20 % was achieved Mammograms from the Canadian National Breast Screening Study ( NBSS ) were review ed by three external experts to provide an objective evaluation of their technical quality , to establish a model for auditing mammograms in a screening program , and to assess whether NBSS mammograms improved over time . The sample review ed included 10 r and omly chosen mammograms from each of 15 screening centers for each calendar year of their operation between 1980 and 1987 . All 830 mammograms were review ed on two consecutive days in r and omized sequence by each reader , and rated 0 - 3 for each of four criteria including positioning and image quality , with a total possible score of 0 - 12 . Although the mammograms were not in temporal sequence when review ed , the scores assigned by each reader were significantly higher for mammograms dating from later years . Subjects ' ages at entry ( 40 - 49 vs 50 - 59 years ) did not affect the score . The largest increase in scores was associated with a 1985 protocol change in which mediolateral oblique positioning replaced straight mediolateral positioning . This study reinforces the importance of monitoring technical quality in screening programs and establishes that the NBSS benefited from technical improvements during its operation . A retrospective review of NBSS mammography by three external review ers confirmed that technical quality improved from 1980 to 1987 . This improvement was associated with improved technology ( film , processing , and units ) and with the quality assurance programs operating during the NBSS , which identified problems and offered remedies Women aged 45 - 64 in 78 general practice s in the city of Edinburgh were followed up for five to seven years and all cause mortality noted . St and ardised mortality ratios were calculated for the individual practice s. Postcodes were available for a 20 % sample of these women and were used to retrieve relevant measures of social class and deprivation from the 1981 census for the smallest division , the enumeration district . Weighted averages gave socioeconomic variables at the level of the general practice . High positive correlations were found between st and ardised mortality ratios and the socioeconomic variables , with the highest being for percentage overcrowding . This study established that the relation between deprivation and excess mortality can be shown in general practice s in one large city and gave a direct relation for women without reference to their husb and s ' occupations , thus obviating problems of assigning social class . The data also partially refute the " social drift " hypothesis as an explanation of the association between mortality and social class BACKGROUND The cl aim that screening for breast cancer with mammography reduces breast cancer mortality is mainly based on the results from the Swedish two-county trial ( WE study ) , where the effect was reported to be 30 % for the age group 50 - 69 years . The two-county trial has recently been criticised for inadequate r and omisation and for not following the study protocol . METHODS We do some simple calculations to study whether the WE study is robust for an alternative statistical analysis . We use stage-specific breast cancer mortality in the Norwegian population as the baseline mortality rate in Sweden . Then we study the expected reduction in overall breast cancer mortality in the WE study while we vary the mortality rate in stage 1 and the stage distribution . RESULTS We show that a 30 % reduction in overall mortality rate is in conflict with observed decline in mortality in stage 1 and the expected stage migration . One either has to decrease mortality in stage 1 , or increase the reduction of tumours with distant metastases , or both , to much higher levels than those reported in Sweden to get a 30 % reduction in overall mortality of breast cancer . CONCLUSIONS Our study adds further evidence to the proposal that the WE study is biased and not valid With increasing evidence of the effectiveness of mass screening in reducing mortality from breast cancer , the Breast Cancer Screening Study of the Health Insurance Plan of Greater New York is review ed for its impact on increased efforts to gain participation among its target population . Initial contact efforts brought a 47 % response rate , and further efforts increased this to 65 % . The additional contact efforts increased response rates among most demographic groups . Women requiring minimum contact efforts were appreciably more likely than the increased effort group to participate in the full set of four screenings . Among those requiring increased efforts , more than 40 % had the full set of screening examinations , and about 80 % had at least one screening examination in addition to the baseline . Differences in breast cancer detection rates among contact effort groups were small , and there was little difference in mortality from breast cancer . Mortality rates from other causes , however , were higher among reluctant participants and highest among women who refused screening . Efforts to increase participation in screening for breast cancer should be linked to women 's concerns with other health problems and to their medical care system Results from several r and omised mammography screening trials haveshown that it is possible to reduce mortalityin breast cancer by mammographic screening at leastfor women above 50 years of age . The purpose of this article is to present data on mortality in breast cancer in study and control groups of the Stockholm trial after 11years of followup , to analyse which age group benefits most from screening . In March 1981 , 40,318women in Stockholm , aged 40 through 64 years , entered a r and omized trial of breast cancer screeningby single view mammography alone , versus no interventionin a control group of 20 000 women . Two screening rounds were performed and the attendancerate was over 80 % in the two rounds . During 1986 the control group was invited onceto screening . Totally 428 and 217 cases ofbreast cancer were diagnosed in the study and control groups respectively . After a mean follow-up of11.4 years a nonsignificant mortality reduction of 26%was observed for the whole study group , witha relative risk ( RR ) of death in breastcancer of 0.74 ( CI(confidence interval)=0.5–1.1 ) . Forwomen aged 50–64 years a significant 38 % mortalityreduction was observed with a RR of 0.62(CI=0.38–1.0 ) . For women aged 40–49 yearsno effect on mortality was found , with aRR of death in breast cancer of 1.08(CI=0.54–2.17 ) . The breakpoint for benefit inthis study seemed to be at 50 yearsof age when 5-year age groups were analysed , but this tendency is uncertain because of thelow statistical power in the analysis of theyounger age groups . Long screening intervals , the useof single-view mammography , and the fact that morethan 50 % of the women in age group40–49 years were still below 50 years ofage when the study was closed , were allfacts that could have influenced the results inage group 40–49 years . Larger studies are neededto answer the question whether mammographic screening canbe successful in younger age groups In an effort to reduce the cost of breast cancer screening several studies have explored the possibility of using risk factors to select a high-risk group of women and then restrict screening to that group . The results of these studies have been almost entirely negative and so it is not possible at present to classify any woman as at such low risk that she need not be screened . Nevertheless it is well known that some groups of women can be identified as being at higher risk than the general population . In this study it is assumed that each woman will be offered one screen at which risk factor information will be collected . The usual screening policy is then one of uniform intervention in which the interval to the next screen is the same for all women : the interval that is currently recommended in the UK is three years . An alternative is a risk strategy in which the time to the next screen depends on the woman 's risk status ; thus the total number of screens available to the population are distributed according to risk status . Using data from the Edinburgh r and omised trial of breast cancer screening these policies have been compared . It is estimated that the proportion of cases detected by screening in the three years following the completion of the initial screening round could be raised from 60 % to 67 % by adopting a risk strategy . Lead time benefits are also quantified as are the comparisons for an established screening programme BACKGROUND In mammographic screening for breast cancer in women aged 40 - 49 , previous studies have found very low estimates of sensitivity and predictive value . Methods of estimation have , however , used primitive models with relatively strong assumptions and less than full use of the data . METHODS Here we estimate the underlying pre clinical incidence , mean sojourn time , sensitivity and positive predictive value by a variety of methods in a r and omized trial of mammographic screening ( The Swedish Two-County Trial ) and a service screening programme ( The Florence Programme , 1975 - 1986 ) in women aged 40 - 49 years . RESULTS In the Two-County study , sensitivity estimates ranged from 72 - 83 % and predictive value from 39 - 89 % . In the Florence programme , sensitivity estimates ranged from 69 - 85 % and predictive value was uniformly estimated as 100 % . CONCLUSIONS The methods involving more explicit modelling of the disease process and fewer assumptions tended to find higher estimates of predictive value in the Two-County study . The results suggest that previously poor sensitivity and predictive value estimates may have been overpessimistic OBJECTIVE To evaluate survival of women with small breast cancers ( 10 mm or less in diameter ) in a series almost unaffected by adjuvant medical treatment . DESIGN Prospect i ve study from a population who were r and omly allocated to be screened by mammography . SETTING University Hospital . SUBJECTS 324 patients with breast cancers 10 mm or less in diameter who were operated on between 1978 - 85 ( 230 detected by screening , 21 interval cases and 73 from the control group ) . MAIN OUTCOME MEASURES Recurrence free survival , recurrence rate , and breast cancer mortality alone and in relation to node involvement during a median follow up of 7 years ( range 4 months-12.5 years ) . RESULTS Survival without distant metastases in life table analyses was 98.7 % in 254 node negative cases and 79.3 % in 30 node positive cases ( p < 0.001 ) . For the whole series survival without distant recurrence was 96.8 % . There was no significant difference in recurrence free survival between cancers detected by screening and those detected clinical ly . Lymph nodes were involved in 9 % of the 221 detected by screening compared with 20 % of the 89 detected clinical ly ( p < 0.03 ) . CONCLUSION There was a very low risk of recurrence in small node negative breast cancers ( irrespective of the method of detection ) indicating that adjuvant treatment may not be necessary for patients with small node negative breast tumours . The good prognosis of these patients also implies that the need for follow up programmes must be discussed because they are probably unnecessary BACKGROUND The objective of this study is to compare the effectiveness of mammographic screening in women with a family history of breast cancer to those without . In the invited arm of a r and omised trial of breast cancer screening , data on family history of breast cancer were available on 29.179 women aged 40 - 74 attending for screening . Among those women , 358 were diagnosed with breast cancer during the trial . METHODS Those with and without a family history were compared with respect to mammographic parenchymal pattern , interval cancer rates , mean sojourn time and sensitivity of screening . In the 358 cancers , the effect of family history was estimated on survival , incidence of advanced cancers and their relationship to screen detection . RESULTS A significantly higher proportion of high risk mammographic patterns was observed in association with family history among women aged 40 - 49 . Interval cancer rates were higher in women with a family history , and in older women at least , mean sojourn time was shortened in women with a family history ( 1.89 years compared to 2.70 ) . Survival was better ( although not significantly so ) in cancers in women with a family history ( relative hazard=0.52 ) independently of detection mode and was significantly poorer in interval cancers then screen detected cancers ( relative hazard=2.72 ) independently of family history . Similarly , interval cancers tended to be larger , and worse malignancy grade in those with and without a family history of breast cancer . CONCLUSIONS These results suggest that the policy often adopted of annual screening for woman aged 40 - 49 , with a family history of breast cancer , is a reasonable one , and that it may also be necessary to shorten the inter-screening interval to one year in women aged over 50 but with a positive family history BACKGROUND False-positive mammography results are common . Biennial screening may decrease the cumulative probability of false-positive results across many years of repeated screening but could also delay cancer diagnosis . OBJECTIVE To compare the cumulative probability of false-positive results and the stage distribution of incident breast cancer after 10 years of annual or biennial screening mammography . DESIGN Prospect i ve cohort study . SETTING 7 mammography registries in the National Cancer Institute-funded Breast Cancer Surveillance Consortium . PARTICIPANTS 169,456 women who underwent first screening mammography at age 40 to 59 years between 1994 and 2006 and 4492 women with incident invasive breast cancer diagnosed between 1996 and 2006 . MEASUREMENTS False-positive recalls and biopsy recommendations stage distribution of incident breast cancer . RESULTS False-positive recall probability was 16.3 % at first and 9.6 % at subsequent mammography . Probability of false-positive biopsy recommendation was 2.5 % at first and 1.0 % at subsequent examinations . Availability of comparison mammograms halved the odds of a false-positive recall ( adjusted odds ratio , 0.50 [ 95 % CI , 0.45 to 0.56 ] ) . When screening began at age 40 years , the cumulative probability of a woman receiving at least 1 false-positive recall after 10 years was 61.3 % ( CI , 59.4 % to 63.1 % ) with annual and 41.6 % ( CI , 40.6 % to 42.5 % ) with biennial screening . Cumulative probability of false-positive biopsy recommendation was 7.0 % ( CI , 6.1 % to 7.8 % ) with annual and 4.8 % ( CI , 4.4 % to 5.2 % ) with biennial screening . Estimates were similar when screening began at age 50 years . A non-statistically significant increase in the proportion of late-stage cancers was observed with biennial compared with annual screening ( absolute increases , 3.3 percentage points [ CI , -1.1 to 7.8 percentage points ] for women age 40 to 49 years and 2.3 percentage points [ CI , -1.0 to 5.7 percentage points ] for women age 50 to 59 years ) among women with incident breast cancer . LIMITATIONS Few women underwent screening over the entire 10-year period . Radiologist characteristics influence recall rates and were unavailable . Most mammograms were film rather than digital . Incident cancer was analyzed in a small sample of women who developed cancer . CONCLUSION After 10 years of annual screening , more than half of women will receive at least 1 false-positive recall , and 7 % to 9 % will receive a false-positive biopsy recommendation . Biennial screening appears to reduce the cumulative probability of false-positive results after 10 years but may be associated with a small absolute increase in the probability of late-stage cancer diagnosis . PRIMARY FUNDING SOURCE National Cancer Institute STUDY OBJECTIVE --To determine whether mortality from breast cancer could be reduced by repeated mammographic screening . DESIGN --Birth year cohorts of city population separately r and omised into study and control groups . SETTING --Screening clinic outside main hospital . PATIENTS --Women aged over 45 ; 21,088 invited for screening and 21,195 in control group . INTERVENTIONS --Women in the study group were invited to attend for mammographic screening at intervals of 18 - 24 months . Five rounds of screening were completed . Breast cancer was treated according to stage at diagnosis . END POINT -- Mortality from breast cancer . MEASUREMENTS AND MAIN RESULTS --All women were followed up and classed at end point as alive without breast cancer , alive with breast cancer , dead from breast cancer , or dead from other causes . Cause of death was taken from national mortality registry and for patients with breast cancer was vali date d independently . Mean follow up was 8.8 years . Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group ; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer ( no significant difference ; relative risk 0.96 ( 95 % confidence interval 0.68 to 1.35 ) ) . In the study group 29 % more women aged less than 55 died of breast cancer ( 28 v 22 ; relative risk 1.29 ( 0.74 to 2.25 ) ) . More women in the study group died from breast cancer in the first seven years ; after that the trend reversed , especially in women aged greater than or equal to 55 at entry . Overall , women in the study group aged greater than or equal to 55 had a 20 % reduction in mortality from breast cancer ( 35 v 44 ; relative risk 0.79 ( 0.51 to 1.24 ) ) . OTHER FINDINGS --In the study group 100 ( 17 % ) cancers appeared in intervals between screenings and 107 ( 18 % ) in non-attenders ; 51 of these women died from breast cancer . Cancers classed as stages II-IV comprised 33 % ( 190/579 ) of cancers in the study group and 52 % ( 231/443 ) in the control group . CONCLUSIONS --Invitation to mammographic screening may lead to reduced mortality from breast cancer , at least in women aged 55 or over Despite encouraging results from screening trials the efficacy of mammography in reducing mortality remains somewhat controversial . Five studies have been done in Sweden . This overview , based on 282,777 women followed for 5 - 13 years in r and omised trials in Malmö , Kopparberg , Ostergötl and , Stockholm , and Gothenburg , reveals a 24 % ( 95 % confidence interval 13 - 34 % ) significant reduction of breast cancer mortality among those invited to mammography screening compared with those not invited . To avoid the potential risk of differential misclassification causes of death were assessed by an independent end-point committee after a blinded review of all fatal breast cancer cases . The mortality reduction was similar , irrespective of the end-point used for evaluation ( " breast cancer as underlying cause of death " or " breast cancer present at death " ) . There was a consistent risk reduction associated with screening in all studies , although the point estimate of the relative risk for all ages varied non-significantly between 0.68 and 0.84 . The cumulative breast cancer mortality by time since r and omisation was estimated at 1.3 per 1000 within 6 years in the invited group compared with 1.6 in the control group . The corresponding figures after 9 years are 2.6 and 3.3 and after 12 years 3.9 and 5.1 . The largest reduction of breast cancer mortality ( 29 % ) was observed among women aged 50 - 69 at r and omisation . Among women 40 - 49 there was a non-significant 13 % reduction . In this younger age group cumulative breast cancer mortality was similar in the invited and control group during the first 8 years of follow-up . After 8 years there was a difference in favour of the invited women . There was no evidence of any detrimental effect of screening in terms of breast cancer mortality in any age group . Among women aged 70 - 74 years screening seems to have had only a marginal impact Objective — To determine the pathological and biological characteristics of breast cancers diagnosed by screening and examined at the Edinburgh University pathology department . Methods — These cancers were classified by screening status : never screened ( n=111 ) , prevalence screen detected ( n=105 ) , and previously screened ( n=74 ) . The last category arose in women who had been regularly screened during the trial ; the cancers were diagnosed as interval cases before the first invitation to service screening ( n=33 ) or were incidence screen detected at that time ( n=41 ) . Results — Association ( for operable invasive cancers , n=250 ) of cancer characteristics with screening status reflects influences of biology ( aggressiveness ) or chronology ( time of diagnosis ) , or both . The prognostic indicators tumour grade , histological type , and oestrogen receptor status were found in a smaller percentage of the patients with poor prognosis among the prevalence screen detected cases ( 9 % , 77 % , 18 % ) than among those previously screened ( 29 % , 84 % , 35 % ) . The chronological factors size and node status were found in a smaller percentage of patients with poor prognosis among women previously screened ( 31 % , 24 % ) than among those never screened ( 62 % , 39 % ) ) . Apart from these two , no other factors improved the diagnosis in the previously screened group compared with the never screened group . Conclusions — These results suggest that favourable characteristics of screen detected cases are often due to the effects of length bias on “ biological factors ” and fail to show that current local screening practice has succeeded in advancing the diagnosis of breast cancers to a less aggressive phase A r and omized controlled trial evaluating mammographic screening was started in two Swedish counties in 1977 . In one of these , Óstergótl and county , the authors performed static cytofluorometry on 161 cancers detected at the second and third screening rounds , 50 interval cancers , and 219 cancers appearing in the nonscreened control group during the same time period . The median follow‐up time was 42 months . No difference in mean S‐phase was found between screening and control group cancers , but interval cancers , appearing between two screenings , had increased mean S‐phase levels ( P = 0.01 ) compared to both of the other groups . A high S‐phase fraction was associated with distant recurrence in both node‐negative and node‐positive tumors . Aneuploid tumors were more often found in the control group ( 67 % ) and among interval cancers ( 72 % ) than among screening detected cancers ( 55 % , P = 0.02 ) . In Cox 's multivariate analysis , including all patients , the lymph node status , tumor size , estrogen receptor content , and S‐phase all contributed independent prognostic information about the clinical course . DNA ploidy predicted the outcome in simple but not in multivariate Cox 's analysis . When analyzing screening‐detected cancers separately , only the S‐phase significantly predicted distant recurrence in multivariate analysis . In tumors with local recurrence , a high S‐phase implicated an increased , although not statistically significant , risk for distant recurrence . Survival with metastatic disease was significantly influenced by the S‐phase level ( P = 0.002 ) . The authors conclude that S‐phase fraction provides valuable kinetic information related to the clinical outcome for all stages of the disease and serves as a prognostic factor in screened population s , which have tumors predominantly in early stages The Health Insurance Plan ( HIP ) of Greater New York conducted a clinical trial to determine if screening for breast cancer with mammography and clinical examination would decrease breast cancer mortality . The extent of disease at diagnosis among breast cancers detected by screening and the effect of screening on breast cancer mortality have been evaluated in the cohort of all HIP women diagnosed with breast cancer within 6 years of entry into the trial and followed at least 18 years after trial entry . Six years was the earliest time at which the number of cases diagnosed in the control group was equal to the number of cases diagnosed in the study group . In the cohorts of women 40 - 49 and 50 - 64 years of age at entry , shifts were significant to lower stages for screen-detected cases . As a result , the study group women in each age cohort had significantly lower breast cancer mortality than control group women when statistical analyses were restricted to data from cases only . In the 40 - 49 age-at-entry cohort , the reduced breast cancer mortality in the study group appears to result from lower mortality in stage I cases as well as from earlier case detection , and this may explain differences between the two age-at-entry cohorts in the length of follow-up time required to demonstrate a mortality reduction due to screening BACKGROUND The Edinburgh r and omised trial of breast-cancer screening recruited women aged 45 - 64 years from 1978 to 1981 ( cohort 1 ) , and those aged 45 - 49 years during 1982 - 85 ( cohorts 2 and 3 ) . Results based on 14 years of follow-up and 270,000 woman-years of observation are reported . METHODS Breast-cancer mortality rates in the intervention group ( 28,628 women offered screening ) were compared with those in the control group ( 26,026 ) with adjustment for socioeconomic status ( SES ) of general medical practice s. Rate ratios were derived by means of logistic regression for the total trial population and for women first offered screening while younger than 50 years . Analyses were by intention to treat . FINDINGS Initial unadjusted results showed a difference of just 13 % in breast-cancer mortality rates between the intervention and control groups ( 156 deaths [ 5.18 per 10,000 ] vs 167 [ 6.04 per 10,000 ] ; rate ratio 0.87 [ 95 % CI 0.70 - 1.06 ] ) , but the results were influenced by differences in SES by trial group . After adjustment for SES , the rate ratio was 0.79 ( 95 % CI 0.60 - 1.02 ) . When deaths after diagnosis more than 3 years after the end of the study were censored the rate ratio became 0.71 ( 0.53 - 0.95 ) . There was no evidence of heterogeneity by age at entry and no evidence that younger entrants had smaller or delayed benefit ( rate ratio 0.70 [ 0.41 - 1.20 ] ) . No breast-cancer mortality benefit was observed for women whose breast cancers were diagnosed when they were younger than 50 years . Other-cause mortality rates did not differ by trial group when adjusted for SES . INTERPRETATION Our findings confirm results from r and omised trials in Sweden and the USA that screening for breast cancer lowers breast-cancer mortality . Similar results are reported by the UK geographical comparison , UK Trial of Early Detection of Breast Cancer . The results for younger women suggest benefit from introduction of screening before 50 years of age Results from the r and omized trial underway in the Health Insurance Plan of Greater New York to determine the efficacy of periodic screening with mammography and palpation of the breast have been examined to determine the effect of screening on racial differences in breast cancer survival rates . Consistent with experience in general population s , the control group showed a lower five-year survival rate among non-White women with breast cancer than among White women . In the study group , 65 per cent of whom participated in the screening program , there was no differential in the survival rates of the two racial groups . The elimination of the unfavorable status among non-Whites through screening does not appear to be explained by various artifacts explored . Secondary prevention measures may offer the possibility of reducing or closing the gap in breast cancer survival rates between White and non-White women Summary The first objective of this study was to analyze the survival rate in a group of 69 breast cancers detected among nonattenders in a r and omized mammographic screening trial in relation to 142 clinical ly detected cancers in a nonscreened control population . By analyzing the cancers of the nonattenders we identified two subgroups , one ( A ) had actively avoided mammography , had cancers in more advanced stages on diagnosis , and had significantly higher mortality from breast cancer than the control group ( p = 0.003 ) . The second subgroup ( B ) had mammography done outside the screening program . This subgroup had a nonsignificant , slightly better survival ( p = 0.19 ) compared to the control group . Concerning stage the cancers in group B were similar to the cancers by the screening program . The second objective was to analyze women 's reasons for nonattendance in the screening program . We interviewed 200 r and omly selected nonattenders ; 33 % stated that they never could imagine having mammography ( definite nonattenders ) , 29.5 % that they for various reasons had missed the mammography but could imagine having it next time ( possible future attenders ) , and 32 % had been examined outside the program . Reasons for nonattendance included disinterest , medical problems , and fear of X-rays . From this interview investigation we believe that the subgroup of definite nonattenders ( 33 % ) is difficult to influence . The second subgroup classified as possible future attenders ( 29.5 % ) we believe can be influenced by more information and a new opportunity to receive mammography , i.e. , a reminder letter . The third subgroup , those examined outside the screening program ( 32 % ) were aware of the benefit of mammography , taking action on their own . Concerning these women 's health this seems acceptable ; screening outside the program seemed equivalent to that inside the program concerning stage and mortality in breast cancer as shown in the first part of the study Criticisms of the Canadian National Breast Screening Study ( NBSS ) assert that reported findings ( more deaths in women aged 40 - 49 allocated to mammography versus no mammography and no difference in mortality between women who had mammography and physical examination versus physical examination alone for those aged 50 - 59 ) may be due to more women with prior breast disease being allocated to the mammography arms of the study . The possibility that allocation was not r and om was examined for NBSS participants in Manitoba , Canada , using health insurance data that were external to and independent of the NBSS . The study design consisted of a retrospective observation study using health insurance ( cl aims ) data to construct health histories of breast disease prior to NBSS entry . Self-reported breast disease from the NBSS entry question naires was compared to breast disease histories on the basis of health insurance cl aims . The setting consisted of one NBSS screening center in Winnipeg , Canada . The patient population consisted of 9477 women with at least one health insurance cl aim in the 24 months prior to NBSS entry . We determined the proportions of women within each study arm who had cl aims for breast disease , breast disease investigation , or xeromammograms in the 24 months prior to NBSS entry , and compared the proportion of women 's self-reports of breast disease or xeromammography with the presence/absence of a cl aim prior to NBSS entry for breast disease or xeromammography . No significant differences in the proportion of women with prior histories of benign breast disease , investigation , or xeromammograms ( p > 0.05 ) were found across the study arms . Nine women in the mammography group versus one in the no mammography group had one prior health insurance cl aim for breast cancer , but eight of these women had no subsequent cl aims for breast cancer . There were no differences across the study arms in the proportion of women who reported a prior history of breast disease or a prior xeromammogram for whom an insurance cl aim was found . Using data external to the NBSS for Manitoba participants , the study found no definitive evidence to support a nonr and om allocation of women with prior breast disease to the mammography arms of the study . However , generalizability to the other NBSS centers can not be assured In a r and omized controlled trial with mammographic screening for early detection of breast cancer , 314 non-palpable breast lesions were examined by open biopsy between 1978 and 1983 . These biopsies were performed after the lesions had been indicated by the hooked wire technique . In 185 cases the findings turned out to be benign while 129 proved to be malignant . Satisfactory initial biopsies were achieved in 95 % of the cases . A model for the management of mammary lesions found in such a screening programme is described and some difficulties are discussed 68 CA A Cancer Journal for Clinicians Since the publication of the results of the Greater New York Trial and the Swedish Two-County Trial in the 1970s and 1980s , there has been a general consensus that screening for breast cancer with mammography reduces mortality from the disease . The results of these pioneering trials for the most part have been subsequently confirmed by later trials in Sweden , Canada , and the United Kingdom . Although some issues endure , most notably those regarding cost-effectiveness of screening in particular age groups , as well as concerns about harms associated with false positive results , the evidence that screening reduces deaths from breast cancer has steadily increased , and the consensus regarding the benefit of screening has grown stronger . The evidence that screening with mammography is associated with a lower breast cancer death rate recently was challenged when The Lancet published a research letter by Olsen and Gotzsche ( OG ) describing their overview of the mammographic screening trials . OG asserted that “ ... the reliable evidence does not indicate any survival benefit of mass screening for breast cancer , ” and they maintained that screening leads to more aggressive treatment ; thus , screening is not only without benefit , but in addition to representing a waste of health re sources , it actually results in net harms . This article has generated considerable print and electronic media attention , with a spectrum of opinions ranging from complete support for the conclusions of OG to complete dissent . Yet , despite the public exchange , the OG report has failed to convince institutional leaders in the United Kingdom , Sweden , the Netherl and s , or the United States to change screening policy . Most have publicly reaffirmed the current recommendations supporting regular mammography . Having thoroughly considered all available information , including the OG report , the US Preventive Services Task Force retained its current recommendation that women have regular mammograms every one to two years , and in fact , exp and ed the recommendation to include women in their forties . In addition , 10 leading medical organizations published a full-page open letter in the New York Times on January 31 , 2002 , supporting the value of early breast cancer detection . In our opinion , which is based on evidence accrued over decades of scientific research on breast cancer screening , and countless , independent expert peer review s of the study design s , data , and conclusions of the trials , the scientific foundation for the value of early breast cancer detection with mammography is sound . To see why , consider Figure 1 , which summarizes the most recently published results of the mammographic screening trials . The results indicate that there is a statistically significant 24 % reduction in breast cancer mortality associated with an invitation to screening . The distinction between “ invited to screening ” versus “ screened ” becomes clear when you consider that a r and omized trial of screening examines mortality rates in the study arm offered screening versus the study arm offered usual care . Mr. Duffy is Principal Scientist , Cancer Research UK , London , Engl and The efficacy of breast carcinoma screening should be enhanced if false‐negative mammography were reduced . Prospect ively collected data from the Canadian National Breast Screening Study were used to examine whether menstrual cycle phase was associated with false‐negative outcomes for mammographic screening BACKGROUND National mammography screening programmes are based on the results of r and omised trials , but the quality of these trials has recently been question ed . The Swedish Two-County trial reported a 31 % reduction in breast cancer mortality and was instrumental for the introduction of screening in many countries . In this trial , official Swedish health registries were used to identify breast cancers and breast cancer deaths in the study population . METHODS We used data from the same registries to estimate the numbers of breast cancer cases and breast cancer deaths among the included women . RESULTS Compared to official Swedish statistics we found that 192 breast cancer cases and 43 breast cancer deaths seem to be missing in the main publication of the Two-County trial ; we found similar discrepancies in two up date s of the trial . These large differences can hardly be explained by r and om fluctuations in the cancer occurrence . CONCLUSION The data reported for the Two-County trial are incomplete . Other data indicate that the mortality results in a recent report were flawed In women drawn from a r and omised , population -based trial of mammography screening for breast cancer the overall actuarial survival and disease-free survival for up to 7 years of observation were similar in 94 patients with interval cancers and 178 control patients with cancer diagnosed independent of screening . The similarity was confirmed by multiple regression analysis . These results contradict the hypothesis that a high growth rate of the primary tumour is associated with a greater metastatic potential and do not support the concept that patients with interval cancers should receive more aggressive local or systemic treatment A r and omised controlled trial to investigate the efficacy of mass screening with single-view mammography in reducing mortality from breast cancer was started in Sweden in 1977 . 162 981 women aged 40 years or more and living in the counties of Kopparberg and Ostergötl and were enrolled in the study and divided at r and om into 2 groups . Each woman in the study group was offered screening every 2 or 3 years depending on age . Women in the control group were not offered screening . This report is confined to the 134 867 women aged 40 - 74 years at date of entry . The results to the end of 1984 show a 31 % reduction in mortality from breast cancer and a 25 % reduction in the rate of stage II or more advanced breast cancers in the group invited to screening . 7 years after the start of the study the excess of stage I cancers in the study group largely outweighs the deficit of advanced cancers In the interval between screening examinations , some cases of breast cancer are invariably detected clinical ly in patients whose mammogram was considered to be normal at the earlier screening . During the first interval in the Stockholm study , 60 interval cancers were detected , giving a rate of 1.8 cases/1000 examinations/24 months . About half of these interval cases ( 31/60 ) were true interval tumours in that no sign of them could be found on the first mammogram ; the other half , non-true , were possible to trace on the first mammogram . It is mainly women under 50 who feature in the interval group , above all in the sub-group of true interval cancers (p<0.05).The incidence of interval cancer rises , as expected , with the length of the interval ( Fig. 1 ) . In the final six months of the 2-year interval the incidence of interval cancers had risen to 88 per cent of the cancers detected in the control group in the same period of time . The cumulative incidence of interval cancers supports the hypothesis that the distribution of sojourn time in the interval 0–2 years is approximately rectangular . This means that shortening the interval by one-half would halve the number of interval cases . If mammography becomes a wide spread screening method for early detection of breast cancer , the number of non-true interval cancers could be a feed back on the effectiveness of the screening . An analysis of the malignancy of the true interval cancers , based on tumour size , axillary status , tumour stage , and estrogen receptor content , shows that these are the more malignant tumours with an unfavourable prognosis , while the control group is intermediate in this respect and the tumours detected at screening have the most favourable prognosis This article provides additional follow-up data of two cohorts from the Malmö Mammographic Screening Trial ( MMST ) . The first cohort , MMST I , contained 7,984 women under age 50 at entry into MMST who were born between 1927 and 1932 . Half were assigned to a control group and were not invited for examination until four years after the code was broken in the MMST in 1988 . The second cohort , MMST II , contained 17,786 women born between 1933 and 1945 . Fifty four percent of these women were r and omly invited to screening between 1978 and 1990 . The remaining 46%--the control group -- was invited to screening between 1991 and 1994 . Nine screening rounds were completed in MMST I , and a mean of five rounds were completed in MMST II ; the screening interval ranged from 18 to 24 months . The effect of screening on breast cancer mortality was assessed by pooling the two cohorts . At the end of follow-up -- December 1993 for MMST I and December 1995 for MMST II -- there was a statistically significant 36 % reduction in breast cancer mortality in the intervention groups ( relative risk = 0.64 ; 95 % CI : 0.45 - 0.89 ; P = 0.009 ) . A harm-benefit analysis showed , however , that for every two breast cancer deaths prevented , one clinical ly insignificant cancer was diagnosed ; for each breast cancer death prevented , 63 cancer-free women had been called back for further examinations ; and for every 20 lives saved , one radiation-induced breast cancer death may have occurred . Recommendations for screening must therefore weigh mortality benefits against these negative effects This article presents additional follow-up analysis of women aged 45 - 49 from the Edinburgh R and omized Trial of Breast Cancer Screening . The screening protocol included four mammographic examinations at two-year intervals and seven annual clinical examinations . Altogether , 21,774 women aged 45 - 49 were recruited from 1978 to 1985 using cluster r and omization . After 10 - 14 years of follow-up , breast cancer mortality has been reduced by 12 % to 18 % ( rate ratios , with and without adjustment for socio-economic status , are 0.88 and 0.82 respectively , with 95 % confidence intervals [ CIs ] of 0.55 - 1.41 and 0.51 - 1.32 ) . These benefits are smaller than that reported previously with shorter follow-up . This article also presents data from an observational study that compared survival beyond baseline ( 50 - 52 years ) of women first offered screening before and after age 50 . Based on six-year data , the results suggest that earlier screening confers follow-up benefit ( hazard ratio for later screening = 1.60 ; 95 % CI : 0.96 - 2.67 ) , but these findings are not statistically significant . The trial is too small to yield statistically significant results by itself , but can make useful contributions to overview and meta-analyses Objective : To estimate the number needed to screen with mammography to save one life , based on a stated amount of screening activity and long-term follow-up for breast cancer death . Setting : A r and omised controlled trial of mammographic screening for breast cancer , with 77,080 women invited to screening and 55,985 not invited . The invited group was offered screening for seven years . Follow-up continued for a total of just over 20 years . Methods : Number needed to screen for seven years to save one life over 20 years was calculated by dividing the number screened ( not the number invited ) by the total number of lives saved . Similarly , we calculated the number of mammographic examinations required to save one life . Results : We estimate that the number of women needed to screen for seven years to save one life over 20 years is 465 ( 95 % CI 324–819 ) . The number of mammographic examinations needed to save one life was 1499 ( 95 % CI 1046–2642 ) . Conclusions : The number needed to screen to save one life is smaller than has been reported in the past . Mammographic screening is effective in absolute terms as well as relative . Long-term follow-up allowed us to estimate the absolute benefit with greater accuracy A r and omized , controlled mammographic screening procedure has been initiated in Sweden . The study has been conducted since 1977 in Kopparberg county and since 1978 in Ostergötl and county . This paper describes the planning and organization of the study as well as the method of screening used . The results of the first 27 months in Kopparberg county are presented Case-control studies have been used in recent years to evaluate the efficacy of cancer screening . However , relatively little work has been done to examine the methodology itself for this purpose . In this paper , it is demonstrated that because of self- selection bias the case-control study can yield a biased estimate of screening efficacy . Further , it is shown how this bias can be assessed using data from a r and omized trial . Using data from the HIP breast cancer screening study , the magnitude of the self- selection bias is estimated and is seen to be substantial Reductions in breast cancer mortality in the Health Insurance Plan of Greater New York trial are examined by age at entry and stage at diagnosis using a stage shift cancer screening model . The results indicate that for women aged 40 - 49 years at entry , benefits are associated with an internal stage shift of stage 1 cancers that have a prognosis poorer than the usual stage 1 cancers . Further , the results indicate that after 18 years of follow-up , of the reduction of 16 fewer deaths in the intervention group , 12 - 15 of the deaths are related to this internal shift . Given that stage 1 cases inherently have relatively good survival , the time required to see the screening benefit is substantial . For women aged 50 - 64 years at entry , the results suggest that benefits are associated primarily with shifts to or within stage 1 . Further , the results indicate that after 6 years , of the reduction of 31 fewer deaths in the intervention group , 22 of the deaths are related to external shifts to stage 1 . Given that stage 2 cancers have poorer survival than stage 1 cancers , screening benefit is seen sooner for the older cohort than for the younger cohort The effect of mammographic screening in reducing mortality from breast cancer is known to be smaller and more delayed in women aged 40 - 49 than in women over 50 . In this study , we investigated how these phenomena relate to histology-specific breast cancer incidence and mortality . The data are from 2,468 women with breast cancer who participated in the Swedish Two-County Trial . The overall relative breast cancer mortality of invited to noninvited women aged 40 - 49 was 0.87 , and the relative mortality from poorly differentiated ( grade 3 ) ductal carcinoma was 0.95 . These results were not statistically significant . The corresponding relative risks for invited women aged 50 - 74 were a statistically significant 0.65 and 0.61 . We conclude that in this trial , with a two-year interscreening interval , the smaller and later effect of invitation to screening on breast cancer mortality in women 40 - 49 years old is due to the failure of screening to reduce mortality from grade 3 ductal carcinoma in this age group In January 1977 , a breast cancer screening program was started in Malmo , which is a city in Sweden with about 235,000 inhabitants . The study was design ed as a r and omized trial and all females born from 1908 to 1932 were allocated to either a study group or a control group . The r and omization was done on an individual basis . Each group consisted of about 21,000 women . The main aim of the study is to demonstrate the effect of mammographic screening on the mortality of breast carcinoma . Mammography is the only screening modality employed . In the first and second screening rounds , two views - the oblique and the craniocaudal - were obtained . All patients were classified according to the system of Wolfe ( 1976 ) . In the third round , females with an N 1 or P 1 pattern underwent only the oblique-view screening and females with the P 2 or DY pattern underwent screening with both views The efficacy of mammographic screening in the reduction of breast carcinoma mortality has been demonstrated in r and omized controlled trials . However , the evaluation of organized screening outside of research setting s ( so‐called “ service screening “ ) faces unique method ologic and conceptual challenges . The current study describes the evaluation of organized mammography screening in a clinical setting and demonstrates the benefit obtained from service screening in two Swedish counties Summary of the Recommendations The U.S. Preventive Services Task Force ( USPSTF ) recommends screening mammography , with or without clinical breast examination ( CBE ) , every 1 to 2 years for women aged 40 and older . This is a grade B recommendation . ( See Appendix Table 1 for a description of the USPSTF classification of recommendations . ) The USPSTF found fair evidence that mammography screening every 12 to 33 months significantly reduces mortality from breast cancer . ( See Appendix Table 2 for a description of the USPSTF classification of levels of evidence . ) Evidence is strongest for women aged 50 to 69 , the age group generally included in screening trials . For women aged 40 to 49 , the evidence that screening mammography reduces mortality from breast cancer is weaker , and the absolute benefit of mammography is smaller , than it is for older women . Most , but not all , studies indicate a mortality benefit for women undergoing mammography at ages 40 to 49 , but the delay in observed benefit in women younger than 50 makes it difficult to determine the incremental benefit of beginning screening at age 40 rather than at age 50 . The absolute benefit is smaller because the incidence of breast cancer is lower among women in their 40s than it is among older women . The USPSTF concluded that the evidence is also generalizable to women aged 70 and older ( who face a higher absolute risk of breast cancer ) if their life expectancy is not compromised by comorbid disease . The absolute probability of benefits of regular mammography increases along a continuum with age , whereas the likelihood of harms from screening ( false-positive results and unnecessary anxiety , biopsies , and cost ) diminishes from ages 40 to 70 . The balance of benefits and potential harms , therefore , grows more favorable as women age . The precise age at which the potential benefits of mammography justify the possible harms is a subjective choice . The USPSTF did not find sufficient evidence to specify the optimal screening interval for women aged 40 to 49 ( see Clinical Considerations ) . The USPSTF concludes that the evidence is insufficient to recommend for or against routine CBE alone to screen for breast cancer . This is a grade I recommendation . No screening trial has examined the benefits of CBE alone ( without accompanying mammography ) compared to no screening , and design characteristics limit the generalizability of studies that have examined CBE . The USPSTF could not determine the benefits of CBE alone or the incremental benefit of adding CBE to mammography . The USPSTF therefore could not determine whether potential benefits of routine CBE outweigh the potential harms . The USPSTF concludes that the evidence is insufficient to recommend for or against teaching or performing routine breast self-examination ( BSE ) . This is a grade I recommendation . The USPSTF found poor evidence to determine whether BSE reduces breast cancer mortality . The USPSTF found fair evidence that BSE is associated with an increased risk of false-positive results and biopsies . Because of design limitations of published and ongoing studies of BSE , the USPSTF could not determine the balance of benefits and potential harms of BSE . Clinical Considerations The precise age at which the benefits from screening mammography justify the potential harms is a subjective judgment and should take into account patient preferences . Clinicians should inform women about the potential benefits ( reduced chance of dying from breast cancer ) , potential harms ( for example , false-positive results , unnecessary biopsies ) , and limitations of the test that apply to women their age . Clinicians should tell women that the balance of benefits and potential harms of mammography improves with increasing age for women between the ages of 40 and 70 . Women who are at increased risk for breast cancer ( for example , those with a family history of breast cancer in a mother or sister , a previous breast biopsy revealing atypical hyperplasia , or first childbirth after age 30 ) are more likely to benefit from regular mammography than women at lower risk . The recommendation for women to begin routine screening in their 40s is strengthened by a family history of breast cancer having been diagnosed before menopause . The USPSTF did not examine whether women should be screened for genetic mutations ( BRCA1 and BRCA2 ) that increase the risk of developing breast cancer , or whether women with genetic mutations might benefit from earlier or more frequent screening for breast cancer . In the trials that demonstrated the effectiveness of mammography in lowering breast cancer mortality , screening was performed every 12 to 33 months . For women aged 50 and older , there is little evidence to suggest that annual mammography is more effective than mammography done every other year . For women aged 40 to 49 , available trials also have not reported a clear advantage of annual mammography over biennial mammography . Nevertheless , some experts recommend annual mammography based on the lower sensitivity of the test and on evidence that tumors grow more rapidly in this age group . The precise age at which to discontinue screening mammography is uncertain . Only two r and omized , controlled trials enrolled women older than 69 , and no trials enrolled women older than 74 . Older women face a higher probability of developing and dying of breast cancer but also have a greater chance of dying of other causes . Women with comorbid conditions that limit their life expectancy are unlikely to benefit from screening . Clinicians should refer patients to mammography screening centers with proper accreditation and quality assurance st and ards to ensure accurate imaging and radiographic interpretation . Clinicians should adopt office systems to ensure timely and adequate follow-up of abnormal results . A listing of accredited facilities is available at www . fda .gov/cdrh/mammography/certified.html . Clinicians who advise women to perform BSE or who perform routine CBE to screen for breast cancer should underst and that there is currently insufficient evidence to determine whether these practice s affect breast cancer mortality and that they are likely to increase the incidence of clinical assessment s and biopsies . The brief review of the evidence that is normally included in USPSTF recommendations is available in the complete recommendation and rationale statement on the USPSTF Web site ( www.preventiveservices.ahrq.gov ) . Recommendations of Others Nearly all North American organizations support mammography screening , although groups vary in the recommended age to begin screening , the interval for screening , and the role of CBE . The American Medical Association ( AMA ) ( 1 ) , the American College of Radiology ( ACR ) ( 2 ) , and the American Cancer Society ( ACS ) ( 3 ) all support screening with mammography and CBE beginning at age 40 . The American College of Obstetricians and Gynecologists ( ACOG ) ( 4 ) supports screening with mammography beginning at age 40 and CBE beginning at age 19 . The Canadian Task Force on Preventive Health Care ( CTFPHC ) ( 5 ) , the American Academy of Family Physicians ( AAFP ) ( 6 ) , and the American College of Preventive Medicine ( ACPM ) ( 7 ) recommend beginning mammography for average-risk women at age 50 . The AAFP and ACPM recommend that mammography in high-risk women begin at age 40 , and the AAFP recommends that all women aged 40 to 49 be counseled about the risks and benefits of mammography before making decisions about screening ( 6 , 7 ) . A 1997 Consensus Development Panel convened by the U.S. National Institutes of Health concluded that the evidence was insufficient to determine the benefits of mammography among women aged 40 to 49 . This panel recommended that women aged 40 to 49 should be counseled about potential benefits and harms before making decisions about mammography ( 8) . In 2001 , the CTFPHC concluded there was insufficient evidence to recommend for or against mammography in women 40 to 49 ( 9 ) . Organizations differ on their recommendations for the appropriate interval for mammography . Annual mammography is recommended by the AMA , ACR , and ACS ( 1 - 3 ) . Mammography every 1 to 2 years is recommended by the CTFPHC , AAFP , and ACPM ( 5 - 7 ) . The ACOG recommends mammography every 1 to 2 years for women aged 40 to 49 and annually for women aged 50 and older ( 4 ) . In its 2001 report , the CTFPHC recommends against teaching BSE to women aged 40 to 69 ( 10 ) . The AMA , ACS , ACOG , and AAFP support teaching BSE ( 1 , 3 , 4 , 6 ) R and omized trials comparing surgical treatments of breast cancer show that radical mastectomy offers no greater benefit than simple mastectomy followed by radiotherapy . Furthermore , in terms of survival , radical mastectomy seems to be no better than wide excision followed by radiotherapy when the disease is clinical ly diagnosed as stage 1 . The incidence of diagnosed breast cancer showed an 18 % increase between 1935 and 1965 and a 50 % increase between 1965 and 1975 . However , breast cancer mortality has remained unchanged for at least the past 40 years . Analysis of survival curves of women with breast cancer suggests that two or more population s exist , with about 40 % suffering fatal outcome unaffected by treatment . The remaining 60 % exhibit a relative mortality only modestly different from that of women of similar ages without evidence of disease . Increasing detection of an entity that is histologically defined as malignant but biologically relatively benign could account for the observed increase in incidence In r and omized controlled trials , screening mammography has been shown to reduce mortality from breast cancer about 25 % to 30 % among women aged 50 to 69 years after only five to six years from the initiation of screening . Among women aged 40 to 49 years , trials have reported no reduction in breast cancer mortality after seven to nine years from the initiation of screening ; after 10 to 14 years there is a 16 % reduction in breast cancer mortality . Given that the incidence of breast cancer for women aged 40 to 49 years is lower and the potential benefit from mammography screening smaller and delayed , the absolute number of deaths prevented by screening women aged 40 to 49 years is much less than in screening women aged 50 to 69 years . Because the absolute benefit of screening women aged 40 to 49 years is small and there is concern that the harms are substantial , the focus should be to help these women make informed decisions about screening mammography by educating them of their true risk of breast cancer and the potential benefits and risks of screening Results in the breast cancer screening project of the Health Insurance Plan of Greater New York that started the end of 1963 have been up date d through December 31 , 1975 . The HIP study is a r and omized trial design ed to test whether periodic screening with clinical examination and mammography results in reduced breast cancer mortality among women aged 40–64 years at the start . Study women were offered screening examinations ; 65 % appeared for initial examinations and a large majority of these women had at least one of the three additional screenings at annual intervals . The control group of women continued to receive their usual medical care . New data support earlier reported results on benefits . During the nine years following date of entry there were 128 breast cancer deaths in the control group as compared with 91 in the study group ( screenees plus refusers ) . The impact of the screening program continues to be confined to women 50 years of age and over with no benefit at ages 40–49 years . Seven‐year case fatality rates show similar relationships . Several issues related to screening benefit are considered . Of major importance is the observation of no reduction among women under 50 in breast cancer mortality . The possibility that under different screening conditions ( e.g. , with current mammography equipment ) a benefit would be found needs to be investigated . There is a clear need for rapidly determining whether a new r and omized trial is the only way to answer the question and whether experience in the 27 NCI‐ACS demonstration projects can provide useful data . Another critical issue concerns the incremental value of mammography in a screening program . Over an eight‐year period after diagnosis , breast cancer cases that were positive only on mammography when screened had a case fatality rate of 14 % ; this compares with 32 % for cases positive only in the clinical examination and 41 % for cases positive on both modalities . Excluding mammography would have reduced the benefit of screening by an estimated one‐third . With regard to risk associated with screening , it is concluded that the increment in risk result ing from radiation exposure in mammography does not offset the benefits of screening above 50 years of age . Below that age , although the risk increment is small , the risk‐benefit balance is negative because of the absence of a demonstrated benefit . Another source of risk is related to the possible increase in biopsies . Assessment of the HIP experience suggests that only timing of biopsies was affected , but the potential for considerable variation if screening is adopted widely exists . Based on current findings in the HIP study , there appears to be strong support for periodic screening at ages 50 years and over with clinical examination and mammography ; to justify screening under 50 , new information from other studies is required We studied the relationship between risk factor information and breast cancer mortality by means of a case control study , nested within the population of the National Breast Screening Study of Canada ( NBSS ) . The characteristics of women aged 40 - 59 years , identified at the initial screen , who subsequently died of breast cancer up to 7 years from the initial screen , were compared with those of controls drawn from the same population . Among the factors evaluated in this study , number of live births and presence of symptoms in the breast revealed on direct question ing were found to be significantly related to breast cancer mortality . The results suggest a decrease in risk of dying of breast cancer associated with one or more live births ( OR : 0.79 , 95 % CI : 0.68 , 0.93 ) , and an increase in risk of dying of breast cancer associated with symptoms in the breast revealed on direct question ing at the initial screen ( OR : 2.01 , 95 % CI : 1.20 , 3.37 ) Breast self‐examination ( BSE ) behavior was analyzed in 89,835 participants in the National Breast Screening Study ( NBSS ) of whom 64,619 were eligible for annual rescreening and 25,216 were followed by mail after a single screen exam . Among those eligible for rescreening , BSE competence scores based on seven BSE criteria significantly improved over time and correlated directly with reported BSE frequencies . Among all participants , the proportion reporting BSE frequencies of ⩾12/year increased over time from approximately 20 % on entry to 50 % to 64 % at final screen . Similarly , reports of zero frequency diminished from 50 % to 10 % to 15 % . Variables such as educational status , age ( fifth versus sixth decades ) , eligibility for mammography , smoking history , and ethnic origin had negligible or no influence on BSE competence . However , women with first‐degree relatives with breast cancer had significantly higher BSE scores . NBSS experience suggests that most women who enter screening programs will up grade their BSE skills if subjected to brief episodes of repeated BSE instruction Mammograms of 15,110 women , representing a r and om selection of all 45 - 69-year-old women living in Malmö and taking part in screening for carcinoma of the breast , were analyzed using Wolfe 's criteria for variations in the parenchymal pattern with ( a ) age at examination and ( b ) age at the birth of her first child . P2 and DY , which are considered high-risk patterns , increased in frequency with advancing age at first birth , being highest in nulliparous women , but decreased with age at examination The authors assess the r and omization strategy that had been used in the Canadian National Breast Screening Study ( NBSS ) . Document experts at a private investigation and security company were hired to assist in review ing instances in which names of subjects were altered in the " allocation books " ( the basic instrument used to assign , at r and om , participants to either the mammography or the usual-care arm ) . The review was restricted to records from 3 NBSS centres where women assigned to the mammography arm had a distinctly higher ( not necessarily significant ) number of deaths from breast cancer than those assigned to the usual-care arm , and to records from 2 centres where , for limited periods , administrative problems were reported . In most cases the underlying , original name could be identified . The document experts found no evidence of a deliberate attempt to conceal the alterations . A search of the NBSS data base for the underlying and superimposed names revealed that only 1 of the women whose name had been deleted or superimpsed died of breast cancer . She was in the mammography arm . The authors ' thorough review of ways in which the r and omization could have been subverted failed to uncover credible evidence of it . They conclude that even if there had been acts of subversion , they could only have been few in number and , given that there was only 1 death from breast cancer in the group review ed , the alterations could have had only a trivial effect on the study findings as reported in 1992 We report the sensitivity and specificity of first screen mammography in a 15-centre r and omized screening trial . Of 44,718 women who received mammography and physical examination at first screening , 238 were diagnosed with breast cancer at first screen , 34 in the 12-month interval after the first screen , and 98 at the second screen . Seventeen of the interval cases and 47 of the second-year cancers were defined as potentially detectable at first screening . Interpretations of first screen mammograms by radiologists at the screening centres were matched to known histological outcomes . Simultaneous blind review of 2908 cases , which included all cancers detected at first and second screenings as well as interval cancers , was done by a single reference radiologist . The sensitivity of the technique as carried out at all NBSS centres was 0.75 , the specificity 0.94 , the positive predictive value 0.07 , and the negative predictive value 0.998 A prospect i ve study of breast cancer risk factors was undertaken in conjunction with an evaluation of periodic breast cancer screening with mammography ( soft-tissue X ray ) and clinical examination in women 40 - 64 years old . The screening study was initiated in December 1963 by the Health Insurance Plan of Greater New York in cooperation with 23 of its affiliated medical groups and then began to be accompanied by the risk-factor study . Among 20211 women initially screened a detection rate of 2.72/1000 women occurred as compared with a rate of 1.62/1000 in the control group ( no special screening ) . The risk-factor data concern cancers detected at the initial examination or the first annual reexamination and the cases detected between these examinations ( total of 101 cancers ) . About 81 % of initially-screened women had a first annual reexamination . Women participating in the initial screening examinations tended to be younger more educated and generally more concerned about cancer . Ratios of relative risks for variables in which a definite or suggestive relationship with breast cancer existed included never-married vs. married ( 2.3 ) 1 - 2 vs. more pregnancies ( 2.0 ) menarche under 12 vs. at 15 or older ( 1.7 ) 30 or more years of menstrual activity vs. less than 30 years ( 1.4 ) 1 or more breast conditions vs. none ( 3.1 ) and history of 1 or more sisters with breast cancer vs. none ( 1.9 ) . No clear-cut relationship emerged involving age at first and age at last pregnancy age at menopause or interval since last menopause . The somewhat greater risk apparent at first glance for women with some college dissipated when adjustments were made for marriage and parity . No relationship involving duration of breast feeding was noted although only a small proportion of the women had long periods of lactation A r and omized trial is presented on the effect of repeated invitation to breast cancer screening with mammography on mortality from breast cancer . The invited group and the control group each consisted of approximately 21,000 women aged 45 - 69 yr at the start of the screening . The attendance rate was 74 % at the first screening and 70 % at the two subsequent screening rounds . The cancer detection rate was 7.5 per 1000 women examined in the first screening round and 2.2 and 2.0 per 1000 woman-years in the second and third screenings with an incidence of 0.9 in the intervals . The incidence in the control group was 2.7 per 1000 woman-years . The proportion of positive biopsies was 61 % in the first screening round , 33 % in the second , and 58 % in the third . After the prevalence screening , the stage distribution was more favourable in the invited group ( including non-attenders ) than in the control group . In the two most recent periods of the programme , 62 out of 160 women with cancer ( 39 % ) in the invited group were in stage II-IV compared with 91 out of 159 ( 57 % ) in the control group . More than 60 % of cancers detected at screening were either non-invasive or invasive with a diameter of 1 cm . The corresponding percentage in the control group was 27 % . The importance of sampling bias is discussed . Although data on mortality still have to be awaited , the results so far clearly indicate a positive effect of screening In a mammography screening programme for the early detection of breast cancer 66 cases of ductal cancer in situ of the breast ( DCIS ) were diagnosed between 1978 and 1984 and prospect ively followed up . In the beginning of the study period , DCIS was treated by mastectomy without axillary clearance but sector resection has been performed increasingly . Since 1982 the latter procedure has become st and ard treatment . Radical resection was confirmed by specimen X‐ray and histopathological examination of whole organ sections . No postoperative radiotherapy was given . Twenty‐eight women had mastectomy and 38 had sector resection . The median . follow‐up times were 77 and 60 months respectively . In the mastectomy group postoperative monitoring did not reveal any local recurrence but one contralateral new invasive cancer was discovered . In the sector resection group five recurrences were found . Three of the latter were new cases of DCIS and two appeared as small invasive cancers ( stage I ) . Mastectomy will cure ductal cancer in situ but has a greater morbidity . Sector resection has been established as the method of choice in stage I invasive cancer and is probably also safe in DCIS . The possible beneficial effect of postoperative local radiotherapy after sector resection for DCIS is currently being analysed in a r and omized trial which started in Sweden in 1987 Critical decisions made 20 years ago by those who planned the r and omized trial at the Health Insurance Plan ( HIP ) of Greater New York to determine the efficacy of periodic screening for breast cancer are detailed . These decisions affected the age group to be screened , screening modalities , frequency of screening , sample size , primary measures for testing efficacy , and period of follow-up ( long term ) . Results of follow-up , 16 years after entry , indicate that mortality due to breast cancer continues to be lower among study women than controls . Numerically , the differential has been stable ; relatively , it has decreased . It is estimated that the study group would have experienced about a 30 % reduction in breast cancer mortality if screening had been maintained . Relative case survival rates over a 14-year period after diagnosis show changes in contours of trend lines that result from screening . The study group 's trend is slightly concave in contrast to the usual convex curve for the controls . The contour of the curve is more decidedly concave among subjects detected through mammography alone than for other subgroups detected through screening , although the relative survival rate remains highest in the mammography only group . Uncertainty persists about effects of screening in the HIP study on breast cancer mortality among women aged 40 - 49 years at entry Background . Several studies have found a smaller effect of breast cancer screening on breast cancer mortality in women aged younger than 50 years compared with older women . Various possible reasons have been suggested for this , but none firmly is established The Canadian National Breast Screening Study ( CNBSS ) was the first study design ed to determine the efficacy of screening for breast carcinoma in women 40 - 49 years old . Women were r and omized to undergo either annual mammography and physical examination or usual care after an initial physical examination [ 1 ] . Women 50 - 59 years old were r and omized to undergo either annual mammography and physical examination or annual physical examination only [ 2 ] . This study , published by epidemiologists on the efficacy of a radiologic examination , therefore , invites evaluation by radiologists Objective Although there is clear evidence from r and omised trials of the effectiveness of mammographic screening in women over 50 in reducing mortality from breast cancer , the benefit of screening in younger women remains less certain . This paper describes a r and omised controlled trial in progress to study the effect on breast cancer mortality of annual mammographic screening of women starting at age 40–41 . Setting Screening centres of the NHS Breast Screening Programme . Methods In 1991 a national multicentre r and omised controlled trial was set up by the United Kingdom Coordinating Committee on Cancer Research ( UKCCCR ) . This trial ( the “ age ” trial ) aims at recruiting 195 000 women aged 40–41 such that 65 000 form a study group and the remaining 130 000 a control group . Women in the study group are invited for annual screening by mammography , and become eligible for the National Health Service Breast Screening Programme ( NHSBSP ) after age 50 . Those in the control group are not offered any additional services , but will also join the national programme after age 50 . All malignant breast histology in trial women is recorded . Analysis The principal method of evaluation will be the comparison of cumulative breast cancer mortality rates in the study and control groups ; interim analyses of prognostic factors of breast cancers will also be possible . Additional NHS screening costs incurred owing to lowering the age of screening will be assessed as part of an economic evaluation . The amount of unscheduled screening occurring in the control group of the trial will also be assessed Objective To assess the effect of mammographic screening for breast cancer in women aged 65 years or over . Setting The Swedish two county trial of screening for breast cancer , in which 77 080 women aged 40–74 ( 21 925 aged 65–74 ) were r and omly allocated to receive regular mammographic screening for breast cancer , and 55 985 women aged 40–74 ( 15 344 aged 65–74 ) were allocated to an unscreened control group Methods One group was screened every 33 months on average , except for those aged 40–49 at r and omisation who were screened every 24 months . The control group was screened once at the conclusion of the trial . The main statistical analysis was the comparison of cumulative mortality with 13 years of follow up between the screened and control groups , in age groups 50–64 and 65–74 , using Poisson regression . This was complemented by subsidiary analyses assessing the lead time , sensitivity , and predicted mortality from the size , node status , and grade of tumours diagnosed in the screened and control groups . Results In the age group 65–74 at r and omisation there was a significant reduction in breast cancer mortality in the screened group , with a relative mortality of 0 68 and 95 % confidence interval of 0 51 to 0 89 . This was backed up by the results of the analyses of lead time , sensitivity , and tumour characteristics Conclusions Women aged 65 or more who are regularly screened can expect a reduced risk of dying from breast cancer Abstract In 1964 a controlled trial was initiated to evaluate the effectiveness of a program of urging subjects to take periodic multiphasic health checkups ( MHC 's ) in preventing or postponing morbidity , disability , and mortality . A group of over 5000 Kaiser Foundation Health Plan members aged 35–54 at entry to the study has been urged to take MHC 's annually . Along with a comparable group of members not so urged , these subjects have been followed for 11 years . Use of outpatient clinic services , other than those services forming part of the MHC was similar in the urged ( study ) group and in non-urged ( control ) group . Overall , hospital use was also similar in the two groups . There was no difference between the overall groups in self-reported disability . However , selfreported disability was significantly less common in the older study group men ( aged 45–54 at entry ) , largely due to less disability from hypertension complications , ischemic heart disease , and back conditions . This provides a hypothesis as to a beneficial effect in a specific age-sex group that should be tested further . Mortality from a set of conditions hypothesized in advance to be most postponable or preventable through periodic MHC 's was significantly lower in the study group as a whole , primarily due to fewer deaths from hypertension complications and colorectal cancer . On the other h and , suicides and lympho-hematopoietic cancer deaths were significantly more common in the study group , though re analysis of the data revealed little relationship between these latter death rates and actual MHC exposure . Total mortality , from all causes combined , was slightly lower in the study group , but this difference was not statistically significant . Though the prevalence of a number of disability and mortality risk factors was somewhat higher in the control group at entry , adjustment for these differences did not eliminate the statistically significant control group excesses in disability ( older men only ) and potentially postponable cause mortality . With regard to processes by which increased study group MHC exposure may have caused the observed health outcome differences , there was more identification and treatment of hypertension , hyperlipidemia , cigarette smoking , obesity , and diabetes in the study group , though the differences were not large . There also was a trend toward earlier diagnoses of colorectal cancer in the study group , due mostly to MHC-related sigmoidoscopy . When the economic impact of all major health-related events was estimated for the older men in the 1965–1975 period , there was a net difference of over $ 2100 per man , favoring the study group . The health outcome rates for the women and the younger men indicated that there would be no savings for these other study group subjects , were similar cost analyses to be made The purpose of the analysis was to resolve the two opposing cl aims regarding the efficacy of surgical treatment of breast cancer , namely the course of the disease is not affected by surgery because breast cancer is an incurable systemic disease , as shown by a previous analysis , results of r and omized breast cancer treatment trials and long-term follow-up of breast cancer patients ; and breast cancer can be cured if detected early , as shown by reduced breast cancer mortality observed in results from r and omized breast cancer-screening trials using mammograms . Seven r and omized breast cancer-screening trials commonly cited as having produced evidence for reduced breast cancer mortality were analysed to identify any flaws in the trial design that would lead to confounding factors that could have affected the results . Flaws were identified in all trials in that the treatment protocol s , by requiring that the type and degree of treatment depended on the stage of the tumour at diagnosis , required that up five factors were varied in each trial , confounding the results . Correlations were sought between some of these factors and the breast cancer mortality reduction observed in some screened groups to determine which factors had the main influence on the observed results . No correlation was found between reduced breast cancer mortality and earlier surgical intervention . In fact , the trial with the most earlier surgical intervention had the smallest reduction in mortality ; and that with the least earlier surgical intervention had the largest reduction in mortality . This demonstrates that the earlier-diagnosis hypothesis is invalid . Some correlation was established between reduced mortality and reduced use of radiotherapy , suggesting that radiotherapy had a greater influence on mortality than surgery . Analysis of deaths from other causes suggests that there are at least two effects involved : immune suppression caused by radiotherapy , and increased classification of breast cancer deaths as deaths from other causes following ischaemic heart damage caused by radiotherapy . Cl aims that mammographic screening reduces breast cancer mortality are therefore unproven . The conclusion from the previous analysis , that surgery has not been shown to reduce mortality for any form of cancer , is therefore still valid . Surgery for breast cancer should therefore be considered as a palliative measure and radiotherapy should be avoided as a routine technique BACKGROUND The efficacy of screening by mammography has been shown in r and omised controlled trials in women aged 50 years and older , but is less clear in younger women . A meta- analysis of all previous trials showed a 15 % mortality reduction in invited women aged 40 - 49 years at study entry , but this finding could be due in part to screening of women after age 50 years . The Age trial was design ed to study the effect on mortality of inviting women for annual mammography from age 40 years . METHODS 160,921 women aged 39 - 41 years were r and omly assigned in the ratio 1:2 to an intervention group of annual mammography to age 48 years or to a control group of usual medical care . The trial was undertaken in 23 NHS breast-screening units in Engl and , Wales , and Scotl and . The primary analysis was based on the intention-to-treat principle and compared mortality rates in the two groups at 10 years ' follow-up . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N24647151 . FINDINGS At a mean follow-up of 10.7 years there was a reduction in breast-cancer mortality in the intervention group , in relative and absolute terms , which did not reach statistical significance ( relative risk 0.83 [ 95 % CI 0.66 - 1.04 ] , p=0.11 ; absolute risk reduction 0.40 per 1000 women invited to screening [ 95 % CI -0.07 to 0.87 ] ) . Mortality reduction adjusted for non-compliance in women actually screened was estimated as 24 % ( RR 0.76 , 95 % CI 0.51 - 1.01 ) . INTERPRETATION Although the reduction in breast-cancer mortality observed in this trial is not significant , it is consistent with results of other trials of mammography alone in this age-group . Future decisions on screening policy should be informed by further follow-up from this trial and should take account of possible costs and harms as well as benefits This article presents up date d data on breast cancer mortality for women under age 50 from the Stockholm Mammographic Screening Trial , as well as a review of some side effects associated with screening in this age group . Approximately 40,000 women aged 40 - 64 ( 14,842 aged 40 - 49 years ) were r and omized to a trial of breast cancer screening by single-view mammography alone ; 20,000 women ( 7,103 aged 10 - 49 ) were r and omized to a control group . In the 40 - 49 age group , 24 and 12 breast cancer deaths were found in the study and control groups , respectively , after 11.4 years of follow-up . The relative risk of breast cancer death in screened to nonscreened women was 1.08 ( 95 % confidence interval : 0.54 - 2.17 ) . The rates of benign surgical biopsies , false positives , and follow-up costs were higher among women under age 50 . Large overview studies are needed , however , to determine whether mammography screening consistently reduces mortality in women 40 - 49 years of age . Side effects such as costs and public aspects of mammography screening in this age group also warrant further study BACKGROUND Over the past 30 years , eight major r and omized controlled trials of breast cancer screening -- with mammography and /or clinical breast examination -- have been conducted . Results from several trials have been up date d during the past year , and initial results of three other trials have been reported . PURPOSE The National Cancer Institute held an International Workshop on Screening for Breast Cancer in February 1993 to conduct a thorough and objective critical review of the world 's most recent clinical trial data on breast cancer screening , consider the new evidence , assess the current state of knowledge , and identify issues needing further research . METHODS Investigators representing the eight r and omized controlled trials of breast cancer screening in women aged 40 - 74 presented published and unpublished data . Evidence relating to the effectiveness of breast cancer screening in different age groups , especially women aged 40 - 49 , was presented . RESULTS For women aged 40 - 49 , r and omized controlled trials consistently demonstrated no benefit from screening in the first 5 - 7 years after study entry . A meta- analysis of six trials found a relative risk of 1.08 ( 95 % confidence interval = 0.85 - 1.39 ) after 7 years ' follow-up . After 10 - 12 years of follow-up , none of four trials have found a statistically significant benefit in mortality ; a combined analysis of Swedish studies showed a statistically insignificant 13 % decrease in mortality at 12 years . Only one trial ( Health Insurance Plan ) has data beyond 12 years of follow-up , and results show a 25 % decrease in mortality at 10 - 18 years . Statistical significance of this result is disputed , however . In women aged 50 - 69 , all studies show mortality reductions ; three of four studies show reductions of about 30 % at 10 - 12 years after study entry . Results from two of these trials were statistically significant . Too few women over age 70 have been included in studies for adequate analysis . CONCLUSIONS For women aged 40 - 49 , r and omized controlled trials of breast cancer screening show no benefit 5 - 7 years after entry . At 10 - 12 years , benefit is uncertain and , if present , marginal ; thereafter , it is unknown . For women aged 50 - 69 , screening reduces breast cancer mortality by about a third . Currently available data for women age 70 or older are inadequate to judge the effectiveness of screening . IMPLICATION S R and omized trials have provided stronger scientific evidence regarding the effectiveness of screening for breast cancer than for any other cancer . However , much still needs to be learned . Periodic gatherings of scientists in the field should speed the process Background The Age trial was a r and omized controlled trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41 . Uptake of invitation to screening mammography in UK women aged below 50 is of interest , particularly in the light of the recent announcement that the national breast screening programme will begin inviting women from age 47 . Methods The trial took place in 23 National Health Service breast screening units in Engl and , Wales and Scotl and between 1991 and 2004 . Data on invitation and attendance during 13 years of trial fieldwork were analysed . The participants were 53,884 women in the intervention arm of the Age trial who were r and omized to receive annual invitation to mammography from age 40 or 41 up to age 48 . The trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N24647151 . Results Uptake of invitation to routine screening was 68 % at first round and 69 % at subsequent rounds . A total of 43,709 women in the intervention arm ( 81 % ) attended at least one routine screen and 23,262 ( 43 % ) attended at least seven screens ; 31,392 women attended 75 % or more of all routine invitations they were offered . Previous trial attendance was a predictor of subsequent uptake ; attendance was inversely related to Townsend deprivation score . Conclusion Uptake in this trial was comparable with that in the UK screening programme for women aged over 50 . There was an inverse relationship between deprivation level and the number of screens attended BACKGROUND In the Swedish two-county trial women aged 40 - 74 years from two counties in Sweden were r and omised to invitation to mammographic screening for breast cancer . METHODS This paper uses r and om effects logistic regression models to analyse recent data from the trial . The analysis accounts for the structure of the trial , where small geographical units are r and omised within larger geographical strata ( blocks of two or three small units that are socio-economically similar ) . RESULTS Fixed effects and a variety of r and om effects models show a strong degree of agreement and yield a significant 29 % or 30 % reduction in breast-cancer mortality . DISCUSSION Fixed effects and r and om effects models agree for this example , because heterogeneity both between strata and within strata between clusters is small and because the effect of treatment does not vary much in different strata A r and omized controlled study on breast cancer screening with mammography was started in Ostergotl and county , Sweden , in 1978 . The basic question asked in this trial is : Can screening for breast carcinoma with single-view mammography as the only screening modality reduce mortality in the disease ? A total of 93,000 females aged 40 years and older living in Ostergotl and county have been selected to the study . R and omization was carried out on the basis of municipalities and parishes . The control group includes 46,000 women and the study group offered examination with single-view mammography comprises 47,000 subjects . These females will be invited to two examinations with an interval of 2–3 years . The second screening is now underway and will be finished in 1983 . The preliminary results are reported Objectives –To analyse the cause of death pattern in the cohorts of women included in the Swedish r and omised mammography screening trials by comparing the groups of invited and control women both with each other and with the general population of Swedish women . Setting –Since 1977 four r and omised trials of mammography screening have been performed in Sweden : Malmö , Kopparberg and ÖOstergötl and ( the two county trial ) , Stockholm , and Gothenburg . Design –Overview of four r and omised mammography screening trials . Results –The total numbers of deaths in the invited and control groups respectively were 15 695 and 11 887 corresponding to a relative risk ( RR ) of 1.00 . There were no significant differences between the invited and control groups for cause-specific mortality , except for breast cancer . When the total mortality in the invited and the control groups was compared with that for Swedish women in general the st and ardised mortality ratio was close to 100 . Conclusions –The cause of death pattern in the invited group was , except for breast cancer , very similar to that in the control group , showing that the groups were comparable . Similarly , the total mortality including breast cancer mortality in the control group was almost identical to that in Swedish women in general . The same was true , with the exception of breast cancer , for the invited group . These observations confirm that the trial cohorts are representative of Swedish women and indicate that the quantitative results from these trials may safely be generalised to the Swedish population This paper summarizes the findings of the first breast cancer screening trial , which was initiated in December 1963 to explore the efficacy of screening . Women aged 40 - 64 years were selected from enrollees in the Health Insurance Plan ( HIP ) of Greater New York and were r and omly assigned to study and control groups . Study group women were invited for screening , an initial examination , and three annual reexaminations . Screening consisted of film mammography ( cephalocaudal and lateral views of each breast ) and clinical examination of breasts . Breast cancer and mortality from breast cancer were examined by treatment group ( study vs. control ) and by entry-age subgroup . By the end of 18 years from entry , the study group had about a 25 % lower breast cancer mortality among women aged 40 - 49 and 50 - 59 at time of entry than did the control group . However , to a large extent the difference among the 40 - 49-year-olds occurred in the subgroup with breast cancer diagnosed after these women had passed their 50th birthday , and utility of screening women in their forties is question able BACKGROUND The radiographic appearance of the female breast varies from woman to woman depending on the relative amounts of fat and connective and epithelial tissues present . Variations in the mammographic density of breast tissue are referred to as the parenchymal pattern of the breast . Fat is radiologically translucent or clear ( darker appearance ) , and both connective and epithelial tissues are radiologically dense ( lighter appearance ) . Previous studies have generally supported an association between parenchymal patterns and breast cancer risk ( greater risk with increasing densities ) , but there has been considerable heterogeneity in risk estimates reported . PURPOSE Our objective was to determine the level of breast cancer risk associated with varying mammographic densities by quantitatively classifying breast density with conventional radiological methods and novel computer-assisted methods . METHODS From the medical records of a cohort of 45,000 women assigned to mammography in the Canadian National Breast Cancer Screening Study ( NBSS ) , a multicenter , r and omized trial , mammograms from 354 case subjects and 354 control subjects were identified . Case subjects were selected from those women in whom histologically verified invasive breast cancer had developed 12 months or more after entering the trial . Control subjects were selected from those of similar age who , after a similar period of observation , had not developed breast cancer . The mammogram taken at the beginning of the NBSS was the image used for measurements . Mammograms were classified into six categories of density , either by radiologists or by computer-assisted measurements . All radiological classification and computer-assisted measurements were made using one craniocaudal view from the breast contralateral to the cancer site in case subjects and the corresponding breast of control subjects . All P values represent two-sided tests of statistical significance . RESULTS For all subjects , there was a 43 % increase in the relative risk ( RR ) between the lower and the next higher category of density , as determined by radiologists , and there was a 32 % increase as determined by the computer-assisted method . For all subjects , the RR in the most extensive category relative to the least was 6.05 ( 95 % confidence interval [ CI ] = 2.82 - 12.97 ) for radiologists and 4.04 ( 95 % CI = 2.12 - 7.69 ) for computer-assisted methods . Statistically significant increases in breast cancer risk associated with increasing mammographic density were found by both radiologists and computer-assisted methods for women in the age category 40 - 49 years ( P = .005 for radiologists and P = .003 for computer-assisted measurements ) and the age category 50 - 59 years ( P = .002 for radiologists and P = .001 for computer-assisted measurements ) . CONCLUSION These results show that increases in the level of breast tissue density as assessed by mammography are associated with increases in risk for breast cancer The 14-year follow-up mortality results from the r and omized breast cancer screening trial of the Health Insurance Plan of Greater New York ( HIP ) were analyzed with respect to the problem of age-specific screening effects . Mortality reduction was measured in three different ways and appears to be homogeneous across age groups . This finding challenges the widespread opinion that the results of the HIP study support the conclusion that breast cancer screening is not effective below age 50 Periodic breast cancer screening with mammography and clinical examination is being evaluated to determine its value in reducing breast cancer mortality among women . Representative sample s of women aged 40 to 64 years enrolled in the Health Insurance Plan of Greater New York are r and omly assigned to study and control groups , each of which will contain 30,000 women . Results of the study to date are consistent with the hypothesis that the screening leads to earlier detection of breast cancers than is ordinarily experienced and that mammography contributes significantly to detection . While these relationships are encouraging , they must be viewed with caution since the study is still in its early stages . Furthermore , the crucial question is whether mortality from breast cancer is lowered because of the screening , and definitive findings on this issue will require at least five years of follow-up Public health planners around the world had been awaiting the preliminary results of the r and omized , controlled trial of breast cancer screening performed by the Canadian National Breast Screening Study ( CNBSS ) during the 1980s . It had been hoped that this large study would answer , with statistical validity , many of the questions concerning breast cancer screening that had not been answered satisfactorily by previous studies . Among the major unresolved issues is the desire to establish " absolute " proof that mammographic screening can benefit women who are between 40 and 49 years old Prognostic markers were analysed in a r and omized screening project for breast carcinoma using mammary radiography as the only screening method . The proportion of small carcinomas ( non-invasive carcinoma and invasive at most 10 mm across ) was significantly larger among carcinomas detected at screening than that of carcinomas appearing in the control group . Furthermore , the rate of axillary metastasis was lower and the proportion of stage I disease significantly larger . The proportion of highly differentiated tubular carcinoma and intraductal carcinoma in situ was significantly larger in the screened group , while the proportion of less differentiated tubuloductal carcinoma , invasive comedocarcinoma and medullary carcinoma with lymphoid infiltration was larger in the comparison group . The findings strongly indicate that carcinomas found at radiographic screening represent , on the average , an earlier stage compared with carcinomas detected in clinical practice The aim of the present study was to analyse the survival rate in a group of breast cancers detected in the intervals between screening examinations in relation to clinical ly detected cancers in a non-screened population . All interval and control cancers were recruited from a r and omized controlled mammography screening trial in Stockholm . The overall survival up to eight years of observation was higher in 191 patients with interval cancers than in 142 control cancers ( p=0.01 ) . There were no significant differences between the two groups with regard to tumor size , stage distribution , or mean age , though the interval group did have a larger proportion of younger women . The similarity was confirmed by multiple regression analysis . The overall survival stage by stage was consistently higher in interval cancers . The survival rate in the true interval cancers was similar to that for those found in retrospect to have been detectable or traceable at the time of screening . No correlation was found between the length of the interval and the survival of patients with interval cancers . These results contradict the hypothesis that a high growth rate is associated with a poorer prognosis and that interval cancers are a more aggressive form of breast neoplasia UNLABELLED The benefit of mammographic screening in reducing mortality from breast cancer is well established . Questions remain with respect to the magnitude of the long-term benefit of modern mammography screening , age specific benefits and the timing of these , and histology specific effects . METHODS The Swedish Two-County Trial was set up in 1977 , with 77,080 women aged 40 - 74 r and omised to invitation to mammographic screening for breast cancer ( active study population , ASP ) and 55,985 women r and omised to no invitation ( passive study population , PSP ) . There is now follow-up for mortality to 31 December 1996 , approximately 18 years average follow-up . We investigated the effect of invitation of screening on breast cancer mortality and incidence of advanced tumours by age group ( 40 - 49 and 50 - 74 ) and histologic type . In addition we estimated progression rates by histologic grade using markov chain models . RESULTS A significant 29 % reduction in breast cancer mortality was observed in association with invitation to screening ( relative risk = 0.71 , 95 % confidence interval 0.60 - 0.83 ) , maintaining the effect observed at previous stages of follow-up . Age-specific analyses show a smaller and later mortality benefit in women aged 40 - 49 . This is related to the fact that there is a considerable benefit from early detection in terms of mortality from aggressive , poorly differentiated cancers in women aged 50 - 74 , whereas the major effect in women aged 40 - 49 is on the less aggressive tumours of good or intermediate differentiation . Among women aged 50 - 74 , the incidence of grade III tumours in the ASP is significantly lower than in the PSP , but this is not the case for women aged 40 - 49 . This is related to the greater prevalence and rapidity of progression with respect to histologic grade , as evidence d by the results of markov chain models and the proportions of grade III tumours by time since last screen . CONCLUSIONS The substantial and significant mortality benefit of invitation to mammographic screening in women aged 40 - 74 is maintained at 18 years of follow-up . To achieve a substantial mortality benefit at an early stage in the screening program in women aged under 50 years , an interscreening interval of 12 - 18 months would be required Combined morphological and cytochemical malignancy grading in addition to tumor stage was applied to assess the malignant potential of so-called interval carcinomas from the Stockholm r and omized mammography screening study . Only interval carcinomas surfacing within two years from screening were included . Fifty-four percent of the tumors were in stage I and 46 % of the carcinomas eligible for DNA analysis were diploid , i.e. low-malignant . An overrepresentation of prognostically unfavorable tumor characteristics was found only within the subgroup ' true ' and ' early ' interval cancer Tumor size , lymph node status , and histologic grade are reported to be important predictors of survival in the first 5 years after the diagnosis of invasive breast carcinoma . However , to the authors ' knowledge , the effect of these factors in the longer term ( > 10 years after diagnosis ) is not yet clear . A r and omized mass screening program using mammography as well as clinical examination in women aged 40 to 64 years result ed in a higher proportion of breast cancer detected with no axillary lymph node involvement and subsequently a substantial reduction in mortality in a study group as compared to a matched control . Both clinical examination and mammography contributed independently to the yield . However , in women under 50 in this study , mammography led to detection of only a small proportion of additional cases , while at age 50 years and over omission of either modality would have led to substantially lower cancer detection rates . The particularly substantial contribution of mammography is underscored by a case fatality rate of only 2 per cent in cancers detected in mammography alone . It would be reasonable to conclude that further follow-up to determine long-term effect of the screening procedures is indicated . It would also seem useful to evaluate the contribution of newer improved methods of mammography R and omized breast cancer screening trials are helpful in establishing evidence of benefit when they yield statistically significant results . The results of individual r and omized screening trials can vary greatly depending on the quality of the images , the frequency of screening , compliance , contamination , sample size , and the length and adequacy of follow‐up . For women 40–49 years of age at entry the first r and omized breast cancer screening trial , the Health Insurance Program of Greater New York ( HIP ) , showed a statistically significant decrease of 24 % in breast cancer mortality at 18 years of follow‐up , virtually the same as the 23 % decrease seen in women 50–59 years of age . At 10–12 years of follow‐up , five of seven r and omized trials have shown nonstatistical decreases in breast cancer mortality . No trials with fewer than 8 years of follow‐up have shown a decrease in mortality for women 40–49 years of age ; whereas seven trials have shown a decrease for women older than 50 years of age BACKGROUND Screening for breast cancer with mammography in women aged 50 years or more has been shown to reduce mortality from breast cancer . However , the extent to which mammography contributes to the reduction of mortality in women who also undergo physical examination of the breasts is not known . This study was design ed to compare breast cancer mortality following annual screening consisting of two-view mammography and physical examination of the breasts with mortality following annual screening by physical examination only . Breast self-examination was taught to all participants . METHODS This trial r and omly and individually assigned 39 405 women aged 50 - 59 years , recruited from January 1980 through March 1985 , to one of the study arms . The women were followed by record linkage with the Canadian National Cancer Registry and National Mortality Data base to December 31 , 1993 , and by active follow-up of breast cancer patients to June 30 , 1996 . RESULTS R and omization achieved virtually equal distribution of demographic and breast cancer risk variables . At the first annual screen , 21 % of the cancers found by mammography alone ( in the mammography plus physical examination group ) were 20 mm or more in size compared with 46 % of those found by physical examination in the mammography plus physical examination group and 56 % in the physical examination-only group . The corresponding percentages for screens 2 - 5 were 10 % , 42 % , and 50 % , respectively . Screening detected 267 invasive breast cancers in the mammography plus physical examination group compared with 148 in the physical examination-only group . By December 31 , 1993 , 622 invasive and 71 in situ breast carcinomas were ascertained in the mammography plus physical examination group , and 610 and 16 were ascertained in the physical examination-only group . At 13-year follow-up , with 107 and 105 deaths from breast cancer in the respective groups , the cumulative rate ratio was 1.02 ( 95 % confidence interval = 0.78 - 1.33 ) . CONCLUSION In women aged 50 - 59 years , the addition of annual mammography screening to physical examination has no impact on breast cancer mortality The gold st and ard for evaluating screening programs is the r and omized controlled trial ( RCT ) . Case-control studies are easier to perform but their role in this area is controversial . The purpose of this article is to compare empirically the results of RCTs and case-control studies conducted to evaluate the efficacy and effectiveness of screening mammography and examine possible explanations for differences in their results . We located eight RCTs and five case-control studies of screening mammography . For women aged 40 - 74 years at screening , comparison of the summary risk estimates of the RCTs ( 0.76 , 95 % CI : 0.69 - 0.83 ) with that of the case-control studies ( 0.44 , 95 % , CI : 0.38 - 0.50 ) showed RCTs to have a significantly higher summary risk estimate than case-control studies ( ratio = 1.74 , 95 % CI : 1.48 - 2.04 ) . It is notable that the RCTs were compromised in most instances by low compliance rates ( 50 - 80 % ) in the treatment groups and by significant use of screening in the control groups ( 20 - 30 % ) . Adjustment of the RCT results for these cross-overs yields results that are in reasonable agreement with the summary estimate for the case-control studies . These findings support the use of case-control studies to estimate the efficacy of mammographic screening where RCTs are not feasible . They suggest that the efficacy of mammography in women aged 50 years and above is somewhat greater than the effectiveness measured by the intent-to-treat analysis of RCTs Objectives To characterize and quantify the differences in the number of cases and breast cancer deaths in the Swedish W-E Trial compared with the Swedish Overview Committee ( OVC ) summaries and to study method ological issues related to trials in secondary prevention . Setting The study population of the W-E Trial of mammography screening was included in the first ( W and E county ) and the second ( E-county ) OVC summary of all Swedish r and omized mammography screening trials . The OVC and the W-E Trial used different criteria for case definition and causes of death determination . Method A Review Committee compared the original data files from W and E county and the first and second OVC . The reason for a discrepancy was determined individually for all non-concordant cases or breast cancer deaths . Results Of the 2615 cases included by the W-E Trial or the OVC , there were 478 ( 18 % ) disagreements . Of the disagreements 82 % were due to inclusion /exclusion criteria , and 18 % to disagreement with respect to cause of death or vital status at ascertainment . For E-County , the OVC inclusion rules and register based determination of cause of death ( second OVC ) rather than individual case review ( W-E Trial and 1st OVC ) result ed in a reduction of the estimate of the effect of screening , but for W-County the difference between the original trial and the OVC was modest . Conclusions The conclusion that invitation to mammography screening reduces breast cancer mortality remains robust . Disagreements were mainly due to study design issues , while disagreements about cause of death were a minority . When secondary research does not adhere to the protocol s of the primary research projects , the consequences of such design differences should be investigated and reported . Register linkage of trials can add follow-up information . The precision of trials with modest size is enhanced by individual monitoring of case status and outcome status such as determination of cause of death OBJECTIVE To estimate the proportion of Canadian National Breast Screening Study ( NBSS ) participants who went outside the trial for a mammogram , based on health insurance cl aims data . METHOD Prospect i ve cohort study linking trial subjects with population -based administrative data . SUBJECTS All NBSS participants enrolled in the Winnipeg screening center who had health insurance cl aims to Manitoba Health ( n = 9,780 ) . ANALYSIS Cl aims for bilateral mammograms were compared by screening arm allocation and age group at enrollment . Mammograms likely to be " screening " were defined based on prior cl aim history . RESULTS For women aged 40 to 49 at enrollment , 5.3 % in the intervention group and 21.8 % in the control group had a cl aim for at least one bilateral mammogram . After excluding nonscreening mammograms these proportions fell to 2.2 % and 14.1 % ( P < 0.0001 ) . For women aged 50 to 59 , 4.5 % in the intervention group and 16.7 % of the control group had at least one cl aim for a bilateral mammogram . These proportions were 2.1 % and 10.5 % for screening ( P < 0.0001 ) . CONCLUSION Health care utilization data can be used to estimate contamination in a screening trial . The levels of contamination result ing from participants going outside the study for a screening test can have an impact on the power of the study and need to be considered when interpreting results and planning future screening studies A r and omized , controlled , population -based breast cancer screening trial has been underway in two counties of Sweden since 1977 ( Kopparberg county ) and since 1978 ( Ostergotl and county ) . The main goal of this study is to answer the question : What is the effect of mammography screening on mortality caused by breast cancer when using the single , mediolateral oblique view as the only screening method ? The preliminary results gained in the first 5 years of screening in Kopparberg county are described here The breast cancer screening program in Malmo was design ed as a controlled study to investigate whether repeated invitation to screening with mammography might reduce the mortality from breast cancer . The program was started in January 1977 in the city of Malmo , which has about 235000 residents . The invited cohort consisted of a 50 % r and om sample of all women born between 1908 and 1932 ( aged 45–69 years ) living in the city at the time of the initiation of the screening . The r and omization was done on an individual basis . Thus , the invited group and the control group were equally large , each consisting of approximately 21 000 women . The study is planned to go on for 10 years and will thus be finished in January 1987 A r and omised controlled trial of mass screening for breast cancer by single-view mammography was begun in Sweden in 1977 . All women aged 40 and older and resident in the counties of Kopparberg and Ostergötl and were enrolled . The present report is confined to the Ostergötl and study , which started in 1978 and comprised 92 934 women . After r and omisation , which was done on the basis of communities rather than individuals , 47 001 women were allocated to the study group and offered repeated mammographic screening ; 45 933 were allocated to the control group . As compliance among women over 74 years of age was poor these were excluded from the present report . The yearly incidence of stage II or more advanced breast cancers after the initial screening round up to and including the second was reduced by 40 per cent in the study group compared with the controls . This effect was less marked in the age group 40 - 49 . After 5.5 years average from the date of entry the absolute number of women with stage II-IV disease in the control group exceeded that for the study group by 44 , whereas there was a large excess of cancer in situ and stage I cancer in the study group In the Edinburgh R and omised Breast Screening Project ( EBSP ) to December 1988 there were 500 cancers in the study population invited to screening and 340 cancers identified in the control population . The size and negative lymph node status characteristics of invasive cancers from the two population s were significantly different ( P less than 0.05 ) . The cancers detected by screening were predominantly ' early stage ' , with 16 % noninvasive ( PTIS ) and 42 % invasive stage I ( pT1 node negative ) , whereas cancers were frequently ' late stage ' ( more than pT2 ) and inoperable in nonattenders ( 44 % ) and controls ( 36 % ) . Grouped according to customary size ranges of invasive cancers , the proportion of cases lymph node positive differed in those screen detected compared with controls , but the benefit in favour of screen detection was not constant . In comparisons of cancers detected at prevalence and incidence screens , as a test of conformity with screening theory , no significant differences were apparent according to size and lymph node status , yet the characteristics of histological type of cancer discriminated significantly ( P less than 0.05 ) . When these same histological characteristics were used to compare survival , the capacity to separate invasive cancers into two groups having good and poor survival probabilities was evident , with a significant improvement for the screen detected poor survival group compared with controls ( P less than 0.05 ) |
13,398 | 29,048,176 | Short menu formats ( less computationally complex representations showing joint-events ) and visual aids demonstrated some of the strongest moderation effects , improving performance for both conditional probability and natural frequency formats .
A number of method ological factors ( e.g. , exposure to both problem formats ) were also found to affect performance rates , emphasizing the importance of a systematic approach . | The natural frequency facilitation effect describes the finding that people are better able to solve descriptive Bayesian inference tasks when represented as joint frequencies obtained through natural sampling , known as natural frequencies , than as conditional probabilities .
The present meta- analysis review s 20 years of research seeking to address when , why , and for whom natural frequency formats are most effective . | Background There is little evidence on how best to present diagnostic information to doctors and whether this makes any difference to clinical management . We undertook a r and omised controlled trial to see if different data presentations altered clinicians ’ decision to further investigate or treat a patient with a fictitious disorder ( “ Green syndrome ” ) and their ability to determine post-test probability . Methods We recruited doctors registered with the United Kingdom ’s largest online network for medical doctors between 10 July and 6 ” November 2012 . Participants were r and omised to one of four arms : ( a ) text summary of sensitivity and specificity , ( b ) Fagan ’s nomogram , ( c ) probability-modifying plot ( PMP ) , ( d ) natural frequency tree ( NFT ) . The main outcome measure was the decision whether to treat , not treat or undertake a brain biopsy on the hypothetical patient and the correct post-test probability . Secondary outcome measures included knowledge of diagnostic tests . Results 917 participants attempted the survey and complete data were available from 874 ( 95.3 % ) . Doctors r and omized to the PMP and NFT arms were more likely to treat the patient than those r and omized to the text-only arm . ( ORs 1.49 , 95 % CI 1.02 , 2.16 ) and 1.43 , 95 % CI 0.98 , 2.08 respectively ) . More patients r and omized to the PMP ( 87/218–39.9 % ) and NFT ( 73/207–35.3 % ) arms than the nomogram ( 50/194–25.8 % ) or text only ( 30/255–11.8 % ) arms reported the correct post-test probability ( p < 0.001 ) . Younger age , postgraduate training and higher self-rated confidence all predicted better knowledge performance . Doctors with better knowledge were more likely to view an optional learning tutorial ( OR per correct answer 1.18 , 95 % CI 1.06 , 1.31 ) . Conclusions Presenting diagnostic data using a probability-modifying plot or natural frequency tree influences the threshold for treatment and improves interpretation of tests results compared to text summary of sensitivity and specificity or Fagan ’s nomogram Is the human mind inherently unable to reason probabilistically , or is it able to do so only when problems tap into a module for reasoning about natural frequencies ? We suggest an alternative possibility : naive individuals are able to reason probabilistically when they can rely on a representation of subsets of chances or frequencies . We predicted that naive individuals solve conditional probability problems if they can infer conditional probabilities from the subset relations in their representation of the problems , and if the question put to them makes it easy to consider the appropriate subsets . The results of seven studies corroborated these predictions : when the form of the question and the structure of the problem were framed so as to activate intuitive principles based on subset relations , naive individuals solved problems , whether they were stated in terms of probabilities or frequencies . Otherwise , they failed with both sorts of information . The results contravene the frequentist hypothesis and the evolutionary account of probabilistic reasoning Abstract Objective To investigate the accuracy of interpretation of probabilistic screening information by different stakeholder groups and whether presentation as frequencies improves accuracy . Design Between participants experimental design ; participants responded to screening information embedded in a scenario . Setting Regional maternity service and national conferences and training days . Participants 43 pregnant women attending their first antenatal appointment in a regional maternity service ; 40 companions accompanying the women to their appointments ; 42 midwives ; 41 obstetricians . Participation rates were 56 % , 48 % , 89 % , and 71 % respectively . Measures Participants estimated the probability that a positive screening test result meant that a baby actually had Down 's syndrome on the basis of all the relevant information , which was presented in a scenario . They were r and omly assigned to scenarios that presented the information in percentage ( n = 86 ) or frequency ( n = 83 ) format . They also gave basic demographic information and rated their confidence in their estimate . Results Most responses ( 86 % ) were incorrect . Obstetricians gave significantly more correct answers ( although still only 43 % ) than either midwives ( 0 % ) or pregnant women ( 9 % ) . Overall , the proportion of correct answers was higher for presentation as frequencies ( 24 % ) than for presentation as percentages ( 6 % ) , but further analysis showed that this difference occurred only in responses from obstetricians . Many health professionals were confident in their incorrect responses . Conclusions Most stakeholders in pregnancy screening draw incorrect inferences from probabilistic information , and health professionals need to be aware of the difficulties that both they and their patients have with such information . Moreover , they should be aware that different people make different mistakes and that ways of conveying information that help some people will not help others Patients are increasingly being exposed to quantitative information about risks for disease and benefits of treatment . Many authors [ 1 - 6 ] believe that the use of such information is an important component of informed decision making ; others cl aim that only patients given such information can make truly informed choices . This position is reflected in the recent decision of the National Institutes of Health Consensus Panel not to make a recommendation about screening mammography for women aged 40 to 49 years but to advocate that these women make their own decisions about screening on the basis of their personal evaluation of risks and benefits [ 7 ] . This strategy , however , is based on the assumption that patients underst and quantitative information . Research in this area has largely focused on how simple changes in the format of numerical information can influence choices , a concept referred to as framing [ 8 - 20 ] . But just as it is premature to worry about wording before knowing whether patients can read , it may be premature to worry about framing before knowing whether patients can underst and and manipulate numbers . In fact , evidence suggests that many persons do not work well with numbers [ 21 , 22 ] . It is likely that quantitative information is only meaningful to the extent that patients have some facility with basic probability and numerical concepts , a construct called numeracy . To learn more about the role of numeracy in communicating information about risk , we studied women 's comprehension of messages about mammography . Our goal was to underst and how numeracy affects women 's ability to gauge the benefit of mammography after receiving quantitative information . We provided women with typical risk reduction expressions about mammography , framed in relative and absolute terms , to study how well they could make use of such information . We hypothesized that the ability to use quantitative risk information would be related to the level of numeracy . Methods Study Design and Sample In December 1995 , we drew a simple r and om sample of 500 women from a registry of female veterans maintained at the Department of Veterans Affairs Medical Center , White River Junction , Vermont . These women were mailed one of four question naires , which differed only in how the same information on average risk reduction with mammography was presented . Reminder letters were sent to nonrespondents after 2 weeks , and new copies of the question naire were mailed after 4 weeks . The study was closed in February 1996 . Because of errors in the registry , 26 entries in our sample were not usable ( 10 of the listed persons were deceased , and 16 either were not female veterans or were listed twice ) . Thus , our possible respondent pool totaled 474 , of which 302 ( 64 % ) returned the question naire . The returned surveys sometimes contained unanswered questions . Such blanks may represent information about the respondent 's abilities , or they may be a marker of an unmotivated respondent or one who has become fatigued from the survey burden . To remove those who were unmotivated or fatigued , we required completion of four of the five questions on the last page of the survey for inclusion in the analyses . Only 15 women did not meet this criterion . Thus , our final sample comprised 287 women , for a 61 % completion rate . Unanswered numeracy questions were considered wrong answers . Restricting the sample to women who answered these questions yielded results similar to those seen with the entire sample . Question naire Design Assessment of Numeracy Numeracy was assessed with three questions and was scored as the total number of correct responses . The first question assessed basic familiarity with probability : Imagine that we flip a fair coin 1,000 times . What is your best guess about how many times the coin would come up heads in 1,000 flips ? _ _ _ _ times out of 1,000 . The second question asked respondents to convert a percentage ( 1 % ) to a proportion ( 10 in 1000 ) : In the BIG BUCKS LOTTERY , the chance of winning a $ 10 prize is 1 % . What is your best guess about how many people would win a $ 10 prize if 1000 people each buy a single ticket to BIG BUCKS?____person(s ) out of 1,000 . The third question reversed this task , asking the respondent to convert a proportion ( 1 in 1000 ) to a percentage ( 0.1 % ) : In ACME PUBLISHING SWEEPSAKES , the chance of winning a car is 1 in 1,000 . What percent of tickets to ACME PUBLISHING SWEEPSAKES win a car?____% . Presentation of Risk Reduction Data We r and omly assigned each of the 500 women to receive one of four question naires ; the question naires differed only in how the information on risk reduction was framed ( Figure 1 ) . Risk reduction data were framed as a 33 % relative risk reduction , a 33 % relative risk reduction together with the baseline risk for death from breast cancer in the next 10 years , a 4 in 1000 absolute risk reduction , or a 4 in 1000 absolute risk reduction together with the baseline risk for death from breast cancer in the next 10 years . Figure 1 . Overview of the task presented to a woman completing the survey and our measures of her ability to accurately apply risk reduction information . Assessment of Perceived Benefit To assess their perceived risk for death from breast cancer with and without mammography ( Figure 1 ) , women were asked to do the following : Imagine 1,000 women exactly like you . Of these women , what is your best guess about how many will die from breast cancer during the next 10 years if they are not screened every year for breast cancer by mammogram _ _ _ _ _ out of 1000 they are screened every year for breast cancer by mammogram _ _ _ _ _ out of 1000 Calculation of Accuracy To see how accurately respondents applied the risk reduction data that they were given , we compared their perceived risk for death from breast cancer with mammography with their perceived risk for death without mammography ( Figure 1 ) . Accuracy was judged by the ability to adjust perceived risk in accordance with the risk reduction data presented . Accuracy was judged solely by the change between perceived risk with mammography and perceived risk without mammography , which we calculated from the responses to these two questions . Thus , women could grossly overestimate their risk while still accurately applying the risk reduction information . In fact , many women did overestimate their perceived risk without mammography , as observed in previous work [ 23 ] . For the two groups presented with the absolute risk reduction , we subtracted each woman 's perceived risk with mammography from her perceived risk without mammography . For example , a woman who perceived her risk to be 100 out of 1000 without mammography and 96 out of 1000 with mammography indicated an absolute risk reduction of 4 out of 1000 . Because the women in these groups were told that mammography decreases the risk for death from breast cancer by 4 in 1000 , only women whose responses indicated an absolute risk reduction of 4 in 1000 were judged to be accurate . For the two groups presented with the relative risk reduction , we determined the percentage reduction between the perceived risk without mammography and the perceived risk with mammography . For example , a woman with a perceived risk of 100 out of 1000 without mammography and 67 out of 1000 with mammography indicated a 33 % risk reduction . The women in these groups were told that mammography decreases the risk for death from breast cancer by 33 % . To allow for rounding off , women whose responses indicated a relative risk reduction between 30 % and 40 % were judged to be accurate . Statistical Analysis For the assessment of both numeracy and accuracy , the percentage of the sample that had correct answers for each measure was calculated as the number of respondents with correct responses divided by the total number of respondents ( n = 287 ) . Chi-square tests and Kruskal-Wallis tests were used to compare participant characteristics across the four groups . All comparisons were two-sided and were considered statistically significant at a P value of less than 0.05 . We used multiple logistic regression to assess the relation between accuracy in applying the risk reduction information ( dependent variable ) and numeracy ( independent variable ) after adjusting for age , income , education , and the framing of the information provided . Role of the Funding Sponsor This research was funded by the Department of Veterans Affairs Fellowship Program in Ambulatory Care and the Department of Defense 's Breast Cancer Research Program . Neither department had any role in the gathering , analysis , or interpretation of the data or in deciding whether to su bmi t the report for publication . Results Study Sample Overall , the study sample consisted of older female veterans , almost all of whom had at least a high school education . Most reported having annual household incomes of less than $ 25 000 , and fewer than one fourth were currently employed ( Table 1 ) . Most reported having had at least one mammogram , and 9 % had a history of breast cancer . No significant differences were seen in any characteristic across the four groups . Table 1 . Characteristics of the Study Sample * Assessment of Numeracy Almost half of the women ( 46 % ) answered the coin-flip question ( which asked how many times a coin would come up heads in 1000 flips ) incorrectly , raising questions about basic underst and ing of probability . Incorrect answers ranged from 0 to 800 and were largely underestimates ( one third of the sample thought that 1000 flips of a fair coin would result in < 300 heads ) . The most common incorrect answers were 25 , 50 , and 250 . Women also had trouble converting between percentages and probability expressions . The difficulty was greater for the conversion of 1 in 1000 to 0.1 % than for the conversion of 1 % to 10 in 1000 . Although 46 % of 287 respondents were unable to convert 1 % to 10 in 1000 , 80 % were unable to convert 1 in 1000 to 0.1 % . The total number of correct responses to these three simple tasks were as OBJECTIVES The natural frequency effect ( NF effect)-whereby framing health risks using information presented as natural frequencies ( NFs ) , instead of conditional probabilities ( CPs ) , results in improved diagnostic problem solving-has led to the recommended use of NFs in clinical practice . This experiment tests , via incentivization of a lab-based decision , the hypothesis that the NF effect reflects differential motivation applied to solving problems that differ in complexity . The study examines if incentive effects are moderated by task complexity and expertise and also explores the extent to which NF frames improve diagnostic underst and ing . METHODS Three-hundred and 25 participants ( 235 novices and 90 medical experts ) were r and omly allocated to a frame ( NF vs. CP ) by task difficulty ( short vs. st and ard menus ) by incentive ( present vs. absent ) between-subjects design . The task was to calculate the positive predictive value ( PPV ) of the hemoccult test for colorectal cancer . Effort , self-efficacy , and diagnostic underst and ing were assessed . RESULTS Incentives increased correct problem solving and the NF effect was replicated . The NF effect did not vary as a function of incentivization , but was slightly attenuated by task complexity and expertise . There was no evidence that effort mediated the incentive effect . The correct PPV ( which is low ) was associated with reduced trust in the test 's diagnostic accuracy . For those who committed errors , NF frames increased the likelihood of underestimating the PPV , with underestimation associated with greater trust in the test . CONCLUSIONS The NF effect is robust to incentives supporting the use of NF frames in clinical setting s. When errors occur , however , NF frames are linked to underestimation |
13,399 | 17,443,635 | On the basis of one study , little can be said about the ability of the peer- review process to detect bias against unconventional drugs .
At present , little empirical evidence is available to support the use of editorial peer review as a mechanism to ensure quality of biomedical research . | BACKGROUND Scientific findings must withst and critical review if they are to be accepted as valid , and editorial peer review ( critique , effort to disprove ) is an essential element of the scientific process .
We review the evidence of the editorial peer- review process of original research studies su bmi tted for paper or electronic publication in biomedical journals .
OBJECTIVES To estimate the effect of processes in editorial peer review .
We hoped to find studies identifying good su bmi ssions on the basis of : importance of the topic dealt with , relevance of the topic to the journal , usefulness of the topic , soundness of methods , soundness of ethics , completeness and accuracy of reporting . | CONTEXT The ability to identify scientific journals that publish high- quality research would help clinicians , scientists , and health-policy analysts to select the most up-to- date medical literature to review . METHODS To assess whether journal characteristics of ( 1 ) peer- review status , ( 2 ) citation rate , ( 3 ) impact factor , ( 4 ) circulation , ( 5 ) manuscript acceptance rate , ( 6 ) MEDLINE indexing , and ( 7 ) Br and on/Hill Library List indexing are predictors of method ological quality of research articles , we conducted a cross-sectional study of 243 original research articles involving human subjects published in general internal medical journals . RESULTS The mean ( SD ) quality score of the 243 articles was 1.37 ( 0.22 ) . All journals reported a peer- review process and were indexed on MEDLINE . In models that controlled for article type ( r and omized controlled trial [ RCT ] or non- RCT ) , journal citation rate was the most statistically significant predictor ( 0.051 increase per doubling ; 95 % confidence interval [ CI ] , 0.037 - 0.065 ; P<.001 ) . In separate analyses by article type , acceptance rate was the strongest predictor for RCT quality ( -0.113 per doubling ; 95 % CI , -0.148 to -0.078 ; P<.001 ) , while journal citation rate was the most predictive factor for non- RCT quality ( 0.051 per doubling ; 95 % CI , 0.044 - 0.059 ; P<.001 ) . CONCLUSIONS High citation rates , impact factors , and circulation rates , and low manuscript acceptance rates and indexing on Br and on/Hill Library List appear to be predictive of higher method ological quality scores for journal articles OBJECTIVE To test the hypothesis that there is a review er bias against publication of a test of an unconventional drug . DESIGN R and omized , controlled , double-blind study of peer review . PARTICIPANTS Convenience sample of 291 medical doctors from a wide variety of specialties drawn from a list of conference participants . METHODS Review ers were r and omly assigned to receive one of two versions of a manuscript . Version M related to an in-vitro experiment on a mainstream drug ( Metoprolol ) . The otherwise identical version V used a highly unconventional drug ( beef spleen cell extract ) for the same experiment . Review ers were asked to complete a st and ardised evaluation sheet including visual analogue scales ( VASs ) on a set of predefined quality criteria . All participants were debriefed after completion of the study . RESULTS The response rate was 61 % . There were no significant differences in VAS ratings between the two versions of the manuscript . Ratings covered the entire range of the VASs . CONCLUSION In the present setting , there was no evidence for a review er-bias against testing an unconventional drug . The low inter-rater reliability , however , suggested inadequate validity of peer review Publication of medical research has high stakes : the communication and legitimization of medical research , the advancement of authors ' careers , priorities in funding decisions , the direction of future research , and the visibility and prestige of journals themselves . Peer review and editing play central roles in the publication process , affecting the acceptance of a manuscript and the form in which it appears . The most commonly heard justification of peer review is that it is an indispensable aid to an editor in assessing the importance of a scientific question and in assessing how well that question has been answered [ 1 , 2 ] . However , it has also been criticized as being inherently conservative , censorial , and , perhaps worst of all , arbitrary [ 3 ] . A frequently heard charge is that peer review delays the dissemination of crucial medical information without commensurate benefit [ 4 - 7 ] . During the last several years , some medical journal editors decided that the value of peer- review and editing practice s should be examined with the same rigor dem and ed for testing medical hypotheses [ 8 , 9 ] . The First International Congress on Peer Review was organized in 1989 [ 10 ] , bringing together medical journal editors and other interested scholars to present and discuss research on peer review ; a second Congress was held in 1993 . The peer- review process has two components : the assessment s by external review ers and the decisions and actions taken by editors , which are partially affected by comments from the review ers . To our knowledge , no study has evaluated the effects of peer review and editing on manuscript quality once the decision to accept has been made , and a computerized search of Index Medicus back to 1966 failed to locate any such studies . In this paper , we present the results of such a study , assessing the change in a manuscript between the times of provisional acceptance and final publication . We studied whether the quality of accepted manuscripts was improved by peer- review and editorial processes and , if it was , which aspects were most improved . Methods Setting The study was conducted at the editorial offices of Annals of Internal Medicine . Annals , a specialty journal in internal medicine , is published twice monthly and has a circulation of approximately 100 000 . Annals receives approximately 2400 manuscripts annually , of which half are reports of original research . During the period of this study , the investigators included the editors of Annals ( RHF and SWF ) and a statistical associate editor ( SNG ) . The Review Process No change was noted in the usual review and editing procedures at Annals during the time of this study . All manuscripts received at Annals were initially review ed by one of two full-time editors or one of two half-time deputy editors , as well as by one of seven associate editors , all of whom are faculty members of medical schools in Philadelphia and have subspecialty interests ( for example , infectious disease , gastroenterology ) . Half of the su bmi ssions were returned to authors without further review and half were sent to at least 2 outside review ers , selected by the associate editor from a data base of about 7000 review ers . After comments from the review ers were received , the original editor and associate editor reassessed each manuscript and chose which ones would be discussed at a weekly editorial conference of editors , deputy editors , medical associate editors , and two statistical associate editors . Factors that affected acceptance decisions included the quality of the research , the importance of the question , the contribution of the finding to its field , the utility and interest for Annals readers , the quality of the presentation , the priority relative to other articles , and available space . Authors were notified either that the editors would not accept the paper , that the editors were willing to reconsider the paper after major revisions , or that the paper was provisionally accepted , pending satisfactory revision . Approximately one third of the articles evaluated by outside review ers were accepted , 15 % of su bmi tted original research articles . Papers to be considered further were sent to authors , along with the comments of the two outside review ers , comments of one of the statistical editors , and a letter from one of the editors or deputy editors ( which summarized the discussion at the weekly conference , the ideas of the associate editor , and suggestions from the editor ) . In addition , each manuscript was review ed by a production editor , and directions for changes in manuscript wording or layout of figures and tables were included . All revised manuscripts were review ed by the editor or deputy editor in charge of the manuscript , the appropriate associate editor , the statistical editor , and the production editor . Some revised manuscripts were also reassessed by the original outside review ers . Approximately half of the revised manuscripts were returned to authors for further revision . Most revised manuscripts ( > 95 % ) were ultimately published . The time taken by this process was approximately 2 weeks for the initial decision to review or reject , 8 additional weeks to review and make an acceptance decision , 8 weeks until final acceptance , and about 4 months until publication . More than 95 % of manuscripts su bmi tted to Annals had a provisional acceptance or rejection decision sent to the authors within 3 months . The average time from su bmi ssion to publication was about 7 months , with initial peer review accounting for approximately 6 weeks . Manuscript Selection and Study Design All original research manuscripts ( articles ) accepted for publication by Annals from March 1992 to March 1993 were entered into the study after obtaining the author 's consent . Commentaries , review s , expository pieces , editorials , and brief reports were not included . This study had a beforeafter design , in which two versions of each manuscript were evaluated : the version originally su bmi tted and the version sent to the printer for publication after all modifications based on peer review , editors ' comments , and copyediting . All before and after manuscripts were in electronic form and were reformatted to make the appearance of the two versions identical . Authors ' names and affiliations were removed . The design of the study was approved by the Institutional Review Board of the University of Pennsylvania School of Medicine . Definition of Quality Manuscript quality can be separated conceptually into two components : the quality of the research itself , and the quality of the research report . The quality of the research report was evaluated in this study . It was defined as follows on the cover sheet of the quality assessment instrument : Whether the authors have described their research in enough detail and with sufficient clarity so a reader could make an independent judgment about the strengths and weaknesses of their data and conclusions . Manuscript Quality Assessment Instrument A 34- question instrument was developed to structure the assessment of the quality of a manuscript ( Appendix ) . Items were derived from published checklists [ 11 - 14 ] , articles about the contents of journal articles [ 15 - 18 ] , the authors ' editorial experience , and the comments of journal editors and method ologists who review ed drafts of the instrument . Each question could be answered on a 5-point ordinal scale , where 1 was worst and 5 was best . The instrument was organized along the same dimensions as a st and ard journal article : Title and Abstract ( 2 items ) , Introduction ( 2 items ) , Methods ( 7 items ) , Results ( 15 items ) , Discussion and Conclusions ( 4 items ) , and General Evaluation ( 4 items ) . An additional question asked for a subjective assessment of the manuscript 's overall quality on a 10-point scale . The instrument differed from previously published quality scoring schemes in several ways . It was not a checklist but rather was a set of structured judgments , grade d ordinally , allowing users the discretion not to penalize a manuscript if a detail was omitted that was not critical to the study 's interpretation . Also , in keeping with the definition of quality given above , each question was about the adequacy of the reporting rather than the quality of the research itself . Assessment A panel of 44 physicians and epidemiologists with training in research methods and in critically assessing the medical literature was recruited to serve as an independent panel of expert assessors ( experts ) . They did not receive any formal training in the use of the assessment instrument , although general guidelines were given on the cover sheet ( Appendix ) . The panel was masked to the design and aims of the study ; they were told only that they were participating in a study of manuscript quality for Annals . Before and after versions of each manuscript were r and omly assigned to different experts to prevent the bias that might have been introduced if they could infer the design of the study and thereby which manuscript had been through the editorial process . Thirty-two manuscript versions were given to two or three experts to assess the reliability of the instrument ; all others were assessed by only one expert . Statistical Analyses The study was design ed to have 90 % power to detect a 0.5 unit change in average score , assuming a within-manuscript st and ard deviation of 1 scale unit , using = 0.05 . The main outcome measure was the percentage of items that were scored 3 or higher on the 5-point scales ( percentage score ) . The average of all score components ( average score ) was also analyzed . Linear regression was used to assess the effect of revision on each of these outcome measures , with terms controlling for manuscript and review er . Item-specific analyses were done on dichotomized item scores ( 0 for ratings 2 and 1 for ratings 3 ) . The change from before revision to after revision in individual items was statistically assessed with conditional logistic regression , which allowed for variable group Abstract Objective To determine the effects of training on the quality of peer review . Design Single blind r and omised controlled trial with two intervention groups receiving different types of training plus a control group . Setting and participants Review ers at a general medical journal . Interventions Attendance at a training workshop or reception of a self taught training package focusing on what editors want from review ers and how to critically appraise r and omised controlled trials . Main outcome measures Quality of review s of three manuscripts sent to review ers at four to six monthly intervals , evaluated using the vali date d review quality instrument ; number of deliberate major errors identified ; time taken to review the manuscripts ; proportion recommending rejection of the manuscripts . Results Review ers in the self taught group scored higher in review quality after training than did the control group ( score 2.85 v 2.56 ; difference 0.29 , 95 % confidence interval 0.14 to 0.44 ; P = 0.001 ) , but the difference was not of editorial significance and was not maintained in the long term . Both intervention groups identified significantly more major errors after training than did the control group ( 3.14 and 2.96 v 2.13 ; P < 0.001 ) , and this remained significant after the review ers ' performance at baseline assessment was taken into account . The evidence for benefit of training was no longer apparent on further testing six months after the interventions . Training had no impact on the time taken to review the papers but was associated with an increased likelihood of recommending rejection ( 92 % and 84 % v 76 % ; P = 0.002 ) . Conclusions Short training packages have only a slight impact on the quality of peer review . The value of longer interventions needs to be assessed CONTEXT The quality of a process can only be tested against its agreed objectives . Editorial peer- review is widely used , yet there appears to be little agreement about how to measure its effects or processes . METHODS To identify outcome measures used to assess editorial peer review as performed by biomedical journals , we analyzed studies identified from 2 systematic review s that measured the effects of editorial peer review on the quality of the output ( ie , published articles ) or of the process itself ( eg , review ers ' comments ) . RESULTS Ten studies used a variety of instruments to assess the quality of articles that had undergone peer review . Only 1 , nonr and omized study compared the quality of articles published in peer- review ed and non-peer- review ed journals . The others measured the effects of variations in the peer- review process or used a before- and -after design to measure the effects of st and ard peer review on accepted articles . Eighteen studies measured the quality of review ers ' reports under different conditions such as blinding or after training . One study compared the time and cost of different review processes . CONCLUSIONS Until we have properly defined the objectives of peer- review , it will remain almost impossible to assess or improve its effectiveness . The research needed to underst and the broader effects of peer review poses many method ologic problems and would require the cooperation of many parts of the scientific community CONTEXT Anxiety about bias , lack of accountability , and poor quality of peer review has led to questions about the imbalance in anonymity between review ers and authors . OBJECTIVE To evaluate the effect on the quality of peer review of blinding review ers to the authors ' identities and requiring review ers to sign their reports . DESIGN R and omized controlled trial . SETTING A general medical journal . PARTICIPANTS A total of 420 review ers from the journal 's data base . INTERVENTION We modified a paper accepted for publication introducing 8 areas of weakness . Review ers were r and omly allocated to 5 groups . Groups 1 and 2 received manuscripts from which the authors ' names and affiliations had been removed , while groups 3 and 4 were aware of the authors ' identities . Groups 1 and 3 were asked to sign their reports , while groups 2 and 4 were asked to return their reports unsigned . The fifth group was sent the paper in the usual manner of the journal , with authors ' identities revealed and a request to comment anonymously . Group 5 differed from group 4 only in that its members were unaware that they were taking part in a study . MAIN OUTCOME MEASURE The number of weaknesses in the paper that were commented on by the review ers . RESULTS Reports were received from 221 review ers ( 53 % ) . The mean number of weaknesses commented on was 2 ( 1.7 , 2.1 , 1.8 , and 1.9 for groups 1 , 2 , 3 , and 4 and 5 combined , respectively ) . There were no statistically significant differences between groups in their performance . Review ers who were blinded to authors ' dentities were less likely to recommend rejection than those who were aware of the authors ' identities ( odds ratio , 0.5 ; 95 % confidence interval , 0.3 - 1.0 ) . CONCLUSIONS Neither blinding review ers to the authors and origin of the paper nor requiring them to sign their reports had any effect on rate of detection of errors . Such measures are unlikely to improve the quality of peer review reports CONTEXT Some journals routinely query potential referees before sending manuscripts ( " askfirst " ) , whereas others just send manuscripts and allow referees to opt out ( " justsend " ) . It is not known which protocol results in more completed review s or shorter review time . METHODS Trial to assess proportion of referee turndowns and length of review process , conducted at editorial office of Obstetrics & Gynecology and involving 283 consecutive qualifying manuscripts . For each , a referee was r and omly assigned to askfirst ( manuscript sent only after affirmative response within 3 days ) and another to justsend ( manuscript sent with request to review ; could opt out ) . RESULTS Only 64 % of askfirst referees assented initially ( 15 % declined [ vs 8 % for justsend , P = .008 ] and 21 % failed to respond within 3 working days , necessitating a replacement ) . But once manuscript was mailed , mean time to file a review was significantly shorter for askfirst ( 21.0 vs 25.0 days , P<.001 ) ; thus , overall time to receipt of review did not differ significantly ( 24.7 vs 25.9 days , P = .19 ) , nor did review quality ( P = .39 ) . CONCLUSION Askfirst led to a higher rate of referee turndown than did justsend , but assenting askfirst referees completed review s faster . The overall time for the review process did not differ between the 2 protocol OBJECTIVE The purpose of our study was to prospect ively determine the incidence and nature of unblinding by authors as to their identities or institutions in their su bmi ssion of original major manuscripts to two radiology journals with double-blinded peer review policies . MATERIAL S AND METHODS The editors of two radiology journals review ed 880 major original manuscripts su bmi tted to their journals during a 6-month period without knowledge of the identities and institutions of the authors . Each manuscript was inventoried for possible author or institutional unblinding and for the specific types of unblinding violations . RESULTS Of 880 manuscripts , 300 ( 34 % ) contained information that potentially unblinded the identities of the authors , their institutions , or both . The editors correctly identified the authors or institutions in 221 ( 74 % ) of the 300 manuscripts , which represented 25 % of the total manuscripts . The most frequent unblinding violations were statement of the authors ' initials within the manuscript , referencing work " in press , " identifying references as the authors ' previous work , and revealing the identity of the institution in the figures . CONCLUSION Despite explicit instructions to authors , 34 % of 880 prospect ively evaluated manuscripts su bmi tted to two radiology journals contained information that potentially or definitely unblinded the identities of the authors or their institutions This study compared the editorial peer review experiences of authors who published in two groups of indexed U.S. medical journals . The study tested the hypothesis that after one journal rejects a manuscript an author selects a less well-known journal for su bmi ssion . Group One journals were defined as those indexed in 1992 MEDLINE that satisfied several additional qualitative measures ; Group Two journals were indexed in the 1992 MEDLINE only . Surveys were sent to the first authors of 616 r and omly selected articles , and 479 surveys were returned , for a response rate of 78.1 % . A total of 20.8 % of Group One and 15.7 % of Group Two articles previously had been rejected . Group One authors were more likely to select a journal for its prestige and article quality , while Group Two authors were more likely to have been invited to su bmi t the manuscript . More than 60 % of both groups felt the peer review had offered constructive suggestions , but that it had changed article conclusions less than 3 % of the time . Both groups thought the review process only marginally improved content , organization , or statistical analysis , or clarified conclusions . Between 3 % and 15 % of all authors received considerable conflicting advice from different review ers . Authors from both groups differed as to their reasons for journal selection , their connections with the publishing journal , and patterns of resu bmi ssion after rejection STUDY OBJECTIVES In 1997 , Annals of Emergency Medicine initiated a protocol by which every original research article , in addition to each regular review , was concurrently evaluated by 1 of 2 methodology and statistical review ers . We characterized and contrasted comments made by the methodology and regular peer review ers . METHODS After pilot testing , interrater reliability assessment , and revision , we finalized a 99-item taxonomy of review er comments organized in 8 categories . Two authors , uninvolved in the writing of review s , classified each comment from a r and om sample of methodology review s from 1999 . For 30 of these review s ( 15 for each methodology review er ) , the 2 authors also scored all ( range 2 to 5 ) regular review s. RESULTS Sixty-five review s by method ologist A , 60 by method ologist B , and 68 by regular review ers were analyzed . Comments by method ologist A most frequently concerned the presentation of results ( 33 % of all comments ) and methods ( 17 % ) . Method ologist B commented most frequently on presentation of results ( 28 % ) and statistical methods ( 16 % ) . Regular review ers most frequently made non- methodology /statistical comments ( 45 % ) and comments on presentation of results ( 18 % ) . Of note , comments made by methodology and regular review ers about methods issues were often contradictory . CONCLUSION The distributions of comments made by the 2 methodology and statistical review ers were similar , although review er A emphasized presentation and review er B stressed statistical issues . The regular review ers ( most of whom were unaware that a dedicated methodology and statistical review er would be review ing the article ) paid much less attention to methodology issues . The 2 dedicated methodology and statistical review ers created review s that were similarly focused and emphasized methodology issues that were distinct from the issues raised by regular review ers OBJECTIVE To study whether review ers aware of author identity are biased in favor of authors with more previous publications . DESIGN R and omized controlled trial . SETTING Editorial office of the Journal of Developmental and Behavioral Pediatrics . PARTICIPANTS Two " blinded " and two " nonblinded " review ers assigned to 57 consecutive manuscripts su bmi tted between September 1991 and March 1992 . OUTCOME MEASURES Spearman rank correlation coefficients were used to compare the sum of rating scores of 1 to 5 ( 1 , accept ; 5 , reject ) given by the two blinded review ers , the two nonblinded review ers , and the editors to the number of articles published previously by the first and senior authors ( as determined from requested curricula vitae ) . Blinded review ers were sent a question naire asking whether they could determine the identity of the authors , how they knew , and whether they thought binding changed the quality or difficulty of their review . RESULTS The Wilcoxon Sign Rank Test disclosed no differences between blinded and nonblinded scores . The number of previous articles by the senior author was significantly correlated ( P < .01 ) with blinded scores ( r = -.45 ) and editors ' decisions ( r = -.45 ) , but not with nonblinded scores ; the number of articles by the first author was correlated ( P < .05 ) with editors ' decisions ( r = -.35 ) but not with blinded or nonblinded scores . Fifty ( 46 % ) of 108 blinded review ers correctly guessed the identity of the authors , mostly from self-references and knowledge of the work ; 86 % believed blinding did not change the quality of their review , and 73 % believed it did not change the difficulty of performing a review . CONCLUSIONS Blinded review ers and editors in this study , but not nonblinded review ers , gave better scores to authors with more previous articles . These results suggest that blinded review ers may provide more unbiased review s and that nonblinded review ers may be affected by various types of bias The objectives of this study were to see whether , in the opinion of authors , blinding or unmasking or a combination of the two affects the quality of review s and to compare authors ’ and editors ’ assessment s. In a trial conducted in the British Medical Journal , 527 consecutive manuscripts were r and omized into one of three groups , and each was sent to two review ers , who were r and omized to receive a blinded or an unblinded copy of the manuscript . Review quality was assessed by two editors and the corresponding author . There was no significant difference in assessment between groups or between editors and authors . Review s recommending publication were scored more highly than those recommending rejection CONTEXT All authors may not be equal in the eyes of review ers . Specifically , well-known authors may receive less objective ( poorer quality ) review s. One study at a single journal found a small improvement in review quality when review ers were masked to author identity . OBJECTIVES To determine whether masking review ers to author identity is generally associated with higher quality of review at biomedical journals , and to determine the success of routine masking techniques . DESIGN AND SETTING A r and omized controlled trial performed on external review s of manuscripts su bmi tted to Annals of Emergency Medicine , Annals of Internal Medicine , JAMA , Obstetrics & Gynecology , and Ophthalmology . INTERVENTIONS Two peers review ed each manuscript . In one study arm , both peer review ers received the manuscript according to usual masking practice . In the other arm , one review er was r and omized to receive a manuscript with author identity masked , and the other review er received an unmasked manuscript . MAIN OUTCOME MEASURE Review quality on a 5-point Likert scale as judged by manuscript author and editor . A difference of 0.5 or greater was considered important . RESULTS A total of 118 manuscripts were r and omized , 26 to usual practice and 92 to intervention . In the intervention arm , editor quality assessment was complete for 77 ( 84 % ) of 92 manuscripts . Author quality assessment was complete on 40 ( 54 % ) of 74 manuscripts . Authors and editors perceived no significant difference in quality between masked ( mean difference , 0.1 ; 95 % confidence interval [ CI ] , -0.2 to 0.4 ) and unmasked ( mean difference , -0.1 ; 95 % CI , -0.5 to 0.4 ) review s. We also found no difference in the degree to which the review influenced the editorial decision ( mean difference , -0.1 ; 95 % CI,-0.3 to 0.3 ) . Masking was often unsuccessful ( overall , 68 % successfully masked ; 95 % CI , 58%-77 % ) , although 1 journal had significantly better masking success than others ( 90 % successfully masked ; 95 % CI , 73%-98 % ) . Manuscripts by generally known authors were less likely to be successfully masked ( odds ratio , 0.3 ; 95 % CI , 0.1 - 0.8 ) . When analysis was restricted to manuscripts that were successfully masked , review quality as assessed by editors and authors still did not differ . CONCLUSIONS Masking review ers to author identity as commonly practice d does not improve quality of review s. Since manuscripts of well-known authors are more difficult to mask , and those manuscripts may be more likely to benefit from masking , the inability to mask review ers to the identity of well-known authors may have contributed to the lack of effect OBJECTIVE To study the association between referee characteristics and their manuscript assessment s , the influence of manuscript language on referees ' judgments , and the usefulness , quality , and extent of referees ' free-text comments . DESIGN Two nonauthentic , but realistic , short manuscripts with a number of common method ological flaws were sent to 180 Sc and inavian referees . Through r and omization , each referee received one of the manuscripts in English and the other manuscript in the national language . A structured assessment of the manuscript quality was expressed on a 5-point scale , and the impact of referee characteristics ( age , gender , experience , and so on ) was analyzed by multiple linear regression . MAIN OUTCOME Manuscript quality assessed by referees . RESULTS A total of 312 review s from 156 referees could be used for the study of referee characteristics and language . With increasing experience , the referees gave lower quality scores ( P < .05 ) . A tendency toward stricter assessment with younger age was seen ( P < .05 ) . No influence of referees ' gender , specialty , or nationality was found . For the test manuscript of the poorest quality , the English version was assessed to be better than the national- language version ( P < .05 ) . A total of 159 of 312 review s included free-text comments applicable for the method ological study . In 54 review s ( 34 % ) , no method ological comments accompanied the assessment , and in six review s they were only incomplete . Wrong sampling unit was mentioned by one fourth of 80 referees . Only one referee mentioned the incorrect use of a parametric test in the analysis of data whose distribution was nonparametric . CONCLUSIONS Experienced and young referees gave a stricter assessment of the manuscripts than their less experienced and older colleagues . An English version seemed to be accepted more easily than a national- language version of the same manuscript . Most referees spontaneously mentioned the shortcomings of the manuscripts only as part of their overall judgment BACKGROUND AND OBJECTIVE The statistical review of biomedical articles should result in an improved quality . The objective of this study was to compare the effects of clinical review and joint clinical and statistical review on manuscript quality , in articles su bmi tted to Medicina Clínica ( Barcelona ) , a Spanish weekly journal of internal medicine . METHOD Original papers arriving between May 2000 and February 2001 were r and omized either to a clinical review group or a clinical and statistical review group . Two evaluators , blinded to the paper 's group , assessed the quality improvement in both groups , from su bmi ssion to publication using a modified version ot the Goodman et al. scale . The protocol required that final versions arrived before the end of May 2001 . RESULTS Final sample size was 43 manuscripts , evaluated before and after peer review . On the intention to treat analysis , the estimated effect of statistical review was 1.35 ( 95 % CI : -0.45 to 3.16 ) positive , but not statistically significant . The analysis of the review ers ' comments revealed some protocol deviations . Taking into account the spontaneous inclusion of statistical experts in the clinical group , the estimated effect was statistically significant , with a confidence interval of 0.3 to 3.7 . CONCLUSION The inclusion of a statistical expert in the peer review process improves manuscript quality , although in the intention to treat analysis the improvement was not statistically significant Abstract Objectives : To examine the effect on peer review of asking review ers to have their identity revealed to the authors of the paper . Design : R and omised trial . Consecutive eligible papers were sent to two review ers who were r and omised to have their identity revealed to the authors or to remain anonymous . Editors and authors were blind to the intervention . Main outcome measures : The quality of the review s was independently rated by two editors and the corresponding author using a vali date d instrument . Additional outcomes were the time taken to complete the review and the recommendation regarding publication . A question naire survey was undertaken of the authors of a cohort of manuscripts su bmi tted for publication to find out their views on open peer review . Results : Two editors ' assessment s were obtained for 113out of 125manuscripts , and the corresponding author 's assessment was obtained for 105 . Review ers r and omised to be asked to be identified were 12 % ( 95 % confidence interval 0.2 % to 24 % ) more likely to decline to review than review ers r and omised to remain anonymous ( 35 % v 23 % ) . There was no significant difference in quality ( scored on a scale of 1to 5 ) between anonymous review ers ( 3.06(SD 0.72 ) ) and identified review ers ( 3.09(0.68 ) ) ( P=0.68 , 95 % confidence interval for difference −align = baseline>0.19 to 0.12 ) , and no significant difference in the recommendation regarding publication or time taken to review the paper . The editors ' quality score for review s ( 3.05(SD 0.70 ) ) was significantly higher than that of authors ( 2.90(0.87))(P<0.005 , 95%confidence interval for difference − align = baseline>0.26 to − align = baseline>0.03 ) . Most authors were in favour of open peer review . Conclusions : Asking review ers to consent to being identified to the author had no important effect on the quality of the review , the recommendation regarding publication , or the time taken to review , but it significantly increased the likelihood of review ers declining to review CONTEXT Better peer review is needed , but proven methods to improve quality are unknown . Our objective was to determine whether written feedback to review ers improves subsequent review s. METHODS Eligible review ers were r and omized to intervention or control ( receiving other review ers ' unscored review s and the editor 's decision letter ) . Study 1 ( September 1998-September 2000 ) included review ers with a median quality score of 3 or lower ; study 2 ( April 2000-January 2002 ) , review ers with median score of 4 or lower . Study 1 was design ed with a power of 0.80 to detect a difference in score of 1 ; study 2 , with a power of 0.80 to detect a difference of 0.5 . All review ers were at a peer- review ed journal ( Annals of Emergency Medicine ) . The main outcome measure was the editor 's routine quality rating ( 1 - 5 ) of all review s ( blinded to study enrollment ) . RESULTS For study 1 , 51 review ers were eligible and r and omized and 35 had sufficient data ( 182 review s ) for analysis . The mean individual review er rating change was 0.16 ( 95 % confidence interval [ CI ] , -0.26 to 0.58 ) for control and -0.13 ( -0.49 to 0.23 ) for intervention . For study 2 , 127 review ers were eligible and r and omized , and 95 had sufficient data ( 324 review s ) . Controls had a mean individual rating change of 0.12 ( 95 % CI , -0.20 to 0.26 ) and intervention review ers , 0.06 ( -0.19 to 0.31 ) . CONCLUSIONS In study 1 , minimal feedback from editors on review quality had no effect on subsequent performance of poor- quality review ers , and the trend was toward a negative effect . In study 2 , feedback to average review ers was more extensive and supportive but produced no improvement in review er performance . Simple written feedback to review ers seems to be an ineffective educational tool Summary A study was design ed to test the hypothesis that experts who review papers for publication are prejudiced against an unconventional form of therapy . Two versions were produced ( A and B ) of a ‘ short report ’ that related to treatments of obesity , identical except for the nature of the intervention . Version A related to an orthodox treatment , version B to an unconventional treatment . 398 review ers were r and omized to receive one or the other version for peer review . The primary outcomes were the review ers ’ rating of ‘ importance ’ on a scale of 1 - 5 and their verdict regarding rejection or acceptance of the paper . Review ers were unaware that they were taking part in a study . The overall response rate was 41.7 % , and 141 assessment forms were suitable for statistical evaluation . After dichotomization of the rating scale , a significant difference in favour of the orthodox version with an odds ratio of 3.01 ( 95 % confidence interval , 1.03 to 8.25 ) , was found . This observation mirrored that of the visual analogue scale for which the respective medians and interquartile ranges were 67 % ( 51 % to 78.5 % ) for version A and 57 % ( 29.7 % to 72.6 % ) for version B. Review ers showed a wide range of responses to both versions of the paper , with a significant bias in favour of the orthodox version . Authors of technically good unconventional papers may therefore be at a disadvantage in the peer review process . Yet the effect is probably too small to preclude publication of their work in peer- review ed orthodox journals CONTEXT To compare telephone , fax , and e-mail methods of prodding tardy review ers . METHODS R and omized trial conducted January 1998 through June 1999 at the main editorial office of Obstetrics & Gynecology . Review ers who had failed to file review s by 28 days after being sent manuscripts ( 7 days after deadline ) were sent identical messages in oral ( telephone ) or written ( fax and e-mail ) form inquiring as to the status of review , asking for its completion as soon as possible , and requesting it be sent by fax or e-mail . RESULTS Of 378 review ers , proportions returning review s within 7 days were essentially identical : telephone , 85 ( 68 % ) of 125 ; fax , 86 ( 67 % ) of 129 ; and e-mail , 84 ( 67 % ) of 124 ( P = .59 ) . In the two thirds who responded , the mean time to return review s did not differ among the 3 groups . CONCLUSION Contacting tardy review ers result ed in a review being received within 7 days in about two thirds of cases , and it made no difference if the contact was made by telephone , fax , or e-mail Peer review ers are blinded sometimes to authors ' and institutions ' names , but the effects of blinding on review quality are not known . We , therefore , conducted a r and omized trial of blinded peer review . Each of 127 consecutive manuscripts of original research that were su bmi tted to the Journal of General Internal Medicine were sent to two external review ers , one of whom was r and omly selected to receive a manuscript with the authors ' and institutions ' names removed . Review ers were asked , but not required , to sign their review s. Blinding was successful for 73 % of review ers . Quality of review s was higher for the blinded manuscripts ( 3.5 vs 3.1 on a 5-point scale ) . Forty-three percent of review ers signed their review s , and blinding did not affect the proportion who signed . There was no association between signing and quality . Our study shows that , in our setting , blinding improves the quality of review s and that research on the effects of peer review is possible BACKGROUND Most scientific journals practise anonymous peer review . There is no evidence , however , that this is any better than an open system . AIMS To evaluate the feasibility of an open peer review system . METHOD Review ers for the British Journal of Psychiatry were asked whether they would agree to have their name revealed to the authors whose papers they review ; 408 manuscripts assigned to review ers who agreed were r and omised to signed or unsigned groups . We measured review quality , tone , recommendation for publication and time taken to complete each review . RESULTS A total of 245 review ers ( 76 % ) agreed to sign . Signed review s were of higher quality , were more courteous and took longer to complete than unsigned review s. Review ers who signed were more likely to recommend publication . CONCLUSIONS This study supports the feasibility of an open peer review system and identifies such a system 's potential drawbacks BACKGROUND The quality of peer review ing in developing countries is thought to be poor . To examine whether this was so , we compared the performance of Indian and non-Indian review ers who were sent original and review articles su bmi tted to The National Medical Journal of India . We also tested whether informing review ers that their comments would be exchanged improved the quality of their review s. METHODS In a prospect i ve , r and omized , blinded study , we sent 100 manuscripts to pairs of peer review ers ( Indian and non-Indian ) of which 78 pairs of completed replies were available for analysis . Thirty-eight pairs of review s were exchanged and 40 were not . The quality of the review s was assessed by two editors who were unaware of the review ers ' nationality and whether they had been told that their review s would be exchanged . The quality of the review s was scored out of 100 ( based on a pre design ed evaluation proforma ) . We also measured the time taken to return a manuscript . RESULTS Overall , non-Indian review ers scored higher than Indians ( mean scores non-Indians first , 56.7 v. 48.6 , p < 0.001 ) , especially those in the non-exchanged group ( 58.4 v. 47.3 , p < 0.001 ) but not the exchanged group ( 54.8 v. 50.0 , p < 0.06 ) . Being informed that review s would be exchanged did not affect the quality of review s by non-Indians ( 54.8 exchanged v. 58.4 non-exchanged ) or of review s by Indians ( 50.0 exchanged v. 47.3 non-exchanged ) . The editors ' assessment of the review ers matched well ( r = 0.59 , p < 0.001 ) . Non-Indians took the same amount of time as Indians to return their review s , although the postage time was at least eight days longer . CONCLUSIONS We found that non-Indian peer review ers were better than Indians and informing them that their views would be exchanged did not seem to affect the quality of their review s. We suggest that Indian editors should also use non-Indian review ers and start training programmes to improve the quality of peer review s in India STUDY OBJECTIVE We sought to determine whether peer review ers who attend a formal interactive training session produce better review s. METHODS Peer review ers were invited to attend a formal , 4-hour , highly interactive workshop on peer review . Attendees received a sample manuscript to read and review in writing in advance . The workshop included presentations on analyzing a study and the journal 's expectations for a quality review , discussion of the sample manuscript 's flaws and how to address them in a review , discussion of the review s written by the attendees , and discussion of real review s of other manuscripts illustrating key points . The performance of attendees on the basis of st and ard editor quality ratings ( 1 to 5 ) was assessed for the 2 years after workshop attendance . Control review ers matched for previous review quality and volume were selected from nonattendees of the workshop . In study 1 , all average review ers received a st and ard written invitation . In study 2 , 75 r and omly selected average review ers were personally and actively recruited with intensive follow-up by means of e-mail and telephone calls in an effort to reduce self- selection bias . RESULTS In study 1 , 25 review ers volunteered for the course , were eligible for study , attended , and were compared with 25 matched control review ers . Of attendees filling out evaluations , 19 % thought it somewhat and 81 % thought it very helpful . All thought it would improve their subsequent review s , and 85 % thought it would improve their review ratings . The mean change in rating after the workshop was 0.11 ( 95 % confidence interval [ CI ] -0.25 to 0.48 ) for control review ers and 0.10 ( 95 % CI -0.20 to 0.39 ) for attendees . In study 2 , of 75 review ers intensively recruited , only 12 ( 41 % ) of those who said they would attend did . All of the participants thought the workshop would improve their performance and ratings . Test scores at the end of the workshop improved in 73 % of participants compared with scores on pretests . The control review ers ' average rating changed by -0.10 ( 95 % CI -0.49 to 0.29 ) versus 0.06 ( 95 % CI -0.34 to 0.23 ) for attendees . CONCLUSION Among invited peer review ers , voluntary attendance at a highly structured and interactive workshop was low and did not improve the quality of subsequent review s , contrary to the predictions of attendees . Efforts to aggressively recruit average review ers to a second workshop were time consuming , had low success rates , and showed a similar lack of effect on ratings , despite improvement in scores on a test instrument . Workshop teaching formats , although traditional , are of unproven efficacy BACKGROUND Academic biomedical journals use peer review and editing to help to select and improve the quality of articles . We have investigated whether articles accepted by the Nederl and s Tijdschrift voor Geneeskunde , the Dutch Journal of Medicine , were improved after peer review and editing ( post-acceptance scientific and copy editing ) . METHODS 400 readers of the journal ( 100 each of medical students , recent medical graduates , general practitioners , and specialists ) were invited to participate in a question naire survey . The first 25 from each group who agreed to participate were included . We posted a pack containing a set of identically appearing typescripts ( ie , blinding ) of the su bmi tted , accepted , and published versions of 50 articles that had been published in Ned Tijdschr Geneeskd . Each evaluator received two of the sets of versions , and each set was evaluated by one person from each group . The package also included two question naires : the first was used to compare the su bmi tted with the accepted version ( 25 questions ) , the second compared the accepted with the published version ( 17 questions ) . The questions were answered on five-point scales , and were about the quality of the articles or were general/overall scores . We analysed the data as scores of 3 - 5 ( ie , improvement ) versus 1 - 2 . FINDINGS After peer review , the quality in 14 of 23 questions ( 61 % ) was significantly improved ( p = 0.03 or smaller ) . In particular , the overall score and general medical value were significantly improved ( p = 0.00001 for each ) . Editing led to significant improvement in 11 of 16 questions ( 69 % , p = 0.017 or smaller ) , and especially in style and readability ( p = 0.001 and p = 0.004 ) . Generally , we found no differences between the scores of the four categories of evaluators . 72 % of the evaluators correctly identified which version was which . INTERPRETATION Evaluations by readers of the Ned Tijdschr Geneeskd indicated significant improvement of published articles after both peer review and editing . We think that peer review and editing are worthwhile tasks . We also think that possible biases would have had a negligible effect on our results ( including the fact that we selected the first 25 evaluators who responded , that some evaluators may have read the published version , and that one question naire may have looked more scientific than the other , more editorial one ) Earlier this year my colleagues and I carried out a Cochrane review of the effects of cholera vaccines . The review was large , but because of the data available we concentrated mainly on the older killed whole cell ( KWC ) variety of vaccines . At the beginning of the review we were aware that cholera KWC vaccines have been discouraged since the 1970s in either endemic or epidemic areas on the grounds that they had low efficacy and short duration ( four to six months ) , required multiple doses , and were less effective in children under 5than in adults . Important adverse effects were said to occur in 30 % of recipients of injected KWC vaccines . Our Cochrane review re-examined the evidence for these statements through a systematic review of r and omised and quasir and omised controlled cholera vaccine trials of over 2.5 m participants conducted world wide since 1963.The overall efficacy of vaccine compared with placebo was 57 % ( 95 % confidence The objectives of this study were to see whether , in the opinion of authors , blinding or unmasking or a combination of the two affects the quality of review s and to compare authors ' and editors ' assessment s. In a trial conducted in the British Medical Journal , 527 consecutive manuscripts were r and omized into one of three groups , and each was sent to two review ers , who were r and omized to receive a blinded or an unblinded copy of the manuscript . Review quality was assessed by two editors and the corresponding author . There was no significant difference in assessment between groups or between editors and authors . Review s recommending publication were scored more highly than those recommending rejection We assessed the reading habits of internists with and without epidemiological training because such information may help guide medical journals as they make changes in how articles are edited and formatted . In a 1998 national self-administered mailed survey of 143 internists with fellowship training in epidemiology and study design and a r and om sample of 121 internists from the American Medical Association physician master file , we asked about the number of hours spent reading medical journals per week and the percentage of articles for which only the abstract is read . Respondents also were asked which of nine medical journals they subscribe to and read regularly . Of the 399 eligible participants , 264 returned surveys ( response rate 66 % ) . Respondents reported spending 4.4 hours per week reading medical journal articles and reported reading only the abstract for 63 % of the articles ; these findings were similar for internists with and without epidemiology training . Respondents admitted to a reliance on journal editors to provide rigorous and useful information , given the limited time available for critical reading . We conclude that internists , regardless of training in epidemiology , rely heavily on abstract s and prescreening of articles by editors |
Subsets and Splits